Clinical and Applied Thrombosis/Hemostasis最新文献

The objective of this survey was to gain a real-world perspective on coagulation testing by evaluating the availability of various coagulation laboratory tests, assessing specific analytic and postanalytic steps in clinical laboratories in Korea.Participants were surveyed using a 65-question questionnaire specifically focused on their coagulation testing practices related to prothrombin time (PT), activated partial thromboplastin time (aPTT), plasma-mixing studies, lupus anticoagulant (LA) tests, platelet function tests, coagulation factor assays, and the composition of hemostasis and thrombosis test panels. The survey was performed between July and September 2022.The survey achieved a 77.9% (81 of 104) response rate. PT or aPTT tests were performed directly at all participating institutions, followed by D-dimer and fibrinogen tests, platelet function test, and plasma-mixing studies in order of frequency. Variations existed in the performance of mixing test and LA assessment. Patterns of coagulating testing differed depending on the size of the hospital. The survey revealed that most laboratories conducted coagulation tests following the international guidelines such as Clinical Laboratory Standards Institute guidelines and the Korean Laboratory Certification system. However, some coagulation tests, including mixing test and LA tests, are yet to be standardized in Korea.Continuous education on coagulation test methods and internal and external quality control are required to encourage laboratories to enhance the performance of coagulation testing.

Introduction: Immature platelets or reticulated platelets are newly released thrombocytes. They can be identified by their large size and high RNA cytoplasm concentration. Immature platelet fraction (IPF) represents the percentage of immature circulative platelets relative to the total number of platelets. The role of IPF in patients undergoing transcatheter aortic valve implantation (TAVI) is unknown. The aim of the current trial was to assess the levels of IPF in patients undergoing TAVI and correlation with clinical outcomes.

Material and methods: Immature platelet fraction levels were measured 3 times in all patients (preprocedure, 1-2 days post-procedure and 1-month post-procedure). Immature platelet fraction measurement was carried out using an autoanalyzer (Sysmex XE-2100). Patients were followed for 12 months. Primary outcomes were defined as complications during hospitalizations, rehospitalization, and mortality.

Results: Fifty-one patients were included in the study. Mean age was 79.8 (±9.6), and 28 (55%) were women. Twenty-one patients (41%) had complications: Of them, 6 of 21 (29%) occurred during hospitalizations (2-vascular complications; 2-sepsis, 2-implantation of a pacemaker), 9 of 21 (43%) patients were rehospitalized after the index admission, and 6 patients died during the follow-up period. Multivariate Cox regression analysis found that IPF < 7% in at least one of the 3 tests was associated with worse outcomes (hazard ratio 3.42; 95% CI 1.11-10.5, P = .032).

Conclusion: Immature platelet fraction >7% in patients undergoing TAVI is associated with worse outcomes. Further studies are needed to better understand this phenomenon.

Cangrelor is a rapid-acting, intravenous P2Y12 inhibitor that can be used in patients after percutaneous coronary intervention who require mechanical circulatory support or as a bridge to procedure. We retrospectively reviewed adult patients who received platelet function testing (PFT) with the VerifyNow P2Y12 assay while on cangrelor from March 2021 through November 2022. All patients were initiated on 0.75 mcg/kg/min of cangrelor with P2Y12 reaction unit (PRU) values collected 12-24 h after initiation. Cangrelor doses were adjusted per protocol to maintain PRU values of 85-208. A total of 42 patients were included. Thirty-eight patients (90.5%) required temporary mechanical circulatory support while on cangrelor, and 4 patients (9.5%) received cangrelor as a bridge to procedure. The median cangrelor maintenance dose was 0.5 (interquartile range [IQR]: 0.375-0.75) mcg/kg/min, and the median time in therapeutic range with a PRU value between 85 and 208 was 66.6% (IQR: 39.6%-100%). No patients experienced stent thrombosis. A composite major adverse cardiovascular event occurred in 4 patients (9.5%), and major bleeding occurred in 16 patients (38.1%). Compared to empiric cangrelor dosing of 0.75 mcg/kg/min, PFT-guided cangrelor dose adjustment was associated with a median drug cost savings of $1605.60 (IQR: $0-4281.56). Utilizing PFT with cangrelor may allow for lower, individualized dosing while preventing stent thrombosis.

