Assessment of Jordanian physicians' knowledge about venous thromboembolism risk and management among COVID-19 patients

Objectives: The aim of this study was to assess Jordanian physicians' awareness about venous thromboembolism (VTE) risk among COVID-19 patients and its treatment protocol. Method(s): This was a cross-sectional-based survey that was conducted in Jordan in 2020. During the study period, a convenience sample of physicians working in various Jordanian hospitals were invited to participate in this study. Physicians' knowledge was evaluated and physicians gained one point for each correct answer. Then, a knowledge score out of 23 was calculated for each. Key Findings: In this study, 102 physicians were recruited. Results from this study showed that most of the physicians realize that all COVID-19 patients need VTE risk assessment (n = 69, 67.6%). Regarding VTE prophylaxis, the majority of physicians (n = 91, 89.2%) agreed that low molecular weight heparin (LMWH) is the best prophylactic option for mild-moderate COVID-19 patients with high VTE risk. Regarding severe/critically ill COVID-19 patients, 75.5% of physicians (n = 77) recognized that LMWH is the correct prophylactic option in this case, while 80.4% of them (n = 82) knew that mechanical prevention is the preferred prophylactic option for severe/critically ill COVID-19 patients with high bleeding risk. Moreover, 77.5% of physicians (n = 79) knew that LMWH is the treatment of choice for COVID-19 patients diagnosed with VTE. Finally, linear regression analysis showed that consultants had an overall higher knowledge score about VTE prevention and treatment in COVID-19 patients compared with residents (P = 0.009). Conclusion(s): All physicians knew about VTE risk factors for COVID-19 patients. However, consultants showed better awareness of VTE prophylaxis and treatment compared with residents. We recommend educational workshops be conducted to enhance physicians' knowledge and awareness about VTE thromboprophylaxis and management in COVID-19 patients.Copyright © 2022 The Author(s). Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved.

Anaesthetic pre-assessment of obese patients in obstetrics: challenges in COVID recovery

Introduction: One in five pregnant women in the UKis obese. Obesity is associated with increased risk of both maternal and foetal adverse outcomes. RCOG guidelines [1] recommend that all women with a booking BMI over 40 kg/m2 should be reviewed antenatally by a senior obstetric anaesthetist to guide risk assessment, medical optimisation and shared decision-making. The 2021 MBRRACE report [2] recommends that all women should be reweighed in the third trimester for accurate VTE risk scoring and prophylactic LMWH dosing. In our institution, reconfiguration of hospital areas as part of the COVID-19 response led to loss of designated clinic space for our obstetric anaesthetic clinic. As a result, our practice since has been to initially offer a telephone consultation followed by a face-to-face review if needed. Finding space for the latter has often been a significant logistical challenge. Our project sought to assess whether our practice continued to meet national standards in the wake of these changes. Method(s): Following audit approval, we retrospectively reviewed all women with a BMI >40 kg/m2 undergoing caesarean section (CS) over a six-month period (1/4/22 to 31/9/22). Result(s): 20 women met inclusion criteria (Category 1-3 CS - 12 women;Category 4 CS - 8 women). 100% of patients had booking height, weight and BMI recorded. 20% (4/20) of patients were reweighed in the 3rd trimester. Only 55% (11/20) of patients had been referred to and reviewed in the antenatal obstetric anaesthetic clinic (Figure). Of the 11 patients referred, 6 were referred later than 30 weeks. Of the 9 patients not referred, 8 had a BMI between 40 and 45 kg/m2. By contrast, 87% (6/7) of patients with BMI over 45 kg/m2 were referred and seen. Discussion(s): Our audit showed that we are not meeting national standards. Possible reasons identified were lack of awareness of the RCOG standards and referral criteria (especially for women with a BMI of 40 to 45 kg/m2) and logistical issues in undertaking face-to-face reviews without designated clinic space. Presentation of our results at the joint anaesthetic, obstetric and midwifery governance meeting has helped identify space in the antenatal clinic for face-to-face reviews, to start from March 2023 and to raise awareness of the national standards to ensure referral of all women with a BMI over 40 kg/m2. A reaudit is planned in 6 months. [Figure presented]Copyright © 2023 Elsevier Ltd

Incidence of heparin resistance and heparin failure in patients receiving extracorporeal membrane oxygenation - an exploratory retrospective analysis

