Analytic Review: Von Willebrand’s Disease-Diagnostic Criteria

Our present criteria for diagnosing von Willebrand’s disease are summarized below and illustrative examples of recently studied patients are shown in Table 1.

A) Prolonged bleeding time and decreased AHG:

When these abnormalities, inherited as an autosomal dominant, are found in several family members, they are considered diagnostic for these patients and for their clinically affected relatives, even though the latter may now show both defects (Case 10). In the absence of family studies, the diagnosis would also be made in individual subjects if a history of bleeding in relatives was consistent with autosomal inheritance (Cases 3,13,18). When family studies are negative (sporadic cases) or no history is attainable, a diagnosis of typical von Wille-brand’s disease would also be made (Cases 1,2,4,14,15,16) unless intrinsic platelet defects were found (see below) or plasma transfusion failed to produce a progressive increase in AHG activity.

B) Prolonged bleeding time, normal AHG:

The diagnosis would be considered "probable" in such a patient if the following criteria were met:

1. There was no evidence of an "intrinsic" platelet abnormality, as indicated by normal values for platelet aggregation, PF-3 availability and ADP release by connective tissue and kaolin

and

2. Platelet adhesiveness, by the modified Salzman test, was abnormal and/or the patient’s bleeding time was shortened by transfusion of plasma in a dosage of 13-15 ml. per Kg. body weight.

C) Normal bleeding time, decreased AHG (Case 17):

A diagnosis of probable von Willebrand’s disease would be made if:

1. An unequivocal pattern of autosomal dominant inheritance, by history, ruled out hemophilia.

2. The Salzman test was abnormal.

3. Transfusion of hemophiliac, as well as normal plasma resulted in a progressive increase in plasma AHG concentration.

D) Normal bleeding time, normal AHG:

The diagnosis would be considered as "possible" if:

1. There was no evidence of intrinsic platelet abnormality (see B 1).

2. The Salzman test was abnormal.

The above criteria are tentative and, undoubtedly, will not satisfy all investigators. To confuse matters even more, some patients who appear to have the "classic" syndrome may also have abnormal platelet factor 3³⁸ or fail to "synthesize" AHG after plasma transfusion.^13,38 Whether even the "classic" syndrome represents a spectrum of disorders remains to be determined.