Therapeutic Dose Of Enoxaparin Research Articles

A case report on therapeutic anticoagulation in the management of a COVID-19 patient on antiplatelets post-CABG — how much is enough?

BackgroundCoronavirus disease (COVID-19) predisposes patients to both arterial and venous thrombosis due to excessive inflammation, platelet activation, endothelial dysfunction, and stasis. Therefore, therapeutic anticoagulant therapy has been an integral part for management in patients with moderate to severe COVID-19 disease. We shall here discuss the concerns of starting anticoagulants in patients with COVID-19 disease who are already on antiplatelets, an unexplored area.Case presentationWe herein report a case of 61-year-old patient with hypertension and diabetes mellitus type 2 with COVID-19 disease. Patient also had coronary artery disease and underwent CABG 4 years ago and was on aspirin 75-mg HS, clopidogrel 75-mg OD, and tab atorvastatin 40-mg HS. Patient was hemodynamically stable and was maintaining a saturation of 66% on room air and a saturation of 96% on 02 by high FiO2 partial rebreathing face mask. On auscultation, crepitations were present in bilateral lower lung fields. The patient was admitted under moderate category of COVID-19 SARS in the intensive care unit (ICU). Despite of standard care and treatment, in next 2 days, the oxygenation deteriorated Pa02/Fi02 < 200, and intermittent noninvasive ventilation had to be started, and patient’s clinical condition fell into the severe disease category, wherein there was a need to start IV methylprednisolone and to start the therapeutic dose of anticoagulant, i.e., enoxaparin. The D-dimer was greater than 1000 ng/mL therapeutic dose of enoxaparin, i.e., 2 U/kg in two divided doses was started. Patient’s condition improved. In the present case, we fraught with the increased risk of bleeding or mortality subsequent to increasing the dose of anticoagulant as the patient was already on antiplatelets.ConclusionsWe emphasize that one must evaluate the risk and benefit of bleeding vs improved oxygenation prior to considering the therapeutic dose of LMW heparin in patients who are already on antiplatelets. A track on d-dimer and fibrinogen levels for dose titration may be useful step in this set of patients. We reiterate upon the formulation of dogmatic guidelines in this context is warranted.

Randomized Trial of Anticoagulation Strategies for Noncritically Ill Patients Hospitalized With COVID-19

BackgroundPrior studies of therapeutic-dose anticoagulation in patients with COVID-19 have reported conflicting results. ObjectivesWe sought to determine the safety and effectiveness of therapeutic-dose anticoagulation in noncritically ill patients with COVID-19. MethodsPatients hospitalized with COVID-19 not requiring intensive care unit treatment were randomized to prophylactic-dose enoxaparin, therapeutic-dose enoxaparin, or therapeutic-dose apixaban. The primary outcome was the 30-day composite of all-cause mortality, requirement for intensive care unit–level of care, systemic thromboembolism, or ischemic stroke assessed in the combined therapeutic-dose groups compared with the prophylactic-dose group. ResultsBetween August 26, 2020, and September 19, 2022, 3,398 noncritically ill patients hospitalized with COVID-19 were randomized to prophylactic-dose enoxaparin (n = 1,141), therapeutic-dose enoxaparin (n = 1,136), or therapeutic-dose apixaban (n = 1,121) at 76 centers in 10 countries. The 30-day primary outcome occurred in 13.2% of patients in the prophylactic-dose group and 11.3% of patients in the combined therapeutic-dose groups (HR: 0.85; 95% CI: 0.69-1.04; P = 0.11). All-cause mortality occurred in 7.0% of patients treated with prophylactic-dose enoxaparin and 4.9% of patients treated with therapeutic-dose anticoagulation (HR: 0.70; 95% CI: 0.52-0.93; P = 0.01), and intubation was required in 8.4% vs 6.4% of patients, respectively (HR: 0.75; 95% CI: 0.58-0.98; P = 0.03). Results were similar in the 2 therapeutic-dose groups, and major bleeding in all 3 groups was infrequent. ConclusionsAmong noncritically ill patients hospitalized with COVID-19, the 30-day primary composite outcome was not significantly reduced with therapeutic-dose anticoagulation compared with prophylactic-dose anticoagulation. However, fewer patients who were treated with therapeutic-dose anticoagulation required intubation and fewer died (FREEDOM COVID [FREEDOM COVID Anticoagulation Strategy]; NCT04512079)

Enoxaparin Posology According to Prothrombotic Status and Bleeding Risk in Hospitalized Patients with SARS-CoV-2 Pneumonia.