Objectives: Unfractionated heparin (UFH) remains the anticoagulation of choice at most centres for patients receiving extracorporeal membrane oxygenation (ECMO). One disadvantage of UFH relies on its individual dosing requirement to achieve target values. In this context heparin resistance has been described, defined as doses exceeding 35,000 IU UFH/d. However, the incidence of heparin resistance and its association with thromboembolic complications despite anticoagulation within target ranges remains unknown. Method(s): This retrospective study included adults receiving venovenous (VV) and venoarterial (VA) ECMO, or extracorporeal CO2-removal (ECCO2R) between 2010 and May 2022. The primary outcome was the incidence of heparin resistance (>35,000 IU of UFH/d). Secondary outcomes were heparin failure (thromboembolic complications despite anticoagulation within target ranges) and survival. A multivariable poisson regression model was fitted to analyse the effect of heparin resistance, COVID-19 and ECMO type on the incidence rate of thromboembolic events. Result(s): Of 197 included patients, 33 (16.8%) had heparin resistance. Patients with COVID-19 (n=51) had a higher rate of heparin resistance compared to nonCOVID-19 patients (37% vs. 9.6%, P<0.001). Thromboembolic complications occurred at a rate of 5.89/100 ECMO days. There was a significant effect of COVID-19 (incidence rate ratio (IRR) 2.12, 95% confidence interval (CI) 1.4 to 3.3, P<0.001) and ECMO type (VA ECMO: IRR 2.35;95% CI 1.43 to 3.87, P<0.001;ECCO2R: IRR 2.63, 95% CI 1.37 to 4.9, P=0.003;reference VV ECMO) on incidence rate of thromboembolic events, but not of heparin resistance (IRR 1.11, 95% CI 0.7 to 1.76, P=0.7). ECMO duration was longer (25d (IQR 11-33) vs. 8d (IQR 4-18), P<0.001) in patients with heparin resistance, but hospital survival did not differ (23 (70%) vs. 91 (57%), P=0.2). Conclusion(s): The study revealed a high incidence of heparin failure in ECMO patients, especially in those with COVID-19. Heparin resistance had no effect on the incidence rate of thromboembolic events, whereas our data suggest an increased risk in patients with COVID19, VA ECMO and ECCO2R.

COVID-19 OUTCOME IN AN ITALIAN RHEUMATOID ARTHRITIS COHORT

BackgroundIt is known that rheumatologic patients often present a course of COVID-19 similar to that of the general population. Some factors are linked to a worse COVID-19 outcome, such as moderate glucocorticoid (GC) dose, high body mass index (BMI), and comorbidities.ObjectivesTo describe the outcome of COVID-19 in patients with rheumatoid arthritis (RA) in terms of symptoms, therapy and need for hospitalization compared to a control group. Also, to evaluate the variation in disease activity before and after COVID-19.MethodsIn this monocentric prospective study, we recruited consecutive adult patients with RA classified according to ACR-EULAR 2010 criteria who received a diagnosis of COVID-19 through molecular or rapid antigen swab tests between September 2020 and December 2022. Demographic and clinical data, including age, BMI, smoking habit, comorbidities, treatment at the diagnosis of COVID-19, duration of COVID-19, symptoms related to the infection and therapy required, together with the vaccination status were collected through a self-administered questionnaire. We compared DAS28-CRP before the infection and at the first visit after the resolution. As controls (Cs), individuals with COVID-19 but with no referred diagnosis of rheumatic/autoimmune disease were recruited.ResultsWe enrolled 111 patients affected by RA (males 15%, median age 56 years, IQR 25) and 89 Cs (males 44%, median age 47 years, IQR 43), whose demographic and clinical characteristics are reported in Table 1. The median RA disease duration was 108 months (IQR 201). At the COVID-19 diagnosis, 62 patients (56%) were assuming csDMARDs, 67 (60%) bDMARDs, and 18 (16%) GC with a median prednisone equivalent dose of 4 mg/day (IQR 1). DAS28-CRP was available for 62 patients, with a median value of 1.67 (IQR 2.71);42 patients (60%) were in remission (Figure 1). Before developing COVID-19, only 35 (32%) RA patients and 42 (47%) Cs had completed the vaccinal cycle, which was performed by mRNA vaccine in all the patients and 87% of Cs. The median COVID-19 duration was 18 days (IQR 18) for RA patients and 14 days (IQR 13.5) for Cs (p>0.7). Cs reported a significantly higher frequency of constitutional symptoms (headache and asthenia) compared to RA patients (p<0.00001). When hospitalization was required, RA patients received heparin more frequently than Cs (p<0.039). Once COVID-19 was resolved, RA patients were evaluated after a median of 2 months (IQR 2). DAS28-CRP was available for 68 patients, with a median value of 1.61 (IQR 1.77);42 patients (68%) were in remission (Figure 1).No differences in terms of COVID-19 duration, clinical manifestations, and therapy emerged comparing RA patients in remission (40;58%) with patients with the active disease before COVID-19 (29;42%). Also, in vaccinated subjects, the outcome of COVID-19 was similar in RA patients and Cs, irrespective of RA activity.ConclusionCOVID-19's impact on patients with RA was not significantly different from the general population, even for patients with active RA. Patients did not suffer from reactivation of RA because of COVID-19. In our opinion, these positive results could be ascribed to the massive vaccination campaign.References[1]Conway R et al, Ir J Med Sci. 2023[2]Andersen KM et al, Lancet Rheumatol. 2022Table 1.Clinical characteristics, COVID-19 symptoms, and therapy of the two groups. Values in brackets are expressed as percentages unless specified. Musculoskeletal diseases: osteoarthritis and osteoporosis.Rheumatoid arthritis N=111Controls N=89P value*ACTIVE SMOKERS13 (12)20 (22)BMI (IQR)24 (7)23(6)COMORBIDITIES64 (58)44 (49)Cardiovascular26 (23)18 (20)Endocrine24 (22)14 (16)Musculoskeletal11 (10)6 (7)Neoplastic12 (11)3 (3)CLINICAL MANIFESTATIONS96 (86)74 (83)Fever50 (45)47 (53)Constitutional symptoms52 (47)75 (84)p <0.00001Respiratory symptoms100 (90)86 (97)Gastrointestinal symptoms12 (11)13 (15)THERAPY88 (79)74 (67)NSAIDs41 (37)31 (35)Glucocorticoids24 (22)21 (30)Antibiotics33 (30)27 (24)Oxygen6 (5)5 (6)Heparin8 (7)0 (0)p <0.039HOSPITALIZATION10 (9)6 (9)*Where not indi ated, p value >0.5Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Report of the Association Between Multisystem Inflammatory Syndrome and Severe Myocarditis

