Therapeutic Anticoagulation In Patients Research Articles

Characterization of the Benefits and Risks of Therapeutic Anticoagulation in Patients Admitted with Severe COVID-19 (CRITAC).

Severe COVID-19 is associated with increased rates of thrombotic complications. Recent provincial recommendations in British Columbia have suggested providing thromboprophylaxis with therapeutic anticoagulation for hospital inpatients with severe COVID-19 who do not have a high risk of bleeding. To characterize the rates of major bleeding, thrombotic events, complications from COVID-19, and adverse effects among patients with severe COVID-19 treated with therapeutic anticoagulation. This retrospective chart review involved patients with laboratory-confirmed COVID-19 who were admitted to 3 sites within a local health authority between April 1 and December 31, 2021, and received therapeutic anticoagulation for thromboprophylaxis. After screening of 1036 patients, 72 patients were included in the study. The mean age of participants was 54 years, 63% (n = 45) were male, and 92% (n = 66) were receiving supplemental oxygen by nasal prongs on admission. The primary outcome, major bleeding, was experienced by 1 patient (1%). Increasing oxygen requirements resulting in progression to high-flow nasal cannula occurred in 11 patients (15%), and 5 patients (7%) required admission to the intensive care unit. One patient (1%) experienced a thrombotic event, and 1 patient (1%) had a minor bleed. The mean duration of hospitalization was 10 (standard deviation 10.8) days. One death occurred during the study period, and no cases of heparin-induced thrombocytopenia were observed. In this study of hospital inpatients with severe COVID-19 who were deemed to be at low risk of bleeding and who received therapeutic anticoagulation, there were low rates of both major bleeding and thrombotic events.

Utility of Routine Surveillance Head Computed Tomography After Receiving Therapeutic Anticoagulation in Patients with Acute Traumatic Intracranial Hemorrhage

IntroductionPatients with traumatic intracranial hemorrhage (tICH) are at increased risk of venous thromboembolism and may require anticoagulation. We evaluated the utility of surveillance computed tomography (CT) in patients with tICH who required therapeutic anticoagulation. MethodsThis single institution, retrospective study included adult patients with tICH who required anticoagulation within 4-weeks and had a surveillance head CT within 24-hours of reaching therapeutic anticoagulation levels. The primary outcome was hematoma expansion (HE) detected by the surveillance CT. Secondary outcomes included 1) changes in management in patients with HE on the surveillance head CT, 2) HE in the absence of clinical changes, and 3) mortality due to HE. We also compared mortality between patients who did and did not have a surveillance CT. ResultsOf 175 patients, 5 (2.9%) were found to have HE. Most (n=4, 80%) had changes in management including anticoagulation discontinuation (n=4), reversal (n=1), and operative management (n=1). Two patients developed symptoms or exam changes prior to the head CT. Of the 3 patients (1.7%) without preceding exam changes, each had only very minor HE and did not require operative management. No patient experienced mortality directly attributed to HE. There was no difference in mortality between patients who did and those who did not have a surveillance scan. ConclusionsOur findings suggest that most patients with tICH who are started on anticoagulation could be followed clinically, and providers may reserve CT imaging for patients with changes in exam/symptoms or those who have a poor clinical examination to follow.

Therapeutic anticoagulation in patients with acute pancreatitis and splanchnic vein thrombosis: a best evidence topic.

A best evidence topic in general surgery was written according to a structured protocol. The clinical question addressed was: in adult patients with splanchnic vein thrombosis in acute pancreatitis, would administration of therapeutic anticoagulation be advisable considering the rates of vessel recanalization and bleeding complications? Four hundred twenty-four papers were found on Ovid Embase and Medline whilst 222 were found on PubMed using the reported literature search. From these, five articles represented the best evidence to the clinical question. The authors, publication dates, countries, patient groups, study outcomes, and results of these papers were tabulated. There were three systematic reviews with meta-analyses, one systematic review without meta-analysis and one randomized, retrospective study. The authors conclude that among patients with splanchnic vein thrombosis in the context of acute pancreatitis, therapeutic anticoagulation improved the rates of recanalization without increasing the risk of bleeding complications. However, there remains a need for randomized studies to address this clinical dilemma to further increase the quality of available evidence.

