Involvement of von willebrand factor in thrombosis following asparaginase‐prednisone‐vincristine therapy for leukemia

Abstract

To determine if factor VIII-von Willebrand factor (vWF) complex is involved in the thrombosis associated with asparaginase-prednisone-vincristine induction therapy for acute lymphoblastic leukemia, plasma vWF was analyzed by sodium dodecyl sulfate-agarose gel electrophoresis and crossed immunoelectrophoresis. Five patients with cerebral thrombosis were studied; all had a decreased platelet count following the complication. Sequential studies of three patients disclosed changes in plasma vWF multimer pattern. One patient who was studied serially from 2 days before to 1 day after the event, had an increase in unusually large plasma vWF multimers that disappeared after the complication. The other two patients who were studied at presentation subsequently showed a decrease in plasma large vWF multimers, especially remarkable in the patient having the sharpest decrease in platelet count. No appreciable difference in vWF multimer pattern, when compared to normal pooled plasma, was found in the remaining two patients who were only studied at presentation, or in the seven controls who received the same treatment but did not develop thrombosis. Crossed immunoelectrophoretic analyses of two patients tested disclosed a right shift of immunoprecipitin line in one and a left shift in the other. Our findings suggest that the thrombotic complications resulted from platelet agglutination by plasma vWF.

A prospective cohort study determining the prevalence of thrombotic events in children with acute lymphoblastic leukemia and a central venous line who are treated with L‐asparaginase

“…[2][3][4][5][6][7][8][9][10][11][12][13][14] However, the true prevalence and extent of TEs in this patient population are unknown. The PARKAA Study was an open, randomized, controlled, extended, Phase II study with the primary objective of determining the prevalence of TEs in children with ALL during treatment with ASP.…”

“…The timing of TEs in children with ALL is very consistent in the literature, occurring either during or immediately after chemotherapy with L-asparaginase (ASP). [2][3][4][5][6][7][8][9][10][11][12][13][14] ASP is an effective chemotherapeutic agent that catalyzes the hydrolysis of L-asparagine. Human lymphoblasts rely on exogenous asparagine, and ASP induces a relative asparagine deficiency, resulting in cell death.…”

Thromboembolic events in children with acute lymphoblastic leukemia (BFM protocols): prednisone versus dexamethasone administration

“…Pui et al 7,16 demonstrated in 1985 and 1987 that an altered von Willebrand factor molecule was found in leukemic children treated with CASP and PRED. Therefore, we have included the determination of von Willebrand factor antigen in the study presented here.…”

<i>L</i>-Asparaginase in Acute Lymphoblastic Leukemia Treatment: The Role of Human Antithrombin III Concentrates in Regulating the Prothrombotic State Induced by Therapy

“…The fact that the iatrogenic damage induced by L-Ase on the hemostatic system is not due to AT III synthesis alone, but also to other factors in the hemostatic balance was confirmed, however [13]. The administration of AT III concentrates alone surely cannot restore hemostasis.…”