Thromboembolic Events With the Woven Endobridge Device: Incidence, Predictive Factors, and Management.

BACKGROUND AND OBJECTIVES: The Woven EndoBridge (WEB) device has been increasingly used to treat wide-neck aneurysms showing a safe and effective profile, but a relatively high number of thromboembolic events (TEEs) have been reported with such treatment. We aimed to evaluate the incidence and management of TEEs and possible predictive factors related to WEB embolization of ruptured and unruptured intracranial aneurysms. METHODS: A single-center database with consecutive aneurysms treated with a WEB device between July 2012 and May 2022 was reviewed for intraoperative and delayed TEEs. Univariate and multivariable analyses were used to determine factors associated with TEEs. RESULTS: A total of 266 independent aneurysms were treated with WEB devices in 245 patients (mean age 55.78 ± 11.64 years, 169 (63.5%) females, 80 (30%) ruptured). The overall rate of TEEs is 13% (35/266), including 8.7% intraoperative. Symptomatic TEEs with clinical sequelae at a 3-month follow-up are reported to be 2.6% (7/266) with no TEE-related mortality. Both the replacement of a WEB device during the procedure (adjusted odds ratio = 2.61, 95% CI 1.24-5.49; P = .01) and ruptured aneurysms (adjusted odds ratio = 2.74, 95% CI 1.31-5.7; P = .007) were independent predictors of TEEs. A case-by-case management of intraprocedural TEE is also presented; tirofiban was successfully used in most cases of this cohort. CONCLUSION: In this study, we demonstrated that ruptured aneurysms and WEB device replacement during the procedure were independent predictive factors for TEEs. As a result, making the correct choice of WEB is crucial for improving treatment outcomes. Moreover, with proper medical management of TEEs, minimal morbidity and no mortality could be achieved, which reinforces the safety of the technique.

Comparison of thromboembolism outcomes in patients with sickle cell disease prescribed hormonal contraception.

Patients with sickle cell disease (SCD) are at a risk of thromboembolism (TE), and use of hormonal contraception can further increase that risk. This study aims to assess patterns of hormonal contraceptive use and compare risk of contraception-related TE between combined hormonal contraceptives (CHCs) and progestin-only contraceptives (POCs). Patients with SCD aged between 12 and 44 years with a new prescription of a hormonal contraceptive in the Centers for Medicare and Medicaid Services Medicaid Analytic eXtract database (2006-2018) were followed up to 1 year. We identified 7173 new users: 44.6% initiated CHC and 55.4% initiated POC. Combined oral contraceptive pills (OCPs; 36.5%) and progestin-only depot medroxyprogesterone acetate (33.9%) were the most frequently prescribed agents. A total of 1.8% of contraception users had a new diagnosis of TE within 1 year of the first identified contraception prescription. There were no significant differences in TE event rates between CHC and POC users (17.2 and 24.7 events per 1000 person-years, respectively). In patients prescribed OCP, there were no differences in TE event rates based on estrogen dose or progestin generation. Transdermal patch had a 2.4-fold increased risk of TE as compared with that of OCP. Although limited by the retrospective study design and use of administrative claims data, this study found no significant differences in TE rates between new users of CHC and POC in patients with SCD. Careful evaluation of underlying TE risk factors should be considered for each patient with SCD before initiation of hormonal contraception.

Initiation of oral anticoagulation in US older adults newly diagnosed with atrial fibrillation during hospitalization.