Venous thromboembolism after spontaneous intracerebral hemorrhage and the status quo of anticoagulation in this population: A retrospective case[sbnd]control study from a tertiary hospital in China

ObjectivePatients with spontaneous intracerebral hemorrhage (sICH) are susceptible to venous thromboembolism (VTE) including pulmonary embolism (PE) and deep venous thrombosis (DVT) due to a variety of risk factors. There are few studies regarding the predictive value of D-dimer for VTE in patients with sICH, and the anticoagulation therapy for these patients are still controversial. The objective of this study is to study the independent predictors of VTE in sICH patients. The rates of anticoagulation therapy and hemorrhagic evens were also investigated. MethodsRetrospective review of patients with sICH admitted to the First Affiliated Hospital of Dalian Medical University from 2012 to 2022 and who developed VTE (PE and/or DVT) during hospitalization. A similar number of sICH patients without VTE were randomly selected into the control group. A variety of clinical characteristics were compared between groups. Univariate and multivariate analyses were performed to identify independent predictors of VTE in patients with sICH. ResultsA total of 270 sICH patients were enrolled in this study, including 132 patients with VTE and 138 patients without VTE. After adjusting for other confounders, the maximum level of D-dimer during hospitalization (odds ratio [OR] 1.061, 95 % confidence interval (CI) 1.014–1.110), Glasgow coma scale (GCS) on admission (OR 1.347, 95 % CI 1.110–1.634), modified Rankin Scale (mRS) at discharge (OR 2.578, 95 % CI 1.546–4.298), neutrophil count (OR 1.056, 95 % CI 1.025–1.088) and hospitalization time (OR 1.089, 95 % CI 1.018–1.164) were independently associated with the sICH patients who developed VTE. The maximum D-dimer plasma level of 5.655 mg/L during hospitalization was the optimal threshold to indicate sICH patients developing VTE with a sensitivity of 83.3 % and a specificity of 67.4 %. No patients with sICH received prophylactic anticoagulation therapy against VTE in the present study. A total of 57.6 % (76/132) of the sICH patients with VTE were administered anticoagulant therapy and the rate of hemorrhagic complication was 9.2 %. ConclusionssICH patients with increased levels of D-dimer, higher GCS scores, higher mRS scores, increased neutrophil counts and longer hospitalization time are more likely to develop VTE complications. Routine and serial monitoring of the D-dimer values may be useful in patients with sICH, and VTE should be considered when the plasma level of D-dimer increases to 5.655 mg/L during hospitalization. In tertiary hospitals in China, the rate of sICH patients with VTE receiving anticoagulation treatment is low. Further studies are necessary to explore the safety and efficacy of VTE therapeutic anticoagulation in patients with sICH.

Anticoagulación terapéutica en pacientes críticamente enfermos con SARS-CoV-2: A propósito de una serie de casos

Thromboembolic events related to SARS-CoV-2 in critically ill patients occur with great frequency according to the current literature. Taking into account the mortality rate related to thrombotic events, it is important to elucidate the role of therapeutic anticoagulation in this entity. ObjectiveTo characterize therapeutic anticoagulation in patients in an intensive care unit (ICU) with a confirmed diagnosis of SARS-CoV-2. Materials and methodsDescriptive study of a retrospective case series made up of patients older than 18 years in the ICU of a hospital in Bogotá, Colombia, with a diagnosis of SARS-CoV-2 confirmed by RT-PCR test. Patients with therapeutic anticoagulation were included and those with coagulopathy and antithrombotic treatment prior to COVID-19 infection were excluded. ResultsA total of 174 patients met the criteria for inclusion in this study. Arterial hypertension was the pathology with the highest presentation with 47.1%. Unfractionated heparin was administered to 115 and low molecular weight heparin to 59. Adverse reactions derived from treatment represented 6.32% of the population. Regarding thromboembolic events, they were 37.36%, where deep vein thrombosis (DVT) predominated with 14.9%. ConclusionHemorrhagic events occurred less frequently compared to thrombotic events, however, more clinical and analytical studies are needed to corroborate this approach.

Effects of Standard-Dose Prophylactic, High-Dose Prophylactic, and Therapeutic Anticoagulation in Patients With Hypoxemic COVID-19 Pneumonia

