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A higher risk of thrombosis has been described as a prominent feature of coronavirus disease 2019 (COVID-19). This systematic review synthesizes current data on thrombosis risk, prognostic implications, and anticoagulation effects in COVID-19. We included 37 studies from 4070 unique citations. Meta-analysis was performed when feasible. Coagulopathy and thrombotic events were frequent among patients with COVID-19 and further increased in those with more severe forms of the disease. We also present guidance on the prevention and management of thrombosis from a multidisciplinary panel of specialists from Mayo Clinic. The current certainty of evidence is generally very low and continues to evolve., (Copyright © 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Controversy exists regarding the use of dose capping of weight-based unfractionated heparin (UFH) infusions in obese and morbidly obese patients. The primary objective of this study was to compare time to first therapeutic activated partial thromboplastin time (aPTT) in hospitalized patients receiving UFH for acute venous thromboembolism (VTE) among three body mass index (BMI) cohorts: non-obese (< 30 kg/m 2 ), obese (30-39.9 kg/m 2 ), and morbidly obese (⩾ 40 kg/m 2 ). In this single-center, retrospective cohort study, patients were included if they ⩾ 18 years of age, had a documented VTE, and were on an infusion of UFH for at least 24 hours. Weight-based UFH doses were calculated using actual body weight. A total of 423 patients met the inclusion criteria, with 230 (54.4%), 146 (34.5%), and 47 (11.1%) patients in the non-obese, obese, and morbidly obese cohorts, respectively. Median times to therapeutic aPTT were 16.4, 16.6, and 17.1 hours in each cohort. Within 24 hours, the cumulative incidence rates for therapeutic aPTT were 70.7% for the non-obese group, 69.9% for the obese group, and 61.7% for the morbidly obese group (obese vs non-obese: HR = 1.02, 95% CI: 0.82-1.26, p = 0.88; morbidly obese vs non-obese: HR = 0.87, 95% CI: 0.62-1.21, p = 0.41). There was no significant difference in major bleeding events between BMI groups (obese vs non-obese, p = 0.91; morbidly obese vs non-obese, p = 0.98). Based on our study, heparin dosing based on actual body weight without a dose cap is safe and effective.

Introduction: Anticoagulation with warfarin affects approximately 140,000 post-cardiac surgery patients every year, yet there remains limited published data in this patient population. Dosing remains highly variable due to intrinsic risk factors that plague cardiac surgery candidates and a lack of diverse literature that can be applied to those who have undergone a cardiac surgery alternative to heart valve replacement (HVR). In the present study, our aim was to compare the warfarin requirements between HVR and non-HVR patients., Methods: This was a single-center, retrospective study of post-cardiac surgery patients initiated on warfarin at Mayo Clinic Hospital, Rochester, from January 1st, 2013 to October 31st, 2016. The primary outcome was the maintenance warfarin dose at the earliest of discharge or warfarin day 10 between patients with HVR and non-HVR cardiac surgeries., Results: A total of 683 patients were assessed during the study period: 408 in the HVR group and 275 in the non-HVR group. The mean warfarin maintenance doses in the HVR and non-HVR groups were 2.55 mg [standard deviation (SD) 1.52] and 2.43 mg (SD 1.21), respectively (adjusted p = 0.65). A multivariable analysis was performed to adjust for gender, age, body mass index and drug interactions., Conclusions: This was the largest study to evaluate warfarin dose requirements in post-cardiac surgery patients and is the first to compare warfarin requirements between HVR and non-HVR patients during the immediate post-operative period. Both groups had similar warfarin requirements, which supports expanding the initial warfarin dosing recommendations of the 9th edition Chest guideline to include non-HVR patients as well as HVR patients.

To reliably assess quality, a standardized electronic approach is needed to identify bleeding events. The study aims were the following: (1) clinically validate an electronic health record-based algorithm for bleeding and (2) assess interrater results to determine validity and reliability. Data were analyzed before and after implementation of a pharmacist-managed warfarin protocol. Bleeding was based on ≥2 of 3 criteria: (1) diagnosis indicating bleeding, (2) lab value decrease suggesting bleeding, and (3) blood product use. All suspected bleeds (234) and a sample (58) not meeting criteria were compared with clinical review. There were 234 bleeding cases identified electronically. Reviewer agreement was 78.2% (κ = 0.565). Algorithm sensitivity was 93.9% and positive predictive value 46.2%. Algorithm identification was least accurate for those with only 2 criteria but good for those with all criteria. This study supports using multiple electronic criteria to identify bleeding events. However, cases having exactly 2 criteria may require manual review for validation.