BACKGROUND: Atrial fibrillation is a common cause of stroke among older adults and is often first detected during hospitalization, given frequent use of cardiac telemetry. METHODS: In a 20% national sample of Medicare fee-for-service beneficiaries, we identified patients aged 65-or-older newly diagnosed with atrial fibrillation while hospitalized in 2016. Our primary outcome was an oral anticoagulant claim within 7-days of discharge. Multivariable logistic regression analyses assessed relationships between anticoagulation initiation and thromboembolic and bleeding risk scores while controlling for demographics, frailty, comorbidities, and hospitalization characteristics. RESULTS: Among 38,379 older adults newly diagnosed with atrial fibrillation while hospitalized (mean age 78.2 [SD 8.4]; 51.8% female; 83.3% white), 36,633 (95.4%) had an indication for anticoagulation and 24.6% (9011) of those initiated an oral anticoagulant following discharge. Higher CHA2 DS2 -VASc score was associated with a small increase in oral anticoagulant initiation (predicted probability 20.5% [95% CI, 18.7%-22.3%] for scores <2 and 24.9% [CI, 24.4%-25.4%] for ≥4). Elevated HAS-BLED score was associated with a small decrease in probability of anticoagulant initiation (25.4% [CI, 24.4%-26.4%] for score <2 and 23.1% [CI, 22.5%-23.8%] for ≥3). Frailty was associated with decreased likelihood of oral anticoagulant initiation (24.7% [CI, 23.2%-26.2%] for non-frail and 18.1% [CI, 16.6%-19.6%] for moderately-severely frail). Anticoagulant initiation varied by primary reason for hospitalization, with predicted probability highest among patients with a primary diagnosis of atrial fibrillation (46.1% [CI, 45.0%-47.3%]) and lowest among those with non-cardiovascular conditions (13.8% [CI, 13.3%-14.3%]) and bleeds (3.6% [CI, 2.4%-4.8%]). CONCLUSIONS: Oral anticoagulant initiation is uncommon among older adults newly diagnosed with atrial fibrillation during hospitalization, even among patients hospitalized primarily for atrial fibrillation and patients with high thromboembolic risk. Clinicians should discuss risks and benefits of oral anticoagulants with all inpatients found to have atrial fibrillation.

Mortality on DOACs Versus on Vitamin K Antagonists in Atrial Fibrillation: Analysis of the Hungarian Health Insurance Fund Database.

PURPOSE: Limited real-world data are available on the survival of patients treated with vitamin K antagonists (VKAs) versus with direct oral anticoagulants (DOACs) for nonvalvular atrial fibrillation (AF). In this nationwide registry, we analyzed the mortality risk of patients with nonvalvular AF taking DOACs versus VKAs, with a special attention to the early treatment period. METHODS: The Hungarian National Health Insurance Fund (NHIF) database was searched to identify patients treated with VKA or DOAC as a thromboembolic prophylaxis for nonvalvular AF between 2011 and 2016. The overall and the early (0-3, 4-6, and 7-12 months) mortality risks with the 2 types of anticoagulation were compared. A total of 144,394 patients with AF treated with either a VKA (n = 129,925) or a DOAC (n = 14,469) were enrolled. FINDINGS: A 28% improvement in 3-year survival with DOAC treatment compared with VKA treatment was shown. Mortality reduction with DOACs was consistent across different subgroups. However, younger patients (30-59 years old) initiated on DOAC therapy had the greatest RRR (53%) in mortality. Furthermore, DOAC treatment also yielded a benefit of greater magnitude (HR = 0.55; 95% CI, 0.40-0.77, P = 0.001) in the lower (0-1) CHA2DS2-VASc score segment and in those with fewer (0-1) bleeding risk factors (HR = 0.50, CI 0.34-0.73, P = 0.001). The RRR in mortality with DOACs was 33% within the first 3 months, and 6% in the second year. IMPLICATIONS: Thromboembolic prophylaxis with DOACs in this study yielded significantly lower mortality compared with VKA treatment in patients with nonvalvular AF. The largest benefit was shown in the early period after treatment initiation, as well as in younger patients, those with a lower CHA2DS2-VASc score, and those with fewer bleeding risk factors.

Is There a Role for Vitamin K Antagonist in the Management of Atrial Fibrillation in 2023?

