Acquired type 2A von Willebrand disease in chronic myelocytic leukemia.

Acquired von Willebrand disease (vWD) has been described in a few patients with chronic myelocytic leukemia (CML). We present here acquired type 2 vWD associated with CML and provide characterization of an inhibitor to von Willebrand factor (vWF) from this patient. His bleeding time was prolonged. Ristocetin-induced platelet agglutination was abolished whereas botrocetin-mediated aggregation was normal. Multimeric analysis of vWF from patient's plasma showed that larger sizes of multimers were reduced. His past and family histories were negative for bleeding tendency. These results suggested that acquired type 2 vWD was present during his clinical course. The inhibitor was purified by Staphylococcal protein A, suggesting an IgG antibody. Both binding of 125I-vWF to GPIb and platelet agglutination by ristocetin were inhibited by the patient IgG with the concentrations of competing substances necessary to inhibit specific binding by 50% (IC50s) of 260 micrograms/ml and 420 micrograms/ml, respectively. However, the IgG had no effect on these studies mediated by botrocetin. The IgG only reacted with intact vWF and a 39/34 kDa fragment of vWF. These results indicate that the recognition of GPIb binding site(s) on vWF by the IgG is a central pathogenesis of acquired type 2 vWD in this case.