Efficacy of emicizumab therapy in two adult patients with type 3 von Willebrand disease.

Type 3 von Willebrand disease (T3VWD) is a rare inherited bleeding disorder caused by the absence of von Willebrand factor (VWF). The traditional treatment for T3VWD has been VWF concentrates, but their effectiveness may be limited due to the development of alloantibodies. Emicizumab, a bispecific mAb, has shown promise in treating hemophilia A and is being studied as prophylaxis for T3VWD. In this case series, two patients with T3VWD received emicizumab prophylaxis and experienced a significant reduction in bleeding episodes and improved quality of life with fewer healthcare encounters. Although breakthrough bleeding was rare, one patient experienced a terminal intracranial bleed. Despite limited clinical experience with emicizumab in T3VWD, these cases suggest that emicizumab may be a valuable prophylactic option for patients with T3VWD. Further research is needed to determine the long-term efficacy and safety profile of emicizumab and optimal therapy for breakthrough bleeds in this patient population.

Inaccuracy of Initial Clinical Mobility Assessment in Venous Thromboembolism Risk Stratification.

BACKGROUND: Venous thromboembolism risk increases in hospitals due to reduced patient mobility. However, initial mobility evaluations for thromboembolism risk are often subjective and lack standardization, potentially leading to inaccurate risk assessments and insufficient prevention. METHODS: A retrospective study at a quaternary academic hospital analyzed patients using the Padua risk tool, which includes a mobility question, and the Johns Hopkins-Highest Level of Mobility (JH-HLM) scores to objectively measure mobility. Reduced mobility was defined as JH-HLM scores ≤3 over ≥3 consecutive days. The study evaluated the association between reduced mobility and hospital-acquired venous thromboembolism using multivariable logistic regression, comparing admitting health care professional assessments with JH-HLM scores. Symptomatic, hospital-acquired thromboembolisms were diagnosed radiographically by treating providers. RESULTS: Of 1715 patients, 33 (1.9%) developed venous thromboembolism. Reduced mobility, as determined by the JH-HLM scores, showed a significant association with thromboembolic events (adjusted OR: 2.53, 95%CI:1.23-5.22, P = .012). In contrast, the initial Padua assessment of expected reduced mobility at admission did not. The JH-HLM identified 19.1% of patients as having reduced mobility versus 6.5% by admitting health care professionals, suggesting 37 high-risk patients were misclassified as low risk and were not prescribed thrombosis prophylaxis; 4 patients developed thromboembolic events. JH-HLM detected reduced mobility in 36% of thromboembolic cases, compared to 9% by admitting health care professionals. CONCLUSION: Initial mobility evaluations by admitting health care professionals during venous thromboembolism risk assessment may not reflect patient mobility over their hospital stay. This highlights the need for objective measures like JH-HLM in risk assessments to improve accuracy and potentially reduce thromboembolism incidents.

Silent cerebral infarction during immune TTP remission: prevalence, predictors, and impact on cognition.

Immune thrombotic thrombocytopenic purpura (iTTP) survivors have increased risk of cardiovascular disease, including strokes, and report persistent cognitive difficulties during remission. We conducted this prospective study involving iTTP survivors during clinical remission to determine the prevalence of silent cerebral infarction (SCI), defined as magnetic resonance imaging (MRI) evidence of brain infarction without corresponding overt neurodeficits. We also tested the hypothesis that SCI is associated with cognitive impairment, assessed using the National Institutes of Health ToolBox Cognition Battery. For cognitive assessments, we used fully corrected T scores adjusted for age, sex, race, and education. Based on the diagnostic and statistical manual 5 criteria, we defined mild and major cognitive impairment as T scores with a 1 or 2 standard deviation (SD) and >2 SD below the mean on at least 1 test, respectively. Forty-two patients were enrolled, with 36 completing MRIs. SCI was present in 50% of the patients (18), of which 8 (44.4%) had prior overt stroke including during acute iTTP. Patients with SCI had higher rates of cognitive impairment (66.7% vs 27.7%; P = .026), including major cognitive impairment (50% vs 5.6%; P = .010). In separate logistic regression models, SCI was associated with any (mild or major) cognitive impairment (odds ratio [OR] 10.5 [95% confidence interval (95% CI), 1.45-76.63]; P = .020) and major cognitive impairment (OR 7.98 [95% CI, 1.11-57.27]; P = .039) after adjusting for history of stroke and Beck depression inventory scores. MRI evidence of brain infarction is common in iTTP survivors; the strong association of SCI with impaired cognition suggests that these silent infarcts are neither silent nor innocuous.