Some patients with COVID-19 have complex hypercoagulable abnormalities that are related to mortality. The optimal dosage of low molecular weight heparin in hospitalized patients with SARS-CoV-2 pneumonia is still not clear. Our objective is to evaluate the effects of adapting the dosage of low molecular weight heparin to thrombotic and bleeding risk scales in this setting. We performed a cohort, retrospective, observational, and analytical study at the Hospital Universitario of Jerez de la Frontera, with patients admitted with SARS-CoV-2 pneumonia from 1 October 2020 to 31 January 2021. They were classified according to whether they received prophylactic, intermediate, or therapeutic doses of enoxaparin. The primary endpoint was intrahospital mortality. Secondary endpoints were the need for invasive ventilation, thromboembolic events, bleeding, and the usefulness of thrombotic and bleeding scales. After binary logistic regression analysis, considering confounding variables, it was found that the use of enoxaparin at therapeutic doses was associated with lower mortality during admission compared to prophylactic and intermediate doses (RR 0.173; 95% CI, 0.038-0.8; p = 0.025). IMPROVE bleeding risk score correlated with a higher risk of minor bleeding (RR 1.263; 95% CI, 1.105-1.573; p = 0.037). In adult hospitalized patients with SARS-CoV-2 pneumonia presenting elevated D-dimer and severe proinflammatory state, therapeutic doses of enoxaparin can be considered, especially if bleeding risk is low according to the IMPROVE bleeding risk score.

The Effectiveness of the Intermediate and Therapeutic Doses of Enoxaparin in COVID-19 Patients: A Comparative Study of Factor Xa Inhibition

Background: Management of anticoagulant therapy in COVID-19 patients is critical. Low-molecular-weight heparin (LMWH) thromboprophylaxis is already recommended, and anti-Factor Xa (anti-FXa) monitoring has been used to titrate LMWH doses. Methods: Through a cross-sectional study, we evaluated anti-FXa activity in patients admitted to the ICU, receiving intermediate dose (30, 40, 50 mg, subcutaneously [SC], twice daily) or therapeutic dose (1 mg/kg, SC, Q12h) of enoxaparin to find whether the patients in these two groups achieved anti-FXa levels in the accepted thromboprophylaxis range. Results: The occurrence of deep vein thrombosis was 26% in the therapeutic-dose group and 17% in the intermediate-dose group. D-dimer values were nearly 3.5-fold higher in those who received a therapeutic dose of anticoagulants than in those who received intermediate-dose thromboprophylaxis. Patients in the therapeutic-dose group had significantly higher IL-6 levels (p ≤ 0.001). More than one-third of the patients in the therapeutic-dose group (n = 8; 42.18%) and approximately half of the patients in the intermediate-dose group (n = 12; 52.2%) achieved the target range level of anti-FXa. Patients who received therapeutic doses were more likely to have anti-FXa levels above the expected range (47.4 vs 13% in the intermediate-dose group; p < 0.05). Conclusion: Therapeutic dose of enoxaparin in critically ill COVID-19-infected patients did not reduce the incidence of thromboembolic events and, on the other hand, may predispose these patients to increased risk of bleeding by increasing anti-FXa activity above the desired level. Administration of intermediate-dose thromboprophylaxis is suggested to achieve anti-FXa levels in the accepted thromboprophylaxis range.

Abstract 13870: Ventricular Fibrillation Arrest in a 27-Year-Old Woman Due to Takotsubo Cardiomyopathy

Introduction: Sudden cardiac death in young patients may be due to coronary artery disease, primary electrical disease, cardiomyopathy, or congenital anomalies. We explore potential causes for sudden cardiac arrest in a young patient. Case Description: A 27-year-old woman was found unconscious. Initial rhythm showed ventricular fibrillation. Cardiopulmonary resuscitation was done for 5 minutes before return of spontaneous circulation. ECG showed ST elevations in aVL, V4, and V5. She was admitted for therapeutic temperature management. Troponin peaked at 1.86 ng/mL on the evening of arrival. Transthoracic echocardiography (TTE) demonstrated hypokinesis of the mid to distal septum, anterior wall, and apex (Figure 1). Repeat TTE 3 days later showed resolution of the wall motion abnormalities. She reported marijuana use and a domestic dispute with her significant other the night prior. Coronary CT angiography showed calcium score of 0 with normal coronary anatomy, no significant coronary artery stenosis, and incidental finding of bilateral pulmonary artery filling defects. Lower limb venous duplex was unremarkable. Therapeutic dose of enoxaparin was started. Cardiac MRI showed no myocardial infarction, scar, or infiltrative disease. An electrophysiology study revealed adequate QT shortening during epinephrine infusion and no inducible ventricular arrhythmias. Genetic testing was unremarkable. She was discharged with a wearable defibrillator before ultimately receiving a subcutaneous implantable cardioverter-defibrillator. Discussion: The presentation of transient regional wall motion abnormalities, with ST-segment elevations and negative ischemic workup, is highly suggestive of Takotsubo cardiomyopathy, mid-ventricular variant. Marijuana use is a risk factor, and the domestic dispute is a potential emotional trigger. This case highlights Takotsubo cardiomyopathy as a possible cause of sudden cardiac arrest in young patients.

