Previous Bleeding Events Research Articles

First-Time Users of Advanced Therapies Among Adult Patients with Persistent or Chronic Primary Immune Thrombocytopenia: Patient Characteristics, Treatment Switching Patterns, and Clinical Outcomes

Background Primary immune thrombocytopenia (ITP) is a rare acquired autoimmune disorder characterized by low platelet count, with an overall age/sex-standardized annual incidence of 6.1 per 100,000 persons in the US in 2016. Patients who fail to respond or maintain a response to initial therapy (e.g., corticosteroids, intravenous immunoglobulins), move to advanced therapies with robust evidence such as thrombopoietin receptor agonists (TPO-RAs [eltrombopag/ romiplostim/ avatrombopag]), rituximab, and fostamatinib, as per the international consensus guidelines. Among patients with primary ITP lasting ≥3 months who are first-time users of advanced therapies, there is limited real-world evidence on patient characteristics, treatment patterns, and clinical outcomes. Objectives The key objectives were to assess patient characteristics, treatment patterns, and clinical outcomes of first-time users of advanced therapy in patients with primary ITP lasting ≥3 months. Methods This retrospective, cohort study included patients identified from Optum de-identified Clinformatics ® Data Mart database, aged ≥18 years with primary ITP lasting 3 months or more, who initiated advanced therapy for the first time between October 1, 2015, and August 31, 2020. Patients were required to have ≥365 days of available data prior to index date, without evidence of conditions associated with secondary ITP. Patients were indexed on the date of initiation of advanced therapies. Baseline characteristics, including demographics, comorbidities, use of medication, and bleeding events requiring medical attention (e.g., intracranial bleeding, gastrointestinal bleeding, hematuria) were assessed 365 days prior to index and reported using descriptive statistics. Treatment patterns and rates of bleeding events, thromboembolic events (TEs), bacterial infections, and hospitalizations were assessed during follow-up, which began one-day after index date and until discontinuation of the index therapy. Patients were censored on death, end of data accrual, disenrollment, or switch to another advanced therapy. Outcomes were reported as the number of events per 1000 person-years and time to first event. Results Total 375 patients with primary ITP lasting ≥3 months, who were first-time users of advanced therapies were included, with 51% (n=192) initiating TPO-RAs, 49% (n=182) initiating rituximab, and <1% (n=2) initiating fostamatinib. Mean (SD) age of overall population was 62 (19) years, and 55.7% were female. About 9% of patients were Black, 4% Asian, and 11% Hispanic ( Table 1). In year prior to index date, previous bleeding events were most common clinical symptoms in patients with ITP initiating advanced therapies (any bleeding, 39.7%). Other frequently reported comorbidities were diabetes (28.5%), coronary artery disease (18.9%), and asthma (17.3%); 13.1% of patients had a TE. About 5% patients reported bacterial infections ( Table 1). Patients initiating TPO-RA and those starting rituximab were observed for a median (interquartile range, IQR) duration of 22.2 (14.5-34.9) months and 27.1 (13.5-43.2) months, respectively. Almost 9% of TPO-RAs initiators switched to rituximab (median [IQR] time to switch: 3.2 [1.7-6.9] months), while 23.6% of rituximab initiators switched to TPO-RAs (median [IQR] time to switch: 3.1 [1.7-7.6] months) during follow-up. After initiating advanced therapies, the rates of any bleeding event and TEs were 288 per 1000 person-years (95% CI: 240-336) and 129 per 1000 person-years (95% CI: 99-158), respectively. Mean (SD) time to first bleeding event was 299 (351) days and that of TE was 257 (325) days. Infection rate was 70 per 1000 person-years ( Table 2). In follow-up, 31% of patients had ≥1 ITP-related hospitalization and 38% had an all-cause hospitalization, resulting in rates of 215 [95% CI: 176-255] and 299 [95% CI: 250-349] per 1000 person-years, respectively. Approximately 5% of patients underwent splenectomy (incidence rate: 27 per 1000 person-years [95% CI: 15-40]) with mean (SD) time of 245 (186) days post initiation of advanced ITP therapy ( Table 2). Conclusion This study demonstrated high clinical burden and need for subsequent additional therapies among patients with primary ITP lasting ≥3 months, which is evident from high rates of switching between advanced therapies, bleeding events requiring medical attention, TEs, and ITP-related hospitalizations.

