Incidence Of Thromboembolic Events Research Articles

Fixed- versus variable-dose prothrombin complex concentrate protocol for vitamin K antagonist reversal.

Fixed-dose prothrombin complex concentrates (PCCs) for the reversal of vitamin K antagonists may decrease the incidence of thromboembolic events, treatment costs, and treatment delays. However, the ideal fixed dose is unknown, with some studies showing inadequate reversal with suboptimal dosing or in patients with a higher international normalized ratio (INR) or weight. This indicates a need for a modified fixed-dose strategy that considers weight and INR. This study was a retrospective chart review comparing efficacy and safety outcomes of the standard variable-dose protocol versus a fixed-dose protocol. The primary outcome was the proportion of patients who achieved INR reversal. Of the total of 113 patients reviewed, INR reversal to < 1.5 was achieved in 23 patients (46%) in the variable-dose group versus 27 patients (43%) in the fixed-dose group (P = 0.83). Of the 27 patients with ICH, INR reversal to ≤ 1.3 was achieved in five patients (71%) in the variable dose group versus ten patients (50%) in the fixed-dose group (P = 0.41). The rate of INR reversal did not differ significantly between groups, but the fixed-dose group used less PCCs and had lower treatment costs.

Incidence of Thrombo-Embolic Events in Relation to Activated Prothrombin Complex Concentrate Exposure: A Literature Meta-Analysis

IntroductionThe development of factor VIII (FVIII) inhibitory antibodies is one of the major challenges of the treatment of hemophilia, because it hinders FVIII replacement for the treatment and prevention of bleeding events (Leissinger 2015). Two products are currently available to control bleeding in patients with inhibitors: the activated prothrombin complex concentrate (aPCC; FVIII inhibitor bypassing activity, FEIBA VH; Shire plc, USA) and recombinant activated factor VII (rFVIIa; NovoSeven, Bagsvaerd, Denmark). Both agents have shown similar efficacy, with some patients responding better to one over the other (Astermark 2007). Both agents have been associated with the development of thromboembolic events (TEEs) (Aledort 2004). Aim of this study was to estimate TEE incidence in patients with congenital hemophilia with inhibitors and acquired hemophilia exposed to aPCC, by using a meta-analytic approach based on published scientific literature.MethodsA systematic review of the literature was carried out in Medline, according to PRISMA guidelines, from inception date to March 2017. The incidence rate of TEEs was estimated via a meta-analytic approach by using a Generalized Linear Mixed Model based on a Poisson distribution.Stratified analyses according to study design (prospective vs. retrospective), hemophilia type (congenital vs. acquired) and treatment modality (on-demand, prophylaxis and surgery) have been conducted.ResultsWe identified a total of 144 papers through the electronic literature search and out of the 61 fully evaluated articles, 39 studies with TEE data related to the use of aPCC in patients with congenital hemophilia with inhibitor or acquired hemophilia were included in the meta-analysis. The studies included were published from 1980 to 2016, providing information on safety related to 678,447 aPCC infusions (7,291 infusions as on-demand treatment, 77,203 in prophylaxis, 3,296 in surgery and 590,657 in unspecified treatment modalities).In the 39 studies included overall, 46 TEEs were reported: 13 disseminated intravascular coagulation (DIC), 11 ischemic coronary syndrome (ICS), 4 pulmonary embolism (PE), 3 thrombotic cerebrovascular accidents (CVA), 3 deep vein thrombosis (DVT), 3 superficial vein thrombosis (SVT), 6 unspecified thrombosis (unreported location) and 3 fibrinogen reduction. No thrombotic microangiopathic events have ever been reported. Out of the 39 studies included, 31 (79%) reported no TEEs.The estimated pooled TEE incidence rate was 2.87 (95% CI 0.32-25.40) per 100,000 aPCC infusions. When stratifying for retrospective and prospective studies, 35 TEEs in 649,343 aPCC infusions (pooled incidence rate, 5.42 per 100,000 infusions), and 11 TEEs in 29,104 infusions (pooled incidence rate, 1.09 per 100,000 infusions) were respectively reported. TEE incidence rate in patients treated with aPCC on-demand was 5.09 per 100,000 infusions, while in patients treated with prophylaxis, no TEEs were reported. Five TEEs were reported in 11 studies in hemophilia patients with inhibitors undergoing surgery, being the pooled TEE incidence rate 112.03 per 100,000 aPCC infusions. Finally, pooled TEEs incidence rate in acquired hemophilia patients was 287.79 per 100,000 infusions, but less than 0.01 per 100,000 infusions in congenital hemophilia patients.ConclusionsThe pooled incidence rate was lower than 3 TEEs per 100,000 aPCC infusions, demonstrating a relatively low risk and confirming previous figures reported (Erlich 2002, Aledort 2004). Stratified analysis showed that the incidence is even lower in patients with congenital hemophilia and no TEE in prophylaxis. These findings provide robust evidence of safety of aPCC over almost 40 years of published studies. DisclosuresRota:ASHLEY COMMUNICATIONS ON BEHALF OF SHIRE FOR SHIRE SYMPOSIUM PARTICIPATION AS A SPEAKER AT THE ISTH 2017 CONGRESS: Honoraria. Cortesi:Shire: Research Funding. Crea:Shire: Employment, Equity Ownership. Gringeri:Shire: Employment. Mantovani:Daiichi Sankyo: Consultancy; Shire: Research Funding; Bayer AG: Consultancy; Boehringer Ingelheim: Research Funding; Janssen-Cilag: Research Funding.

