The arterial microvascular thrombotic events in thrombocythemia including erythromelalgia, atypical and typical cerebral and ocular transient ischemic attacks, and acute coronary syndromes already occur at platelet counts > 400 x 10(9)/L and are sensitive to low-dose aspirin, which does not elicit bleedings at platelet counts < 1,000 x 10(9)/L. An increasing platelet count in thrombocythemia to above 1,000 x 10(9)/L is accompanied by the acquisition of a von Willebrand factor deficiency due to the loss of intermediate and large von Willebrand factor multimers. The arterial thrombotic condition in thrombocythemia changes into an overt spontaneous bleeding tendency at mean platelet counts of about 2,000 +/- 1,000 x 10(9)/L due to an acquired von Willebrand disease type II with normal values for von Willebrand factor antigen concentration but absence of intermediate and large von Willebrand factor multimers in plasma. At platelet counts between 1,000 and 2,000 x 10(9)/L, thrombosis and bleeding frequently occur in sequence or paradoxically, and low-dose aspirin does prevent thrombotic complications but aggravates or may elicit bleeding symptoms. Reduction of the platelet count < 1,000 x 10(9)/L significantly restores the von Willebrand factor deficiency with the reappearance of the intermediate and some of the large von Willebrand factor multimers and the disappearance of the bleeding tendency, but the thrombotic tendency persists as long as platelet counts are above the upper limit of normal. The acquisition of von Willebrand factor deficiency at increasing platelet counts can readily explain the paradox of thrombosis and bleeding in thrombocythemia and has important clinical implications.