Thrombosis Journal最新文献

Objectives: Cerebral venous sinus thrombosis (CVST) can cause sinus obstruction and stenosis, with potentially fatal consequences. High-resolution magnetic resonance imaging (HRMRI) can diagnose CVST qualitatively, although quantitative screening methods are lacking for patients refractory to anticoagulation therapy and who may benefit from endovascular treatment (EVT). Thus, in this study, we used radiomic features (RFs) extracted from HRMRI to build machine learning models to predict response to drug therapy and determine the appropriateness of EVT.

Materials and methods: RFs were extracted from three-dimensional T1-weighted motion-sensitized driven equilibrium (MSDE), T2-weighted MSDE, T1-contrast, and T1-contrast MSDE sequences to build radiomic signatures and support vector machine (SVM) models for predicting the efficacy of standard drug therapy and the necessity of EVT.

Results: We retrospectively included 53 patients with CVST in a prospective cohort study, among whom 14 underwent EVT after standard drug therapy failed. Thirteen RFs were selected to construct the RF signature and CVST-SVM models. In the validation dataset, the sensitivity, specificity, and area under the curve performance for the RF signature model were 0.833, 0.937, and 0.977, respectively. The radiomic score was correlated with days from symptom onset, history of dyslipidemia, smoking, fibrin degradation product, and D-dimer levels. The sensitivity, specificity, and area under the curve for the CVST-SVM model in the validation set were 0.917, 0.969, and 0.992, respectively.

Conclusions: The CVST-SVM model trained with RFs extracted from HRMRI outperformed the RF signature model and could aid physicians in predicting patient responses to drug treatment and identifying those who may require EVT.

Background: Alpha-thalassemia (α-thalassemia) is one of the most common monogenic diseases in Saudi Arabia and is associated with significant morbidity. Premarital testing programs in Saudi Arabia reduce the burden of hemoglobinopathy disorders, and ongoing monitoring is required. We aimed to explore the molecular nature of α-globin genes and identify the most common genotypes and regions with a high risk of α-thalassemia in Saudi Arabia.

Methods: This retrospective study was conducted between January 2021 and December 2022. Six hundred twenty-five samples from patients with microcytic hypochromic anemia in Saudi Arabia were analyzed using reverse dot blot hybridization (RDBH)-based multiplex-PCR, which screens for the known 21 mutations of α-globin genes.

Results: Seven mutations in the α-globin gene were identified in 88.96% (556) patients. The most frequent abnormality of a-globin genes was -α^3.7 (62.3%), followed by α2^IVS1(-5nt) (20.7%) and α2 polyA-1 (α2^T.Saudi) (14.1%). Interestingly, α2 polyA-2 (α2^T.Turkish) was identified in Saudi and presented with -MED, causing Haemoglobin H disease. The incidence of α-thalassemia in Saudi Arabia's cities showed significant differences (P = 0.004). Jeddah City had the highest percentage of cases (25%), followed by Makkah (23%), Taif (13.3%), and Al-Ahassa (12.4%).

Conclusion: The study provides current knowledge about the molecular nature of α- thalassemia, highlights the common genotypes that could contribute to disease occurrence in the Saudi population, and sheds light on Saudi regions with a high incidence. It also recommends further studies in a larger population and with differently composed molecular assays to verify these findings.