Results from the 208-Week (4-Year) Follow-up of RESPONSE Trial, a Phase 3 Study Comparing Ruxolitinib (Rux) with Best Available Therapy (BAT) for the Treatment of Polycythemia Vera (PV)

Results from the 208-Week (4-Year) Follow-up of RESPONSE Trial, a Phase 3 Study Comparing Ruxolitinib (Rux) with Best Available Therapy (BAT) for the Treatment of Polycythemia Vera (PV)

Venous Thromboembolism (VTE) in Adults with Non Hodgkin Lymphoma (NHL) a Retrospective Cohort Study

Introduction. One major complication of cancer and cancer treatment is venous thromboembolism (VTE). The incidence of thromboembolic complications in patients with hematological malignancies reaches up to 12.1% in patients with acute myeloid leukemia and ranges from 1.5% to 59.5% in patients with lymphoma and these patients had a 10-fold higher risk for the development of venous thrombosis, than patients with lung and gastrointestinal cancers. Known pro-thrombotic risk factors in patients with cancer include; older age, systemic inflammation, central venous catheters (CVCs), thrombophilia, infections/sepsis, obesity, immobilization and advanced disease, but the risk is further increased by chemotherapy, but the trade-off between safety and efficacy of primary thromboprophylaxis in cancer patients treated with chemotherapy is uncertain.Aim: Aim of our study was to determine incidence of thromboembolic events in patients with NHL and to establish the risk factors and identify patients with prophylactic therapy for thrombosis.Patients and Methods. We conducted a retrospective cohort study, including all patients registered in the Hematology Department over the age of 18 years diagnosed with NHL between January 2007 and June 2017 in Mexico city.Results. Data was retrieved from the medical records of all 262 patients (100%) (female 118 , male 149) in a Mexican Hematology Center. The median follow-up was 5.7 years (range 1-10). Only 6 patients (2.2-%) were treated with thromboprophylaxis. The incidence of symptomatic VTE was 1.5% (1- PE, 3- DVT), in the four patients VTE events occurred in the older age category (50-60 years) and all of them with NHL diffuse large B cell lymphoma (DLBCL) and clinical stage III-IV.In univariate analysis, DLBCL was associated with increased risk of VTE compared to follicular lymphoma (FL) in the first year after diagnosis; this association was no longer significant in adjusted analysis. Major risk factors for VTE included history of VTE before NHL diagnosis, stage III/IV disease and BMI ≥ 30. The cumulative incidence of VTE was highest in the period following diagnosis and decreased over time for both histologies.While the VTE did not significantly affect the treatment of NHL it caused increased morbidity.Conclusions. VTE is a relatively uncommon complication of NHL and its treatment, causing increased acute and long-term morbidity. DLBCL is associated with increased risk of VTE compared to FL. This risk is markedly attenuated when adjusting for additional risk factors.The strongest predictors for development of VTE included: time period during chemotherapy administration, history of VTE, clinical stage III/IV and BMI >30. This knowledge can assist clinicians in identifying NHL patients at high risk for VTE. DisclosuresNo relevant conflicts of interest to declare.

Discontinuation of oral anticoagulation therapy after successful atrial fibrillation ablation: A systematic review and meta-analysis of prospective studies.

