Platelet von Willebrand factor: an important determinant of the bleeding time in type I von Willebrand's disease

We studied 17 patients with moderate to mild type I von Willebrand's disease (vWd) and correlated the bleeding time with the plasma von Willebrand factor antigen (vWf Ag), the plasma vWf activity (ristocetin cofactor), the platelet vWf Ag, and the platelet vWf activity. We found an excellent correlation between the bleeding time and the platelet vWf activity and, to a lesser extent, between the bleeding time and the platelet vWf Ag. The length of the bleeding time was inversely proportional to the level of the platelet vWf (P less than .001) or, to a lesser extent, the platelet vWf Ag (P less than .05). The plasma vWf Ag and activity did not correlate significantly with the bleeding time. These studies indicate that the platelet vWf is one of the important bleeding time factors in type I vWd and that the platelet vWf plays an important role in the early steps of hemostasis.     

Platelet-type von Willebrand's disease: characterization of a new bleeding disorder

An autosomally transmitted bleeding diathesis sharing some, but not all, features previously described in von Willebrand's disease (vWd) was studied in five patients representing three generations of a single family. Bleeding times in the upper normal range in conjunction with low-normal platelet counts, normal factor VIII coagulant activity and VIII-related antigen, decreased VIII-ristocetin cofactor activity, selective decrease of the higher molecule weight factor VIII/von Willebrand factor (VIII/vWF) multimers, and increased ristocetin- induced platelet agglutination at low ristocetin concentrations were characteristic. Binding of patient VIII/vWF to washed normal platelets was within normal limits, whereas binding of normal VIII/vWF to patient platelets was significantly increased (p less than 0.001 at 0.6 mg/ml ristocetin). This disorder accordingly appears to involve an intrinsic platelet abnormality affecting platelet-VIII/vWF interactions. It is proposed that the concept of vWD be broadened to include patients with this abnormality, which may appropriately be called "Platelet-type von Willebrand's disease."     

Massive postoperative intramuscular bleeding in acquired von Willebrand's disease

We describe a case of acquired von Willebrand's disease (vWD) associated with monoclonal gammopathy with undetermined significance (MGUS) in a 54-year-old man who was admitted with hemarthrosis and extensive thigh muscle hematoma following arthroscopic surgery and postoperative prophylaxis with low molecular weight heparin. Coagulation tests were compatible with acquired vWD: prolonged activated partial thromboplastin time (aPTT) (56.1 s), decreased levels of factor VIII coagulant activity (23%), low concentrations of von Willebrand's factor (vWF) antigen (13%), and undetectable ristocetin cofactor activity (<10%). Infusion of a vWF-containing factor VIII concentrate failed to normalize the plasma levels of vWF-related parameters. Only additional intravenous administration of immunoglobulins led to a transient normalization of ristocetin cofactor activity, vWF antigen, and factor VIII coagulant activity. While the spontaneous bleeding tendency in this case was mild, surgery and administration of prophylactic doses of low molecular weight heparin led to life-threatening bleeding.     

Failure of AHF concentration to control bleeding in von Willebrand's disease.

A newly available dried concentrate of antihemophilic factor (Profilate, Abbott Laboratories) was compared with standard, blood-bank prepared cryoprecipitate in the control of bleeding in a patient with von Willebrand's disease. Profilate effectively raised plasma levels of factor VIII but produced only half the expected increase in plasma ristocetin aggregation factor (RAF), and this RAF did not bind readily to the platelets in the presence of ristocetin. Furthermore, the Profilate had little effect upon the bleeding time or the clinical hemorrhage. In contrast, the cryoprecipitate did increase plasma RAF to the expected level, and this RAF bound readily to the patient's platelets in the presence of ristocetin. Cryoprecipitate promptly controlled bleeding. We conclude that the RAF present in Profilate retains in vitro activity but is incapable of augmenting platelet function in vivo.     

von Willebrand's disease in Scandinavia and on difficulties in diagnosing von Willebrand's disease type I.

The research on von Willebrand's disease performed in Sweden and Finland since the late 1920s is reviewed. The difficulties in diagnosing mild von Willebrand's disease, due to intra-individual variability, is discussed in relation to making correct pedigrees for genetic studies. As shown by some examples, new techniques for genetic studies will eliminate such difficulties and lead to better understanding of the pathogenesis.     

Hydroxyethyl starch induced acquired von Willebrand's disease.

Hydroxyethyl starch (HES) (Hespan, DuPont) is a widely used synthetic volume expander which in standard doses of up to 1.5l in 24 h has no significant effect on coagulation (Munsch et al. 1988). However, the data sheet states that in large volumes HES may alter the coagulation mechanism. We now report a case of HES induced acquired von Willebrand's disease (vWD) in which severe bleeding occurred.     

Arthropathy in von Willebrand's disease

Summary A 62-year-old woman with severe von Willebrand's disease and a long history of joint complaints is presented. Her history, the progressive radiological findings, the demonstration of haemarthrosis and a literature review support the view that some patients with von Willebrand's disease can suffer from an incapacitating arthropathy akin to that seen in haemophilia.     

Gastro-intestinal bleeding in acquired von Willebrand's disease: efficacy of high-dose immuno-globulin where substitution treatments failed

Summary. We report a case of acquired von Willebrand's disease with severe and persistent gastro-intestinal bleeding from multiple bleeding points. He received maximum substitution treatment including factor VIII concentrates, cryoprecipitate and platelets. He also received DDAVP. There was no change in the rate of blood loss.
He was then treated with high-dose intravenous gammaglobulin and the blood loss stopped abruptly. He remained well for several months when bleeding recommenced and he again responded promptly to gamma-globulin. This is a useful maintenance treatment for patients with acquired von Willebrand's disease.