PURPOSE OF REVIEW: To address the following question: Are vitamin K antagonists (VKA) obsolete as stroke prevention therapy for patients with atrial fibrillation (AF) and thromboembolic risk factors? RECENT FINDINGS: A patient-level meta-analysis of the pivotal phase III randomized trials confirmed the favorable treatment effect of direct oral anticoagulants (DOAC) over VKA in multiple key patient subgroups. Among patients with AF and rheumatic heart disease (85% of whom had mitral stenosis), a randomized trial showed that rivaroxaban was not superior to VKA for stroke prevention. Caution should be exercised when prescribing DOAC for AF-related stroke prevention for patients with elevated body mass indices or history of bariatric surgery, patients with bioprosthetic heart valves, and those who require treatment with drugs that interact with cytochrome P450 and P-glycoprotein. Drug costs associated with DOAC remain considerably higher than VKA, by up to 30-fold. Direct oral anticoagulants are preferable over VKA in the large majority of eligible patients with AF and thromboembolic risk factors. The use of DOAC should be avoided for patients with mechanical heart valves or moderate/severe rheumatic mitral stenosis. Vitamin K antagonist is a reasonable option for patients who are under-represented in randomized trials, when there are significant drug-drug interactions or when patients cannot afford DOAC agents due to their higher costs.

SARS-COV-ATE risk assessment model for arterial thromboembolism in COVID-19.

Patients with SARS-CoV-2 infection are at an increased risk of cardiovascular and thrombotic complications conferring an extremely poor prognosis. COVID-19 infection is known to be an independent risk factor for acute ischemic stroke and myocardial infarction (MI). We developed a risk assessment model (RAM) to stratify hospitalized COVID-19 patients for arterial thromboembolism (ATE). This multicenter, retrospective study included adult COVID-19 patients admitted between 3/1/2020 and 9/5/2021. Among 3531 patients from the training cohort, 15.5% developed acute in-hospital ATE, including stroke, MI, and other ATE, compared to 13.4% in the validation cohort. The 16-item final score was named SARS-COV-ATE (Sex: male = 1, Age [40-59 = 2, > 60 = 4], Race: non-African American = 1, Smoking = 1 and Systolic blood pressure elevation = 1, Creatinine elevation = 1; Over the range: leukocytes/lactate dehydrogenase/interleukin-6, B-type natriuretic peptide = 1, Vascular disease (cardiovascular/cerebrovascular = 1), Aspartate aminotransferase = 1, Troponin-I [> 0.04 ng/mL = 1, troponin-I > 0.09 ng/mL = 3], Electrolytes derangement [magnesium/potassium = 1]). RAM had a good discrimination (training AUC 0.777, 0.756-0.797; validation AUC 0.766, 0.741-0.790). The validation cohort was stratified as low-risk (score 0-8), intermediate-risk (score 9-13), and high-risk groups (score ≥ 14), with the incidence of ATE 2.4%, 12.8%, and 33.8%, respectively. Our novel prediction model based on 16 standardized, commonly available parameters showed good performance in identifying COVID-19 patients at risk for ATE on admission.

The Economic Burden of Thromboembolic Events Among Patients with Immune-Mediated Diseases.

INTRODUCTION: Thromboembolic events (TEs) are associated with considerable costs. However, there is a paucity of evidence quantifying the economic burden associated with TEs among patients with immune-mediated diseases (IMDs). METHODS: This retrospective cohort study used the IBM MarketScan® Commercial and Medicare Supplemental Claims databases (2014-2018). Commercially insured adults with IMDs were classified into two cohorts based on diagnosis of TEs (deep vein thrombosis, pulmonary embolism, ischemic stroke, myocardial infarction). Patients in the TE cohort were matched on type of IMD, age, sex, and year of diagnosis to patients in the no TE cohort. In the TE cohort, the index date was the date of first TE following first IMD diagnosis. In the no TE cohort, the index date was assigned so the duration from first IMD diagnosis to index date matched the duration for the corresponding patient in the TE cohort. All-cause total healthcare costs were compared between cohorts in the 30-day and 1-year periods following the index date (inclusive). Unadjusted comparisons were conducted using Wilcoxon signed-rank tests. Adjusted results were estimated using generalized estimating equations with robust sandwich estimator. RESULTS: Overall, 9681 matched patients were included in each cohort (mean age 61.1 years; 63.7% female). The TE cohort had higher proportions of comorbidities than the no TE cohort (Charlson Comorbidity Index [1.5 vs. 0.9]; p < 0.0001). Adjusted all-cause total healthcare costs were significantly greater in the TE cohort versus no TE cohort in the 30-day and 1-year periods following the index date (cost difference: 30-day, $17,574; 1-year, $36,459; both p < 0.0001) and were driven by inpatient costs (cost difference: 30-day, $14,864; 1-year, $23,360; both p < 0.0001). TE-related healthcare costs were $15,955 and $20,239 in the 30-day and 1-year periods, respectively. CONCLUSION: Among patients with IMDs, TEs are associated with substantial economic burden within 30-days and 1-year following the event.