The safety of discontinuing oral anticoagulant (OAC) therapy after atrial fibrillation (AF) ablation remains controversial. A meta-analysis was performed to assess the safety and feasibility of discontinuing OAC therapy after successful AF ablation. PubMed and Embase were searched up to October 2020 for prospective cohort studies that reported the risk of thromboembolism (TE) after successful AF ablation in off-OAC and on-OAC groups. The primary outcome was the incidence of TE events. The Mantel-Haenszel method with random-effects modeling was used to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs). A total of 11,148 patients (7,160 in the off-OAC group and 3,988 in the on-OAC group) from 10 studies were included to meta-analysis. No significant difference in TE between both groups was observed (OR, 0.73; 95%CI, 0.51-1.05; I2 = 0.0%). The risk of major bleeding in off-OAC group was significantly lower compared to the on-OAC group (OR, 0.18; 95%CI, 0.07-0.51; I2 = 51.7%). Our study suggests that it may be safe to discontinue OAC therapy in patients after successful AF ablation. Additionally, an increased risk of major bleeding was observed in patients on OAC. However, the results of this meta-analysis should be interpreted with caution because of the heterogeneity among the included study designs. Large-scale and adequately powered randomized controlled trials are warranted to confirm these findings.

Therapeutic Doses of Anticoagulation Did Not Benefit Patients with COVID-19 and Elevated

Compared with other respiratory infections, COVID-19 is associated with higher incidence of thromboembolic events — moreover, these complications are

A Systematic Review of Anticoagulation Strategies for Patients with Atrial Fibrillation in Critical Care

Atrial fibrillation (AF) is the most common cardiac arrhythmia in critically ill patients. There is a paucity of data assessing the impact of anticoagulation strategies on clinical outcomes for general critical care patients with AF. Our aim was to assess the existing literature to evaluate the effectiveness of anticoagulation strategies used in critical care for AF. A systematic literature search was conducted using MEDLINE, EMBASE, CENTRAL, and PubMed databases. Studies reporting anticoagulation strategies for AF in adults admitted to a general critical care setting were assessed for inclusion. Four studies were selected for data extraction. A total of 44,087 patients were identified with AF, of which 17.8 to 49.4% received anticoagulation. The reported incidence of thromboembolic events was 0 to 1.4% for anticoagulated patients, and 0 to 1.3% in nonanticoagulated patients. Major bleeding events were reported in three studies and occurred in 7.2 to 8.6% of the anticoagulated patients and in up to 7.1% of the nonanticoagulated patients. There was an increased incidence of major bleeding events in anticoagulated patients with AF in critical care compared with nonanticoagulated patients. There was no significant difference in the incidence of reported thromboembolic events within studies between patients who did and did not receive anticoagulation. However, the outcomes reported within studies were not standardized, therefore, the generalizability of our results to the general critical care population remains unclear. Further data are required to facilitate an evidence-based assessment of the risks and benefits of anticoagulation for critically ill patients with AF.

Risk of Thromboembolism in Non-Valvular Atrial Fibrillation With or Without Clinical Hyperthyroidism.

Background:Patients with hyperthyroidism have higher risk of atrial fibrillation (AF). However, the risk of thromboembolic event in patients with hyperthyroidism-related AF is controversial.Objectives:The aim of the study was to examine the risk of thromboembolic events in AF patients with/without hyperthyroidism.Methods:The national retrospective cohort study enrolled AF population was derived from the Taiwan National Health Insurance Research Database. The comparison between the AF patients with clinical hyperthyroidism (HT-AF group) and AF patients without hyperthyroidism (non-thyroid AF group) was made in a propensity score matched cohort and in a real-world setting, of which, the CHA2DS2-VASc level was treated as a stratum variable. The outcomes were ischemic stroke and systemic thromboembolism.Results:There were 3,880 patients in HT AF group and 178,711 in non-thyroid AF group. After propensity score analysis, the incidence of thromboembolism event and ischemic stroke were lower in HT AF patients than non-thyroid AF patients (1.6 versus 2.2 events per 100 person-years; HR, 0.73; 95% CI, 0.64–0.82 and 1.4 versus 1.8 events per 100 person-years; HR, 0.74; 95% CI, 0.64–0.84, respectively) in the 4.3 ± 3.2 year follow up period. The differences persistently existed in those receiving anticoagulants or not. In AF patients without anticoagulants, the incidence densities of ischemic stroke/systemic thromboembolism were significantly lower in HT AF group than those in non-thyroid AF group at CHA2DS2-VASc scores ≤ 4 (HR, 0.41; 95% CI, 0.35–0.48, p < 0.001), while the differences disappeared in case of score ≥ 5 (HR, 0.80; 95% CI, 0.63–1.02, p = 0.071).Conclusion:Patients with HT AF had lower incidence of thromboembolic events as compared to non-thyroid AF patients. The threshold of CHA2DS2-VASc score for anticoagulation in AF patients with clinical hyperthyroidism should be further evaluated.HighlightsThe incidence of thromboembolic event was different between hyperthyroidism-related atrial fibrillation (HT-AF) and non-thyroid AF patients.Hyperthyroidism did not confer additional risk of thromboembolic event at CHA2DS2-VASc of ≤ 4.The benefit of anticoagulation strategy in patients with hyperthyroidism-related AF should be further evaluated, especially at low CHA2DS2-VASc score.

