Safety of Low Dose Enoxaparin in Thrombocytopenic Hematopoeitic Stem Cell Recepients: A Single Institution'a Case Series.

Abstract

When faced with a severely thrombocytopenic cancer patient with acute or chronic thrombus, oncologists often avoid antithrombotic treatment until the platelet count is above 50 x 109/L. Few attempts have been made to examine the feasibility of safely administering low-molecular-weight-heparins (LMWHs) in the presence of concurrent thrombocytopenia. We retrospectively investigated the safety of low-dose LMWH in hematopoeitic stem cell transplantation (HSCT) patients, a population at risk of bleeding. Our initial experience with the safe use of the LMWH enoxaparin in an HSCT patient published in 2002 (Annals of Pharmacotherapy 2002; 36:1478) was extended to 26 patients. Between August 2001 and August 2004, 26 HSCTs patient received at least one dose of enoxaparin during thrombocytopenia. Patients'baseline characteristics are shown below.Table 1. Baseline characteristics of the study patients (n=26)Two patients received enoxaparin twice during 2 successive thrombocytopenic periods, thereby accounting for 28 safety evaluations. Subcutaneous enoxaparin 40 mg once daily was given in 85% (22/26) of the cohort. Minor bleeding occurred in 4 patients (15%) whereas major episodes developed in 2 patients (8%). These two patients experienced retroperitoneal bleeding during the transition full/low- dose anticoagulation. Dose/platelet count at the time of bleeding were: 2.35 mg/kg/d and 81 x 109/L, and 1.15 mg/kg/d and 52 x 109/L in the first and second patient respectively. The latter patient had an elevated serum creatinine at 2 mg/dl. The mean number of platelets days < 55 x 109/L and < 20 x 109/L were 16.5 days (95% CI=8.04–24.96) and 4.14 days (95% CI=2.35–5.93) respectively. The mean number of platelet transfusion was 4.93 (95% CI=2.65–7.21). The mean number of low-dose enoxaparin administration days when platelet < 55x 109/L and 20 x 109/L were 9.89 days (95% CI= 3.26–16.53) and 2.25 days (95%CI=0.57–3.93) respectively. The mean number of enoxaparin interruptions during thrombocytopenia was 2.75 days (95%CI=1.11–4.39). During thrombocytopenia, the median 4-hour post-dose anti-Xa level was 0.28 units/ml (range:0.04–0.4 units/ml; n=5). The present case series descriptively suggests that low-dose enoxaparin may be safely administered platelet count in the range of 20–55 x 109/L in HSCT patients who weigh > 55 Kg. The safety of low-dose LMWHs below 20 x 109/L remains to be established. Importantly, the transition from/to low-dose enoxaparin should be done at a higher platelet count threshold than 55 x 109/L, all the more in the presence of compromised renal function.Table 1. Baseline characteristics of the study patients (n=26)Age (median; range)53 years (24–67)Gender (M/F)17/9Weight (median; range)83.4 Kg (53–176)Type of HSCT¹Autologous (20), Allogeneic (2), non-myeloablative (3), cyclophosphamide priming (3)Thrombotic event²upper extremity DVT (11), lower extremity DVT (9), pulmonary embolism (5), miscellaneous events (5)Number of patients on full-dose enoxaparin prior to thrombocytopenia (%)14 (54%)Indications for HSCTmultiple myeloma (10), lymphoma (9), leukemia (2), breast cancer (2), miscellaneous indications (3)Two patients received enoxaparin during 2 successive thrombocytopenic periods ¹, 2 patients had upper and lower extremity DVT, 2 patients had lower extremity DVT and pulmonary embolism²Age (median; range)53 years (24–67)Gender (M/F)17/9Weight (median; range)83.4 Kg (53–176)Type of HSCT¹Autologous (20), Allogeneic (2), non-myeloablative (3), cyclophosphamide priming (3)Thrombotic event²upper extremity DVT (11), lower extremity DVT (9), pulmonary embolism (5), miscellaneous events (5)Number of patients on full-dose enoxaparin prior to thrombocytopenia (%)14 (54%)Indications for HSCTmultiple myeloma (10), lymphoma (9), leukemia (2), breast cancer (2), miscellaneous indications (3)Two patients received enoxaparin during 2 successive thrombocytopenic periods ¹, 2 patients had upper and lower extremity DVT, 2 patients had lower extremity DVT and pulmonary embolism²