Given the high risk of thrombosis and anticoagulation-related bleeding in patients with hypoxemic COVID-19 pneumonia, identifying the lowest effective dose of anticoagulation therapy for these patients is imperative. To determine whether therapeutic anticoagulation (TA) or high-dose prophylactic anticoagulation (HD-PA) decreases mortality and/or disease duration compared with standard-dose prophylactic anticoagulation (SD-PA), and whether TA outperforms HD-PA; and to compare the net clinical outcomes among the 3 strategies. The ANTICOVID randomized clinical open-label trial included patients with hypoxemic COVID-19 pneumonia requiring supplemental oxygen and having no initial thrombosis on chest computer tomography with pulmonary angiogram at 23 health centers in France from April 14 to December 13, 2021. Of 339 patients randomized, 334 were included in the primary analysis-114 patients in the SD-PA group, 110 in the HD-PA, and 110 in the TA. At randomization, 90% of the patients were in the intensive care unit. Data analyses were performed from April 13, 2022, to January 3, 2023. Patients were randomly assigned (1:1:1) to receive either SD-PA, HD-PA, or TA with low-molecular-weight or unfractionated heparin for 14 days. A hierarchical criterion of all-cause mortality followed by time to clinical improvement at day 28. Main secondary outcome was net clinical outcome at day 28 (composite of thrombosis, major bleeding, and all-cause death). Among the study population of 334 individuals (mean [SD] age, 58.3 [13.0] years; 226 [67.7%] men and 108 [32.3%] women), use of HD-PA and SD-PA had similar probabilities of favorable outcome (47.3% [95% CI, 39.9% to 54.8%] vs 52.7% [95% CI, 45.2% to 60.1%]; P = .48), as did TA compared with SD-PA (50.9% [95% CI, 43.4% to 58.3%] vs 49.1% [95% CI, 41.7% to 56.6%]; P = .82) and TA compared with HD-PA (53.5% [95% CI 45.8% to 60.9%] vs 46.5% [95% CI, 39.1% to 54.2%]; P = .37). Net clinical outcome was met in 29.8% of patients receiving SD-PA (20.2% thrombosis, 2.6% bleeding, 14.0% death), 16.4% receiving HD-PA (5.5% thrombosis, 3.6% bleeding, 11.8% death), and 20.0% receiving TA (5.5% thrombosis, 3.6% bleeding, 12.7% death). Moreover, HD-PA and TA use significantly reduced thrombosis compared with SD-PA (absolute difference, -14.7 [95% CI -6.2 to -23.2] and -14.7 [95% CI -6.2 to -23.2], respectively). Use of HD-PA significantly reduced net clinical outcome compared with SD-PA (absolute difference, -13.5; 95% CI -2.6 to -24.3). This randomized clinical trial found that compared with SD-PA, neither HD-PA nor TA use improved the primary hierarchical outcome of all-cause mortality or time to clinical improvement in patients with hypoxemic COVID-19 pneumonia; however, HD-PA resulted in significantly better net clinical outcome by decreasing the risk of de novo thrombosis. ClinicalTrials.gov Identifier: NCT04808882.

The use of fondaparinux and rituximab for recurrent thrombotic events in antiphospholipid syndrome.

Limited evidence exists to guide the management of recurrent thrombosis occurring despite therapeutic anticoagulation in patients with thrombotic antiphospholipid syndrome (APS). In this case series, fondaparinux, with or without an antiplatelet agent, provided an effective and safe option in three patients with thrombotic APS, all two triple and one single positive for antiphospholipid antibodies, who had recurrent venous and/or arterial thromboembolism. Rituximab was also used in all patients. Recurrent events occurred despite therapeutic anticoagulation, including at high-intensity, with warfarin and subsequent low-molecular-weight heparin. There were no major bleeding events. Adjunctive therapies used for thrombosis included catheter-directed thrombolysis and rituximab.

Predicting poor response to anti-coagulation therapy in cerebral venous thrombosis using a simple clinical-radiological score

BackgroundMultiple studies have attempted to determine predictors of poor clinical outcomes in cerebral venous thrombosis (CVT). Fewer studies target to identify predictors of poor response to anticoagulation therapy in CVT. ObjectiveWe aimed to determine the predictors of poor clinical response to therapeutic anticoagulation in patients with acute CVT. MethodsWe performed a retrospective analysis of patients therapeutically anticoagulated for acute CVT. We defined poor clinical outcomes as death, need for mechanical thrombectomy during the hospitalization, or a modified Rankin Scale (mRS) > 3 at clinical follow-up. Bivariate and multivariate analyses identified factors associated with poor outcomes in anticoagulated patients for acute CVT, and we used the identified factors to create the PRACT-CVT (Poor Response to Anticoagulation Therapy in CVT) score. ResultsWe included 109 patients anticoagulated with acute CVT. The mean patient age was 37 years old (SD 19); nine patients were > 65 years, ten patients were < 10 years, and 64 (59%) were female. Twenty-one (19%) patients had poor clinical outcomes. Age > 65 or < 10 years (OR: 3.16, 95% CI: 1.06–9.44), a GCS ≤ 12 upon presentation (OR: 19.2, 95% CI: 4.05–91.4), focal motor deficits at admission (OR: 5.03, 95% CI: 1.64–15.44), clinical deterioration following admission (OR: 28.18, CI: 4.81–164.86), seizures following admission (OR: 5.59, 95% CI: 1.27–24.51), evidence of brain bleeding/ischemia on admission (OR: 4.67, 95% CI: 1.42–15.34), involvement of the superior sagittal sinus (OR: 3.88, CI: 1.33–11.32), or involvement of both transverse sinuses (OR: 3.87, 95% CI: 1.01–14.90) predicted poor clinical outcome despite therapeutic anticoagulation. A PRACT-CVT score (0–22 points) of ≥ 7 points provided a sensitivity of 71% and a specificity of 95% for predicting poor clinical outcomes with anticoagulation alone. ConclusionPatients with acute CVT aged > 65 or < 10 years old, presenting with a GCS ≤ 12, with focal motor deficits, showing clinical deterioration after admission, having clinical seizures during hospitalization, with brain bleeding/ischemia on initial neuroimaging, involvement of the superior sagittal sinus, or involvement of both transverse sinuses had poor response to anticoagulation. Clinicians may employ the PRACT-CVT score to predict poor response to anticoagulation for acute CVT.