Introduction: The people worldwide have been affected by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection since its appearance in December, 2019. Kawasaki disease-like hyperinflammatory shock associated with SARS-CoV-2 infection in previously healthy children has been reported in the literature, which is now referred to as a multisystem inflammatory syndrome in children (MIS-C). Some aspects of MIS-C are similar to those of Kawasaki disease, toxic shock syndrome, secondary hemophagocytic syndrome, and macrophage activation syndrome. Case Presentation: This study reported an 11-year-old boy with MIS-C presented with periorbital and peripheral edema, abdominal pain, elevated liver enzymes, severe right pleural effusion, moderate ascites, and severe failure of right and left ventricles. Conclusion(s): Due to the increasing number of reported cases of critically ill patients afflicted with MIS-C and its life-threatening complications, it was recommended that further studies should be carried out in order to provide screening tests for myocardial dysfunction. Adopting a multidisciplinary approach was found inevitable.Copyright © 2023, Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.

Managing severe warm autoimmune haemolytic anaemia after the SARS-Cov- 2 vaccine with emergency splenectomy and eculizumab

Autoimmune haemolytic anaemia (AIHA) is rare but described after the SARS-CoV- 2 Pfizer-BioNTech vaccine. We present a case of severe refractory warm AIHA after this vaccine, managed with emergency splenectomy and complement inhibition with eculizumab. A male in his teens with a history of liver transplant for biliary atresia (aged 2 years) and AIHA (aged 6 years) presented to his district general hospital with jaundice, dark urine, fatigue and chest discomfort 48 h after the first dose of SARS-CoV- 2 Pfizer-BioNTech vaccine (BNT162b2 mRNA). Investigations revealed haemoglobin (Hb) of 70 g/L and bilirubin of 98 mumol/L, which was treated as AIHA. The patient initially responded to prednisolone (1 mg/kg, 60 mg) but subsequently deteriorated and failed to respond to second-line rituximab (375 mg/m2) and two units of packed red blood cells (PRBC). By day 29 the patient had developed life-threatening anaemia culminating in a Hb of 35 g/L (after transfusion), lactate dehydrogenase (LD) of 1293 units/L and bilirubin of 228 mumol/L. This necessitated an immediate transfer to our tertiary centre for specialist support. Further investigations revealed a haptoglobin <0.1 g/L and direct antiglobulin test (DAT) strongly positive for IgG (4+) and negative for C3d. The peripheral blood film showed severe anaemia, nucleated red cells, anisocytosis and spherocytes with no autoagglutination, schistocytes or platelet clumps. Thrombocytopaenia (platelets 49 +/- 109/L) was present. Differentials were ruled out, such as paroxysmal nocturnal haemoglobinuria and heparin-induced thrombocytopaenia. HIV and hepatitis serology were negative, as were adenovirus, cytomegalovirus and Epstein-Barr virus PCR assays. A CT showed splenomegaly of 15.5 cm. Urinalysis found urobilinogen and bilirubin at high concentrations and negative urinary haemosiderin. Together, the investigations were consistent with warm AIHA. On day 29, four units of PRBC were transfused alongside 100 mg methylprednisolone and 1 g/kg IVIG. On day 30 the patient deteriorated despite the escalated treatment: Hb had only increased to 54 g/L, bilirubin was 200 mumol/L and LD was rising. Considering this life-threatening fulminant haemolysis, an emergency splenectomy was performed. This slowed haemolysis but did not completely ameliorate it: by day 33 the patient had received 15 units of PRBC. Thus, eculizumab, a terminal complement pathway inhibitor, was trialled to arrest intravascular haemolysis, alongside rituximab, repeat IVIG 1 g/kg, prednisolone 40 mg and tacrolimus 2 mg. This showed a favourable response, requiring less frequent transfusions and settling haemolysis. This case highlights the rare complication of warm AIHA with the SARS-CoV- 2 Pfizer-BioNTech vaccine, the use of emergency splenectomy for disease control, and the potential of eculizumab for refractory cases.