Immune-mediated diseases and thromboembolic events: a modified Delphi panel

Introduction A multidisciplinary panel of physicians was convened to gain understanding of the relationship between thromboembolic events (TEs) and immune-mediated diseases (IMDs). The primary objective of the panel was to assess areas of consensus on the IMD most prone to TE as well as modifiable and unmodifiable factors that might exacerbate or mitigate the risk of TEs. Methods Thirteen nationally recognized physicians were selected based on their contributions to guidelines, publications and patient care. The modified Delphi panel consisted of four rounds of engagement: (1) a semi-structured interview, (2) an expert panel questionnaire, (3) an in-person panel discussion, and (4) a consensus statement survey. Results Ulcerative colitis and Crohn’s disease were identified as two of four IMDs with the highest TE risk. Consensus was reached on several non-modifiable and modifiable characteristics of high-risk. Approaches to reduce TE incidence were identified such as altering treatment, requiring the monitoring of patients for TEs and modifying patient behaviors. Janus kinase inhibitors and corticosteroids were identified as therapies that required further evaluation given their potential TE risk. Discussion The panel reached a consensus that several IMDs are at an elevated risk of TEs. Physicians are unable to control most patient level risk factors but can control the therapies being used. Consequently, physicians should consider the specific IMD, be aware of TE risk factors, and take into account risk factors in selecting the therapies to optimally manage their conditions and to reduce the risk of TEs in this population.

Off-label reduced-dose apixaban does not reduce hemorrhagic risk in Taiwanese patients with nonvalvular atrial fibrillation: A retrospective, observational study.

East Asians are reportedly at high risk of anticoagulant-related bleeding; therefore, some physicians prefer to prescribe low-dose direct oral anticoagulants (DOACs). Little is known about the therapeutic effectiveness and safety of off-label reduced-dose apixaban in East Asians with nonvalvular atrial fibrillation (AF). We aimed to investigate the effectiveness and safety of off-label reduced-dose apixaban in Taiwanese patients with nonvalvular AF.This retrospective cohort study enrolled 1073 patients with nonvalvular AF who took apixaban between July 2014 and October 2018 from 4 medical centers in southern Taiwan. The primary outcomes included thromboembolic events (stroke/transient ischemic attack or systemic embolism), major bleeding, and all-cause mortality.Among all patients, 826 (77%) patients were classified as the “per-label adequate-dose” treatment group (i.e., consistent with the Food and Drug Administration label recommendations) while 247 (23%) patients were the “off-label reduced-dose” treatment group. The mean follow-up period was 17.5 ± 13 months. The “off-label reduced-dose” group did not have a lower major bleeding rate than the “per-label adequate-dose” group (4.8% vs 3.8%, adjusted hazard ratio [HR] 1.20, 95% confidence interval [CI] 0.69–2.09), but had a nonsignificantly higher incidence of thromboembolic events (4.23% vs 3.05%, adjusted HR: 1.29, 95% CI: 0.71–2.34).An off-label reduced-dose apixaban treatment strategy may not provide incremental benefits or safety for Taiwanese patients with nonvalvular AF.

A new look at the correction of COVID-19-mediated pulmonary gas exchange disorders

Aim. To assess the effect of meglumine sodium succinate on the effectiveness of basic therapy in correcting gas exchange abnormalities in patients with severe COVID-19 infection complicated by bilateral community-acquired pneumonia.&#x0D; Methods. The analysis of the effectiveness of therapy of 12 patients with a diagnosis of New coronavirus infection COVID-19 (confirmed), severe form U07.1. Complication: bilateral multifocal pneumonia was carried out. The patients were divided into two groups: 7 received, as part of standard therapy, a solution of meglumine sodium succinate in a daily dose of 5 ml/kg during stay in the intensive care unit; 5 patients received a similar volume of Ringer's solution and formed the control group. In the arterial and venous blood of all patients, the indicators of acid-base state and water-electrolyte balance, glycemia and lactatemia were measured at several stages: (1) at admission to the intensive care unit, (2) 24 hours after the start of intensive therapy, (3) after 812 hours, (4) after 24 hours. On the 28th day of observation, mortality, the duration of treatment in the intensive care unit and the incidence of thrombotic complications in the groups were assessed. The Friedman nonparametric hypothesis test was used to assess intragroup dynamics, and the nonparametric Mannhitney U test for intergroup comparisons.&#x0D; Results. In the group of patients who received meglumine sodium succinate, there was a significant decrease in the incidence of thromboembolic events during 28 days of treatment: myocardial ischemia event rate ratio from 0.89 [95% confidence interval (CI) 0.191.16] in the control group to 0.55 (95% CI 0.060.81) in the study group at p=0.043; pulmonary embolism event from 0.50 (95% CI 01.0) in the control group to 0.28 (95% CI 01.0) in the study group at p=0.041. There was also a decrease in the duration of intensive care unit length of stay to 6.11.1 days in the study group versus 8.91.3 days in the control group.&#x0D; Conclusion. Compared with standard infusion therapy, the use of meglumine sodium succinate leads to a faster normalization of ventilation-perfusion ratios in patients with severe coronavirus infection.