Risk of Thromboembolic Events and Associated Healthcare Costs in Patients with Inflammatory Bowel Disease.

INTRODUCTION: Inflammatory bowel disease (IBD) is associated with greater risk of thromboembolic events (TEs) due to the link between systemic inflammation and hypercoagulability. This study assessed the rates of TEs among patients with IBD versus patients without immune-mediated disease (IMD) and the cost of TEs among patients with IBD in the United States. METHODS: This study used the IBM MarketScan® Commercial and Medicare Supplemental Databases (2014-2018). To assess the incremental rates of TEs (deep vein thrombosis [DVT], pulmonary embolism [PE], ischemic stroke [IS], myocardial infarction [MI]), patients with IBD were matched to patients without IMD. Unadjusted and adjusted incidence rate ratios (IRRs) of TEs were used to compare cohorts. To assess the cost of TEs, patients with IBD with TEs were matched to patients with IBD without TEs. Costs were assessed 30 days and 1 year post index date. RESULTS: There were 34,687 matched pairs included in the rates of TE analyses. Compared to patients without IMD, patients with IBD had greater rates of DVT (adjusted IRR [95% confidence interval] 2.44 [2.00, 2.99]; p < 0.01) and PE (1.90 [1.42, 2.54]; p < 0.01). Increased rates were not observed for IS and MI. There were 1885 matched pairs included in the cost of TE analyses. Patients with IBD with TEs incurred greater healthcare costs over 30 days and 1 year versus patients without TEs (adjusted total cost difference: 30 days $20,784; 1 year $44,630; p < 0.01 for both). CONCLUSIONS: Patients with IBD experienced greater rates of DVT and PE compared to patients without IMD; this elevated risk was associated with a substantial economic burden.

Risk assessment and prognostic analysis of patients with splenic infarction in emergency department: a multicenter retrospective study.

Splenic infarction is a thromboembolic disease that is frequently missed in acute settings. Previous reviews were rarely presented from a clinical perspective. We aimed to evaluate the clinical characteristics, risk factors with diagnostic value, and prognostic factors using large cohort data and a matched case-control study method. A retrospective medical record review of six hospitals in Taiwan from January 1, 2005, to August 31, 2020, was conducted. All patients who underwent contrast CT with confirmed the diagnosis of splenic infarction were included. Their characteristics were presented and compared to a matched control group with similar presenting characteristics. Prognostic factors were also analyzed. A total of 130 cases were included, two-thirds of whom presented with abdominal pain. Atrial fibrillation was the most common associated predisposing condition, followed by hematologic disease. A higher proportion of tachycardia, positive qSOFA score, history of hypertension or atrial fibrillation, leukocytosis, and thrombocytopenia were found in splenic infarction patients compared to their counterparts. An underlying etiology of infective endocarditis was associated with a higher proportion of ICU admission. Splenic infarction patients often presented with left upper abdominal pain and tachycardia. A history of hypertension, atrial fibrillation, a laboratory result of leukocytosis or thrombocytopenia may provide a clue for clinicians to include splenic infarction in the differential list. Among the patients diagnosed with splenic infarction, those with an underlying etiology of infectious endocarditis may be prone to deterioration or ICU admission.

