1. science
2. medicine
3. surgery

“EFFICACY OF TRANEXAMIC ACID IN
DECREASING BLOOD LOSS DURING AND
AFTER CESAREAN SECTION : A RANDOMIZED
CASE CONTROLLED PROSPECTIVE STUDY”
BY
Dr. NITAM DEKA
M.B.B.S.,
Dissertation submitted to the
Rajiv Gandhi University of Health Sciences, Karnataka, Bangalore.
In Partial fulfillment
of the requirements for the degree of
MASTER OF SURGERY
IN
OBSTETRICS AND GYNAECOLOGY
Under the guidance of
Dr. A.C. RAMESH M.D.,
PROFESSOR
DEPARTMENT OF OBSTETRICS & GYNAECOLOGY
J.J.M. MEDICAL COLLEGE
DAVANGERE – 577 004.
2013
i
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
KARNATAKA
DECLARATION BY THE CANDIDATE
I hereby declare that this dissertation/thesis entitled “EFFICACY OF
TRANEXAMIC ACID IN DECREASING BLOOD LOSS DURING AND
AFTER CESAREAN SECTION : A RANDOMIZED CASE CONTROLLED
PROSPECTIVE STUDY” is a bonafide and genuine research work carried out
by me under the guidance of Dr. A.C. RAMESH
M.D.,
Professor, Department of
Obstetrics & Gynecology, J.J.M. Medical College, Davangere.
ii
CERTIFICATE BY THE GUIDE
This is to certify that this dissertation entitled “EFFICACY OF
TRANEXAMIC ACID IN DECREASING BLOOD LOSS DURING AND
AFTER CESAREAN SECTION : A RANDOMIZED CASE CONTROLLED
PROSPECTIVE
STUDY”
is
a
bonafide
research
work
done
by
Dr. NITAM DEKA in partial fulfillment of the requirement for the degree of
MASTER OF SURGERY IN OBSTETRICS AND GYNECOLOGY.
iii
CERTIFICATE BY THE CO-GUIDE
This is to certify that this dissertation entitled “EFFICACY OF
TRANEXAMIC ACID IN DECREASING BLOOD LOSS DURING AND
AFTER CESAREAN SECTION : A RANDOMIZED CASE CONTROLLED
PROSPECTIVE
STUDY”
is
a
bonafide
research
work
done
by
Dr. NITAM DEKA in partial fulfillment of the requirement for the degree of
MASTER OF SURGERY IN OBSTETRICS AND GYNECOLOGY.
iv
ENDORSEMENT BY THE HOD,
THE PRINCIPAL/HEAD OF THE INSTITUTION
This is to certify that this dissertation entitled
“EFFICACY OF
TRANEXAMIC ACID IN DECREASING BLOOD LOSS DURING AND
AFTER CESAREAN SECTION : A RANDOMIZED CASE CONTROLLED
PROSPECTIVE
STUDY”
is
a
bonafide
research
work
Dr. NITAM DEKA under the guidance of Dr. A.C. RAMESH
M.D.,
done
Professor,
Department of Obstetrics & Gynaecology, J.J.M. Medical College, Davangere.
v by
COPYRIGHT
Declaration by the Candidate
I hereby declare that the Rajiv Gandhi University of
Health Sciences,
Karnataka shall have the rights to preserve, use and disseminate this dissertation /
thesis in print or electronic format for academic / research purpose.
© Rajiv Gandhi University of Health Sciences, Karnataka.
vi ACKNOWLEDGEMENT
I derived great pleasure and satisfaction in preparing this dissertation and I would like
to take this opportunity to thank every one who has made it possible.
I
convey
my
heartfelt
gratitude
and
sincere
thanks
to
my
guide
Dr. A.C. RAMESH M.D., Professor, Department of Obstetrics and Gynecology, J.J.M.
Medical College, Davangere, who with his knowledge and experience has provided able
guidance and constant encouragement throughout the course of my postgraduate studies and
residency and in the preparation of this dissertation.
It gives me immense pleasure to thank Dr. T.G. SHASHIDHAR M.D., D.G.O.,
Professor and HOD, Department of Obstetrics and Gynecology, for her valuable guidance
during this study and throughout my PG course and residency in Davangere.
I am ever grateful to Dr. A. RAJSHEKHAR
M.D.,
Professor and Director of PG
Studies, for his constant support and suggestions throughout my postgraduate studies.
My sincere thanks to Dr. B.R. DAKSHAYINI M.D., Ex. HOD and Professor,
for her valuable guidance and encouragement during my study period.
I express my sincere thanks to Dr. BANDAMMA R.K. M.D., Professor,
Department of Obstetrics and Gynaecology, J.J.M. Medical College, Davangere for
her co-guidance, support and advice during the course of study.
I express my sincere thanks to my Professors
Dr.DHARMA REDDY
M.D.,
Dr.SHUKLA SHETTY
Dr. MANJUNATH. G.H.
D.G.O.,
M.D.,
M.D.,
Dr. H.M.
SHIVAMURTHY M.D., Dr.K.C.NATARAJA M.D., Dr.V.S.RAJU, M.D., D.G.O., Dr. VANITHA
V.G.
M.D.,
Dr. H.V.RAVIGOWDA
Dr.G.Y.AGASIMANI
M.D.,
Dr. SAPNA I.S.,
M.D.,
and Dr. VEENA G.R.,
Dr. LAKSHMI DEVI K.
Dr. SHOBHA DHANANJAYA
Dr. SOWBHAGYA KOUJALAGI
M.D.,
M.D.,
M.D., D.G.O.,
Dr.H.N.MALLIKARJUNAPPA
M.D.,
M.D.,
Dr. S.N. ANURADHA
Dr. NIVEDITHA M.
M.D.,
Dr. ANITHA G.S.
M.D., D.G.O.,
M.D.,
D.G.O.
M.D.,
Dr. SMITHA A.J.,
Dr. SHASHIREKHA
M.D.,
for their valuable help and
encouragement.
I extend my thanks to Assistant Professor Dr. ASHWINI
KAMATKAR
M.D.,
Dr. HALESHA B.
M.D.,
Dr. MADHU K.N.,
M.D.,
M.D.,
Dr. SAROJA C.
Dr. LATHA
M.D.,
and
Dr. CHARITHA M.D.
I am extremely grateful to Dr. MANJUNATH ALUR
College, and Dr. H. GURUPADAPPA
M.D.,
M.D.,
Principal, J.J.M. Medical
Director of PG Studies and research, J.J.M.
Medical College, Davangere.
vii I am indebted to my loving PARENTS, my father Mr. KHAGENDRA DEKA and
my mother Mrs. MINAKSHI DEKA and my Brother PARIJ DEKA for their constant
encouragement and support.
I would like to convey my thanks to my friends for their help and guidance.
I thank Mr. P.S. MAHESH, Chief Librarian and other staff of the central library for
their help during my research.
I thank Dr. RAJASHREE Professor, Department of Community
Medicine, S.S.I.M.S.H, Davangere for her help in statistical analysis of this
dissertation.
My sincere thanks to SUPERINTENDENTS of Chigateri General Hospital, Bapuji
Hospital and Women and Children Hospital of Davangere for permitting me to carry out this
study in their hospital.
My sincere thanks to Mr. SANJEEV KUMAR G.P. of
M/s. GUNDAL
Computers Center, Davangere, for his meticulous computerised laser typing and styling of
this dissertation work.
I thank all my PATIENTS, who formed the backbone of this study without whom
this study would not have been possible.
viii
LIST OF ABBREVATIONS USED
ARR- Absolute risk reduction
BL- Blood loss
BT- Bleeding time
CI- Confidence interval
Cm- Centimeter
CPD- Cephalopelvic disproportion
CS- Cesarean section
CT- Clotting time
EACA- Epsilon aminocaproic acid
Gm- Gram
Hb- Hemoglobin
Hct- Hematocrit
L- Litre
LSCS- Lower segment cesarean section
Mg- Milligram
min- minutes
Ml- milliliter
Pt- Patient
RR- Relative ratio
t-PA- Tissue plasminogen activator
TXA- Tranexamic acid
ix ABSTRACT
Background: Cesarean section (CS) rates have increased to as high as 25 to 30 % in
many areas of the world. Delivery by CS can cause more complications than normal
vaginal delivery and one of the most common complications is primary or secondary
postpartum haemorrhage (20%). Tranexamic acid is a synthetic derivative of the
amino acid lysine that exerts its antifibrinolytic effect through the reversible blockade
of the lysine binding sites on plasminogen molecules. Tranexamic acid has been
shown to be very useful in reducing blood loss and incidence of blood transfusion in a
variety of surgeries.
Objective: To study the efficacy of tranexamic acid in reducing blood loss during and
after the lower segment cesarean section.
Methods: A randomized, case controlled, prospective study was conducted on 200
women undergoing lower segment cesarean section (LSCS). 100 of them were given
tranexamic acid immediately before LSCS & were compared with 100 others to whom
tranexamic acid was not given. Blood loss was collected and measured during two
periods. The first period was from placental delivery to end of LSCS and second from
the end of LSCS to 2 hours postpartum. Vital signs at time of delivery, at 1 hour & 2
hour postpartum & apgar score at 1min & 5 min were studied in both the groups.
Results: Tranexamic acid significantly reduced the quantity of blood loss from the
end of LSCS to 2 hours postpartum: 71.5 ml in the study group versus 112.6 ml in the
control group (p=0.0002). It also significantly reduced the quantity of blood loss from
placental delivery to 2 hours post-partum: 360.9 ml in the study group, versus 443 ml
in the control group. (P=0.0008). No complications or side effects were reported in
either group.
x CONCLUSION(S): Tranexamic acid significantly reduced the amount of blood loss
during and after the lower segment cesarean section and its use was not associated
with any side effects like nausea, vomiting, diarrhoea & thrombosis. Tranexamic acid
can be used effectively in women undergoing LSCS.
Key words: Tranexamic acid; Cesarean section; Postpartum; Antifibrinolytic
xi TABLE OF CONTENTS
PAGE NO
1.
INTRODUCTION
01
2.
OBJECTIVES
04
3.
REVIEW OF LITERATURE
05
4.
METHODOLOGY
40
5.
RESULTS
45
6.
DISCUSSION
60
7.
CONCLUSION
64
8.
SUMMARY
65
9.
BIBLIOGRAPHY
67
10.
ANNEXURES
ANNEXURE-I
:
PROFORMA
79
ANNEXURE-II
:
CONSENT FORM
84
ANNEXURE-II
:
MASTER CHART
88
ZY
xii LIST OF TABLES
SL.NO
TABLES
PAGE.NO
1
Distribution based on patient characteristics in both
groups
45
2
Distribution of cases according to age group
46
3
Distribution with respect to indication s of LSCS in
both groups
47
4
Effect of tranexamic acid: Comparison of blood loss
from time of placental delivery to completion of skin
closure
48
5
Effect of tranexamic acid: Comparison of blood loss
from completion of skin closure to 2 hrs postpartum
49
6
Total blood loss
50
7
Effect of tranexamic acid: Comparison of incidence of
Patient with Blood loss ≥ 500 ml in both the groups
51
8
Comparison of duration of surgery between the two
groups
52
9
The difference in Hb% postoperative - both in cases
and control groups
53
10
Vital signs at the time of placental delivery in both the
groups
54
11
Vital signs 1 hr after surgery in both the groups
55
12
Vital signs 2 hr after surgery in both the groups
56
13
Comparison of apgar score in both the groups
57
14
Comparison of adverse drug reaction in both the groups
58
xiii LIST OF GRAPHS
SL.NO
FIGURES
PAGE.NO
1
Bar diagram showing distribution of cases according to
age group
46
2
Distribution with respect to indication s of LSCS in both
groups
47
3
Placental delivery to end of CS
48
4
End of CS to 2 hrs postpartum
49
5
Total blood loss
50
6
Effect of tranexamic acid: Comparison of incidence of
Patient with Blood loss ≥ 500 ml in both the groups
51
7
The difference in Hb% postoperative - both in cases and
control groups
53
8
Vital signs at the time of placental delivery in both the
groups
54
9
Vital signs 1 hr after surgery in both the groups
55
10
Vital signs 2 hr after surgery in both the groups
56
11
Comparison of apgar score in both the groups
57
12
Comparison of adverse drug reaction in both the groups
59
xiv LIST OF FIGURES
SL.NO
FIGURES
PAGE.NO
1
Chemical structure of Tranexamic acid
5
2
Innervation and blood supply of anterior abdominal wall
32
3
Venous drainage of anterior abdominal wall
32
4
The blood supply of the uterus and its adnexa
36
5
Cesarean section delivery
37
6
Fibrinolytic system
38
7
Tranexamic acid injection
39
xv Introduction
INTRODUCTION
Cesarean section (CS) rates have increased to as high as 25 to 30 % in
many areas of the world. (1) Delivery by CS can cause more complications than
normal vaginal delivery and one of the most common complications is primary
or secondary postpartum hemorrhage (20%). It leads to increased maternal
mortality and morbidity. In order to reduce maternal mortality and morbidity
caused by bleeding, it is important to reduce the amount of bleeding during and
after lower segment cesarean section (LSCS).1
Blood loss frequently leads to transfusion of allogeneic blood products,
which expose patients to the risk of transfusion-related adverse effects such as
febrile non-hemolytic transfusion reactions, transfusion errors and blood-borne
infections . Concerns about blood safety, continual blood shortages and rising
costs of blood bank operations have generated interest in the reduction of
transfusion requirements during and after surgery. A popular approach is to
minimize peri-operative bleeding through the prophylactic use of the
antifibrinolytic agents aprotinin, tranexamic acid (TXA), and epsilon
aminocaproic acid (EACA).2
Tranexamic acid is a synthetic derivative of the amino acid lysine that
exerts its antifibrinolytic effect through the reversible blockade of the lysine
binding sites on plasminogen molecules. 3,4 Intravenous administration of
tranexamic acid has been routinely used for many years to reduce haemorrhage
during and after surgical procedures like coronary artery bypass, scoliosis
surgery, oral surgery, orthotopic liver transplantation, total hip or knee
arthroplasty, and urinary tract surgery. Tranexamic acid has been shown to be
1 very useful in reducing blood loss and incidence of blood transfusion in these
surgeries.
Tranexamic acid potentates the blood clotting system and is used to treat
and prevent bleeding. The mechanism of action of tranexamic acid is related to
its antifibrinolytic effect, which makes this drug potentially very effective in
the third stage of labour. During placental delivery, rapid degradation of
fibrinogen and fibrin occurs, as well as an increase in the activation of
plasminogen activators and fibrin degradation products due to activation of the
fibrinolytic system. This activation can last up to six to 10 hours postpartum,
which may cause more haemorrhage. The antifibrinolytic effect of tranexamic
acid in the third stage of labour could make it a safe and effective alternative or
adjunct to other regimens currently used in the third stage of labour for
prevention of PPH. Tranexamic acid could reduce blood loss associated with
complications such as placenta praevia and lower genital tract trauma, as well
as bleeding from the upper segment placental site. Use of tranexamic acid
could potentially have prevented some PPH cases if it was given to women
with the risk factors for PPH, as reported in the Cochrane review on treatment
of PPH. Therefore, it may be particularly useful in preventing cases of PPH due
to factors other than uterine atony, where uterotonics will not be effective.