Physician-Pharmacist Collaborative Clinic Model to Improve Anticoagulation Quality in Atrial Fibrillation Patients Receiving Warfarin: An Analysis of Time in Therapeutic Range and a Nomogram Development.

Background: Poor time in therapeutic range (TTR) control is associated with an increased risk of stroke and bleeding in atrial fibrillation (AF) patients receiving warfarin. This study aimed to determine whether the physician–pharmacist collaborative clinic (PPCC) model could improve the anticoagulation quality as well as to create a nomogram for predicting anticoagulation quality in AF patients. Methods: This retrospective observational study enrolled AF patients who either initially received warfarin or returned to warfarin after withdrawal between January 1, 2016 and January 1, 2021, at our institution. The primary outcome was dynamic changes in TTRs (a TTR of ≥60% considered high anticoagulation quality). The secondary outcomes were thromboembolic and bleeding events during follow-up. We compared the dynamic changes in TTRs between the general clinic (GC) and PPCC groups in both the original and propensity score matching (PSM) cohorts. In addition, we explored the potential predictors of high anticoagulation quality and subsequently formulated a nomogram to predict anticoagulation quality. Results: A total of 265 patients with AF were included, comprising 57 patients in the PPCC group and 208 patients in the GC group. During a median follow-up period of 203 days, the PPCC group had a shorter time (76 vs. 199 days, p < 0.001) and more patients achieved a TTR ≥60% (73.7 vs. 47.1%, p = 0.002 by log-rank test) than the GC group. The results from the PSM cohort confirmed this finding. No significant differences in the incidences of thromboembolic events (5.3 vs. 5.3%, p = 1.000) and bleeding events (4.3 vs. 3.5%, p = 1.000) were observed between the two groups. Four variables were explored as predictors related to high anticoagulation quality: treatment within a PPCC, history of bleeding, history of bleeding, and the presence of more than four comorbidities. The nomogram revealed a moderate predictive ability (c-index: 0.718, 95% confidence interval (95%CI): 0.669–0.767) and a moderately fitted calibration curve. Conclusion: The PPCC model contributed to improved anticoagulation quality in AF patients receiving warfarin. The nomogram might be an effective tool to predict anticoagulation quality and could aid physicians and pharmacists in the selection of patients who will likely benefit from sustained and active intervention.

Outcomes of Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome in COVID-19 Patients: A Propensity-Matched Analysis.

It remains unclear to what extent the outcomes and complications of extracorporeal membrane oxygenation (ECMO) therapy in COVID-19 patients with acute respiratory distress syndrome (ARDS) differ from non-COVID-19 ARDS patients. In an observational, propensity-matched study, outcomes after ECMO support were compared between 19 COVID-19 patients suffering from ARDS (COVID group) and 34 matched non-COVID-19 ARDS patients (NCOVID group) from our historical cohort. A 1:2 propensity matching was performed based on respiratory ECMO survival prediction (RESP) score, age, gender, bilirubin, and creatinine levels. Patients’ characteristics, laboratory parameters, adverse events, and 90-day survival were analyzed. Patients’ characteristics in COVID and NCOVID groups were similar. Before ECMO initiation, fibrinogen levels were significantly higher in the COVID group (median: 493 vs. 364 mg/dL, p < 0.001). Median ECMO support duration was similar (16 vs. 13 days, p = 0.714, respectively). During ECMO therapy, patients in the COVID group developed significantly more thromboembolic events (TEE) than did those in the NCOVID group (42% vs. 12%, p = 0.031), which were mainly pulmonary artery embolism (PAE) (26% vs. 0%, p = 0.008). The rate of major bleeding events (42% vs. 62%, p = 0.263) was similar. Fibrinogen decreased significantly more in the COVID group than in the NCOVID group (p < 0.001), whereas D-dimer increased in the COVID group (p = 0.011). Additionally, 90-day mortality did not differ (47% vs. 74%; p = 0.064) between COVID and NCOVID groups. Compared with that in non-COVID-19 ARDS patients, ECMO support in COVID-19 patients was associated with comparable in-hospital mortality and similar bleeding rates but a higher incidence of TEE, especially PAE. In contrast, coagulation parameters differed between COVID and NCOVID patients.