How to handle the delayed or missed dose of rivaroxaban in patients with non-valvular atrial fibrillation: model-informed remedial dosing.

BACKGROUND: Rivaroxaban is an oral anticoagulant widely used for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). During long-term anticoagulant therapy, delayed or missed doses are common. This study aimed to explore appropriate remedial dosing regimens for non-adherent rivaroxaban-treated patients. METHODS: Monte Carlo simulation based on a previously established rivaroxaban population pharmacokinetic/pharmacodynamic (PK/PD) model for patients with NVAF was employed to design remedial dosing regimens. The proposed regimens were compared with remedial strategies in the European Heart Rhythm Association (EHRA) guide by assessing deviation time in terms of drug concentration, factor Xa activity, and prothrombin time. RESULTS: The proposed remedial dosing regimens were dependent on delay duration. The missed dose should be taken immediately when the delay does not exceed 6 h; a half dose is advisable when the delay is between 6 and 20 h. A missed dose should be skipped if less than 4 h remains before the next dose. The proposed regimens resulted in shorter deviation time than that of the EHRA guide. CONCLUSION: PK/PD modeling and simulation provide valid evidence on the remedial dosing regimen of rivaroxaban, which could help to minimize the risk of bleeding and thromboembolism.

Assessment of Incidence and Factors Associated With Severe Maternal Morbidity After Delivery Discharge Among Women in the US.

Importance: Previous efforts to examine severe maternal morbidity (SMM) in the US have focused on delivery hospitalizations. Little is known about de novo SMM that occurs after delivery discharge. Objective: To investigate the incidence, timing, factors, and maternal characteristics associated with de novo SMM after delivery discharge among women in the US. Design, Setting, and Participants: In this retrospective cohort study, data from the IBM MarketScan Multi-State Medicaid database and the IBM MarketScan Commercial Claims and Encounters database were used to construct a sample of women aged 15 to 44 years who delivered between January 1, 2010, and September 30, 2014. Severe maternal morbidity was reported by the timing of diagnosis, and the associated maternal characteristics were examined. Women in the Medicaid and commercial insurance sample were classified into 3 distinct outcome groups: (1) those without any SMM during the delivery hospitalization and the postdelivery period (reference group), (2) those who exhibited at least 1 factor associated with SMM during the delivery hospitalization, and (3) those who exhibited any factor associated with de novo SMM after delivery discharge (defined as SMM that was first diagnosed in the inpatient setting during the 6 weeks [or 42 days] after discharge from the delivery hospitalization, conditional on no factor associated with SMM being identified during delivery). Data were analyzed from February to July 2020. Exposures: Timing of SMM diagnosis. Main Outcomes and Measures: Women with SMM were identified using diagnosis and procedure codes from the International Classification of Diseases, Ninth Revision, Clinical Modification for the 21 factors associated with SMM that were developed by the Centers for Disease Control and Prevention. Results: A total of 2 667 325 women in the US with delivery hospitalizations between 2010 and 2014 were identified; of those, 809 377 women (30.3%) had Medicaid insurance (30.3%; mean [SD] age, 25.6 [5.5] years; 51.1% White), and 1 857 948 women (69.7%; mean [SD] age, 30.6 [5.4] years; 36.4% from the southern region of the US) had commercial insurance. Among those with Medicaid insurance, 17 584 women (2.2%) experienced SMM during the delivery hospitalization, and 3265 women (0.4%) experienced de novo SMM after delivery discharge. Among those with commercial insurance, 32 079 women (1.7%) experienced SMM during the delivery hospitalization, and 5275 women (0.3%) experienced de novo SMM after hospital discharge. A total of 5275 SMM cases (14.1%) and 3265 SMM cases (15.7%) among women with commercial and Medicaid insurance, respectively, developed de novo within 6 weeks after hospital discharge; of those, 3993 cases (75.7%) in the commercial insurance cohort and 2399 cases (73.5%) in the Medicaid cohort were identified in the first 2 weeks after discharge. The most common factors associated with SMM varied based on the timing of diagnosis. In the Medicaid population, non-Hispanic Black women (adjusted odds ratio [aOR], 1.53; 95% CI, 1.48-1.58), Hispanic women (aOR, 1.46; 95% CI, 1.37-1.57), and women of other races or ethnicities (aOR, 1.40; 95% CI, 1.33-1.47) had higher rates of SMM during delivery hospitalization than non-Hispanic White women; however, only the disparity between Black and White women (aOR, 1.69; 95% CI, 1.57-1.81) persisted into the postdischarge period. Conclusions and Relevance: In this study, 15.7% of SMM cases in the Medicaid cohort and 14.1% of SMM cases in the commercial insurance cohort first occurred after the delivery hospitalization, with notable disparities in factors and maternal characteristics associated with the development of SMM. These findings suggest a need to expand the focus of SMM assessment to the postdelivery discharge period.