Pretreatment with P2Y12 inhibitors and relationship with clinical outcomes in NSTEMI: Analysis of 2 Argentinian registries

Abstract Introduction Pretreatment with P2Y12 inhibitors has been widely studied in the context of NSTEMI patients, with varying results. General consensus is that this strategy should be avoided, unless a long wait time is expected before angiography can be performed. However, it is unclear whether this strategy is associated with a reduction in clinical outcomes, or an increase in bleeding events. Purpose To analyze frequency of pretreatment in NSTEMI in our medium, and association with clinical outcomes. Methods We analyzed the results of two Argentinian acute coronary syndrome registries from 2017 and 2022. We explored incidence of pretreatment, and drug used. We evaluated first through univariate analysis the relationship between pretreatment use and a clinical composite outcome of in hospital events: Myocardial infarction + Mortality + In stent thrombosis + post MI angina + Stroke/TIA. We also explored the relationship of pretreatment with bleeding events (BARC 2 or higher). We later conducted a logistic regression with other clinical variables: Age, gender, diabetes, previous bleeding events, previous MI, aspirin use, anticoagulation, killip-kimball scale and ejection fraction. Results 1297 patients were included in the analysis, after excluding STEMI patients, patients with current use of P2Y12 inhibitors at time of event, and patients who did not undergo angiography. 75.6% were men, 25.6% diabetic, 27,1% smokers, 70.3% hypertensive, and 23.1% had a previous acute coronary syndrome. Mean age was 55.3 years old. Mean GRACE score was 113,5 and CRUSADE 23,8. 44% of patients recieved pretreatment, mostly with clopidogrel (93.5%). Patients that recieved pretreatment were more frequently hypertensive (73.8% vs 67%, p=0.01) and had a higher incidence of previous MI (27% vs 19%, p=0.002). GRACE score was significantly lower in patients that were pretreated (111,5 vs 115, p=0.04). Pretreatment use was significantly associated with a higher incidence of the composite clinical outcome, occuring in 10.1% of patients pretreated and in 6.9% of patients not pretreated (OR 1.56 (1.06-2.3) p=0.02. Bleeding events were numerically more frequent with pretreatment (8.7% vs 5.9%), though did not reach statistical significance (OR 1.51 (0.99-2.3) p=0.054). In multivariate analysis, after adjusting for multiple clinical variables, pretreatment was no longer associated with a higher incidence of clinical outcomes, though also not with a lower incidence (OR 1.4 (0.89-2.3) p=0.13). Discussion Pretreatment, mostly with clopidogrel, did not show a relationship with either benefit or harm with regard to ischemic and bleeding outcomes in NSTEMI patients.

Risks of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19: nationwide self-controlled cases series and matched cohort study

ObjectiveTo quantify the risk of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19.DesignSelf-controlled case series and matched cohort study.SettingNational registries in Sweden.Participants1 057 174 people who tested positive for SARS-CoV-2 between 1 February 2020 and 25 May 2021 in Sweden, matched on age, sex, and county of residence to 4 076 342 control participants.Main outcomes measuresSelf-controlled case series and conditional Poisson regression were used to determine the incidence rate ratio and risk ratio with corresponding 95% confidence intervals for a first deep vein thrombosis, pulmonary embolism, or bleeding event. In the self-controlled case series, the incidence rate ratios for first time outcomes after covid-19 were determined using set time intervals and the spline model. The risk ratios for first time and all events were determined during days 1-30 after covid-19 or index date using the matched cohort study, and adjusting for potential confounders (comorbidities, cancer, surgery, long term anticoagulation treatment, previous venous thromboembolism, or previous bleeding event).ResultsCompared with the control period, incidence rate ratios were significantly increased 70 days after covid-19 for deep vein thrombosis, 110 days for pulmonary embolism, and 60 days for bleeding. In particular, incidence rate ratios for a first pulmonary embolism were 36.17 (95% confidence interval 31.55 to 41.47) during the first week after covid-19 and 46.40 (40.61 to 53.02) during the second week. Incidence rate ratios during days 1-30 after covid-19 were 5.90 (5.12 to 6.80) for deep vein thrombosis, 31.59 (27.99 to 35.63) for pulmonary embolism, and 2.48 (2.30 to 2.68) for bleeding. Similarly, the risk ratios during days 1-30 after covid-19 were 4.98 (4.96 to 5.01) for deep vein thrombosis, 33.05 (32.8 to 33.3) for pulmonary embolism, and 1.88 (1.71 to 2.07) for bleeding, after adjusting for the effect of potential confounders. The rate ratios were highest in patients with critical covid-19 and highest during the first pandemic wave in Sweden compared with the second and third waves. In the same period, the absolute risk among patients with covid-19 was 0.039% (401 events) for deep vein thrombosis, 0.17% (1761 events) for pulmonary embolism, and 0.101% (1002 events) for bleeding.ConclusionsThe findings of this study suggest that covid-19 is a risk factor for deep vein thrombosis, pulmonary embolism, and bleeding. These results could impact recommendations on diagnostic and prophylactic strategies against venous thromboembolism after covid-19.

