A 67-year-old woman with adrenal cortical carcinoma had nephrectomy, adrenalectomy, inferior vena cava thrombectomy, splenectomy, and liver wedge biopsy. Surgical margins were clear of tumor, but examination of a liver biopsy specimen showed the presence of cancer. Four months after these procedures were done, scans of the abdomen showed progressive disease in the liver. The patient was then referred for chemotherapy. While hospitalized, she experienced acute shortness of breath during the first cycle of cisplatin and etoposide. Spiral computed tomography showed a tumor and bilateral pulmonary thrombus. Therapy with low-molecular-weight heparin was initiated, and the patient's platelet count was 285 cells/mm³. Two weeks later, the platelet count was 242 cells/mm³, but it then increased to 1114 cells/mm³ after 4 weeks of enoxaparin therapy. No other recent changes had been made in the patient's other medications, which included ranitidine, metoclopramide, dexamethasone, and vitamins. Enoxaparin therapy was discontinued and warfarin therapy was initiated while the patient received a second cycle of chemotherapy. Within 1 week, her platelet count decreased to 297 cells/mm³; within 1 month, however, it increased to 395 cells/mm³. Four months later, after two more cycles of chemotherapy and no disease progression, her platelet count was 355 cells/mm³.

The temporal relation between thrombocytosis and enoxaparin treatment and the lack of correlation to other known causes suggest enoxaparin as the potentially causative agent. Enoxaparin is a low-molecular-weight heparin approved for use in the prophylaxis of deep venous thrombosis. No reports in the medical literature have associated enoxaparin with thrombocytosis, and only five such cases have been reported to the manufacturer or to the Food and Drug Administration (Rhone-Poulenc Rorer. Personal communication). Four cases involved use of enoxaparin after surgery, with platelet counts increased to a maximum of 1200 cells/mm³. The fifth case was that of an anemic patient whose platelet count doubled to 450 cells/mm³ after 1 week of enoxaparin therapy. In none of these patients did the adverse effects occur secondary to thrombocytosis.

Extreme thrombocytosis has several causes. Cancer, splenectomy, and pharmacologic effects have all been associated with this condition [1, 2]. The reactive thrombocytosis seen after splenectomy occurs during the first few weeks of drug therapy and typically resolves within a few months. Thrombocytosis associated with malignant disease seems to progress with the cancer, and our patient's disease had not changed significantly. Correlation with the use and discontinuation of enoxaparin therapy suggests that this drug was the most likely causative agent. Unfortunately, our patient did not consent to collection of bone marrow aspirate to test the effect of enoxaparin on megakaryocytes in culture.

Clinicians should be aware of the potential rare association of enoxaparin with thrombocytosis. Further study of the causative mechanisms is warranted.