Seminars in thrombosis and hemostasis最新文献

The transfusion of platelets and fresh frozen plasma (FFP) to critically ill neonates in neonatal intensive care units (NICUs) is a common intervention, yet it is still widely performed without adhering to international guidelines. The guidance itself on the therapeutic management of neonatal coagulation disorders is generally limited due to the absence of strong indications for treatment and is mainly aimed at the prevention of major hemorrhagic events such as intraventricular hemorrhage (IVH) in premature neonates. Historically, the underrepresentation of neonates in clinical studies related to transfusion medicine had led to significant gaps in our knowledge regarding the best transfusion practices in this vulnerable group and to a wide variability in policies among different neonatal units, often based on local experience or guidance designed for older children or adults, and possibly increasing the risk of inappropriate or ineffective interventions. Platelet transfusion and, particularly, FFP administration have been linked to potentially fatal complications in neonates and thus any decision needs to be carefully balanced and requires a thorough consideration of multiple factors in the neonatal population. Despite recent advances toward more restrictive practices, platelet and FFP transfusions are still subject to wide variability in practices.This review examines the existing literature on platelet and FFP transfusions and on the management of massive hemorrhage in neonates, provides a summary of evidence-based guidelines on these topics, and highlights current developments and areas for ongoing and future research with the aim of improving clinical practices.

The relationship between non-O blood groups and thromboembolic events has been suggested by several studies, although the exact underlying mechanisms are not fully elucidated. However, the correlation between ABO blood groups with the opposite pole of hemostasis, hemorrhage, has been investigated less thoroughly. Non-O blood groups confer an overall increased risk of single, recurrent, and provoked thromboembolic episodes. On the other hand, blood group O has been associated with more severe bleeding events and less favorable manifestations in individuals with hemorrhagic disorders. Therefore, ABO blood group screening may have a role in both thrombotic and hemorrhagic risk assessment and could potentially be added to available clinical prediction systems. This strong belief is supported by the ongoing research. Nevertheless, up to date, the majority of studies represent important heterogeneity, and given the frequency of non-O blood groups, a natural reluctance to incorporate blood groups in risk assessment models arises. Therefore, a more targeted approach should be considered to provide safe outcomes. The in vitro estimation of the thrombotic and hemorrhagic profile of each blood group separately, the quantitative estimation of VWF, FVIII, and platelet function in several disease settings and in well-organized studies, could be useful to establish a clear relationship of ABO blood types with hemostatic and thrombotic disorders. This may ensure a safe approach to categorizing a patient's risk, managing treatment, and influencing prognosis.

Demonstrating the efficacy of new treatments in any condition may be a challenging endeavor, and is particularly the case in sepsis. In the early 21st century, recombinant activated protein C showed a survival benefit in severe sepsis; however, subsequent studies could not replicate these results, leading to the discontinuation of this agent. Several potential reasons have been proposed for the unfavorable results of trials, including choosing an inappropriate outcome target. Concerning anticoagulant therapies, some studies have targeted sepsis with disseminated intravascular coagulation (DIC) and demonstrated clinical benefits, while other studies have focused on severe sepsis or septic shock independent of whether patients had DIC. The timing for treatment initiation, dosage, and duration of anticoagulant agents could be significant factors contributing to the limitations faced in these trials. Moreover, relying solely on 28-day mortality as the primary endpoint for sepsis trials may not be appropriate, as it can be influenced by various factors beyond anticoagulant therapies, and discernment in a shorter period might be more pertinent. Success in clinical trials is more likely if these issues are addressed and improvements are made. Recent clinical trials concentrating on anticoagulants are increasingly targeting sepsis or septic shock with coagulopathy, and adopting composite endpoints, including DIC resolution, is anticipated to overcome some of these challenges.