Disseminated intravascular coagulation: epidemiology, biomarkers, and management.

Disseminated intravascular coagulation (DIC) is a systemic activation of the coagulation system, which results in microvascular thrombosis and, simultaneously, potentially life-threatening haemorrhage attributed to consumption of platelets and coagulation factors. Underlying conditions, e.g. infection, cancer, or obstetrical complications are responsible for the initiation and propagation of the DIC process. This review provides insights into the epidemiology of DIC and the current understanding of its pathophysiology. It details the use of diagnostic biomarkers, current diagnostic recommendations from international medical societies, and it provides an overview of emerging diagnostic and prognostic biomarkers. Last, it provides guidance on management. It is concluded that timely and accurate diagnosis of DIC and its underlying condition is essential for the prognosis. Treatment should primarily focus on the underlying cause of DIC and supportive treatment should be individualised according to the underlying aetiology, patient's symptoms and laboratory records.

Improved outcomes in CABG patients with atrial fibrillation associated with surgical left atrial appendage exclusion.

BACKGROUND: We sought to determine the impact of left atrial appendage clip exclusion (LAACE) on coronary artery bypass grafting (CABG) outcomes among patients with pre-existing atrial fibrillation (AF). METHODS: From October 1, 2015 to October 1, 2017, 4210 Medicare beneficiaries with pre-existing AF underwent isolated CABG (i.e., without ablation) with (n = 931) or without (n = 3279) LAACE. Inverse probability of treatment weighting was used to evaluate the effect of concomitant LAACE on short- and long-term outcomes after CABG. Long term risks of thromboembolism and mortality were assessed using competing-risk regression and Cox proportional hazard models. RESULTS: Operative mortality, length of stay, and 30-day readmission did not differ between groups. Thromboembolism risk was 26% lower for the CABG + LAACE group compared with isolated CABG over a 2-year time-to-event analysis (sub hazard ratio [sHR] 0.74, 95% confidence interval [CI] 0.54-1.00, p = .049). There were no differences in ischemic stroke rates. All-cause mortality risk was 45% lower for CABG + LAACE during the late follow-up period (91-730 days; HR 0.55, 95% CI 0.32-0.95, p = .031). The late period annual absolute all-cause mortality rate was 3.7% for CABG + LAACE and 6.9% for isolated CABG. There were lower readmission rates (31% vs. 43%, p < .001) and total inpatient days (4.0 days vs. 7.2 days, p < .01.) for the CABG + LAACE during follow-up. Total hospital in and out-patient treatment costs were similar between groups through one year. CONCLUSIONS: Concomitant LAA exclusion via an epicardial closure device is associated with reduced CABG mortality, thromboembolic events, and readmissions in patients with pre-existing atrial fibrillation.

Using big data to retrospectively validate the COMPASS-CAT risk assessment model: considerations on methodology.