Management of Anticoagulation/Antiplatelet Medication and Venous Thromboembolism Prophylaxis in Elective Spine Surgery: Concise Clinical Recommendations Based on a Modified Delphi Process.

STUDY DESIGN: Delphi method. OBJECTIVE: To gain consensus on the following questions: (1) When should anticoagulation/antiplatelet (AC/AP) medication be stopped before elective spine surgery?; (2) When should AC/AP medication be restarted after elective spine surgery?; (3) When, how, and in whom should venous thromboembolism (VTE) chemoprophylaxis be started after elective spinal surgery? SUMMARY OF BACKGROUND DATA: VTE can lead to significant morbidity after adult spine surgery, yet postoperative VTE prophylaxis practices vary considerably. The management of preoperative AC/AP medication is similarly heterogeneous. MATERIALS AND METHODS: Delphi method of consensus development consisting of three rounds (January 26, 2021, to June 21, 2021). RESULTS: Twenty-one spine surgeons were invited, and 20 surgeons completed all rounds of questioning. Consensus (>70% agreement) was achieved in 26/27 items. Group consensus stated that preoperative Direct Oral Anticoagulants should be stopped two days before surgery, warfarin stopped five days before surgery, and all remaining AC/AP medication and aspirin should be stopped seven days before surgery. For restarting AC/AP medication postoperatively, consensus was achieved for low-risk/medium-risk/high-risk patients in 5/5 risk factors (VTE history/cardiac/ambulation status/anterior approach/operation). The low/medium/high thresholds were POD7/POD5/POD2, respectively. For VTE chemoprophylaxis, consensus was achieved for low-risk/medium-risk/high-risk patients in 12/13 risk factors (age/BMI/VTE history/cardiac/cancer/hormone therapy/operation/anterior approach/staged separate days/staged same days/operative time/transfusion). The one area that did not gain consensus was same-day staged surgery. The low-threshold/medium-threshold/high-threshold ranges were postoperative day 5 (POD5) or none/POD3-4/POD1-2, respectively. Additional VTE chemoprophylaxis considerations that gained consensus were POD1 defined as the morning after surgery regardless of operating finishing time, enoxaparin as the medication of choice, and standardized, rather than weight-based, dose given once per day. CONCLUSIONS: In the first known Delphi study to address anticoagulation/antiplatelet recommendations for elective spine surgery (preoperatively and postoperatively); our Delphi consensus recommendations from 20 spine surgeons achieved consensus on 26/27 items. These results will potentially help standardize the management of preoperative AC/AP medication and VTE chemoprophylaxis after adult elective spine surgery.

Healthcare utilization differences between an apixaban-based and warfarin-based strategy for acute venous thromboembolism in patients with end-stage kidney disease.

INTRODUCTION: Evidence suggests that an apixaban-based strategy to treat acute venous thromboembolism (VTE) in patients with End-Stage Kidney Disease (ESKD) may be safer than a warfarin-based strategy. Apixaban has an additional advantage of not requiring bridging with heparin which often necessitates long hospitalizations for patients with ESKD. We sought to determine if an apixaban-based strategy is associated with less healthcare utilization than a warfarin-based strategy. MATERIAL AND METHODS: We employed a new-user, active-comparator retrospective cohort study using inverse probability of treatment weights (IPTW) to adjust for confounding demographic and clinical variables. Patients with ESKD newly initiated on either apixaban or warfarin for an acute VTE between 2014 and 2018 in the United States Renal Data System were included. Outcomes were presence of index hospitalization, length of index hospitalization, total hospital days, total hospital days excluding index hospitalization, total emergency department (ED) visits that did not result in hospitalization, and total skilled nursing facility days. RESULTS: At six months, patients who received apixaban were less likely to have an index hospitalization, had a shorter index hospitalization (median of 4.0 vs 8.0 days, p < 0.001), and had fewer total hospital days. The IPTW and index year-adjusted incidence rate ratios of total hospital days at one, three, and six months were 0.83 (95 % confidence intervals (CI) 0.79-0.86), 0.84 (95 % CI 0.81-0.88), and 0.88 (95 % CI 0.83-0.92) for apixaban compared to warfarin. CONCLUSION: Among patients with ESKD and VTE, resource utilization for an apixaban-based strategy appears to be lower than for a warfarin-based strategy.

