We appreciate Dr. Williams's interest in our report of thrombocytosis associated with the use of enoxaparin in a patient with adrenocortical carcinoma. We argue that the patient's clinical course is not consistent with other known causes. Thrombocytosis in association with splenectomy is first noted within 2 weeks after the procedure and typically resolves over a few months, although the reactive process occasionally takes years to resolve [1, 2]. As Dr. Williams notes, neoplastic processes may also be associated with severe thrombocytosis, usually because of increased platelet production [2, 3]. Our patient's platelet counts were normal, about 250 000 to 300 000 cells/mm³, before and after splenectomy. They remained at this level for nearly 5 months after surgery, and the baseline level was unaffected by the patient's slowly progressive disease or chemotherapy. The patient received a course of chemotherapy after starting enoxaparin therapy that was identical to the one she received before starting treatment with this new drug. Her platelet levels quadrupled within 4 weeks of starting enoxaparin therapy and returned to normal levels within 2 weeks of drug withdrawal, with no other changes in medications or clinical status of tumor bulk. Given this time course, it is unlikely that the patient's asplenia or carcinoma caused thrombocytosis.

Although the patient may have had a hypercoagulable state associated with her cancer, there was no evidence of disseminated intravascular coagulation before or during this period. Before and after splenectomy, blood counts remained in the normal narrow range, as noted above. The prothrombin time was 14.8 seconds, the ratio for a control to patient standardization was 1.2, the activated partial thromboplastin time was 28.4 seconds, and blood films showed no histocytes. Furthermore, the platelet count has remained unchanged throughout the year since the initial observation. This is strong evidence against a significant microangiopathic coagulopathy. The case as we reported it, in association with this additional information, clarifies the temporal association of enoxaparin use with thrombocytosis and the prompt resolution of thrombocytosis after drug withdrawal. No other causative factors were found.

Dr. Williams is appropriately skeptical about our assigning causality on the basis of clinical observation alone. Information on the serum levels of thrombopoietin and interleukin-11 during and after the discontinuation of enoxaparin therapy in patients with this potential association would be helpful. In addition, data on the effect of enoxaparin on megakaryocyte cultures of these patients with and without the presence of patient serum, thrombopoietin, and interleukin-11 would also be informative. The intent of our report was to point out this possible association and stimulate interest in these laboratory correlative studies.