Membrane dysfunction in patients with severe COVID-19 treated with venovenous extracorporeal membrane oxygenation - analysis from a pooled data from a single centre

Objectives: It is well known that severe COVID-19 is associated with complex immunological and inflammatory dysregulation. Both these physiopathological events translate to a high risk of major thrombotic or hemorrhagic events. In patients treated with venovenous extracorporeal membrane oxygenation (VVECMO), membrane dysfunction might affect systemic oxygenation and limit its duration-expectancy. This study aimed to assess the possible causes of extracorporeal membrane failure in COVID-19 patients and its impact on outcome. Method(s): Retrospective, single-center, observational case-control study involving adult COVID-19 patients admitted to an ECMO referral centre in a tertiary university hospital. All patients required VVECMO for acute respiratory failure, including 48 cases who needed one or more extracorporeal membrane exchanges and 45 controls (no membrane exchange). These two groups were compared for demographic characteristics, severity of the disease using validated scores (SAPS II and SOFA), duration of ECMO run, coagulation assessment, cumulative anticoagulation dose, associated complications, and outcomes (ICU and hospital mortality). Result(s): Most patients were males (71.0%) and younger than 50 years (79.5%). Median ECMO run duration was significantly longer in the case group (35.0 vs 14.0 days, p <0.001), as well as ICU length-of-stay (45.5 vs 28 days, p <0.001). Membrane exchange tended to be associated with sepsis (56% vs 33%, p=0.037), major hemorrhage (58% vs 43%, p=0.022), heparin-induced thrombocytopenia (25% vs 9%, p=0.054), higher D-dimer title (17.36 ng/dL vs 7.5 ng/dL, p=0.07) and lower platelet counts (133.000/muL vs 154.000/muL). Median SAPS II (32.0 vs 33.0, p=0.20) and the mortality (27% vs 24%, p >0.99) were similar between these groups. Conclusion(s): In patients with SARS-CoV-2 pneumonia and severe hypoxemia treated with VVECMO support the emergence of infection, coagulopathy and inflammation were associated with high risk of membrane dysfunction. No impact on mortality could be confirmed from these data. Anticoagulation monitoring and dosing strategies should be reinforced to promote membrane protection.

Post-Covid Myocarditis Simulating Acute Coronary Syndrome

Background: Acute myocarditis corresponds to an acute inflammation of the myocardium whose origin is most often viral. Several viruses can be incriminated to note the parvovirus B19, the virus herpes of the group 6 and to a lesser degree the virus of the hepatitis C (VHC) [18,19]. Since 2019 and with the discovery of SARS COV2 some cases of myocarditis associated with covid have been noted, this last association is rare and is present in only 5% of cases [8]. The diagnosis of myocarditis is sometimes difficult and can lead to confusion with acute coronary syndrome, especially in cases of ST-segment elevation on the EKG, hence the interest of magnetic resonance imaging, which has made it possible in recent years to reduce the rate of unnecessary coronary angiography, especially in the case of young subjects with no cardiovascular risk factors. in this context we report the case of a 33 year old patient with no cardiovascular risk factors and no medical or surgical antecedents who was admitted to the emergency department for the management of acute chest pain related to acute post-covid myocarditis, the patient was initially admitted to the cardiology intensive care unit where he was put in condition and under analgesic treatment and under therapeutic protocal of covid 19 and under anticoagulation based on low molecular weight heparin at preventive dose with a good clinical evolution he was transferred thereafter to the clinical cardiology then declared outgoing under treatment of covid 19 with an appointment of control in 1 month.

The endothelium is the main target of coronavirus infection

Background. The world currently has a wealth of clinical experience in the treatment of SARS-Co-2. However, more and more work is emerging that opens up new data on the manifestations of this viral disease and its consequences, which can affect both the change in its clinical picture and the quality of life of patients with COVID-19. Therefore, this work was aimed to summarize the results of literature research and our experience of intensive care of endothelial dysfunction in coronavirus infection. Material and methods. The work is based on the results of a study on the Internet search engines Google and PubMed, with the keywords: intensive care SARS-CoV-2, pathophysiological changes in coronavirus in- fection, endothelial dysfunction. Results. This review presents the pathogenetic links of COVID-19, mechanisms of viral endothelial damage, mechanisms of hypercoagulopathy, the main directions of prevention and treatment of endothelial dysfunction. Conclusions. The examination convincingly showed that SARS-CoV-2 infection promotes the development of endotheliitis in various organs as a result of viral infection. The presence of COVID-19-induced endotheliitis can explain the systemic microcirculation disorders in various vascular channels and their clinical consequences. © 2022. The Authors.

