Journal of Thrombosis and Haemostasis最新文献

Pregnancy is a prothrombotic state due to an estrogen-driven shift in the coagulation system, increased venous stasis, and external restriction of blood flow caused by the gravid uterus. Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in pregnancy. Preventing, recognizing, and treating thrombosis in pregnancy, as well as the postpartum period, often challenges decision making in the clinical setting. In early pregnancy, guidance with respects to thrombophilia testing and anticoagulation in increasing the likelihood of live birth among patients with recurrent miscarriages is evolving. This review explores emerging data that support clinical decision making in thrombosis care in women with common thrombotic complications in pregnancy. The first case outlines VTE diagnosis in pregnancy, initial anticoagulation management, management around delivery and postpartum, and subsequent long-term anticoagulation treatment. The second case examines testing for inherited and acquired thrombophilia in the setting of recurrent miscarriage and the management of obstetric antiphospholipid syndrome. Lastly, the third case reviews VTE risk assessment and prevention in pregnancy and the postpartum period, as well as duration and dose of postpartum thromboprophylaxis. Review of these common clinical scenarios surrounding thrombotic complications in pregnancy demonstrates recent advances in high-quality data, current gaps in knowledge, and variation in expert opinion. Ultimately, multidisciplinary discussion and teamwork remain key to optimal, safe care. Clinicians must prioritize collaborative, high-quality trials and prospective clinical management studies to better understand and define best practice in this population.

Pulmonary embolism (PE) is a common cardiovascular disease diagnosis in emergency departments that can be associated with significant morbidity and mortality. One of the first steps after diagnosing PE is to risk stratify for adverse outcomes using risk scores such as PE Severity Index and European Society of Cardiology risk scheme. While intermediate- and high-risk PE patients should be admitted to the hospital, there is increasing evidence to support early discharge and home-based anticoagulation therapy for low-risk patients. The Hestia criteria encompass many of the clinicians' considerations for who may be suitable for early discharge, considering both medical and social factors. Additionally, professional guidelines have provided algorithms on determining which low-risk patients may be suitable. Despite this, low-risk acute PE patients are still often admitted for inpatient treatment. In this review, we present a case-based approach on how to risk stratify and evaluate patients who may be good candidates for early discharge and home therapy.

Blood flow is vital to life, yet disturbed flow has been linked to atherosclerosis, thrombosis, and endothelial dysfunction. The commonly used hemodynamic descriptor "disturbed flow" found in disease and medical devices is not clearly defined in many studies. However, the specific flow regime-laminar, transitional, or turbulent-can have very different effects on hemostasis, thrombosis, and vascular health. Therefore, it remains important to clinically identify turbulence in cardiovascular flow and to have available assays that can be used to study effects of turbulence. The objective of the current communication was to 1) provide clarity and guidance for how to clinically identify turbulence, 2) define standard measures of turbulence that can allow the recreation of flow conditions in a benchtop assay, and 3) review how cells and proteins in the blood can be impacted by turbulence based on current literature.

A growing number of patients receiving antithrombotic therapy require dental procedures. Dental interventions in these patients can be challenging, as the risk of bleeding from the continuation of antithrombotic therapy needs to be weighed against the thromboembolic risk associated with drug interruption or de-escalation. Most minor dental procedures, including simple dental cleaning and filling, pose minimal bleeding risk, and antiplatelet or anticoagulation therapy can be continued without interruption. Local hemostatic measures, such as tranexamic mouthwash, can be used, as needed, to reduce bleeding events following these interventions. Managing antithrombotic therapy during more invasive dental interventions and oral surgeries with a higher risk of perioperative bleeding necessitates the consideration of specific factors influencing the bleeding risk and thromboembolism. In patients receiving antithrombotic therapy for primary prevention, temporary interruption is reasonable. In others, the decisions may be more complex and more nuanced. In this article, we review the current evidence for managing patients receiving oral antiplatelet or anticoagulant drugs scheduled for various dental procedures and present a practical approach for the periprocedural management of antithrombotic treatments.

Background: Despite uncertain benefit-risk profile near the end of life, antithrombotic therapy (ATT) is prevalent in patients with terminal cancer.

Objectives: To examine adherence and persistence with ATT in terminally ill cancer patients and investigate risks of major and clinically relevant bleeding, venous thromboembolism (VTE), and arterial thromboembolism (ATE) by ATT exposure.

Methods: Using a Danish nationwide cohort of terminal cancer patients, ATT adherence in the year following terminal illness declaration was measured by the proportion of days covered (PDC) by prescription. Discontinuation was defined as a treatment gap of ≥30 days between prescription renewals. One-year cumulative incidences of bleeding complications, VTE, and ATE were calculated, considering the competing risk of death.

