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Biomedical subjects

H J Weiss

Publications and source records attributed to H J Weiss.

At least 145 records · Page 8Linked to original sources
PubMed1973

Defective ristocetin-induced platelet aggregation in von Willebrand's disease and its correction by factor VIII.

The antibiotic ristocetin, in concentrations of 1.0-1.5 mg/ml, aggregated normal platelets in citrated platelet-rich plasma by a mechanism in which the release reaction played only a minor role. Platelet aggregation by ristocetin in a concentration of 1.2 mg/ml was absent or markedly decreased in 10 patients with von Willebrand's disease. Lesser degrees of abnormality were obtained with a concentration of 1.5 mg/ml. The magnitude of the defect in ristocetin-induced platelet aggregation correlated well with the degree of abnormality of the bleeding time and the levels of antihemophilic factor (AHF, VIII(AHF)) procoagulant activity. In all patients, the defect in ristocetin-induced platelet aggregation was corrected in vitro by normal plasma. Correction was also obtained with a fraction of normal cryoprecipitate that eluted in the void volume with VIII(AHF) after chromatography on a gel that excludes molecules larger than 5 x 10(6). A similar fraction, devoid of VIII(AHF) activity, obtained from patients with von Willebrand's disease had no corrective effect, but fractions obtained from patients with hemophilia were just as effective as those obtained from normal subjects. The correction activity of plasma and partially purified factor VIII was inhibited by a rabbit antibody to human factor VIII but not by a human antibody against VIII(AHF) procoagulant activity. The studies provide further evidence that patients with von Willebrand's disease are deficient in a plasma factor that is necessary for normal platelet function. The activity of this factor appears to be associated with factor VIII but is unrelated to VIII(AHF) procoagulant activity.

Adenosine↗
PubMed1973

Quantitative assay of a plasma factor deficient in von Willebrand's disease that is necessary for platelet aggregation. Relationship to factor VIII procoagulant activity and antigen content.

In a previous paper, we showed that the abnormality of ristocetin-induced platelet aggregation in platelet-rich plasma in 10 patients with von Willebrand's disease could be corrected by a factor in normal plasma that was present in the same fractions as factor VIII procoagulant activity (antihemophilic factor, AHF, VIII(AHF)) when prepared by chromatography on Bio-Gel 5 M (Bio-Rad Laboratories, Richmond, Calif.). This observation suggests that patients with this disorder are deficient in a plasma factor, associated with the factor VIII molecule, that is necessary for normal platelet function. In the present paper, we describe, an assay for this factor, the von Willebrand factor (VIII(VWF)), based on the observation that a log-log relationship exists between the amount of ristocetin-induced aggregation of washed, normal platelets and the concentration of normal plasma present in the test system. We assayed the activity of VIII(VWF) as well as antihemophilic factor procoagulant activity (VIII(AHF)) and factor VIII antigen (VIII(AGN)) in 15 patients with von Willebrand's disease and 20 normal subjects. A highly significant correlation (r approximately 0.80) between VIII(VWF) and both VIII(AHF) was found in normal subjects and in patients with von Willebrand's disease. This finding, in addition to the observation that agarose gel chromatography fractions that have VIII(AHF) procoagulant activity also have VIII(VWF) activity, strongly suggests that the von Willebrand factor is associated with the factor VIII molecule. VIII(VWF) in normal plasma was not inhibited by human anti-VIII, and VIII(VWF) levels were normal in hemophilic plasma. Thus, the VIII(VWF) site on the factor VIII molecule appears to be different from that determining VIII(AHF). Finally, the activity of VIII(VWF) appeared to correlate better with the bleeding time than either VIII(AHF) or VIII(AGN). This suggests that VIII(VWF) assayed in this study may be the "anti-bleeding factor" that is deficient in von Willebrand's disease. These findings are consistent with a decreased synthesis of the factor VIII molecule in von Willebrand's disease and suggest the possibility of additional abnormalities of the site on the molecule that determines the activity of VIII(VWF).

Adult↗
PubMed1973

Ultrastructural findings in storage pool disease and aspirin-like defects of platelets.

Previous studies have shown that abnormalities in collagen-induced platelet aggregation may be due to an impaired release of storage pool ADP, the agent ultimately responsible for platelet aggregation. In some patients and in normal subjects who ingest aspirin, the storage pool of ADP is present in normal amounts, but the mechanism for releasing it appears to be defective ("aspirin-like" defect). In these subjects, the centripetal reorientation of the platelet granules, which may be early structural changes of the release reaction, failed to occur. In one preleukemic patient with an aspirin-like defect, the elements of the open-channel system were also increased. In a second group of patients the impairment of aggregation is due to a deficiency of storage pool ADP. In these patients with storage pool disease, the initial ultrastructural changes associated with the collagen-induced release reaction were normal. The most striking abnormality was a marked decrease in the number of platelet dense bodies. Since the platelets of these patients are deficient in both serotonin and the storage pool of adenine nucleotides, the findings suggest that, in human platelets, these substances are normally stored in the dense bodies. A defect in the formation or function of the dense bodies may account for the abnormalities of platelet aggregation in storage pool disease.

Adenosine Diphosphate↗