How does renal or hepatic impairment affect Heparin dosing?

1.

Elsevier ClinicalKey Drug Monograph

Content last updated: May 1, 2024.

Contraindications And Precautions Use heparin cautiously in patients with underlying hepatic disease as these patients often have coagulopathies and are at increased risk for anticoagulant-associated bleeding. Patients with inherited antithrombin deficiency usually have antithrombin concentrations 40% to 60% of normal but may have resistance to heparin and require higher doses to achieve the desired therapeutic response. Patients with acquired antithrombin deficiency, as seen with severe hepatic disease (e.g., cirrhosis), renal disease (e.g., nephrotic syndrome), or disseminated intravascular coagulation (DIC), may not respond to heparin.

Pharmacokinetics Subcutaneous heparin concentrations reach steady-state between 4 and 10 hours. **• Special Populations** **Hepatic Impairment** The rate of clearance of unfractionated heparin may be decreased in persons with hepatic impairment and plasma heparin concentrations may be higher compared to persons with normal hepatic function. **Renal Impairment** The rate of clearance of unfractionated heparin may be decreased in persons with renal impairment and plasma heparin concentrations may be higher compared to persons with normal renal function. **Pediatrics** Neonates Premature neonates (n = 25, gestational age 25 to 36 weeks) had a significantly shorter plasma half-life (35.5 to 41.6 minutes), larger volume of distribution (57.8 to 81 mL/kg), and faster clearance (1.37 to 1.49 mL/kg/minute) after an IV bolus dose of 100 units/kg compared to adults receiving an IV bolus dose of 75 units/kg (half-life = 63.3 minutes, Vd = 36.6 mL/kg, CL = 0.43 mL/kg/minute). **Geriatric** Persons older than 60 years may have higher plasma concentrations of heparin and longer activated partial thromboplastin times (aPTTs) compared with younger persons after similar doses of heparin.

2.

Elsevier ClinicalKey Clinical Overview

Treatment Patients with chronic kidney disease Unfractionated heparin is recommended for patients with acute venous thromboembolism and severe renal failure Use of low-molecular-weight heparin is controversial in patients with kidney disease owing to bleeding risk, but it may be acceptable for some patients with lesser degrees of renal insufficiency. If used, administer under guidance of a nephrologist For maintenance and, if indicated, extended treatment of venous thromboembolism, warfarin is the preferred anticoagulant in patients with severe renal disease Though direct oral anticoagulants are attractive alternatives to warfarin therapy, large-scale clinical trials of direct oral anticoagulants in treatment of venous thromboembolism excluded patients with severe kidney disease so safety in these patients and those on dialysis is not well-characterized Accumulating data (largely from atrial fibrillation experience) suggest that direct oral anticoagulants are safe and effective in severe kidney disease, including end-stage kidney disease; most studies in this setting have focused on apixaban. If used, administer under guidance of a nephrologist For lesser degrees of renal dysfunction, use of direct oral anticoagulants may be reasonable; dose reduction may be necessary Patients with cirrhosis These patients have bleeding coagulopathy due to defective coagulation factor synthesis but can also be in a hypercoagulable state due to decreased antithrombin III, protein C, and protein S activity, leading to portal vein thrombosis and other venous thromboembolism events

Treatment Table Title: Anticoagulation agents for special populations. Table Caption: Abbreviations: BMI: body mass index; DOAC: direct oral anticoagulant; DVT, deep vein thrombosis; IV, intravenous; VTE, venous thromboembolism. Table Heads: Special population| Preferred drug| Discussion points Table Rows: Patients with malignancy| DOAC (rivaroxaban, apixaban or edoxaban) or low- molecular-weight heparin| Efficacy for acute and extended therapy similar between low-molecular-weight heparin and DOACs; however, DOACs are associated with greater risk of bleeding in gastrointestinal and genitourinary cancers Pregnant patients| Low-molecular-weight heparin| Warfarin is contraindicated Children| Low-molecular-weight heparin and warfarin| Dabigatran and rivaroxaban both approved for use in children after at least 5days of parenteral anticoagulant Patients with acute kidney injury or chronic kidney disease| IV unfractionated heparin, followed by warfarin, is suggested for initial anticoagulation with severe renal failure DOACs may be used cautiously for mild to moderate renal insufficiency | Unfractionated heparin is preferred for severe renal failure with creatinine clearance less than 30 mL/minute Use of DOACs in renal dysfunction requires dose reduction or avoidance depending on the particular agent Patients with cirrhosis| Low-molecular-weight heparin| Low-molecular-weight heparin is preferred over warfarin owing to difficulty in relying on INR to monitor warfarin dosing Patients with heparin-induced thrombocytopenia| Argatroban| Subcutaneous

3.

Low Molecular Weight Heparins (LMWHs), Elsevier ClinicalKey Drug Class Overview

Content last updated: January 1, 2012.

LMWHs are excreted via the kidney; therefore, delayed elimination and subsequent accumulation may occur in patients with renal impairment. Patients with renal impairment should be observed for signs and symptoms of bleeding during LMWH therapy. Anti-factor Xa monitoring may be considered in patients with severe renal impairment to avoid toxicity and ensure therapeutic concentrations. In patients with a CrCl < 30ml/min, tinzaparin and dalteparin use is not recommended; however, enoxaparin has been studied in this population and dose adjustment recommendations are available. In a study comparing enoxaparin and tinzaparin for 8 days in 55 elderly patients with CrCl between 20 and 50 ml/min, enoxaparin was found to accumulate, but tinzaparin did not[50260].