Prevalence and Course of Covid-19 in Patients with Congenital Bleeding Disorders in Russia

Introduction: Published data on the course of COVID-19 in patients with congenital bleeding disorders (CBDs) is limited. There are questions about howCOVID-19 affects the course of CBDs and, conversely, how CBDs affect the course of coronavirus infection? Some authors suggest that patients with CBDs to be less severely affected by COVID-19. The aim of the study: analysis of the prevalence and course of COVID-19 in patients with CBDs in Russia. Method(s): A web-based questionnaire was developed to collect data. The survey was conducted in the period from 25.06.2022 to 31.07.2022. A cluster of 187 patients from different regions and cities of Russia were interviewed. Result(s): The average age of patients was 37 years. The survey group consisted of 144 patients with hemophilia A, 16 with hemophilia B, 24 with vonWillebrand's disease and 1 patient with factor VII deficiency. COVID-19 affected 115 (61.5%) of 187 surveyed patients and 22 (19%) patients suffered from coronavirus infection twice. Hospitalisation was required for 14 (12.3%) patients. At the beginning of the disease, 82 (71%) patients were on prophylactic treatment with the factor concentrates;11 (10%) received therapy with emicizumab, 20 (17%) received therapy with the factor concentrates on demand and 2 (1.7%) received bypass agents. During COVID-19 different types of bleeding were observed in 9 (7.8%) patients: hemarthrosis, ecchymosis, hematomas, epistaxis, menorrhagia, haemorrhoid bleeding. Due to COVID-19 the blood coagulation parameters were monitored for 15 (13%) of 115 patients who had been ill. The haemostatic therapy regimen was changed in 19 (16.5%) patients. Anticoagulant therapy was received by 8 (7%) patients. There were no thrombotic cases. A change in the course of the underlying disease after COVID-19 was noted by 21 (18%) patients, of which 11 noted an increase in joint pain and 9 reported the appearance of pain in previously intact joints. Discussion/Conclusion: The absence of thrombotic complications in patients with CBDs and COVID-19 suggests that hypocoagulability state may be protective against COVID-19 hypercoagulability-related adverse effects. However, the aggravating condition is an increase in joint pain and the involvement of new joints possible due to both hemostatic disorders and autoimmune reaction.