Clinical evaluation of the safety and efficacy of enoxaparin in patients with COVID-19.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), increases thrombotic risk in hospitalised patients. The rate of thrombosis in patients with COVID-19 is unclear. The role of heparin, frequently used in the management of hospitalised patients, also needs to be clarified. In this study, we investigated the efficacy and safety of enoxaparin given at prophylactic or therapeutic dose in hospitalised patients with COVID-19, and evaluated its role in the development of disease in terms of mortality, and incidence of thrombotic and bleeding events. We included 141 patients with SARS-CoV-2 infection, admitted to five different wards (one intensive care unit, 2 sub-intensive care units, and 2 general infectious disease units) of Cotugno Hospital, a tertiary care hospital in Naples, Italy, between March and May 2020. Over a median time of 17 days (IQR 11-25), enoxaparin was given to 90/141 patients (63.8%) of whom 65 took a prophylactic and 25 a therapeutic dose. We documented 14 episodes of thrombosis (9.9%); almost all were cases of pulmonary embolism. No significant difference in terms of thromboembolic prevention was found between those patients not receiving anticoagulants and those on prophylactic or therapeutic dose of enoxaparin. Five episodes of major bleeding occurred (3.5%); therapeutic dose of enoxaparin was associated with a greater bleeding risk than prophylactic dose (p=0.002). During follow-up, 31 patients (22%) died; these were mostly elderly men with two or more comorbidities at admission. No advantages of enoxaparin, either as prophylaxis or at high doses, in terms of mortality were observed. At multivariate analysis, low estimated glomerular filtration rate, and high total bilirubin and fasting hyperglycemia were independently associated with a higher mortality. We did not observe advantages in terms of either thromboembolic prevention or mortality of enoxaparin, which however was more frequently used in patients with more severe disease. Prophylactic enoxaparin was not seen to be associated with bleeding risk.

Bivalirudin vs. Enoxaparin in Intubated COVID-19 Patients: A Pilot Multicenter Randomized Controlled Trial.

(1) Background: In COVID-19 patients, the occurrence of thromboembolic complications contributes to disease progression and mortality. In patients at increased risk for thrombotic complications, therapeutic enoxaparin should be considered. However, critically ill COVID-19 patients could develop resistance to enoxaparin. Bivalirudin, a thrombin inhibitor, may be an alternative. This pilot multicenter randomized controlled trial aims to ascertain if bivalirudin may reduce the time spent under invasive mechanical ventilation, as compared to enoxaparin. (2) Methods: Intubated COVID-19 patients at risk for thrombo-embolic complications were randomized to receive therapeutic doses of enoxaparin or bivalirudin. We ascertained the time spent under invasive mechanical ventilation during the first 28 days from Intensive Care Unit (ICU) admission. A standardized weaning protocol was implemented in all centers. In addition, we assessed the occurrence of thromboembolic complications, the number of patients requiring percutaneous tracheostomy, the gas exchange, the reintubation rate, the ICU length of stay, the ICU and 28-days mortalities. (3) Results: We enrolled 58 consecutive patients. Bivalirudin did not reduce the time spent under invasive mechanical ventilation as compared to enoxaparin (12 [8; 13] vs. 13 [10; 15] days, respectively; p = 0.078). Thrombotic (p = 0.056) and embolic (p = 0.423) complications, need for tracheostomy (p = 0.423) or reintubation (p = 0.999), the ICU length of stay (p = 0.076) and mortality (p = 0.777) were also similar between treatments. Patients randomized to bivalirudin showed a higher oxygenation at day 7 and 15 after randomization, when compared to enoxaparin group. (4) Conclusions: In intubated COVID-19 patients at increased risk for thromboembolic complications, bivalirudin did not reduce the time spent under invasive mechanical ventilation, nor improved any other clinical outcomes.

P400 CLINICAL IMPACT OF PROPHYLACTIC ANTICOAGULANT TREATMENT WITH ENOXAPARIN IN CORONAVIRUS DISEASE 2019 (COVID–19)ELDERLY PATIENTS

IntroductionCOVID–19 patients are at increased risk of venous thromboembolism. The WHO/ISSrecommends daily prophylactic anticoagulation therapy with low–molecular weight heparins in COVID–19 patients. Our study evaluated the efficacy of a prophylactic therapy with enoxaparin on clinical outcomes in COVID–19 patients.MethodsThis is a retrospective analysis of 125 SARS–CoV–2 patients hospitalized from 16 MARCH 2020 to MAY 7th, 2021. In this phase of COVID–19 pandemic, man and woman in–patients and out–patients received enoxaparin either at prophilattics or therapeutic dosage. Based on these criteria, we examined 85 patients who received PROPHILATTICenoxaparin (group E, Enoxaparin) and 40 subjects undergone THERAPEUTIC Enoxaparin (group T, Therapeutic). Of them, 95 patients were hospitalized after Sars–Cov2 positive swab and 30 received prophilatic dosage at home.ResultsAfter applying a propensity score matching for age and gender, considering hospitalized patients, there were no significant differences between the two groups (E, T). During hospitalization, a significantly higher percentage of patients of E group developed ARDS (37 vs 13, p = 0.0001) and needed for non–invasive ventilation No significative difference between the two groups was found about incidence of intubation (20 in E vs. 19 in T group; p = 0.4) and pulmonary embolism (17 vs 5, p = 0.4). In–hospital death occurred in 17 E group patients and in 10 T group patients (p = 0.251). No difference on 30–days mortality was found between two groups (p = 0.287). N. 15 patients of T group experienced emorragic events and interrupted enoxaparin therapy. N. 17 of them experienced adverse events (mailny thrombocitopenia).ConclusionsAmong patients with SARS–CoV–2 infection, a therapeutic dose of enoxaparin is not associated with prognostic benefit and did not affect in–hospital and 30–days mortality. A risk–adapted approach to reduce the dose of anticoagulation agent should be considered in selected COVID–19 patients with evidence of coagulopathy. In summary, current data suggest the use of therapeutic–dose LMWH to reduce VTE, it, may increase bleeding, and should be avoided in hospitalized patients with severe COVID–19 in critical care settings.. Lastly, randomized trials in this patient population are still ongoing and novel antithrombotic strategies in critically ill COVID–19 patients are needed.