Tranexamic acid is an effective agent for the reduction of blood loss,
which has been widely used in various areas of medicine. It is an inhibitor of
fibrinolysis that blocks the lysme-hinding site of plasminogen to fibrin. It has
been used to decrease blood loss for many years in cases of haemorrhage, and
is reported to reduce intraoperative and postoperative blood loss.
2 In this study, the efficacy of tranexamic acid in the reducing the blood
loss during and after LSCS was investigated.
3 Objectives
OBJECTIVES
•
To study the efficacy and safety of tranexamic acid in reducing blood
loss during and after the lower segment cesarean section.
4 Review of Literature
R
REVIEW
W OF LITERAT
TURE
TRA
ANEXAM
MIC ACI D
FORMUL
LATION
Cheemical
N
Name:
t
trans-4-(am
minomethy l)
cycloohexanecarrboxylic
acid. Strucctural Form
mula:
Fig. 1: Chemiccal structu
ure of tran examic ac id
Empirical Forrmula: C8H
H15NO2
Molecularr Weight: 1157.2
Traanexamic acid
a
is a white
w
crystaalline powdder. Inert ingredientss in the
tablets are microcrysstalline celllulose, talcc, magnesiuum stearatee, silicone dioxide
& povidonne. The aquueous soluttion for injection has a pH of 6. 5 to 8.0.
BLOOD COAGULA
C
ATION & THE FIBR
RINOLYT
TIC SYSTE
EM
Thee blood c oagulationn cascade is the seecond keyy element in the
formation of the haeemostatic seal
s
at sitees of tissue injury, t he first beeing the
aggregatioon & the depositionn of the platelets.
p
T
The
cascaade consistts of a
sequence of reactionn that leadds to the cleavage
c
o f the prothhrombin in
nto two
fragments,, one of which
w
is ennzyme thro
ombin; throombin in tuurn cleavees small
peptides from
fr
fibrin ogen to prroduce fibrrin monom
mer, which then polym
merizes
5
to insoluble fibrin. Thrombin also activates factor XIII, an enzyme that
catalyzes the formation of covalent bonds between fibrin molecules to form
clot resistant to dissolution.5
The fibrinolytic system is activated by the deposition of fibrin & assists
in the maintenance of an open lumen in damaged blood vessels. A balance
between the formation & lyses of fibrin is required to maintain & remold the
haemostatic seal during several days in which the injured vessel wall will be
repaired. (5) Fibrinolysis is mediated through the activation of plasminogen,
the plasma precursor of the proteolytic enzyme – Plasmin. Plasminogen binds
to lysine residues on the surface of the fibrin & is converted to plasmin by
activator released from the endothelial cells known as tissue plasminogen
activator (t-PA) that simultaneously binds with fibrin. Plasmin then degrades
fibrin into large fragments known as x & y; these are subsequently broken
down into soluble fibrin degradation products. (3) Excessive fibrinolysis is
prevented by the greater affinity of fibrinogen for fibrin than for fibrinogen &
the increased ability of t-PA to activate plasminogen when it is bound to fibrin.
In addition, plasma contains protease inhibitors called alpha-2 antiplasmin that
rapidly inactivates any plasmin that escapes from a fibrin clot. 5
Defective formation or excessively rapid dissolution of fibrin results in
excessive or recurrent bleeding. Antifibrinolytic drugs that stabilize fibrin
structures can prevent that unwanted dissolution of haemostatic fibrin. Two
synthetic derivative of amino acid lysine, tranexamic acid & EACA have
antifibrinolytic activity in humans. The activity of the trans- isomer of
tranexamic acid was first described in 1964, since which time the drug has been
used in a variety of clinical settings.6
6 CLINICAL PHARMACOLOGY
The antifibrinolytic effect of the tranexamic acid results from the
formation of a reversible complex of the drug with plasminogen. Human
plasminogen contains lysine-binding sites that are important for interactions
with not only synthetic antifibrinolytic amino acid derivatives but also alpha-2
antiplasmin & fibrin.3
Tranexamic
acid
almost
completely
blocks
the
interaction
of
plasminogen & heavy chain of plasmin with the lysine residues of fibrin
monomer,
primarily
through
its
high
affinity
lysine-binding
site
of
plasminogen. 6 Saturation of this site with tranexamic acid prevents binding of
plasminogen to the surface of fibrin. This process retards fibrinolysis because
although plasmin is still formed, it is unable to bind to fibrinogen or fibrin
monomer. Conversely, when the binding site of plasmin is blocked by
tranexamic acid, inactivation by alpha-2 antiplasmin cannot proceed.
Comparisons of the binding potencies & EACA in fibrinolytic test systems
have
shown
tranexamic
acid
to
be
more
potent
by
a
factor
of
between 6 & 10.4,7-8
Tranexamic acid binds more strongly than aminocaproic acid to both the
strong & weak receptor sites of the plasminogen molecule in a ratio
corresponding to the difference in potency between the compounds.
Tranexamic acid in a concentration of 1 mg/ml does not aggregate platelets in
vitro.
Tranexamic acid in concentration up to 10 mg/ml of blood has no
influence on the platelet count, the coagulation time or various coagulation
7 factors in whole blood or citrated blood from normal subjects. On the other
hand, tranexamic acid in concentration of 10 mg & 1 mg/ml blood prolongs
thrombin time. 9
The plasma protein binding of tranexamic acid is about 3% at
therapeutic plasma levels & seems to be fully accounted for by its binding to
plasminogen. Tranexamic acid does not bind to serum albumin.10
Absorption of tranexamic acid after oral administration in humans
represents approximately 30 to 50% of the ingested dose & bioavailability is
not affected by food intake.11
After an intravenous dose of 1gm, the plasma concentration time curve
shows triexponential decay with a half-life of about 2 hours for the terminal
elimination phase. The initial volume of distribution is about 9-12 liters.
Urinary excretion is the main route of elimination via glomerular filteration.
Overall, renal clearance is equal to overall plasma clearance (110 to
116ml/min) & more than 95% of the dose is excreted in the urine as the
unchanged drug. Excretion of tranexamic acid is about 90% at 24 hours after
IV administration of 10mg/kg body weight. After oral administration of 10-15
mg/kg body weight, the cumulative urinary excretion at 24 hours is 39% & at
48 hours, 41% of the ingested dose or 78% & 82% of the absorbed material.
(12) Only a small fraction of the drug is metabolized. After oral administration,
1% of the dicarboxylic acid & 0.5% of the acetylated compound are excreted.
The plasma peak level after 1 gm oral dose is 8 mg/l & after 2 gm,
15mg/l, both obtained 3 hours after dosing. 13
8 Antifibrinolytic concentration of tranexamic acid remain in different
tissue for about 17 hours, & in the serum, upto 7-8 hours.
Tranexamic acid passes through the placenta. The concentration in cord
blood after an IV injection of 10mg/kg to pregnant women is about 30mg/l, as
high as in the maternal blood. Tranexamic acid diffuses rapidly into joint fluid
& the synovial membrane. In the joint fluid, the same concentration is obtained
as in the serum. The biological half-life of tranexamic acid in the joint fluid is
about 3 hours. 14
The concentration of tranexamic acid in a number of other tissues is
lower than in blood. In the breast milk, the concentration is about one
hundredth of the serum peak concentration. Tranexamic acid concentration in
CSF is about one tenth of that of the plasma. The drug passes into the aqueous
humor, the concentration being about one tenth of the plasma concentration.15
Tranexamic acid has been detected in semen where it inhibits
fibrinolytic activity but does not influence sperm migration. Concurrent
administration of heparin does not interfere with the antifibrinolytic activity of
tranexamic acid. 16
Comparison of tranexamic acid with other agents
Comparison of tranexamic acid with other agents have been carried out
mainly in nonrandomised non blinded studies, although comparable efficacy to
EACA & superiority over desmopressin have been shown in placebo-controlled
trials.17,18
Initial data analysis in one of the study suggested similar efficacy for
tranexamic acid 1 mg/kg/hr (after loading dose of 10mg/kg) & desmopressin
9 0.3 mg/kg (before & after the surgery) in terms of proportion of patients who
received blood transfusion.19
However, subsequent two analyses indicated that 8% of all patients who
received tranexamic acid alone or tranexamic acid with desmopressin & 21% of
those receiving desmopressin required transfusion (p=0.024).
Cochrane review of comparison of tranexamic acid with aprotinin as
antifibrinolytic
use
for
minimising
preoperative
allogenic
blood
transfusion-2005, Issue-4.19
This review studied 61 trials of aprotinin (7027) participants. Aprotinin
reduced the rate of RBC transfusion by a relative 30% (RR=0.70; 95%CI– 0.64
to 0.76). The average absolute risk reduction (ARR) was 20.4% (95%CI- 15.6%
to 25.3%). On average, aprotinin use saved 1.1 units of RBC (95%CI- 0.69 to
1.47). Aprotinin also significantly reduced the need for reoperation due to
bleeding (RR=0.40; 95%CI- 0.25 to 0.66).
They found 18 trials of tranexamic acid (TXA) (1,342 participants).
TXA reduced the rate of RBC transfusion by a relative 34% (RR=0.66; 95%CI–
0.54 to 0.81). This represented an ARR of 17.2% (95%CI- 8.7% to 25.7%).
TXA use resulted in a saving of 1.03 units of RBC (95%CI- 0.67 to 1.39%) in
those requiring transfusion. They found 4 trials of epsilon aminocaproic acid
(EACA) (208 participants). EACA use resulted in a statistically nonsignificant
reduction in RBC transfusion (RR=0.48; 95%CI– 0.19 to 1.19).
Comparison between tranexamic acid & aprotinin
Eight trials made head to head comparison between TXA & Aprotinin.
There was no significant difference between the two drugs in the rate of RBC
transfusion (RR=1.21; 95%CI– 0.83 to 1.76) for TXA compared to aprotinin.
10 USES OF TRANEXAMIC ACID IN GYNAECOLOGY
1) Menorrhagia:
Excessive menstrual bleeding is a common condition among women
attending outpatient department. 20 Although it is a subjective complaint, the
term menorrhagia encompasses both heavily bleeding associated with uterine
disorder & dysfunctional bleeding with no apparent underlying pelvic disease.
Analysis of population studies has indicated that the median volume of blood
loss during a normal period is approx 30 ml, with menorrhagia being diagnosed
when the total loss is in excess of 80 ml.21
In double blind study of Preston et.al, 56% of patients who recieved
tranexamic acid 1.5g/day achieved a menstrual blood loss of less than
80ml/cycle after two months.22
2)
Bleeding associated with pregnancy:
Bleeding during pregnancy is associated with a 3-4 fold increase in
perinatal morbidity. 23,24,25 Tranexamic acid, 1gm intravenously can be used in
subjects with abruptio placenta. This reduces perinatal mortality by 8% & there
were no cases of diathesis or thrombosis & no maternal death.26
Tranexamic acid, 3gm intravenous infusion over 24 hours was also used
with good effect in a woman with central placenta praevia who presented as an
obstetric emergency with very heavy bleeding.27
A multi-centric, randomized trial suggested that tranexamic acid 1 gm
given prior to LSCS significantly reduced bleeding after placental delivery to 2
hours postpartum with no side effects or complications. 28
11 3)
Conisation of cervix:
Double-blind placebo controlled study with open surgical technique in
45 patients showed a significant reduction (71%, p<0.05) in postoperative
blood loss in those who recieved oral dosage of 1.5 gm/day for 12 days after
surgery.29
OTHER USES OF TRANEXAMIC ACID:
1) Coronary artery by-pass surgery
The most common regimen consists of a loading dose of 10 mg/kg
followed by an infusion of 1mg/kg/hour had significantly reduced requirement
of blood transfusion after cardiac surgery. 30,31,32
2) Acute upper GI bleeding:
Reduction of transfusion requirement in-patient with hemmorhage of the
stomach or duodenum by tranexamic acid was first reported in 1973,33 & small
number of additional studies has been conducted since that time.
Meta analysis of the 6 studies showed treatment with 4.5 gm/day
tranexamic acid in peptic ulceration to be associated with 20-30% reduction in
the need for surgery & 40% reduction in mortality with peptic ulcer.34,35,36,37
3) Dental extraction in patients with hemophilia:
Administer 10mg/kg body wt of tranexamic acid intravenously together
with replacement therapy. Following surgery, a dose of 25mg/kg may be given
orally three or four times daily for 2 to 8 days. Bleeding complication with
drug ranged from 0 to 6.7% & it was 13.3 to 40 % in placebo group. 38,39
12 Alternatively, tranexamic acid can be administered entirely orally,
25mg/kg body wt three to four times a day beginning one day prior to
surgery.40,41,42 Parenteral therapy, 10mg/kg body weight three to four times can
be used for patients unable to take oral medication.43,44
4) Tranexamic acid in traumatic hemmorhage:
For people aged 5-45 years, trauma is second only to HIV/AIDS as a
cause of death. Each year, worldwide, over 3 million, people die as a result of
trauma, many after reaching the hospital. 45 Among trauma patients who do
survive to reach the hospital, exsanguinations is a common cause of death,
accounting for nearly half of in-hospital trauma deaths. 46 CNS injury, ocular
trauma & multiorgan failure account for most of the remainder, both of which
can be exacerbated by severe bleeding.47,48
The hemostatic system helps to mantain the integrity of the circulatory
system after severe vascular injury, whether traumatic or surgical in origin.49
Major surgery & trauma trigger similar haemostatic responses, & any
consequent massive blood loss prevents an extreme challenge to the
coagulation system. Part of the response to surgery & trauma, in any patient, is
stimulation of clot breakdown (fibrinolysis), which may become pathological
(hyperfibrinolysis) in some. 49 Antifibrinolytic agents have been shown to
reduce blood loss in patients with both normal &exaggerated fibrinolytic
responses to surgery, & do so without apparently increasing the risk of
postoperative complications; of note, there are no increased risk of venous
thromboembolism. 50
13 Systemic antifibrinolytic agents are widely used in major surgery to
prevent fibrinolysis & thus reduce surgical blood loss. A recent systematic
review51,52 of randomized, controlled trials of antifibrinolytic agents (mainly
aprotinin or tranexamic acid) in elective surgical patients identified 89 trials,
including 8580 randomized patients (74 trials in cardiac, 8 in orthopedic, 4 in
liver & 3 in vascular surgery). The results showed that these treatments reduced
the numbers needing transfusion by one third, reduced the volume needed per
transfusion by 1 unit, & halved the need for further surgery to control
bleeding.53,54
These differences were all highly statistically significant. There was also
no statistically significant reduction in the risk of death (RR=0.85; 95%
confidence interval 0.63-1.14) in the anti-fibrinolytic treated group.
Because the hemostatic abnormalities that occur after injury are similar
to those after surgery, it is possible that antifibrinolytic agents will also reduce
blood loss, the need for transfusion, & mortality after trauma.
