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In Reply

Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY

Charles W. Francis

Department of Medicine, School of Medicine and Dentistry, Rochester, NY

Anna Falanga

Department of Hematology/Oncology, United Hospital of Bergamo, Bergamo, Italy

Gary H. Lyman

Department of Medicine, Duke University, Durham, NC

We agree with Dr Atkins that the use of anticoagulants in patients with intracranial malignancy can be challenging, and the issues involved have recently been reviewed in this Journal.¹ There is a high risk of venous thromboembolism (VTE) in these patients that contributes to both morbidity and mortality, and the risk of hemorrhage is also increased without anticoagulation, and even more with anticoagulation. We believe that the benefits of anticoagulation are greater than the risks in most patients with intracranial malignancies who experience VTE.

As noted however, patients with certain intracranial malignancies, including thyroid, melanoma, renal cell carcinoma, and choriocarcinoma, have a particularly high risk of hemorrhage, and anticoagulants should be used with great caution in these patients. Excessive levels of anticoagulation can also lead to hemorrhage and should be avoided. Indeed, in the retrospective review cited in the letter,² both patients with fatal intracranial hemorrhage were over-anticoagulated. The risk of hemorrhage at the lower levels of anticoagulation achieved with prophylactic regimens is likely much lower, although data from large clinical studies are lacking. We agree that additional randomized controlled trials are needed to guide treatment in this difficult area.

We also agree with Dr Singh et al that there is little evidence to guide providers regarding anticoagulant prophylaxis in patients with thrombocytopenia. In a study of ambulatory cancer patients receiving chemotherapy, the rate of VTE in patients with a baseline platelet count less than 200,000/µL was 1.25% (0.5% per month), and this was substantially lower than the rate of nearly 4% (1.7% per month) in patients with platelet count of at least 350,000/µL (P for trend = .0003).³ Furthermore, as noted by Dr Singh et al, patients with low platelet counts are generally excluded from trials of thromboprophylaxis, and the risk of bleeding complications in these patients is unknown. Based on a review of the available evidence, the American Society of Clinical Oncology Guidelines Panel does not recommend anticoagulant prophylaxis in patients with platelet count less than 50,000/µL.⁴

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

Although all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a "U" are those for which no compensation was received; those relationships marked with a "C" were compensated. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.

Employment or Leadership Position: None Consultant or Advisory Role: Charles W. Francis, Eisai Inc (C) Stock Ownership: None Honoraria: Alok A. Khorana, Eisai Inc, Sanofi-aventis; Charles W. Francis, Eisai Inc Research Funding: None Expert Testimony: None Other Remuneration: None

REFERENCES

1. Gerber DE, Grossman SA, Streiff MB: Management of venous thromboembolism in patients with primary and metastatic brain tumors. J Clin Oncol 24:1310-1318, 2006[Abstract/Free Full Text]

2. Schiff D, DeAngelis LM: Therapy of venous thromboembolism in patients with brain metastases. Cancer 73:493-498, 1994[CrossRef][Medline]

3. Khorana AA, Francis CW, Culakova E, et al: Risk factors for chemotherapy-associated venous thromboembolism in a prospective observational study. Cancer 104:2822-2829, 2005[CrossRef][Medline]

4. Lyman GH, Khorana AA, Falanga A et al: American Society of Clinical Oncology Guideline: Recommendations for venous thromboembolism prophylaxis and treatment in patients with cancer. J Clin Oncol 25:5490-5505, 2007[Abstract/Free Full Text]

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