1. No category

Blodkoagulation
i klinisk praxis!
Peter Svensson
Centre for Thrombosis and Haemostasis, Malmö
Blood coagulation
Summary
Blodkoagulation
Primär hemostas
Plasmakoagulation
Antikoagulation
Fibrinolys
Kampen mellan fast och flytande förs
på pro- och antikoagulanta ytor
Intakt endotel/skadat endotel
Vilande blodceller/aktiverade blodceller
– Trombocyten i nyckelposition
A Hillarp
Normala trombocyter
Aktiverade trombocyter
Primary haemostasis mediated
by platelet-protein interaction
Deficiency:
Von Willebrand
Platelet disorders
Symtom:
Bleeding
ASA
ADHESION
AGGREGATION
Frisättning av
granula innehåll
vWF
Fibrinogen
GPIb
Trombocyt
Ca2+
Fosfolipid
R
Arakidonsyra
R
R
R
Tromboxan A2
R
R
Adrenalin
ADP
GpIIb/IIIa
Tromboxan
PAF
clopidogrel
Trombin
Kollagen
Trombocyt
Model for the relationship of von Willebrand factor (VWF) level to risk of bleeding,
thrombosis, and VWF mutations
Sadler, J. E. Hematology 2009;2009:106-112
Oral anticoagulants ie warfarin
Plasma and PCC
Deficiency: Hemofilia. Symtom ; bleeding
NEJM 2008
ANTIKOAGULATION
Brister - trombos
XII
XIIa
XI
TF
VIIa
XIa
TF
VII
TFPI
IX
IXa
VIIIa
X
Protein C systemet
Xa
Va
Antitrombin
Protrombin
Trombin
Fibrinogen
Fibrin
•Tranexsamsyra
(hämmar omvandlingen av plasminogen till plasmin)
Koagulation
ännu en gång…….
Kärlskada
Primär hemostas
Plasmakoagulation
Antikoagulation
Fibrinolys
Trombbildning filmat med
intravitalmikroskopi
Grönt = vävnadsfaktor
Rött = trombocyter
Lila = fibrin
Furie & Furie NEJM 2008
Is bloodcoagulation difficult?
Management of NOAC and “major”
bleeding complications in patients on
new anticoagulants.
Professor Peter J Svensson
Centre for Thrombosis and Haemostasis, SUS , Malmö
Prevalence of atrial fibrillation
> 2.5 % in the general population
Andersson et al JIM 2012, SBU 2013 april
Friberg et al JIM 2013
Indications for OAC
Atrial fibrillation
> 80%
VTE
10%
Mechanical heart valves
5%
Other
5%
Increase of OAC with 5-10% per year
30 % is over the age of 80 years among
patients with OAC
Auricula 2014
Outcomes from RCT
warfarin arm
• A Stroke and embolism
• 1.66 (95% CI 1.41-1.91)%
• B Myocardial infarction
•
0.76 (95% CI 0.57-0.96) %
• C All cause mortality
•
3.83 (95% CI 3.07-4.58) %
• D Composite outcome
•
•
4.80 (95% CI 4.22- 5.38) %
(Composite outcome includes stroke, non-CNS
embolism, myocardial infarction, and all-cause
death)
Agarwal et al Arch Intern Med. 2012;172(8):623-631
Major bleeding in RCT
warfarin
• The definition of major and minor bleeding
varied considerably across the included
studies; hence, a valid pooled estimate for
these outcomes could not be calculated.
The incidence of major bleeding episodes
ranged from 1.40% to 3.40% per year.
Agarwal et al Arch Intern Med. 2012;172(8):623-631
Intracranial Hemorrhage
warfarin
• The annual rate of intracranial hemorrhage
in patients with AF taking warfarin ranged
from 0.33% to 0.80% per year.
• Meta-analysis of intracranial hemorrhage
yielded a pooled event rate of
0.61% (95% CI, 0.48%- 0.73%) per year.