A simple & widely practicable treatment that reduces blood loss
following trauma may prevent thousands of premature trauma deaths each year
& could reduce exposure to the risks of blood transfusion. Blood is a scarce &
expensive resource, & major concerns remain about the risk of transfusiontransmitted infection. Trauma is common in parts of the world where the safety
of blood transfusion is not ensured. A recent study in Uganda estimated the
population-attributable fraction of HIV aquisition because of blood transfusion
to be around 2%, although some estimates are much higher. Only 43% of the
191 World Health Organisation (WHO) member states test blood for HIV &
Hepatitis B & C viruses. Every year, unsafe transfusion & injection practices
14 are estimated to account for 8-16 million hepatitis B infections, 2.3-4.7 million
hepatitis C infections, & 80,000-160,000 HIV infections.55
The Clinical Randomization of an Antifibrinolytic in Significant
Hemmorhage (CRASH2) trial will be a large, international, placebo-controlled
trial of the effects of the early administration of the antifinrinolytic agent
tranexamic acid on death vascular events, & transfusion requirements.56
5) Orthopedic surgery:
Intravenous infusion of tranexamic acid in dose of 10-15mg/kg/hour in 2
well designed clinical studies showed statistical significant reduced in
postoperative blood loss & blood transfusion in total knee/hip arthroplasty. 57,58
6) Orthotopic liver transplantation:
Intravenous infusion of tranexamic acid in dose of 40mg/kg/hour to a
maximum dose of 20 gm in a patient undergoing primary isolated orthotopic
liver transplantation had significantly reduced intra & post-operative blood
loss.59,60,61
7) Urinary tract surgery:
Men undergoing prostatectomy showed significant reduction in urinary
blood loss when tranexamic acid 1.5-3 gm daily was given for 3 days after
surgery.62, 63
8) Hereditary angioneurotic edema:
This condition is characterized by recurrent, circumscribed & non
pitting sub-epithelial edema that can involve any part of the body. (64,65)
Double-blind studies were done, which shows a reduction in the number &
15 severity of attacks of edema in patients treated with tranexamic acid with dose
of 1.5 gm/day for 7 days after attack.66,67,68
9) Subarachnoid hemmorhage:
Rupture of an intracranial aneurysm result principally in bleeding into
the subarachnoid space & subsequent brain damage occurs due to destruction of
brain parenchyma, increase intracranial pressure brain shift & hydrocephalus.
In an analysis of 672 patients participating in the International Cooperative
Study on the timing of Aneurysm Surgery, in which patients who recieved
antifibrinolytic therapy (tranexamic acid or EACA) & those who did not, were
compared, inhibition of fibrinolysis was assocaited with a significant reduction
in the rate of re-bleeding (11.7 v/s 19.4%; p=0.01)
STORAGE:
Store at 250 C (770F); excursions permitted to 150-300 C (590-860 F)
[see USP Controlled Room Temperature).
ADVERSE DRUG REACTION:
Along with its needed effects, a medicine may cause some unwanted
effects. Although not all of these side effects may occur, if they do occur they
may need medical attention. The same effect that makes tranexamic acid help
prevent or stop bleeding also may cause blood clots that could be dangerous.
The following possible signs & symptoms of blood clots occur:
Headache (severe & sudden); loss of coordination (sudden); pain in
chest, groin or legs, especially the calves; shortness of breath (sudden); slurred
speech (sudden); vision changes (sudden); weakness or numbness in arm or
leg.73, 74, 75
16 In addition, the following side effects may occur:
Blurred vision or other changes in vision; dizziness or lightheadedness;
unusual tiredness or weakness.76, 77, 78
Other side effects may occur that usually do not need medical attention.
These side effects may go away during treatment as ones body adjusts to the
medicine. Medical help may be needed if any of these side effects may persist
or is bothersome:
•
Nausea or vomiting
•
Dairrhoea
•
Dry ejaculation
•
Unusual menstrual discomfort
•
Watery eyes.79, 80
DRUG INTERACTION:
Till yet, no drug interaction reported.
OVERDOSE:
There is no known case of overdosage of tranexamic acid tablets &
injection. Symptoms of over dosage may be nausea, vomiting, orthostatic
hypotension.
CONTRAINDICATIONS:
1. In patients with aquired defective colour vision, since this prohibits
measuring one end-point that should be followed as a measure of
toxicity.
17 2. In patients with subarachnoid hemmorhage, anecdotal experience
indicates that cerebral edema & cerebral infarction may be caused by
tranexamic acid in such patients.
3. In patients with active intravascular clotting or past history of
thromboembolic episode.
4. Heart disease, kidney disease, & liver disease.
Tranexamic acid in reducing bleeding in caeserian section
A study conducted by (Mayur G, Ashoo G, Pankaj D) showed that
tranexamic acid reduces significant blood loss from the end of LSCS to 2 hours
postpartum, 75.71 ml in the study group verses 133.03 ml in the control group
(P = .001). It also significantly reduces the quantity of blood loss from
placental delivery to 2 hour postpartum, 372.71 ml in the study group versus
469.70 ml in the control group ( P = 0.003) . No complication like thrombosis
was reported in either group1. 84
GaiMy; WULF, SuQF, Tastsumoto K conducted a prospective
randomised case control trial. In this study 180 primipara were randomised into
2 groups. In the study group, 91 women received tranexamic acid immediately
before LSCS where as in control group 89 women did not, the quantity of blood
loss measured in study group from the end of CS to 2 hour postpartum. 42.75
+/-40.45 ml in the study group versus 73.98 +/- 77.09 ml in control group 2. 85
Yang H, Zheng S, shi C conducted a study in china 4 group were
allotted
Group I
=
tranexamic acid 1gm by slow IV
Group II
=
tranexamic acid 0.5 g by slow IV
18 Group III
=
aminomethyl benzoic acid 0.5gm IV
Group IV
=
No treatment
Vaginal bleeding was precisely collected, and examined immediately
after the expulsion of placenta and from placental expulsion to 2 hours after
delivery. The amount of blood loss was measured by both methods of weight
and volume. There were no significant differences of blood loss immediately
after the expulsion of placenta among the 4 groups (P>0.05). For the average
blood loss at 2 hours postpartum, it was 129.7 ml, 133.9 ml, 168.5 ml, and
178.2 ml for group I, II, III and IV respectively, while the total blood loss for
the four group was 243.3 ml, 242.9 ml, 308.1 ml, and 314.8 ml respectively.
The average blood loss of group I and II was significantly less than group III
and (P<0.01), however, there was no significant difference between group I and
group II (P>0.05). The occurrences of postpartum hemorrhage were 6.4%,
13.3%, 20.7% and 25.3% for group I, II, III and IV respectively. There were no
adverse effects noted. Tranexamic acid is efficient and safe in reducing the
postpartum blood loss. 1.0 g of Tranexamic acid has the best efficacy, followed
by 0.5 g of Tranexamic acid 3. 86
Lindoff C, Rybo G, Astedt B carried out a retrospective analysis of case
reports of 2102 patient with various bleeding disorder during pregnancy. Of the
256 patients treated with AMCA 169 were delivered by cesarean section. Of
the remaining 1846 patients, 443 were delivered by Cesarean section. The
relationship between the use of Tranexamic acid and occurrence of thromboembolism was calculated with 95% confidence limits. Of the Tranexamic
treated group two patients had pulmonary embolism. Of the control 3 patients
had deep vein thrombosis. Thus the finding in this high risk group of women
19 with complicated pregnancies, frequently entailing delivery by Caesarean
section, provided no evidence of any thrombogenic effect of Tranexamic acid.80
Leila Sekhavat; Afsar Tabatabaii et.al (2009) conducted a prospective
randomised study on 90 primiparas divided into two groups who underwent CS.
The study group, 45 women, received tranexamic acid immediately before CS,
whereas the control group, 45 women received placebo. Blood loss volume was
measured from the end of CS to 2 h postpartum and compared between the two
groups. Hemoglobin (Hb) and hematocrit (Hct) were tested 24 h after CS and
compared between the two groups. Their results showed that tranexamic acid
significantly reduced the blood loss from the end of CS to 2 h postpartum;
28.02 ± 5.53 mL in the tranexamic group versus 37.12 ± 8.97 ml in the control
group (p = 0.000). Hb 24 h after CS was significantly greater in tranexamic
group than control group (12.57 ± 1.33 in the tranexamic group and 11.74 ±
1.14 in the control group, p = 0.002). No complications or side effects were
reported in either group. 87
Svanberg L, Astedt B, Nilsson IM used tranexamic acid in 67
consecutive antenatal patients with abruption placentae. They concluded that
routine immediate treatment with tranexamic acid can reduce the perinatal
mortality in cases of abruptio placentae.26
Tranexamic acid in reducing bleeding in other gynaec. surgeries
Caglar GS, Tasci Y et.al (2008) studied effect of tranexamic acid use on
perioperative and postoperative bleeding and blood transfusion requirements in
women undergoing myomectomy through a case control study. Their results
revealed statistically significant differences between the two groups when
20 compared for postoperative and total blood loss and duration of surgery
(p<0.01, p=0.03 and p=0.03, respectively). Perioperative blood loss and blood
transfusion requirements were similar between the two groups (p=0.12 and
p=0.25, respectively). There were no complications in either group. 88
Tranexamic acid in reducing menstrual bleeding
Lethaby A, Farquhar C, Cooke I, reviewed various studies regarding use
of antifibrinolytics in heavy menstrual bleeding. They concluded that
antifibrinolytic therapy causes a greater reduction in objective measurements of
heavy menstrual bleeding when compared to placebo or other medical therapies
(NSAIDS, oral luteal phase progestagens and ethamsylate). This treatment is
not associated with an increase in side effects compared to placebo, NSAIDS,
oral luteal phase progestagens or ethamsylate. Flooding and leakage and sex
life is significantly improved after tranexamic acid therapy when compared
with oral luteal progestogens.89
Tranexamic acid in reducing bleeding in cardiac surgery
Brown RS, Thwaites BK, Mongan PD conducted a prospective,
randomized placebo-controlled, double blind study of adult patient undergoing
coronary artery bypass grafting surgery. They concluded that efficacy of
tranexamic acid in decreasing bleeding and blood transfusions after open heart
surgery. Tranexamic acid administered before and during the operation was
effective in decreasing both bleeding and transfusion. When Tranexamic acid
was administered immediately after the operation, it had a minor beneficial
effect. 90
21 RW Reid, AA Zimmerman et.al (1997) conducted a prospective,
randomized, double-blind study design, to study the efficacy of tranexamic acid
versus placebo in decreasing blood loss in pediatric patients undergoing repeat
cardiac surgery. They found that children who were treated with tranexamic
acid had 24% less total blood loss (26 +/- 7 vs 34 +/- 17 ml/kg) compared with
children who received placebo (univariate analysis P = 0.03 and multivariate
analysis P < 0.01). Additionally, the total transfusion requirements, total donor
unit exposure, and financial cost of blood components were less in the
tranexamic acid group.91
C J Dunn, K L Goa reviewed use of tranexamic acid & its indications.
They concluded that Tranexamic acid is useful in a wide range of haemorrhagic
conditions. The drug reduces postoperative blood losses and transfusion
requirements in a number of types of surgery, with potential cost and
tolerability advantages over aprotinin, and appears to reduce rates of mortality
and urgent surgery in patients with upper gastrointestinal haemorrhage.
Tranexamic acid reduces menstrual blood loss and is a possible alternative to
surgery in menorrhagia, and has been used successfully to control bleeding in
pregnancy. 92
Tranexamic acid in reducing bleeding in orthopedic surgery
Rajesparan K, Biant LC et.al (2009) studied the effect of an intravenous
bolus of tranexamic acid on blood loss in total hip replacement. They
concluded that tranexamic acid reduced the early post-operative blood loss and
total blood loss (p = 0.03 and p = 0.008, respectively) but not the intraoperative
blood loss. The tranexamic acid group required fewer transfusions (p = 0.03)
and had no increased incidence of deep-vein thrombosis. The reduction in early
22 post-operative blood loss was more marked in women (p = 0.05), in whom this
effect was dose-related (r = -0.793). 93
Orpen NM, Little C et.al (2006) studied effect of tranexamic acid on
total knee arthroplasty by conducting a prospective, randomised, double blind,
controlled trial. They concluded that one injection of 15 mg/kg of tranexamic
given at the time of cementing the prosthesis in total knee arthroplasty, before
deflation of the tourniquet, significantly decreases the amount of blood loss in
the early post-operative period. The treatment was not associated with an
increase in thromboembolic complications.94
23 POSTPARTUM HAEMORRHAGE
In
spite
of
marked
improvements
in
management,
postpartum
haemorrhage remains a significant contributor to maternal morbidity both in
developing countries and in hospitals equipped with all modern medicine has to
offer.
Prevention, early recognition and prompt appropriate intervention are
keys to minimizing its impact.
Postpartum hemorrhage is the third major cause of maternal mortality
next to pregnancy induced hypertension (preeclampsia) and infection.
Primary postpartum hemorrhage is the loss of blood in excess during the
first 24 hours after birth of the infant. When it occurs between 24 hours after
delivery and within puerperium it is designated as secondary postpartum
haemorrhage.
Pritchard has shown that mean blood loss with vaginal and caesarean
section is 500m1 and 1000 ml respectively. Any greater loss is termed as
postpartum hemorrhage.
Another proposed definition for PPH is a 10% change in haematocrit.
Coombs has suggested a clinical definition of “need for blood transfusion”.
This definition is complicated by large variations in practice patterns
and attitudes towards transfusion by both patients and physicians.
The diagnosis of PPH therefore remains a clinical assessment that
includes any amount of blood loss that threatens the women’s haemodynamic
stability. Any amount of bleeding from or into the genital tract following birth
of the baby up to the end of the puerperium which adversely affects the general
24 condition of the patient as evidenced by rise in pulse rate and falling blood
pressure is called postpartum hemorrhage.
However, the degree of haemodynamic compromise or shock parallels
the amount of blood lost. Some women experience mild symptoms and
maintain their blood pressure at a blood loss of 500 to 1000 ml (10 to 15
percent of circulating volume), losses of 2000 to 3000 ml (35 to 45 percent of
circulating volume) will cause marked hypotension, with cardiovascular
collapse, air hunger, anuria and severe shock.
25 Clinical findings in PPH19
Findings
Blood loss
Degree of Shock
Compensation Mild
Symptoms and
signs
Severe
1000 - l500
ml
l500 –
2000ml
2000- 3000
ml
15-25%
25-35%
35-45%
Slight fall
Marked fall
None
(80 – 100
mmHg)
(70 – 80
mm Hg)
Profound
fall
Palpitations
Weakness
Restlessness
Collapse
Dizziness
Sweating
Pallor
Air hunger
Tachycardia
Tachycardia
Oliguria
Anuria
500 - l000ml
10 - 15%
Blood Pressure
Change (systolic
pressure)
Moderate
(50-70
mmHg)
Incidence:
The incidence of Postpartum haemorrhage varies from 2 - 11%.
Postpartum hemorrhage complicates approximately 4% of deliveries in most
large obstetric services. While haemorrhage was the cause of maternal death in
19.8% cases, postpartum haemorrhage and retained placenta were responsible
in 13.7% and 3% cases respectively of all complications noticed during labour.