Clinical evaluation of the safety and efficacy of enoxaparin in patients with COVID-19.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), increases thrombotic risk in hospitalised patients. The rate of thrombosis in patients with COVID-19 is unclear. The role of heparin, frequently used in the management of hospitalised patients, also needs to be clarified. In this study, we investigated the efficacy and safety of enoxaparin given at prophylactic or therapeutic dose in hospitalised patients with COVID-19, and evaluated its role in the development of disease in terms of mortality, and incidence of thrombotic and bleeding events. We included 141 patients with SARS-CoV-2 infection, admitted to five different wards (one intensive care unit, 2 sub-intensive care units, and 2 general infectious disease units) of Cotugno Hospital, a tertiary care hospital in Naples, Italy, between March and May 2020. Over a median time of 17 days (IQR 11-25), enoxaparin was given to 90/141 patients (63.8%) of whom 65 took a prophylactic and 25 a therapeutic dose. We documented 14 episodes of thrombosis (9.9%); almost all were cases of pulmonary embolism. No significant difference in terms of thromboembolic prevention was found between those patients not receiving anticoagulants and those on prophylactic or therapeutic dose of enoxaparin. Five episodes of major bleeding occurred (3.5%); therapeutic dose of enoxaparin was associated with a greater bleeding risk than prophylactic dose (p=0.002). During follow-up, 31 patients (22%) died; these were mostly elderly men with two or more comorbidities at admission. No advantages of enoxaparin, either as prophylaxis or at high doses, in terms of mortality were observed. At multivariate analysis, low estimated glomerular filtration rate, and high total bilirubin and fasting hyperglycaemia were independently associated with a higher mortality. We did not observe advantages in terms of either thromboembolic prevention or mortality of enoxaparin, which however was more frequently used in patients with more severe disease. Prophylactic enoxaparin was not seen to be associated with bleeding risk.

Efficacy and Safety of Therapeutic-Dose Heparin vs Standard Prophylactic or Intermediate-Dose Heparins for Thromboprophylaxis in High-risk Hospitalized Patients With COVID-19

Hospitalized patients with COVID-19 are at risk for venous and arterial thromboembolism and death. Optimal thromboprophylaxis dosing in high-risk patients is unknown. To evaluate the effects of therapeutic-dose low-molecular-weight heparin (LMWH) vs institutional standard prophylactic or intermediate-dose heparins for thromboprophylaxis in high-risk hospitalized patients with COVID-19. The HEP-COVID multicenter randomized clinical trial recruited hospitalized adult patients with COVID-19 with D-dimer levels more than 4 times the upper limit of normal or sepsis-induced coagulopathy score of 4 or greater from May 8, 2020, through May 14, 2021, at 12 academic centers in the US. Patients were randomized to institutional standard prophylactic or intermediate-dose LMWH or unfractionated heparin vs therapeutic-dose enoxaparin, 1 mg/kg subcutaneous, twice daily if creatinine clearance was 30 mL/min/1.73 m2 or greater (0.5 mg/kg twice daily if creatinine clearance was 15-29 mL/min/1.73 m2) throughout hospitalization. Patients were stratified at the time of randomization based on intensive care unit (ICU) or non-ICU status. The primary efficacy outcome was venous thromboembolism (VTE), arterial thromboembolism (ATE), or death from any cause, and the principal safety outcome was major bleeding at 30 ± 2 days. Data were collected and adjudicated locally by blinded investigators via imaging, laboratory, and health record data. Of 257 patients randomized, 253 were included in the analysis (mean [SD] age, 66.7 [14.0] years; men, 136 [53.8%]; women, 117 [46.2%]); 249 patients (98.4%) met inclusion criteria based on D-dimer elevation and 83 patients (32.8%) were stratified as ICU-level care. There were 124 patients (49%) in the standard-dose vs 129 patients (51%) in the therapeutic-dose group. The primary efficacy outcome was met in 52 of 124 patients (41.9%) (28.2% VTE, 3.2% ATE, 25.0% death) with standard-dose heparins vs 37 of 129 patients (28.7%) (11.7% VTE, 3.2% ATE, 19.4% death) with therapeutic-dose LMWH (relative risk [RR], 0.68; 95% CI, 0.49-0.96; P = .03), including a reduction in thromboembolism (29.0% vs 10.9%; RR, 0.37; 95% CI, 0.21-0.66; P < .001). The incidence of major bleeding was 1.6% with standard-dose vs 4.7% with therapeutic-dose heparins (RR, 2.88; 95% CI, 0.59-14.02; P = .17). The primary efficacy outcome was reduced in non-ICU patients (36.1% vs 16.7%; RR, 0.46; 95% CI, 0.27-0.81; P = .004) but not ICU patients (55.3% vs 51.1%; RR, 0.92; 95% CI, 0.62-1.39; P = .71). In this randomized clinical trial, therapeutic-dose LMWH reduced major thromboembolism and death compared with institutional standard heparin thromboprophylaxis among inpatients with COVID-19 with very elevated D-dimer levels. The treatment effect was not seen in ICU patients. ClinicalTrials.gov Identifier: NCT04401293.

