The Treatment of Haemorrhage in von Willebrand's Disease and the Blood Level of Factor VIII (AHG)

Abstract

THE treatment of haemorrhage in patients severely affected with von Willebrand's disease has presented difficulty. Not only do these patients have a capillary defect evidenced by a greatly prolonged bleeding-time test but also a low level of Factor VIII in the blood. It has usually been assumed that adequate control requires that both defects be corrected. From the observations of Weiss (1962), Cornu, Larrieu, Caen andBernard (1963) and from our own records the duration of the bleeding recorded by the bleeding-time test is shortened erratically and for short periods of time following suitable treatment. The preparations with the best ability to shorten the bleeding time are those derived from fresh plasma collected into siliconecoated or plastic containers: such fractions are not readily available. When patients with von Willebrand's disease are treated with preparations containing Factor VIII the elevation of the Factor-VIII level in the blood continues for longer than in haemophilic patients. Also the administration of haemophilic plasma causes a rise in the blood level of Factor VIII (Nilsson, Blomback and Blombick, 1960; Cornu et al., 1963). It seems that these patients have some ability to form Factor VIII but lack an essential stimulating factor which is present in normal and haemophihc plasma. It is therefore much easier to raise the blood level of Factor VIII than effectively to reduce the bleeding time.

The effects of epinephrine infusion in patients with von Willebrand's disease.

“…Although it has both practical and conceptual importance, the cause of the sustained rise in VIIIAJI after transfusion in VWD, greater than that calculated from the quantity of VIIIAHF transfused, is not understood (4)(5)(6)(7). Previous studies have suggested that this posttransfusion VIIIAHF has physicochemical (8) and procoagulant (4)(5)(6)(7) properties like those of normal plasma Factor VIII.…”

“…Previous studies have suggested that this posttransfusion VIIIAHF has physicochemical (8) and procoagulant (4)(5)(6)(7) properties like those of normal plasma Factor VIII. While susceptible to inactivation by both human and rabbit anti-Factor VIII antibodies (9), it has been reported that the "stimulated Factor VIII" does not precipitate with rabbit anti-Factor VIII (9,10), an observation which suggests an incomplete Factor VIII may be produced in these patients.…”

Antihemophilic Factor Antigen. LOCALIZATION IN ENDOTHELIAL CELLS BY IMMUNOFLUORESCENT MICROSCOPY

“…Defective platelet function-and a prolonged bleeding time-in von Willebrand's disease is attributed to VWF deficiency and fractions of normal plasma correct these abnormalities in vivo and in vitro (24)(25)(26)(27)(28). As AHF procoagulant activity and VWF are usually present in the same fractions obtained from normal plasma, it has been suspected for many years that the two activities might be present on a single molecule.…”

Biochemical Characteristics of Therapeutic Plasma Concentrates Used in the Treatment of von Willebrand Disease

“…Many clinicians prefer con centrates to cryoprecipitate (until recently the blood product of choice) because they are treated with virucidal methods, as yet not widely applicable to cryoprecipitate, that minimize the risk of transmission of bloodborne infectious agents. All concentrates are efficacious in correcting the coagulation fac tor VIII defect present in patients with von Willebrand disease [1], As a result, they are usually efficacious in controlling soft-tis sue and postoperative hemorrhages, that are mainly determined by low factor VIII levels [2]. On the other hand, the effect of concen trates on the prolonged bleeding time -the laboratory hallmark of the primary hemosta sis defect in von Willebrand disease -is usual ly not consistent and limited to the early post infusion period [1,3].…”