Clinical characteristics and risk factors of patients with COVID-19 developing barotrauma

Background: At our hospital, people with COVID-19 (coronavirus disease 2019) had a high rate of pulmonary barotrauma. Therefore, the current study looked at barotrauma in COVID-19 patients getting invasive and non-invasive positive pressure ventilation to assess its prevalence, clinical results, and features. Methodology: Our retrospective cohort study comprised of adult COVID-19 pneumonia patients who visited our tertiary care hospital between April 2020 and September 2021 and developed barotrauma. Result(s): Sixty-eight patients were included in this study. Subcutaneous emphysema was the most frequent type of barotrauma, reported at 67.6%;pneumomediastinum, reported at 61.8%;pneumothorax, reported at 47.1%. The most frequent device associated with barotrauma was CPAP (51.5%). Among the 68 patients, 27.9% were discharged without supplemental oxygen, while 4.4% were discharged on oxygen. 76.5% of the patients expired because of COVID pneumonia and its complications. In addition, 38.2% of the patients required invasive mechanical breathing, and 77.9% of the patients were admitted to the ICU. Conclusion(s): Barotrauma in COVID-19 can pose a serious risk factor leading to mortality. Also, using CPAP was linked to a higher risk of barotrauma.Copyright © 2021 Muslim OT et al.

Incidence of Heparin Induced Thrombocytopenia (HIT) in patients with severe COVID-19

Introduction To prevent and treat thrombotic complications in patients hospitalized with severe COVID-19 infection, anticoagulation treatments primarily with heparin and low molecular weight heparin have been recommended. Heparin-induced thrombocytopenia (HIT) is a rare but conceivably fatal reaction to heparin that is characterized by a sudden drop in platelet count accompanied by new onset of thrombosis 4-10 days after heparin exposure. The purpose of this retrospective study was to investigate the prevalence of thrombocytopenia and HIT in hospitalized COVID-19 patients, as well as their association with mortality. Methods 3,672 plasma samples were collected from patients admitted to the first wave of COVID-19 in our institution at New York City (March to May 2020). All patients admitted with a platelet count of less than 150 k/ul were assigned to the thrombocytopenic group. In addition, two groups with similar demographics and normal platelet counts were randomly selected based on discharge outcome: alive vs. deceased (n= 88 per group). PF4 IgG Elisa and heparin neutralization were carried out in accordance with the manufacturer's instructions. A positive HIT result required an optical density (OD) greater than 0.4 and heparin neutralization greater than 50%. Statistical analysis was done in R studio (V.1.4.1717) to analyze demographics (age, gender, ethnicity), initial laboratory data, anticoagulation on admission, and thrombosis. Results Only 86 of the 3,672 (2.3%) patients admitted had thrombocytopenia. Only 1 of the 86 patients tested positive for HIT (1.1%). 4 cases of the non-survivors (4.5%) tested positive for HIT compared to none of the survivors in the two groups with normal platelet counts. One of these 4 cases had a history of thrombosis (DVT). Interestingly, the PF4 Elisa ODs in non-survivors were significantly higher than in survivors (0.09 vs. 0.06, p-value< 0.001). Although the platelet count did not differ significantly between the two groups, the mean platelet volume (MPV) on admission and its maximum peak during hospitalization were significantly higher in non-survivors than in survivors. Conclusions We only found HIT positive cases among non-survivors, implying that HIT is associated with COVID severity. The incidence of HIT in severe COVID-19 patients appears to be higher than the pre-COVID-19 historical rates of HIT in hospitalized patients (<1%). Although thrombocytopenia is relatively uncommon in COVID-19 patients, the MPV was significantly higher in non-survivors, suggesting that platelet activation and destruction may explain the higher rate of HIT in COVID-19.

Effect of weight-adjusted intermediate-dose versus fixed-dose prophylactic anticoagulation with low-molecular-weight heparin on venous thromboembolism among noncritically and critically ill patients with COVID-19: the COVI-DOSE trial, a multicenter, randomised, open-label, phase 4 trial.