The incidence is 0.5% amongst hospital deliveries and Postpartum haemorrhage
causes 10 - 16% maternal deaths in India.
Postpartum haemorrhage complicates approximately 3.9% of cesarean
deliveries and is responsible for most of the use of blood and blood products in
obstetric units. Postpartum bleeding has serious consequences and the
proportions range from less than 10 percent to nearly 60 percent of maternal
death in various countries.
26 Maternal Deaths due to PPH: Selected countries
Country
Maternal Deaths due to
PPH (%)
Maternal Deaths per 100, 000
Live Births
Hong Kong
30
7
India
16
570
Indonesia
43
650
Philippines
53
280
Burkina Faso
59
930
Egypt
32
170
Kenya
16
650
Morocco
29
610
Nigeria
20
1000
South Africa
15
230
Brazil
20
220
Guatemala
2
200
Honduras
33
220
Mexico
24
110
Epidemiology
The etiologies of primary PPH are most easily understood as
abnormalities of one or more of four basic processes.
⎯ Tone
⎯ Tissue
⎯ Trauma
⎯ Thrombin
27 Risk factors in PPH
Abnormalities of
uterine contraction
(tone)
Retained products of
conception (tissue)
Genital tract trauma
(trauma)
Etiology process
- Over distended uterus
-
Uterine muscle
exhaustion
-
Intra amniotic infection
-
Functional / anatomic
distortion of the uterus
-
Retained products
Abnormal placenta
Retained cotyledon or
succinturiate lobe
-
-
Retained blood clots
Lacerations of the cervix,
vagina or perinium
Extensions, lacerations at
caesarean section
Uterine rupture
-
Uterine inversion
-
Pre – existing states
Hemophilia A
Von willebrand’s disease
Acquired in pregnancy
ITP
Thrombocytopenia with
pre – eclampsia
DIC
Pre – eclampsia
Dead fetus in utero
Severe infection
Abruption
Amniotic fluid embolus
Therapeutic anti coagulation
-
Abnormalities of
coagulation (thrombin)
-
28 Clinical risk factors
- Polyhydromnios
- Multiple gestation
- Macrosomia
- Rapid Labour
- Prolonged labour
- High parity
- Fever
- Prolonged ROM
- Fibroid uterus
- Placenta previa
- Uterine abnormalities
- Incomplete placenta at
delivery
- Previous uterine
surgery
- High parity
- Abnormal placenta on
US
- Atonic uterus
- Precipitous delivery
- Operative delivery
- Malposition
- Deep engagement
- Previous uterine
surgery
- High parity
- Fundal Placenta
- H/O hereditary
coagulation
- H/O of liver diasese
- Bruising
- Elevated BP
- Fetal demise
- Fever, WBC
- Antepartum
hemorrhage
- Sudden collapse
-
H/O blood clot
Bleeding will occur, if for some time the uterus is not able to contract
well enough to arrest the bleeding at the placental site. Retained products of
conception or blood clots, or genital tract trauma may cause large blood losses
postpartum, especially if not promptly identified.
29 CESAREAN SECTION
Cesarean delivery is one of the most commonly performed operations
today. As medical science and especially obstetrics has evolved over the recent
years, there has been a parallel and steady increase in the rate of cesarean
births.
From times when childbirth was an event not necessitating medical
attention to the present times when concerns are voiced about high cesarean
delivery rates, obstetrics has for sure, traveled a long way.
SURGICAL ANATOMY FOR CESAREAN DELIVERY :
THE ABDOMINAL WALL :
Cesarean delivery is defined as the birth of the fetus through an incision
in the abdominal wall and uterine wall. Knowledge of the layered structure of
the abdominal wall permits the surgeon to enter the abdominal cavity during
cesarean delivery with maximum efficiency and safety. The summary of the
abdominal wall layers is provided in following box.
Skin
Subcutaneous layer
Camper’s fascia
Scarpa’s fascia
Musculo-aponeurotic layer
Rectus sheath
Rectus abdominis muscle
External oblique muscle
Internal oblique muscle
Transverse abdominal muscle
Transversalis fascia
Peritoneum
30 As the incision for the caesarean section is made, the above layers are
incised.
Skin :
Blood supply :
The skin near the midline is supplied by the branches of the superior
epigastric artery (branch of the internal thoracic artery), the inferior epigastric
artery (branch of the external iliac artery) and the superficial epigastric artery,
which is a branch of the femoral artery. The superficial arteries accompany the
cutaneous nerves.
Those that accompany the lateral cutaneous nerves are
branches of the posterior intercostal arteries, while those that travel with the
anterior cutaneous nerves are derived from the superior and inferior epigastric
vessels. The superficial inferior epigastric vessels run a diagonal course in the
subcutaneous tissue from the femoral vessels toward the umbilicus, beginning
as a single artery which branches extensively as it nears the umbilicus. The
skin of the flanks is supplied by branches from the intercostals, lumbar and
deep circumflex iliac arteries.
The venous blood is collected by a network of veins that radiate from
the umbilicus The network above the umbilicus drains via the lateral thoracic
vein & the axillary vein into the superior vena cava and below the umbilicus
via the superficial epigastric & great saphenous veins into the femoral vein, and
finally into the inferior vena cava. A few small veins, the paraumbilical veins,
connect the network through the umbilicus and along the ligamentum teres to
the portal vein.
31 Fig. 2 : Innerv ation and blood sup
pply of ant erior abdoominal wa
all.
Fig. 3 : Venous drrainage off anterior abdomina
a
l wall.
32
Blood supply of the abdominal wall :
The main arterial supply of the abdominal wall consists of the superior
epigastric, musculophrenic, deep circumflex iliac and Inferior epigastric
vessels.
The medial
part of the
abdominal wall receives blood from the
epigastric arteries, while the musculophrenic and deep circumflex iliac arteries
supply the lateral wall. The lateral wall is also supplied by the lower intercostal
and lumbar arteries (T8 toT12 and LI). This freely anastomosing vascular
system provides one continuous arterial and venous channel on both sides of
the anterior abdominal wall, extending from the subclavian vessels cephalad
to the external iliac vessels caudal. The linea alba is relatively bloodless. The
limited vascular supply in this area of fascial fusion can impair wound healing
when lower midline incisions are used. Thus, a secure closure is mandatory in
such incisions.
The Superior epigastric artery, one of the terminal branches of the
internal thoracic artery, enters the upper part of the rectus sheath. The artery
descends behind the rectus muscle, supplying the upper central part of the
anterior abdominal wall and anastomoses with the inferior epigastric artery.
The inferior epigastric artery is a branch of the external iliac artery just
above the inguinal ligament. It runs upward and medially along the medial side
of the deep inguinal ring. It pierces the fascia transversalis to enter the rectus
sheath anterior to the arcuate line. It ascends behind the rectus muscle,
supplying the lower central part of the anterior abdominal wall and
anastomoses with the superior epigastric artery.
33 The deep circumflex iliac artery is a branch of the external iliac artery
just above the inguinal ligament. It runs upward and laterally towards the
antero-superior iliac spine and then continues along the iliac crest. It supplies
the lower lateral part of the abdominal wall. The lower two posterior intercostal
arteries, branches of the descending thoracic aorta and 4 lumbar arteries,
branches of the abdominal aorta, pass forward between the muscle layers and
supply the lateral part of the abdominal wall.
The epigastric vessels are subject to injury, particularly when a muscle
splitting incision is used. Also, the deep circumflex or musculophrenic vessels
can be injured when an extraperitoneal approach is chosen:
The venous blood from the skin is connected in to a network of veins
that radiate from the umbilicus. The network drains above into the axillary vein
via the lateral thoracic vein and below into the femoral vein via the superficial
epigastric & great saphenous veins. A few small veins, the paraumbilical veins,
connect the network through the umbilicus and along the ligamentum teres to
the portal vein. They form a clinically important porto-systemic venous
anastomosis.
The superior epigastric, inferior epigastric, and deep circumflex iliac
veins follow the arteries of the same name and drain into the internal thoracic
and external iliac veins. The posterior intercostal veins drains into the azygous
veins and the lumbar veins drain into the inferior vena cava.
34 Blood supply of the uterus:
The uterine artery is the predominant vessel supplying the uterus. There
are two uterine arteries, one arising on either side as a branch of the anterior
division of the internal iliac artery. It runs medially towards the cervix, crosses
the ureter above the lateral vaginal fornix and 2 cm lateral to cervix, ascends
upwards along the lateral uterine wall between the two leaves of the broad
ligament and then underneath the fallopian tube anastomoses with the ovarian
artery. The uterine vessels anastomose with each other extensively. Each
uterine artery gives rise to anterior and posterior arcuate branches along the
length of the uterus. These pass transversely into the uterine myometrium
giving off radial branches before anastomosing with their counterpart. The
radial branches, before reaching the endometrium, supply a basal branch to the
basal zone of decidua and enter into the decidua as the tortuous spiral arteries.
There is marked spiraling of the uterine arteries that reaches its
maximum at 20 weeks. Later, they become straight and engorged, with the
blood flow increasing from 50 ml / min to 450 - 650 ml / min.
The uterine veins, which too become engorge during pregnancy, run
along with the arteries and drain in to the internal iliac veins.
The ovarian artery arises from the abdominal aorta just below the renal
artery. It descends along the retroperitoneal space along the posterior
abdominal wall, crossing the ureter near its origin from the renal pelvis, and
enters the suspensory ligament of the ovary.
It courses underneath the
fallopian tube before anastomosing with the uterine artery.
35 The ovarian vein, arising from the pampiniform plexus at the ovarian
hilum courses along with the ovarian arteries and drains into the inferior vena
cava on the right side and in to the left renal vein on the left side.
Fig. 4 : The blood supply of the uterus and its adnexa
The blood loss during caesarean section could be because of inferior
epigastric artery, injury or extension of the uterine artery.
It could also be
because of upper uterine segment incision or manual removal of placenta etc.
The use of tranexemic acid decreases the blood loss by 30%.
Tranexemic acid acts by inhibiting the plasminogen activator and there
by the inhibiting the fibrin degradation.
36 Fig. 5 : Cesarean
C
s ection dell ivery
37
Fig. 6 : Fibrinolytic system
38 Fig. 7 : Tranexamic acid injection
39 Methodology
METHODOLOGY
Participant and study design:The main source of data for the study are patients form the teaching
hospital attached to J.J.M. Medical College, Namely –
•
Bapuji Hospital, Davangere.
•
Chigateri General Hospital, Davangere.
•
Women and Children Hospital, Davangere.
100 patients admitted to the above mentioned hospitals during the study
period of 2 years from November 2010 to November 2012 are included in the
study.
Inclusion criteria :
•
Term primipara with a singleton delivered by CS
•
Regular perinatal care
•
Adherence to research regulations
•
Informed consent obtained.
Exclusion criteria :
•
Severe medical and surgical complications including the heart, liver and
kidney, brain disease and blood disorders.
•
Allergy to tranexamic acid.
•
History of thromboembolic disorders.
•
Abnormal placenta : such as placenta previa, placenta abruption,
placental adhesions caused by repeated artificial abortions.
•
Severe pregnancy complications such as severe pre-eclampsia.
40 •
Multiple pregnancies, macrosomia, poly hydromnios
•
Complication with myoma.
Study group :
Preparation of tranexamic acid injection solution : 1 gm/10ml
tranexamic acid diluted with 20ml of 5% glucose.
Administration :
10 minutes before incision, tranexamic acid 1gm IV slowly infused
(over 5 min). After delivery of the neonate, oxytocin 10 units IV drip and 20
units into the intra uterine wall were administered simultaneously.
Control group :
No tranexamic acid was given. Oxytocin was administered as in the
study group.
CLINICAL OBSERVATIONS AND LABORATORY EXAMINATIONS:
Clinical observations :
1. Vital signs : Heart rate (HR) : Respiratory rate (RR), Blood pressure
(BP), were checked immediately after placental delivery and 1 and 2
hour after birth respectively.
2. The extent of postpartum hemorrhaging : The blood was measured by
weigh and volume during two periods following placental delivery to the
end of surgery and from the end of the operation to 2 hours after birth.
3. Uterine contractility and placental separation.
41 4. Neonatal manifestations.
5. Side effects caused by tranexamic acid.
Laboratory examinations :
1. Complete blood count (CBC) and urine analysis before delivery and on
the third day after delivery.
2. Liver and renal function test were performed. 1 day before delivery and
the third day after birth.
3. Prothrombin time and activity were tested in the two group before
delivery and the third day after birth.
BLOOD COLLECTION AND CALCULATION OF THE QUANTITY OF
BLOOD:
Blood collection :
Blood will be collected via suction container, soaked gauge pads and
operation table sheets can be weighted. Blood measurements can be obtained
post partum during two separate periods from placental delivery to 2 hours post
partum.
The study shall ignore estimates of amniotic fluid and bleeding that
occurred prior to placental delivery.
CALCULATION OF QUANTITY OF BLOOD :
The quantity of blood = (weight of used materials + unused material –
weight of all materials prior to surgery)
/ 1.05, plus the volume included in
the suction container after placental delivery.
42 Evaluation of the efficacy and safety of tranexamic acid in cesarean
section.
1) Efficacy
a. The quantity of blood postpartum
b. The incidence of postpartum hemorrhage
2) Safety
a. Vital signs
b. General and local reactions caused by tranexamic acid
c. Laboratory findings.
RESARCH HYPOTHESIS :
Research hypothesis is that tranexamic acid given prior to LSCS,
decreases blood loss during and after LSCS. No major adverse effects noted.
SAMPLE SIZE
All cases 100 in each group with inclusion and exclusion criteria are
selected during the period of October 2010 to October 2012 (time bound study)
Number of cases:
In study group=100
In control group=100
TOTAL = 200
Alternative cases were included in each group, which were admitted to
C.G. Hospital, Bapuji Hospital and WCH Hospital, attached to J.J.M. Medical
College, Davangere.
43 STATISTCAL ANALYSIS:
1.
Arithmetic mean = Sum of all the values = ΣX
No. of values
n
2. Standard deviation, SD =
∑ ( X − X )2
n −1
4. Student’s unpaired t test
T=
Difference of means
S.E of difference of means
5. Paired t test
T= mean of paired differences
S.E of paired differences
Fisher’s exact test
Cases
Group 1
Group 2
Total
Category I
A
B
A+B
Category II
C
D
C+D
A+C
B+D
N=A+B+C+D
Fisher’s test = (A+B)! (C+D)! (A+C)! (B+D)!
N! A! B! C! D!
44 Results
RESULTS
This is a prospective randomised case control study commencing from
October 2010 to October 2012. Two hundred pregnant women undergoing
LSCS in C.G. Hospital, Bapuji Hospital and WCH Hospital, attached to J.J.M.
Medical College, Davangere, were included in this study.
100 women comprised study group – subject who received tranexamic
acid, & 100 women comprised control group – subject who did not received
tranexamic acid.
