ABSTRACT
Background: Thrombosis is a frequent and severe complication in COVID-19 patients admitted to the intensive care unit (ICU). Lupus anticoagulant (LA) is a strong acquired risk factor for thrombosis in various diseases and is frequently observed in COVID-19 patients. Whether LA is associated with thrombosis in patients with severe COVID-19 is currently unclear. Aim(s): To investigate if LA is associated with thrombosis in critically ill COVID-19 patients. Method(s): The presence of LA and other antiphospholipid antibodies was assessed in COVID-19 patients admitted to the ICU. Informed consent was obtained by an opt-out approach and the study was approved by the local medical ethical committee. LA was determined with dilute Russell's Viper Venom Time (dRVVT) and LA-sensitive Activated Partial Thromboplastin Time (aPTT) reagents. Statistical analysis to study the association of LA and other antiphospholipid antibodies with thrombosis occurrence was performed using logistic regression. Result(s): Out of 169 COVID-19 patients, 116 (69%) tested positive for at least one antiphospholipid antibody upon admission to the ICU. Forty (24%) patients tested positive for LA;of whom 29 (17%) tested positive with a dRVVT, 19 (11%) tested positive with an LA-sensitive aPTT and eight (5%) tested positive on both tests. Fifty-eight (34%) patients developed thrombosis after ICU admission. The odds ratio (OR) for thrombosis in patients with LA based on a dRVVT was 2.4 (95%-CI: 1.1-5.4), which increased to 5.1 (95%-CI: 1.7-15.4) in patients on or below the median age of this study population (64 years). LA-positivity based on a dRVVT or LA-sensitive aPTT was only associated with thrombosis in patients younger than 65 years (OR: 4.2, 95%-CI: 1.5-11.7). Conclusion(s): LA on admission is strongly associated with thrombosis in critically ill COVID-19 patients, especially in patients <65 years of age.
ABSTRACT
Introduction: Delivery in type 3 VWD with alloantibodies, a rare clinical entity with few treatment options, is a very high-risk situation. Methods: Case report Results: A 28 yo patient with type 3 VWD and alloantibodies to VWF and FVIII became pregnant after extensive preconceptional counselling. Previous ITI was unsuccessful and complicated by anaphylaxis. The pregnancy was complicated by a mild COVID-19 infection in the 2nd trimester, but otherwise uncomplicated. Delivery was induced at 38 4/7 weeks with prostaglandin and rFVIIa (NovoSeven®) started when in active labor. After a rapid vaginal delivery and afterbirth, manual placental removal was performed and a Bakri balloon inserted for ongoing bleeding despite rFVIIa 90μg/kg every 2h. As bleeding still continued, plasma-derived VWF was infused with initial excellent recovery and successful embolization of the aa uterinae was performed. Another infusion of VWF to prevent rebleeding resulted in minimal recovery and an allergic reaction despite prednisolone and clemastine. Rebleeding did not occur and patient was discharged at day 8. At day 12 she was readmitted because of endometritis followed by vaginal bleeding unresponsive to rFVIIa. Re-embolization was performed and off label emicizumab started to prevent rebleeding. A loading dose of 6mg/kg on day 1 and 3mg/kg on day 2 was given, followed by 3mg/kg EOW from the 2nd week onwards. As the infection was uncontrolled by broadspectrum antibiotics, hysterectomy was performed at dag 29, again complicated by diffuse bleeding requiring direct intra-abdominal packing and rFVIIa 90μg/kg every 2 hours in addition to emicizumab. A week after unpacking, asymptomatic pulmonary embolisms and thrombosis of the left v iliaca were discovered on CT. rFVIIa was stopped, prophylactic LMWH started and a third embolization performed when bleeding reoccurred. Two months after delivery she was discharged with low dose LMWH, emicizumab and antibiotics because of an intra-abdominal abcess. Discussion/Conclusion: Delivery in patients with severe bleeding disorders in the presence of alloantibodies is a high-risk situation. Emicizumab was partially helpful in maintaining hemostatic control. Besides bleeding, postpartum patients receiving intensive correction of coagulation and especially with additional risk factors like surgery and infection, are also at risk for thrombotic events.