Chronic myeloid leukemia (CML) evolves from Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) with unexpected frequency.

Myeloproliferative neoplasms (MPN) are chronic clonal disorders characterized by overproduction of myeloid-lineage blood cells and potential risk of evolution to acute myeloid leukemia (AML). Chronic myeloid leukemia (CML) is distinct from other MPNs in that its pathophysiology stems from the BCR-ABL fusion protein of the Philadelphia chromosome (Ph +). Though there are known cases of Ph- and Ph + MPNs coexisting in a single patient, overall prevalence has never been quantified in a prospective cohort. Here, we review our center's MPN registry, which shows 0.6% of Ph- MPN patients later developed CML. This development occurred no less than 10 and up to 36 years after Ph- MPN diagnosis. This rate of chronic transformation exceeds what is expected, as the incidence of CML in the United States is 2 per 100,000 people-years. The probability of this CML case rate in an average-risk population is less than 0.001%, suggesting there are shared risk factors between Ph- and Ph + MPNs. We speculate that these risk factors may include exposures, genetic predispositions, or be inherent to disease biology. Abrupt-onset leukocytosis heralded post-MPN CML in all cases here and suggests this salient clinical feature should trigger hematologists to consider this diagnosis and perform appropriate testing.

The Impact of an Antithrombotic Stewardship Program on Heparin-Induced Thrombocytopenia Management.

Background: An antithrombotic stewardship program was implemented to reduce IV DTI use and increase fondaparinux and direct oral anticoagulant (DOAC) use for suspected or confirmed Heparin-induced thrombocytopenia (HIT). Objectives: This study evaluated the impact of an antithrombotic stewardship program on IV DTI utilization in patients with HIT. Methods: A retrospective analysis of adults receiving IV DTIs or fondaparinux from July 2016 to July 2017 (pre-stewardship) and October 2017 to July 2019 (post-stewardship) was conducted. Results: The median duration of IV DTI administration was not significantly different in HIT-negative patients between the pre- and post-stewardship cohorts (1.6 days (25th percentile (p25), 75th percentile (p75): .5, 3.3) vs 1.7 days (p25, p75: .9, 3.9), P = .31). The median duration of IV DTI administration in HIT-positive patients was 9.9 days (p25, p75: 7.6, 21.0) pre-stewardship and 7.3 days (p25, p75: 4.8, 16.5) post-stewardship (P = .18). For HIT-positive patients, the time from HIT diagnosis to discharge was 12.8 days (p25, p75: 8.9, 24.9) and 9.2 days (p25, p75: 4.0, 18.1) in the pre- and post-stewardship cohorts, respectively (P = .07). Fondaparinux and DOAC prescribing rates were 40.7% and 62.2% in the pre- and post-stewardship cohorts, respectively (P = .09). The percentage of patients with no contraindications to IV DTI alternatives receiving these agents increased from 31.2% to 78.6% (P = .01) following stewardship implementation. Conclusions: Intravenous DTI alternative utilization increased significantly after stewardship implementation. Stewardship implementation was associated with a non-statistically significant trend towards decreased IV DTI utilization and decreased length of stay for HIT-positive patients.

Alert-Triggered Patient Education Versus Nurse Feedback for Nonadministered Venous Thromboembolism Prophylaxis Doses: A Cluster-Randomized Controlled Trial.

