Publications by authors named "Cuker A"

Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction with significant thromboembolic risk. Though there are models for use of non-heparin anticoagulants, heparin remains the preferred anticoagulant in many operative settings, especially cardiovascular surgery and percutaneous cardiac intervention. The natural history of HIT can be stereotyped into phases using HIT laboratory testing to guide clinical management and determine whether heparin re-exposure can be considered.

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Heparin-induced thrombocytopenia (HIT) is an immune reaction to heparin associated with thrombocytopenia, thrombotic risk, and a high risk of morbidity and mortality. Given the frequent use of heparin and the common occurrence of thrombocytopenia in hospitalized patients, the diagnosis and management of HIT is a recurrent challenge in everyday inpatient care. This article presents practical guidance and tools to support the individual clinician providing evidence-based care to patients with suspected or confirmed HIT.

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The management of immune thrombocytopenia (ITP) is continuously evolving with the development and introduction of newer therapies and a better understanding of the disease. Corticosteroids still represent the cornerstone of first-line treatment. Patients who fail to achieve remission with a short course of corticosteroids require subsequent therapy.

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Objectives: Evidence-based protocols for managing bleeding emergencies in patients with immune thrombocytopenia (ITP) are lacking. We conducted a systematic review of treatments for critical bleeding in patients with ITP.

Methods: We included all study designs and extracted data in aggregate or individually for patients who received one or more interventions and for whom any of the following outcomes were reported: platelet count response, bleeding, disability, or death.

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Background: While bleeding around pregnancy is well described in von Willebrand disease (VWD), the risk of pregnancy loss is less certain.

Objectives: We aimed to describe the frequency of pregnancy loss in females with VWD compared with those with a similar mucocutaneous bleeding phenotype and no VWD or compared with nonbleeding disorder controls.

Methods: Female patients were consecutively approached in 8 specialty bleeding disorder clinics between 2014 and 2023.

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Background: Concerns have been raised regarding the updated Beers Criteria that recommended avoiding rivaroxaban use for long-term treatment of older adults with nonvalvular atrial fibrillation (AF).

Objectives: We sought to compare the effectiveness and safety of rivaroxaban with oral anticoagulants in older adults with nonvalvular AF.

Methods: We used an administrative healthcare database and included adults with AF aged ≥65 years who were new users of rivaroxaban or the comparators.

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COVID-19-related critical and acute illness are associated with an increased risk of venous thromboembolism (VTE). These evidence-based recommendations of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other healthcare professionals in decisions about the use of anticoagulation for thromboprophylaxis in patients with COVID-19-related critical illness, acute illness, and those being discharged from the hospital, who do not have suspected or confirmed VTE. ASH formed a multidisciplinary panel, including three patient representatives, and applied a conflicts of interest management policy to minimize potential bias.

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Nowadays, unfractionated heparin (UFH) use is limited to selected patient groups at high risk of both bleeding and thrombosis (patients in cardiac surgery, in intensive care unit, and patients with severe renal impairment), rendering its management extremely challenging, with many unresolved questions despite decades of use. In this narrative review, we revisit the fundamental concepts of therapeutic anticoagulation with UFH and address five key points, summarizing controversies underlying the use of UFH and discussing the few recent advances in the field: (1) laboratory tests for UFH monitoring have significant limitations; (2) therapeutic ranges are not well grounded; (3) the actual influence of antithrombin levels on UFH's anticoagulant activity is not well established; (4) the concept of UFH resistance lacks supporting data; (5) scarce data are available on UFH use beyond acute venous thromboembolism. We therefore identified key issues to be appropriately addressed in future clinical research: (1) while anti-Xa assays are often considered as the preferred option, we call for a vigorous action to improve understanding of the differences between types of anti-Xa assays and to solve the issue of the usefulness of added dextran; (2) therapeutic ranges for UFH, which were defined decades ago using reagents no longer available, have not been properly validated and need to be confirmed or reestablished; (3) UFH dose adjustment nomograms require full validation.

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Article Synopsis
  • AAV-based gene therapy shows promising results for treating severe hemophilia A (HA) and hemophilia B (HB) in adult males, with studies indicating a significant reduction in annualized bleeding rates (ABR) and infusion rates (AIR).
  • In hemophilia A, gene therapy led to an average decrease of 7.58 bleeding events and 117.2 factor infusions annually, while hemophilia B saw reductions of 5.64 bleeding events and 58.92 infusions.
  • While both therapies resulted in favorable outcomes, factor expression durability was better in HB compared to HA, with serious adverse events reported in about 19-21% of subjects but no cases of thrombosis or inhibitor
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  • Iptacopan, a new oral medication approved by the FDA, targets paroxysmal nocturnal hemoglobinuria, a rare blood disorder, offering an alternative to existing intravenous treatments that can lead to persistent anemia.
  • Recent phase 3 studies highlight its effectiveness as a standalone therapy compared to traditional complement C5 inhibitors.
  • A comprehensive cost-effectiveness analysis revealed that iptacopan not only provided better quality-adjusted life years (QALYs) but also saved healthcare costs, making it a more favorable option over the standard-of-care in various countries, including Brazil, Japan, and the U.S.
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  • Fidanacogene elaparvovec is a genetic therapy for hemophilia B that showed promising results in a phase 1-2a study, maintaining high levels of factor IX activity.* -
  • In a phase 3 study involving men aged 18 to 65 with severe hemophilia B, the therapy led to a significant 71% reduction in bleeding episodes over 15 months compared to standard prophylactic treatment.* -
  • Despite some participants needing glucocorticoids for side effects, the therapy was generally safe, with no serious adverse infusion events reported.*
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Interactions between food and oral anticoagulants (OACs), particularly vitamin K antagonists such as warfarin, are widely recognized and may also be clinically relevant for direct OACs. Pharmacokinetic and pharmacodynamic interactions with food or herbs can lead to anticoagulation potentiation, increased risk of bleeding, or reduced drug efficacy, all compromising patient safety. We conducted a systematic search for randomized controlled trials (RCTs) on PubMed for assessments of interactions between OACs and various ingestants.

