For Less Work, Better Anticoagulation

Avoid Unfractionated Heparin

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Current guidelines recommend using direct oral factor Xa inhibitors such as rivaroxaban (Zarelto) or apixaban (Eliquis) for the acute treatment of veno-thrombotic disease (VTE) if the patient can take and absorb oral medications. (1) Low molecular weight heparin, enoxaparin (Lovenoz), is recommended if the patient cannot take oral medications.

This makes a lot of sense. Rivaroxaban produces anticoagulation in 2.5 to 4 hours after administration.(2) It has a half-life of 5 to 9 hours, but is approved for once daily dosing. Similarly apixaban rapid produces rapid anticoagulation within 1-2 hours of administration. (3) It has a half-life of about 12 hours and is approved for twice daily dosing. Subcutaneous enoxaparin also has an onset of anti-coagulation within 2 hours and is given twice daily.

These onsets of action are much faster than unfractionated heparin because unfractionated heparin requires dose adjustments, and the dose adjustments are based on either activated partial thromboplastic or anti-activated X levels, which require blood samples. All of this is a lot of work for the phlebotomists, nurses and covering clinicians.

Low-molecular-weight heparin ((LMWH) also has a lower incidence of heparin-induced thrombocytopenia. (4)

But this Substack newsletter and blog is entitled “500 Rules of Cardiology,” so what about LMWH for acute cardiovascular syndromes (ACS)? According to an older review (4) and to Francis Kiernan, MD, the former Director of Hartford Hospital's Cardiac Cath Lab, enoxaparin has been studied in ACS and is effective in reducing cardiac events and mortality. Indeed, early studies that primarily employed a non-invasive, non-angioplasty approach to ACS suggested that LMWH was superior to unfractionated heparin, but later studies suggested that this efficacy came with an increased risk of hemorrhage. So, LMWH is an alternative to heparin in ACS management, but with possible increased risk of bleeding. LMWH remains a choice in guidelines, but according to Dr. Kiernan, it is usually used with ACS patients who are going to be treated with a non-invasive, non-angioplasty strategy.

Consider saving your colleagues some work by avoiding unfractionated heparin and using direct oral anticoagulants or LMWH for in-hospital anticoagulation, especially in patients with VTE. Also, consider LMWH for patients with ACS who will be treated noninvasively. It’s hard to beat LMWH’s rapid onset and reduced requirement for blood samples for dose adjustments, although both the direct oral anticoagulants and LMWH have significant renal clearance, so may require some dose adjustment in these patients.

The Rule – Avoid unfractionated heparin when possible because direct oral anticoagulants and LMWH can reduce the work needed to care for hospitalized patients requiring anticoagulation.

1. Stufflefield WB. Et.al. Factors in Initial Anticoagulation Choice in Hospitalized Patients With Pulmonary Embolism. AMA Netw Open. 2025. PMID: 39752158

2. Ansell JD, Outpatient Anticoagulant Therapy. 2013, Consultative Hemostasis and Thrombosis (Third Edition) https://www.sciencedirect.com/topics/neuroscience/rivaroxaban

3. Hurst KV et.al. Quick reference guide to apixaban. Vasc Health Risk Manag. 2017 Jul 10;13:263–267. PMID: 28744136

4. Lee S, Gibson CM. Enoxaparin in acute coronary syndromes. Expert Rev Cardiovasc Ther. 2007 May;5(3):387-99. PMID: 17489664

Francis Kiernan, MD, reviewed and commented on this presentation.

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