Role of CT angiography and therapeutic anticoagulation in patients presenting to the emergency department with acute gastrointestinal bleeding.

Acute gastrointestinal bleeding (GIB) is associated with morbidity and mortality. There can be a low threshold for practitioners to assess for active GIB and computed tomography angiography (CTA) examinations are performed frequently, even for stable patients and those who are therapeutically anticoagulated. We aimed to assess the predictive value of CTA for acute GIB and the influence of CTA on treatment. Retrospective single-centre study over a 2-year period. A total of 227 patients with mean age 67.7 years (SD 17.86), 58.6% male. 84.4% were for lower GIB. 49 patients were on therapeutic anticoagulation (21.6%). 45 CTAs were positive (19.8%). 22 patients received embolisation, and 15 received acute endoscopic treatment. CTA sensitivity was 68.6% and specificity 89.1%. The PPV was 53.3% and NPV 93.9%. The odds ratio of a positive CTA requiring treatment for patients on therapeutic anticoagulation was 1.1 (P = 0.932) compared with the odds of patients not taking therapeutic anticoagulation 21.5 (P < 0.001). The risk ratio for requiring treatment if not taking anticoagulation was 6.2. A total of 19 patients (9.1%) met the definition of CI-AKI as a result of the CTA. A pre-existing eGFR of less than 20 was associated with significantly increased odds of developing CI-AKI (OR 3.95, P = 0.031, 95%CI 1.135-13.782). The presence of anticoagulation has a significant impact on the decision not to perform interventional treatments on patients with acute GIB when CTA is positive. Anticoagulant reversal and volume resuscitation are important front-line measures, and CTA may have a role for those anticoagulated who are haemodynamically unstable after resuscitation.

Comparison of standard prophylactic, intermediate prophylactic and therapeutic anticoagulation in patients with severe COVID-19: protocol for the ANTICOVID multicentre, parallel-group, open-label, randomised controlled trial

IntroductionCOVID-19 induces venous, arterial and microvascular thrombosis, involving several pathophysiological processes. In patients with severe COVID-19 without macrovascular thrombosis, escalating into high-dose prophylactic anticoagulation (HD-PA) or therapeutic anticoagulation (TA) could...

Outcomes of Patients with Extended Anticoagulation Using Low Dose Doacs Compared to Standard Therapeutic Anticoagulation