Background: Venous thromboembolism is a major complication of coronavirus disease 2019 (COVID-19). We hypothesized that a weight-adjusted intermediate dose of anticoagulation may decrease the risk of venous thromboembolism COVID-19 patients. Methods: In this multicenter, randomised, open-label, phase 4, superiority trial with blinded adjudication of outcomes, we randomly assigned adult patients hospitalised in 20 French centers and presenting with acute respiratory SARS-CoV-2. Eligible patients were randomly assigned (1:1 ratio) to receive an intermediate weight-adjusted prophylactic dose or a fixed-dose of subcutaneous low-molecular-weight heparin during the hospital stay. The primary outcome corresponded to symptomatic deep-vein thrombosis (fatal) pulmonary embolism during hospitalization (COVI-DOSE ClinicalTrials.gov number: NCT04373707). Findings: Between May 2020, and April 2021, 1000 patients underwent randomisation in medical wards (noncritically ill) (80.1%) and intensive care units (critically ill) (19.9%); 502 patients were assigned to receive a weight-adjusted intermediate dose, and 498 received fixed-dose thromboprophylaxis. Symptomatic venous thromboembolism occurred in 6 of 502 patients (1.2%) in the weight-adjusted dose group and in 10 of 498 patients (2.1%) in the fixed-dose group (subdistribution hazard ratio, 0.59; 95% CI, 0.22-1.63; P = 0.31). There was a twofold increased risk of major or clinically relevant nonmajor bleeding: 5.9% in the weight-adjusted dose group and 3.1% in the fixed-dose group (P = 0.034). Interpretation: In the COVI-DOSE trial, the observed rate of thromboembolic events was lower than expected in patients hospitalized for COVID-19 infection, and the study was unable to show a significant difference in the risk of venous thromboembolism between the two low-molecular-weight-heparin regimens. Funding: French Ministry of Health, CAPNET, Grand-Est Region, Grand-Nancy Métropole.

Anti-factor Xa vs aPTT for heparin monitoring in extracorporeal membrane oxygenation.

PURPOSE: The goal of this study was to evaluate the correlation of anti-factor Xa (anti-Xa) and activated partial thromboplastin time (aPTT) measures with heparin dosing in adult patients on extracorporeal membrane oxygenation (ECMO) support. METHODS: This was a retrospective cohort study evaluating adult patients managed on ECMO for at least 24 hours who received unfractionated heparin for systemic anticoagulation and were monitored per protocol using anti-Xa and/or aPTT coagulation assays. The primary outcome was the correlation between aPTT and anti-Xa measures. The secondary outcomes included, but were not limited to, the number of hemorrhagic and thrombotic events. RESULTS: Twenty-seven patients were included in this study. In the 227 events where both laboratory values were collected, a weak correlation was found between anti-Xa and aPTT (Spearman's correlation coefficient = 0.4, P = 0). In the 12 hemorrhagic events that occurred, aPTT was collected for only 10 events. Fifty percent of those events were associated with supratherapeutic aPTT, while none of the hemorrhagic events were associated with a supratherapeutic anti-Xa level. Two thrombotic events occurred, one of which had subtherapeutic anti-Xa and aPTT and the other of which had neither an anti-Xa nor aPTT measure on the day the event occurred. CONCLUSION: In a population of patients on ECMO, many of whom had coronavirus disease 2019 (COVID-19), there was a weak association between aPTT and anti-Xa measures. Hemorrhagic evens were more common than thrombotic events; however, a relationship between these events and aPTT or anti-Xa levels was not determined. The applicability of these findings to an ECMO population without COVID-19 is unknown and will require further study.

Does COVID-19 infection acquired in different pregnancy trimester influence placental pathology?

OBJECTIVES: To determine the morphological characteristics of the placentas from COVID-19 positive mothers in regard to the trimester of COVID-19 infection onset and low weight molecular heparin (LMWH) treatment. METHODS: Placentas were collected in the period April 1st till September 1st 2021 after delivery at Department of Obstetrics and Gynecology University Hospital Split, Croatia, and sent for pathological examination. Medical history and pathology reports were used to collect the data. Pregnant women were divided based on the onset of COVID-19 infection and stratified into low molecular weight heparin (LMWH)+ or LMWH-. Depending on the data distribution, the following test were used: chi-squared test. Student's t-test, Mann-Whitney U test, ANOVA and Kruskal-Wallis test. RESULTS: In 38% of patients the onset of COVID-19 infection was the 1st trimester of pregnancy, in 27% in the 2nd and 35% of women were infected in the 3rd trimester The fetal vascular malperfusion (FVM) occurrence was statistically significantly higher in the LMWH- group and if the onset of infection was in the 2nd trimester, while the perivillous fibrin deposition was most likely to happen if the COVID-19 infection that occured in the 1st trimester of pregnancy. CONCLUSIONS: The onset of COVID-19 infection has the influence on trophoblast damage and subsequent morphological appearance of the placenta. LMWH use in COVID positive pregnant women decreases the rate of the FVM in examined placentas.

Edoxaban Versus Low-Molecular-Weight Heparin in Hospitalized COVID-19 Patients With Atrial Fibrillation.