Background Many hospitalized patients are not administered prescribed doses of pharmacologic venous thromboembolism prophylaxis. Methods and Results In this cluster-randomized controlled trial, all adult non-intensive care units (10 medical, 6 surgical) in 1 academic hospital were randomized to either a real-time, electronic alert-triggered, patient-centered education bundle intervention or nurse feedback intervention to evaluate their effectiveness for reducing nonadministration of venous thromboembolism prophylaxis. Primary outcome was the proportion of nonadministered doses of prescribed pharmacologic prophylaxis. Secondary outcomes were proportions of nonadministered doses stratified by nonadministration reasons (patient refusal, other). To test our primary hypothesis that both interventions would reduce nonadministration, we compared outcomes pre- versus postintervention within each cohort. Secondary hypotheses were tested comparing the effectiveness between cohorts. Of 11 098 patient visits, overall dose nonadministration declined significantly after the interventions (13.4% versus 9.2%; odds ratio [OR], 0.64 [95% CI, 0.57-0.71]). Nonadministration decreased significantly (P<0.001) in both arms: patient-centered education bundle, 12.2% versus 7.4% (OR, 0.56 [95% CI, 0.48-0.66]), and nurse feedback, 14.7% versus 11.2% (OR, 0.72 [95% CI, 0.62-0.84]). Patient refusal decreased significantly in both arms: patient-centered education bundle, 7.3% versus 3.7% (OR, 0.46 [95% CI, 0.37-0.58]), and nurse feedback, 9.5% versus 7.1% (OR, 0.71 [95% CI, 0.59-0.86]). No differential effect occurred on medical versus surgical units. The patient-centered education bundle was significantly more effective in reducing all nonadministered (P=0.03) and refused doses (P=0.003) compared with nurse feedback (OR, 1.28 [95% CI, 1.0-1.61]; P=0.03 for interaction). Conclusions Information technology strategies like the alert-triggered, targeted patient-centered education bundle, and nurse-focused audit and feedback can improve venous thromboembolism prophylaxis administration. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03367364.

Safety and effectiveness of apixaban versus warfarin for acute venous thromboembolism in patients with end-stage kidney disease: A national cohort study.

BACKGROUND: Patients with end-stage kidney disease (ESKD) are at significantly increased risk for both thrombosis and bleeding relative to those with normal renal function. The optimal therapy of venous thromboembolism (VTE) in patients with ESKD is unknown. OBJECTIVE: To compare the safety and effectiveness of apixaban relative to warfarin in patients with ESKD and acute VTE. DESIGN, SETTING AND PARTICIPANTS: New-user, active-comparator retrospective United States population-based cohort with inverse probability of treatment weighting, using the United States Renal Data System data from 2014 to 2018. We included adults with ESKD on hemodialysis or peritoneal dialysis who were newly initiated on apixaban or warfarin for an acute VTE. MAIN OUTCOME AND MEASURES: The coprimary outcomes were major bleeding, recurrent VTE, and all-cause mortality within 6 months of anticoagulant initiation. Secondary outcomes were intracranial hemorrhage and gastrointestinal bleeding. The primary analyses were based on intent-to-treat defined by the first drug received and accounted for competing risks of death. Sensitivity analyses included varied follow-up time, as-treated analyses, and dose-specific apixaban subgroups. RESULTS: The apixaban and warfarin cohorts included 2302 and 9263 patients, respectively. Apixaban was associated with a lower risk of major bleeding (hazard ratio [HR] 0.81, 95% confidence interval [CI]: 0.70-0.94), intracranial bleeding (HR 0.69, 95% CI 0.48-0.98), and gastrointestinal bleeding (HR 0.82, 95% CI 0.69-0.96). Recurrent VTE and all-cause mortality were not significantly different between the groups. CONCLUSION: Apixaban was associated with a lower risk of bleeding relative to warfarin when used to treat acute VTE in patients with ESKD on dialysis.

Effectiveness of Healthcare Delivery, Quality, and Safety a Patient Education Bundle on Venous Thromboembolism Prophylaxis Administration by Sex.

INTRODUCTION: Venous thromboembolism (VTE) is a frequent cause of preventable harm among hospitalized patients. Many prescribed prophylaxis doses are not administered despite supporting evidence. We previously demonstrated a patient-centered education bundle improved VTE prophylaxis administration broadly; however, patient-specific factors driving nonadministration are unclear. We examine the effects of the education bundle on missed doses of VTE prophylaxis by sex. METHODS: We performed a post-hoc analysis of a nonrandomized controlled trial to evaluate the differences in missed doses by sex. Pre-intervention and intervention periods for patients admitted to 16 surgical and medical floors between 10/2014-03/2015 (pre-intervention) and 04/2015-12/2015 (intervention) were compared. We examined the conditional odds of (1) overall missed doses, (2) missed doses due to patient refusal, and (3) missed doses for other reasons. RESULTS: Overall, 16,865 patients were included (pre-intervention 6853, intervention 10,012), with 2350 male and 2460 female patients (intervention), and 6373 male and 5682 female patients (control). Any missed dose significantly reduced on the intervention floors among male (odds ratio OR 0.55; 95% confidence interval CI, 0.44-0.70, P < 0.001) and female (OR 0.59; 95% CI, 0.47-0.73, P < 0.001) patients. Similar significant reductions ensued for missed doses due to patient refusal (P < 0.001). Overall, there were no sex-specific differences (P-interaction >0.05). CONCLUSIONS: Our intervention increased VTE prophylaxis administration for both female and male patients, driven by decreased patient refusal. Patient education should be applicable to a wide range of patient demographics representative of the target group. To improve future interventions, quality improvement efforts should be evaluated based on patient demographics and drivers of differences in care.

