Case: A 34 year old female with no PMHX presents to the ED with unilateral right lower extremity swelling, dyspnea, and moderate pleuritic chest pain.  Vitals: BP 130/65, HR 68, RR 20, SPO2 89% on room air, Temp 37.8. A CT finds evidence of PE bilaterally at the segmental level. BNP and troponin are both mildly elevated.  Point of care cardiac ultrasound shows mild RV dilation. After interviewing the patient, you don’t identify any contraindications to anticoagulation. Pregnancy testing is negative.  Her renal function is normal. You consider what is the preferred agent for anticoagulation in this patient.

This patient shows evidence of a submassive PE given evidence of RV strain on POCUS and elevation of BNP and troponin.  While the management of submassive PE in terms of use of catheter directed therapies or thrombolysis is controversial, the overall need for anticoagulation is not.  Traditionally, unfractionated heparin (UFH) delivered as an infusion has been the initial treatment. But other options, such as low molecular weight heparin (LMWH) or use of direct oral anticoagulants (DOACs - specifically rivaroxaban and apixaban) have been investigated as alternative initial options.

Why seek an alternative to UFH?  Chiefly, the pharmacokinetics of UFH are not reliable compared to LMWH and DOAC.  Acutely, therapeutic dosing with UFH has been shown to be difficult to achieve (1).  LMWH has been shown as non-inferior to UFH in terms of outcomes (2, 3). Further, the need for infusion can give rise to errors as well as increases the expense of medication administration.  Rivaroxaban and apixaban have been studied as initial anticoagulation agents and found to be effective without increased risk of bleeding (4, 5). Patients with acute renal failure, those at high bleeding risk, and those with anticipated invasive procedures should use UFH.  This is because LMWH and DOACs are renally cleared, reversal agents for LMWH and DOACs are not consistently or as rapidly effective, and LMWH and DOACs have a longer half-life relative to UFH. DOACs have not been sufficiently studied in pregnancy and should be avoided in pregnant patients.

In our case, the patient requires supplemental oxygen and is not a candidate for immediate outpatient PE therapy.  Because no further interventions were planned (such as thrombolysis or catheter directed therapy), the risk of bleeding is low, and the patient’s renal function was normal, the physicians opted to prescribe rivaroxaban and admit to the hospital for further management.

References:

1. Prucnal CK, Jansson PS, Deadmon E, Rosovsky RP, Zheng H, Kabrhel C. Analysis of Partial Thromboplastin Times in Patients with Pulmonary Embolism During the First 48 Hours of Anticoagulation with Unfractionated Heparin. Acad Emerg Med. October 2019. doi:10.1111/acem.13872.

2. Quinlan DJ, McQuillan A, Eikelboom JW. Low-molecular-weight heparin compared with intravenous unfractionated heparin for treatment of pulmonary embolism: a meta-analysis of randomized, controlled trials. Ann Intern Med. 2004;140(3):175-183. doi:10.7326/0003-4819-140-3-200402030-00008.

3. Robertson L, Jones LE. Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for the initial treatment of venous thromboembolism. Cochrane Vascular Group, ed. Cochrane Database of Systematic Reviews. 2017;50(10):781-785. doi:10.1002/14651858.CD001100.pub4.

4. EINSTEIN Investigators, Bauersachs R, Berkowitz SD, et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010;363(26):2499-2510. doi:10.1056/NEJMoa1007903.

5. Agnelli G, Büller HR, Cohen A, et al. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013;369(9):799-808. doi:10.1056/NEJMoa1302507.

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