The OAC3-PAD Risk Score Predicts Major Bleeding Events one Year after Hospitalisation for Peripheral Artery Disease

There is a paucity of evidence concerning the risk of bleeding after hospitalisation for symptomatic peripheral artery disease (PAD) in everyday clinical practice, as randomised clinical trials commonly exclude patients with heightened risk. The current study aimed to develop a pragmatic risk score that enables prediction of major bleeding during the first year after index discharge. Unselected retrospective data from the second largest insurance fund in Germany, BARMER, were used to identify patients with a first hospitalisation for PAD registered between 1 January 2010 and 31 December 2018. Within a separate training cohort, final predictors were selected using penalised Cox regression (least absolute shrinkage and selection operator with ten fold cross validation) with one year major bleeding requiring hospitalisation as outcome. The risk score was internally validated. Four different risk groups were constructed. A total of 81 930 patients (47.2% female, 72.3 years) underwent hospitalisation for symptomatic PAD. After one year, 1 831 (2.2%) of the patients had a major bleeding event. Independent predictors were previous oral anticoagulation, age over 80, chronic limb threatening ischaemia, congestive heart failure, severe chronic kidney disease, previous bleeding event, anaemia, and dementia. The OAC3-PAD risk score exhibited adequate calibration and discrimination between four risk groups (c= 0.69, 95% confidence interval 0.67 - 0.71) from low risk (1.3%) to high risk (6.4%). A pragmatic risk score was developed to predict the individual major bleeding risk classifying a fifth of the cohort as high risk patients. Individual prediction scores such as the one proposed here may help to inform the risk and benefit of intensified antithrombotic strategies.

Do We Sometimes Turn a Blind Eye To Post-Discharge Bleeding Complications?

Behrendt et al. analysed insurance data from Germany and identified approximately 82 000 patients hospitalised and treated for peripheral artery disease (PAD) between 2010 and 2018.1 It was found that 2.2% of the patients suffered from a major bleeding event within the first year after discharge. The identified independent predictors were previous oral anticoagulation, age > 80, chronic limb threatening ischaemia, congestive heart failure, chronic kidney disease, previous bleeding event, anaemia, and dementia (OAC3-PAD).

Intracranial Hemorrhage in Patients with Anticoagulant Therapy Undergoing Stereotactic Radiosurgery for Brain Metastases: A Bi-Institutional Analysis.