Agarwal et al Arch Intern Med. 2012;172(8):623-631
Major bleeding in patients with atrial fibrillation
receiving vitamin K antagonists: a systematic
review of randomized and observational studies
• A total of 47 studies (16 RCTs and 31 observational
studies) were included.
• Cumulative follow-up was 61 563 patient-years for RCTs
and 484 241 patient-years for observational studies.
• The overall median incidence of major bleeding was 2.1
per 100 patient-years (range, 0.9–3.4 per 100 patientyears) for RCTs and 2.0 per 100 patient-years (range,
0.2–7.6 per 100 patient-years) for observational studies.
Roskell et al Europace 2013; 15: 787-797
Warfarin in Sweden
Outcomes
Outcomes and age
OAC treatment in Sweden
(estimated)
~200.000 patients > 3 million PK(INR) tests
10.000.000 inhabitants, around 2% of the population
are under treatment with OAC
Preventing ~ 25.000 tromboemboli per year
Major bleeding (CNS, GI) > 3000-5000 per year
(hospitalization)
CNS (intracranial hemorrhages) 500 – 700 per year
Bridging ? Everything from going to the dentist to
major surgery ~ 45.000 engagements per year
Auricula 2013
Warfarin as prophylax for stroke in
patients with atrial fibrillation


Globaly 3.000.000 stroke is associated to atrial fibrillation
Oral anticoagulants reduces the risk for stroke and mortality
Stroke
Mortality
67%
26%
Hart RG et al. Ann Intern Med. 2007;146:857-867
New Oral Anti-Coagulants NOAC
Or
Direct Oral Anticoagulants DOAC
Dabigatran
(Pradaxa)
Rivaroxaban Apixaban Edoxaban Warfarin
(Xarelto)
(Eliquis) (Lixiana) (Waran)
Prodrug
yes
no
no
no
no
Factor Xa-inhibitor
no
yes
yes
yes
yes
Trombin inhibitor
yes
no
no
no
no
Bioavailability (%)
6
>80
>50
45
100
Time to peak (h)
2
3
3
1,5
120
T½ (h)
12-17
9
9-14
9-11
50
Interactions
Proton pump CYP3A4
CYP3A4
inhibitors
P-glyco-protein P-glycoP-glyco-protein
protein
CYP3A4
P-glycoprotein
Long list
Renal excretion (%)
80
33
25
35
1
Antidot (specific)
no
no
no
no
yes
Själander A och Svensson P , http://www.internetmedicin.se/dyn_main.asp?page=4356
Atrial Fibrillation
Stroke or systemic embolic events
NOACs 42.411 partisipants vs 29.272 participants received warfarin
New oralanticoagulants significantly
reduced stroke or systemic embolic events
by 19% compared with warfarin (RR 0·81,
95% CI 0·73–0·91; p<0·0001), mainly
driven by a reduction in haemorrhagic
stroke (0·49, 0·38–0·64; p<0·0001).
Atrial Fibrillation
Efficacy and Saftey
New oral anticoagulants also significantly
reduced all-cause mortality (0·90, 0·85–0·95;
p=0·0003) and intracranial haemorrhage
(0·48, 0·39–0·59; p<0·0001), but increased
gastrointestinal bleeding (1·25, 1·01–1·55;
p=0·04)
Lancet 2014; 383: 955-62
Major bleeding in RCT
NOAC (annually)
Major
Bleeding
Gastro
intestinal
bleeding
Intracrainial
bleeding
ReLy
(dabigatran)
2.71% (110 mg)
3.11% (150 mg)
1.12 %
1,51 %
0,23 %
0.30 %
N Eng J Med
2009
Rocket
(rivaroxaban)
3.6%
0.5%
N Eng J Med
2011
Aristotele
(apixaban)
2.13
0.76%
0.33%
N Eng J Med
2011
Engage AFTIMI
(edoxaban)
1.61 % (30 mg)
0.82 %
1.51 %
0.26%
0.39 %
N Eng J Med
2013
2.75 %
(60 mg)
Managment and Outcomes of major bleeding
during treatment with dabigatran or warfarin
Bleeding reports from 5 phase III trials with warfarin vs
dabigatran (patients 1034 patients with 1121 major
bleeds)
Patients with major bleeds on dabigatran were older had
lower kidney function and more frequently used aspirin
or NSIDs than those on warfarin.