External validation is a prerequisite in order for a prediction model to be introduced into clinical practice. Nonetheless, methodologically intact external validation studies are a scarce finding. Utilization of big datasets can help overcome several causes of methodological failure. However, transparent reporting is needed to standardize the methods, assess the risk of bias and synthesize multiple validation studies in order to infer model generalizability. We describe the methodological challenges faced when using multiple big datasets to perform the first retrospective external validation study of the Prospective Comparison of Methods for thromboembolic risk assessment with clinical Perceptions and AwareneSS in real life patients-Cancer Associated Thrombosis (COMPASS-CAT) Risk Assessment Model for predicting venous thromboembolism in patients with cancer. The challenges included choosing the starting point, defining time sensitive variables that serve both as risk factors and outcome variables and using non-research oriented databases to form validated definitions from administrative codes. We also present the structured plan we used so as to overcome those obstacles and reduce bias with the target of producing an external validation study that successfully complies with prediction model reporting guidelines.

A regimen with caplacizumab, immunosuppression, and plasma exchange prevents unfavorable outcomes in immune-mediated TTP.

The anti-von Willebrand factor nanobody caplacizumab was licensed for adults with immune-mediated thrombotic thrombocytopenic purpura (iTTP) based on prospective controlled trials. However, few data are available on postmarketing surveillance. We treated 90 iTTP patients with a compassionate frontline triplet regimen associating therapeutic plasma exchange (TPE), immunosuppression with corticosteroids and rituximab, and caplacizumab. Outcomes were compared with 180 historical patients treated with the standard frontline treatment (TPE and corticosteroids, with rituximab as salvage therapy). The primary outcome was a composite of refractoriness and death within 30 days since diagnosis. Key secondary outcomes were exacerbations, time to platelet count recovery, the number of TPE, and the volume of plasma required to achieve durable remission. The percentage of patients in the triplet regimen with the composite primary outcome was 2.2% vs 12.2% in historical patients (P = .01). One elderly patient in the triplet regimen died of pulmonary embolism. Patients from this cohort experienced less exacerbations (3.4% vs 44%, P < .01); they recovered durable platelet count 1.8 times faster than historical patients (95% confidence interval, 1.41-2.36; P < .01), with fewer TPE sessions and lower plasma volumes (P < .01 both). The number of days in hospital was 41% lower in the triplet regimen than in the historical cohort (13 vs 22 days; P < .01). Caplacizumab-related adverse events occurred in 46 patients (51%), including 13 major or clinically relevant nonmajor hemorrhagic events. Associating caplacizumab to TPE and immunosuppression, by addressing the 3 processes of iTTP pathophysiology, prevents unfavorable outcomes and alleviates the burden of care.

Advances in the management of atrial fibrillation with a special focus on non-pharmacological approaches to prevent thromboembolism: a review of current recommendations.

Atrial fibrillation (AFIB) is the most common heart rhythm abnormality and is associated with significant morbidity and mortality. While the treatment of AFIB involves strategies of rate with or without rhythm control, it is also essential to strategize appropriate therapies to prevent thromboembolic complications arising from AFIB. Previously, anticoagulation was the main treatment option which exposed patients to higher than usual risk of bleeding. However, with the advent of new technology, novel therapeutic options aimed at surgical or percutaneous exclusion or occlusion of the left atrial appendage in preventing thromboembolic complications from AFIB have evolved. This review evaluates recent advances and therapeutic options in treating AFIB with a special focus on both surgical and percutaneous interventions which can reduce and/or eliminate thromboembolic complications of AFIB.

Viscoelastic testing in liver transplantation.

Despite the lack of large randomized clinical studies, viscoelastic tests (VETs) have been a critical armamentarium for hemostatic control in liver transplantation (LT) since the 1960s. Many transplant institutions have adopted VETs in their clinical practice. Several small-size randomized clinical trials on LT patients have suggested that VET-guided hemostatic treatment algorithms have led to decreased indications for and amounts of transfused blood products, especially fresh-frozen plasma, compared to standard laboratory-based hemostatic management. VETs have also been reported to offer insight into the diagnosis and prediction of LT patients' development of hypercoagulability-related morbidity and mortality. There is still a need for VET device-specific hemostatic algorithms in LT, and clinicians must take into account the tendency to underestimate the coagulation capacity of VETs in patients with end-stage liver disease where hemostasis is rebalanced.