Simple SummaryPatients suffering from cancer are at risk of various comorbidities that may require therapeutic anticoagulant therapy (ACT). Brain metastases (BM) are a common sequela of late-stage cancer and are often non-invasively treated with stereotactic radiosurgery (SRS). Although brain tumors and BM may cause intracranial hemorrhage (ICH), with potentially devastating consequences, the actual risk of bleeding complications for patients receiving ACT while undergoing SRS is mostly unknown. This bi-institutional analysis aimed to assess the incidence of ICH after SRS in patients with ACT. The results showed that ICHs mostly occurred in patients with BM originating from malignant melanomas and in those that showed signs of ICH before SRS treatment. In general, the bleeding events did not cause morbidity or mortality, suggesting the relatively safe use of ACT in patients with small- to medium-sized BM. Nevertheless, further studies are necessary to validate our reported findings.Background: Stereotactic radiosurgery (SRS) is a well-established treatment modality for brain metastases (BM). Given the manifold implications of metastatic cancer on the body, affected patients have an increased risk of comorbidities, such as atrial fibrillation (AF) and venous thromboembolism (VTE), which includes pulmonary embolism (PE) and deep-vein thrombosis (DVT). These may require therapeutic anticoagulant therapy (ACT). Limited data are available on the risk of intracranial hemorrhage (ICH) after SRS for patients with BM who are receiving ACT. This bi-institutional analysis aimed to describe the bleeding risk for this patient subgroup. Methods: Patients with ACT at the time of single-fraction SRS for BM from two institutions were eligible for analysis. The cumulative incidence of ICH with death as a competing event was assessed during follow-up with magnetic resonance imaging or computed tomography. Results: Forty-one patients with 97 BM were included in the analyses. The median follow-up was 8.2 months (range: 1.7–77.5 months). The median and mean BM volumes were 0.47 and 1.19 cubic centimeters, respectively. The most common reasons for ACT were PE (41%), AF (34%), and DVT (7%). The ACT was mostly performed utilizing phenprocoumon (37%), novel oral anticoagulants (32%), or low-molecular-weight heparin (20%). Nine BM from a group of five patients with ICH after SRS were identified: none of them caused neurological or any other deficits. The 6-, 12-, and 18-month cumulative bleeding incidences per metastasis were 2.1%, 12.4%, and 12.4%, respectively. The metastases with previous bleeding events and those originating from malignant melanomas were found to more frequently demonstrate ICH after SRS (p = 0.02, p = 0.01). No surgical or medical intervention was necessary for ICH management, and no observed death was associated with an ICH. Conclusion: Patients receiving an ACT and single-fraction SRS for small- to medium-sized BM did not seem to have a clinically relevant risk of ICH. Previous bleeding and metastases originating from a malignant melanoma may favor bleeding events after SRS. Further studies are needed to validate our reported findings.

Predictive performance of different bleeding risk scores in patients with atrial fibrillation and acute coronary syndrome or undergoing percutaneous coronary intervention

This study aims to evaluate the predictive values of the HAS-BLED, ORBIT, ATRIA, REACH, PARIS, and PRECISE-DAPT scores in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI) who received both anticoagulant and antiplatelet therapy. 930 patients were consecutively recruited and followed up for 1 year. The primary endpoints were BARC class ≥3 bleeding and BARC class ≥2 bleeding. BARC class ≥3 bleeding occurred in 36 patients(3.9%), while BARC class ≥2 bleeding was seen in 134 patients (14.4%). The predictive performance of the HAS-BLED score for BARC class ≥3 bleeding was unsatisfactory (c-statistic = 0.575). The discrimination of the ATRIA, ORBIT, PARIS, and PRECISE-DAPT scores was also low-to-moderate. The REACH score was useless in bleeding risk stratification for this population. Multivariable logistic regression indicated that previous bleeding events and hemoglobin were two independent predictors of BARC class ≥3 bleeding. Compared to the HAS-BLED score, the model constructed by previous bleeding events and hemoglobin displayed a significant improvement in bleeding risk prediction [c-statistics: 0.704 vs. 0.575 (p = .008), NRI = 0.662,IDI = 0.049]. In patients with AF and ACS or undergoing PCI who received anticoagulant+antiplatelet therapy, the HAS-BLED, ORBIT, ATRIA, REACH, PARIS, and PRECISE-DAPT scores displayed only low-to-moderate performance in predicting BARC class≥3 bleeding. Future studies are required to develop more reliable scoring systems for bleeding risk evaluation in this population.