Major bleeding with dabigatran were more frequently
treated with blood transfusion than warfarin but less
frequently with plasma
Patients with dabigatran and major bleeding had shorter
stays at ICU than those that recived warfarin.
Majeed A et al. Circulation. 2013;128:2325-2332
Thirty-day mortality rate after a major bleeding event.
After adjustment for sex, age, weight, renal function,
and concomitant antithrombotic therapy, the pooled odds ratio
for 30-day mortality with dabigatran versus warfarin was
0.66 (95% confidence interval, 0.44–1.00; P=0.051).
Majeed A et al. Circulation. 2013;128:2325-2332
Managment of major bleeding events in patients with
rivaroxaban vs warfarin: results from the Rocket AF trail
The risk of major bleeding were 3.52 events / 100 patients years in both
arms (rivaroxaban & warfarin)
The transfused packed red blood cells was similar in both arms (2.4 Units)
Transfusion with platlets, cryoprecipitate were low.
Fresh frozen plasma (FFP) was significantly less in the rivaroxaban arm
Protrombincomplex concentrate ( PCC ) were adiministered less in the
rivaroxaban arm.
Location of bleeding rivaroxaban n= 431; GI 49,9%, CNS 12.8%, Other,
37,3%
Outcomes; Once a major bleed had occured, all cause death after bleeding
was similar between both arms (rivaroxaban vs warfarin) (20.4 vs 26,1% p=
ns)
Piccini J P et al. Eur Heart J 2014;35:1873-1880
The time to ISTH major bleeding events according to the randomized treatment (rivaroxaban
or warfarin).
Piccini J P et al. Eur Heart J 2014;35:1873-1880
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author
2014. For permissions please email: [email protected]
Real life data Major bleeding
Rates, management and outcome of bleeding complication during
rivaroxaban therapy in daily care: results from the Dresden NOAC
registry, Beyer-Westendorf et al: Blood; 2014 online May 23.
1776 patients followed October 2011 to december 2013
Rates of major bleeding for SPAF indication was 3.1 % (95% CI 2.2-4.3)
The majority of bleeding occured spontananosly 77.4%
Surgical or interventional treatment was needed in 37,8% of patients
(mainly endoscopic treatment for GI bleeding). The majority of
patients could be managed conservativley
Prothrombincomplex concentrate (PCC) was given to 9.1% of the
patients (PCC was controlling bleeding in 5 of the 6 patients)
Result’s NOACs
> 850 patients in Auricula
Number
Events per 100
treatment years
Major bleeding (any)
12
2.03
(1.10-3.46)
-Intracranial bleeding
2
0.38
(0.06-1.12)
-Gastrointestinal bleeding
7
Thrombosis (any)
14
1.18
(0.52-2.34)
2.37
(1.35-3.89)
-Ischemic stroke / TIA
11
1.86
(0.98-3.24)
Mortality
12
2.03
(1.10-3.46
Labaf A et al Thromb J 2014
Different laboratory tests
(coagulation-tests)
1.Tests that are availbale in most laboratories,
easy to perform and semiquantitative for use in
ie emergency situations. The test should
indicating supra or subtherapeutic
anticoagulation
2. Test that gives quantitative results to
determine the anticoagulant effect (drug level)
3 (HPCL-tandem mass spectrometry)
J Throm Haemost 2013; 11: 756-60
Substance
group
Direct
FIIainhibitors
Karin Strandberg 2013
1. Screeningmethods
affected
2.Methods for
measuring/
monitoring
APTT
Thrombin
time (TT)
INR
ECT
Substance
group
Direct
FXainhibitors
Karin Strandberg 2013
1. Screeningmethods
affected
2.Methods for
measuring/
monitoring
APTT
Anti Xaactivity
INR
Effect of FII and FX inhibitores on
coagulation assays
FII
Effect
FII
Measuring
FX
Effect
FX
Measuring
PT (INR)
+
-
(+)
?
