Chapter 110. Coagulation Disorders (Part 11)

Treatment with FFP is the most effective way to correct hemostasis in patients with liver failure. Infusion of FFP (5–10 mL/kg; each bag contains ~200 mL) is sufficient to ensure 10–20% of normal levels of clotting factors but not correction of PT or aPTT. Even high doses of FFP (20 mL/kg) do not correct the clotting times in all patients.
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Chapter 110. Coagulation Disorders (Part 11) Chapter 110. Coagulation Disorders (Part 11) Treatment with FFP is the most effective way to correct hemostasis inpatients with liver failure. Infusion of FFP (5–10 mL/kg; each bag contains ~200mL) is sufficient to ensure 10–20% of normal levels of clotting factors but notcorrection of PT or aPTT. Even high doses of FFP (20 mL/kg) do not correct theclotting times in all patients. Monitoring for clinical symptoms and clotting timeswill determine if repeated doses are required 8–12 h after the first infusion.Platelet concentrates are indicated when platelet counts are Acquired Inhibitors of Coagulation Factors An acquired inhibitor is an immune-mediated disease characterized by thepresence of an autoantibody against a specific clotting factor. FVIII is the mostcommon target of antibody formation, but inhibitors to prothrombin, FV, FIX, FX,and FXI are also reported. The disease occurs predominantly in older adults(median age of 60 years) but occasionally in pregnant or postpartum women withno previous history of bleeding. In 50% of patients with inhibitors, no underlyingdisease is identified at the time of diagnosis. In the remaining half, the causes areautoimmune diseases, malignancies (lymphomas, prostate cancer), dermatologicdiseases, and pregnancy. Previous history of open surgery in which topicalthrombin is used, especially preparations containing bovine FV, is sometimesassociated. Bleeding episodes occur commonly into soft tissues and in thegastrointestinal or urinary tracts and skin. In contrast to hemophilia, hemarthrosisis rare. Retroperitoneal hemorrhages and other life-threatening bleeding mayappear suddenly. The overall mortality in untreated patients ranges from 8 to 22%,and most deaths occur within the first few weeks after presentation. The diagnosisis based on the prolonged aPTT with normal PT and TT. The aPTT remainsprolonged after mixture of the test plasma with equal amounts of pooled normalplasma for 2 h at 37°C. The Bethesda assay using FVIII-deficient plasma asperformed for inhibitor detection in hemophilia will confirm the diagnosis. Majorbleeding is treated with high doses of human or porcine FVIII, PCC/PCCa, orrecombinant FVIIa. High-dose intravenous gamma globulin and anti-CD20monoclonal antibody (rituximab) have been reported to be effective in patientswith autoantibodies to FVIII. In contrast to hemophilia, inhibitors innonhemophilia patients are sometimes responsive to prednisone alone or inassociation with cytotoxic therapy (e.g., cyclophosphamide). The presence of lupus anticoagulant can be associated with venous orarterial thrombotic disease. However, bleeding has also been reported in lupusanticoagulant; it is due to the presence of antibodies to prothrombin, which resultsin hypoprothrombinemia. Both disorders show a prolonged PTT that does notcorrect on mixing. To distinguish acquired inhibitors from lupus anticoagulants,the dilute Russells viper venom test and the hexagonal-phase phospholipids testwill be negative in patients with an acquired inhibitor and positive in patients withlupus anticoagulants. Moreover, lupus anticoagulant interferes with the clottingactivity of many factors (FVIII, FIX, FXII, FXI), whereas acquired inhibitors arespecific to a single factor. Further Readings Caldwell SH et al: Coagulation disorders and hemostasis in liver disease:Pathophysiology and critical assessment of current management. Hepatology44:1039, 2006 [PMID: 17006940] Hoyer LW: Hemophilia A. N Engl J Med 330:39, 1994 Key NS, Negrier C: Coagulation factor concentrates: Past, present, andfuture. Lancet 370:439, 2007 [PMID: 17679021] Levi M, Opal SM: Coagulation abnormalities in critically ill patients.Critical Care 10:222, 2006 [PMID: 16879728] Mannucci PM, et al: Recessively inherited coagulation disorders. Blood104:1243, 2004 [PMID: 15138162] Stafford DW: The vitamin K cycle. J Thromb Haemost 3:1873, 2005[PMID: 16102054]