Edoxaban Treatment in routiNe clinical prActice in patients with non-valvular Atrial Fibrillation (ETNA-AF) in Iberia: Baseline data

Introduction and ObjectivesAtrial fibrillation (AF) is the most common form of arrhythmia worldwide and a significant health burden. Edoxaban, a recent novel oral anticoagulant (NOAC), is being investigated in the European real-world ETNA-AF study of patients with non-valvular atrial fibrillation (NVAF). The aim of this study was to characterize the Iberian edoxaban-treated cohort of ETNA-AF at baseline and to compare it with previously retrieved Portuguese data. MethodsPatients with NVAF treated with edoxaban and followed in Portuguese and Spanish centers were consecutively enrolled between June 2017 and January 2018. Only patients with a previous clinical decision to receive edoxaban were included. Patients’ baseline demographic and clinical parameters, medical history, and AF-related characteristics were retrieved. ResultsA total of 892 NVAF patients, with a mean age of 73.9 years, were included, 75.3% of whom received high-dose (60 mg) and 24.7% low-dose (30 mg) edoxaban. Most patients (55.9%) were male. Of the patients receiving 30 mg and 60 mg edoxaban, 55.9% and 37.9%, respectively, had an estimated CHA2DS2-VASc score ≥4. Previous bleeding event rates were low, with a predominance of clinically relevant non-major bleeding (1.9%). Most patients (47.5%) with NVAF had paroxysmal AF, followed by 26.4% with permanent AF. Median overall CHA2DS2-VASc score was 3.0 and median HAS-BLED score was 2.0. Previous treatments mostly included vitamin K antagonists (35.7%). A considerably higher proportion of patients on low-dose edoxaban required dose adjustments (71.4% vs. 8.6%). Overall adherence to label dosing recommendations was 86.5%. ConclusionsThis study provides valuable data on disease and patient profiles and will provide valuable insights into disease management and progression, as well as the safety, effectiveness, and patterns of cardiovascular events associated with edoxaban.

Bleeding of unknown cause and unclassified bleeding disorders; diagnosis, pathophysiology and management.

Bleeding of unknown cause (BUC), also known as unclassified bleeding disorders (UBD), has been defined as a clear bleeding tendency in the presence of normal haemostatic tests. There are challenges in the diagnosis and management of these patients. BUC/UBD encompasses a heterogenous group of disorders which may include undiagnosed rare monogenic diseases, polygenic reasons for bleeding; and patients without a clear bleeding disorder but with a previous bleeding event. Nevertheless, these patients may have heavy menstrual bleeding or be at risk of bleeding when undergoing surgical procedures, or childbirth; optimizing haemostasis and establishing a mode of inheritance is important to minimize morbidity. The bleeding score has been used to clinically assess and describe these patients, but its value remains uncertain. In addition, accurate distinction between normal and pathological bleeding remains difficult. Several studies have investigated cohorts of these patients using research haemostasis tests, including thrombin generation and fibrinolytic assays, yet no clear characteristics have consistently emerged. Thus far, detailed genetic analysis of these patients has not been fruitful in unravelling the cause of bleeding. There is a need for standardization of diagnosis and management guidelines for these patients. This review gives an overview of this field with some suggestions for future research.

Oral anticoagulant therapy in atrial fibrillation older patients with previous bleeding.

Oral anticoagulant therapy (OAT) with direct oral anticoagulant (DOACs) is the established treatment to reduce thromboembolic risk in patients with atrial fibrillation (AF). Bleeding risk scores are useful to identify and correct factors associated with bleeding risk in AF patients on OAT. However, the clinical scenario is more complex in patients with previous bleeding event, and the decision about whether and when starting or re-starting OAT in these patients remains a contentious issue. Major bleeding is associated with a subsequent increase in both short- and long-term mortality, and even minimal bleeding may have prognostic importance because it frequently leads to disruption of antithrombotic therapy. There is an unmet need for guidance on how to manage antithrombotic therapy after bleeding has occurred. While waiting for observational and randomized data to accrue, this paper offers a perspective on managing antithrombotic therapy after bleeding in older patients with AF.