Outcomes of Catheter-Related Arterial and Venous Thrombosis After Enoxaparin Therapy in Neonates and Infants With Congenital Heart Disease.

Outcomes of catheter-related arterial and venous thrombosis after enoxaparin therapy in neonates and infants with congenital heart disease. A single-center retrospective cohort study. Cardiac ICU. Patients under 1 year old cared for in the cardiac ICU at Nicklaus Children's Hospital from January 2015 to January 2019 and treated with enoxaparin for central vascular catheter-related arterial and venous thrombosis. None. One-hundred fifty-six events of central catheter-related arterial and venous thrombosis were included in the study. Arterial thrombi accounted for 109 (69.9%) and venous thrombi for 47 (30.1%) of the events. Femoral vessels were the most commonly affected site (88.5%). Therapeutic outcomes were analyzed in 106 events, excluding those without follow-up imaging. The analysis was stratified by age into neonates and infants and catheter types into arterial and venous catheter groups. Therapeutic dose of enoxaparin was higher in neonates (median 1.8 mg/kg/dose) compared with infants (1.6 mg/kg/dose; p = 0.001). Complete resolution was seen in 68%, partial resolution in 19%, nonresolution in 13% of the events. The complete resolution was higher for arterial than venous (85% vs 65.6%; p = 0.032) thrombi with a shorter duration of enoxaparin treatment (23 vs 43 d; p = 0.014). Complete resolution was lowest in neonates with venous thrombosis (42.9%). The median time to complete resolution by Kaplan-Meier analysis was 24.9 days in the overall cohort, 34.3 days in neonates, 24.9 days in infants, 20 days in arterial, and 44.9 days in venous catheter group. A high proportion of vascular catheter-related thrombi identified in infants with congenital heart disease resolve with enoxaparin treatment. In all patients with thrombosis, arterial versus venous thrombosis is associated with greater odds of resolution.

Two Weeks of Low Molecular Weight Heparin for Isolated Symptomatic Distal Vein Thrombosis (TWISTER study)

BackgroundTreatment of low-risk patients with isolated symptomatic distal deep vein thrombi (IDDVT) is uncertain. Objective: assess whether two weeks of therapeutic anticoagulation is efficacious/safe for IDDVT. Primary outcome: symptomatic three-month venous thromboembolism (VTE) incidence in the two-week anticoagulation group. Secondary outcomes included post-thrombotic syndrome (PTS) and bleeding. MethodsProspective multicentre cohort study. Consecutive low-risk IDDVT patients enrolled within 72 h of diagnosis and treated with therapeutic dose enoxaparin or rivaroxaban. At two weeks, patients had repeat complete whole leg compression ultrasound (CUS)/clinical review. If resolution of leg symptoms AND no radiological evidence of thrombus extension, anticoagulation was stopped. If ongoing symptoms and/or radiographic extension within distal veins, anticoagulation was continued for four more weeks. Patients with extension into the popliteal vein on two-week ultrasound were treated off-study. Patients were reviewed at three and six months. Findings/interpretation241 eligible patients received ≥2 weeks anticoagulation. 167/241 (69%) were assigned to the 2-week anticoagulation group; 71/241 (30%) to the six-week anticoagulation group; 3/241 patients (1%) had extension into the popliteal vein on two-week CUS.Two patients in the two-week anticoagulation group had symptomatic IDDVT recurrence in ≤3 months; VTE recurrence 2/156; 1.3%(95% CI 0.05–4.85%). 69% of patients had complete resolution of symptoms within two weeks. Six-month PTS rates were 8/184, 4.4%(95% CI 2.1–8.5%). No major bleeding was reported.Our findings suggest it's safe/efficacious to stop therapeutic anticoagulation at two weeks in low-risk IDDVT patients with resolution of symptoms/no extension on ultrasound.This could replace 6–12 weeks of anticoagulation for ambulatory, low-risk IDDVT patients. Trial registrationClinicalTrials.govNCT01252420

Failure of therapeutic enoxaparin to prevent massive deep vein thrombosis and cerebral venous sinus thrombosis in a pregnant patient with combined factor v leiden mutation and antithrombin iii deficiency

Women with combined inherited thrombophilia are at high risk of developing thrombotic events, especially when they are pregnant. Low-molecular-weight (LMW) heparins are the preferable agents for anticoagulation during pregnancy. Despite the fact that they have been proven to be effective in the treatment and prevention of venous thromboembolism, thrombotic events can still happen. Here, we report a case of a 40-year-old white pregnant woman with combined factor V Leiden mutation and antithrombin III deficiency who developed massive deep vein thrombosis and cerebral venous sinus thrombosis despite being on therapeutic doses of enoxaparin.