Table 1 : Distribution based on patient characteristics in both groups
Study group
(Mean ± SD )
n = 100
Control group
(Mean ± SD)
n = 100
‘Z’ test
P Value
Age (years)
23.62 ± 3.429
24.5 ± 3.982
Z= 1.19
P= 0.239 NS
Height (cm.)
152.56 ± 5.75
153.2 ± 6.0
Z= 0.54
P= 0.588 NS
Weight (kg.)
52.54 ± 7.86
53.5 ± 7.45
Z= 0.63
P= 0.532 NS
Table 1 shows that possible confounding variables like age, height,
weight are matched effectively in both the groups.
Mean age was 23.62 yrs in study group & 24.5 yrs in the control group
(P=0.239). The difference in age of subjects of both the groups was not
statistically significant.
Mean height was 152.56 cms in study group & 153.2 cms in the control
group (P=0.588). The difference in height of subjects of both the groups was
not statistically significant.
45 Me an weight was 52.544 kgs in sttudy groupp & 53.5 kkgs in the control
group (P= 0.532). Thhe differencce in weig
ght of subjeects of botth the grou
ups was
not statistiically signiificant.
Table 2 : Distributtion of cases accordiing to age group
Age (Y
Years)
Casees
Co
ontrols
Total
%
199-24
75
68
143
71
1.5
25 -29
20
31
51
25
5.5
300-34
4
0
4
2
35 -39
1
1
2
1
Tootal
100
100
200
10
00
M ean
23.399
23.18
2
S
SD
3.000
2.82
P* Va lue, sig
0.61 NS
* Student'ss unpaired t test
Tabble 2 show s distributiion of casees accordinng to age ggroup. Maj ority of
the patientts in both groups
g
wer e between 19-24 yearrs of age.
No.of cases
Fig. 1 : Bar
B diagram
m showingg distributtion of casees accordiing to age group
80
0
70
0
60
0
50
0
40
0
30
0
20
0
10
0
0
75
6
68
31
Cases
20
0
Control
4
19‐24
4
25‐‐29
30‐34
Age in yearrs
46
0
1
1
35‐39
Table 3 : Distributtion with respect
r
to indication
i
s of LSCS
S in both groups
g
Indicatioon of LSCS
S
Studyy group
(No. of
o cases)
Control group
(No. of cases)
c
Primi with
w breech
8
5
Fetal distress
58
61
Obli que lie
3
1
Transvverse lie
1
1
Ceephalopelviic dispropoortion
12
9
Low
w BPP
6
6
Failure to
t progresss
7
8
Fail innduction
3
4
Precious pregnancyy
3
Chi-squaree (X²)= 4.7777 P= 0.57727 Statisstically nott significannt.
5
Tabble 3 show s distribut ion accord
ding to indiication of LSCS in both
b
the
groups. Thhere was noo statisticaal significan
nce in indiication of L
LSCS betw
ween the
two groupps. The indication of LSCS
S can haave baringg on amo
ount of
intraoperattive blood loss. The fact that these
t
weree matched adequately
y in the
study grouup removess the effect of these co
onfoundingg variabless.
Graph-2 : Distributtion with respect
r
to indication
n s of LSC S in both groups
g
No.of cases
80
0
Study group
60
0
Control ggroup
40
0
20
0
0
47
Table 4 : Effect of tranexami
t
ic acid: Co
omparison of blood lloss from time
t
of
placen
ntal deliveery to com
mpletion off skin closu
ure
C
Cases
Controls
Blood Looss
(ml)
Meann
SD
Mean
SD
Mean
Differencce
P* Vaalue, sig
Placentaal
delivery to
t
end of C S
316.900
73.96
397.00
96.36
80.1
P<0.0
001 HS
Tabble 4 show
ws mean blood
b
losss from tim
me of placcental deliv
very to
completionn of skin closure
c
wa s 316 ml in the studyy group & it was 39 7 ml in
the controol group (P
P= 0.001),, suggestin
ng that theere was sttatistically highly
significantt difference in bloodd loss in bo
oth the grooups. Patieents who received
tranexamicc acid hadd 80 ml lesss blood lo
oss than p atients whho didn’t received
tranexamicc acid.
Graph‐3 : Place
ental de
elivery tto end o
of CS
400.0
00
350.0
00
300.0
00
250.0
00
200.0
00
150.0
00
100.0
00
50.0
00
0.0
00
Cases
Controls
48
Table 5 : Effectt of tranexxamic acid
d: Comparrison of bloood loss frrom
comp
pletion of skin
s
closurre to 2 hrs postpartu
um
C
Cases
Blood Looss
(ml)
Controls
Meann
SD
Mean
SD
Mean
Differencce
P* Vaalue, sig
End of CS
S to
2 hrs
45.800
postpartuum
8.55
79.70
17.14
33.9
P<0.0
001 HS
Tabble 5 reveeals mean blood loss from tiime of coompletion of skin
closure to 2 hours poostpartum was 45.80 ml in the study grouup & it waas 79.70
ml in the control group
g
(P= 0.001), su
uggesting that there was statiistically
highly siggnificant diifference in
i blood lo
oss in bothh the grouups. Patien
nts who
received trranexamic acid had 33.9
3
ml lesss blood looss than paatients who
o didn’t
received trranexamic acid.
Graph‐4
4 : End of CS to
o 2 hrs p
postparttum
80.00
70.00
60.00
50.00
40.00
30.00
20.00
10.00
0.00
Cases
Contro
ols
49
Tablle 6 : Tota
al blood lo ss
C
Cases
Controls
Blood Looss
(ml)
Meann
SD
Total
362.700
77.50
Mean
SD
Mean
Differencce
P* Vaalue, sig
114
P<0.0
001 HS
476.70 105.90
Tabble – 6 sh ows mean blood losss from pl acental de livery to 2 hours
postpartum
m was 3622.70 ml in the study
y group annd it was 476.70 mll in the
control group (p<00.001) su ggesting that theree was staatistically highly
oth the grooups. Pate ints who r eceived
significantt differencee in blood loss in bo
tranexamicc acid had 114 ml leess blood loss
l
than patients
p
whho didn’t received
tranexamicc acid.
Graph‐5 : Total blood loss
500.00
0
450.00
0
400.00
0
350.00
0
300.00
0
250.00
0
200.00
0
150.00
0
100.00
0
50.00
0
0.00
0
Cases
Conttrols
50
mic acid: Compariso
C
on of incid
dence of Pa
atient
Table 7 : Effect off tranexam
with
h Blood looss ≥ 500 ml
m in both the group s
PPH
Cases
Control s
Presentt
2
7
Absentt
98
93
Total
100
100
P=0.085 NS
N
Fisher's exxact test
Tabble 7 show s incidencee of blood loss ≥ 5000 ml in botth the grou
ups. The
difference was foundd to be statiistically no
ot significaant. (P= 0.0085).
Grap
ph‐6 : Efffect of tranexaamic acid: Comparison off inciden
nce of P
Patient w
with Blood loss ≥ 5
500 ml in both tthe grou
ups 100%
Ab
bsent
80%
60%
Preesent
98
9
93
2
7
40%
20%
0%
Cases
Contro
ols
51
Table 8 : Comparison of duration of surgery between the two groups
Duration
(min.)
Study
Control
Mean
P value
43.84 ± 6.1
42.22 ± 6.58
1.28
P = 0.205 NS
Table 8 shows mean duration of surgery, which was 43.84 min in the
study group & 42.22 min in the control group. There was no statistical
difference in the duration of surgery between the two groups. (P= 0.167).
Operating time can affect the amount of blood loss, but it was not a
confounding variable in our study.
52 Table – 9 : The diffeerence in Hb%
H
posttoperative - both in ccases and control
groups
Controls
Cases
Hb%
%
M
Mean
S
SD
Meean
SD
D
Meaan
Differren
ce
P* Value,
V
sig
Before Deelivery
10.84
0
0.75
11..04
0.899
0.2004
0.0
08 NS
After De livery
9.62
0
0.78
9. 11
1.633
0.5111
0.0
005 S
Differeence
1.22
0
0.68
1.9
93
1.344
0.7115
P<
<0.001
HS
* Student'ss unpaired t test
Tabble – 9 shoows fall in Hb% is more in patiients – not given tran
nexamic
acid. Diffeerence in Hb
H in the caases 1.22 gm%,
g
diffeerence in H
Hb in contro
ol cases
1.93 gm% . mean diffference is 0.715 gm%
% which is highly siggnificant, P-0.001.
12.00
Graaph‐7 : The diffference in Hb%
% postope
erative ‐ both iin casess and control groups
10.00
Caases
8.00
Co
ontrols
6.00
4.00
2.00
0.00
Before Deelivery
After Delive
ery
53
Difference
Table 100: Vital siggns at the time of pllacental deelivery in b
both the groups
Vital signs
s
Study
Co
ontrol
Mean
P value
v
Heart ratee (bpm)
86.14 ± 7.225
84.81 ± 8.35
0.86
P = 0.394
NS
N
Respiratoory rate
(breath/min)
19.38 ± 2.229
19.94
4 ± 2.14
1.26
P = 0.21
0
NS
Systoli c BP
(mmH
Hg)
1
121.08
± 100.1
119.8
81 ± 9.47
0.65
P = 0.514
NS
N
Diastoliic BP
(mmH
Hg)
7
77.08
± 7.004
76.88 ± 7.61
0.14
P = 0.892
NS
N
Tabble 10 show
ws mean heeart rate, reespiratory rate, systo lic blood pressure
p
& diastoliic blood p ressure at the time of placenttal deliveryy in the study
s
&
control grooup. There was no staatistically significantt differencee in the vital signs
at the timee of placenttal deliveryy in both th
he groups.
Graaph‐8 : V
Vital signs at th
he time o
of place
ental de
elivery in both tthe grou
ups
140
0
Mean average
120
0
100
0
Study
80
0
Control
60
0
40
0
20
0
0
Heart raate
Respiiratory raate
Syystolic BP
54
Diastolic BP
T
Table
11: Vital
V
signss 1 hr afterr surgery in both th e groups
Vital signs
s
Study
Co
ontrol
Mean
P value
v
Heart ratee (bpm)
86.14 ± 7.005
82.18 ± 8.92
2.46
P = 0.066
NS
N
Respiratoory rate
(breath/min)
19.6 ± 2.225
19.98 ± 2.49
0.8
P = 0.426
NS
N
Systoli c BP
(mmH
Hg)
1
128.24
± 111.5
124.4
44 ± 8.75
1.32
P = 0.065
NS
N
Diastoliic BP
(mmH
Hg)
80.48 ± 6.777
77.44
4 ± 5.41
1.36
P = 0.08
0
NS
Tabble 11 show
ws mean heeart rate, reespiratory rate, systo lic blood pressure
p
& diastolicc blood preessure at 1 hour after delivery inn the studyy & controll group.
There was no statistiically signiificant diffference in t he vital siggns at 1 ho
our after
delivery inn both the groups.
g
Graph‐‐9 : Vitaal signs 1
1 hr afte
er surge
ery in bo
oth the groups
140
0
Mean average
120
0
100
0
Study
80
0
Control
60
0
40
0
20
0
0
Heart raate
Respiiratory raate
Syystolic BP
55
Diastolic BP
T
Table
12 : Vital
V
signss 2 hr afterr surgery in both th e groups
Co
ontrol
Mean
P va
alue
7
± 7.555
Heart ratee (bpm) 79.96
82.16
6 ± 7.08
0.36
P = 0.0
094 NS
Respiratoory rate
(breath/min)
19.44 ± 2.557
19.58
8 ± 2.75
0.26
P = 0.7
798 NS
Systoli c BP
(mmH
Hg)
127.16 ± 12
1
119.7
72 ± 11.5
0.465
P = 0.6
647 NS
Diastoliic BP
(mmH
Hg)
81.04 ± 6.112
78.28
8 ± 5.39
1.39
P = 0.1
101 NS
Vital signs
s
Study
Tabble 12 show
ws mean heeart rate, reespiratory rate, systo lic blood pressure
p
& diastolicc blood preessure at 2 hour after delivery inn the studyy & controll group.
There was no statistiically signiificant diffference in t he vital siggns at 2 ho
our after
delivery inn both the groups.
g
Graph‐10 : Vitaal signs 2 hr aftter surgery in bo
oth the groups
140
0
Mean average
120
0
100
0
Study
80
0
Control
60
0
40
0
20
0
0
Heart raate
Respiiratory raate
Syystolic BP
56
Diastolic BP
T
Table
13 : Comparisson of apg
gar score in
n both the groups
Apgar sccore
Study
Conttrol
Mean
P v alue
1 min
n
8. 88 ± 1.19
8.64 ± 1.34
0.95
P = 0.3
345 NS
5 min
n
9.44 ± 0.639
9.22 ± 0.79
1.25
P = 0.2
213 NS
Tabble 13 reve als mean Apgar
A
scoree at 1 & 5 min in new
wborns of subjects
s
in both thee groups. Study
S
groupp had mean
n Apgar sc ore of 8.888 at 1min & 9.4 at
5 min, whiile newborrns born to subjects in
n control group
g
had m
mean Apgaar score
of 8.64 att 1 min & 9.22 at 5 min. There
T
was no statisttically sign
nificant
difference in Apgar score in booth the gro
oups. (P= 0.345
0
at 1 min & 0.2
213 at 5
min). Thu s, tranexam
mic acid has
h no sign
nificant di fference inn relation to fetal
outcome.
Graph‐‐11 : Compariso
on of ap
pgar sco
ore in bo
oth the groups
9.4
Mean average
9.2
Study
9
Control
8.8
8.6
8.4
8.2
1 min
5 min
57
Table 14: Comparison of adverse drug reaction in both the groups
Study
Control
Mean
P value
Nausea
16
13
0.66
P = 0.508 NS
Vomiting
09
08
0.08
P = 1.135 NS
Diarrhoea
01
00
1.01
P = 0.312 NS
Signs of
thrombosis
00
00
Table 14 shows adverse drug reactions due to use of tranexamic acid.
Nausea, vomiting & diarrhea occurred in 16, 9, 1 cases respectively in the
study group & 13, 8, 0 cases respectively in the control group. None of the
subjects had any evidence of thrombosis.
The incidence of the side effects like nausea, vomiting, & diarrhea were
not increased in the study group as compared to the control group suggesting
that the use of tranexamic acid had no significant adverse drug reaction. In
addition there was no increase in incidence of thrombosis in study group.
The fear that by locally & hasten hemostasis, tranexamic acid may also
increase susceptibility of pregnant mother (hypercoagulable) to thrombosis.
This fear has proved to be misplaced in the present study.
58 Graph
h‐12 : Co
omparisson of adverse d
drug reaction in botth the groups
16
14
Mean average
12
10
Study
Control
8
6
4
2
0
Nauseaa
Vom
miting
D
Diarrhoea
59
Signs of thrombosis
Discussion
DISCUSSION
Tranexamic acid exerts its antifibrinolytic effect by blocking the lysine
binding locus of the plasminogen & plasmin molecules, thereby preventing the
binding of plasminogen & plasmin to the fibrin substrate. Tranexamic acid also
inhibits conversion of plasminogen to plasmin by plasminogen activators. It has
been used in the treatment of bleeding for many years. 3,4
During placental delivery, fibrinogen & fibrin are rapidly degraded,
whereas plasminogen activators & fibrin degradation products (FDP) increase
due to activation of fibrinolytic system. This activation can last up to 6-10 hrs
postpartum, causing more bleeding. It was because of this activation of
fibrinolytic system that we decided to use tranexamic acid in this trial.
