14-09: Acquired Disorders of Coagulation

1. ACQUIRED ANTIBODIES TO FACTOR II

Patients with antiphospholipid antibodies occasionally have antibody specificity to coagulation factor II (prothrombin) that accelerates factor II clearances and can lead to severe hypoprothrombinemia and bleeding. Mixing studies may or may not reveal the presence of an inhibitor, as the antibody typically binds to a non-enzymatically active portion of the molecule leading to accelerated clearance, but characteristically the PT is prolonged and levels of factor II are low. FFP should be administered to treat bleeding. Treatment is immunosuppressive.

2. ACQUIRED ANTIBODIES TO FACTOR V

Products containing bovine factor V (such as topical thrombin or fibrin glue, frequently used in surgical procedures) can lead to formation of an anti–factor V antibody that cross-reacts with human factor V. Clinicopathologic manifestations range from a prolonged PT in an otherwise asymptomatic individual to severe bleeding. Mixing studies suggest the presence of an inhibitor, and the factor V activity level is low. In cases of serious or life-threatening bleeding, IVIG or platelet transfusions, or both, should be administered, and immunosuppression (as for acquired inhibitors to factor VIII) may be offered.

3. ACQUIRED ANTIBODIES TO FACTOR VIII

Acquired hemophilia A due to factor VIII inhibitors is the most common acquired factor-specific bleeding disorder. Spontaneous antibodies to factor VIII can occur in adults without a prior history of hemophilia; older adults and patients with lymphoproliferative malignancy or autoimmune disease and those who are postpartum or postsurgical are at highest risk. The clinical presentation, which should be viewed as a medical emergency, typically includes extensive soft tissue ecchymoses, hematomas, and mucosal bleeding, as opposed to hemarthrosis characteristic of congenital hemophilia A. The aPTT is typically prolonged and does not correct upon mixing; factor VIII activity is low and a Bethesda assay reveals the titer of the inhibitor. Inhibitors of low titer (less than 5 BU) may often be overcome by infusion of high doses of factor VIII concentrates, whereas high-titer inhibitors (greater than 5 BU) must be treated with serial infusions of activated prothrombin complex concentrates, recombinant human activated factor VII, or recombinant porcine factor VIII. Emicizumab is also a treatment option. Along with establishment of hemostasis by one of these measures, immunosuppressive treatment with corticosteroids with or without oral cyclophosphamide or rituximab must be instituted to eradicate the autoantibody. Treatment with IVIG and plasmapheresis can be considered in refractory cases. Unlike in congenital factor VIII deficiency of hemophilia A, the patient’s bleeding does not correlate well with the factor VIII activity level, so the clinician must be concerned with any elevation of aPTT secondary to acquired factor VIII inhibitor. All such patients require immediate referral to a hematologist.