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Background: Critically ill COVID-19 patients are at risk for venous thromboembolism (VTE). Therefore, they receive thromboprophylaxis and, when appropriate, therapeutic unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). To monitor heparins in COVID-19 disease, whole-blood rotational thromboelastometry (ROTEM) may be a promising alternative to the aPTT and anti-Xa assays., Objective: To evaluate the ROTEM INTEM/HEPTEM ratios in mechanically ventilated COVID-19 patients treated with UFH and therapeutic LMWH., Material and Methods: A subcohort of mechanically ventilated COVID-19 patients of the prospective Maastricht Intensive Care Covid (MaastrICCht) cohort was studied. Anti-Xa, aPTT, and ROTEM measurements following treatment with UFH or therapeutic dose of LMWH (nadroparin) were evaluated using uni- and multivariable linear regression analysis and receiver operating characteristics., Results: A total of 98 patients were included, of which 82 were treated with UFH and 16 with therapeutic LMWH. ROTEM-measured INTEM/HEPTEM CT ratio was higher in patients using UFH (1.4 [1.3-1.4]) compared to patients treated with LMWH (1.0 [1.0-1.1], p < 0.001). Both the aPTT and anti-Xa were associated with the CT ratio. However, the β-regression coefficient (95%CI) was significantly higher in patients on UFH (0.31 (0.001-0.62)) compared to therapeutic LMWH (0.09 (0.05-0.13)) for comparison with the anti-Xa assay. Furthermore, ROC analysis demonstrated an area under the curve for detecting UFH of 0.936(0.849-1.00), 0.851(0.702-1.000), and 0.645(0.465-0.826) for the CT ratio, aPTT, and anti-Xa, respectively., Conclusion: The ROTEM INTEM/HEPTEM CT ratio appears a promising tool to guide anticoagulant therapy in ICU patients with COVID-19 disease, but associations with clinical endpoints are currently lacking., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Renke H. Olie has received research support and honoraria from 10.13039/100004326Bayer, 10.13039/100004319Pfizer/BMS, Leo Pharma, Portola, and 10.13039/100004339Sanofi. Hugo ten Cate received funding for research from 10.13039/100004326Bayer and 10.13039/100004319Pfizer, is a stakeholder in Coagulation Profile, is a consultant for Alveron, and has served on advisory boards for 10.13039/100004326Bayer, 10.13039/100004319Pfizer, Daiichi, Leo, and Gilead. Yvonne Henkens has received ROTEM cartridges free of charge for previous research unrelated to the current manuscript. All others report no conflicts of interest., (© 2023 Published by Elsevier Ltd.)

Background: Low-molecular-weight heparins (LMWH) are the most commonly used anticoagulants for the treatment and prophylaxis of venous thromboembolism in pregnancy. Hypersensitivity skin reactions associated with the use of LMWH are frequently seen, but are probably underreported., Objective: To evaluate the incidence of hypersensitivity skin reactions due to the use of LMWH in pregnancy, and the subsequent management of anticoagulation., Patients/methods: From 1999 to 2009, we followed consecutive women who used therapeutic anticoagulation for venous indications. Women visited a combined obstetric/coagulation clinic and were seen by a thrombosis specialist every two months until six weeks postpartum. All women were started on nadroparin., Results: We included 135 pregnancies in 88 women. Overall, in 52 of 135 pregnancies (39%), women switched at least once to another anticoagulant because of the development of hypersensitivity skin reactions. Switching to another preparation of LMWH was effective in 77% of the cases. In 23% of the cases skin reactions recurred and another switch had to be made., Conclusion: In almost half of the pregnancies, women had to switch at least once to another anticoagulant preparation due to the development of hypersensitivity skin reactions on LMWH. In most cases, skin reactions did not recur on the second preparation of LMWH used.

Background: Low-molecular-weight heparins (LMWH) are the most commonly used anticoagulant during pregnancy for prevention or treatment of VTE. However, the size of the associated risk of postpartum haemorrhage (PPH) is unknown., Objective: To assess the bleeding risk of high dose LMWH, also in relation to time between last dose LMWH and delivery., Material and Methods: From 1999 to 2009, we followed 88 pregnant women who were started on therapeutic anticoagulation. Controls were pregnant women without LMWH, matched 1:4 for parity, mode of delivery, age, gestational age and delivery date. PPH was defined as >500 ml blood loss for vaginal delivery (severe PPH in vaginal delivery as >1000 ml) and >1000 ml for cesarean section (CS). Women were divided into subgroups by the interval between last dose of anticoagulation and delivery (<12, 12-24 hrs, >24 hrs)., Results: Risk of PPH after vaginal delivery was 30% and 18% for LMWH-users and non-users, respectively (OR 1.9, 95%CI 1.1-3.5). Risk of severe PPH after vaginal delivery was not different (5.6 vs 5.0%; OR 1.1; 0.4-3.6). Risk of PPH after CS was 12% in LMWH-users and 4% in non-users (OR 2.9; 0.5-19.4). Both events of LMWH-users occurred after emergency CS. The risk of PPH associated with delivery within 24 hours after last dose of LMWH was 1.2 fold higher (95%CI 0.4-3.6) compared to a larger interval., Conclusion: High dose LMWH carries an increased risk of more than 500 mL blood loss after vaginal delivery. However, this results not in more clinical relevant severe PPHs. The interval between last dose of LMWH and delivery does not influence the risk of PPH., (Copyright © 2012 Elsevier Ltd. All rights reserved.)