SUCCESSFUL USE OF BIVALIRUDIN DURING THE THIRD TRIMESTER OF PREGNANCY WHILE ON EXTRACORPOREAL MEMBRANE OXYGENATION

SESSION TITLE: Close Critical Care Calls SESSION TYPE: Case Reports PRESENTED ON: 10/18/2022 11:15 am - 12:15 pm INTRODUCTION: Heparin is the preferred anticoagulant for use in pregnancy while on extracorporeal membrane oxygenation (ECMO) (1). Alternatives to heparin in this patient population are not well studied as heparin-induced thrombocytopenia is rare in pregnancy. Parenteral non-heparin anticoagulants available in the United States include the direct thrombin inhibitors argatroban and bivalirudin, both of which are utilized in ECMO. Guidelines recommend avoidance of these agents in pregnancy if at all possible (2). Whereas case reports support the safe use of argatroban in pregnancy, to our knowledge, there are no known documented reports of bivalirudin use in this patient population (3). Here we describe the successful use of bivalirudin during pregnancy. CASE PRESENTATION: A 25 year old G2P1 was transferred to our institution at 28 weeks gestation for further management of acute hypoxic respiratory failure secondary to COVID-19. On hospital day 2 the patient was urgently placed on venovenous (VV) ECMO for refractory hypoxemia, high dead space with acidosis, and the inability to provide adequate gas exchange and lung protection with mechanical ventilation alone. Following ECMO cannulation with a 25f cannula in the right femoral vein and a 21f cannula in the right internal jugular vein, she was anticoagulated with heparin at a rate of 12 units/kg/hr. This was titrated to target a PTT goal of 60-80 seconds. On ECMO day 2, the TEG demonstrated a markedly hypocoagulable state, and the heparin nomogram called for increasing heparin dosing based on PTT. Given the already high dose of heparin that the patient was on (32.9 units/kg/hr), the decision was made to switch from heparin to bivalirudin to prevent over anticoagulation and reduce bleeding risk. Bivalirudin was titrated to a goal PTT of 50-60 seconds, with an initial rate of 0.15 mg/kg/hr (dose range 0.15-0.22 mg/kg/hr). Therapy was continued and on ECMO day 11, at 29w6d the patient delivered via cesarean section. Bivalirudin was discontinued 2.5 hours prior to the surgical procedure which resulted with no fetal bleeding complications. The patient was decannulated from ECMO on day 20 and was later discharged from the hospital. The newborn is developing well and meeting age adjusted milestones. DISCUSSION: Bivalirudin was selected based on institutional experience and the pharmacokinetic properties of the drug (half-life of 25 minutes) as we considered a situation where an emergent delivery may be indicated. Bivalirudin successfully prevented clotting of the circuit with no maternal or fetal bleeding complications during its use. CONCLUSIONS: Our case report describes a multidisciplinary approach to managing a pregnant patient on ECMO requiring anticoagulation using an alternative medication to heparin. This is the first documented use of bivalirudin in pregnancy. Reference #1: ELSO Guidelines for Cardiopulmonary Extracorporeal Life Support Extracorporeal Life Support Organization, Version 1.4 August 2017. Ann Arbor, MI, USA www.elso.org. Reference #2: Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141(Suppl): e691S–736S Reference #3: Young SK, Al-Mondhiry HA, Vaida SJ, et al. Successful use of argatroban during the third trimester of pregnancy: case report and review of the literature. Pharmacotherapy 2008;28: 1531–6. DISCLOSURES: No relevant relationships by Jacqueline Finger No relevant relationships by Caitlin Gluck No relevant relationships by Cameron Hypes No relevant relationships by John Rathbun

Congenital Bleeding Disorders and COVID-19 - An Emphasis on the Role of Thrombosis as One of the Main Causes of Morbidity and Mortality in COVID-19.

A turbulent coagulation system is a prominent feature of Coronavirus Disease 2019 (COVID-19), with venous thromboembolism (VTE) a leading cause of death. Our hypothesis is that patients with inherited hypocoagulability, like congenital bleeding disorders (CBD), enjoy a protective effect against COVID-19-induced hypercoagulability and related fatal consequences. Our primary and follow-up observations revealed this effect, at least among patients with moderate to severe congenital bleeding disorders, particularly coagulation factor deficiencies. Theoretically, patients with inherited hypocoagulobility have only a potential protective effect against COVID-19-related hypercoagulability. Yet the lower rate of morbidity and mortality in patients with CBDs suggests that hypercoagulability and thrombotic events are the main cause of death in COVID-19. Therefore, appropriate and timely administration of anticoagulants could significantly decrease the rate of morbidity and mortality in COVID-19.

Intracerebral bleeding after Janus-kinase inhibitor baricitinib for COVID-19.

OBJECTIVES: Intracerebral hemorrhage/bleeding (ICH) after an infection with SARS-CoV-2 (COVID-19) treated with the Janus-kinase inhibitor baricitinib has not been reported. CASE PRESENTATION: A 86yo Caucasian female suddenly developed aphasia with a systolic blood pressure of 220 mmHg. Cerebral imaging revealed an ICH in the left temporal lobe without mass effect and no need for neurosurgical intervention. Her previous history was positive for arterial hypertension, hyperlipidemia, heart failure, renal insufficiency, hyperuricemia, macula degeneration, lumbalgia, and glaucoma bilaterally. Additionally, she had experienced an infection with SARS-CoV-2 with onset 44 days earlier having been treated with ceftriaxone (2 g/d for 7 d), dexamethasone (6 mg for 6 d), and bariticinib (2 mg for 6 d). CONCLUSIONS: Though ICH was time-linked to COVID-19, a causal relation could not be unequivocally established. Whether baricitinib increased the bleeding risk remains speculative. As long as causalities between ICH and baricitinib remain unproven, it should be given with caution and only under close blood pressure monitoring.