Journal of Thrombosis and Haemostasis最新文献

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.

Antiphospholipid syndrome is an autoimmune disorder characterized by the development of spontaneous venous, arterial, or microvascular thrombosis and/or pregnancy-related complications (eg, miscarriages, fetal loss) in the presence of persistent antiphospholipid (aPL) antibodies. Current state-of-the-art treatment consists of indefinite anticoagulation with vitamin K antagonists to prevent recurrence of thrombotic events. This, however, represents only a symptom-control-oriented treatment approach. To date, no curative option eradicating aPL antibodies permanently or addressing the underlying pathomechanism has been established. Here, we report the case of a woman with systemic lupus erythematosus and antiphospholipid syndrome with triple aPL antibody-positivity who developed recurrent deep venous thrombosis. After receiving chimeric antigen receptor T-cell therapy for aggressive B-cell lymphoma, sustained eradication of all 3 aPL antibody subtypes was observed, suggesting a promising role of immunotherapies targeting anti-CD19 for the treatment of prothrombotic autoimmune disorders.

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.

Background: Whether primary or just as a complication from the progression of pulmonary arterial hypertension (PAH), thrombosis seems to be an important player in this condition. The crosstalk between red blood cells (RBCs) and pulmonary microvascular endothelial cells (PMVECs) and their role in PAH remain undefined.

Objectives: The goals of this study were to assess the role of RBC-PMVEC interaction in microvascular thrombosis and thrombotic vascular remodeling under hypoxic conditions.

Methods: We established an in vitro hypoxic coincubation model of RBC and PMVEC as well as a hypoxic mouse model. We investigated erythrophagocytosis (EP), ferroptosis, thrombosis tendency, and pulmonary hemodynamics in experimental PAH.

Results: Increased EP in PMVEC triggered ferroptosis, enhanced procoagulant activity, and exacerbated vessel remodeling under hypoxic conditions. In the PAH mouse model induced by chronic hypoxia, EP-induced ferroptosis followed by upregulated TMEM16F led to a high tendency of thrombus formation and thrombotic vascular remodeling. Inhibition of ferroptosis or silencing of TMEM16F could alleviate hypercoagulable phenotype, reverse right ventricular systolic pressure, right ventricular hypertrophy index, and remodeling of pulmonary vessels.

Conclusion: These results illustrate the pathogenic RBC-PMVEC interactions in PAH. Inhibition EP, ferroptosis, or TMEM16F could be a novel therapeutic target to prevent PAH development and thrombotic complications.

Background: Despite appropriate treatment, up to 50% of patients with proximal deep vein thrombosis will develop postthrombotic syndrome (PTS). Once PTS occurs, there is no specific treatment, and some patients constantly experience intolerable symptoms. Hence, prevention of PTS is important.

Objectives: To characterize vein wall remodeling after thrombus and investigate the effects of antiproliferative agent on postthrombotic vein wall remodeling in murine and human subjects.

Methods: Features of postthrombotic vein wall remodeling in murine and human subjects were characterized using imaging and histologic examinations. Paclitaxel-loaded hydrogels were used to assess the effects of antiproliferative agent on the remodeling in murine model. Based on the abovementioned results, a pilot study was conducted to assess the effects of paclitaxel-coated balloon dilation in patients with severe PTS experiencing intolerable symptoms. The control cohort was obtained by 1:1 propensity score matching from a prospective database.

Results: Structural and functional alterations in postthrombotic vein wall were verified by imaging and histologic examinations, and predominant active α-smooth muscle actin-positive cells and fibroblast-specific protein 1-positive cells proliferation was observed. In the murine model, the application of paclitaxel-loaded hydrogels inhibited the remodeling. In the pilot clinical study, patients receiving drug-coated balloon demonstrated benefits in Villalta scores and venous clinical severity scores compared with those not receiving drug-coated balloon, and no severe adverse events were reported except for thrombosis recurrence.

Conclusion: Cell proliferation plays an important role in postthrombotic vein wall remodeling. Inhibition of cell proliferation inhibits the remodeling in murine model and may reduce signs and symptoms in patients with severe PTS.