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General Hematology

Cohort Study: Higher serious bleeding rates linked to diltiazem in elderly atrial fibrillation patients on anticoagulation

26 Apr, 2024 | 12:35h | UTC

Study Design and Population:
This retrospective cohort study analyzed data from 204,155 Medicare beneficiaries aged 65 years or older diagnosed with atrial fibrillation. The study focused on new users of the anticoagulants apixaban or rivaroxaban who commenced treatment with either diltiazem or metoprolol between January 2012 and November 2020, with follow-up extending up to 365 days.

 

Main Findings:
Patients treated with diltiazem exhibited a significantly increased risk of serious bleeding, including bleeding-related hospitalization and death, compared to those treated with metoprolol. The hazard ratio (HR) for serious bleeding events was 1.21, with a rate difference (RD) of 10.6 per 1000 person-years. Notably, the risk escalated with diltiazem doses exceeding 120 mg/day, indicating a dose-response relationship. Secondary outcomes, such as ischemic stroke or systemic embolism, did not show significant differences between the treatment groups.

 

Implications for Practice:
The findings suggest that in older adults with atrial fibrillation treated with apixaban or rivaroxaban, diltiazem increases the risk of serious bleeding, especially at higher doses. These results underscore the importance of cautious medication management and might influence clinical decisions regarding the choice of ventricular rate control in this population.

 

Reference (link to abstract – $ for full-text):

Ray, W. A., Chung, C. P., Stein, C. M., et al. (2024). Serious Bleeding in Patients With Atrial Fibrillation Using Diltiazem With Apixaban or Rivaroxaban. JAMA, Published online April 15, 2024. doi:10.1001/jama.2024.3867


High efficacy of exagamglogene autotemcel in achieving transfusion independence in β-Thalassemia

25 Apr, 2024 | 23:29h | UTC

Study Design and Population:

This open-label, single-group, phase 3 trial investigated the efficacy of exagamglogene autotemcel (exa-cel), a nonviral CRISPR-Cas9 gene-edited cell therapy, in patients aged 12 to 35 with transfusion-dependent β-thalassemia. Various genotypes were included, and participants underwent myeloablative conditioning followed by exa-cel infusion. The primary endpoint was to achieve and maintain transfusion independence.

 

Main Findings:

Of the 52 patients treated, 35 with sufficient follow-up showed that 32 (91%) achieved transfusion independence for at least 12 months, significantly surpassing the study’s efficacy threshold. The average total hemoglobin during this period was 13.1 g/dL, with fetal hemoglobin averaging 11.9 g/dL and widely distributed across red cells. The treatment’s safety profile was compatible with the expected outcomes of myeloablative conditioning and autologous hematopoietic stem cell transplantation, with no reported deaths or cancer developments.

 

Implications for Practice:

The successful achievement of transfusion independence in a high percentage of patients suggests that exa-cel is a promising treatment option for transfusion-dependent β-thalassemia. This study supports the potential for gene-edited cell therapies to significantly improve outcomes in genetic blood disorders. Continued monitoring and further research are recommended to fully understand the long-term implications and safety of such treatments.

 

Reference: 

Reference: Locatelli, F. et al. (2024). Exagamglogene Autotemcel for Transfusion-Dependent β-Thalassemia. New England Journal of Medicine. doi: 10.1056/NEJMoa2309673.


CRISPR-Cas9 gene editing in sickle cell disease shows high efficacy in preventing vaso-occlusive crises

25 Apr, 2024 | 23:21h | UTC

Study Design and Population: This phase 3, single-group, open-label randomized clinical trial investigated the efficacy of exagamglogene autotemcel (exa-cel), a nonviral CRISPR-Cas9 gene-edited therapy, in patients aged 12 to 35 years with severe sickle cell disease. The study included patients who experienced at least two severe vaso-occlusive crises annually in the two years prior to screening. The therapeutic intervention involved editing CD34+ hematopoietic stem and progenitor cells (HSPCs) and administering a myeloablative conditioning regimen with busulfan.

Main Findings: Of the 44 participants treated, 30 with sufficient follow-up demonstrated a significant response. Ninety-seven percent (29 of 30) remained free from severe vaso-occlusive crises for at least 12 consecutive months, and 100% (30 of 30) avoided hospitalization for these crises over the same period. The intervention showed a high safety profile, consistent with myeloablative busulfan conditioning and autologous HSPC transplantation, with no cancers reported during the follow-up.