Background: Reduced or low-dose direct oral anticoagulants (DOACs) have been studied in randomized control trials for the extended prevention of venous thromboembolism (VTE) after 6 months of treatment at the therapeutic doses. The real-world effectiveness as well as utilization of this approach in clinical practice compared to continuing at therapeutic doses is unknown.Aims: Evaluate the efficacy of reduced-dose DOACs compared to standard therapeutic anticoagulation in patients with extended anticoagulation.Methods: Consecutive patients with VTE were identified using the Mayo Clinic VTE Registry from March 1st , 2013 to December 31st, 2020. Patients were followed prospectively for outcomes of VTE recurrence, death, major bleeding and clinically relevant non major bleeding (CRNMB) either in person or by survey. Type of anticoagulation and dose changes were recorded, and progressing to a low dose was treated as an endpoint. In the models relating it to the outcome, it was treated as a time-dependent covariate in the cox models. After completing standard anticoagulation treatment for 3 months with any anticoagulant, patients continuing anticoagulation were divided into two groups: standard therapeutic anticoagulation (any drug) vs those who transitioned to rivaroxaban 10 mg daily or apixaban 2.5mg twice daily any time after 3 months. Patients with recurrent VTE, major or CRNMB during the first 3 months were excluded from further analysis.Results: 219 patients (153 on Apixaban and 66 on Rivaroxaban) were identified in the low dose DOAC and 2521 in the standard anticoagulation group. The mean age was 60.7 years, mean weight was 93.2 Kg and 55.9% were males (Table 1). Patients on low dose DOACs were about the same age and weight compared to standard anticoagulation group. Among all diagnosis categories, patients with active cancer were less likely to be prescribed low dose DOACs (HR 0.56; 95%CI 0.42-0.73; P<0.001), while low dose DOACs prescription was more likely in patients with pulmonary embolism (HR 1.45; 95%CI 1.11-1.89; P=0.007). The median months to start a low dose DOAC after completing the 3 months was 3.1 months with standard deviation of 6.6 months and interquartile range 2.8 months. There was no statistically significant association in the likelihood of going to a low dose group in relation to VTE recurrence (HR 1.36; 95%CI 0.42-4.45; P=0.61) or major bleeding (HR 0.59; 95%CI 0.08-4.37; P=0.61). However, transitioning to low dose DOAC was associated with reduced mortality (HR 0.53; 95%CI 0.35-0.80; P=0.003). Also, patients on low dose DOACs were more likely to have a CRNMB (HR 2.76; 95%CI 1.15-6.62; P=0.02).Conclusion: In this study of patients continuing anticoagulation past 3 months for an initial acute venous thromboembolic event, transitioning to low dose DOACs was not associated with any statistically significant association with VTE recurrence or major bleeding. However, mortality was lower and CRNMB was higher in this unadjusted analysis. Our results show that physicians are not always waiting until 6 months to transition to low doses and low doses are being utilized in cancer patients. Further research is needed to better understand the higher risk for CRNMB identified in this group. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Anticoagulation in cancer-associated thromboembolism with thrombocytopenia: a prospective, multicenter cohort study

AbstractVenous thromboembolism (VTE) with concurrent thrombocytopenia is frequently encountered in patients with cancer. Therapeutic anticoagulation in the setting of thrombocytopenia is associated with a high risk of hemorrhage. Retrospective analyses suggest the utility of modified-dose anticoagulation in this population. To assess the incidence of hemorrhage or thrombosis according to anticoagulation strategy, we performed a prospective, multicenter, observational study. Patients with active malignancy, acute VTE, and concurrent thrombocytopenia (platelet count <100 000/µL) were enrolled. The cumulative incidences of hemorrhage or recurrent VTE were determined considering death as a competing risk. Primary outcomes were centrally adjudicated and comparisons made according to initial treatment with full-dose or modified-dose anticoagulation. A total of 121 patients were enrolled at 6 hospitals. Seventy-five patients were initially treated with full-dose anticoagulation (62%) and 33 (27%) with modified-dose anticoagulation; 13 (11%) patients received no anticoagulation. Most patients who received modified-dose anticoagulation had a hematologic malignancy (31 of 33 [94%]) and an acute deep vein thrombosis (28 of 33 [85%]). In patients who initially received full-dose anticoagulation, the cumulative incidence of major hemorrhage at 60 days was 12.8% (95% confidence interval [CI], 4.9-20.8) and 6.6% (95% CI, 2.4-15.7) in those who received modified-dose anticoagulation (Fine-Gray hazard ratio, 2.18; 95% CI, 1.21-3.93). The cumulative incidence of recurrent VTE at 60 days in patients who initially received full-dose anticoagulation was 5.6% (95% CI, 0.2-11) and 0% in patients who received modified-dose anticoagulation. In conclusion, modified-dose anticoagulation appears to be a safe alternative to therapeutic anticoagulation in patients with cancer who develop deep vein thrombosis in the setting of thrombocytopenia.

Current conception about the pathogenesis and intensive care of severe COVID-19 (review)

The aim of the research. The aim of this work was to summarize the scientific literature data on the pathogenesis and intensive care of the severe course of coronavirus infection.&#x0D; Materials and methods. Databases such as PubMed, Google Scholar, Scopus and Web Of Science 2020-2021 were used for literary searches.&#x0D; Results. An intense inflammatory response against the SARS-CoV-2 virus in COVID-19 patients causes a cytokine storm and hypercoagulability with the development of acute respiratory distress syndrome (ARDS) and multiple organ failure. Approximately 17 % to 35 % of hospitalized patients with COVID-19 are treated in the intensive care unit, most often due to hypoxemic respiratory failure and the development of ARDS, and between 29 % and 91 % of patients in intensive care units require invasive ventilation.&#x0D; In addition to acute respiratory failure, hospitalized patients may have acute renal failure (9 %), liver dysfunction (19 %), coagulation disorders (10 %–25 %), and septic shock (6 %).&#x0D; More than 75 % of hospitalized patients require additional oxygen therapy. Respiratory support could vary from the need for oxygen supplementation through a nasal catheter to invasive ventilation or extracorporeal membrane oxygenation in patients with the most severe ARDS.&#x0D; The uncontrolled inflammation and coagulation seen in COVID-19 patients is similar to multifactorial ARDS, where a plethora of evidence has demonstrated the ability of long-term corticosteroid therapy (CST) to reduce inflammation-coagulation-fibroproliferation and accelerate recovery.&#x0D; With regard to the assessment of the benefits of therapeutic anticoagulation in patients with elevated D-dimer, the question has not yet been finally resolved, and research devoted to this is still ongoing.&#x0D; Conclusions. The approaches to respiratory, anticoagulant, anti-inflammatory therapy in critically ill patients with COVID-19 require further research to determine the optimal treatment tactics