P5591Efficacy and safety of lower dose slow infusion of t-PA for intermediate-risk pulmonary embolism patients with risk for bleeding

Abstract Background Current guidelines do not recommend thrombolytic therapy for the treatment of intermediate-risk pulmonary embolism (PE) because of the tight balance between the benefit and safety with classic protocols. Aim The aim of this study was to compare the new thrombolytic protocol with lower-dose slow-infusion (LDSI) of tissue plasminogen activator (tPA) to classic 2-hours tPA infusion protocol or no-reperfusion in patients with intermediate-high risk PE with higher bleeding risk regarding 30-day efficacy and safety. Methods Among 849 patients with PE from the Serbian multicenter registry, 469 patients who fulfilled criteria for intermediate-risk PE were involved in the study. After propensity score matching 425 patients [263 (61.9%), 99 (23.3%) and 63 (14.8%) were treated with no-reperfusion, classic tPA protocol (100 mg for 2 hours) and LDSI of tPA (2–5 mg/hour either vie local catheter or systemic venous infusion with dose range of 25–50 mg)]. The basic characteristics of patients were well balanced between groups except that patients treated with LDSI of tPA had significantly higher usage of drugs which can be associated to bleeding and more previous bleeding events. Thirty day all-cause and PE-caused mortality and 7-day major bleeding were the main efficacy and safety end-points, respectively. Results All-cause and PE-cause 30-day mortality were 8.7% vs 16.2% vs 1.6% (Log rank p=0.007) and 4.5% vs 11.0% vs 0.0% (Log rank p=0.008) in patients with no-reperfusion, classic tPA protocol and LDSI of tPA protocol, respectively. Major bleeding at 7 days were 2.7% vs 8.1% vs 14.3% (Log rank p=0.001) in patients with no-reperfusion, classic tPA protocol and LDSI of tPA protocol, respectively. There was one fatal intracranial bleeding during catheter infusion of tPA. Conclusion Lower-dose slow-infusion of tPA protocol decreased significantly all-cause and PE-cause mortality at 30-day at the cost of excess of non-fatal major bleeding at 7-day in patients with intermediate-risk PE and higher risk for bleeding. Acknowledgement/Funding None

Left atrial appendage closure in atrial fibrillation patients with prior major bleeding or ineligible for oral anticoagulation.

AimsOral anticoagulation (OAC) reduces the ischaemic stroke risk in patients with atrial fibrillation (AF), but in turn leads to an increased risk of adverse bleeding events. Alternatively, left atrial appendage closure (LAAC) using a mechanical device might overcome these bleeding complications. However, evidence regarding LAAC in patients at high bleeding risk is scarce. This study evaluates the clinical features of AF patients with previous bleeding that underwent LAAC.MethodsIn this retrospective cohort study patients with previous major bleeding or a bleeding predisposition scheduled for transcatheter LAAC were included. The frequency and type of previous bleeding events and prevalence of bleeding and ischaemic stroke during follow-up were evaluated.ResultsA total of 73 patients (58% male, age 72.1 ± 7.2 years; CHA2DS2-VASc 4.5 [3.0–5.0]; HAS-BLED 4.0 [3.0–4.0]; 46% paroxysmal AF) were included. Previous bleeding occurred from intracranial (n = 50, 69%), gastro-intestinal (n = 13, 18%) or multiple (n = 16, 22%) foci. After OAC discontinuation due to bleeding, 19% suffered subsequent stroke. LAAC was successful in 96% of patients. During a median of almost 3 years’ follow-up recurrent major bleeding occurred in 4 patients (5.5%) despite OAC discontinuation in 93.2%. A total of 6 ischaemic strokes were observed, resulting in an annualised stroke rate of 2.9% compared to a calculated expected stroke rate of 6.7%.ConclusionsPercutaneous LAAC may provide an alternative strategy to long-term OAC therapy in AF patients with a high bleeding risk. During follow-up, both ischaemic stroke and recurrent bleeding rates were lower than expected based on the CHA2DS2-VASc and HAS-BLED scores respectively.

Real-practice thromboprophylaxis in atrial fibrillation.

This retrospective observational study was based on databases of the Local Health Authority of Treviso, Italy. It evaluated the prevalence and the effectiveness of oral anticoagulation treatment (OAT) for the management of nonvalvular atrial fibrillation (NVAF) in everyday clinical practice. Out of 6,138 NVAF patients, only 3,024 received vitamin K antagonist (VKA). Potential barriers decreasing the probability of being treated with VKA were female sex, older age, antiplatelet treatment and history of bleeding. In addition, VKA-treatment was not in line with current ESC and AIAC guidelines, since the patients at high or low risk of stroke were under- or over-treated, resp. Among VKAtreated patients, 73 % of subjects were not at target with anticoagulation. OAT resulted to be effective in reducing stroke risk. However, stroke events were significantly influenced also by previous stroke or transient ischemic attack (hazard ratio, HR = 2.99, p < 0.001) and by previous bleeding events (HR = 1.60, p < 0.001).