Coagulation disorders in Duchenne muscular dystrophy? Results of a registry-based online survey.

Different complications of hemostasis have been reported in patients with Duchenne Muscular Dystrophy (DMD). These comprise an increased rate of bleeding-symptoms during scoliosis surgery but also thromboembolic complications such as pulmonary embolism, cerebral infarction, deep vein thrombosis or cardiac thrombus. For this cross-sectional study, personalized online survey-links were forwarded to 682 registered patients with a genetically confirmed diagnosis of DMD via the German-Austrian DMD patient registry (www.dmd-register.de). The questionnaire enquired data regarding the degree of mobility, disposition to hematoma, epistaxis and gum bleeding, occurrence of peri- and postsurgical hemorrhage, stroke, deep vein thrombosis, and cardiac thromboembolism. Further data on regular medication and age were recorded. Three-hundred-fifty-one DMD-patients completed the questionnaire (response rate of 51.5%). Of those, 164 (46.7%) were ambulatory and 187 (53.3%) were non-ambulatory. Age distribution was homogeneous. Two participants had a history of thromboembolic events (0.6%). Correlations analysis revealed no coherence with the degree of mobility, age or regular medication. A bleeding tendency was reported by 76 participants (21.7%). No significant correlations with age or degree of mobility were found. We found no association with underlying genetic variants. Results of this patient registry-based survey do not indicate a distinct DMD-specific risk for thromboembolic events that exceeds the risk by typical comorbidities of chronic immobility and cardiac insufficiency in advanced stages of the disease. The results of this survey suggest a mild bleeding tendency in this DMD cohort, whereas a selection bias cannot be excluded.

Edoxaban and the Issue of Drug-Drug Interactions: From Pharmacology to Clinical Practice.

Edoxaban, a direct factor Xa inhibitor, is the latest of the non-vitamin K antagonist oral anticoagulants (NOACs). Despite being marketed later than other NOACs, its use is now spreading in current clinical practice, being indicated for both thromboprophylaxis in patients with non-valvular atrial fibrillation (NVAF) and for the treatment and prevention of venous thromboembolism (VTE). In patients with multiple conditions, the contemporary administration of several drugs can cause relevant drug-drug interactions (DDIs), which can affect drugs' pharmacokinetics and pharmacodynamics. Usually, all the NOACs are considered to have significantly fewer DDIs than vitamin K antagonists; notwithstanding, this is actually not true, all of them are affected by DDIs with drugs that can influence the activity (induction or inhibition) of P-glycoprotein (P-gp) and cytochrome P450 3A4, both responsible for the disposition and metabolism of NOACs to a different extent. In this review/expert opinion, we focused on an extensive report of edoxaban DDIs. All the relevant drugs categories have been examined to report on significant DDIs, discussing the impact on edoxaban pharmacokinetics and pharmacodynamics, and the evidence for dose adjustment. Our analysis found that, despite a restrained number of interactions, some strong inhibitors/inducers of P-gp and drug-metabolising enzymes can affect edoxaban concentration, just as it happens with other NOACs, implying the need for a dose adjustment. However, our analysis of edoxaban DDIs suggests that given the small propensity for interactions of this agent, its use represents an acceptable clinical decision. Still, DDIs can be significant in certain clinical situations and a careful evaluation is always needed when prescribing NOACs.

The assessment of patients with the antiphospholipid antibody syndrome: where are we now?

The antiphospholipid antibody syndrome (APS), a chronic autoimmune thrombophilia with an increased mortality and morbidity, has been recognized for more than three decades. Unlike other autoimmune rheumatic conditions such as systemic lupus erythematosus, myositis and Sjögren's syndrome, relatively few attempts have been made to develop activity, damage or disease-specific quality of life indices for APS. In this review of the literature, we consider those attempts that have been made to develop assessment tools for patients with APS, but also reflect upon the nature of the condition, to discuss, in particular, whether an activity index is appropriate for this disease.