OBJECTIVE: During the first wave of the SARS-CoV-2 pandemic, management of anticoagulation therapy in hospitalized patients with atrial fibrillation (AF) was simplified to low-molecular-weight heparin (LMWH) followed by oral anticoagulation, mainly owing to the risk of drug-drug interactions. However, not all oral anticoagulants carry the same risk. METHODS: Observational, retrospective, and multicenter study that consecutively included hospitalized patients with AF anticoagulated with LMWH followed by oral anticoagulation or edoxaban concomitantly with empirical COVID-19 therapy. Time-to-event (mortality, total bleeds, and admissions to ICU) curves, using an unadjusted Kaplan-Meier method and Cox regression model adjusted for potential confounders were constructed. RESULTS: A total of 232 patients were included (80.3 ± 7.7 years, 50.0% men, CHA2DS2-VASc 4.1 ± 1.4; HAS-BLED 2.6 ± 1.0). During hospitalization, patients were taking azithromycin (98.7%), hydroxychloroquine (89.7%), and ritonavir/lopinavir (81.5%). The mean length of hospital stay was 14.6 ± 7.2 days, and total follow-up was 31.6 ± 13.4 days; 12.9% of patients required admission to ICU, 18.5% died, and 9.9% had a bleeding complication (34.8% major bleeding). Length of hospital stay was longer in patients taking LMWH (16.0 ± 7.7 vs 13.3 ± 6.5 days; P = .005), but mortality and total bleeds were similar in patients treated with edoxaban and those treated with LMWH followed by oral anticoagulation. CONCLUSIONS: Mortality rates, arterial and venous thromboembolic complications, and bleeds did not significantly differ between AF patients receiving anticoagulation therapy with edoxaban or LMWH followed by oral anticoagulation. However, the duration of hospitalization was significantly lower with edoxaban. Edoxaban had a similar therapeutic profile to LMWH followed by oral anticoagulation and may provide additional benefits.

Alpha-1-antitrypsin antagonizes COVID-19: a review of the epidemiology, molecular mechanisms, and clinical evidence.

Alpha-1-antitrypsin (AAT), a serine protease inhibitor (serpin), is increasingly recognized to inhibit SARS-CoV-2 infection and counter many of the pathogenic mechanisms of COVID-19. Herein, we reviewed the epidemiologic evidence, the molecular mechanisms, and the clinical evidence that support this paradigm. As background to our discussion, we first examined the basic mechanism of SARS-CoV-2 infection and contend that despite the availability of vaccines and anti-viral agents, COVID-19 remains problematic due to viral evolution. We next underscored that measures to prevent severe COVID-19 currently exists but teeters on a balance and that current treatment for severe COVID-19 remains grossly suboptimal. We then reviewed the epidemiologic and clinical evidence that AAT deficiency increases risk of COVID-19 infection and of more severe disease, and the experimental evidence that AAT inhibits cell surface transmembrane protease 2 (TMPRSS2) - a host serine protease required for SARS-CoV-2 entry into cells - and that this inhibition may be augmented by heparin. We also elaborated on the panoply of other activities of AAT (and heparin) that could mitigate severity of COVID-19. Finally, we evaluated the available clinical evidence for AAT treatment of COVID-19.

Optimal dosing of heparin for prophylactic anticoagulation in critically ill COVID-19 patients a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: The optimal amount of anticoagulation for critically ill COVID-19 patients is controversial. Therefore, we aimed to evaluate the efficacy and safety of escalated doses of anticoagulation in critically ill patients with severe COVID-19. MATERIALS AND METHODS: We conducted a systematic search of three major databases, including PubMed, Cochrane Library, and Embase, from inception to May 2022. Randomized controlled trials (RCTs) were included comparing therapeutic or intermediate doses to standard prophylactic doses of anticoagulants in critically ill COVID-19 patients, with heparins as the only anticoagulation therapy considered. RESULTS: Out of the six RCTs, 2130 patients were administered escalated dose anticoagulation (50.2%) and standard thromboprophylaxis therapy (49.8%). The escalated dose showed no significant impact on mortality (RR, 1.01; 95% CI, 0.90-1.13). Although there was no significant difference in DVT (RR, 0.81; 95% CI, 0.61-1.08), the risk of PE was significantly reduced in patients receiving escalated dose anticoagulation (RR, 0.35; 95% CI, 0.21-0.60), with an increased risk of bleeding events (RR, 1.65; 95% CI, 1.08-2.53). CONCLUSION: This systematic review and meta-analysis fail to support escalated anticoagulation doses to reduce mortality in critically ill COVID-19 patients. However, higher doses of anticoagulants appear to reduce thrombotic events while increasing the risk of bleeding effectively.