Although the relationship between venous thromboembolism (VTE) and cancer has been a subject of study, knowledge of the contribution of thrombophilia to thrombosis in patients with cancer is still very limited. The aim of this article is to collect present knowledge on the contribution of inherited thrombophilia to VTE in cancer patients. We performed a search in Google Scholar and PubMed and selected 21 from 76 returned articles. Then we made a narrative review of the selected articles. We describe 11 studies on the contribution of inherited thrombophilia to VTE in cancer patients in general and 10 on that contribution in specific types of cancer: 1 in colorectal cancer, 4 in breast cancer, 1 in gynecologic cancer and 4 in hematopoietic malignancies. All studies investigate the relation of factor V Leiden (FVL) to VTE, 13 that of the prothrombin G20210A mutation (PTG20210A) and 7 studies also investigate other inherited thrombophilias, such methylenetetrahydrofolate reductase gene mutations, although only 2 investigate the contribution of deficiencies of the natural anticoagulants. Studies are very heterogeneous, in design and sample size and conclusions differ considerably. There is no consensus on the contribution of inherited thrombophilia to VTE in cancer patients except for acute lymphoblastic leukemia in children. Probably, that contribution is not the same for all types of cancer and more studies are needed to bring more knowledge on this subject.

Cerebral venous sinus thrombosis (CVST) is a rare neurovascular condition that has been observed in individuals with coronavirus disease 2019 (COVID-19). This systematic review aimed to explore the sex differences and characteristics of concurrent COVID-19 and CVST cases. A total of 212 CVST patients were included in the study. Women with CVST had a slightly higher mean age compared to men (47.359 years vs 46.08 years). Women were more likely to report symptoms such as fever (56.1%) and decreased sense of smell or taste (71.4%), while men more frequently experienced nausea or vomiting (55.6%), headache (62.9%), and seizures (72%). Notably, current smokers, who were predominantly men, had a higher occurrence of CVST. On the other hand, women had a higher likelihood of CVST risk factors such as oral contraceptive pill (OCP) use and autoimmune diseases. Treatment approaches also showed sex-based differences. Unfractionated heparin was administered more often to women with CVST (63.2%). The in-hospital mortality rate for CVST patients was 21.3%, with men having a significantly higher mortality rate than women (65.2% vs 34.8%, P = .027). Survival analysis revealed that factors such as smoking history, diabetes mellitus, hypertension, OCP use, COVID-19 symptoms, CVST symptoms, and the need for intubation significantly influenced survival outcomes. Understanding these sex differences in COVID-19-related CVST is crucial for accurate diagnosis and effective management, ultimately leading to improved patient outcomes. Our findings highlight the importance of considering sex as a factor in the evaluation and treatment of individuals with COVID-19 and concurrent CVST.

In patients with end-stage renal disease (ESRD), heart failure with reduced ejection fraction (HFrEF) is a common comorbidity. Thromboinflammatory processes in both conditions represent complex pathophysiology, demonstrated by dysregulation of thromboinflammatory biomarkers, and commonly resulting in the combined pathology of cardiorenal syndrome. We sought to investigate the effects of HFrEF on these biomarkers in patients with ESRD, and observe the relationship to mortality. Blood samples from 73 patients with ESRD (mean age 67 ± 13 years, 56% male) and 40 healthy controls were analyzed via enzyme-linked immunosorbent assay and other chromogenic methods for angiopoietin-2 (Ang2), endogenous glycosaminoglycans, fatty acid binding protein, interleukin-6, lipopolysaccharide, free fatty acids, NT-pro B-type natriuretic peptide, tumor necrosis factor α, vascular endothelial growth factor, and von Willebrand factor. Patients were stratified into those with or without HFrEF (EF < 50%). Patients had highly prevalent comorbidities including coronary artery disease 46%, diabetes 69%, hypertension 97%, and smoking 49%. Most biomarkers were upregulated in ESRD compared to controls. Patients with HFrEF and ESRD had greater interleukin-6 and NT-pro B-type natriuretic peptide and lesser lipopolysaccharide compared to ESRD only. Spearman correlations between most biomarkers were increased in HFrEF + ESRD over ESRD only. Ang-2 was associated with mortality in this cohort. The dysregulation of thromboinflammation in ESRD is somewhat amplified in comorbid HFrEF. Correlation among biomarkers in this cohort indicates the mechanisms of thromboinflammatory biomarker generation in ESRD and HFrEF share an integrative process. Ang2, interleukin-6, and lipopolysaccharide show promise as biomarkers for risk stratification among patients with both HFrEF and ESRD.

