Prophylactic Unfractionated Heparin in Antepartum Hospitalizations

Abstract

OBJECTIVE: To assess the effect of gestational age–based dosing of unfractionated heparin (UFH) compared with standard dosing of UFH for thromboprophylaxis on an elevated serum activated partial thromboplastin time (aPTT) during prolonged antepartum hospitalizations. METHODS: This was a randomized trial of pregnant persons who were admitted in the antepartum period for at least 72 hours. Participants were randomly allocated to the standard dose of UFH (5,000 units subcutaneously every 12 hours) or the gestational age–based dose of UFH (first trimester [less than 14 weeks]: 5,000 units subcutaneously every 12 hours; second trimester [14–27 6/7 weeks]: 7,500 units subcutaneously every 12 hours; third trimester (28 weeks or more): 10,000 units subcutaneously every 12 hours). The primary outcome was the proportion of antepartum patients who had an elevated serum aPTT value above the normal range (more than 36.2 seconds) 6 hours after an UFH dose. Secondary outcomes included the development of venous thromboembolism (VTE) and reported side effects of heparin administration. RESULTS: Between December 15, 2020, and April 1, 2022, 97 patients with antepartum hospitalizations were screened and 46 were randomized: 22 allocated to standard dosing and 24 allocated to gestational age–based dosing of UFH. A significantly greater proportion of antepartum patients who received gestational age–based dosing had an abnormal elevation in aPTT compared with those who received standard dosing (33.3% vs 4.8%, P=.02). Gestational age–based dosing resulted in higher maximum [interquartile range] aPTT (30.4 [27.4, 37.5] vs 26.6 [23.0, 29.6], P=.01) and anti-Xa levels (0.09 [0.09, 0.11] vs 0.09 [0.09, 0.09], P=.04). There was no significant difference in VTE between groups (P=.47). CONCLUSION: Gestational age–based dosing of UFH for thromboprophylaxis of antepartum hospitalizations was associated with significantly increased rates of elevated coagulation parameters compared with standard fixed dosing. This study suggests a need for close monitoring if higher doses of UFH during pregnancy are used later in gestation. The efficacy of gestational age–based dosing compared with standard dosing for UFH to prevent thromboembolic events remains an area for future investigation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04635839.