APTT
++
Qualitative
+
Qualitative
Thrombin time
+++
Qualitative
-
-
Diluted TT
++
Quantitative
-
-
ACT
+
?
+
?
Ecarin clotting
time
++
Quantitative
Anti- IIa assay
(chromogenic)
++
Quantitative
-
-
Anti- Xa assay
(chromogenic)
-
-
++
Quantitative
J Throm Haemost 2013; 11: 756-60
NOAC – broad terapeutic window
Broad
terapeutic
window
Thrombosis
Bleeding
Dabigatran ~ 50-200 µg/l
Rivaroxaban ~ 25-400 µg/l
Apixaban ~ < 300 µg/l ??
NOAC
Dose, concentration or intensity of anticoagulation
FDA
• Is kidney function important to measure and
monitor for NOAC ??
CKD
Chronic Kidney Disese
CKD*stadium
No CKD
Description
Normal
GFR*
(mL/min/1,73 m2)
≥90
≥90
1
Normal with i.e. proteinuria
2
Mild
60–89
3
Moderate
30–59
4
Severe
15–29
5
Kidney failure
ESRD*
<15 or dialysis
*GFR = glomerulär filtrationshastighet; Njurskada definieras som t ex mikroalbuminuri; CKD =
chronic kidney disease; ESRD = end-stage renal disease (terminal njursvikt)
1. Koro CE, et al. Clin Ther 2009; 31: 2608–17. 2. National Kidney Foundation. Am J Kidney Dis
2002;39(suppl1):S1–S266.
Major bleeding event rate according to
renal function in RCT for AF
Schulman Thromb Haemost 2014;111;575-582
How I handle NOAC in my
clinical practice
Anticoagulation clinic; 12.000 patients
NOAC >3000 patients
Start on NOACs
Information (nurse 15- 20 minutes)
Basic laboratory tests ( Hemoglobin,
platlets and coagulation test APTT INR
and kidney function eGFR)
First year on NOAC eGFR 3, 6 and 12
months after start.
Bergman et al Thromb Res. 2013
How I handle NOAC in my
clinical practice
Strategies to minimize the risk of bleeding
Review the patients risk factors; age,
weight, renal function
Prescribe the dose of NOAC that is
recommended
Have a strategy for discontinue NOAC
before surgery and how to resume NOAC
after surgery
Local guidelines / Education!!!!
What is the size of the
”bridging” issue
Peri-Procedual Bleeding and Thromboembolic Events with
Dabigatran compared to Warfarin: Results from the RE-LY trail
A total of 4591 (25%) patients underwent at least
one invasive procedure during the study.
Pacemaker/ICD 10%
Dental procedure 10%
Different Diagnostic procedures 10%
Cataract removal 9.5%
Colonoscopy 9%
Hip or knee Replacement 6%
Circulation 2012; 126:343-48
Clinical recommendations
www.ssth.se
Dabigatran 2011
Rivaroxaban 2012
Apixaban 2013
European Heart Rhythm Association
Practical Guide 2015
How I handle major bleeding
with NOAC.
Asses vital signs
Blood tests and kidney function test
(estimate half life of the drug)
Coagulation test (indication of drug on-board)
Supportiv care (blood)
Surgical interventions (endoscopic treatment )
Tranexamic acid!