Purpose: The impact of therapeutic hypothermia (TH) on unfractionated heparin (UFH) management is essentially unknown. The aim of this study was to evaluate the effect of TH on UFH dosing and activated partial thromboplastin (aPTT) response., Materials and Methods: Consecutive patients treated from 2005 to 2011 who received intravenous UFH via a dosing nomogram during TH were included. First, heparin doses and aPTT responses were compared between 2 core temperature groups, less than or equal to 33°C and greater than 35°C. Next, the first aPTT, drawn at 6 hours for temperature less than or equal to 33°C, was assessed. Lastly, a linear model was developed to predict the mean aPTT, based on temperatures and heparin doses., Results: Of the 156 TH patients, 68 were included. At temperatures less than or equal to 33°C, 76.3% of all aPTT levels and 81.0% of the first aPTTs were above goal range, respectively. Using a linear model, an UFH dose of 12 U/kg per hour predicts an aPTT of 134 seconds at less than or equal to 33°C., Conclusions: Using guideline-recommended heparin dosing without dose adjustment for temperature changes produced excessive aPTT during the cooling phase for TH patients. Reduction in the UFH dose of 43% to 54% may be required during TH. We recommend frequent aPTT monitoring during the cooling and rewarming phases to attain a desired aPTT range., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Study Objective: To identify specific risk factors for excessive anticoagulation, defined as an international normalized ratio (INR) higher than 5, in hospitalized adults receiving warfarin therapy using a pharmacist-managed dosing protocol., Design: Retrospective nested case-control study., Setting: Large academic tertiary care medical center., Patients: Hospitalized nonsurgical patients 18 years or older who received at least one dose of warfarin according to the pharmacist-managed protocol from January 1, 2009, to January 31, 2012, were included. Patients who experienced an INR higher than 5 were designated as case patients; those who received warfarin for at least as many days as the case patients but who did not experience an INR more than 5 were deemed control patients. Controls were matched to cases in a 2:1 ratio by age, sex, INR goal, and type of warfarin therapy (new start or continuation)., Measurements and Main Results: A total of 87 case patients were matched to 174 controls. Ten different hypothesized risk factors were examined. Two variables, severity of illness score (odds ratio [OR] 4.89, p<0.001) and poor nutritional status (OR 4.27, p<0.001), demonstrated strong independent associations with risk of excessive anticoagulation. Administration of interacting drugs that highly potentiate warfarin's effect (OR 2.26, p=0.011) and concurrent diarrheal illness (OR 4.75, p<0.001) also displayed a statistically significant risk for excessive anticoagulation., Conclusion: Even in a highly standardized system for warfarin dosing by a pharmacist-managed protocol, higher disease severity and poor nutritional status placed hospitalized patients at greater risk of experiencing excessive anticoagulation. In addition, administration of interacting drugs that highly potentiate warfarin's effect or the occurrence of diarrheal illness may predict increased risk., (© 2013 Pharmacotherapy Publications, Inc.)

Objective: To assess bleeding and activated partial thromboplastin time (APTT) in relation to body mass index (BMI) in patients prescribed weight-based dosing of intravenous unfractionated heparin (UFH) for cardiac indications without a maximum (dose-capped) initial bolus or capped initial infusion rate., Patients and Methods: Consecutive patients admitted to an academic medical center from February 1, 2002, through November 31, 2003, who were treated with a UFH nomogram consisting of a 60-U/kg intravenous bolus plus an initial continuous intravenous infusion of 12 U/kg hourly and titrated to a goal APTT range corresponding to thromboplastin-adjusted target heparin levels of 0.3 to 0.7 U/mL by anti-Xa assay were evaluated for this retrospective cohort study. Patients were excluded if they concomitantly received a fibrinolytic, glycoprotein IIb/IIIa inhibitor, or any other antithrombotic agent (except warfarin). Study patients were divided into quartiles by BMI., Results: Of the 1054 patients included in the study, 807 (76.6%) had an initial bolus dose higher than 4000 U, and 477 (45.3%) had an initial infusion rate higher than 1000 U/h. Despite a significant difference among BMI quartiles in proportion of supratherapeutic first APTT values (P<.001), no statistically significant difference was found in bleeding frequency (P=.26) or frequency of first APTT within the goal range (P=.27). Logistic regression analyses revealed that BMI was not a significant predictor of bleeding or first APTT within the goal range., Conclusion: We did not find any difference in the proportion of first APTT values in the goal range or an increased risk of bleeding in obese patients treated with UFH without a capped initial dose. Our data demonstrate the safe use of weight-based UFH without a capped initial bolus dose or capped initial infusion rate in patients with medical cardiac conditions.

To overcome errors in prescribing, calculating doses, and monitoring intravenous heparin, a computerized heparin nomogram system (HepCare) was developed to improve heparin safety using interactive cues between the prescriber, nurse, pharmacist, and the laboratory. The frequency of deviations decreased from 0.5 per patient before HepCare with the protocol to 0.006 per patient with HepCare and the protocol. The goal activated partial thromboplastin time results of the HepCare system (group I) were compared with patients who were not treated using the HepCare system (group II). There was a higher mean percentage of activated partial thromboplastin times within goal range in group I vs. II-44% vs. 27% (p<0.01). There were reminders of a drop in platelet count in 6% of patients, hemoglobin drop in 0.7%, and validation activated partial thromboplastin time values in 7% of patients by HepCare. HepCare-guided intravenous heparin resulted in significant improvements in safety, quality assurance, and targeted activated partial thromboplastin time values.