Four-quadrant transverse abdominis plane block: A relatively new frontier for postoperative analgesia after major abdominal surgery

Four-quadrant transverse abdominis plane block: A relatively new frontier for postoperative analgesia after major abdominal surgery

Spontaneous bilateral pectoralis major hematoma secondary to therapeutic dose of enoxaparin in elderly Covid-19 patient

Type 1 respiratory failure secondary to ventilation-perfusion mismatch by micro-thrombus in the pulmonary vasculature and subsequent damage to the endothelial cells is by far the most typical presentation of Covid-19 pneumonia. Computed tomography pulmonary angiogram remains the investigation of choice to diagnose pulmonary embolism or micro-thrombi; however, it is not possible due to extreme hemodynamic instability or oxygen requirements in patients, making the transfer to the scanner a precarious affair. Therefore, clinicians worldwide use anticoagulant treatment doses based on clinical features, blood investigations, or echocardiography following local or national guidelines. In this report, we describe a case of bilateral pectoralis major hematoma due to treatment dose of enoxaparin in an elderly Covid-19 patient admitted in our ICU. This case report emphasises the need for extra precaution and vigilance while using treatment dose of anticoagulants for suspected pulmonary embolism in Covid-19 patients.

Assessment of anti-factor Xa activity in critically ill COVID-19 patients receiving three different anticoagulation regimens

Introduction:Critically ill COVID-19 patients are at increased risk of thrombosis with an enhanced risk of bleeding. We aimed to explore the role of anti-factor Xa levels in optimizing the high-intensity anticoagulation’s safety and efficacy and finding possible associations between D-dimer levels, cytokine storm markers, and COVID-19-induced coagulopathy or thrombophilia.Methods:Retrospective cohort study conducted on 69 critically ill COVID-19 patients who received three regimens of higher intensity anticoagulation.Results:Seventeen patients (24.6%) received high-dose enoxaparin prophylaxis, 29 patients (42%) received therapeutic doses of enoxaparin, and 23 patients (33.3%) were on therapeutic unfractionated heparin infusion. Fewer than one-third of the whole cohort (n = 22; 31.8%) achieved the target range of anti-factor Xa. The patients were divided into three subgroups based on anti-factor Xa target status within each anticoagulation regimen; when compared, the only association observed among them was for interleukin-6 levels, which were significantly higher in both the “above the expected range” and “below the expected range” groups compared with the “within the expected range” group (p = 0.009). Major bleeding episodes occurred in 14 (20.3%) patients and were non-significantly more frequent in the “below the expected anti-factor Xa range group” (p = 0.415). Seven patients (10.1%) developed thrombosis. The majority of patients had anti-factor Xa levels below the expected ranges (four patients, 57.1%).Conclusion:Conventional anti-factor Xa ranges may not be appropriate as a predictive surrogate for bleeding in critically ill COVID-19. The clinical decision to initiate therapeutic anticoagulation preemptively may be individualized according to thrombosis and bleeding risks. Cytokine storm markers, namely, interleukin-6, may play a role in COVID-19-induced coagulopathy or thrombophilia.

INFLUENCE OF DIFFERENT THROMBOPROPHYLAXIS REGIMENS WITH ENOXAPARIN ON THE COURSE AND OUTCOMES IN PATIENTS WITH SEVERE CORONAVIRUS DISEASE

Disorders of the hemostasis system play one of the key roles in the mechanism of pathogenesis of coronavirus disease. The prevalence of thromboembolic complications in patients with severe COVID-19 reaches 20–30%. Key guidelines provide guidance on the need for prophylactic doses of enoxaparin. However, the results of intensive care remain unsatisfactory and the search for the optimal dosing regimen of enoxaparin continues. The aim of the study was to compare the effect of different regimens of enoxaparin on the results of intensive care in patients with acute respiratory distress syndrome (ARDS) caused by SARS-nCoV.Materials and methods. A single-center prospective comparative study was conducted, which for the period May-October 2020 included 91 patients with severe coronavirus disease with the development of bilateral pneumonia and ARDS. Depending on the dosage regimen of enoxaparin, patients were divided into three groups. Patients of group 1 (n = 14) received 4000 anti-Xa MO of enoxaparin per day, group 2 (n = 20) – 8000-1200 anti-Xa MO, group 3 (n = 57) – 1600–2000 anti-Xa MO / days. Statistical analysis of the results was performed using the program «Statistica 10». Estimated median, minimum and maximum values, standard deviation. Significance of differences in indicators was assessed using the nonparametric Wilcoxon test. The results were considered reliable at values of p &lt;0.05. Data are presented as M ± SD [min-max]. The relative risk (RR) and the odds ratio (OR) of adverse events (thromboembolic complications and mortality) were assessed.Results. In group 1, 9 episodes of pulmonary embolism were recorded, which corresponds to 64.3%, in group 2 – 7 episodes (35.0%), and in group 3 – 13 (22.4%), (p13 = 0.04 ). The overall mortality rate was 69.23% and was significantly lower in group 3 – 56.9% than in group 1 – 92.9%, and group 2 – 85.0%.Conclusions. The use of therapeutic doses of enoxaparin is one of the key areas of therapy and has a positive effect on outcomes in patients with coronavirus disease, reducing the incidence of thromboembolic complications.

