Intravascular Coagulation with Use of Human Prothrombin Complex Concentrates

Abstract

Prothrombin complex concentrates are used in the treatment of the congenital bleeding disorders associated with Factors II, VII, IX, and X deficiencies. They have also been extensively used to treat acquired coagulation abnormalities secondary to vitamin K deficiency, warfarin ingestion, and various types of liver disease. The reported complications of prothrombin complex concentrates administration include hepatitis, anaphylaxis, and thrombosis. This paper documents the development of disseminated intravascular coagulation in association with the administration of prothrombin complex concentrates to patients with liver disease.

Use of human factor VIIa in the treatment of two hemophilia A patients with high-titer inhibitors.

“…However, such concentrates also have been reported to be thrombogenic (6)(7)(8). Activated prothrombin complex concentrates contain Factors IX, X, VII, and prothrombin in both activated and zymogen forms.…”

“…Recently, the use concentrates of the unactivated and activated prothrombin-complex have met with limited success in some cases (1)(2)(3)(4)(5), while in others, evidence of disseminated intravascular coagulation or thromboembolic complications were observed (6)(7)(8). The putative hemostatic agent(s) in these preparations has never been identified, although Factor VIIa has been suggested as one possibility (9).…”

Binding of human factor VII and VIIa to monocytes.

“…60 Ml of Factor VIII-deficient plasma (George King Biomedical, Inc., Overland Park, KS), 60 MI of rabbit brain cephalin (1-9 dilution of stock suspension) and 60 Al of the sample to be assayed diluted appropriately in HRB with 0.005 M sodium citrate, were incubated 30 s at 37°C. The reaction was then started by addition of 60 Ml of 25 mM CaC12 at 37°C.…”

Factor VIII-bypassing activity of bovine tissue factor using the canine hemophilic model.

“…In many cases, concentrate therapy is restricted to organ-threatening or lifethreatening bleeding in these patients. Activated prothrombin concentrates have shown efficacy, but are expensive, less active than replacement therapy with factor VIII, and can cause disseminated intravascular coagulation (15)(16)(17). The active component(s) of these preparations is still a matter of controversy (12)(13)(14), although originally proposed to be activated products of the clotting factors II, VII, IX, and X (32).…”

“…A variety of methods have been utilized to treat bleeding episodes in inhibitor patients, including immunosuppression (3), antibody depletion through plasmapheresis (4), high-dose factor VIII therapy leading to immune tolerance (5)(6)(7), and repeated treatment with factor VIII combined with immunosuppression (8). Prothrombin complex concentrates have proven to be partially effective (9-1 1) but their use is controversial owing to uncertainty with regard to the putative factors responsible (12)(13)(14), thrombogenicity (15)(16)(17), and the risk of viral infections. One component of prothrombin complex concentrates, factor VIIa, has been reported to be efficacious in the treatment of hemophiliacs with inhibitors (18).…”