ALBERT

Description: The vitamin B12 and folate content of human platelets have been determined. The B12 concentration was sixfold that in red cells and one-sixth that in leukocytes. In normal whole blood, with a platelet count of 300,000 per cu. mm., the B12 activity contributed by platelets would be 6-21 pg. per ml. The contribution of platelets to the folate activity of normal whole blood averaged 0.4-1.7 ng. per ml. The folate activity in platelets was one-fifth that in an equal volume of red cells, but unlike red cell folate, was not increased by incubating platelet extracts with plasma.

Description: This is an electron microscopic study of the spleen in a case of hemoglobin H disease. The patient showed evidence in the peripheral blood of marked erythrocyte fragmentation. The spleen acted upon the abnormal erythrocytes in two major ways: 1. The erythrocytes entered the sinus lumen simultaneously via two intercellular slits on opposite sides of a lining cell and then split into two sphered fragments (which lay free in the sinus lumen) and the long, thin connecting fragment (which was retained in the cordal compartment and phagocytized). 2. Small, dense, spherical portions of erythrocytes were retained in the cord while the major portion of the cell was released into the sinus lumen. This is suggestive of pitting of rigid intracellular precipitates. The erythrocytes emerged from their passage through the cords and maintained bizarre forms in the sinus lumen. It is possible that the contents of these cells may be partially gelated to account for this.11 This gelation is thought to largely underlie their behavior in their circulation through the spleen. Evidence of increased erythrocytic breakdown was found in the numerous large macrophages present in the cords.

Description: 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.