The coronavirus disease 2019 (COVID-19) pandemic introduced unprecedented disruptions to health care delivery, compelling rapid adaptations in anticoagulation management. Direct oral anticoagulants (DOACs), already displacing warfarin due to their convenience and reduced monitoring requirements, appeared well-positioned for broader adoption during pandemic-induced lockdowns. This commentary examines whether the pandemic catalyzed a meaningful shift in anticoagulant prescribing patterns from vitamin K antagonists (VKAs) to DOACs, drawing on data from the United Kingdom, Australia, the United States, Europe, and Asia. In the United Kingdom, national guidance led to an abrupt and large-scale switch to DOACs, with sustained changes postpandemic. In contrast, Australia and the United States exhibited continuity in preexisting trends, with modest, transient shifts that did not persist. Asian and European data revealed a gradual trajectory toward DOACs, likely driven by long-term policy and infrastructure rather than acute pandemic pressures. While no universal transformation occurred, the pandemic accentuated existing preferences and exposed system-level vulnerabilities in warfarin monitoring. The global experience suggests that the COVID-19 crisis served as a selective accelerant of DOACs adoption, where health care systems and policies facilitated change. As health systems prepare for future disruptions, equitable access to DOACs and investment in remote care infrastructure will be essential to ensuring continuity and safety in anticoagulation therapy.

In 2025, the International Society on Thrombosis and Haemostasis (ISTH) released updated definitions and diagnostic criteria for disseminated intravascular coagulation (DIC), reflecting advances in understanding its pathophysiology. DIC is now defined as an acquired, life-threatening condition involving systemic coagulation activation, impaired fibrinolysis, and endothelial injury. The revised framework emphasizes the condition's dynamic nature, progressing from preclinical abnormalities to overt clinical manifestations such as bleeding and organ dysfunction. A major innovation in the 2025 update is the phase-based classification of DIC: Pre-DIC, early-phase DIC, and overt DIC. Early-phase DIC-also referred to as subclinical or compensated DIC-is characterized by laboratory abnormalities preceding clinical symptoms. Overt DIC represents the advanced stage with clear evidence of coagulopathy and organ failure. Importantly, the new criteria are tailored to the underlying disease, such as sepsis, trauma, or malignancy. For example, the sepsis-induced coagulopathy score is now acknowledged as a tool for detecting early-phase DIC in septic patients. The overt DIC scoring system has been refined, including revised D-dimer thresholds: Levels >3× and >7 × , the upper normal limit now corresponds to 2 and 3 points, respectively. Platelet count, prothrombin time-international normalized ratio, and fibrinogen levels remain key indicators. The criteria also classify DIC into thrombotic and hemorrhagic phenotypes. Thrombotic DIC is marked by microvascular thrombosis and organ dysfunction, while hemorrhagic DIC is characterized by bleeding due to consumption of coagulation factors. By introducing clearer definitions and individualized approaches, these updates aim to enable earlier diagnosis and more effective management of DIC across clinical contexts.

Chronic use of multiple drugs increases risk of adverse drug reactions, drug interactions and poor therapeutic adherence. In elderly or frail patients, some drugs may become ineffective or even harmful with advancing age and worsening clinical conditions. Nonsteroidal anti-inflammatory drugs (NSAIDs) have been extensively used for decades and, as a class, are both often inappropriately prescribed and involved in polypharmacotherapy untoward effects. In view of the dynamic and mutual relationship between inflammation and hemostasis in various clinical scenarios, use of anti-inflammatory agents, including NSAIDs, may tip this difficult balance in patients with hemostatic disorders. Rather than on well-established actions such as the clinically relevant antiplatelet action of low-dose aspirin and gastrointestinal bleeding, this review focuses on less highlighted, emerging or sometimes overlooked NSAID efficacy and safety endpoints. For instance, preclinical studies suggest that the antiplatelet action of low-dose aspirin enhances immune system activity against cancer cells, resulting in metastasis prevention. While use of NSAIDs in patients with coagulation disorders may have an acceptable risk-to-benefit ratio in selected patients, clinical judgement is required especially in cases of renal impairment that can be worsened by NSAIDs or in cases with high bleeding risk. In the context of polypharmacotherapy, attenuation of aspirin antiplatelet action by concomitant and inaccurately timed ibuprofen treatment may undermine the clinical benefit of aspirin in cardiovascular prevention. Thus, collaborative cross-disciplinary efforts of pharmacologists and clinicians would be desirable in order to enhance appropriateness, efficacy and safety of NSAID treatment in different settings of care.