Implications for Practice: The results suggest that exa-cel can effectively eliminate severe vaso-occlusive crises in patients with sickle cell disease, marking a substantial advance in treatment options. These findings may pave the way for broader application of gene-editing therapies in hematologic diseases, pending further research on long-term outcomes and safety.

Reference: Frangoul, H. et al. (2024). Exagamglogene Autotemcel for Severe Sickle Cell Disease. N Engl J Med, Online ahead of print. DOI: 10.1056/NEJMoa2309676.


Nested Case-Control Study: Increased risk of major bleeding in atrial fibrillation patients with concomitant SSRI and oral anticoagulant use

23 Mar, 2024 | 20:48h | UTC

Study Design and Population

This nested case-control study investigated the association between the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and oral anticoagulants (OACs) on the risk of major bleeding among patients with atrial fibrillation. Conducted within the UK’s Clinical Practice Research Datalink, the study included 42,190 cases of major bleeding matched to 1,156,641 controls based on age, sex, cohort entry date, and follow-up duration. Patients initiating OACs between January 2, 1998, and March 29, 2021, were included, with risk-set sampling utilized for control selection.

Main Findings

The study found that concomitant use of SSRIs and OACs was associated with a 33% increased risk of major bleeding compared to OAC use alone, with the highest risk observed within the first 30 days of concurrent use. The increased risk was consistent across different ages, sexes, and patient histories, including those with chronic kidney disease or previous bleeding events. Notably, the elevated risk of bleeding extended up to 6 months of concomitant use but did not vary significantly with the potency of SSRIs or the type of OAC used (direct OACs or vitamin K antagonists).

Implications for Practice

These findings underscore the need for healthcare professionals to closely monitor patients with atrial fibrillation who are prescribed SSRIs in addition to OACs, particularly during the initial months of treatment. This study highlights the importance of managing bleeding risk factors and suggests reconsidering the necessity and duration of concomitant SSRI and OAC use. Future research should focus on strategies to mitigate this bleeding risk and explore alternative treatments for managing depression in patients requiring anticoagulation.

Reference

Rahman AA, Platt RW, Beradid S, et al. (2024). Concomitant Use of Selective Serotonin Reuptake Inhibitors With Oral Anticoagulants and Risk of Major Bleeding. JAMA Netw Open, 7(3):e243208. DOI: 10.1001/jamanetworkopen.2024.3208.


Phase 2 RCT: Low-dose aspirin significantly reduces hepatic fat in MASLD patients without cirrhosis

20 Mar, 2024 | 17:48h | UTC

Study Design and Population: This phase 2, randomized, double-blind, placebo-controlled clinical trial was carried out over six months at a single hospital in Boston, Massachusetts. The study included 80 participants aged 18 to 70 years diagnosed with metabolic dysfunction–associated steatotic liver disease (MASLD) but without cirrhosis. Participants were randomly assigned to receive either 81 mg of daily aspirin (n=40) or placebo (n=40).

Main Findings: The trial revealed that aspirin significantly reduced the mean absolute change in hepatic fat content by -10.2% compared with placebo, as measured by proton magnetic resonance spectroscopy (MRS), with a statistically significant difference (P=0.009). Furthermore, aspirin treatment notably decreased relative hepatic fat content, increased the proportion of patients achieving a 30% or greater reduction in hepatic fat, and reduced both absolute and relative hepatic fat content as assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF). Adverse events were mostly minor, with upper respiratory infections and arthralgias being the most common.

Implications for Practice: These findings suggest that low-dose aspirin may be an effective intervention for reducing liver fat in adults with MASLD without cirrhosis, potentially offering a simple, accessible treatment option. However, the results are preliminary and call for further confirmation in larger, more diverse populations. The study underscores the importance of considering low-dose aspirin as part of management strategies for MASLD, pending further research.

