Perioperative oral eltrombopag versus intravenous immunoglobulin in patients with immune thrombocytopenia:a non-inferiority, multicentre, randomised trial

Background: Patients with immune thrombocytopenia are at risk of bleeding during surgery, and intravenous immunoglobulin is commonly used to increase the platelet count. We aimed to establish whether perioperative eltrombopag was non-inferior to intravenous immunoglobulin. Methods: We did a randomised, open-label trial in eight academic hospitals in Canada. Patients were aged at least 18 years, with primary or secondary immune thrombocytopenia and platelet counts less than 100 × 109 cells per L before major surgery or less than 50 × 109 cells per L before minor surgery. Previous intravenous immunoglobulin within 2 weeks or thrombopoietin receptor agonists within 4 weeks before randomisation were not permitted. Patients were randomly assigned to receive oral daily eltrombopag 50 mg from 21 days preoperatively to postoperative day 7 or intravenous immunoglobulin 1 g/kg or 2 g/kg 7 days before surgery. Eltrombopag dose adjustments were allowed weekly based on platelet counts. The randomisation sequence was generated by a computerised random number generator, concealed and stratified by centre and surgery type (major or minor). The central study statistician was masked to treatment allocation. The primary outcome was achievement of perioperative platelet count targets (90 × 109 cells per L before major surgery or 45 × 109 cells per L before minor surgery) without rescue treatment. We did intention-to-treat and per-protocol analyses using an absolute non-inferiority margin of –10%. This trial is registered with ClinicalTrials.gov, NCT01621204. Findings: Between June 5, 2013, and March 7, 2019, 92 patients with immune thrombocytopenia were screened, of whom 74 (80%) were randomly assigned: 38 to eltrombopag and 36 to intravenous immunoglobulin. Median follow-up was 50 days (IQR 49–55). By intention-to-treat analysis, perioperative platelet targets were achieved for 30 (79%) of 38 patients assigned to eltrombopag and 22 (61%) of 36 patients assigned to intravenous immunoglobulin (absolute risk difference 17·8%, one-sided lower limit of the 95% CI 0·4%; pnon-inferiority=0·005). In the per-protocol analysis, perioperative platelet targets were achieved for 29 (78%) of 37 patients in the eltrombopag group and 20 (63%) of 32 in the intravenous immunoglobulin group (absolute risk difference 15·9%, one-sided lower limit of the 95% CI –2·1%; pnon-inferiority=0·009). Two serious adverse events occurred in the eltrombopag group: one treatment-related pulmonary embolism and one vertigo. Five serious adverse events occurred in the intravenous immunoglobulin group (atrial fibrillation, pancreatitis, vulvar pain, chest tube malfunction and conversion to open splenectomy); all were related to complications of surgery. No treatment-related deaths occurred. Interpretation: Eltrombopag is an effective alternative to intravenous immunoglobulin for perioperative treatment of immune thrombocytopenia. However, treatment with eltrombopag might increase risk of thrombosis. The decision to choose one treatment over the other will depend on patient preference, resource limitations, cost, and individual risk profiles. Funding: GlaxoSmithKline and Novartis

Recent Randomized Trials of Antithrombotic Therapy for Patients With COVID-19: JACC State-of-the-Art Review

Endothelial injury and microvascular/macrovascular thrombosis are common pathophysiological features of coronavirus disease-2019 (COVID-19). However, the optimal thromboprophylactic regimens remain unknown across the spectrum of illness severity of COVID-19. A variety of antithrombotic agents, doses, and durations of therapy are being assessed in ongoing randomized controlled trials (RCTs) that focus on outpatients, hospitalized patients in medical wards, and patients critically ill with COVID-19. This paper provides a perspective of the ongoing or completed RCTs related to antithrombotic strategies used in COVID-19, the opportunities and challenges for the clinical trial enterprise, and areas of existing knowledge, as well as data gaps that may motivate the design of future RCTs. © 2021 American College of Cardiology Foundatio

Illustrated State-of-the-Art Capsules of the ISTH 2023 Congress

This year’s Congress of the International Society of Thrombosis and Haemostasis (ISTH) took place in person in Montréal, Canada, from June 24-28, 2023. The conference, held annually, highlighted cutting-edge advances in basic, translational, population and clinical sciences relevant to the Society. As for all ISTH congresses, we offered a special, congress-specific scientific theme; this year, the special theme was immunothrombosis. Certainly, over the last few years, COVID-19 infection and its related thrombotic and other complications have renewed interest in the concepts of thromboinflammation and immunothrombosis; namely, the relationship between inflammation, infection and clotting. Other main scientific themes of the Congress included Arterial Thromboembolism, Coagulation and Natural Anticoagulants, Diagnostics and Omics, Fibrinolysis and Proteolysis, Hemophilia and Rare Bleeding Disorders, Hemostatic System in Cancer, Inflammation and Immunity, Pediatrics, Platelet Disorders, von Willebrand Disease and Thrombotic Microangiopathies, Platelets and Megakaryocytes, Vascular Biology, Venous Thromboembolism and Women’s Health. Among other sessions, the program included 28 State-of-the-Art (SOA) sessions with a total of 84 talks given by internationally recognized leaders in the field. SOA speakers were invited to prepare brief illustrated reviews of their talks that were peer reviewed and are included in this article. These illustrated capsules highlight the major scientific advances with potential to impact clinical practice. Readers are invited to take advantage of the excellent educational resource provided by these illustrated capsules. They are also encouraged to use the image in social media to draw attention to the high quality and impact of the science presented at the Congress