Pharmacological Agents Targeting Coagulopathy in COVID-19: A Review

Infection with severe acute respiratory syndrome coronavirus (SARS-CoV-2) and the resultant syndrome COVID-19 has wrecked the entire world. The disease mostly manifests as mild viral pneumonia but in a small proportion of patients it can produce an intense inflammatory and prothrombotic state leading to multiorgan failure and even death. Varying incidences of venous thromboembolism (VTE) have been found in COVID-19 patients. This review describes the role of various pharmacological agents used prophylactically as well as therapeutically for thromboembolism in such patients. The anticoagulants which are administered as antithrombotic therapy can be used parenterally (heparin and direct thrombin inhibitors) or orally (direct oral thrombin inhibitors). The mechanism of action, pharmacology, usage, and adverse effects of such agents has been discussed especially in the context of ongoing COVID-19 pandemic. As a result of various completed and ongoing clinical trials, scientific community has collected promising evidence and formulated guidelines regarding the role of anticoagulants in COVID-19 patients. © The Author(s), under exclusive licence to Springer Nature Singapore Pte Ltd. 2021.

Multisystem Inflammatory Syndrome in Children Requiring ECMO: Anticoagulation strategies and Lessons Learned

Intro: Multisystem Inflammatory Syndrome in Children (MIS-C) is a post-infectious inflammatory response after exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which can cause acute cardiac dysfunction requiring mechanical circulatory support (MCS). MCS utilization for MIS-C is complicated by a propensity for thrombosis, which threatens circuit integrity. This study describes a cohort of MIS-C patients requiring MCS, their outcomes, and the anticoagulation strategies utilized. Method(s): A retrospective case series of patients diagnosed with MIS-C needing veno-arterial extracorporeal membrane oxygenation (VA-ECMO) at Children's Healthcare of Atlanta from March 1, 2020 to June 30, 2022. VA-ECMO variables, laboratory data, complications, and outcomes were collected. Result(s): Seven patients (all male) with severe MIS-C required VA-ECMO for acute cardiac dysfunction. Median age was 13 years (range 4-15 years). Median ICU stay was 13 days (range 6-17 days) with a median ECMO duration of 7 days (IQR 3-8 days) and median mechanical ventilation duration of 8 days (IQR 5-11 days). All seven patients survived to hospital discharge with good neurologic outcomes. Median time to qualitatively normal ventricular function by echocardiogram was 9.5 days (IQR 3-21 days). Heparin was initially used in 6 patients, bivalrudin initially used in 1 patient, and 1 patient converted from heparin to bivalirudin for refractory systemic thrombosis. Median heparin dose was 206u/kg/d (IQR 192-276u/kg/d) with median anti-Xa levels of 0.75 (IQR 0.1-1.1) and median daily PTT 102 seconds (IQR 83-107 seconds). Median daily PTT of patients receiving bivalirudin was 86 seconds (80-93 seconds). Median R-values by thromboelastography were 38 seconds (IQR 25-55 seconds). Two patients required catheter directed thrombolysis with tissue plasminogen activator (t-PA) for refractory intracardiac thrombi, both were initially started on heparin. Significant cannula thrombosis occurred in 2 patients, 1 initially started on heparin and 1 initially on bivalrudin. Bleeding resulting in compartment syndrome occurred in one patient on heparin requiring fasciotomy of the upper extremities, this patient was not receiving t-PA. Conclusion(s): Anticoagulation management for MIS-C patients requiring ECMO is fraught with challenges. A successful management strategy may necessitate higher heparin assay levels, the use of direct thrombin inhibitors for refractory thrombosis, and the deployment of catheter directed thrombolysis. In this case series, CDT was safely and successfully used in two patients. Further studies are required to understand the optimal anticoagulation strategy for these patients to minimize complications.

Economic aspects of COVID-19 treatment in a hospital setting

In April 2020 in order to prevent the spread of the new coronavirus infection COVID-19 on the territory of the Russian Federation, strict quarantine measures were introduced. In the shortest possible time, a large number of general hospitals were repurposed into COVID hospitals, recommendations were issued on the management of patients with a new coronavirus infection based on the existing global experience. The limited resources of the healthcare system in a pandemic require research into the pharmacoeconomic aspects of COVID-19. In the course of the study, a continuous retrospective analysis of the case histories of 6255 patients admitted to the Central Clinical Hospital RZD-Medicine was carried out. During the study period, 22% of patients received biological therapy. The average mortality rate of patients on biological therapy is 11.6%. An individual selection of the therapeutic dose of low molecular weight heparins was carried out, which showed high clinical efficacy. The developed methods were assessed from the perspective of pharmacoeconomics. The increase in the degree of damage to the lung tissue in patients with COVID-19, as well as the presence of concomitant diseases, entails an increase in the cost of treatment. Biotherapy can reduce the cost of treating patients with CT-4 by 16% by reducing the length of stay in the intensive care unit, the need for mechanical ventilation and reducing mortality.Copyright © 2021 Infectious Diseases: News, Opinions, Training. All rights reserved.