Background: Venous thromboembolism (VTE) is a frequent and significant complication of cancer and of chemotherapy, with an estimated risk of 0.04%/month (0.5%/year). Patients with thrombocytopenia are widely perceived to be at low-risk for VTE. Conversely, thrombocytosis may contribute to risk of VTE, but this has not been well-studied. We conducted a prospective analysis to determine the association of platelet counts with the incidence of symptomatic VTE in cancer patients receiving chemotherapy.
Methods: The Awareness of Neutropenia in Cancer (ANC) Study Group is currently enrolling patients with breast, lung, colon, ovary and other cancers, at 137 sites nationwide, with an accrual goal of 4,500 patients. Patients are registered at the time of initiation of a new chemotherapy regimen, and followed for 4 cycles. The association of VTE with platelet counts and other clinical variables was studied in univariate analysis and in a multiple logistic regression model.
Results: A total of 2,151 patients treated with at least one cycle of chemotherapy were available for analysis. Of these, 18.1% had platelet counts <200,000 and 21.5% had counts ≥350,000 prior to initiating chemotherapy. Symptomatic VTE occurred in 46 patients, for an incidence of 2.14% over a median follow-up of 2.5 months (0.85%/month). The incidence of VTE by quartiles of pre-chemotherapy platelet counts is shown in the figure. VTE occurred in 4.34% (1.73%/month) of patients with platelet counts of ≥ 350,000 prior to initiation of chemotherapy. This was significantly greater than 1.8% (0.72%/month) incidence in those with baseline counts of <200,000 (p=0.035). Similarly, the mean platelet count prior to chemotherapy was higher for patients who developed VTE than for those who did not (351,000 versus 288,000, p=0.007). Platelet counts during chemotherapy were also associated with risk for VTE. The mean platelet count at nadir during the cycle VTE occurred was 202,000. This was significantly greater than the mean nadir count of 157,000 for corresponding cycles in patients who did not develop VTE (p=0.007). Other clinical variables associated with development of VTE included primary site of cancer, ECOG performance status ≥ 2, and baseline use of erythropoietin or colony-stimulating factors. A baseline platelet count of ≥ 350,000 continued to be significantly associated with VTE after adjusting for other risk factors in a multivariate analysis (odds ratio 3.00, 95% CI 1.61–5.55, p=0.0005).
Conclusion: This is the first report describing an independent association of platelet counts with symptomatic VTE in cancer patients receiving chemotherapy. Patients with platelet counts of ≥ 350,000 prior to initiation of chemotherapy are at a three-fold greater risk for developing VTE. The role of platelets in the pathogenesis of chemotherapy-associated thrombosis warrants further study. Platelet counts should be taken into account when defining high-risk patients for thromboprophylaxis.