Our study showed that tranexamic acid significantly reduces bleeding
from time of placental delivery to 2 hrs postpartum in LSCS. Results show that
study group patients had mean blood loss of 362.70ml ± 110.3 as standard
deviation, while control group patients had mean blood loss of 476.70ml ±
88.552 as standard deviation. Thus, there is reduction in blood loss by about
30% & was found to be statistically highly significant (p value= 0.001). There
was reduction in blood loss in both the parameters, i.e. from time of placental
delivery to completion of skin closure & from completion of skin closure to 2
hrs postpartum. Tranexamic acid also reduced the incidence of postpartum
hemmorhage (patients with blood loss ≥ 500 ml ) in the study group as
compared to control group. In my study 2 cases seen in study group and 7 cases
in control group which is P-0.085 which insignificant.
But other studies have
shown significant decrease in PPH in patients who received tranexamic acid.
60 Similar study carried out by Ming-ying Gai, Lian-fang Wu & coworkers
(28) in China showed that tranexamic acid significantly reduces bleeding from
the time of placental delivery to 2 hrs postpartum. The study group showed
total blood loss reduction by 30% as compared to control group. Tranexamic
acid also reduced the incidence of postpartum hemmorhage by 25.7% in the
study group (22 cases Vs 35 cases in the study & controlled group respectively)
(P value was 0.029). These results correlated well with our study.
Zheng SR, Yang HX, et al 81 showed similar results. Tranexamic acid
significantly reduced postpartum blood loss after vaginal delivery. The
occurrence of postpartum hemmorhage was 6.4% in study group as compared
to 25.3% in control group, which was statistically significant. There were no
significant adverse effects. Therefore, tranexamic acid is efficient & safe in
reducing postpartum hemmorhage.
Bresnoc K, et al82 evaluated tranexamic acid in postpartum hemmorhage
& showed that tranexamic acid significantly decreased the amount of blood
loss & the incidence of postpartum hemmorhage in subjects with vaginal
delivery to the tune of about 20% as compared to control group. The results
were found similar to that in our study.
Gohel M, et al84 evaluated tranexamic acid in caesarean section. They
showed that showed that tranexamic acid reduces significant blood loss from
the end of LSCS to 2 hours postpartum, 75.71 ml in the study group verses
133.03 ml in the control group (P = .001). It also significantly reduces the
quantity of blood loss from placental delivery to 2 hour postpartum, 372.71 ml
in the study group versus 469.70 ml in the control group ( P = 0.003) . These
results were comparable to our study.
61 Leila Sekhavat; Afsar Tabatabaii et.al87 conducted a prospective
randomised study on 90 primiparas divided into two groups who underwent CS.
Their results showed that tranexamic acid significantly reduced the blood loss
from the end of CS to 2 h postpartum; 28.02 ± 5.53 mL in the tranexamic group
versus 37.12 ± 8.97 mL in the control group (p = 0.000). These results were
comparable to our study.
There was no significant alteration in the vital signs of subjects
following tranexamic acid administration at time of delivery & at 1 hr & 2 hr
postpartum. These findings were similar to findings in studies of Ming-ying
Gai, Lian-fang Wu, et al 28 , Zheng SR, Yang HX, et al 81 , Bresnoc K, et al 82 & M
gohel et al 87 .
The incidence of thrombosis during pregnancy & puerperium is 5-6
times higher than that in the general population. When the anti fibrinolytic drug
tranexamic acid is administered, the increased risk of thrombosis should be
considered, especially in the LSCS postpartum population. In our study, not a
single patient developed signs of thrombosis.
Suanberg & coworkers26 reported 67 cases treated by tranexamic acid
because of abruptio placenta, & thrombosis occurred in none of these cases.
Bekassy Z, Astedt A 83 , included 3014 women including 45 pregnant women &
gave
tranexamic
acid
to
prevent
bleeding
at
conisation
of
cervix,
thromboembolic episodes were absent.
Zheng SR, Yang HX et al 81 . Chinese study of 400 pregnant women with normal
vaginal deliveries who received tranexamic acid during labour; no thrombosis
occurred.
62 Ming-ying Gai, Lian-fang Wu & coworkers 28 in China in their study of
tranexamic acid in LSCS showed no thrombosis in study group. Similar results
were found in study of M gohel et al.
In our study, there was no statistical difference in Apgar score at 1 & 5
minutes of the baby in both the groups. Therefore, tranexamic acid had no
effect on the Apgar score of the baby. Similar results were found in study done
by Ming-ying Gai, Lian-fang Wu 28 & coworkers in China & Zheng SR, Yang
HX et al 81 .
The side effects of tranexamic acid as nausea, vomiting & diarrhea were
not statistically significant in both the groups in our study. These results were
similar with previous studies.
All data demonstrated that tranexamic acid can be used safely without
increasing the occurrence of thrombosis, but still need more cases to be
observed for the occurrence of thrombosis.
63 Conclusion
CONCLUSION
1) Tranexamic acid significantly reduced the amount of blood loss during
& after the lower segment cesarean section.
2) Its use was not associated with any adverse drug reaction like nausea,
vomiting, diarrhea or thrombosis. Fetal outcome as evaluated by apgar
score was not adversely affected by use of tranexamic acid.
3) Tranexamic acid can be used safely in subjects with lower cesarean
section.
64 Summary
SUMMARY
•
The possible confounding factors like age, height, weight & gravidity
were comparable in both the groups.
•
Distribution with respect to indication of LSCS like fetal distress,
cephalopelvic disproportion, abnormal presentation, previous LSCS &
arrest of descent was comparable in both the groups.
•
Study group showed marked decrease in the amount of blood loss from
time of placental delivery to 2 hours postpartum as compared to the
control group (around 110 ml)
•
Study group showed significant decrease in blood loss from time of
delivery to completion of skin closure as compared to control group
(around 80 ml)
•
Study group showed marked decrease in blood loss as compared to
controls from time of completion of skin closure to 2 hr postpartum
(around 33 ml).
•
There is significant difference in the postoperative Hb, the mean
difference being 0.71 gm%.
•
There was no significant difference in the vital signs of the subjects of
the two groups at the time of placental delivery, 1 & 2 hours after the
surgery.
•
Tranexamic acid had no significant difference in the birth weight &
apgar score of newborns born in both the groups.
65 •
The incidence of adverse effect like nausea, vomiting & diarrhea is not
increased in the study group. In addition, incidence of thrombosis is not
increased with the tranexamic acid in the study group.
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78 Annexures
ANNEXURE – I
PROFORMA
Name
:
Hospital : BH/CGH/WCH
Age
:
I P No
:
DOA
:
Occupation :
Address
:
DOD :
Booked/Un Booked :
Condition of patient
on discharge :
Diagnosis :
PRESENTING COMPLAINTS
Amenorrhea
:
Labor Pains
: Yes/No
Leaking Pervagina
: Yes/No
Bleeding Pervagina
: Yes/No
Appreciates Foetal Movements Well : Yes/No
Antenatal checkup
: Regular/Irregular
Against tetanus
: Immunised/Not
History Suggestive of PET
:
History Suggestive of UTI
:
OBSTETRIC HISTORY
Married Life :
Gravida :
ConsanguinousMarriage:Yes/No
Para:
Living :
HISTORY OF PREVIOUS PREGNANCIES
79 Abortion :
MENSTRUAL HISTORY :
Age of Menarche
Previous Menstrual Cycle
Last Menstrual Period
Expected date of Delivery
Expected date of Delivery
according to Ultrasound
:
:
:
:
:
MEDICAL HISTORY
Tuberculosis :Yes/No
Diabetes
Rheumatic Heart Disease :Yes/No
: Yes/No
Hypertension
: Yes/No
Bronchial Asthma : Yes/No
PAST HISTORY
Blood Transfusion
: Yes/No
Eclampsia
: Yes/No
PET
: Yes/No
FAMILY HISTORY
Tuberculosis
: Yes/No
Diabetes
:Yes/No
Hypertension
: Yes/No
Twin Pregnancy
: Yes/No
Congenital Anomalies : Yes/No
PERSONAL HISTORY
Diet
: Vegetarian/Non-Vegetarian/Mixed
Appetite
: Normal/Decreased
Sleep
: Normal/Disturbed
Bladder Habits
: Frequency-Regular/Increased/Decreased
Bowel Habits
: Regular/Irregular
80 GENERAL PHYSICAL EXAMINATION
Built
:
Nourishment :
Pallor
:
Pulse
:
Height :
BP
:
Weight :
Cyanosis :
Icterus:
Breast :
Thyroid
Oedema :
Lymphadenopathy :
Stature :
:
Spine
Gait
:
:
SYSTEMATIC EXAMINATION
Central Nervous System :
Cardio Vascular System :
Respiratory System
Perabdomen
:
- Height of the Uterus :
- Acting/Relaxed
:
- Lie
:
- Presentation
:
- Position
:
- Head
:
- Foetal Heart Sound :
Vulvovaginal Examination- External Genitalia :
Per Speculum
- Vagina
- Cervix
: pale/Pink/Discharge
: Position- Anterior/Central/Posterior
: Bleeding/Leaking
Per vaginal- Cervix
- Length
:
- Dilatation
:
- Consistency :
- Position
81 :
Vertex - Station
:
Modified Bishop Score
:
Membranes
:
Pelvis assessment
: Adequate/Inadequate
CPD
: Present/Absent
INVESTIGATIONS
Urine
-
Albumin
-
Sugar
-
Microscopy :
:
Blood - Hb%
:
- Blood Grouping and typing :
- HIV
U.S.G
Presentation
-
Amount of liquor Placental
- Site
- Maturity
Cong. Anomalies Estimated foetal weight Average Gestational age
Diagnosis :
Any induction :
Yes / No
Induction delivery interval
:
82 :
:
- Hbs Ag
:
- RBS
:
Indication for caesarean section :
Time of decision taken for caesarean section :
Time of giving tranostat :
Time of incision :
On table findings :
Single / Live / Term - _________ Baby
of weight ______ kg at time __________
Placental weight
: ____________
Liquor : __________________
Any on table or postoperative complications :
After delivery of placenta
:
Dry mop weight (A) __________
After soakage weight (B) ___________
Total blood loss : (B) – (A) _________
Preop Hb% ______________
Calculation of quantity of blood loss :
The quantity of blood = (weight of used materials + unused materials - weight of all
materials prior to surgery) / 1.05, plus the volume included in the suction container
after placental delivery.
Vitals 2 hours after CS
After 48 hours Hb% ___________________ (post op)
83 SAMPLE INFORMED CONSENT FORM
TITLE OF THE TOPIC: “EFFICACY OF TRANEXAMIC ACID IN
DECREASING BLOOD LOSS DURING AND AFTER CESAREAN SECTION : A
RANDOMIZED CASE CONTROLLED PROSPECTIVE STUDY”
PRINCIPAL INVESTIGATOR
:
Dr. Nitam Deka
PG GUIDE NAME
:
Dr A.C. Ramesh, Professor
Co-GUIDE
:
Dr. Bandamma, Professor
PURPOSE OF RESARCH
I have been informed that this study will test the efficacy of tranexamic
acid in reducing blood loss during and after cesarean section. No side effects
were noted in mother as well as in neonate.
PROCEDURE
I understand that I will be assigned a group of patients for LSCS.I will
be examined and a series of questions will be asked by resarcher. My history
and physical finding will be recorded. My results will be evaluated in a
systemic way. I will not be asked for any follow up.
RISK AND DISCOMFORTS
I understand that I may have some discomfort due to IV administration
of tranexamic acid .There are no major risks involved and side effects are
minimal.
84 BENEFITS
I understand that my participation in the study will have direct benefit to
me, it is mainly designed to decreases the blood loss during and after LSCS.
CONFIDENTIALITY
I understand that medical information produced by this study will
become part of hospital record and will be subject to confidentiality record and
privacy regulation of J.J.M. Medical College & Hospital. Information of a
sensitive personal nature will not be a part of the medical record, but will be
stored in the investigators research file and identified only by code number; the
code key connecting name to numbers will be kept in a separate secure
location.
If the data are used for publication in the medical literature or for
teaching purpose no names will be used and other identifiers such as
photographs and audio or video tapes will be used only with my special written
permission. I understand that I may see the photographs and videotapes and
hear the audio tapes before giving this permission.
I understand that the relevant designated authority and industrial sponsor
are permitted to have access to my medical record and to the data produced by
the study for audit purpose. However, they are required to maintain
confidentiality.
REQUEST FOR MORE INFORMATION
I understand that I may ask more questions about the study at any time
and understand that I will be informed of any significant new finding
85 discovered during the course of this study which might influence my continued
participation.
If during the study or later I wish to discuss my participation or
concerns regarding this study with a person not directly involved I am aware
that the other staff members are available to talk with me.
The copy of this consent form will be given to me to keep for careful
reading.
REFUSAL OR WITHDRAWAL OF PARTICIPATION
I understand that my participation is voluntary and that I may refuse to
participate or withdraw consent and discontinue participation in the study at
any time without prejudice to my present or future care in the hospital and also
understand that the researcher may terminate my participation in the study if at
any time she feels the need and explain me the reason to do so and help to
arrange for my further appropriate treatment.
INJURY STATEMENT
I understand that in the unlikely event or any injury due to my
participation in the study will be reported promptly, then medical treatment
will be available to me but no further compensation would be provided by the
hospital. I understand that by my agreement to participate in this study I am not
waiving any of my legal rights.
86 I have explained to Mrs. __________________________________ the
purpose of the research, the procedures required and the possible risks and
benefits to the best of ability.
Investigator:
Date:
I confirm that the researcher has explained to me the purpose of research
the study procedures that I will undergo and the possible risks and discomforts
as well as benefits that I may experience. Alternatives to my participation in
the study have also been discussed. I have read and I understand this consent
form. Therefore, I agree to give my consent to participate as a subject in this
research project.