Thromboprophylaxis in people hospitalized with COVID-19: Assessing intermediate or standard doses in a retrospective cohort study.

Background and Objectives: Current clinical guidelines recommend thromboprophylaxis for adults hospitalized with coronavirus disease 2019 (COVID-19), yet it is unknown whether higher doses of thromboprophylaxis offer benefits beyond standard doses. Methods: We studied electronic health records from 50 091 adults hospitalized with COVID-19 in the United States between February 2020 and February 2021. We compared standard (enoxaparin 30 or 40 mg/day, fondaparinux 2.5 mg, or heparin 5000 units twice or thrice per day) versus intermediate (enoxaparin 30 or 40 mg twice daily, or up to 1.2 mg/kg of body weight daily, heparin 7500 units thrice per day or heparin 10 000 units twice or thrice per day) thromboprophylaxis. We separately examined risk of escalation to therapeutic anticoagulation, severe disease (first occurrence of high-flow nasal cannula, noninvasive positive pressure ventilation or invasive mechanical ventilation), and death. To summarize risk, we present hazard ratios (HRs) with 95% confidence intervals (CIs) using adjusted time-dependent Cox proportional hazards regression models. Results: People whose first dose was high intensity were younger, more often obese, and had greater oxygen support requirements. Intermediate dose thromboprophylaxis was associated with increased risk of therapeutic anticoagulation (HR, 3.39; 95% CI, 3.22-3.57), severe disease (HR, 1.22; 95% CI, 1.17-1.28), and death (HR, 1.37; 95% CI, 1.21-1.55). Increased risks associated with intermediate-dose thromboprophylaxis persisted in subgroup and sensitivity analyses varying populations and definitions of exposures, outcomes, and covariates. Conclusions: Our findings do not support routine use of intermediate-dose thromboprophylaxis to prevent clinical worsening, severe disease, or death among adults hospitalized with COVID-19.

Update on Guidelines for the Prevention of Cancer-Associated Thrombosis.

Patients with cancer are at high risk of developing arterial and venous thromboembolism (VTE). They constitute 15% to 20% of the patients diagnosed with VTE. Depending on the type of tumor, cancer therapy, and presence of other risk factors, 1% to 25% of patients with cancer will develop thrombosis. The decision to start patients with cancer on primary thromboprophylaxis depends on patient preference, balancing risk of bleeding versus risk of thrombosis, cost, and adequate organ function. Currently, guidelines recommend against the use of routine primary thromboprophylaxis in unselected ambulatory patients with cancer. Validated risk assessment models can accurately identify patients at highest risk for cancer-associated thrombosis (CAT). This review summarizes the recently updated NCCN Guidelines for CAT primary prophylaxis, with a primarily focus on VTE prevention. Two main clinical questions that providers commonly encounter will also be addressed: which patients with cancer should receive primary thromboprophylaxis (both surgical and medical oncology patients) and how to safely choose between different anticoagulation agents.

Enoxaparin Thromboprophylaxis in Children Hospitalized for COVID-19: A Phase 2 Trial.

