- Vitamin K deficiency: impairs production of factors II (prothrombin), VII, IX, and X; vitamin K is a cofactor in the carboxylation of glutamate residues on prothrombin complex proteins; major source of vitamin K is dietary (esp. green vegetables), with minor production by gut bacteria. Laboratory features: elevated PT and PTT.
- Liver disease: results in deficiencies of all clotting factors except VIII. Laboratory features: elevated PT, normal or elevated PTT.
- Other disorders: DIC, fibrinogen deficiency (liver disease, l-asparaginase therapy, rattlesnake bites), other factor deficiencies, circulating anticoagulants (lymphoma, SLE, idiopathic), massive transfusion (dilutional coagulopathy).
Treatment: Bleeding Disorders Thrombocytopenia Caused by Drugs Discontinue use of possible offending agents; expect recovery in 7-10 days. Platelet transfusions may be needed if platelet count <10,000/µL. Hit Discontinue heparin promptly. A direct thrombin inhibitor such as lepirudin (0.4-mg/kg bolus, 0.15-mg/kg per hour infusion; PTT target 1.5-2.5 × baseline) or argatroban (2-µg/kg per min infusion; PTT target 1.5-3 × baseline) should be used for treatment of thromboses. Do not use low-molecular-weight heparin (LMWH), as antibodies often cross-react. Fondaparinux is also effective. Chronic ITP Prednisone, initially 1-2 mg/kg per day, then slow taper to keep the platelet count >60,000/µL. Dexamethasone 40 mg/d for 4 days, q2-4 weeks may be even more effective. intravenous immunoglobulin (IVIg) (2 g/kg in divided doses over 2-5 days) to block phagocytic destruction may be useful. Rituximab is effective in pts refractory to glucocorticoids. Eltrombopag (50 mg PO qd) boosts platelet production and allows delay or avoidance of splenectomy. Splenectomy, danazol (androgen), or other agents (e.g., vincristine, cyclophosphamide, fludarabine) are indicated for refractory pts or those requiring >5-10 mg prednisone daily. DIC Control of underlying disease most important; platelets, fresh-frozen plasma (FFP) to correct clotting parameters. Heparin may be beneficial in pts with acute promyelocytic leukemia. TTP Plasmapheresis and FFP infusions (plasma exchange), possibly IV IgG; recovery in two-thirds of cases. Plasmapheresis removes inhibitors of the vWF cleavage enzyme (ADAMTS13), and FFP replaces the enzyme. Disorders of Platelet Function Remove or reverse underlying cause. Dialysis and/or cryoprecipitate infusions (10 bags/24 h) may be helpful for platelet dysfunction associated with uremia. Hemostatic Disorders Withdraw offending drugs, replace vitamin C, plasmapheresis, and plasma infusion for TTP. Hemophilia A Factor VIII replacement for bleeding or before surgical procedure; degree and duration of replacement depends on severity of bleeding. Give factor VIII (e.g., Recombinate) to obtain a 15% (for mild bleeding) to 50% (for severe bleeding) factor VIII level. The duration should range from a single dose of factor VIII to therapy bid for up to 2 weeks. Dose is calculated as follows: Factor VIII dose = (Target level - baseline level) × weight (kg) × 0.5 unit/kg Up to 30% of pts may develop anti-factor VIII antibodies; activated factor VII or factor eight inhibitor bypass agent (FEIBA) may stop or prevent bleeding in these pts. Hemophilia B Recombinant factor IX (e.g., Benefix), FFP or factor IX concentrates (e.g., Proplex, Konyne). Because of the longer half-life, once-daily treatment is sufficient. Dose is calculated as follows: Factor IX dose = (Target level - baseline level) × weight (kg) × 1 unit/kg Von Willebrand Disease Desmopressin (1-deamino-8-d-arginine vasopressin) increases release of vWF from endothelial stores in type 1 vWD. It is given IV (0.3 µg/kg) or by nasal spray (2 squirts of 1.5-mg/mL fluid in each nostril). For types 2A, 2M, and 3, cryoprecipitate (plasma product rich in factor VIII) or factor VIII concentrate (Humate-P, Koate HS) is used: up to 10 bags bid for 48-72 h, depending on the severity of bleeding. Vitamin K Deficiency Vitamin K, 10 mg SC or slow IV. Fresh-frozen plasma. |
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