Thrombosis Journal最新文献

Background: Hypothermia and acidosis individually inhibit haemostasis. We designed this study with the aim to investigate whether rivaroxaban combined with hypothermia or acidosis exhibit synergistic inhibitory effects on haemostasis using ROTEM^®.

Methods: Patients with a clinical indication to start rivaroxaban treatment were prospectively included. Blood samples were collected before initiation of treatment and the day after. All blood samples were in vitro modified with respect to temperature (incubated and analysed at 28, 33, 37 and 40 degrees Celsius (°C)) and pH (6.8, 7.0, 7.2 and 7.4). The temperature and acidosis effects on the ROTEM EXTEM variables clotting time (CT), clot formation time (CFT) and alpha-angle (AA) were measured along with the individual effect of rivaroxaban on the same variables. The additive effect was calculated. The observed (potential synergistic) effects for the temperature and pH modified rivaroxaban samples on the same ROTEM variables, were registered. Differences between the additive and observed (potential synergistic) effects were analysed using matched non-parametric hypothesis testing.

Results: In total, 13 patients were included. Hypothermia and rivaroxaban exhibited a synergistic effect on CT at 28 °C (p = 0.0002) and at 33 °C (p = 0.0007). The same applied for acidosis at pH 6.8 (p = 0.003) and pH 7.0 (p = 0.003). There were no signs of synergistic effects of rivaroxaban and temperature or acidosis on CFT. In AA there were signs of synergism at 28 °C (p = 0,001), but not at other tested temperatures or pH levels.

Conclusions: The combination rivaroxaban together with hypothermia or acidosis demonstrated inhibitory synergistic effects on haemostasis.

Trial registration: The study was retrospectively registered 2023-03-01 at ClinTrials.gov with NCT05669313.

Recent years have seen ticagrelor, a potent P2Y12 inhibitor, emerge as a significant advancement in the peri-thrombolytic management of patients with ST-segment elevation myocardial infarction (STEMI), offering a promising alternative to traditional antiplatelet drugs like clopidogrel. This review critically examines the efficacy and safety of ticagrelor during the peri-thrombolytic phase in STEMI patients, drawing on evidence from key clinical trials such as TREAT and MIRTOS, as well as other relevant studies. These investigations underscore ticagrelor's superior platelet inhibition capabilities, which are crucial for minimizing thrombotic complications post-thrombolysis without increasing bleeding risks. Despite its potential, clopidogrel remains the guideline-recommended choice for such patients, leaving the appropriateness of ticagrelor in this context open to debate. By summarizing the current evidence and identifying gaps in our understanding, this study advocates for targeted research to clarify the long-term benefits and optimal deployment of ticagrelor, highlighting its evolving significance in cardiovascular care.

Bleeding events in patients receiving direct oral anticoagulation (DOAC) can be life-threatening even at therapeutic DOAC plasma concentrations, as anticoagulation impairs hemostasis and should therefore be identified immediately after hospital admission. The anticoagulatory effects of DOAC are typically not measurable in standard coagulation tests, such as PT or aPTT. Specific calibrated anti-FXa-tests allow specific drug monitoring, but they are too time-consuming for critical bleeding events and are commonly not available for 24 h/7 days in routine care. However, recent advances in point-of-care (POC) viscoelastic testing (VET) have shown a promising approach for rapid and quantitative detection of DOAC plasma concentrations using the Russell viper venom factor V activator (RVV for FXa-inhibitors) test or the ecarin clotting time (thrombin inhibitors). In acute bleeding situations, direct FXa inhibitors can be reversed by specific antidote andexanet alfa or hemostasis can be improved by prothrombin complex factor concentrates (PCCs). After reversal, confirmation of reversal efficacy is often requested, but no routine assays are currently available. Thus, the emergency management of bleeding DOAC patients is usually "blinded" with regard to reversal efficacy. POC VET laboratory assays might therefore also be helpful for measuring DOAC effects after reversal. We present a case series demonstrating the usefulness of RVV-clotting time post-DOAC reversal with andexanet alfa.

Essential thrombocythemia (ET) is a myeloproliferative malignancy caused by the excessive proliferation of megakaryocytes in the bone marrow, resulting in the overproduction of peripheral platelets. ET can lead to thrombotic events, such as ischemic stroke (IS), though it is a rare cause of IS. Bilateral medial medullary infarction (BMMI), also known as "Y appearance" infarction due to its distinctive imaging morphology, is a rare clinical subtype of IS which typically has a poor prognosis and a high mortality rate. Herein, we report the case of a 43-year-old male with a history of ET. The patient's platelet count was poorly controlled, and he did not receive regular treatment. After developing symptoms such as dizziness, dysphagia, choking on water, slurred speech, blurred vision, and bilateral limb numbness. Head magnetic resonance imaging revealed a "Y appearance" infarction in the bilateral medial medulla. After admission, the patient was administered intravenous antiplatelet therapy with tirofiban. However, when he was switched to oral aspirin after three days, he experienced decreased muscle strength and worsening symptoms. Therefore, tirofiban was continued for 14 days. Upon discharge, the patient experienced residual limb numbness. His National Institutes of Health Stroke Scale score was 1, Modified Rankin Scale score was 0, and platelet count had decreased to the normal range. During the 9-month follow-up period after discharge, the patient still had only mild limb numbness. Our report presents a special case of "Y appearance" infarction due to ET. Owing to fluctuations in the patient's condition, he received long-term high-dose tirofiban, which ultimately led to a significant improvement in his symptoms.

