HOW TO APPROACH TO A PATIENT WITH BLEEDING DISORDERS EVALUATION OF THE BLEEDING PATIENT DEFINITION • Hemostasis The arrest of bleeding from an injured blood vessel, involving the combined regulatory activity of vascular, platelet, and plasma factors Primary Hemostasis Vessel wall function Platelet functions of Adhesion, Aggregation Secondary hemostasis Plasma coagulation factors leading to fibrin deposition ,clot formation Tertiary hemostasis Clot retraction Cross link of fibrin clot Fibrinolysis • Clotting The Coagulation of blood is a complex process by which fluid form of blood changes to semi solid or solid form. • Bleeding Extavasation of blood from an ruptured blood vessel to the internal or external tissue. HEMOSTASIS AND THROMBOSIS •    Dependent on 3 factors: Vascular endothelium Platelets Coagulation system 1. CLINICAL ASPECTS OF BLEEDING 1. CLINICAL ASPECTS OF BLEEDING Evaluation of patients with bleeding is a multi-step process: • Complete history • Detailed physical exam • Laboratory evaluation HISTORY  Is there a personal or family history of bleeding after surgical procedures, dental procedures, childbirth, or trauma?  When the bleeding episode started?  Has the patient received medications that can cause or make worse a bleeding problem? Many drugs can contribute to bleeding; semisynthetic penicillins cephalosporins calcium channel blocker dipyridamole thiazides alcohol quinine, quinidine chlorpromazine, sulfonamides INH, rifampin methyldopa phenytoin, barbiturates, warfarin, heparin, thrombolytic agents NSAIDs, ASA allopurinol TMP/SMX PHYSICAL EXAM 1. Assess volume status (correct shock if present) 2. Look for hepatosplenomegaly 3. Do a rectal exam for evidence of GI bleeding 4. Examine oropharynx for evidence of petechiae HEREDIATARY TELANGECTASIAS • Mouth: Gum Bleed Gum Hypertrophy Telangectasias Angular stomatitis SUBCONJUNCTIVAL HAEMORRHAGE PHYSICAL EXAM    Look for physical signs and symptoms of diseases related to capillary fragility: Cushing’s syndrome, Marfan syndrome or exogenous steroids "senile purpura”  Petechiae secondary to coughing, sneezing, Valsalva maneuver, blood pressure measurement  vasculitis ("palpable purpura")  Telangiectasias (Osler-Weber-Rendu syndrome) (HHT) PETECHIAE VASCULITIS (PALPABLE RASH) 2. HEMATOLOGIC DISORDERS CAUSING BLEEDING – Platelet disorders – Coagulation factor disorders CLINICAL DIFFERENTIATION PLATELET DEFECT VS COAGULATION DEFECT PLATELETS DEFECTS • Generally have immediate onset of bleeding after trauma • Bleeding is predominantly in skin, mucous membranes, nose, GI tract, and urinary tract • Bleeding may be observed as petechiae (<3 mm) or ecchymoses (>3 mm COMPARISON OF PLATELET AND COAGULAYION DISORDERS Platelet Disorders Coagulation Factor Disorder Site of bleeding Skin, mucous membrane and soft tissue Deep in soft tissues (joints and muscles) Physical Finding Petechiae, ecchymoses Hematoma, Hemarthrosis Family History Autosomal dominant Autosomal or X-linked recessive Bleeding after cuts and scratches Yes No Bleeding after surgery and trauma Immediate, usually mild Delayed (1-2 days), often severe CLINICAL ASPECTS OF BLEEDING COAGULATION DEFECTS • "Deep" bleeding (in the joint spaces, muscles, and retroperitoneal spaces) is common. Observed on exam as hematomas and hemarthroses. Hematoma LABORATORY EVALUATION OF BLEEDING CBC and smear Platelet count Thrombocytopenia RBC and platelet morphology TTP, DIC, etc. LABORATORY EVALUATION OF BLEEDING Platelet function von Willebrand factor vWD Bleeding time In vivo test (non-specific) Coagulation PT analyzer (PFA) Platelet function Qualitative platelet extrinsic/common pathways disorders PTT BLEEDING Intrinsic/common pathways TIME • 5-10% of patients hospitalized patients have a Coag. factor assays prolonged bleeding time Specific factor deficiencies • Most of the prolonged bleeding times are due to aspirin or drug ingestion 50:50 bleeding mix • Prolonged time does not predict excess surgical blood loss