1. APPROACH TO BLEEDING DISORDERS

2. History of Bleeding Spontaneous vs. trauma/surgery-induced Ecchymoses without known trauma Medications or nutritional supplements

3. 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)

4. Clinical Presentations Subcutaneous bleeding - Cushing's syndrome - Chronic steroid use - Senile purpura Epistaxis - hereditary hemorrhagic telangiectasia - vwd

5. Clinical Presentations Menorrhagia - vWD,factor XI deficiency and symptomatic carriers of hemophilia A

7. Prohemorrhagic medications and dietary supplements NSAID’s Aspirin Fish oil (omega 3 FA) Vitamin E

9. 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

10. 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

12. SCREENING ASSAYS PT aPTT Platelet count

13. 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

14. 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

15. Antiphospholipid Antibodies Antibodies to phospholipids (cardiolipin) or phospholipid-binding proteins (β 2- microglobulin detected by ELISA

16. OTHER COAULATION TESTS Thrombin time and Reptilase Time –Fibrinogen conversion to fibrin Anti-Factor Xa Plasma Inhibitory Activity -LMWH activity -UFH activity

17. Platelet Function Bleeding time PFA-100 vWF assays platelet aggregometry

18. 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

19. Prolonged prothrombin time (PT)  Factor VII deficiency  Vitamin K deficiency – early  Warfarin anticoagulation Hemostatic Disorders and Coagulation Test Abnormalities

20. Prolonged aPTT and PT  Factor II, V or X deficiency  Vitamin K deficiency – late  Direct thrombin inhibitors

21. Prolonged thrombin time  Heparin or heparin-like inhibitors  Mild or no bleeding – dysfibrinogenemia  Frequent, severe bleeding – afibrinogenemia Hemostatic Disorders and Coagulation Test Abnormalities

22. 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

23. 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