Reference

Simon TG et al. (2024). Randomized Clinical Trial: Low-Dose Aspirin Significantly Reduces Hepatic Fat in MASLD Patients Without Cirrhosis. JAMA, 331(11), 920-929. DOI: 10.1001/jama.2024.1215. Access the study here: [Link]


RCT | Restrictive vs. liberal red blood cell transfusion strategy for critically injured patients

11 Aug, 2023 | 15:08h | UTC

The Restrictive Red Blood Cell Transfusion Strategy for Critically Injured Patients (RESTRIC) trial: a cluster-randomized, crossover, non-inferiority multicenter trial of restrictive transfusion in trauma – Journal of Intensive Care

 


NICE Updated Guideline | Venous thromboembolic diseases

7 Aug, 2023 | 15:05h | UTC

Venous thromboembolic diseases: diagnosis, management and thrombophilia testing  – National Institute for Health and Care Excellence

 


Global prevalence, years lived with disability, and trends in anemia burden by severity and cause, 1990–2021

3 Aug, 2023 | 13:43h | UTC

Prevalence, years lived with disability, and trends in anaemia burden by severity and cause, 1990–2021: findings from the Global Burden of Disease Study 2021 – The Lancet Haematology

News Release: New study reveals global anemia cases remain persistently high among women and children. Anemia rates decline for men – Institute for Health Metrics and Evaluation

 

Commentary on Twitter

 


RCT | Ferric derisomaltose plus tranexamic acid may reduce blood transfusion risk by 50% in hip surgery

3 Aug, 2023 | 13:18h | UTC

Ferric derisomaltose and tranexamic acid, combined or alone, for reducing blood transfusion in patients with hip fracture (the HiFIT trial): a multicentre, 2 × 2 factorial, randomised, double-blind, controlled trial – The Lancet Haematology (link to abstract – $ for full-text)

 


BSH guideline for anticoagulant management of pregnant individuals with mechanical heart valves

2 Aug, 2023 | 14:01h | UTC

British Society for Haematology guideline for anticoagulant management of pregnant individuals with mechanical heart valves – British Journal of Haematology

 


Review | Perioperative iron deficiency anemia

31 Jul, 2023 | 14:02h | UTC

Perioperative iron deficiency anaemia – BJA Education

 


Systematic Review | Monocyte distribution width as a diagnostic marker for infection

26 Jul, 2023 | 13:26h | UTC

Monocyte Distribution Width as a Diagnostic Marker for Infection – CHEST

Related: Comparison of the Diagnostic Accuracies of Monocyte Distribution Width, Procalcitonin, and C-Reactive Protein for Sepsis: A Systematic Review and Meta-Analysis – Critical Care Medicine

 

Commentary on Twitter

 


Cohort Study | The role of antiphospholipid syndrome and specific antibodies in predicting SLE pregnancy complications

25 Jul, 2023 | 13:44h | UTC

Pregnancy outcomes in 1869 pregnancies in a large cohort from the Spanish Society of Rheumatology Lupus Register (RELESSER) – Seminars in Arthritis and Rheumatism (link to abstract – $ for full-text)

Commentary: SLE and Pregnancy Outcomes – RheumNow

 


Consensus Paper | De-escalation or abbreviation of dual antiplatelet therapy in acute coronary syndromes and PCI

24 Jul, 2023 | 13:08h | UTC

De-escalation or abbreviation of dual antiplatelet therapy in acute coronary syndromes and percutaneous coronary intervention: a Consensus Statement from an international expert panel on coronary thrombosis – Nature Reviews Cardiology (if the link is paywalled, try this one)

 


Guideline Synopsis | Diagnosis and management of priapism

21 Jul, 2023 | 13:47h | UTC

Diagnosis and Management of Priapism – JAMA (free for a limited period)

Original Guideline: The Diagnosis and Management of Recurrent Ischemic Priapism, Priapism in Sickle Cell Patients, and Non-Ischemic Priapism: An AUA/SMSNA Guideline – Journal of Urology

 


RCT | No definitive benefit of enoxaparin over placebo in preventing VTE in hospitalized older adults

17 Jul, 2023 | 13:57h | UTC

Enoxaparin versus Placebo to Prevent Symptomatic Venous Thromboembolism in Hospitalized Older Adult Medical Patients – NEJM Evidence

 


M-A | P2Y12 inhibitors show superior efficacy over aspirin for secondary prevention in CAD

11 Jul, 2023 | 14:06h | UTC

P2Y12 Inhibitor or Aspirin Monotherapy for Secondary Prevention of Coronary Events – Journal of the American College of Cardiology (link to abstract – $ for full-text)

Related:

Monotherapy with a P2Y12 inhibitor or aspirin for secondary prevention in patients with established atherosclerosis: a systematic review and meta-analysis – The Lancet (link to abstract – $ for full-text)

RCT | Clopidogrel is better than Aspirin for chronic maintenance monotherapy after percutaneous coronary intervention.

