Investigation of plasma von Willebrand factor and circulating platelet aggregating activity in mitomycin C‐related hemolytic‐uremic syndrome

Abstract

We have studied the ability of the plasma to induce aggregation of both homologous and heterologous platelets in four patients with hemolytic-uremic syndrome (HUS) associated with chemotherapy with mitomycin C (MMC). Neither platelet aggregation was elicited by patients' plasmas nor the in vitro addition of purified von Willebrand factor (vWF) had any effect on the aggregation pattern. In addition, ristocetin-induced binding of patients' vWF to formaldehyde-fixed platelets was normal, and multimeric vWF analysis revealed a normal structure of patients' plasmatic vWF whatever the clinical stage in which it was studied. These findings suggest that, in spite of the existence of common clinical and biological features in the various forms of HUS, the pathogenesis of MMC-related HUS may be, at least in part, different from that of the other forms of HUS in which both platelet-aggregating activity and alterations in the vWF are found.

Abnormalities of von willebrand factor multimers in drug‐associated thrombotic microangiopathies

“…It may reflect the binding of unusually large and the The results of this investigation differ from the findings of the two earlier studies involving mitomycin Cand cyclosporin A-induced thrombotic microangiopathies [ 10,l I], in which no abnormal vWF multimers were detected. The method of gel electrophoresis is likely to account for the discrepancy between our results and the earlier studies [ 10,111. The SDS-1% agarose gel system used in our analysis is superior to SDS-1.6% agarose or agarose-acrylamide in the detection of unusually large vWF multimers [2].…”

“…The increased quantity of vWF antigen observed in patient 2 has been seen previously in some patients with thrombotic microangiopathies [2,6,10,11]. Increased levels of plasma vWF may be associated with vascular endothelial cell damage or stimulation [ 171.…”

A review of hemolytic uremic syndrome in patients treated with gemcitabine therapy

“…Some researchers suggest the level of serum factors such as tumor necrosis factor-␣, interleukin-1␤, and interleukin-6 as well as von Willebrand factor (vWF) antigen and low molecular weight vWF multimers may be used to distinguish between malignancy-associated HUS and chemotherapy-associated HUS. [67][68][69][70][71][72][73] However, such studies remain experimental and are not readily available in the majority of community settings.…”

“…51,78,80 -82 Other authors postulate that microvascular injury is the cause of the condition. [67][68][69][70][71][72][73] However, to our knowledge there is no known mechanism to account for gemcitabine being a causative agent of HUS. MMC, a chemotherapy agent known to be associated with HUS, is an antibiotic that contains quinone, urethane, and aziridine groups.…”

Von willebrand factor availability in platelet concentrates stored for 5 days

“…Multimeric analyses were performed by mean of SDS-agarose gel electrophoresis [8] and autoradiographs of the electrophoretic runs were scanned in an EC 910 Transmission densitometer equipped with an EF 934 densitometer software (EC Apparatus Corporation, FL). Statistic analyses were made by the Snedecor "F" test.…”