Alteration of Coagulation in Intensively Transfused Hemophilic Patients

Bleeding may occasionally occur in adequately transfused hemophilic patients. To investigate this phenomenon, 11 patients with classical hemophilia had serial coagulation studies performed during intensive transfusion therapy with factor VIII concentrates given for surgical procedures. The studies included kaolin partial thromboplastin times (KPTT), fibrinogen, monomer, and fibrin split products (FSP) levels, and assays for factor VIII by the one-stage PTT method (PTT-VIII), thromboplastin generation time method (TGT-VIII), and immunologic method (VIII Ag). After an initial correcting dose, factor VIII concentrates were administered once to twice daily in a dose to keep the minimal level above 20 percent. Alterations of coagulation assays were most pronounced 7–10 days postoperatively. These included (1) KPTT values at least 20 seconds longer than expected for the percent factor VIII;(2) TGT-VIII levels consistently higher than PTT-VIII levels (mean difference was 20 percent);(3) VIII Ag values from 216–660 percent of normal. Fibrin monomer and FSP tests were frequently positive and fibrinogen levels ranged from 300–700 mgm percent. Four patients exhibited spontaneous wound bleeding on postoperative days 7, 7, 9, and 12 in spite of adequate factor VIII levels. These studies and the results of in vitro experiments with factor VIII concentrates suggest that altered proteins or degradation products of fibrinogen or factor VIII may produce spurious values for coagulation tests and may be associated with an increased bleeding tendency and/or abnormal wound healing.