The effects of anticoagulant therapy re-initiation after gastrointestinal bleeding: A systematic review and meta-analysis.

Long-term anticoagulant/antithrombotic therapy is widely used for the management of thromboembolic conditions. Gastrointestinal bleeding is a common collateral manifestation of anticoagulant/antithrombotic therapy that complicates its administration. The continuation or discontinuation of anticoagulant/antithrombotic therapy after an episode of gastrointestinal bleeding has been a matter of debate. Despite recent positive reports from retrospective cohort studies suggesting a reduction in morbidity- and mortality-related outcomes with continued administration of anticoagulant/antithrombotic agents (even after gastrointestinal bleeding), no consensus or comparisons about the efficacies of continued or discontinued antithrombotic administration exist. Therefore, we developed this current state-of-evidence analysis evaluating the comparative effects of continuation and discontinuation of anticoagulant/antithrombotic drugs after gastrointestinal bleeding on the overall incidences of gastrointestinal bleeding, thromboembolic events and mortality events. We performed a systematic academic literature search according to the PRISMA guidelines across five databases: Web of Science, Embase, CENTRAL, Scopus and MEDLINE. Moreover, we conducted a random effect meta-analysis to compare the effects of continuation and discontinuation of anticoagulant/antithrombotic drugs after an event of gastrointestinal bleeding on the overall incidences of gastrointestinal bleeding, thromboembolic events and mortality events. We found seven eligible studies (from 1397 candidates) with 2532 participants (mean age, 73.1 ± 4.1years). Our meta-analysis revealedlower odds of thromboembolic events (OR, -0.21), mortality outcomes (OR, -0.39) and an increase in the incidence of gastrointestinal bleeding (OR, 2.4) in the group with continued anticoagulant/antithrombotic therapy than in the group discontinuing the therapy. We provide an updated evidence on the comparative effects between continuation and discontinuation of anticoagulant/antithrombotic drugs after gastrointestinal bleeding events based on the overall incidences of gastrointestinal bleeding, thromboembolic events and mortality events. This study reports confirm an overall lower incidence of thromboembolic events and mortality outcomes for the continuation group than for the discontinuation group.

Impact of a pharmacist driven anticoagulation reversal program at a large academic medical center.

In major/life-threatening bleeding, administration of timely and appropriate reversal agents is imperative to reduce morbidity and mortality. Due to complexities associated with the use of reversal agents, a clinical pharmacist-driven anticoagulation reversal program (ARP) was developed. The goal of this program was to ensure appropriateness of reversal agents based on the clinical scenario, optimize selection and avoid unintended consequences. This study describes the impact of a pharmacist-driven anticoagulation program on patient outcomes and cost. A single center retrospective chart review of adult patients whom the ARP was consulted from October 2018 to January 2020 was performed. Patients were included in the efficacy analysis if they were > 18years of age and presented with acute bleeding. Patients were excluded from the efficacy analysis if the recommended reversal agent was not administered, if a repeat head CT was not available for patients who presented with intracranial hemorrhage (ICH), or if the patient was not bleeding. All patients were included in the economic evaluation. The primary outcome was the percentage of patients who achieved effective hemostasis within 24h of anticoagulation reversal. Secondary outcomes include incidence of thromboembolic events, in-hospital mortality, and cost avoidance. One hundred twenty-one patients were evaluated by the ARP with 92 patients included in the efficacy analysis. The primary sites of bleeding were ICH in 46% and gastrointestinal (GI) in 29%. Hemostasis was achieved in 84% of patients. Thrombotic events occurred in 7.4% of patients and in-hospital mortality was 26.4%. Total cost avoidance was $1,005,871.78. To our knowledge, this is the first study to evaluate the impact of a pharmacist-driven ARP on clinical and economic outcomes. Implementation of a pharmacist-driven ARP was associated with favorable outcomes and cost savings.

MO212LATE EVIDENCE OF SARS-COV-2 INFECTION IN A PATIENT WITH ACUTE KIDNEY INJURY (AKI) AND MASSIVE DEEP VEIN THROMBOSIS (DVT) STARTING FROM A HEMODIALYSIS CENTRAL VENOUS CATHETER (CVC)