Results: During 2013-2022, 86 732 terminally ill cancer patients were identified (median age, 75 years; 47% female; median survival, 57 days). At terminal illness declaration, 37.5% were receiving ATT (66.6% platelet inhibitors, 23.0% direct oral anticoagulants, and 10.4% vitamin K antagonists [VKAs]). The mean PDC with ATT was 88% (SD, 30%), highest among platelet inhibitor users (mean PDC, 89%) and lowest among VKA users (73%). One-year ATT discontinuation incidence was 7.9% (95% CI, 7.7%-8.1%). Most patients continued ATT until death (74.8% platelet inhibitors, 58.8% direct oral anticoagulants, and 61.6% VKAs). Patients receiving ATT had a lower 1-year VTE risk but higher risks of ATE and major bleeding.

Conclusion: Despite uncertain benefit-risk profile, most terminally ill cancer patients continue ATT until the end of life. These findings provide insights into current ATT utilization and discontinuation dynamics in the challenging context of terminal illness.

Ischemic stroke is a common cause of morbidity and mortality worldwide. The majority of affected individuals are older, with clear cardiovascular or embolic risk factors; however, up to a fifth of cases may occur in patients under the age of 50 years. In this review, we discuss some common hematological causes of ischemic stroke in this age range, with a focus on antiphospholipid syndrome, myeloproliferative neoplasms, immune thrombocytopenic purpura, and sickle cell disease. We review the etiology of stroke associated with these conditions and explore important management considerations that may be unique to these settings. These include the choice of antithrombotic agents, cytoreduction in myeloproliferative neoplasms, management of thrombocytopenia in immune thrombocytopenic purpura, and treatment of sickle cell disease.

Background: Postthrombotic syndrome (PTS) is a chronic condition following deep vein thrombosis (DVT) and is associated with pain, swelling, and restricted use of the affected limb. In pediatric age groups, its incidence and risk factors are not well-known.

Methods: This observational cohort study of all consecutive children (≤18 years) with DVT treated at the Emma Children's Hospital Amsterdam between January 2001 and January 2021 was conducted to identify incidence and risk factors for PTS in neonates aged ≤2 months and children aged >2 months. PTS was diagnosed using the modified Villalta scale.

Results: In total, 315 patients were included. The 20-year incidence of PTS was 20.0% in neonates and 40.0% in children. In neonates, involvement of ≥3 vessels (odds ratio [OR], 6.6; 95% CI, 1.6-26.4) and incomplete thrombus resolution (OR, 3.0; 95% CI, 1.1-8.0) were risk factors for PTS. In children, involvement of ≥3 vessels (OR, 6.2; 95% CI, 2.2-17.8), recurrent DVT (OR, 3.7; 95% CI, 1.3-10.3), and incomplete thrombus resolution (OR, 5.2; 95% CI, 1.6-17.0) were associated with PTS. Exercise ≥3 times/wk (OR, 0.4; 95% CI, 0.2-0.9), central venous catheter-related DVT (OR, 0.2; 95% CI, 0.1-0.5), and provoked DVT (OR, 0.4; 95% CI, 0.1-0.97) were protective factors for PTS.

Conclusion: This study demonstrated a high incidence of pediatric PTS. Additionally, risk factors for PTS differed between neonates and children. These findings provide a basis for better prevention and management of PTS that may differ between neonates and children.

Background: The vitamin K-dependent coagulation factor protein Z (PZ), encoded by the PROZ gene, is canonically considered to have anticoagulant effects through negative regulation of factor Xa. Paradoxically, higher circulating PZ concentrations have repeatedly been associated with an elevated risk of acute ischemic stroke.

Objectives: We performed a large-scale genetic association study to examine the relationship between germline genetic variants in PROZ and the risk of ischemic stroke.

Methods: Using whole-exome sequencing and clinical data for 416 711 participants in the UK Biobank (UKB), we identified individuals with rare (minor allele frequency ≤0.1%) putatively function-altering variants in PROZ. Using Firth's logistic regression and controlling for known stroke risk factors, we evaluated the association between variant carrier status and noncardioembolic ischemic stroke (NCEIS). Additionally, we evaluated differences in the plasma levels of 1472 proteins between PROZ variant carriers and noncarriers in a subset of 48 893 UKB participants.

Results: After accounting for missing data, qualifying variants in PROZ were identified in 414 UKB participants (99.0% heterozygous). Variant carriers had a significantly increased risk of NCEIS (odds ratio, 2.34; 95% CI, 1.15-4.13; P = .02) but not of venous thromboembolism, myocardial infarction, or peripheral artery disease. Plasma proteomics analysis revealed that PROZ variant carriers had significantly elevated levels of 2 proteins related to the response to cerebral ischemia, peroxiredoxins 1 and 6 (PRDX1: fold change, 1.83; P = 1.3 × 10^-5; PRDX6: fold change, 1.78; P = 9.6 × 10^-10).

Conclusion: Lifelong exposure to decreased PZ levels confers a significantly increased risk of NCEIS, consistent with the role of PZ as an anticoagulant factor.