This document summarizes various inherited and acquired bleeding disorders: 1. It describes disorders of blood coagulation including hemophilia A and B due to factor VIII and IX deficiencies, von Willebrand disease, and liver disease-related deficiencies. 2. Common tests used to evaluate hemostasis such as PT, PTT, bleeding time, and factor assays are outlined. 3. Causes of abnormal coagulation test results and approaches to initial evaluation of a bleeding patient are provided.

1. DR.G BALAJI . PROF.DR.G. SUNDARAMURTHY’S UNIT

12. Blood Coagulation & Tests

34. Partial Thromboplastin Time (PTT) Prothrombin time (PT) Intrinsic pathway Extrinsic pathway Common pathway Thrombin time Thrombin Surface activating agent (Ellagic acid, kaolin) Phospholipid Calcium Thromboplastin Tissue factor Phospholipid Calcium Fibrin clot Fibrin Clot

35. Initial Evaluation of a Bleeding Patient - 1 Normal PT Normal PTT Consider evaluating for: Mild factor deficiency Monoclonal gammopathy Abnormal fibrinolysis Platelet disorder (  2 anti-plasmin def) Vascular disorder Elevated FDPs Urea solubility Normal Abnormal Factor XIII deficiency

36. Initial Evaluation of a Bleeding Patient - 2 Normal PT Abnormal PTT Test for factor deficiency: Isolated deficiency in intrinsic pathway (factors VIII, IX, XI) Multiple factor deficiencies (rare) Repeat with 50:50 mix 50:50 mix is normal 50:50 mix is abnormal Test for inhibitor activity: Specific factors: VIII,IX, XI Non-specific (anti-phospholipid Ab)

37. Initial Evaluation of a Bleeding Patient - 3 Abnormal PT Normal PTT Test for factor deficiency: Isolated deficiency of factor VII (rare) Multiple factor deficiencies (common) (Liver disease, vitamin K deficiency, warfarin, DIC) Repeat with 50:50 mix 50:50 mix is normal 50:50 mix is abnormal Test for inhibitor activity: Specific: Factor VII (rare) Non-specific: Anti-phospholipid (rare)

38. Initial Evaluation of a Bleeding Patient - 4 Abnormal PT Abnormal PTT Test for factor deficiency: Isolated deficiency in common pathway: Factors V, X, Prothrombin, Fibrinogen Multiple factor deficiencies (common) (Liver disease, vitamin K deficiency, warfarin, DIC) Repeat with 50:50 mix 50:50 mix is normal 50:50 mix is abnormal Test for inhibitor activity: Specific : Factors V, X, Prothrombin, fibrinogen (rare) Non-specific: anti-phospholipid (common)

41. Lab Results in Hemophilia, VWD and Vit K Def Haemophilia V W Disease Vit K Deficiency Bleeding Time Normal Increased Normal PT Normal Normal Increased APTT Increased + Increased ± Increased V111 levels Decreased ++ Decreased Normal vWF levels Normal Decreased Normal

42. Hemophilia A Hemophilia B Von Willebrand Disease Inheritance X linked X linked Autosomal dominant Factor deficiency VIII IV VWF Bleeding site(s) Muscle,joint Surgical Muscle ,joint Mucous Skin Prothrombin time Normal Normal Normal Activated PTT Prolonged Prolonged Prolonged Bleeding time Normal Normal Prolonged or normal Factor VIII Low Normal Normal VWF Normal Normal Low Factor IX Normal Low Normal Platelet aggregation Normal Normal Normal

44. Summary