Background and AimsCOVID-19 has heterogeneous clinical manifestations. SARS-CoV-2 related AKI and hypercoagulability are negative prognostic factors. The incidence of thromboembolic events is about 30%, of AKI up to 20%. We report a patient with severe AKI who required hemodialysis (HD) and developed a massive DVT developing from the femoral CVC, and belatedly testing positive for SARS-CoV-2 in the absence of typical pulmonary involvement.MethodA 53-year-old male with a clinical history of hypertension, type II diabetes mellitus, in therapy with metformin and ace-inhibitor, was admitted to our E.R. with diarrhea, nausea and vomiting for about 2 days. Main signs: ideomotor slowdown, mild hypohydration and reduced urine output (unrelevant sediment). Initial blood tests showed severe AKI with hyperkalemic metabolic acidosis and hyponatremia (sCreatinine 18.76 mg/dl, BUN 161 mg/dl, K+ 7.8 mmol/l, Na+ 128 mmol/L, HCO3- 9.8 mmol/l). Mild neutrophilic leukocytosis with lymphopenia was detected, with slightly increased inflammation indices (CRP 1.05 mg / dl, D-dimer 720 ng / ml). CT scan: absence of typical SARS-CoV-2 signs, normal kidneys, no dilation of urinary tract. SARS-CoV-2 rapid antigen test and the first molecular swab test were negative. After femoral CVC insertion, HD was needed for a few sessions. Broad range antibiotic therapy was also set.On Day 3: a second SARS-CoV-2 PCR swab test resulted negative. He never manifested fever or dyspnea.On Day 6, despite an improvement of renal function (sCr 2.7 mg/dl), the patient, although he walked, presented right leg pain with signs of DVT. Ultrasound and angio-CT scan documented peri-catheter DVT extended to the common femoral and external iliac vein and superficial femoral vein involvement, without pulmonary embolism. I.v. therapy with sodium heparin was therefore started with quite a difficulty in reaching the expected range.On day 8, massive flittene appeared, the CVC was removed and a caval filter was placed; marked neutrophilic leucocytosis and increased inflammatory indices (CRP 11.50 mg/dl) was documented. Nevertheless, thrombosis has progressed to the entire venous axis and the inferior cava. Through a tibial vein introducer local i.v. alteplase was also started. Just after, copious bleeding from the site of the removed CVC followed by haemorrhagic shock occurred and the patient was transferred to the ICU (D-dimer 219800 ng/ml). The same day a third swab for SARS-CoV-2 resulted positive while a further CT-scan did not show signs of virus-like interstitial pneumonia. On the following day (day 9) the patient underwent thrombus aspiration (Aspirex®S device) and fasciotomy of the right leg for a compartment syndrome.ResultsDespite the continuation of heparin, PTT ratio was never >1.5, with an extension of DVT and also involvement of the contralateral iliac vein, as well as a worsening of the clinical-laboratory picture and patient’s death on day 14. Serum complement, autoantibodies (ANA, ANCA, ENA, ANTI-dsDNA, anti-cardiolipin, AMA, anti-B-glycoprotein) and factor V Leiden test were normal. All blood cultures were found to be sterile.ConclusionOur case confirms the heterogenicity of COVID-19 manifestations, often without pulmonary involvement. According to our experience from the onset of the pandemic, SARS-CoV-2 can also be found later in patients with already advanced organ damage. In this case, in the absence of other possible factors, AKI and intestinal involvement may have been early signs of COVID-19, with a virus initially not detectable in the nasopharyngeal mucosa. Furthermore, the increased thromboembolic risk of COVID-19 should not be underestimated in the presence of risk factors as external devices, also given the difficult management of anticoagulation target. Anticoagulant prophylaxis in cases with doubtful symptomatology and CVC must be considered even in non-bedridden patients, due to the current risk of SARS-CoV-2 infection.

Arterial Thrombosis and Acute Limb Ischemia as a Complication of COVID-19 Infection.

COVID-19 refers to viral respiratory infections and is the predisposing factor for the development of venous and arterial thrombotic events due to a pronounced inflammatory response, platelet activation, endothelial dysfunction, and stasis. Recent studies have confirmed a high incidence of thromboembolic events, especially in the group of patients with severe coronavirus pneumonia. There have been an increasing number of reports of peripheral arterial thrombosis as well. Most cases of arterial thrombosis are noted in critical ill patients in intensive care setting. However, an increase of adverse arterial events was also noted in cases of asymptomatic or mild forms of COVID-19. Herein, we report a case of patient with asymptomatic SARS-CoV-2 infection, who developed a threatening lower limb ischemia. Our own clinical observation suggests that COVID-19-associated arterial thrombosis can be successfully treated by embolectomy, administration of in-hospital parenteral anticoagulation, and continuation of antithrombotic therapy with a "vascular" dose of rivaroxaban after discharge.