If bleeding is severe or life-threatening
Prothrombin complex concentrate
(rVIIa or aPCC)
Evidence for non specific
antidotes
Animal
studies
Human
studies
Van Ryn Blood 2011
Van Ryn Haematologica 2008
Pragst J Throm Haemost 2012
+
Marlu Thromb Haemost 2012
Eerenberg , Circulation 2011
Rivaroxaban +
Godier Anestesia 2012
Perzbom Throm and Haem 2012
+
Marlu Thromb Haemost 2012
Eerenberg , Circulation 2011
Apixaban
Martin J Int Card 2013
Dabigatran
+
+
1. PCC ( Protrombin Complex Concentrate)
3 factor (F II, F IX, F X)
4 factor (F II, F VII, F IX, F X)
2. aPCC (FEIBA) (F II, aF VII, F IX, F X)
3. rVIIa (Novo Seven)
S.Kaatz et al., Am. J. Hematol. 87:S141–S145, 2012
Babilonia & Trujillo Thrombosis Journal 2014; 12:8
Major Bleeding on
NOAC
Stop NOAC
Basic laboratory test
Calculate kidneyfunktion (GFR) – estimate
half-life of the NOAC
If availabele TT for dabigatran and anti-Xa
level for rivaroxaban and apixaban
Clinically significant bleeding
Transfusion support
Red cells?
Platlets ? (< 50x 109 / l)
Charcoal ?? NOAC < 3h
Local haemostasis
”endoscopic treatment for GI bleeding ”
Life-threating bleeding
Consider
3 or 4 faktor PCC (25-50 IU/ kg and mybe
another dose within 3 h
Tranexamic acid 15-30 mg iv
(aPCC – FEIBA)
(rVIIa)
Dialysis (dabigatran)
Svensson PJ 2014
www.ssth.se
Specific antidote NOAC
Specific antidotes are under development and in clinical trails for
dabigatran and for anti-factor Xa agents
ClinicalTrails.gov (August 2014)
”Reversal of Dabigatran Anticoagulant effect with Idarucizumab ”
aDabi-Fab is a humanized antibody fragment that binds dabigatran and
reverses its anticoagulant effects in vitro and in vivo.
”Phase 2 Healthy Volunterr Study to Evaluate tha Ability of
PRT06445 to reverse the Blood Thinner Drugs on Laboratory
Tests”
r-Antidote (PRT064445) is a catalytically inactive recombinant protein
that lacks the membrane-binding ƴ-carboxyglutamatic acid domain of
nativ factor Xa while retaining the ability to bind factor Xa inhibitores
Schile et al Blood 2013; 121: 3554-62
Lu et al, Nat Med 2013; 19: 446-51
Antidot
Bridging
NEJM Bridging
(Dalteparin 100 E / kg)
VTE Bridging
Fall
Kvinna med FF och behandlas med NOAC som nu skall genomgå
tandbehandling med us och tandstenssanering.
Planering
Kvinna med FF och behandlas med NOAC. Us visar att en tand behöver
rotfyllas
Planering
Kvinna med FF och behandlas med NOAC . Us visar att en tand behöver
extraheras.
Planering
Kvinna med FF och behandlas med NOAC som har genomgått en
tandbehandling. Extraktion av en infekterad tand. Återkommer på pga
blödning.
Åtgärd
Managment of new oral anticoagulants related life threating or major
bleeding in real life : a brief report
online 12 august 2014
J Thromb Trombolysis Masotti et al.
Four hospitals in Tuscany, Italy September 2013- February 2014
Eight patients on NOACs 4 males and 4 females mean age 84 years
All bleedings were major bleeding according to ISTH definition and
were spontaneus and from GI tract.
Laboratory tests, mean aPTT 56s, INR 1,9 and eGFR < 30 in 4
patients
Treatment; NOACs witheld and fluid replacement was initiated
One patient recived 4 factor PCC and tranexamicacid
Normalisation of all coagulation parameters occured within a median
time of 3 days
All patients were discharged alive from the hospital
Treatment options in AF patients –
Old vs. New Drugs ?