BACKGROUND: Evidence regarding the safety and efficacy of anticoagulant thromboprophylaxis among pediatric patients hospitalized for coronavirus disease 2019 (COVID-19) is limited. We sought to evaluate safety, dose-finding, and preliminary efficacy of twice-daily enoxaparin as primary thromboprophylaxis among children hospitalized for symptomatic COVID-19, including primary respiratory infection and multisystem inflammatory syndrome in children (MISC). METHODS: We performed a phase 2, multicenter, prospective, open-label, single-arm clinical trial of twice-daily enoxaparin (initial dose: 0.5mg/kg per dose; max: 60mg; target anti-Xa activity: 0.20-0.49IU/mL) as primary thromboprophylaxis for children <18 years of age hospitalized for symptomatic COVID-19. Study endpoints included: cumulative incidence of International Society of Thrombosis and Haemostasis-defined clinically relevant bleeding; enoxaparin dose-requirements; and cumulative incidence of venous thromboembolism within 30-days of hospital discharge. Descriptive statistics summarized endpoint estimates that were further evaluated by participant age (±12 years) and clinical presentation. RESULTS: Forty children were enrolled and 38 met analyses criteria. None experienced clinically relevant bleeding. Median (interquartile range) dose to achieve target anti-Xa levels was 0.5 mg/kg (0.48-0.54). Dose-requirement did not differ by age (0.5 [0.46-0.52] mg/kg for age ≥12 years versus 0.52 [0.49-0.55] mg/kg for age <12 years, P = .51) but was greater for participants with MISC (0.52 [0.5-0.61] mg/kg) as compared with primary COVID-19 (0.48 [0.39-0.51] mg/kg, P = .010). Two children (5.3%) developed central-venous catheter-related venous thromboembolism. No serious adverse events were related to trial intervention. CONCLUSIONS: Among children hospitalized for COVID-19, thromboprophylaxis with twice-daily enoxaparin appears safe and warrants further investigation to assess efficacy.

The APB study: apixaban pharmacokinetics in bariatric patients before to 1 year after vertical sleeve gastrectomy or Roux-en-Y gastric bypass.

BACKGROUND: The optimal regimen for prevention and treatment of venous thromboembolism in bariatric surgical patients remains controversial. Direct oral anticoagulants are potentially advantageous over other agents, but inadequate evidence exists regarding their effects in bariatric surgical patients. OBJECTIVES: To investigate single-dose pharmacokinetic (PK) and pharmacodynamic (PD) parameters of apixaban when administered to patients undergoing vertical sleeve gastrectomy (VSG) or Roux-en-Y gastric bypass (RYGB) and to determine whether the PK and PD parameters are affected by type of bariatric surgery and weight loss in the immediate and postoperative period up to 12 months. SETTING: University Hospital and A Bariatric Center of Excellence, Baltimore, Maryland. METHODS: Adults with a body mass index ≥35 kg/m2 approved for bariatric surgery were enrolled in a single-center, open-label, nonrandomized, single-dose clinical study (NCT No. 02406885; www. CLINICALTRIALS: gov). Apixaban PK and PD parameters were measured after a single 5 mg dose of the drug was given preoperatively and at 1, 6, and 12 months postoperatively in patients undergoing VSG and RYGB. Change in PK parameters was assessed as maximum concentration, time to maximum concentration, elimination half-life, and area under the concentration-time curve from 0-72 hours and change in PD parameters were assessed by chromogenic factor X activity. RESULTS: Of 33 patients enrolled, 28 (14 VSG, 14 RYGB) completed all visits and were analyzed. Most patients (89%) were female, with a mean age of 43.8 years and a body mass index of 48.7 kg/m2. Area under the concentration-time curve from 0-72 hours increased from baseline to 1 month (1009.1 to 1232.9 ng/mL/hr, P = .002), returned to baseline at 6 months (1000.9 ng/mL/hr, P = .88), and decreased significantly at 12 months (841.8 ng/mL/hr, P = .001). Maximum concentration did not change significantly. Predose factor X activity dropped significantly from 113% preoperatively to 89.8 % at 12 months postoperatively (P < .0001). Three-hour postdose factor X activity was significantly lower at 1, 6, and 12 months postoperatively versus preoperatively. However, the magnitude of the decrease from predose to 3-hour postdose was not significantly altered by surgery. CONCLUSION: The effect of either VSG or RYGB on apixaban PK and PD parameters is minimal. Factor X activity after 5 mg apixaban was lower in postoperative versus preoperative bariatric patients, but this effect appears to be primarily the result of a decrease in factor X activity from bariatric surgery itself and not a postoperative change in apixaban PK and PD parameters. Future studies should investigate the safety, efficacy, and clinical outcomes of apixaban and other direct oral anticoagulants perioperatively and beyond 12 months following bariatric surgery.

Case Series of Thrombosis With Thrombocytopenia Syndrome After COVID-19 Vaccination-United States, December 2020 to August 2021.

