Thrombosis Journal最新文献

Background: Antithrombin, a key regulator of the coagulation cascade, is often decreased in patients with sepsis-associated disseminated intravascular coagulation (DIC). Antithrombin is commonly supplemented when activity levels fall to 70% or below in Japan. While there is considerable interindividual variability in antithrombin activity following treatment, the factors contributing to this variability remain unclear. This study aims to identify the determinants of post-treatment antithrombin activity levels and to investigate the potential association between antithrombin activity and bleeding risk.

Methods: We conducted a retrospective analysis using data from the post-marketing surveillance of antithrombin concentrate in patients with sepsis-associated DIC. Changes in antithrombin activity were calculated as: (Day 1 activity - baseline activity [%]) divided by the daily dose (international units [IU] per kilogram of body weight). Logistic regression analysis was employed to identify factors associated with changes in antithrombin activity following supplementation and factors related to bleeding risk. Additionally, Kaplan-Meier survival curves were used to examine the relationship between antithrombin activity and 28-day survival outcomes.

Results: A total of 1,524 patients were included in the analysis. The median baseline antithrombin activity was 49%, which increased to 74% on day 1 post-treatment. The mean change in antithrombin activity was 0.99% /IU/kg and followed a normal distribution. The SOFA score ≥ 13 (p = 0.035) and FDP score ≥ 3 (≥ 25μg/mL), part of the JAAM DIC score, (p = 0.016) were significantly associated with lower antithrombin activity increase. Patients achieving ≥ 1% /IU/kg increase showed a higher 28-day survival rate (relative risk: 0.72, p = 0.004). No significant association was found between antithrombin doses or activity changes and bleeding risk.

Conclusion: A higher SOFA score and FDP level were associated with a smaller increase in post-treatment antithrombin activity. There was no clear association between antithrombin doses and bleeding risk. The present study suggests the necessity of individualized dosing beyond weight-based regimens.

Background: Rapid diagnosis and treatment of deep vein thrombosis (DVT) reduce morbidity and mortality.

Objective: This study aimed to investigate the time to diagnostic imaging, time to treatment, and outcomes associated with the delayed treatment of DVT.

Methods: We retrospectively investigated 110 patients who were diagnosed with proximal DVT in outpatient clinics in a single academic centre in Thailand from January 2019 to September 2020. We recorded demographic data, clinical presentations, time to diagnostic imaging (ultrasound of the legs), and time to treatment. We recorded outcomes, including death, pulmonary embolism (PE), recurrent DVT, and thrombus resolution 3 months after the diagnosis of DVT.

Results: Of all 110 patients, 42 (38.2%) were male. Median age (IQR) was 68.5 (58-80) years. The median (IQR) time to diagnostic imaging was 7 days (2-27). The median (IQR) interval from the first OPD visit to the initiation of treatment was 14 days (3-31). The delayed diagnosis (more than 7 days from the first clinic visit to diagnostic imaging) was observed in 54 (49%) patients with DVT. The delay in treatment (more than 7 days from the first clinic visit to treatment) was observed in 67 (60.9%) patients. The maximum time to treatment was 160 days. Death and PE occurred in 9% and 33% of patients with delayed treatment, while they occurred in 5% and 20% of those with early treatment, respectively. No recurrent DVT was observed. Among 25 patients who had follow-up imaging, residual thrombus occurred in 71% of patients with delayed treatment and 63% of those with early treatment.

Conclusion: Half of the DVT patients had delays in diagnosis and treatment of proximal DVT. The routine request option was associated with a delayed diagnosis. The importance of early diagnosis and treatment of DVT should be raised among physicians, and improvement strategies are warranted.

Background: Cerebrovascular disease (CVD) remains a leading cause of death in the United States. Although the role of conventional stroke risk factors is well established, the impact of coagulation disorders-both inherited and acquired-on long-term CVD mortality remains underexplored.

Methods: We conducted a cross-sectional analysis using U.S. death certificate data from the CDC WONDER platform (1999-2020). Adults aged ≥ 25 years with CVD as the underlying cause and any coagulation disorder listed as a contributing cause were included. Age-adjusted mortality rates (AAMRs) were calculated per 100,000 population. Joinpoint regression was used to evaluate temporal trends, estimating Annual Percent Change (APC) and Average Annual Percent Change (AAPC) across subgroups.

Results: Between 1999 and 2020, 54,545 CVD-related deaths occurred among adults with coagulation disorders. The overall AAMR was 1.16, with a significant decline over time (AAPC: - 0.58%, 95% CI: - 0.87 to - 0.28; p = 0.0010). Males had higher mortality than females (1.35 vs. 1.01), but females showed greater declines (AAPC: - 0.96% vs. - 0.32%). Black and American Indian individuals experienced the highest rates but also the steepest improvements (AAPCs: - 1.87% and - 2.02%, respectively). In contrast, Hispanic populations showed early declines followed by recent increases. Only the Northeast region had a statistically significant mortality reduction. Rural residents and those in the South had stagnant trends. Mortality rose sharply with age, peaking in adults ≥ 85 years, although older groups also showed significant declines. Most deaths (77%) occurred in inpatient settings.