Acute pulmonary embolism (APE) is a potentially fatal disease. Early risk stratification is essential to determining appropriate treatment. We aimed to investigate the predictive value of the Naples Prognostic Score (NPS) for 30-day all-cause mortality in patients with APE. In this retrospective analysis, 325 hospitalized patients with APE were divided into Groups 0 (n = 131), 1 (n = 153), and 2 (n = 41) according to the NPS. The primary outcome event was all-cause mortality during 30 days of follow-up from the day of admission. The correlation between NPS, clinical features, and outcomes in each group was evaluated. The patients were divided into two groups, survivor (n = 294) and nonsurvivor (n = 31), according to their prognosis. The results of the comparison between the three NPS groups revealed that patients with older age, faster heart rate, lower systolic blood pressure, low albumin and total cholesterol levels, high neutrophil to lymphocyte ratio (NLR), low lymphocyte-to-monocyte ratio (LMR), right heart dilatation, heart failure, malignancy, and lower extremity venous thrombosis had significantly higher 30-day all-cause mortality (P < 0.05). Area under the receiver operating characteristic curve (AUC) for NPS to predict all-cause death within 30 days in patients with APE was 0.780 (95% confidence interval [CI] = 0.678-0.855), with sensitivity being 80.6% (95% CI = 0.667-0.946) and specificity being 72.1% (95% CI = 0.670-0.772). Kaplan-Meier (KM) curves showed that Group 2 APE patients had the highest risk of all-cause mortality compared with the other two groups (log-rank test, P = 0.0004). Forest plot visualization using the Cox proportional hazard model showed a significant increase in the risk of 30-day all-cause mortality by 239% (hazard ratio [HR] = 3.385 [1.115-10.273], P = 0.031) and 338% (HR = 4.377 [1.228-15.598], P = 0.023), and the trend test showed a statistical difference (P = 0.042). The study concluded that NPS is a novel, reliable, and multidimensional prognostic scoring system with good prediction of 30-day all-cause mortality in patients with APE.

Systemic lupus erythematosus (SLE) patients have an increased risk of cardiovascular disease and thrombotic events, and the presence of antiphospholipid antibodies further raises the risk of these complications. Here we report a case of a patient with SLE and triple positivity for antiphospholipid antibodies who developed a popliteal artery thrombosis in the context of a severe hyperhomocysteinemia after the introduction of methotrexate (MTX) treatment. MTX is one of the most prescribed medications for a wide spectrum of autoimmune diseases, including SLE. On the other hand, by interfering with folate metabolism, it may induce hyperhomocysteinemia, which, in turn, may increase the risk of vascular complications. Current recommendations suggest screening and, when possible, treating classical and disease-related cardiovascular risk factors in all lupus patients. Based on what observed in our case, we suggest a follow-up of homocysteine levels after the introduction of drugs capable of inducing hyperhomocysteinemia, such as MTX, in SLE patients at high cardiovascular risk.

Background: Disseminated intravascular coagulation (DIC) is a common and critical complication in sepsis. Antithrombin activity, which is considered a biomarker for disease severity, was measured in septic DIC treated with antithrombin concentrates in this study.

Methods: We conducted a retrospective analysis of post-marketing survey data that included 1,800 patients with sepsis-associated DIC and antithrombin activity of 70% or less who were treated with antithrombin concentrates. The changes in sequential organ failure assessment (SOFA) score, DIC score, and antithrombin activity were sequentially assessed. Logistic regression analysis and receiver operating characteristic (ROC) curve analysis were performed to evaluate the performance of antithrombin activity to assess 28-day survival. Furthermore, the relationship between post-treatment antithrombin activity and survival was examined by Logistic regression analysis.

Results: Sex, baseline SOFA score, baseline antithrombin activities, and the presence of pneumonia and soft tissue infection were significantly associated with 28-day mortality. The area under the curve for mortality was 0.639 for post-treatment antithrombin activity, and higher than those of baseline- and delta antithrombin activities. Logistic regression analysis revealed that higher post-treatment antithrombin activity was associated with better 28-day survival. When post-treatment antithrombin activity was more than 80%, the estimated survival was 88.2%. Whereas, the survival was 74.4% when the antithrombin activity was 80% or less (P < 0.0001). However, the relationship between post-treatment antithrombin activity and 28-day survival was considerably different between patients who recovered from DIC by Day 6 compared to those who did not. Similarly, the estimated 28-day survival, based on antithrombin activity, varied among patients with high and low SOFA scores, and the calculation needs to be adjusted based on the severity of the condition.

