Treatment with Dalteparin is Associated with a Lower Risk of Bleeding Compared to Treatment with Unfractionated Heparin in Patients with Renal Insufficiency

Abstract

BACKGROUND: Low molecular weight heparins (LMWHs) have been cautiously used in patients with chronic kidney disease (CKD) due to fear of accumulation. Dalteparin, however, has shown minimal tendency to accumulate in patients with CKD and may be safe to use in this patient population. OBJECTIVE: We compared the incidence of clinically significant bleeding in patients with CKD receiving therapeutic doses of dalteparin to that of patients with CKD receiving therapeutic doses of UFH. DESIGN: This was a retrospective cohort study. SUBJECTS: Inpatients with CKD (GFR<60 ml/min) who were treated with therapeutic dalteparin or UFH were included in the study MAIN MEASURES: Primary outcome was major bleeding within 10 days of anticoagulation, identified by ICD-9 code and confirmed by chart review. Demographic characteristics, laboratory values, comorbidities, prior bleeding history and inpatient medications were extracted for each admission from the electronic medical record. Logistic regression models were created to examine the association between choice of anticoagulant and bleeding rates, after adjustment for demographic and clinical characteristics. KEY RESULTS: Dalteparin-treated patients were significantly less likely to experience a major bleed than patients treated with UFH (1.14 % vs. 3.49 %, p<0.001). The reduced likelihood of bleeding associated with dalteparin treatment remained significant after adjustment for patient characteristics (HR 0.39, 95 % CI: 0.21-0.70, p < 0.0001). A stratified analysis for subgroups with GFR< 30 mL/min and with GFR between 30 and 60 mL/min showed that dalteparin was still associated with lower odds of bleeding compared to treatment with unfractionated heparin, but the difference was nonsignificant for GFR< 30 (HR 0.35,), even after adjustment (OR 0.37, 95 % CI: 0.11-1.22). CONCLUSION: In patients with CKD, treatment with therapeutic dose dalteparin was associated with lower rates of bleeding than treatment with unfractionated heparin. For patients with severe CKD (GFR< 30), dalteparin was shown to be at least as safe as unfractionated heparin.KEY WORDS: dalteparin; renal insufficiency; bleed; heparin.

Renal function and clinical outcome of patients with cancer-associated venous thromboembolism randomized to receive apixaban or dalteparin. Results from the Caravaggio trial

“…Among LMWH, dalteparin seems to be associated with acceptable bleeding risk in patients with RI. 16 , 30 , 31 Among direct oral anti-Xa anticoagulants, dose reduction for patients with RI was evaluated for edoxaban in the treatment of VTE. No dose adjustment has been tested in clinical trials for the treatment of VTE with apixaban or rivaroxaban.…”

Analysis of risk factors for bleeding events in anticoagulated patients

“…Sabe-se que a eliminação da heparina sódica pode ocorrer de algumas formas; uma parte da heparina sódica é captada pelos pulmões e fígado; e a maior parte é filtrada para a urina. 19 Existem alguns outros fatores que podem alterar a eliminação da heparina. A hipotermia, especialmente abaixo dos 25ºC, pode retardar a eliminação da heparina .…”

“…20 Porém, a insuficiência renal é o principal fator relacionado à eliminação, podendo prolongar o efeito anticoagulante da heparina. 19 Portanto, pacientes com insuficiência renal têm risco aumentado de complicações hemorrágicas, o que se confirma nos resultados deste estudo. Identificou-se que os pacientes com insuficiência renal têm 1,04 vez mais risco de eventos hemorrágicos.…”

The Role of Tinzaparin in Oncology

“…113 Sufficient data are lacking in the case of dalteparin. 111,120 This conclusion appears paramount for the subpopulation of patients with cancer, as they combine multiple factors that aggravate their renal function, such as older age, dehydration, and use of nephrotoxic agents for anticancer treatment, and other comorbidities, such as hypertension, diabetes mellitus, and so on.…”