Management of therapeutic unfractionated heparin in COVID‐19 patients: A retrospective cohort study

BackgroundPatients hospitalized with severe acute respiratory syndrome coronavirus 2 infection are at risk for thrombotic complications necessitating use of therapeutic unfractionated heparin (UFH). Full‐dose anticoagulation limits requirements for organ support interventions in moderately ill patients with coronavirus disease 2019 (COVID‐19). Given this benefit, it is important to evaluate response to therapeutic anticoagulation in this population. ObjectivesThe aim of this study was to assess therapeutic UFH infusions and associated bleeding risk in patients with COVID‐19. Patients/MethodsThis retrospective cohort study includes patients at Brigham and Women’s Hospital, Boston, Massachusetts, receiving weight‐based nursing‐nomogram titrated UFH infusion during a 10‐week surge in COVID‐19 hospitalizations. Of 358 patients on therapeutic UFH during this interval, 97 (27.1%) had confirmed COVID‐19. Patient characteristics, laboratory values, and information regarding UFH infusion and bleeding events were obtained from the electronic medical record. ResultsPatients who were COVID‐19 positive had fewer therapeutic activatrd partial thromboplastin times (aPTTs) compared to COVID‐19–negative patients (median rate, 40.0% vs 53.1%; P < .0005). Both major and clinically relevant nonmajor bleeding were increased in COVID‐19–positive patients, with major bleeding observed in 10.3% (95% confidence interval [CI], 5.7%‐17.9%) of patients who were COVID‐19 positive and 3.1% (95% CI, 1.6%‐5.9%) of patients who were COVID‐19 negative (P< .005). In logistic regression, bleeding events were associated with receiving UFH for longer than 7 days, but not platelet count, coagulation, or inflammatory measurements. ConclusionsOur data indicate a higher incidence of bleeding complications in patients with COVID‐19 receiving weight‐based nursing‐nomogram titrated UFH infusions despite a higher prevalence of subtherapeutic aPTTs in this population. These data underscore the need for prospective studies aimed at improving the quality and safety of therapeutic anticoagulation in patients with COVID‐19.

Intracranial Hemorrhage in Hospitalized SARS-CoV-2 Patients: A Case Series

The SARS-CoV-2 virus causing Coronavirus Disease 2019 (COVID-19) is a global pandemic with almost 30 million confirmed worldwide cases. Prothrombotic complications arising from those affected with severe symptoms have been reported in various medical journals. Currently, clinical trials are underway to address the questions regarding anticoagulation dosing strategies to prevent thrombosis for these critically ill patients. However, given the increasing use of therapeutic anticoagulation in patients admitted with COVID-19 to curtail this prothrombotic state, our institution has witnessed six cases of devastating intracranial hemorrhage as well as thrombosis leading to five fatalities and we examine their hospital course and anticoagulation used.

The prognostic impact of therapeutic anticoagulation after biological aortic valve replacement