Participant:
Date:
Guardian:
Date:
87 MASTER CHART
WITH TRANOSTAT Sl No
IP No
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
678402
678602
678531
678635
678798
679079
678799
678804
678783
678847
679204
679237
679141
679302
679525
679523
679476
680012
679303
679403
680377
680588
680598
686547
681108
631368
679592
679933
681471
2236
2254
2174
2272
Hospital Age Parity
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
WCH
WCH
WCH
WCH
23
22
29
25
35
27
26
22
22
22
24
20
34
20
24
22
26
25
24
30
27
27
28
26
25
23
23
25
22
19
22
21
20
Primi
G2A1
Primi
G3A2
G4A2
G5A4
Primi
Primi
Primi
Primi
G3A2
Primi
Primi
Primi
G2A1
G2A1
G2A1
Primi
Primi
G3A2
Primi
G2A1
G2A1
G3A2
Primi
Primi
Primi
G2A1
G2A1
Primi
Primi
Primi
Primi
Indications for caesarean Time of giving tranostat
Time of giving incision
FD
FD
FTP
FD
PP
FI
FD
Primi, Breech
FD
FD
FTP
FD
PP
Oblique lie
Transverse lie
CPD
FD
FD
FD
PP
FD
FD
CPD
FD
Low BPP
CPD
FTD
FI
CPD
FD
FTP
FD
FD
3.45 PM
2.46 PM
2.55 PM
12.22 PM
9.14 AM
2.10 PM
1.48 PM
10.50 AM
10.20 AM
10.20 AM
2.20 Pm
1.50 PM
9.30 AM
4.50 PM
2.20 PM
2:00 PM
10:00 AM
9.10 AM
9.48 AM
4.10 PM
9.20 AM
9.50 AM
10.48 PM
9.20 AM
10.18 AM
10.40 AM
9.30 AM
10.18 AM
9.50 AM
10:00 AM
8:00 PM
6:00 AM
8:00 AM
3.58 PM
2.58 PM
3.06 PM
12.32 AM
9.26 AM
2.20 PM
2:00 PM
11 AM
10.30 AM
10.32 AM
2.30 PM
2:00 PM
9.40 AM
5:00 PM
2.32 PM
2.10 PM
10.10 AM
9.22 AM
10 AM
4.21 PM
9.30 AM
10 AM
11.00 PM
9.30 AM
10.30 AM
10.50 AM
9.30 AM
10.29 AM
10.00 AM
10.12 AM
8.12 PM
6.10 AM
8.10 AM
Vitals BP After Before After Delivery
Delivery Delivery
HB% (gm/dl)
Blood loss (ml)
Before Placental End of CS to 24Hrs Fall in Delivery
Before delivery to After Hb% 2 hrs Total Delivery
SBP (mm of SBP (mm of DBP (mm DBP (mm end of CS postpartum
delivery (gm/dl)
Hg)
Hg)
of Hg)
of Hg)
300
340
340
320
300
300
320
340
300
280
300
340
340
300
800
300
320
280
300
280
280
250
300
300
250
300
280
300
280
320
300
320
300
40
40
50
80
60
50
40
40
40
40
40
40
40
40
80
40
40
40
50
50
50
50
50
40
40
40
40
40
50
40
40
40
40
340
380
390
400
360
350
360
380
340
320
340
380
380
340
880
340
360
320
350
330
330
300
350
340
290
340
320
340
330
360
340
360
340
10.4
11
10
12.6
11
12.6
10
11
10.6
10.6
9.8
10.2
10.6
9.8
11
10
11
10.3
11
10.8
10
9.8
10
9.6
10.4
11
10.6
11
12
9.8
10.4
11.4
11
9.6
10
8.8
11.4
10
11.8
8.8
9.6
9.8
9.8
8.6
9
9.4
9
8.2
9
10.2
9.4
10
9.8
9
9
8.8
8.8
9.8
10.2
10
10.2
11
8.8
9.6
9.8
10
0.8
1
1.2
1.2
1
0.8
1.2
1.4
0.8
0.8
1.2
1.2
1.2
0.8
2.8
1
0.8
0.9
1
1
1
0.8
1.2
0.8
0.6
0.8
0.6
0.8
1
1
0.8
1.6
1
120
130
120
130
120
130
120
124
110
110
100
130
116
120
124
120
110
120
100
110
120
130
120
114
120
120
100
130
120
130
120
130
120
120
140
120
140
120
136
120
130
110
120
100
130
124
130
126
124
110
120
110
120
120
136
120
120
120
130
110
140
114
136
120
130
120
80
76
84
90
80
80
80
80
80
70
70
70
84
80
80
76
70
84
70
84
80
76
84
70
76
70
70
80
76
90
80
80
80
80
86
86
96
80
82
80
84
80
82
80
70
86
82
80
80
70
86
85
96
80
90
86
76
76
80
76
88
76
96
80
80
80
Use of Complicatio
Side Effect
Heart Respirat additional ns
rate ory rate Oxytocics
80
82
80
82
80
84
80
86
82
78
80
84
88
80
100
80
82
80
82
80
84
80
86
82
78
80
84
88
80
78
80
84
88
16
18
16
17
19
18
16
18
17
16
16
18
18
17
20
16
18
16
17
19
18
16
18
17
16
16
18
18
17
16
16
18
18
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
+
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
PPH
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
Vomiting
‐
Nausea
‐
‐
Vomiting
‐
Nausea
‐
‐
‐
‐
‐
‐
‐
‐
‐
Nausea
‐
‐
Vomiting
‐
‐
‐
‐
‐
‐
Nausea
‐
‐
Nausea
Sl No
IP No
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
2233
2316
2327
2233
2330
2361
2363
2358
681798
681807
682375
682477
682129
682125
682603
682337
682011
682553
683267
68339
683159
683374
683389
683462
686874
686988
686993
687030
687131
687245
687315
687461
687291
687553
687664
687594
687769
Hospital Age Parity
WCH
WCH
WCH
WCH
WCH
WCH
WCH
WCH
BH
BH
BH
Bh
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
19
23
20
19
20
21
20
20
24
22
19
26
20
24
22
26
30
20
24
21
24
24
23
28
21
23
23
22
21
24
22
22
28
23
24
26
24
Primi
G2A1
Primi
Primi
Primi
G2A1
Primi
Primi
G3A2
Primi
Primi
Primi
Primi
Primi
Primi
Primi
Primi
Primi
Primi
Primi
Primi
Primi
G2A1
Primi
Primi
Primi
Primi
G2A1
Primi
G2A1
Primi
Primi
Primi
Primi
G2A1
Primi
Primi
Indications for caesarean Time of giving tranostat
Time of giving incision
fD
CPD
FD
FD
FD
CPD
CPD
FD
FD
FD
FD
PP
Oblique lie
CPD
FTP
Breech
PP
FD
FD
Breech
FD
FD
CPD
Low BPP
FD
FD
FD
FD
Low BPP
FD
FD
FD
PP
Breech
FTP
FD
FD
8.40 PM
7.50 AM
7.15 AM
9.00 AM
8.30 AM
8.15 PM
9:00 AM
2.10 PM
11.30 PM
9.10 PM
6.20 PM
4:00 PM
1.30 PM
9:00 AM
6:00 PM
9:00 AM
10:00 AM
5:00 AM
12.40 PM
6.20 PM
10:00 AM
6.40 AM
9.20 AM
8.45 AM
3.45 PM
2.46 PM
2.55 PM
12.22 PM
9.14 AM
2.10 PM
1.48 PM
10.50 AM
10.20 AM
10.20 AM
2.20 Pm
1.50 PM
9.30 AM
8.50 PM
8.00 AM
7.25 AM
9.10 AM
8.42 AM
8.25 PM
9.12 AM
2.20 PM
11.40 PM
9.20 PM
6.30 PM
4.10 PM
1.40 PM
9.12 AM
6.10 PM
9.10 AM
10.10 AM
5.10 AM
12.50 PM
6.30 PM
10.12 AM
6.55 AM
9.30 AM
8.55 AM
3.58 PM
2.58 PM
3.06 PM
12.32 AM
9.26 AM
2.20 PM
2:00 PM
11 AM
10.30 AM
10.32 AM
2.30 PM
2:00 PM
9.40 AM
Vitals BP After Before After Delivery
Delivery Delivery
HB% (gm/dl)
Blood loss (ml)
Before Placental End of CS to 24Hrs Fall in Delivery
Before 2 hrs Total delivery to After Hb% Delivery
SBP (mm of SBP (mm of DBP (mm DBP (mm end of CS postpartum
delivery (gm/dl)
Hg)
Hg)
of Hg)
of Hg)
300
800
320
300
250
300
280
300
340
350
280
300
280
300
250
340
300
320
300
360
380
320
280
300
320
300
260
300
320
320
300
340
280
300
320
300
320
40
60
50
40
50
40
50
50
40
50
40
50
40
50
60
40
40
50
50
40
50
40
50
40
50
40
50
50
40
60
40
60
50
40
40
40
50
340
860
370
340
300
340
330
350
380
400
320
350
320
350
310
380
340
370
350
400
430
360
330
340
370
340
310
350
360
380
340
400
330
340
360
340
370
9.6
12
10.6
11.4
9.8
10
11.6
12.4
11
10
12
11.6
9.6
10
11
10.4
10
10.6
11.2
11.4
10.4
10
11
11.4
11
10
11
11.2
11
12.4
11.6
10.2
9.8
9.4
10.4
9.8
10.2
8.8
9.2
10
10.6
9
9
11
11.2
9.6
8.8
11.2
10.8
8.8
9
9.8
9.2
9
9.4
10
10.1
8.8
9
10.2
10.6
9.8
8.8
10.2
10
10
10.8
10.4
8.8
8.4
8.8
9.2
8
9
0.8
2.8
0.6
0.8
0.8
1
0.6
1.2
1.4
1.2
0.8
0.8
0.8
1
1.2
1.2
1
1.2
1.2
1.3
1.6
1
0.8
0.8
1.2
1.2
0.8
1.2
1
1.6
1.2
1.4
1.4
0.6
1.2
1.8
1.2
124
110
110
100
130
116
130
124
100
130
110
120
120
130
120
116
100
120
114
100
124
130
120
120
130
124
110
110
120
130
120
110
130
136
130
120
130
126
110
114
116
136
120
130
120
110
136
116
120
116
130
120
120
110
110
120
100
120
140
114
130
130
130
110
110
132
140
130
110
130
138
132
120
130
80
80
70
70
70
84
84
80
70
70
76
80
84
86
84
80
70
84
70
70
80
80
76
80
80
80
76
80
80
80
84
80
80
80
80
80
80
84
80
82
80
86
88
84
80
76
80
86
80
80
88
90
90
86
76
76
70
80
90
76
86
80
96
80
80
90
94
90
80
80
82
84
80
80
Use of Complicatio
Side Effect
Heart Respirat additional ns
rate ory rate Oxytocics
80
100
80
82
80
82
80
84
80
86
82
78
80
84
88
80
80
82
80
82
80
84
80
86
82
78
80
84
88
80
80
82
80
82
80
84
80
17
20
16
18
16
17
19
18
16
18
17
16
16
18
18
17
16
18
16
17
19
18
16
18
17
16
16
18
18
17
16
18
16
17
19
18
16
‐
+
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
PPH
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
Vomiting
‐
‐
‐
‐
Vomiting
‐
‐
Nausea
‐
‐
‐
‐
Nausea
‐
‐
‐
‐
Vomiting
‐
‐
‐
‐
Nausea
‐
‐
‐
Nausea
‐
‐
‐
Vomiting
‐
Nausea
Sl No
IP No
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
687780
687928
687949
687953
690544
690510
690587
690704
690714
690721
690873
690857
690909
690923
691078
690949
691151
691346
691453
691500
691576
691700
691717
691774
691785
692017
692246
692189
692301
692326
Hospital Age Parity
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
24
20
24
24
22
22
25
21
23
30
25
23
21
25
22
23
24
24
23
24
21
22
19
24
24
21
23
21
23
20
Primi
Primi
G2A1
Primi
Primi
Primi
G2A1
Primi
Primi
Primi
G2A1
Primi
Primi
G2A1
Primi
Primi
Primi
G2A1
Primi
G2A1
Primi
Primi
Primi
Primi
G2A1
Primi
Primi
Primi
Primi
Primi
Indications for caesarean Time of giving tranostat
Time of giving incision
FD
FD
FD
FD
FTP
FD
fD
FD
FD
PP
Low BPP
FD
FD
FD
CPD
FD
FD
CPD
FD
FD
FI
FD
CPD
FD
FD
FD
FD
Breech
FD
Low BPP
4.50 PM
2.20 PM
2:00 PM
10:00 AM
9.10 AM
9.48 AM
4.10 PM
9.20 AM
9.50 AM
10.48 PM
9.20 AM
10.18 AM
10.40 AM
9.30 AM
10.18 AM
9.50 AM
10:00 AM
8:00 PM
6:00 AM
8:00 AM
8.40 PM
7.50 AM
7.15 AM
9.00 AM
8.30 AM
8.15 PM
9:00 AM
2.10 PM
11.30 PM
9.10 PM
5:00 PM
2.32 PM
2.10 PM
10.10 AM
9.22 AM
10 AM
4.21 PM
9.30 AM
10 AM
11.00 PM
9.30 AM
10.30 AM
10.50 AM
9.30 AM
10.29 AM
10.00 AM
10.12 AM
8.12 PM
6.10 AM
8.10 AM
8.50 PM
8.00 AM
7.25 AM
9.10 AM
8.42 AM
8.25 PM
9.12 AM
2.20 PM
11.40 PM
9.20 PM
Vitals BP After Before After Delivery
Delivery Delivery
HB% (gm/dl)
Blood loss (ml)
Before Placental End of CS to 24Hrs Fall in Delivery
Before 2 hrs Total delivery to After Hb% Delivery
SBP (mm of SBP (mm of DBP (mm DBP (mm end of CS postpartum
delivery (gm/dl)
Hg)
Hg)
of Hg)
of Hg)
300
280
300
340
300
340
340
320
300
300
320
340
300
280
300
340
340
300
280
300
320
280
300
300
360
380
320
280
300
320
50
50
50
40
40
40
50
80
60
50
40
40
40
40
40
40
40
40
40
40
40
40
50
50
40
50
40
50
40
50
350
330
350
380
340
380
390
400
360
350
360
380
340
320
340
380
380
340
320
340
360
320
350
350
400
430
360
330
340
370
11.4
10.4
11
10.4
10.4
11
10
12.6
11
12.6
10
11
10.6
10.6
9.8
10.2
10.6
9.8
10
10
11
10.3
11
11.2
11.4
10.4
10
11
11.4
11
10
9.8
9.8
9.2
9.6
10
8.8
11.4
10
11.8
8.8
9.6
9.8
9.8
8.6
9
9.4
9
8.8
9
10.2
9.4
10
10
10.1
8.8
9
10.2
10.6
9.8
1.4
0.6
1.2
1.2
0.8
1
1.2
1.2
1
0.8
1.2
1.4
0.8
0.8
1.2
1.2
1.2
0.8
1.2
1
0.8
0.9
1
1.2
1.3
1.6
1
0.8
0.8
1.2
110
124
100
110
120
120
100
110
120
110
130
126
120
130
130
120
130
100
130
100
114
124
110
116
110
126
120
110
130
110
116
130
110
120
120
120
110
100
126
110
144
130
130
130
136
120
130
110
120
106
116
130
116
120
114
126
120
110
140
110
70
80
60
70
80
70
60
80
84
80
86
76
84
80
84
76
80
70
80
70
70
80
70
80
76
84
80
80
80
84
76
88
70
80
80
70
70
70
90
80
96
80
88
80
86
80
80
82
80
74
76
84
76
86
80
90
80
80
92
90
