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S D Berkowitz

Publications and source records attributed to S D Berkowitz.

40 records · Page 3Linked to original sources
PubMed1987

Proteolytic degradation of von Willebrand factor after DDAVP administration in normal individuals.

The infusion of 1-deamino-8-D-arginine vasopressin (DDAVP) in normal individuals is followed by an increase in factor VIII/von Willebrand factor (vWF) in plasma, by an increase in intensity of all sizes of multimers, and by the appearance of larger multimers of vWF than those seen in the resting state. Since the larger multimers are rapidly cleared and proteolysis is known to cause disaggregation of large multimers, we evaluated the degree of vWF proteolysis after DDAVP administration. DDAVP was infused into eight normal adult volunteers, and the relative proportions of the intact 225 kilodalton (kDa) subunit and the 189, 176, and 140 kDa vWF fragments were compared before and at different times after DDAVP infusion. The relative proportion of the 176 kDa fragment was increased, whereas that of the other species was decreased, thereby indicating that proteolytic fragmentation had occurred. However, plasmin did not appear to be responsible because the vWF fragments characteristically produced by this enzyme could not be detected. Concomitant analysis of vWF multimeric structure showed that these changes were accompanied by an increase in the relative proportion of the satellite bands, which suggests that they were proteolytically generated. Proteolysis may explain, at least in part, rapid clearance of larger vWF multimers released by DDAVP.

Adolescent↗
PubMed1986

Subunit composition of plasma von Willebrand factor in patients with the myeloproliferative syndrome.

In order to evaluate the role of proteolysis in acquired von Willebrand's disease (vWD) associated with the myeloproliferative syndrome, we have determined the relative quantity of von Willebrand factor (vWF) fragments as compared with the intact 225 kDa subunit in four patients. The plasma vWF of each individual lacked large multimers; each had a prolonged bleeding time; and both platelet and leukocyte counts were elevated. Plasma was obtained from blood drawn into 1 mmol/L leupeptin, 6 mmol/L N-ethylmaleimide, and 5 mmol/L EDTA to prevent in vitro proteolysis. vWF was isolated from plasma by immunoadsorbent chromatography, reduced, subjected to SDS-5% polyacrylamide gel electrophoresis, and immunoblotted with a mixture of 55 anti-vWF monoclonal antibodies. In three patients with essential thrombocytosis (ET) the 176 and 140 kDa fragments were increased in proportion to the intact 225 kDa subunit indicating increased proteolysis. Treatment of one ET patient with CCNU (Lomustine) decreased the platelet count and, to a lesser extent, the white blood cell count. This was associated with a correction of the bleeding time, a partial correction of the multimeric abnormality, and a lessening of vWF cleavage. In a patient with polycythemia rubra vera (PRV) the proportion of the 176 kDa fragment was increased to the upper limit of normal but there was no definite evidence of increased proteolysis. These studies provide evidence that proteolysis plays a role in the acquired von Willebrand's disease associated with the myeloproliferative syndrome. However, other mechanisms must also be considered.

Bleeding Time↗