Antithrombotic therapy and platelet transfusions in hematologic malignancy patients presenting chemotherapy-induced thrombocytopenia: a French survey.

Patients with hematologic malignancies are at high risk for both thrombosis and bleeding. During the prolonged periods of thrombocytopenia experienced by patients who are receiving intensive chemotherapy, clinicians often hesitate to prescribe any protection against thrombosis. In case of anticoagulant prescription, it is the prescribers' responsibility to weigh risks and benefits for each patient. Current guidelines exist but do not take into account types of thrombosis, patients' comorbidities, or previous bleeding events. We proposed to gain insight into hematologists' beliefs about antithrombotic prescription in hematologic malignancy patients, to design future clinical trials. Therefore, we conducted a survey in France to evaluate the practices among a panel of hematologists. We found that more than 92% of the respondents prescribed therapeutic anticoagulation in case of pulmonary embolism or deep venous thrombosis. In the case of therapeutic anticoagulation, only 64% of the physicians reconsidered treatment under a platelet threshold of 50 ×109 /L. None of the respondents decided to renounce treatment, nor to discontinue it because of thrombocytopenia, except in distal venous thrombosis or superficial vein thrombosis. One-fifth of clinicians proposed the insertion of a vena cava filter. As observed in the United States and Canada, we noticed discrepancies between recommendations and current practices in France. This highlights the urgent need to conduct studies to evaluate both efficacy and safety of antithrombotics in patients with hematologic cancer and thrombocytopenia.

Anemia is associated with bleeding and mortality, but not stroke, in patients with atrial fibrillation: Insights from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial

Patients with atrial fibrillation (AF) are prone to cardiovascular events and anticoagulation-related bleeding complications. We hypothesized that patients with anemia are at increased risk for these outcomes. We performed a post hoc analysis of the ARISTOTLE trial, which included >18,000 patients with AF randomized to warfarin (target international normalized ratio, 2.0-3.0) or apixaban 5 mg twice daily. Multivariable Cox regression analysis was used to determine if anemia (defined as hemoglobin <13.0 in men and <12.0 g/dL in women) was associated with future stroke, major bleeding, or mortality. Anemia was present at baseline in 12.6% of the ARISTOTLE population. Patients with anemia were older, had higher mean CHADS2 and HAS-BLED scores, and were more likely to have experienced previous bleeding events. Anemia was associated with major bleeding (adjusted hazard ratio [HR], 1.92; 95% CI, 1.62-2.28; P<.0001) and all-cause mortality (adjusted HR, 1.68; 95% CI, 1.46-1.93; P<.0001) but not stroke or systemic embolism (adjusted HR, 0.92; 95% CI, 0.70-1.21). The benefits of apixaban compared with warfarin on the rates of stroke, mortality, and bleeding events were consistent in patients with and without anemia. Chronic anemia is associated with a higher incidence of bleeding complications and mortality, but not of stroke, in anticoagulated patients with AF. Apixaban is an attractive anticoagulant for stroke prevention in patients with AF with or without anemia.

A score to predict the risk of emergency caesarean delivery in women with antepartum bleeding and placenta praevia

