sensitive to mild to moderate deficiencies of fibrinogen; the TT may be the only prolonged screening test in those instances. What is the differential diagnosis? ▲ Congenital deficiency of fibrinogen (hypofibrinogenemia or afibrinogenemia) or a qualitative abnormality (dysfibrinogenemia). ▲ Acquired causes. • Drugs (e.g. heparin, direct thrombin inhibitors) • Specific inhibitors directed to either factor II or fibrinogen (extremely rare) • Disseminated intravascular coagulation (due to increased fibrin degradation products in the circulation that interfere with fibrin polymerization) • Acquired hypofibrinogenemia – Severe liver disease – Massive hemorrhage – May occur with systemic t-PA treatment Fibrinogen Common V II X VIII IX XI VII XII Pathway Fibrin Clot Intrinsic Pathway Extrinsic Pathway Fibrinogen Common V II X VIII IX XI VII XII Pathway Fibrin Clot Intrinsic Pathway Extrinsic Pathway 30 5. APPROACH TO THE EVALUATION OF THE BLEEDING PATIENT Paula James History ▲ The history is the most important tool in determining the pre-test probability of the existence of a bleeding disorder and helping to distinguish congenital from acquired causes. ▲ Details to inquire about on history. • Onset of bleeding – spontaneous or with hemostatic challenges (dental extractions, surgery, postpartum) • Location of bleeding – skin, mucous membranes, muscles, joints • Pattern of bleeding – bruises, petechiae, hematomas • Duration and severity of bleeding episode • Menstrual history • Treatments / interventions required to stop bleeding – local pressure, cautery / packing for nosebleeds, other interventions • History or symptoms of anemia / iron deficiency – fatigue, prior iron supplementation • Previous blood transfusions • Medication history • Family history of bleeding problems ▲ A congenital bleeding disorder would more often be associated with a lifelong history of excessive bleeding or bruising and a positive family history for bleeding; however, the lack of family history does not rule out a congenital bleeding disorder. ▲ Standardized bleeding assessment tools (BATs) should be used to assess bleeding risk. An example is the condensed MCMDM-1 VWD bleeding questionnaire for von Willebrand disease and platelet function disorders. ▲ The condensed MCMDM-1 may be useful in the prediction of operative bleeding, however prospective, peri-operative validation studies have not been done. Physical Examination ▲ Should include examination of: • Skin – pallor, jaundice, size and location of bruises, petechiae, hematomas, telangiectasia • Hepatosplenomegaly and lymphadenopathy • Joints – range of motion, evidence of hypermobility 5. Evaluation of Bleeding Patient 31 ! Standardized bleeding assessment tools (BATs) should be used to assess bleeding risk. ! A T T E N T I O N The bleeding history is the most important predictor of a bleeding disorder. A T T E N T I O N Investigations ▲ Initial investigations should be directed by the history and include: • CBC and peripheral blood film • PT / INR and APTT • + / - Thrombin time • + / - Fibrinogen • + / - Hepatic, renal function • + / - Ferritin ▲ The initial investigations may be normal in both VWD and PFD. ▲ Subsequent investigations will depend on the clinical history and initial test results and may include: • von Willebrand screen • Testing of specific coagulation factors • Platelet function testing ▲ Ideally, specialized investigations should be done under the supervision of a hematologist. 32 5. APPROACH TO THE EVALUATION OF THE BLEEDING PATIENT Diagnostic Approach ▲ Congenital causes of bleeding include: • von Willebrand disease (VWD) • Platelet function disorders (PFD) • Hemophilia A and B • Factor XI deficiency • Other coagulation factor deficiencies • Collagen vascular disorders (Ehlers Danlos Syndrome) • Hypo / dysfibrinogenemia VWD is the most common congenital cause of bleeding. ▲ Acquired causes of bleeding include: • Medications (e.g. antiplatelet agents, anticoagulants, antidepressants, anticonvulsants) • Hepatic or renal disease • ITP (immune thrombocytopenia purpura) • Bone marrow disorders • Acquired coagulation factor deficiencies (Factor VIII, von Willebrand Factor)