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Article Synopsis
  • The term atypical hemolytic uremic syndrome (aHUS) originated in the 1970s to differentiate between familial/sporadic cases and typical epidemic cases associated with Shiga toxin.
  • Over time, aHUS has become a broad term for various diseases that don't relate to Shiga toxin, complicating the definition and treatment strategies due to its diverse causes.
  • A group of experts used a consensus-building method called the Delphi approach to discuss and clarify the terminology and issues surrounding aHUS in light of advancements in medical science and targeted therapies.
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Background: The risk of venous thromboembolism (VTE) is 15 to 35-fold higher in the postpartum period compared to non-pregnant individuals. Clinical practice guidelines recommend the use of postpartum thromboprophylaxis with low molecular weight heparin (LMWH) for 6 weeks in individuals at high risk of developing VTE. However, a marked reduction in the risk of VTE risk occurs beyond the third week of the postpartum period.

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Direct oral anticoagulants (DOACs) have significant advantages over vitamin K antagonists including lack of need for routine laboratory monitoring. However, assessment of DOAC effect and concentration may be important to guide clinical management including need for DOAC reversal, particularly in acute or emergent situations. In this manuscript, the authors describe tests to screen for DOAC presence and tests that have demonstrated equivalence to gold standard testing for quantifying DOAC exposure.

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Article Synopsis
  • * The International Society on Thrombosis and Haemostasis developed a comprehensive clinical practice guideline to assist patients, caregivers, and healthcare professionals in making informed treatment decisions for congenital hemophilia A and B.
  • * A diverse panel of experts prioritized 13 key clinical questions regarding treatment strategies, utilizing the GRADE approach for systematic evidence review, and sought public feedback on their recommendations.
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While advanced liver disease was previously considered to be an acquired bleeding disorder, there is increasing recognition of an associated prothrombotic state with patients being at higher risk of atrial fibrillation (AF) and stroke and venous thromboembolism (VTE) including portal vein thrombosis (PVT). We review the available literature on epidemiology, pathophysiology, and risk factors and provide guidance on anticoagulant management of these conditions in adults with cirrhosis. In patients with Child-Pugh A or B cirrhosis and AF, we recommend anticoagulation with standard-dose direct oral anticoagulants (DOACs) in accordance with cardiology guideline recommendations for patients without liver disease.

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Primary cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia caused by cold-reactive antibodies that bind to red blood cells and lead to complement-mediated hemolysis. Patients with primary CAD experience the burden of increased health resource utilization and reduced quality of life. The standard-of-care (SOC) in patients with primary CAD has included cold avoidance, transfusion support, and chemoimmunotherapy.

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We evaluated the cost-effectiveness of prophylaxis with recombinant von Willebrand factor (rVWF) vs with plasma-derived von Willebrand factor (pdVWF) for patients with severe Von Willebrand disease. We found that rVWF is a cost-saving factor replacement compared with pdVWF across all willingness-to-pay thresholds in the United States.

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The American Society of Hematology (ASH) develops a variety of resources that provide guidance to clinicians on the diagnosis and management of blood diseases. These resources include clinical practice guidelines (CPGs) and other forms of clinical advice. Although both ASH CPGs and other forms of clinical advice provide recommendations, they differ with respect to the methods underpinning their development, the principal type of recommendations they offer, their transparency and concordance with published evidence, and the time and resources required for their development.

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Article Synopsis
  • Balancing the safety and effectiveness of antithrombotic drugs in patients with gastrointestinal disorders is complex due to issues with drug absorption and increased bleeding risks.
  • The review focuses on enteral antithrombotic therapy for patients with cardiovascular conditions and gastrointestinal issues, outlining risk assessment and methods to reduce gastrointestinal bleeding (GIB).
  • It emphasizes the importance of teamwork in customizing antithrombotic therapy, based on medical society guidelines and the unique needs of patients with both cardiovascular and gastrointestinal conditions.
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While awaiting confirmatory results, empiric therapy for patients suspected to have immune thrombotic thrombocytopenic purpura (iTTP) provides benefits and also accrues risks and costs. Rapid assays for ADAMTS13 may be able to avoid the cost and risk exposure associated with empiric treatment. We conducted, to our knowledge, the first cost-effectiveness evaluation of testing strategies with rapid vs traditional ADAMTS13 assays in patients with intermediate- to high-risk PLASMIC scores, with and without caplacizumab use.

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