USE OF PROTHROMBIN COMPLEX CONCENTRATES (PCC) IN HEMOPHILIACS WITH INHIBITORS: LACK OF CORRELATION BETWEEN CLINICAL RESPONSE AND LABORATORY PARAMETERS

Abstract

Proplex (P), Konyne, and Auto-Factor IX (A) are PCC which can promote hemostasis in patients with hemophilia A with circulating inhibitors against Factor VIII. This is achieved by the variable amounts of procoagulant substances (presumably activated clotting proteins) present in the PCC. Six patients have received 337 infusions of PCC for 95 bleeding episodes, including iliopsoas hemorrhage, life-threatening upper airway bleeding, pseudotumor, and surgical procedures (laminectomy, laparatomy, dental extractions). No untoward thrombotic complications occurred, and circulating inhibitor levels fell in 4/6 patients while remaining constant in the 2 others. Many infusions were beneficial, but clinical responses were variable and unpredictable over a wide dosage range. To evaluate this inconsistency, we tested 15 different lots of P and A and found all of them to contain activated factors as evidenced by: (1) the ability of 1:100 to 1:5000 dilutions to shorten the unactivated partial thromboplastin time (PTT) of normal and hemophilic plasma in vitro, and (2) transient shortening of patients' prothrombin time and PTT after each dose. There was no correlation between these laboratory parameters of accelerated coagulation and cessation of bleeding. Therefore, efficacy of PCC must be judged primarily by clinical response rather than by laboratory tests demonstrating activation of coagulation.

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