BACKGROUND: Thrombosis with thrombocytopenia syndrome (TTS) is a potentially life-threatening condition associated with adenoviral-vectored COVID-19 vaccination. It presents similarly to spontaneous heparin-induced thrombocytopenia. Twelve cases of cerebral venous sinus thrombosis after vaccination with the Ad26.COV2.S COVID-19 vaccine (Janssen/Johnson & Johnson) have previously been described. OBJECTIVE: To describe surveillance data and reporting rates of all reported TTS cases after COVID-19 vaccination in the United States. DESIGN: Case series. SETTING: United States. PATIENTS: Case patients receiving a COVID-19 vaccine from 14 December 2020 through 31 August 2021 with thrombocytopenia and thrombosis (excluding isolated ischemic stroke or myocardial infarction) reported to the Vaccine Adverse Event Reporting System. If thrombosis was only in an extremity vein or pulmonary embolism, a positive enzyme-linked immunosorbent assay for antiplatelet factor 4 antibodies or functional heparin-induced thrombocytopenia platelet test result was required. MEASUREMENTS: Reporting rates (cases per million vaccine doses) and descriptive epidemiology. RESULTS: A total of 57 TTS cases were confirmed after vaccination with Ad26.COV2.S (n = 54) or a messenger RNA (mRNA)-based COVID-19 vaccine (n = 3). Reporting rates for TTS were 3.83 per million vaccine doses (Ad26.COV2.S) and 0.00855 per million vaccine doses (mRNA-based COVID-19 vaccines). The median age of patients with TTS after Ad26.COV2.S vaccination was 44.5 years (range, 18 to 70 years), and 69% of patients were women. Of the TTS cases after mRNA-based COVID-19 vaccination, 2 occurred in men older than 50 years and 1 in a woman aged 50 to 59 years. All cases after Ad26.COV2.S vaccination involved hospitalization, including 36 (67%) with intensive care unit admission. Outcomes of hospitalizations after Ad26.COV2.S vaccination included death (15%), discharge to postacute care (17%), and discharge home (68%). LIMITATIONS: Underreporting and incomplete case follow-up. CONCLUSION: Thrombosis with thrombocytopenia syndrome is a rare but serious adverse event associated with Ad26.COV2.S vaccination. The different demographic characteristics of the 3 cases reported after mRNA-based COVID-19 vaccines and the much lower reporting rate suggest that these cases represent a background rate. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

Optimizing Thromboembolism Prophylaxis for the Contemporary Age of Multiple Myeloma.

Venous thromboembolism (VTE) is a major complication in all patients with cancer. Compared with the general population, patients with multiple myeloma (MM) have a 9-fold increase in VTE risk, likely because of their malignancy, its treatments, and other additional patient-related factors. In MM, thromboembolism events tend to occur within 6 months of treatment initiation, regardless of treatment regimen; however, the use of immunomodulatory agents such as thalidomide or lenalidomide, especially in combination with dexamethasone or multiagent chemotherapy, is known to create a significant risk for VTE. Currently, official recommendations for VTE prophylaxis in MM outlined in various national guidelines or multidisciplinary society panels are based on expert opinion, because data from randomized controlled trials are scarce. Large studies which have mainly focused on the efficacy of thromboprophylaxis in patients with cancer at higher risk for VTE either had a very low representation of patients with MM, or excluded them all together, limiting our ability to draw evidence-based conclusions on how to effectively protect MM population from VTE. In this brief perspective, we highlight some of the greatest challenges that have hampered the field concerning the availability of high-quality clinical trial data for the formulation of best VTE prophylaxis strategies in patients with newly diagnosed MM, as well as the rationale for the latest updates in the NCCN Guidelines on this topic.

Effect of Crizanlizumab, a P-Selectin Inhibitor, in COVID-19: A Placebo-Controlled, Randomized Trial.

COVID-19 is characterized by vascular inflammation and thrombosis, including elevations in P-selectin, a mediator of inflammation released by endothelial cells. We tested the effect of P-selectin inhibition on biomarkers of thrombosis and inflammation in patients with COVID-19. Hospitalized patients with moderate COVID-19 were randomly assigned to receive either placebo or crizanlizumab, a P-selectin inhibitor, in a double-blind fashion. Crizanlizumab reduced P-selectin levels by 89%. Crizanlizumab increased D-dimer levels by 77% and decreased prothrombin fragment. There were no significant differences between crizanlizumab and placebo for clinical endpoints. Crizanlizumab was well tolerated. Crizanlizumab may induce thrombolysis in the setting of COVID-19. (Crizanlizumab for Treating COVID-19 Vasculopathy [CRITICAL]; NCT04435184).