Acute thromboembolic events (TE) within 30 days of COVID-19 infection in cancer patients.

e18691 Background: Increased rates of TE have been reported in patients (pts) with coronavirus disease (COVID-19), even without prior predisposition to thrombosis. Patients with cancer are already predisposed to a hypercoagulable state. We aimed to assess whether COVID-19 further increased the risk of TE in pts with active cancer at Montefiore Medical Center, Bronx, NY. Methods: The EMR of 90 cancer pts diagnosed with COVID-19 from March 15th to April 10th, 2020 were reviewed. COVID-19 testing was performed by PCR of nasal swab samples. Active cancer was defined as disease treated &lt;1 year. Reports of imaging studies performed &lt;30 days of the COVID-19+ test, either for new symptoms or for other reasons, were reviewed for new arterial (ATE) and/or venous thromboses (VTE). Patient were followed for 30 days from the date of COVID-19+ test for development of TE, hospital length of stay (LOS) and mortality. Results: Of 90 pts, 11 (12.2%) were found to have 13 new TE within 30 days of COVID-19+ test, 8 (8.9%) arterial and 5 (5.6%) venous. Of the 8 ATE, 7 were new strokes and/or microvascular cerebral disease (MCD) and 1 was a spleen infarct (SI). Of the 5 VTE, 3 were deep venous thrombosis, 1 pulmonary embolism (PE) and 1 patient presented with a superficial VTE. Two patients had 2 new TE each; stroke/PE and MCD/SI, respectively. Peak D-dimer (DD) value was higher in the TE group; mean DD (SD), TE vs no TE, 7.1 (3.4) vs 6.4 (7) ug/mL, p=0.03. Pts on either prophylactic or therapeutic anticoagulation (AC) had less TE; AC vs no AC, 9.1% vs 90.9%, p=0.0003. Only 1 pt on Enoxaparin prophylaxis developed TE. Of the 20 pts on therapeutic AC, 25% were newly started due to concern for thrombosis; the rest were already receiving AC for other reasons. Mortality was higher in the TE group; HR, TE vs no TE, 2.6, 95% CI (1.2 - 5.6), p=0.009. There was no correlation of cancer type, disease stage (metastatic or not), administration of prior chemotherapy or immunotherapy, common comorbidities, patient setting (inpatient, ICU, outpatient, ED visit), LOS or ventilation status with increased incidence of TE. Conclusions: Pts with COVID-19 have high rates of TE, and this is true for our pts with cancer. A high incidence of ATE was noted. TE was associated with increased mortality.[Table: see text]

Isolated Kidney Infarct and Lupus Anticoagulant Positivity in a Young Patient with Mild SARS-CoV-2 Infection

The incidence of thromboembolic events in COVID-19 is reportedly higher in intensive care unit (ICU) patients (29.4%) as compared to non-ICU patients (11.5%), while data on thromboembolic events in non-hospitalized, self-limiting COVID-19 is unavailable.

Multiple intravenous tranexamic acid doses in total knee arthroplasty in patients with rheumatoid arthritis: a randomized controlled study

BackgroundWe aimed to determine the efficacy and safety of multiple doses of intravenous tranexamic acid (IV-TXA) on perioperative blood loss in patients with rheumatoid arthritis (RA) who had undergone primary unilateral total knee arthroplasty (TKA).MethodsFor this single-center, single-blind randomized controlled clinical trial, 10 male and 87 female participants with RA, aged 50–75 years, who underwent unilateral primary TKA were recruited. The patients received one dose of 1 g IV-TXA 10 min before skin incision, followed by articular injection of 1.5 g tranexamic acid after cavity suture during the surgery. The patients were randomly assigned (1:1) into two groups and received an additional single dose of IV-TXA (1 g) for 3 h (group A) or three doses of IV-TXA (1 g) for 3, 6, and 12 h (group B) postoperatively. Primary outcomes were total blood loss (TBL), hidden blood loss (HBL), and maximum hemoglobin (Hb) level decrease. Secondary outcomes were transfusion rate and D-dimer levels. All parameters were measured postoperatively during inpatient hospital stay.ResultsThe mean TBL, HBL, and maximum Hb level decrease in group B (506.1 ± 227.0 mL, 471.6 ± 224.0 mL, and 17.5 ± 7.7 g/L, respectively) were significantly lower than those in group A (608.8 ± 244.8 mL, P = 0.035; 574.0 ± 242.3 mL, P = 0.033; and 23.42 ± 9.2 g/L, P = 0.001, respectively). No episode of transfusion occurred. The D-dimer level was lower in group B than in group A on postoperative day 1 (P < 0.001), and the incidence of thromboembolic events was similar between the groups (P > 0.05).ConclusionIn patients with RA, three doses of postoperative IV-TXA further facilitated HBL and Hb level decrease without increasing the incidence of adverse events in a short period after TKA.Trial registrationThe trial was registered in the Chinese Clinical Trial Registry (ChiCTR1900025013).