Prospective Cohort of Catheter Related Thrombosis in Patients Treated with One Month of Anticoagulation after Catheter Removal

Background: The duration of anticoagulation in patients with catheter-related thrombosis (CRT) has not been studied in a systematic fashion and is not standardized in clinical practice. Consensus guidelines have a weak recommendation for anticoagulation for 3 months after catheter removal in patients with upper extremity CRT, but this is mainly extrapolated from treatment of lower extremity deep vein thrombosis. Shorter durations of anticoagulation have been used in practice to balance the risk of bleeding and recurrent thrombosis; however, prospective data are lacking to evaluate the efficacy and safety of this practice. CRT is a frequent complication in the cancer population, who commonly requires central venous catheters for treatment. We proposed a prospective cohort study to determine the incidence of post-thrombotic syndrome (PTS), thrombosis recurrence, and bleeding in cancer patients with CRT treated with one month of anticoagulation after catheter removal. Methods: This is a multi-institutional prospective cohort study in patients with cancer and documented upper extremity CRT. Enrolled patients were treated with a standardized protocol with therapeutic doses of enoxaparin for one month after catheter removal. Patients with platelet count &amp;lt;50 x 109/L, creatinine clearance &amp;lt;30 ml/min, history of thrombosis, or ongoing need for catheters were excluded. Demographics, catheter data, and cancer history were collected at baseline visit when catheter was removed. Incidence of bleeding, recurrent thrombosis, PTS using the modified Villalta scale, and functional limitation using the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire were assessed at months 1, 3, and 6 after catheter removal. A modified Villalta score of 5 or higher was classified as the presence of PTS and a score of 15 or higher as severe PTS. Higher DASH scores indicated worse functional disability. Binomial tests with 95% confidence intervals (CI), Skillings-Mack and Wilcoxon signed ranks tests, and Pearson correlations on log transformed values were done. Unadjusted p-values &amp;lt;0.05 were considered statistically significant. Results: Twenty-seven patients from three institutions were enrolled. Seven (26%) patients discontinued study prior to month 1, with median study duration for those who continued of 176 [interquartile range (IQR): 158-186] days. The etiologies of study discontinuation were change in therapy (n=3, 11%), requiring another catheter (n=2, 7%), bleeding (n=1, 4%), and lost to follow-up (n=1, 4%). Eleven (41%) were female, and 21 (78%) were Caucasian (Table 1). Median age was 59 (IQR: 48-65) years. The most proximal location of the veins involved with the thrombus included veins proximal to subclavian (n=5, 19%), subclavian (n=6, 22%), internal jugular (n=6, 22%), and axillary (n=7, 26%). Patients with hematologic malignancies comprised 70% (n=19) of the cohort. All patients were treated with therapeutic doses of enoxaparin for a median of 32 (IQR: 30-52) days after catheter removal. During the 6-month study duration, the incidence of recurrent thrombosis was 0% (n=0/20, 95% CI: 0%-17%), and that of major hemorrhage was 5% (n=1/20, 95% CI: 0.13%-25%). Number of patients who had at least one PTS occurrence in any visit and either arm was 15% (n=3/20, 95% CI: 3.2%-38%), and no patients had severe PTS. Higher DASH scores were associated with higher PTS scores (Table 2). DASH score differed across all visits [month 1: median 6.16 (IQR: 2.08-19.97), month 3: 1.28 (0-11.67), month 6: 0 (0-10.42), p=0.040]. Pairwise comparisons revealed that no differences in DASH scores were seen between month 1 versus 6 (p=0.44) and month 3 and 6 (p=0.098). In contrast, month 6 had significantly lower and improved DASH score compared to month 1 (p=0.0066). No deaths occurred. Conclusions: Cancer patients with CRT frequently require central venous catheters. Treatment with anticoagulation for one month after catheter removal was associated with a low incidence of PTS, no recurrent thrombosis, and an improvement in functional disability over time in a cohort of 27 patients. The presence of PTS was associated with higher functional disability. Disclosures Baumann Kreuziger: Quercegen pharmaceuticals: Consultancy; CSL Behring: Consultancy.

Comparison between Prophylactic versus Therapeutic Doses of Low-Molecular-Weight Heparin in Severely Ill Coronavirus Disease 2019 Patients in Relation to Disease Progression and Outcome