ObjectiveTo identify antenatal events associated with emergency caesarean sections in women presenting with antepartum bleeding and placenta praevia and to establish a score to predict the risk of emergency caesarean after a first bleeding episode has resolved. Study designThis retrospective multicentre study included 250 women presenting with antepartum bleeding and placenta praevia from 20 weeks of gestation until term in three maternity units. The score was constructed from data from 163 women after identification of antenatal risk factors associated with emergency caesareans for profuse bleeding due to placenta praevia. It was validated on a second independent cohort of 87 women. ResultsThree variables were significantly associated with emergency caesareans: major or complete praevia, defined as complete or partial praevia (OR=33.15 (95% CI 4.3–257); p=0.001), occurrence of 3 or more episodes of antepartum of uterine bleeding (OR=2.53 (95% CI 1.1–5.86); p=0.03), and a first (sentinel) bleeding episode before 29 weeks of gestation (OR=2.64 (95% CI 1.17–5.98); p=0.02). A fourth variable, moderate or severe antepartum uterine bleeding, was significantly associated with emergency caesareans in the univariate but not the multivariate analysis (p=0.006). These four variables were incorporated into a weighted scoring system that included major praevia (4 points), three or more episodes of antepartum bleeding (3), first bleeding episode before 29 weeks of gestation (3), and bleeding episode estimated as moderate or severe (1). A score ≥6/11 had a sensitivity of 83% and a specificity of 65% for predicting an emergency caesarean in the score development group and 95% and 62% in the validation group. ConclusionA scoring system for placenta praevia with previous bleeding events, based on intensity, gestational age at sentinel bleed (before 29 weeks), number of bleeding episodes (≥3) and type of praevia (major) might be helpful to guide obstetric management and especially to determine the need for admission.

Risk factors for small bowel bleeding in chronic nonsteroidal anti-inflammatory drug users.

The incidence of nonsteroidal anti-inflammatory drugs (NSAIDs)-induced enteropathy is currently increasing. However, the predictors of small bowel bleeding (SBB) associated with NSAIDs are unknown. This study aimed to assess the risk factors of SBB in chronic NSAIDs users. We retrospectively compared the medical records of 147 patients receiving NSAIDs in a tertiary-care setting (31 with SBB and 116 without previous bleeding events) and analyzed the predictors of SBB. In total, 31 patients underwent video capsule endoscopy to detect SBB, 74.2% of whom showed the evidence of SBB. Non-invasive treatment was performed in 90.3% of the patients. Multivariate logistic regression analysis revealed that the presence of coronary artery disease [adjusted odds ratio (aOR) 12.43, 95% confidence interval (CI) 1.19-130.34, P = 0.04], use of thienopyridine (aOR 16.93, 95% CI 3.78-75.72, P < 0.001) and prior use of rebamipide (aOR 0.31, 95% CI 0.12-0.82, P = 0.02) were independently associated with SBB in NSAIDs users. Coronary artery disease and co-use of thienopyridine were associated with SBB in NSAIDs users. The patients with coronary artery disease co-using thienopyridine need to be monitored for the occurrence of SBB when they were prescribed with NSAIDs.

GW24-e1871 A survey of anticoagulation therapy of nonvalvular atrial fibrillation in elderly patients

ObjectivesTo investigate the current status of antithrombotic treatment in elderly patients with nonvalvular atrial fibrillation. The general feature were recorded and risk factors of stroke thromboembolism were estimated in order...

Benign perimesencephalic hemorrhage occurring after previous aneurysmal subarachnoid hemorrhage: a case report

IntroductionBoth aneurysmal subarachnoid hemorrhage and benign perimesencephalic hemorrhage are well-described causes of spontaneous subarachnoid hemorrhage that arise as a result of different pathologic processes. To the best of the authors' knowledge, there have been no reports of both vascular pathologies occurring in the same individual.Case presentationA 51-year-old Caucasian woman with a history of aneurysmal subarachnoid hemorrhage presented five years after her initial treatment with ictal headache, meningismus, nausea and emesis similar to her previous bleeding event. Computed tomographic imaging revealed perimesencephalic bleeding remote from her previously coiled anterior communicating artery aneurysm. Both immediate and delayed diagnostic angiography revealed no residual filling of the previously coiled aneurysm and no other vascular anomalies, consistent with benign perimesencephalic hemorrhage. The patient had an uneventful hospital course and was discharged to home in good condition.ConclusionsThis report for the first time identifies benign perimesencephalic hemorrhage occurring in the setting of previous aneurysmal subarachnoid hemorrhage. The presence of a previously treated aneurysm can complicate the process of diagnosing benign perimesencephalic hemorrhage. Fortunately, in this case, the previously treated anterior communicating artery aneurysm was remote from the perimesencephalic hemorrhage and could be ruled out as a source. The patient's prior aneurysmal subarachnoid hemorrhage did not worsen the anticipated good outcome associated with benign perimesencephalic hemorrhage.