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 37oC 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

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 1Treatment with fibrinolytic therapy