The contribution of iron deficiency to the risk of peripartum transfusion: a retrospective case control study

Abstract Background Iron deficiency in pregnancy is associated with inferior maternal and fetal outcomes. Postpartum depression, prematurity, intrauterine growth restriction, impaired childhood cognition and transfusion are all sequelae of maternal iron deficiency anemia. Transfusion to women of childbearing age has important consequences including increasing the risk of hemolytic disease of the fetus and newborn with future pregnancies. The relative contribution of iron deficiency to transfusion rates in the peripartum period is unknown. This study aimed to identify the prevalence of iron deficiency and anemia in pregnant women that received peripartum transfusions relative to age-matched non-transfused controls. Methods We performed a retrospective case-control study of all women that were transfused in the peripartum period from January, 2014 to July, 2018. Cases were compared to the next age matched control to deliver at our institution. The primary objective was to determine the proportion of patients with iron deficiency in pregnancy or anemia in pregnancy in cases and controls. Charts were reviewed for predisposing risk factors for iron deficiency, laboratory measures of iron deficiency and anemia, iron supplementation history and maternal and fetal outcomes. Factors associated with peripartum transfusion were analyzed using a multivariate logistic regression. Results 169 of 18, 294 (0.9%) women were transfused in the peripartum period and 64 (44%) of those transfused received 1 unit. Iron deficiency or anemia were present in 103 (71%) transfused women and 74 (51%) control women in pregnancy (OR 2.34, 95% CI: 3.7–18.0). Multivariate analysis identified social work involvement (adjusted OR 4.1, 95% CI: 1.8–10.1), intravenous iron supplementation in pregnancy (adjusted OR 3.8, 95% CI: 1.2–17.4) and delivery by unscheduled cesarean section (adjusted OR 2.8, 95% CI: 1.3–6.2) as significant predictors of peripartum transfusion. Conclusions Pregnant women being followed by a social worker, receiving intravenous iron supplementation in pregnancy or who deliver by unscheduled cesarean section are more likely to receive a red blood cell transfusion. Women with iron deficiency or anemia in pregnancy are at increased risk of peripartum blood transfusions and warrant early and rigorous iron supplementation

Effectiveness of therapeutic heparin versus prophylactic heparin on death, mechanical ventilation, or intensive care unit admission in moderately ill patients with covid-19 admitted to hospital: RAPID randomised clinical trial

Contains fulltext : 239974.pdf (Publisher’s version ) (Open Access

Correction to: The contribution of iron deficiency to the risk of peripartum transfusion: a retrospective case control study

Following publication of the original article [1], we have been notified that there is a missing conflict of interest

The Influence of Socioeconomic Status on Selection of Anticoagulation for Atrial Fibrillation.

IMPORTANCE:Without third-party insurance, access to marketed drugs is limited to those who can afford to pay. We examined this phenomenon in the context of anticoagulation for patients with nonvalvular atrial fibrillation (NVAF). OBJECTIVE:To determine whether, among older Ontarians receiving anticoagulation for NVAF, patients of higher socioeconomic status (SES) were more likely to switch from warfarin to dabigatran prior to its addition to the provincial formulary. DESIGN, SETTING AND PARTICIPANTS:Population-based retrospective cohort study of Ontarians aged 66 years and older, between 2008 and 2012. EXPOSURE:Socioeconomic status, as approximated by median neighborhood income. MAIN OUTCOMES AND MEASURE:We identified two groups of older adults with nonvalvular atrial fibrillation: those who appeared to switch from warfarin to dabigatran after its market approval but prior to its inclusion on the provincial formulary ("switchers"), and those with ongoing warfarin use during the same interval ("non-switchers"). RESULTS:We studied 34,797 patients, including 3183 "switchers" and 31,614 "non-switchers". We found that higher SES was associated with switching to dabigatran prior to its coverage on the provincial formulary (p<0.0001). In multivariable analysis, subjects in the highest quintile were 50% more likely to switch to dabigatran than those in the lowest income quintile (11.3% vs. 7.3%; adjusted odds ratio 1.50; 95% CI 1.32 to 1.68). Following dabigatran's addition to the formulary, the income gradient disappeared. CONCLUSIONS AND RELEVANCE:We documented socioeconomic inequality in access to dabigatran among patients receiving warfarin for NVAF. This disparity was eliminated following the drug's addition to the provincial formulary, highlighting the importance of timely reimbursement decisions

Baseline Characteristics of Elderly Ontarians with Non-Valvular Atrial Fibrillation.

<p>Baseline Characteristics of Elderly Ontarians with Non-Valvular Atrial Fibrillation.</p