Direct oral anticoagulants (DOACs) changed stroke prevention and decreased the risk of ischemic and hemorrhagic complications in patients on oral anticoagulation (OAC) therapy. The numbers of patients prescribed DOACs has increased rapidly. Availability of specific reversal agents opened new avenues in the prevention and management of DOAC complications. An ideal specific reversal agent for a DOAC in acute stroke is an agent which lacks safety concerns and immediately reverses DOAC anticoagulation activity, thereby enabling effective treatment. Reversal of anticoagulant activity is mandatory in patients with acute ischemic stroke (AIS) before performing therapeutic procedures such as intravenous thrombolysis (IVT) and neurosurgery in intracranial hemorrhage (ICH) in order to improve clinical outcomes. In this manuscript we pursue an interdisciplinary approach in discussing advantages and concerns of specific reversal agents in acute stroke DOAC-treated patients in everyday clinical practice.

Introduction: Essential thrombocythemia (ET) involves the proliferation of megakaryocytes and platelets and is associated with an increased risk of thrombosis. We aimed to evaluate thrombotic risks in patients with epigenetic regulator mutations and generate a model to predict thrombosis in ET.

Materials and methods: This cohort study enrolled patients aged > 15 years diagnosed with ET at the Songklanakarind Hospital between January 2002 and December 2019. Twenty-five targeted gene mutations, including somatic driver mutations (JAK2, CALR, MPL), epigenetic regulator mutations (TET2, DNMT3A, IDH1, IDH2, TET2, ASXL1, EZH2, SF3B1, SRSF2) and other genes relevant to myeloid neoplasms, were identified using next-generation sequencing. Thrombotic events were confirmed based on clinical condition and imaging findings, and thrombotic risks were analyzed using five survival models with the recurrent event method.

Results: Ninety-six patients were enrolled with a median follow-up of 6.91 years. Of these, 15 patients experienced 17 arterial thrombotic events in total. Patients with JAK2 mutation and IDH1 mutation had the highest frequency of thrombotic events with somatic driver mutations (17.3%) and epigenetic regulator mutations (100%). The 10-year thrombosis-free survival rate was 81.3% (95% confidence interval: 72.0-91.8%). IDH1 mutation was a significant factor for thrombotic risk in the multivariate analysis for all models. The Prentice, William, and Peterson (PWP) gap-time model was the most appropriate prediction model.

Conclusions: The PWP gap-time model was a good predictive model for thrombotic risk in patients with ET. IDH1 mutation was significant risk factors for thrombosis; however, further studies with a larger sample size should confirm this and provide more insight.

Background: Acute venous thromboembolism (VTE) in children presents unique challenges due to the limitations of standard anticoagulation therapies. Herein, we aimed to systematically review randomized controlled trials (RCTs) evaluating the efficacy and safety of direct oral anticoagulants (DOACs) in pediatric patients with acute VTE.

Methods: PubMed and Embase databases were searched for RCTs comparing DOACs to standard anticoagulation in pediatric VTE patients. Efficacy outcomes included VTE recurrence and all-cause mortality, while safety outcomes comprised major bleeding and other adverse events.

Results: Three RCTs with 790 participants were included. When compared with standard anticoagulation, DOACs demonstrated a reduced risk of VTE recurrence (risk difference[RD] = -3%, 95% confidence interval[CI]: -6% to 0%, P = 0.04) and an increased risk of any adverse event (RD = 8%, 95% CI: 1% to 14%, P = 0.02). No significant differences were found in all-cause mortality, major bleeding, clinically relevant non-major bleeding, or total bleeding between the DOAC and control groups.

Conclusion: DOACs, primarily dabigatran and rivaroxaban, are non-inferior to standard anticoagulants in reducing VTE recurrence in pediatric patients, with comparable safety profiles. Further research is essential to confirm these findings.