My own interpretation!
Old
New
Effect
+
Saftey
+
”Bridging”
+
Adherens
Antidot
(+)
+
Transition between drugs
+
Patient preference
+
Time consuming
Guidelines
Gaps (ie real world data)
More patients could be treated
+
+
Needed
+
0
DDD (definierade dygnsdoser), månadsvis t.o.m. juli 2015
2015-07
2015-06
2015-05
2015-04
2015-03
2015-02
2015-01
2014-12
2014-11
2014-10
2014-09
2014-08
2014-07
2014-06
2014-05
2014-04
2014-03
2014-02
2014-01
2013-12
2013-11
2013-10
2013-09
2013-08
2013-07
2013-06
2013-05
2013-04
2013-03
2013-02
2013-01
2012-12
2012-11
2012-10
2012-09
2012-08
2012-07
2012-06
2012-05
2012-04
2012-03
2012-02
2 000 000
2012-01
2011-12
2011-11
2011-10
2011-09
2011-08
2011-07
2011-06
2011-05
2011-04
2011-03
2011-02
2011-01
2010-12
2010-11
2010-10
2010-09
2010-08
2010-07
2010-06
2010-05
2010-04
2010-03
2010-02
2010-01
Vissa antikoagulantia, uthämtade recept, Riket
4 000 000
3 500 000
3 000 000
2 500 000
B01AA03 - warfarin
B01AE07 - dabigatranetexilat (Pradaxa)
B01AF01 - rivaroxaban (Xarelto)
B01AF02 - apixaban (Eliquis)
1 500 000
1 000 000
500 000
NOAC
Praktiska råd
NOAK i klinisk praxis
• Ges till en allt större andel patienter
• Många äldre, multipelt sjuka
• Behov av att monitorera njurfunktion
• Hantera blödningar samt blödningsrisk vid
akuta eller planerade ingrepp
Byte mellan antikoagulantia
• Från warfarin till NOAK - starta behandlingen
när PK(INR) är < 2,0.
• Från NOAK till warfarin
– eGFR > 50 ml/min:
Warfarin 2-3 dagar innan
NOAK avslutas.
– eGFR 31-50 ml/min:
Warfarin 1 dag innan NOAK
avslutas.
– eGFR 15-30 ml/min:
Warfarin 1 dag efter NOAK
avslutas.
Njursvikt hos patienter med förmaksflimmer och
antikoagulantia
Jönsson
K et al. Thrombosis
Research 2011; 128: 341-345
Jönsson
et al. Thromb
Res. 2011 Oct;128(4):341-5
Gedigna guidelines
Jönsson et al. Thromb Res. 2011 Oct;128(4):341-5
Kliniska rekommendationer
www.ssth.se
•
•
•
•
Dabigatran 2011
Rivaroxaban 2012
Apixaban 2013
Trombocythämmare 2014
Hantering av NOAK vid elektiv kirurgi
• Standardriskpatient/ingrepp – vänta 2 T1/2
• Högriskpatient/ingrepp – vänta 4 T1/2
• Ingen bridging med LMH
Lågriskingrepp/kirurgi
•
•
•
•
•
•
Endoskopi med biopsi
Prostata eller urinblåsebiopsi
Radiofrekvensablation av SVT
Elektrofysiologi
Angiografi
Pacemakerinplantation
Högriskingrepp/kirurgi
•
•
•
•
•
•
•
•
Lungvensisolering, VT ablation
LP, spinalanestesi
Thoraxkirurgi
Bukkirurgi
Större ortopedisk kirurgi
Leverbiopsi
TUR-P
Njurbiopsi
Njurfunktion och halveringstider
eGFR
(ml/min)
Dabigatran
Apixaban
Edoxaban
Rivaroxaban
>80
12-17h
12h
10-14h
5-9h (yngre)
11-13h
(äldre)
60-80
14h
14h
8.6h
8.5h
30-60
18h
17h
9.4h
9h
15-30
28h
17h
17h
9.5h
≤15
Inga data
Inga data
Inga data
Inga data
Tid från sista tablett till elektiv kirurgi
• Låg/standardriskingrepp
1 dag
• Högriskingrepp eller njursvikt 2 dagar
• fXa, eGFR 15-30, högrisk
3 dagar
• Dabigatran, eGFR 15-30, högrisk
4 dagar
Återstart av antikoagulantia
• Mindre kirurgi:
– 6-8 timmar efter ingrepp eller nästa dag
• Standardrisk:
– 24-48h efter kirurgi
• Högriskpatient/kirurgi:
– Profylax med LMH postoperativt
– Återinsätt vid full hemostas.