Introduction: The predominant coagulation abnormalities in patients with coronavirus disease 2019 (COVID-19) suggest a hypercoagulable state and are consistent with uncontrolled clinical observations of an increased risk of venous thromboembolism. Aim and Objectives: To compare the effect of prophylactic versus therapeutic doses of enoxaparin in the treatment of severe cases of COVID-19 infection. Materials and Methods: This was a retrospective observational study conducted at Latifa hospital, Dubai. Fifty-nine patients enrolled from March to June 2020 and divided into 2 groups: patients who received the prophylactic dose of enoxaparin (group 1) and patients who received the therapeutic dose of enoxaparin (group 2). Results: The mean age of all cases was 47.2 ± 10.4 years, while the mean weight was 76.4 ± 13.4 kg. Males represented 79.7% of cases. Blood group “O” was the most frequent blood group (40.9%). None of the cases were smokers or using alcohol. Bronchial asthma, lung diseases, diabetes mellitus, hypertension, CKD, cardiac disease, thyroid disease, and immunodeficiency were present in 1.7, 1.7, 39, 27.1, 5.1, 1.7, 5.1, and 1.7% respectively. There was no significant difference between both study groups regarding personal and medical characteristics, except for hypertension where 35.9% of group 2 (therapeutic) cases were hypertensive compared to 10% of group 1 cases (prophylactic). There was a significant difference between both study groups regarding inflammatory markers improvement duration, duration of MV and O₂ support duration, with longer duration among (therapeutic) group 2 cases compared to group 1 cases (prophylactic). There was a highly significant difference between both study groups regarding ICU admission, as 64% of group 1 cases were admitted compared to 25% of group 1 cases. Similarly, 38.5% of group 2 cases needed MV compared to only 10% of group 1 cases, which was statistically significant. There was no significant difference between both groups regarding bleeding tendency and mortality (p value 0.54). Conclusion: Our results showed that use of prophylactic dose of enoxaparin might have some benefits compared to the therapeutic dose in terms of less duration of ICU and hospital stay, duration of oxygen support, need and duration of MV, and normalization of inflammatory markers. However, there was no significant difference between the 2 regimens regarding the mortality.

FULMINANT MYOCARDITIS IN A PATIENT WITH SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2

SESSION TITLE: Medical Student/Resident Chest Infections Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-COV2) has lead to unprecedented morbidity and mortality seen in modern times. In addition to acute respiratory distress syndrome (ARDS), there is a range of multi-organ dysfunction complications including fulminant myocarditis. CASE PRESENTATION: A 61 year old male presented with 6 days of fever, malaise, dyspnea, and cough. He was previously seen with similar symptoms and discharged on azithromycin with instructions to self-isolate. Medical history includes hypertension and hypothyroidism. On exam he was in respiratory distress with severe hypoxia on non-re-breather mask requiring emergent intubation and bilateral crepitations. EKG showed sinus tachycardia with diffuse ST depressions. Labs revealed leukocytosis 12K/uL, lactic acidosis 7.8mmol/L, procalcitonin 17.8ng/mL, troponin peaked at 17.7ng/mL, thyroid function was normal, and d-dimer was >20ug/mL. Chest x-ray showed diffuse bilateral interstitial opacities and small left pleural effusion. Echocardiogram revealed global hypokinesis with left ventricular ejection fraction 30% and small pericardial effusion with visceral thickening. SARS-COV2 PCR testing was positive. Testing for influenza, S. pneumonia, and legionella were negative. He developed shock and was placed on norepinephrine, furosemide, cefepime, doxycycline, hydroxychloroquine, therapeutic dose enoxaparin, and high dose methylprednisone. His ventilator settings were placed with high positive end-expiratory pressures and low tidal volumes. He was deemed too unstable to prone; extracorporeal membrane oxygenation (ECMO), as well as, intravenous immunoglobulin treatment were being considered. Unfortunately, he had cardiac arrest and died despite resuscitation efforts. DISCUSSION: Viral myocarditis is a recognized cause of heart failure and cardiogenic shock. Ideally, ischemic cardiomyopathy should be excluded via coronary angiogram but non-invasive methods such as echo or cardiac MRI may be suggestive (acute global hypokinesis or regional wall motion abnormalities that do not match coronary vessel anatomy).1 The proposed mechanisms of myocyte damage include: active replication of live virus within the myocardium, cytokine release due to innate immune response, viral proteins that cause direct myocardial injury, lymphocyte-mediated myocardial injury, inhibition of heme metabolism, and hypercoagulable state leading to microthrombi in small coronary vessel thrombosis as well as pulmonary emboli.2 Current treatment options involve anti-platelets/anticoagulation, antivirals and anti-malarials, high dose steroids, immunoglobulin, ECMO, and plasma exchange.3 CONCLUSIONS: The management of critically ill patients with SARS-COV2 is challenging and multifaceted. The course may be complicated by fulminant myocarditis with cardiogenic shock for which the prognosis can be grave despite the current treatment methods. Reference #1: Michael Jeserich, Stavros Konstantinides, Gabor Pavlik, Christoph Bode, and Annette Geibel. Non-invasive imaging in the diagnosis of acute viral myocarditis. Clin Res Cardiol. 2009 Dec; 98(12): 753–763. Published online 2009 Sep 11. doi: 10.1007/s00392-009-0069-2 Reference #2: Toshitaka Yajima and Kirk U. Knowlton. Viral Myocarditis. Circulation. 2009;119:2615–2624 https://doi.org/10.1161/CIRCULATIONAHA.108.766022 Reference #3: Riccardo M. Inciardi, MD; Laura Lupi, MD; Gregorio Zaccone, MD; et al. Cardiac Involvement in a Patient With Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. Published online March 27, 2020. doi:10.1001/jamacardio.2020.1096 DISCLOSURES: No relevant relationships by Lakshmi Ayyagari, source=Web Response No relevant relationships by Jason Lofters, source=Web Response No relevant relationships by John Lui, source=Web Response No relevant relationships by Gene Otuonye, source=Web Response No relevant relationships by Matthew Tavares, source=Web Response