Conclusions: Post-treatment antithrombin activity measurement was helpful in estimating the 28-day survival in patients with sepsis-associated DIC. However, patient outcomes vary considerably depending on factors that include baseline SOFA score, age, and baseline antithrombin activity. These variables play a substantial role in determining patient prognosis and should be considered when evaluating and interpreting the results.

Background: Venous thromboembolic events (VTE) are a significant cause of morbidity and mortality following traumatic injury. We examined demographic characteristics, chemoprophylaxis, and outcomes of VTE patients with blunt trauma requiring hospitalization.

Methods: A retrospective review of adult blunt trauma hospitalizations with and without VTE between 2012 and 2019 was conducted. Deaths in the emergency department were excluded. Univariate and multivariable analyses, including machine learning classification algorithms for VTE, were performed.

Results: Of 10,926 admitted adult blunt trauma patients, 177 had VTE events. VTE events occurred at a median of 6 [IQR 3-11] days, with 7.3% occurring within 1 day of admission. VTE patients were more often male, and more often underwent surgery. They had higher injury severity as well as longer intensive care unit and hospital lengths of stay. While VTE occurred throughout the spectrum of injury severity, 27.7% had low injury severity (ISS < = 9). In multivariable analyses, both heparin and enoxaparin had reduced adjusted odds ratios for VTE.

Conclusion: Approximately 7.3% of VTE events occurred within one day of admission. A substantial proportion of VTE events occurred in patients with low injury severity (ISS < = 9). Subcutaneous unfractionated heparin and enoxaparin chemoprophylaxis were both inversely associated with VTE. These findings underscore the need for vigilance for VTE identification in blunt trauma patients throughout their hospitalization and VTE prevention efforts.

Current clinical practice guidelines lack explicit guidance on the indications and appropriate timing of venous ultrasound (US) in lower extremity deep vein thrombosis (DVT) follow-up. Moreover, abnormal findings reported on venous US in DVT follow-up or suspected recurrent DVT may be difficult for clinicians to interpret, which carries risk of harm from inappropriate use of anti- coagulation and increased healthcare resource utilization. Due to the above factors, over-use of ultrasound in diagnosis and follow-up of lower extremity DVT has been reported in western health systems. We have undertaken a case-based discussion and a scoping review of existing guidelines on the use of venousUS following prior diagnosis of DVT, to guide appropriate interpretation of commonly reported US abnormalities and provide our suggestions in the light of best available evidence on appropriate timing to perform follow-up US in management of lower extremity DVT.

Background: Previous cohort studies have shown that exogenous sex hormone use, such as testosterone replacement therapy and oestrogen-containing contraceptives, can increase the risk of venous thromboembolism (VTE). However, the relationship between endogenous sex hormone levels and VTE remains unclear. The goal of the present study was to explore the causal roles of endogenous sex hormones, including hormone-binding globulin (SHBG), bioactive testosterone (BT), and total testosterone (TT), in VTE and its two subgroups, deep vein thrombosis (DVT) and pulmonary embolism (PE).

Methods: We used a genome-wide association study of sex hormones as exposure data and Finnish VTE data as the outcome. Inverse variance weighting, MR-Egger, and weighted median were used for two-sample Mendelian randomisation (MR). Sensitivity analyses included MR-Egger, MR-PRESSO, Cochrane Q test, MR Steiger, leave-one-out analysis, and funnel plot, combined with multivariate MR and replicated MR analyses using larger VTE data from the global biobank meta-analysis initiative. Linkage disequilibrium score regression (LDSC) was used to determine genetic associations and estimate sample overlap.

Results: Our findings genetically predicted that an increase in serum SHBG levels by one standard deviation (SD) caused 25% higher odds for VTE (OR: 1.25, 95% CI: 1.01-1.55) and 58% higher odds for PE (OR: 1.58, 95% CI: 1.20-2.08). LDSC supported the genetic correlation between these two traits and replicated analyses confirm SHBG's genetic effect on VTE in both sexes (OR: 1.46, 95% CI: 1.20-1.78) and in females (OR: 1.49, 95% CI: 1.17-1.91). In addition, an increase in serum TT levels by one SD caused 32% higher odds for VTE (OR: 1.32, 95% CI: 1.08-1.62) and 31% higher odds for DVT (OR: 1.31, 95% CI: 1.01-1.69); however, LDSC and replicated analyses did not find a genetic correlation between TT and VTE or its subtypes. No significant correlation was observed between BT and all three outcome traits.

