APPROACH TO BLEEDING DISORDERS
History of Bleeding Spontaneous vs. trauma/surgery-induced Ecchymoses without known trauma Medications or nutritional supplements
Clinical Presentations Spontaneous hemarthroses - factors VIII and IX deficiency - severe deficiencies of fibrinogen, prothrombin, and FV, VII, and X Mucosal bleeding symptoms - platelet disorders - von Willebrand disease (vWD)
Clinical Presentations Subcutaneous bleeding - Cushing's syndrome - Chronic steroid use - Senile purpura Epistaxis - hereditary hemorrhagic telangiectasia - vwd
Clinical Presentations Menorrhagia - vWD,factor XI deficiency and symptomatic carriers of hemophilia A
Prohemorrhagic medications and dietary supplements NSAID’s Aspirin Fish oil (omega 3 FA) Vitamin E
Systemic Diseases that Cause or Exacerbate Bleeding Bruising or mucosal bleeding may be a presentation of: - liver disease, renal impairment, hypothyroidism, paraproteinemias or amyloidosis, and bone marrow failure
History of Thrombosis Risk Factors –Arterial : Atherosclerosis –Venous: Immobility, surgery, medical conditions, HRT, Obesity, Genetic. Idiopathic event is the stongest predictor of recurrence of venous thromboembolis Age is an important risk factor for thromboembolism Thrombotic events often has more than one contributing event
SCREENING ASSAYS PT aPTT Platelet count
MIXING STUDIES Evaluate prolonged Aptt or less commonly PT Factor deficiency vs presence of inhibitor Normal plasma and patient plasma in a 50:50 ratio Incubate ar 37 o C for 30, 60, and/or 120 min Factor deficiencies –with corection Lupus anticoagulant - no correction
Specific Factor Assay Requested based on clinical situation and the results of coagulation screening tests Precise diagnosis and effective management patient's plasma is mixed with plasma deficient in the factor being studied
Antiphospholipid Antibodies Antibodies to phospholipids (cardiolipin) or phospholipid-binding proteins (β 2- microglobulin detected by ELISA
OTHER COAULATION TESTS Thrombin time and Reptilase Time –Fibrinogen conversion to fibrin Anti-Factor Xa Plasma Inhibitory Activity -LMWH activity -UFH activity
Platelet Function Bleeding time PFA-100 vWF assays platelet aggregometry
Hemostatic Disorders and Coagulation Test Abnormalities Prolonged (aPTT) No clinical bleeding – factors XII, high- molecular-weight kininogen, protein kinase Variable, but usually mild, bleeding – factor XI, mild FVIII and FIX Frequent, severe bleeding – severe deficiencies of FVIII and FIX Heparin
Prolonged prothrombin time (PT) Factor VII deficiency Vitamin K deficiency – early Warfarin anticoagulation Hemostatic Disorders and Coagulation Test Abnormalities
Prolonged aPTT and PT Factor II, V or X deficiency Vitamin K deficiency – late Direct thrombin inhibitors
Prolonged thrombin time Heparin or heparin-like inhibitors Mild or no bleeding – dysfibrinogenemia Frequent, severe bleeding – afibrinogenemia Hemostatic Disorders and Coagulation Test Abnormalities
Prolonged PT and/or aPTT not correct with mixing with normal plasma Bleeding – specific factor inhibitor No symptoms, or clotting and/or pregnancy loss – lupus anticoagulant Disseminated intravascular coagulation Heparin or direct thrombin inhibitor Hemostatic Disorders and Coagulation Test Abnormalities
Abnormal clot solubility Factor XIII deficiency Inhibitors or defective cross-linking Hemostatic Disorders and Coagulation Test Abnormalities Rapid clot lysis Deficiency of 2-antiplasmin or plasminogen activator inhibitor 1 Treatment with fibrinolytic therapy