Use of Complicatio
Side Effect
Heart Respirat additional ns
rate ory rate Oxytocics
86
82
78
80
84
88
80
80
82
80
82
80
84
80
86
82
78
80
84
88
80
80
82
80
82
80
84
80
86
82
18
17
16
16
18
18
17
16
18
16
17
19
18
16
18
17
16
16
18
18
17
16
18
16
17
19
18
16
18
17
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
Nausea
‐
‐
Nausea
‐
Diarrhoea
‐
‐
‐
Nausea
‐
‐
Vomiting
‐
Nausea
‐
‐
‐
Nausea
‐
‐
‐
‐
Nausea
‐
‐
Vomiting
‐
MASTER CHART
WITHOUT TRANOSTAT Blood loss (ml)
Sl No
IP No
Hospital
Age (Yrs)
Parity
Indications for caesarean Time of giving tranostat
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
678436
378503
678740
678151
678549
679481
679559
679604
679361
679361
679760
679760
679881
679999
679903
679972
679604
680038
680381
680972
680543
680666
680727
680957
681324
681306
681453
681816
681460
681777
682043
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
26
26
24
20
20
36
25
27
20
26
25
28
26
20
26
26
24
26
25
21
22
22
26
28
28
24
27
26
26
27
24
Primi
Primi
Primi
Primi
Primi
G2A1
G4A3
Primi
Primi
Primi
Primi
Primi
G2A1
Primi
Primi
G2A1
Primi
Primi
G2A1
Primi
Primi
G3A2
Primi
G2A1
G2A1
Primi
G2A1
Primi
Primi
Primi
Primi
FD
FD
FTP
Primi+Breech
FD
FD
PP
FD
FD
FTP
FD
FD
FD
CPD
FD
FD
FD
Oblique lie
FD
FD
CPD
FD
Transverse lie
FD
FD
FI
FD
FD
CPD
FI
FD
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
Time of End of CS giving Placental to 2 hrs Before incision delivery to Total postpart
Delivery
end of CS
um
3.58 PM
2.58 PM
3.06 PM
12.32 AM
9.26 AM
2.20 PM
2:00 PM
11 AM
10.30 AM
10.32 AM
2.30 PM
2:00 PM
9.40 AM
5:00 PM
2.32 PM
2.10 PM
10.10 AM
9.22 AM
10 AM
4.21 PM
9.30 AM
10 AM
11.00 PM
9.30 AM
10.30 AM
10.50 AM
9.30 AM
10.29 AM
10.00 AM
10.12 AM
8.12 PM
380
350
400
350
380
360
380
340
340
380
400
380
360
800
360
400
400
360
380
350
380
320
380
400
700
400
300
380
600
400
380
80
60
60
80
60
60
80
80
90
80
80
80
80
90
90
80
70
80
80
90
60
80
90
80
120
80
60
80
200
80
70
Vitals BP After Before After Delivery
Delivery
Delivery
HB% (gm/dl)
460
410
460
430
440
420
460
420
430
460
480
460
440
890
450
480
470
440
460
440
440
400
470
480
820
480
360
460
800
480
450
10.6
11
11.8
12
10.6
12
9.8
12
10.8
11
9.8
10
11
10.8
12
11.6
10
9.8
11.8
12.4
10.2
11.4
10.8
11
13.4
11
10
10.6
12.2
11.8
10.8
Before 24Hrs Delivery
Fall in Hb% After (gm/dl)
SBP (mm SBP (mm of DBP (mm DBP (mm delivery of Hg)
Hg)
of Hg)
of Hg)
1.4
10
10
9.8
8.8
10.2
7.8
11
9.4
9.4
8.4
7.8
8.8
8.4
10.6
10
8.4
8
10
10.2
8.4
10
9
9.2
11.1
9.2
9
9.8
10
10.4
9.2
9.2
1
1.8
2.2
1.8
1.8
2
1
1.4
1.6
1.4
2.2
2.2
2.4
1.4
1.6
1.6
1.8
1.8
2.2
1.8
1.4
1.8
1.8
2.3
1.8
1
0.8
2.2
1.4
1.6
120
114
120
100
110
120
130
120
114
120
130
110
120
110
120
110
120
114
134
130
130
130
120
120
120
130
110
120
110
130
130
120
116
126
110
110
130
136
120
120
124
136
110
120
120
114
110
120
124
136
140
130
140
120
124
130
126
110
126
110
136
130
80
80
80
70
80
80
84
80
70
76
86
80
84
84
80
70
80
70
80
84
80
86
80
80
76
80
80
80
80
84
76
80
86
86
76
80
86
90
80
76
80
98
80
86
90
76
70
80
76
86
88
80
94
80
82
84
80
82
80
80
90
76
Use of Heart Respirat additional Complications
rate
ory rate Oxytocics
80
82
80
82
80
84
80
86
82
78
80
84
88
80
100
80
82
80
82
80
84
80
86
82
78
80
84
88
80
78
80
16
18
16
17
19
18
16
18
17
16
16
18
18
17
20
16
18
16
17
19
18
16
18
17
16
16
18
18
17
16
16
‐
‐
+
+
+
-
PPH
PPH
PPH
-
Blood loss (ml)
Sl No
IP No
Hospital
Age (Yrs)
Parity
Indications for caesarean Time of giving tranostat
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
678860
2008
2016
2019
2041
2045
2051
2113
2114
2161
2144
2073
2252
2258
2316
2331
2335
2351
2348
2371
2384
3397
688424
688292
688387
688554
688557
688618
688561
688637
688740
688562
688863
688758
688896
BH
WCH
WCH
WCH
WCH
WCH
WCH
WCH
WCH
WCH
WCH
WCH
WCH
WCH
WCH
WCH
WCH
WCH
WCH
WCH
WCH
WCH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
25
21
22
20
22
21
22
20
22
21
28
21
22
21
22
21
19
28
21
20
22
22
23
24
23
23
22
25
23
21
24
20
23
23
21
Primi
Primi
G2A1
Primi
Primi
Primi
G2A1
Primi
Primi
Primi
G3A2
Primi
Primi
Primi
Primi
Primi
Primi
G3A2
Primi
Primi
Primi
Primi
G2A1
Primi
Primi
Primi
Primi
G3A2
Primi
Primi
Primi
Primi
Primi
G2A1
Primi
DTA
Breech
FD
FD
DTA
FD
FD
FD
CPD
FD
PP
FD
FD
Breech
Oblique lie
FD
FD
PP
FD
FD
FD
Transverse lie
FD
FD
FD
FD
CPD
FD
FD
Breech
FD
FD
FD
FD
FTP
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
Time of End of CS giving Placental to 2 hrs Before incision delivery to Total postpart
Delivery
end of CS
um
6.10 AM
8.10 AM
8.50 PM
8.00 AM
7.25 AM
9.10 AM
8.42 AM
8.25 PM
9.12 AM
2.20 PM
11.40 PM
9.20 PM
6.30 PM
4.10 PM
1.40 PM
9.12 AM
6.10 PM
9.10 AM
10.10 AM
5.10 AM
12.50 PM
6.30 PM
10.12 AM
6.55 AM
9.30 AM
8.55 AM
3.58 PM
2.58 PM
3.06 PM
12.32 AM
9.26 AM
2.20 PM
2:00 PM
11 AM
10.30 AM
400
380
350
400
350
380
360
380
340
340
380
400
380
360
800
360
400
400
360
380
350
380
320
380
400
700
400
300
380
380
400
380
400
380
350
80
80
60
60
80
60
60
80
80
90
80
80
80
80
90
90
80
70
80
80
90
60
80
90
80
120
80
60
80
90
80
70
80
80
60
Vitals BP After Before After Delivery
Delivery
Delivery
HB% (gm/dl)
480
460
410
460
430
440
420
460
420
430
460
480
460
440
890
450
480
470
440
460
440
440
400
470
480
820
480
360
460
470
480
450
480
460
410
10
10.6
11
11.8
12
10.6
12
9.8
12
10.8
11
9.8
10
11
10.8
12
11.6
10
9.8
11.8
12.4
10.2
11.4
10.8
11
13.4
11
10
10.6
10.8
11.8
10.8
10
10.6
11
Before 24Hrs Delivery
Fall in Hb% After (gm/dl)
SBP (mm SBP (mm of DBP (mm DBP (mm delivery of Hg)
Hg)
of Hg)
of Hg)
8.2
1.4
10
10
9.8
8.8
10.2
7.8
11
9.4
9.4
8.4
7.8
8.8
8.4
10.6
10
8.4
8
10
10.2
8.4
10
9
9.2
11.1
9.2
9
9.8
9
10.4
9.2
8.2
1.4
10
1.8
9.2
1
1.8
2.2
1.8
1.8
2
1
1.4
1.6
1.4
2.2
2.2
2.4
1.4
1.6
1.6
1.8
1.8
2.2
1.8
1.4
1.8
1.8
2.3
1.8
1
0.8
1.8
1.4
1.6
1.8
9.2
1
116
120
110
124
110
120
120
124
114
130
130
110
124
120
130
110
120
124
120
100
110
110
134
120
136
120
110
110
134
120
130
130
110
134
100
120
120
110
130
116
126
120
124
120
140
130
120
132
120
140
110
120
130
124
106
110
110
140
126
140
130
110
110
130
126
130
130
110
140
100
84
80
76
70
84
76
80
86
80
80
80
80
88
80
70
80
80
80
76
70
70
80
80
76
82
70
70
80
84
76
84
80
80
82
70
88
80
76
80
90
80
80
82
86
96
80
86
80
80
76
80
80
84
82
76
70
80
90
86
86
76
70
80
88
86
86
80
80
82
70
Use of Heart Respirat additional Complications
rate
ory rate Oxytocics
84
88
80
100
80
82
80
82
80
84
80
86
82
78
80
84
88
80
80
82
80
82
80
84
80
86
82
78
80
84
88
80
80
82
80
18
18
17
20
16
18
16
17
19
18
16
18
17
16
16
18
18
17
16
18
16
17
19
18
16
18
17
16
16
18
18
17
16
18
16
+
+
-
PPH
PPH
-
Blood loss (ml)
Sl No
IP No
Hospital
Age (Yrs)
Parity
Indications for caesarean Time of giving tranostat
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
689129
688905
688931
688933
689130
689271
689254
689032
689043
689046
689245
689171
689153
689288
689442
689314
689305
689402
689420
689576
689482
689386
689705
689715
689610
689629
695531
693658
693650
693681
692367
693381
693402
693785
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
BH
22
22
21
19
28
21
20
22
21
21
23
19
21
23
20
25
23
26
22
25
22
24
19
23
25
25
21
23
25
21
20
28
21
22
Primi
Primi
Primi
Primi
G3A2
Primi
Primi
Primi
Primi
Primi
Primi
Primi
Primi
Primi
Primi
G4A3
Primi
Primi
Primi
Primi
Primi
Primi
Primi
G2A1
Primi
Primi
Primi
G2A1
G3A2
Primi
Primi
Primi
Primi
G2A1
FD
FD
FD
FD
PP
FD
FD
FD
FD
FD
FTP
FD
FD
CPD
FI
PP
DTA
PP
FD
CPD
FD
CPD
FTP
Low BPP
Low BPP
FD
FD
FD
CPD
Breech
FD
PP
FD
FI
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
Time of End of CS giving Placental to 2 hrs Before incision delivery to Total postpart
Delivery
end of CS
um
10.32 AM
2.30 PM
2:00 PM
9.40 AM
5:00 PM
2.32 PM
2.10 PM
10.10 AM
9.22 AM
10 AM
4.21 PM
9.30 AM
10 AM
11.00 PM
9.30 AM
10.30 AM
10.50 AM
9.30 AM
10.29 AM
10.00 AM
10.12 AM
8.12 PM
6.10 AM
8.10 AM
8.50 PM
8.00 AM
7.25 AM
9.10 AM
8.42 AM
8.25 PM
9.12 AM
2.20 PM
11.40 PM
9.20 PM
400
350
380
360
380
340
340
380
400
380
360
800
360
400
400
360
380
350
380
320
380
400
700
400
300
380
380
400
380
400
360
380
350
380
60
80
60
60
80
80
90
80
80
80
80
90
90
80
70
80
80
90
60
80
90
80
120
80
60
80
80
80
70
80
80
80
90
60
Vitals BP After Before After Delivery
Delivery
Delivery
HB% (gm/dl)
460
430
440
420
460
420
430
460
480
460
440
890
450
480
470
440
460
440
440
400
470
480
820
480
360
460
460
480
450
480
440
460
440
440
11.8
12
10.6
12
9.8
12
10.8
11
9.8
10
11
10.8
12
11.6
10
9.8
11.8
12.4
10.2
11.4
10.8
11
13.4
11
10
10.6
11.8
11.8
10.8
10
9.8
11.8
12.4
10.2
Before 24Hrs Delivery
Fall in Hb% After (gm/dl)
SBP (mm SBP (mm of DBP (mm DBP (mm delivery of Hg)
Hg)
of Hg)
of Hg)
10
9.8
8.8
10.2
7.8
11
9.4
9.4
8.4
7.8
8.8
8.4
10.6
10
8.4
8
10
10.2
8.4
10
9
9.2
11.1
9.2
9
9.8
10
10.4
9.2
8.2
8
10
10.2
8.4
1.8
2.2
1.8
1.8
2
1
1.4
1.6
1.4
2.2
2.2
2.4
1.4
1.6
1.6
1.8
1.8
2.2
1.8
1.4
1.8
1.8
2.3
1.8
1
0.8
1.8
1.4
1.6
1.8
1.8
1.8
2.2
1.8
130
110
120
118
110
130
134
130
120
110
118
124
100
120
110
124
114
110
124
130
110
130
120
100
124
130
114
124
130
110
130
110
120
100
130
110
114
120
110
136
140
140
120
110
120
126
106
130
120
130
120
110
126
136
110
140
120
110
120
130
120
120
140
116
136
116
124
106
80
70
70
80
70
84
80
80
80
70
80
76
70
84
70
80
70
70
80
86
80
84
80
70
70
80
70
80
80
80
90
84
80
70
80
70
70
80
76
88
80
84
80
70
80
70
76
90
80
84
70
70
80
90
84
96
80
70
70
80
70
80
86
84
94
90
86
76
Use of Heart Respirat additional Complications
rate
ory rate Oxytocics
82
80
84
80
86
82
78
80
84
88
80
80
82
80
82
80
84
80
86
82
78
80
84
88
80
80
82
80
82
80
84
80
86
82
17
19
18
16
18
17
16
16
18
18
17
16
18
16
17
19
18
16
18
17
16
16
18
18
17
16
18
16
17
19
18
16
18
17
+
+
-
PPH
PPH
-
KEY TO MASTER CHART
LSCS - Lower segment cesarean section
D
- Diarrhea
N
-Nausea
V
- Vomiting
T
-Thrombosis
Pt
- Patient
DOO - Date of Operation
BL
- Blood loss
HR
- Heart rate
RR
- Respiratory rate
SBP
- Systolic blood pressure
DBP - Diastolic blood pressure
G
- Gravida
A
- Abortion
FI
- Failed induction
BPP
- Biophysical profile
FTP
- Failure to progress
FD
- Fetal distress
CPD - Cephalo-pelvic disproportion
Y
- Yes
N
- No
Primi - Primigravida