Akut blödning eller behov av akut kirurgi
• Protrombinkomplexkoncentrat (PCC) –
Ocplex® eller Confidex®
– < 15 timmar sedan senaste NOAK-dos ges 2000E
Ocplex® eller Confidex®
– 15-24 timmar sedan senaste NOAK-dos ges 1500E
– Ocplex® eller Confidex®
Antidot
När skall vi använda dom
ARIPAZINE (PER977; ciraparantag)
– What is it? This is a synthetic small molecule (D-arginine compound) which
has broad activity against various old (heparin, low molecular weight heparin)
and new oral anticoagulants (dabigatran, rivaroxaban, apixaban and
edoxaban). It is being developed by Perosphere.
– What anticoagulant drugs might it reverse? Apixaban, edoxaban,
rivaroxaban, dabigatran, heparin, LMWH.
– Clinical trial status: A human volunteer study of 80 individuals
receiving aripazine published in the New England Journal of Medicine shows
that clotting assays (whole-blood clotting time) that were prolonged by
edoxaban, decreased after the test persons received aripazine. Another
healthy volunteer study is presently ongoing [NCT02207257].
Ansell JE et al. Use of PER977
to reverse the anticoagulant effect of edoxaban.
N Engl J Med 2014(Nov 5)
ANDEXANET (PRT064445)
•
– What is it? Recombinant, modified factor Xa molecule that is being developed
as a direct reversal agent for patients receiving a Factor-Xa inhibitor who
suffer a major bleeding episode or who require emergency surgery. It sort-of
sops up the anti-Xa anticoagulant, making a patient’s own factor Xa available
again to participate in the coagulation process. It is being developed by
Portola.
– What anticoagulant drugs might it reverse? Apixaban, edoxaban,
rivaroxaban.
Clinical trial status: Healthy volunteer studies to (a) evaluate the ability of
Andexanet to reverse the effects of several anticoagulant drugs on laboratory tests
(NCT01758432) and (b) reverse apixaban [NCT02207725] and
rivaroxaban[NCT02220725] are presently ongoing
Lu G et al. A specific antidote for reversal of anticoagulation
by direct and indirect inhibitors of coagulation factor Xa.
Nature Medicine 2013;19(4):446-453.
IDARUCIZUMAB (BI 655075)
– What is it? It is a humanized antibody fragment directed against dabigatran;
generated from mouse monoclonal antibody against dabigatran; humanized
and reduced to a FAb fragment. It is being developed by BoehringerIngelheim.
– What anticoagulant drugs might it reverse? Dabigatran.
– Clinical trial status: (a) A phase 3 study of patients on dabigatran with major
bleeding or needing emergency surgery is ongoing [NCT02104947. (b) Three
phase 1 studies to determine the effect of idarucizumab on coagulation tests
in dabigatran-treated healthy volunteers have been completed (NCT01688830,
NCT01955720; NCT02028780).
Schiele F et al. A specific antidote for dabigatran:
functional and structural characterization.
Blood 2013;121(18):3554-3562
Malmö Centre for Thrombosis and Haemostasis
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