Inhibitors (e.g., antibodies) • Not recommended for routine testing in preoperative patients Fibrinogen assay Decreased fibrinogen THROMBIN TIME Thrombin • Measures rate time of fibrinogen conversion to fibrin Qualitative/quantitative fibrinogen • Procedure: – Add thrombin with patient plasmaMeasure time to clot defects • Variables: D-dimer – Source and quantity of thrombin Fibrinolysis (DIC) CAUSES OF PROLONGED THROMBIN TIME • Heparin • Hypofibrinogenemia • Dysfibrinogenemia • Paraprotein • Thrombin inhibitors (Hirudin) • Thrombin antibodies PLATELETS APPROACH TO THE THROMBOCYTOPENIC PATIENT • History – Is the patient bleeding? 2. Are there symptoms of a secondary illness? (neoplasm, infection, autoimmune disease) 3. Is there a history of medications, alcohol use, or recent transfusion? • History 4. Are there risk factors for viral infection? 5.Is there a family history of thrombocytopenia? 6. Do the sites of bleeding suggest a platelet defect? • Assess the number and function of platelets – CBC with peripheral smear – Bleeding time – Platelet aggregation study – PFA CLASSIFICATION OF PLATELET DISORDER • Quantitative disorders – Abnormal distribution – Dilution effect – Decreased production – Increased destruction CLASSIFICATION OF PLATELET DISORDERS • Qualitative disorders – Inherited disorders (rare) – Acquired disorders • • • • Immune Medications Chronic renal failure Cardiopulmonary bypassLiver disease INHERITED PLATELET DISORDERS • May-Hegglin: Thrombocytopenia Large platelets Neutrophils – Dohle bodies .Glazmann’s thrombasthenia: Congenital deficiency or abnormality of GP IIb-IIIa • Bernard-Solier syndrome: Congenital deficiency or abnormality of GP Ib ACQUIRED PLATELET DISORDERS • Decreased production: Ineffective thrombopoiesis - MDS • Increased destruction: Immune Non-immune • Poor aggregation INCREASED PLATELETS DESTRUCTION ITP IS A DIAGNOSIS OF EXCLUSION ! COAGULATION FACTOR DEFECTS Inherited Coagulation factor bleeding disorders – vonWillebrand’s disease – Hemophilia (A and B) HEMOPHILIA Clinical manifestations (hemophilia A & B are indistinguishable) – Prolonged bleeding after surgery or dental extractions – Hemarthrosis (most common) – Soft tissue hematomas – Other sites of bleeding Urinary tract CNS, neck (may be life-threatening) ACQUIRED BLEEDING DISORDERS: Vitamin K deficiency – – – – Liver disease Warfarin overdose DIC Inhibitors to CF VITAMIN K DEFICIENCY • Source of vitamin K : Green vegetables Synthesized by intestinal flora • Required for synthesis Factors II, VII, IX ,X Protein C and S • Causes of deficiency : Malnutrition Billiary obstruction Malabsorption Antibiotic therapy DIC DISSEMINATED INTRAVASCULAR COAGULATION • Sepsis • Trauma – Head injury – Fat embolism • Malignancy PATHOGENESIS OF DIC Consumption of coagulation factors; presence of FDPs  aPTT  PT  TT  Fibrinogen Presence of plasmin  D-dimer Intravascular clot  Platelets Schistocytes HEMOSTASIS IN LIVER DISEASE LIVER DISEASE AND HEMOSTASIS • Decreased synthesis of II, VII, IX, X, XI, and fibrinogen • Dietary Vitamin K deficiency (Inadequate intake or malabsortion) • Dysfibrinogenemia • Enhanced fibrinolysis (Decreased alpha-2-antiplasmin) • DIC • Thrombocytopenia due to hypersplenism MANAGEMENT OF HEMOSTATIC DEFECTS IN LIVER DISEASE Treatment for prolonged PT/PTT  Vitamin K 10 mg SQ x 3 days - usually ineffective  Fresh-frozen plasma infusion: 25-30% of plasma volume (1200-1500 ml) (immediate but temporary effect) Treatment for low fibrinogen  Cryoprecipitate (1 unit/10kg body APPROACH TO BLEEDING DISORDERS SUMMARY • Identify and correct any specific defect of hemostasis – Laboratory testing is always needed to establish the cause of bleeding – Screening tests (PT,PTT, platelet count) will often allow placement into one of the broad categories – Specialized testing is usually necessary to establish a specific diagnosis • Use non-transfusional drugs whenever possible • RBC transfusions for surgical procedures or large blood loss THANK YOU!