Abstract
Objectives: To study the incidence of bleeding complications during thromboprophylaxis with dalteparin in patients with acute medical illness and renal failure.
Design: Prospective, cohort study.
Setting: Community Hospital.
Main outcome: The primary safety outcome was the incidence of major and minor bleeding, while the primary efficacy outcomes were objectively verified symptomatic DVT, pulmonary embolism, and objectively verified asymptomatic DVT detected on routine compression ultrasonography. Secondary outcomes included anti-Xa heparin levels.
Patients: 56 consecutives patients (29 males, age 77.86±10.27 y, 27 females, age 84.60±6,78 y) admitted with acute medical illness were considered for the study. Eligible patients were 18 years or older and had none of the following: hepatic failure (prothrombin time <50%), platelet count <100.000/ml, chronic use of warfarin, or an ongoing requirement for anticoagulation. Two doses of dalteparin were prescribed as dictated by a venous thromboembolism risk score. 44 patients judged to be at high risk (age >75 y, 44 of 56, 78%, active cancer, 5 of 56, 8.9%, previous venous thromboembolism, 1 of 56, 1.8%) received a dose of 5.000 IU daily; the other 12 received 2.500 IU daily. Dalteparin was given at 8 am for 6 days. The timing of anti-Xa activity determination and of compression ultrasound examination of leg veins is shown in table 1.
Methods
Results: there was 1 case (1 of 56, 1.8%) of nose bleeding at the third day of treatment in a patient with moderate renal failure. The bled was easily stopped. None of the following variables: dose of dalteparin, age, sex, creatinine clearance, and anti-Xa activity when entered in a regression model were able to predict the hemorrhagic complication. There were no cases of venous thromboembolism. Though, peak anti-Xa activity was higher in patients with marked renal impairment, it never reached therapeutic levels (>0.5 IU/mL).
anti-Xa activity at day 6
Conclusions: The modest (and not significant) increase in anti-Xa activity in patients with reduced creatinine clearance was not associated with a clinically apparent risk of bleeding. Thromboprophylaxis with dalteparin appears safe even in acutely ill medical patients with renal failure.
day 0 Creatinine Clearance anti-Xa activity before Dalteparin CUS day 6 Creatinine Clearance anti-Xa activity 4 h after Dalteparin CUS CrCl >90 ml/min CrCl >89–60 ml/min CrCl >59–30 ml/min CrCl <29 ml/min p=0.45 Patients 5 12 26 13 anti-Xa activity IU/mL 0.012±0.02 0.016±0.054 0.066±0.12 0.20±0.66