Conclusion: Our study provides evidence that elevated serum SHBG levels, as predicted by genetics, increase VTE risk. However, the causal effect of testosterone levels on VTE requires further investigation.

Background: Hemophilia A (HEMA) is an X-linked bleeding disorder caused by reduced/absent coagulation factor VIII expression, as a result of pathogenic variants in the F8 gene. Preimplantation prevention of HEMA should ideally include direct pathogenic F8 variant detection, complemented by linkage analysis of flanking markers to identify the high-risk F8 allele. Linkage analysis is particularly indispensable when the pathogenic variant cannot be detected directly or identified. This study evaluated the suitability of a panel of F8 intragenic and extragenic short tandem repeat markers for standalone linkage-based preimplantation genetic testing for monogenic disorder (PGT-M) of the Inv22 pathogenic variant, an almost 600 kb paracentric inversion responsible for almost half of all severe HEMA globally, for which direct detection is challenging.

Methods: Thirteen markers spanning 1 Mb and encompassing both F8 and the Inv22 inversion interval were genotyped in 153 unrelated females of Viet Kinh ethnicity.

Results: All individuals were heterozygous for ≥ 1 marker, ~ 90% were heterozygous for ≥ 1 of the five F8 intragenic markers, and almost 98% were heterozygous for ≥ 1 upstream (telomeric) and ≥ 1 downstream (centromeric) markers. A prospective PGT-M couple at risk of transmitting F8 Inv22 were fully informative at four marker loci (2 intra-inversion, 1 centromeric, 1 telomeric) and partially informative at another five (2 intra-inversion, 3 centromeric), allowing robust phasing of low- and high-risk haplotypes. In vitro fertilization produced three embryos, all of which clearly inherited the low-risk maternal allele, enabling reliable unaffected diagnoses. A single embryo transfer produced a clinical pregnancy, which was confirmed as unaffected by amniocentesis and long-range PCR, and a healthy baby girl was delivered at term.

Conclusion: Robust and reliable PGT-M of HEMA, including the common F8 Inv22 pathogenic variant, can be achieved with sufficient informative intragenic and flanking markers.

Background: Immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disease characterized by increased platelet destruction and impaired thrombopoiesis. The changes in platelet indices depend on the morphology and volume of platelets. Serum lipids have been found to affect platelet formation and activity in certain diseases, thus inducing the corresponding variation of platelet indices.

Methods: Mendelian randomization (MR) analysis was performed based on databases. The clinical data from 457 ITP patients were retrospectively collected and analyzed, including platelet indices, serum lipids, hemorrhages and therapeutic responses.

Results: MR analysis showed low high-density-lipoprotein-cholesterol (HDL-C), low apolipoprotein A-1, high triglyceride (TG) and high apolipoprotein B (ApoB) caused high platelet distribution width (PDW); high low-density-lipoprotein-cholesterol (LDL-C) increased mean platelet volume (MPV). In ITP, there were positive correlations between platelet count with TG, PDW with HDL-C and ApoB, and plateletcrit with TG and non-esterified fatty acid, and the correlation had gender differences. Bleeding scores were negatively correlated with cholesterol and LDL-C. LDL-C and homocysteine were risk factors for therapeutic responses.

Conclusions: Serum lipids, especially cholesterol were tightly correlated with platelet indices, hemorrhage and therapeutic effects in ITP patients. These results provide clinical references for the management of serum lipids, and highlight the necessity to further explore the relationship between lipids and pathogenesis of ITP.

Trial registration: No: NCT05095896, October 14, 2021, retrospectively registered.