Abstract Background Recent guidelines state that in patients with surgical biological aortic valve replacement (AVR), the use of anti-platelet therapy is as a valid alternative to postoperative anticoagulation (AC) in the absence of a further indication for AC. However, the prognostic impact of different anti-thrombotic strategies after biological AVR has not clearly been investigated so far and outcome data remain scare and inconclusive. Moreover, the AC strategy of patients presenting with post-operative atrial fibrillation (POAF), has not been investigated so far. Therefore, we aim to picture the therapeutic AC approach after biological AVR and whether the presence of POAF effects decision making with regard to anti-thrombotic management. Methods Within this prospective observational study 515 patients undergoing elective cardiac valve and or coronary artery bypass graft (CABG) surgery were enrolled. All patients were continuously screened for the development of POAF and followed until the primary endpoint (mortality) was reached. Logistic regression analysis was performed to elucidate the effect of AC on outcome. Results A total of 200 individuals underwent biological AVR (including 81 [40.3%] combined AVR+CABG surgeries, median age: 77 years [IQR: 71–80 years]; 133 [66.3%] male gender). 97 (48.3%) patients received therapeutic AC at the time of discharge, including 42 (43.4%) on vitamin K antagonists (VKA), 53 (54.6%) on low-dose low-molecular weight heparin (LMWH) and 2 (2.0%) non-vitamin K antagonist oral anticoagulants (NOACs). 103 (51.2%) patients received another anti-thrombotic approach including 23 (22.3%) on dual anti-platelet therapy (DAPT) and 72 (69.9%) with prophylactic LMWH. Interestingly, the fraction of patients that received AC were comparable between POAF (CHA2DS2-Vasc score 4, IQR: 3–5) and non-POAF individuals (51.9% vs. 44.6%; p=0.304). After a median follow-up time of 1069 days (IQR: 673–1475 days) 21 patients (10.4%) died, referring to 9 (8.3%) non-POAF and 12 (13.0%) POAF individuals. We found that a therapeutic AC after surgery showed a strong and inverse association with 3-year mortality with a crude odds ratio (OR) of 0.31 (95% CI 0.12–0.79; p=0.015). The prognostic potential remained stable after adjustment for potential confounders (p=0.029). Conclusion Therapeutic AC showed a strong and independent inverse association with 3-year mortality, mirroring a potential benefit on outcome compared to anti-platelet therapy or low-dose LMWH. However, the fraction of patients receiving therapeutic AC was considerably low – especially NOACs were not commonly used. Despite its association with fatal cardiac adverse events, the presence of POAF was not a relevant value for decision making for the initiation of AC. Further prognostic data on both thromboembolic and bleeding events are needed to elucidate a net-benefit of therapeutic AC in patients with surgical biological AVR who have an indication for AC or present with POAF. Kaplan-Meier Survival plot Funding Acknowledgement Type of funding source: None

Empiric Therapeutic Anticoagulation and Mortality in Critically Ill Patients With Respiratory Failure From SARS-CoV-2: A Retrospective Cohort Study.

The pathophysiology of respiratory failure associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains under investigation. One hypothesis is that progressive endothelial damage from the virus leads to microvascular thrombosis. It is uncertain if empiric therapeutic anticoagulation provides benefit over standard deep vein thrombosis (DVT) prophylaxis in critically ill patients with SARS-CoV-2. A retrospective cohort study was performed to evaluate adult patients admitted to the intensive care unit at 3 hospitals with polymerase chain reaction-confirmed SARS-CoV-2-associated respiratory failure requiring invasive mechanical ventilation. A Kaplan-Meier survival analysis was used to compare patients who were initiated on therapeutic anticoagulation prior to the time of intubation and those receiving standard DVT prophylaxis doses. The primary outcome was the difference in the 28-day mortality of patients between the 2 groups.Twenty-eight-day mortality did not differ between groups, occurring in 26.1% of patients who received therapeutic anticoagulation and 29.5% of those who received a prophylactic dose only (hazard ratio, 0.52; P = .055). There was no difference in 28-day mortality between groups in patients who were admitted with a serum D-dimer ≥ 2 µg/mL (hazard ratio, 0.67; P = .41).Empiric therapeutic anticoagulation in patients who require invasive mechanical ventilation for confirmed SARS-CoV-2 infection does not improve 28-day mortality compared with standard DVT prophylaxis, even among those with elevated D-dimer levels.

(S029) Managing therapeutic anticoagulation in bariatric surgery patients.

Patients that undergo bariatric surgery are at risk of bleeding. Some obesity-related comorbidities including venous thromboembolism and heart disease can often require therapeutic anticoagulation. Previous small institutional studies have demonstrated that bariatric surgery can be performed in this patient population. This study attempts to identify best practices in stopping and restarting therapeutic anticoagulation in patients undergoing bariatric surgery. A retrospective analysis was completed of our institution's database using anticoagulant medications to identify patients on therapeutic anticoagulation. Patients not on therapeutic anticoagulation were excluded, as well as patients that were started on therapeutic anticoagulation only in the post-operative period or those whose anticoagulation was stopped and not restarted. Indications for anticoagulation were recorded, as well as patient demographics and comorbid conditions. The patient chart was examined for when anticoagulation was stopped before surgery, when it was restarted after surgery, and whether or not the patient was therapeutically bridged. Baseline and post-operative hemoglobin values were recorded, as well as bleeding events, transfusions, reoperation, length of stay, and readmissions. Binary variables were compared across groups using Chi-square and Fisher's exact tests, and continuous variables were analyzed using T test. There were 2933 bariatric operations performed between January 1, 2012 and August 31, 2019. Of these patients, 64 were on therapeutic anticoagulation before and after the operation for one or more indications, including history of VTE (39), atrial fibrillation (27), clotting disorder (6), ventricular assist device (5), previous PCI (4), or mechanical valve (2). There were 4 (6.2%) patients that experienced bleeding events. All four patients were on Coumadin pre-operatively. Three patients experienced extraluminal bleeding, and one patient had intraluminal bleeding, and all events occurred within 72h of the operation. All four patients had their anticoagulation restarted prior to the bleeding event becoming evident, with anticoagulation in these patients restarted an average of 1.25days after surgery. There were no conditions that predisposed a patient to bleeding. There was no significant difference in amount of time anticoagulation was stopped before surgery in bleeding versus non-bleeding patients, and there appeared to be no increased risk of bleeding in patients that were on therapeutic bridging therapy. There were no thrombotic complications from the interruption in anticoagulation therapy. Bariatric surgery can be safely performed in patients on therapeutic anticoagulation, though this population is at greater risk for bleeding complications in the perioperative period. Meticulous hemostasis in the operating room is the most important aspect of preventing bleeding complications.