Meta-analysis of randomized trials: Clopidogrel is better than aspirin for the secondary prevention of cardiovascular events.

#ACC21 – RCT: Clopidogrel better than aspirin for chronic maintenance monotherapy after percutaneous coronary intervention.

 

Commentary on Twitter

 


Review | Hypereosinophilic syndrome (HES) and eosinophilic granulomatosis with polyangiitis (EGPA): two sides of the same coin

7 Jul, 2023 | 16:01h | UTC

HES and EGPA: Two Sides of the Same Coin – Mayo Clinic Proceedings

 


Update on transfusion-related acute lung injury: an overview of its pathogenesis and management

30 Jun, 2023 | 14:31h | UTC

Update on transfusion-related acute lung injury: an overview of its pathogenesis and management – Frontiers in Immunology

 


Post hoc analysis | Low-dose aspirin linked to increased risk of anemia in older adults

29 Jun, 2023 | 14:06h | UTC

Summary: In a post hoc analysis of the ASPREE randomized controlled trial, the impact of daily low-dose aspirin on anemia, hemoglobin, and serum ferritin concentrations in elderly individuals was investigated. The study included 19,114 community-dwelling individuals aged 70 years and older (or ≥65 years for Black and Hispanic individuals) from Australia and the United States.

Findings reveal an increased incidence of anemia in the aspirin group compared to the placebo group (51.2 events versus 42.9 events per 1000 person-years, respectively). This correlates to a 20% increase in risk (hazard ratio, 1.20 [95% CI, 1.12 to 1.29]). Hemoglobin concentrations displayed a more pronounced decline in the aspirin group by 0.6 g/L per 5 years. Additionally, among participants with ferritin measures, the aspirin group exhibited a greater prevalence of ferritin levels less than 45 µg/L at year 3 and overall decline in ferritin by 11.5%. The study found similar results even in the absence of major bleeding.

This research underscores the risk of anemia and decline in ferritin in otherwise healthy older adults taking low-dose aspirin, highlighting the need for periodic monitoring of hemoglobin levels. However, the study lacked data on the causes of anemia, indicating the need for further research.

Article: Effect of Low-Dose Aspirin Versus Placebo on Incidence of Anemia in the Elderly: A Secondary Analysis of the Aspirin in Reducing Events in the Elderly Trial – Annals of Internal Medicine (link to abstract – $ for full-text)

News Release: Low-dose aspirin may increase anaemia risk in healthy older adults: study – Monash University

Commentaries:

Aspirin Use Ups Risk of Anemia in Elderly Patients: ASPREE – TCTMD

Low-dose aspirin associated with 20% increase in risk of anemia among older adults – ACP Internist

Original Study: Effect of Aspirin on All-Cause Mortality in the Healthy Elderly – New England Journal of Medicine

 


M-A | Prophylactic intravenous tranexamic acid and thromboembolism in non-cardiac surgery

29 Jun, 2023 | 14:03h | UTC

Prophylactic intravenous tranexamic acid and thromboembolism in non-cardiac surgery: a systematic review, meta-analysis and trial sequential analysis – Anaesthesia

 


Podcast | Antiplatelets, anticoagulation for coronary artery disease and atrial fibrillation

28 Jun, 2023 | 13:11h | UTC

#400 Antiplatelets, Anticoagulation for Coronary Artery Disease and Afib – The Curbsiders

 


Review | Renal thrombotic microangiopathy

27 Jun, 2023 | 13:34h | UTC

Renal Thrombotic Microangiopathy: A Review – American Journal of Kidney Diseases

 

Commentary on Twitter

 


Report | Global, regional, and national prevalence and mortality burden of sickle cell disease, 2000–2021

23 Jun, 2023 | 13:40h | UTC

Global, regional, and national prevalence and mortality burden of sickle cell disease, 2000–2021: a systematic analysis from the Global Burden of Disease Study 2021 – The Lancet Haematology

News Release: Sickle cell disease is 11 times more deadly than previously recorded – Institute for Health Metrics and Evaluation

 

Commentary on Twitter (thread – click for more)

 


Review | Nonsurgical management of major hemorrhage

22 Jun, 2023 | 15:16h | UTC

Nonsurgical management of major hemorrhage – Canadian Medical Association Journal

 


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