Thrombocytopenia following hematopoietic stem cell transplantation (HSCT) is a common complication that is associated with a remarkable increase in morbidity and mortality. Post-HSCT thrombocytopenia is a multifactorial condition with several mechanisms, including reduced platelet production in bone marrow, immune-mediated platelet destruction, and consumptive thrombocytopenia. Graft-versus-host disease (GVHD), medications, infections, and autoimmune mechanisms are potential risk factors for post-HSCT thrombocytopenia. Management of post-HSCT thrombocytopenia primarily focuses on supportive care through platelet transfusions. Moreover, immunosuppressive agents are used to target immune-mediated mechanisms. Thrombopoietin receptor agonists and complement inhibitors are novel treatment options with promising results and fewer side effects. However, further research is essential to establish treatment protocols and improve patient care. In this review, we provide a better understanding of the pathophysiology and risk factors associated with post-HSCT thrombocytopenia for early detection and intervention, ultimately aiming to reduce complications.

Thrombosis is the most common manifestation of antiphospholipid syndrome (APS), but concurring evidence of the mechanisms leading to a hypercoagulable state and thereby thrombosis is lacking. Existing reviews on this topic often include both animal and in vitro models. Additionally, studies with a systematic approach and stringent methodology, focusing exclusively on human studies, are lacking. Therefore, we conducted a scoping review of studies with human subjects, focusing on the mechanisms contributing to hypercoagulability in thrombotic APS (T-APS). The process was guided by the PRISMA Extension for Scoping Reviews and performed according to a preregistered protocol in Open Science Framework (https://osf.io/tjdwv). A systematic search of Ovid (EMBASE) and MEDLINE (PubMed) was performed on October 10, 2024. Records investigating mechanisms of hypercoagulability in adults (≥18 years) with T-APS, published between January 2000 and October 2024, were included. A total of 4,160 titles and abstracts were screened, 115 articles were assessed in full text, of which 35 studies fulfilled the predefined eligibility criteria for inclusion. Of the included studies, 8 focused on primary hemostasis, 10 on secondary hemostasis, 9 on fibrinolysis, 4 on neutrophil extracellular traps, 6 on endothelial cells, 3 on complement factors, 5 on monocytes, 3 on oxidized low-density lipoprotein complexes, 2 on oxidative stress, and 1 on amyloid-β1-40. No clear consensus was found regarding the underlying cause of hypercoagulability in T-APS, highlighting the need for further studies with human subjects. Nonetheless, this scoping review indicates that hypercoagulability in T-APS is possibly multifactorial, with no single mechanism being solely responsible.

The antiphospholipid syndrome (APS) is a complex autoimmune disease that causes a state of hypercoagulability that can result in recurrent venous and arterial thromboses. APS may lead to cardiac manifestations requiring cardiac surgery with cardiopulmonary bypass. Perioperative anticoagulation management in APS patients is complex. This complexity arises from both the prothrombotic nature of APS and interference of antiphospholipid antibodies (aPLs) with phospholipid-dependent coagulation assays like activated clotting time (ACT). Given that current literature on cardiopulmonary bypass (CPB) management in APS patients is largely limited to isolated case reports and lacks a comprehensive synthesis, this review summarizes the cardiac manifestations of APS, challenges posed by CPB, and current strategies for intraoperative anticoagulation management, including heaprin dosing, anticoagulation monitoring methods and protamine reversal practices. We further highlight gaps in evidence and propose a practical three-category framework for managing aPL-positive patients undergoing CPB.

Clot waveform analysis (CWA) extends routine coagulation assays (activated partial thromboplastin time [aPTT] and prothrombin time [PT]) by incorporating continuous optical monitoring to generate kinetic profiles of clot formation. This method provides both qualitative and quantitative information on hemostasis, with increasing evidence for its clinical utility in detecting factor deficiencies and characterizing thrombotic and bleeding disorders. Despite the growing body of evidence, translation of CWA into routine clinical practice remains limited.This review identifies three principal barriers: (1) variability arising from differences in optical detection methods (absorbance vs. transmittance), (2) interreagent variation even within the same analyzer platform, and (3) lack of a clear distinction between standard CWA, performed with commercially available reagents, and modified CWA, incorporating in-house adjustments. To address these challenges, we encourage adopting distinct nomenclature for detection modalities (CWA-A; A for absorbance and CWA-T; T for transmittance), establishing standardized reporting requirements including reagent and platform details, and establishing quality assurance frameworks for CWA.Standardization of terminology and reporting will enhance reproducibility, enable cross-study comparisons, and accelerate the clinical translation of CWA from the laboratory bench to the bedside.