Therapeutic anticoagulation in patients with traumatic brain injuries and pulmonary emboli.

Patients with traumatic intracranial hemorrhage (ICH) and concomitant pulmonary embolus (PE) have competing care needs and demand a careful balance of anticoagulation (AC) versus potential worsening of their ICH. The goal of this study is to determine the safety of therapeutic AC for PE in patients with ICH. This is a retrospective single-center study of patients older than 16 years with concomitant ICH and PE occurring between June 2013 and December 2017. Early AC was defined as within 7 days of injury or less; late was defined as after 7 days. Primary outcomes included death, interventions for worsening ICH following AC, and pulmonary complications. Multivariate logistic regression was used to evaluate for clinical and demographic factors associated with worsening traumatic brain injury (TBI), and recursive partitioning was used to differentiate risk in groups. Fifty patients met criteria. Four did not receive any AC and were excluded. Nineteen (41.3%) received AC early (median, 4.1; interquartile range, 3.1-6) and 27 (58.7%) received AC late (median, 14; interquartile range, 9.7-19.5). There were four deaths in the early group, and none in the late cohort (21.1% vs. 0%, p = 0.01). Two deaths were due to PE and the others were from multi-system organ failure or unrecoverable underlying TBI. Three patients in the early group, and two in the late, had increased ICH on computed tomography (17.6% vs. 7.4%, p = 0.3). None required intervention. This retrospective study failed to find instances of clinically significant progression of TBI in 46 patients with computed tomography-proven ICH after undergoing AC for PE. Therapeutic AC is not associated with worse outcomes in patients with TBI, even if initiated early. However, two patients died from PE despite AC, underlining the severity of the disease. Intracranial hemorrhage should not preclude AC treatment for PE, even early after injury. Care management, Level IV.

The Interplay Between Coagulation and Inflammation Pathways in COVID-19-Associated Respiratory Failure: A Narrative Review.

The novel coronavirus disease (COVID-19) pandemic has caused an unprecedented worldwide socio-economic and health impact. There is increasing evidence that a combination of inflammation and hypercoagulable state are the main mechanisms of respiratory failure in these patients. This narrative review aims to summarize currently available evidence on the complex interplay of immune dysregulation, hypercoagulability, and thrombosis in the pathogenesis of respiratory failure in COVID-19 disease. In addition, we will describe the experience of anticoagulation and anti-inflammatory strategies that have been tested. Profound suppression of the adaptive and hyperactivity of innate immune systems with macrophage activation appears to be a prominent feature in this infection. Immune dysregulation together with endotheliitis and severe hypercoagulability results in thromboinflammation and microvascular thrombosis in the pulmonary vasculature leading to severe respiratory distress. Currently, some guidelines recommend the use of prophylactic low molecular weight heparin in all hospitalized patients, with intermediate dose prophylaxis in those needing intensive care, and the use of therapeutic anticoagulation in patients with proven or suspected thrombosis. Strong recommendations cannot be made until this approach is validated by trial results. To target the inflammatory cascade, low-dose dexamethasone appears to be helpful in moderate to severe cases and trials with anti-interleukin agents (e.g., tocilizumab, anakinra, siltuximab) and non-steroidal anti-inflammatory drugs are showing early promising results. Potential newer agents (e.g., Janus kinase inhibitor such as ruxolitinib, baricitinib, fedratinib) are likely to be investigated in clinical trials. Unfortunately, current trials are mostly examining these agents in isolation and there may be a significant delay before evidence-based practice can be implemented. It is plausible that a combination of anti-viral drugs together with anti-inflammatory and anti-coagulation medicines will be the most successful strategy in managing severely affected patients with COVID-19.