Conclusions: Although overall CVD mortality declined modestly, widening disparities by sex, race, region, and age group signal critical gaps in prevention and care.

Bleeding diathesis' diagnosis can be challenging due to the high number of disorders with hemorrhagic symptomatology. Sitosterolemia is a rare disease characterized by increased sterols plasma levels and cardiovascular, cutaneous, articular, and hematological manifestations, including anemia and macrothrombocytopenia. The disorder is caused by ABCG5 and ABCG8 mutations.We present a case of a patient with bleeding diathesis, macrothrombocytopenia, a moderate defect of primary hemostasis and a pathological platelet aggregation analysis, with an initial diagnosis of Bernard-Soulier variant syndrome. After performing a genetic study using an exome analysis, the patient had two ABCG8 gen variants, one pathogenic (NP_071882.1:p.Trp536Ter (NM_022437.2:c.1608G > A) variant, ClinVar ID: 499930) and the other one probably pathogenic (NP_071882.1:p.Leu465Arg (NM_022437.2:c.1394T > G) variant), changing the diagnosis to sitosterolemia, which has its own therapeutic approach.This case report shows the importance of the genetic analysis. Sitosterolemia should be suspected in the presence of macrothrombocytopenia, stomatocytes in the blood smear and hemolytic anemia, performing a genetic study including ABCG5 and ABCG8 gene variants.

Background: Angiogenesis inhibitors are vital in cancer treatment but are increasingly linked to thromboembolic events (TEEs), impacting patient outcomes. Despite extensive clinical trials, real-world data on TEEs associated with these agents remain limited. This study examines real-world TEEs patterns using the FDA Adverse Event Reporting System (FAERS).

Method: A retrospective pharmacovigilance analysis was conducted using FAERS data spanning from 2014 to 2024. Reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) was applied to identify significant safety signals. A signal was considered present when the lower limit of the 95% confidence interval for ROR (ROR025) > 1 and that for information component (IC025) > 0, with a minimum requirement of three or more reported cases.

Results: A total of 13,897 TEEs were identified, with 34.9% classified as arterial thromboembolism events (ATEs), 26.5% as venous thromboembolism events (VTEs), and 38.6% as TEEs of unknown origin (other TEEs). Our findings indicate a significant correlation between the use of angiogenesis inhibitors and an increased reporting frequency of TEEs. The disproportionality analysis revealed strong signals for several agents, with the top five drugs being cediranib, aflibercept, ramucirumab, cabozantinib, and sunitinib. The median time-to-onset (TTO) was 32 days (IQR: 6-141), with 48.5% of cases occurring within the first month and 12% persisting beyond one year. Temporal analysis demonstrated a declining incidence pattern, confirmed by Weibull distribution (shape parameter β = 0.63, indicating early failure type). The most frequently reported outcomes of TEEs associated with angiogenesis inhibitors were hospitalization and other serious events.

Conclusion: This study provides a real-world assessment of TEES risk associated with angiogenesis inhibitors. Identifying high-risk agents and temporal patterns underscores the need for early monitoring and highlights their contribution to TEEs in clinical practice.

Background: Majority of people with "kissing carotids", an anatomical variation of the cervical carotid arteries showing tortuosity, kinking or coiling and coming in proximity at the midline are asymptomatic. Less than 1% of the general population have Protein S Deficiency. This report discusses a rare case of a young female with co-existent Protein S deficiency and kissing carotids, who presented with sequential thrombosis in both arterial and venous cerebral circulation systems and further discusses potential mechanisms of arterial thrombosis in Protein S deficiency and medical options for secondary stroke prophylaxis in this context.

Case presentation: A 29-year-old female presented with sudden left hemiparesis and dysarthria. Index Brain MRI revealed acute non-haemorrhagic infarcts in the right middle cerebral artery (MCA) territory. Index brain MRA of cerebral vessels revealed abrupt cut off of the right MCA M1 segment following arterial thrombosis with extracranial kissing internal carotid arteries. Interval imaging of her brain and cerebral vasculature on day 4 of admission following a convulsion revealed left transverse cerebral venous sinus thrombosis. Laboratory workup confirmed low Protein S activity of only 18% (normal 55-123). She was started on rivaroxaban for lifelong secondary arterial stroke prophylaxis.

Conclusions: This is an index sub-Saharan case report of a young female with co-existent Protein S deficiency and kissing carotids phenomenon presenting with sequential cerebral arterial and venous thromboses. Potential mechanisms of arterial thrombosis in Protein S deficiency in which case warfarin may not be a preferred singular option for secondary arterial stroke prophylaxis are discussed.