Use of porcine factor VIII for surgical procedures in hemophilia A patients with inhibitors.
We have described the use of polyelectrolyte fractionated porcine factor VIII (HYATE:C, Porton Speywood Ltd, Wrexham, UK) to provide hemostasis in 45 patients with hemophilia A complicated by inhibitor antibodies. The cases were collected from hemophilia care providers in seven nations and represent some of the experience with porcine factor VIII generated over the past 12 years. A wide variety of procedures was performed with varying degrees of associated hemostatic challenge in a difficult treatment group. The patients were representative of the hemophilia population in general and ranged in age from 1 to 67 years. The results of our survey should encourage clinicians to consider use of porcine factor VIII to provide hemostatic coverage in hemophilia patients with inhibitors who require surgical procedures. Hemostatic coverage was satisfactory in the vast majority of episodes; there have been only a small number of easily controlled, well-tolerated adverse reactions, which were usually self-limited in nature. No life-threatening reactions to porcine factor VIII were seen during coverage for surgical procedures in our survey, although serious reactions can occur as noted above. This is remarkable, since surgical patients usually are treated with higher doses of porcine factor VIII for greater periods of time than most other hemophilic patients treated for hemarthroses or soft-tissue bleeding, for example. Thrombocytopenia in association with porcine factor VIII therapy has been a major concern since the first crude preparations were used in the 1950s. Modern series, however, note the incidence of thrombocytopenia in only a minority of patients treated with the current polyelectrolyte fractionated preparations of porcine factor VIII. In our series, thrombocytopenia with platelet counts of less than 150 x 10(9)/L occurred in 11 of 54 treatment episodes (20%). The mechanism for thrombocytopenia demonstrated in a previous study involves porcine von Willebrand factor, which may copurify with porcine factor VIII and cause platelet aggregation and/or clearance from the circulation. The phenomenon of thrombocytopenia appears to be related to the administration of high doses of porcine factor VIII in some cases; however, in other patients, it may develop inconsistently at modest doses. It may be that there are idiosyncratic differences between patients that determine the dose of porcine factor VIII likely to cause thrombocytopenia. As yet, there is no way to predict which patient will develop thrombocytopenia while being treated with porcine factor VIII.(ABSTRACT TRUNCATED AT 400 WORDS)
Lozier
J N
JN
Department of Medicine, University of North Carolina, Chapel Hill.
Santagostino
E
E
Kasper
C K
CK
Teitel
J M
JM
Hay
C R
CR
D000818:Animals; D001323:Autoantibodies / Q000097:blood; D005169:Factor VIII / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000276:immunology / Q000627:therapeutic use*; D006467:Hemophilia A / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D013514:Surgical Procedures, Operative; D013552:Swine; D013921:Thrombocytopenia / Q000139:chemically induced
D001323:Autoantibodies; D005169:Factor VIII