Background: The association between uric acid and pulmonary embolism(PE) remains controversial, and there has been limited investigation into how uric acid influences pulmonary embolism across different age groups. Our study aimed to elucidate the relationship between uric acid levels and pulmonary embolism, considering variations across age groups.

Methods: A total of 368 patients who underwent computed tomography pulmonary angiography from July 2018 to May 2022 were included in the analysis. Subsequently, the cohort was stratified by age, with separate univariate and multivariate logistic regression analyses conducted for the elderly (aged ≥ 60 years) and non-elderly (aged < 60 years), respectively.

Results: The study revealed that patients with PE exhibited higher uric acid levels compared to those without (325.11 ± 137.02 vs. 298.26 ± 110.54 (umol/l), p = 0.039). This disparity persisted even after adjusting for multiple confounders (OR = 1.002, 95% CI 1.000-1.005, p = 0.042). Additionally, a notable age difference was observed between PE and non-PE patients (65.7 ± 16.12 vs. 61.42 ± 15.03 (umol/l), p = 0.009). Subsequently, upon age stratification, significant differences (p < 0.05) in serum uric acid were noted between PE and non-PE patients in both elderly and non-elderly populations. However, elevated uric acid levels were independently associated with PE only in the elderly following adjustment for multiple confounders (OR = 1.003, 95% CI 1.001-1.005, p = 0.008).

Conclusion: High uric acid levels are an independent risk factor for pulmonary embolism in the elderly (≥ 60 years).

Background: Carotid artery stenting (CAS) is a key treatment option for moderate to severe carotid artery stenosis. Carotid stent thrombosis (CST), a rare complication of CAS, has gained significant attention because of its catastrophic nature. More evidences are needed to guide the diagnosis and treatment of CST.

Case presentation: This study reports a rare case of sub-acute CST following CAS in a 50-year-old male patient who had experienced repeated cerebrovascular events on the premise of taking antiplatelet drugs. He also suffered an occlusion of the left middle cerebral artery (MCA) in the M2 segment, likely caused by an embolus detached from the stent thrombus. The cause of CST in this patient was presumed to be dual antiplatelet resistance (AR), as indicated by genetic testing. After treated with guide catheter-directed thrombolysis, thrombus aspiration, and a second round of thrombolysis, his in-stent thrombus was basically cleared. His M2 occlusion was resolved by mechanical thrombectomy using the Solitaire FR/Stent with Intermediate Catheter Assisting technique. The patient recovered well after replacement of antiplatelet drugs, and no new thromboembolic event occurred during the 13-month follow-up period.

Conclusions: The occurrence rate of AR-related CST may be underestimated as the cause of majority CST cases remains unclear. Implementation of genetic test for aspirin and clopidogrel resistance may be helpful to find the possible cause of CST and to avoid future repeated cerebrovascular events by replacement of antiplatelet drugs.

Homozygous familial hypercholesterolemia (HoFH), is a rare genetic disorder characterized by dual mutations in the low-density lipoprotein receptor (LDLR) gene, leading to dysfunctional or absent LDLRs, often accompanied by severe premature Atherosclerotic Cardiovascular Disease (ASCVD) and exhibiting refractoriness to aggressive pharmacological interventions. Double filtration plasmapheresis (DFPP), a form of lipoprotein apheresis (LA), has been effectively utilized as an adjunctive treatment modality to reduce serum LDL-C levels in refractory cases of HoFH. Here, we report a case of a 36-year-old female with HoFH who developed xanthomas on her limbs and waist at age 7. Despite maximum-tolerated doses of statins from age 32, combined with ezetimibe and evolocumab, her LDL-C levels remained critically elevated at 12-14 mmol/L. Her genetic testing confirmed a homozygous LDLR mutation. At 35 years old, she experienced exertional chest pain, and percutaneous coronary intervention revealed severe calcific left main stenosis, necessitating stent implantation. Subsequently, she initiated once every 1-2 months DFPP. Pre-DFPP, her LDL-C and total cholesterol (TC) levels were 13.82 ± 3.28 and 15.45 ± 0.78 mmol/L, respectively. Post-DFPP, her LDL-C and TC levels significantly decreased to 2.43 ± 0.33 mmol/L (81.76 ± 4.11% reduction) and 3.59 ± 0.41 mmol/L (76.76 ± 2.75% reduction), respectively. Lipoprotein (a) and triglycerides also decreased by 89.10 ± 1.39% and 42.29 ± 15.68%,respectively. Two years later, there was no progression of coronary artery disease, and her symptoms and xanthomas regressed significantly. Collectively, DFPP effectively reduces LDL-C levels in refractory cases of HoFH and contributes to delaying ASCVD progression, representing an efficacious adjunctive therapeutic modality.

Background: Sepsis is a life-threatening condition that affects 49 million people annually. Managing sepsis-associated coagulopathy poses a significant challenge due to its high mortality rates in intensive care. Recent reports suggest that administering heparin may offer potential survival benefits in sepsis and coronavirus disease cases. However, there is currently no established evidence supporting the use of heparin for sepsis. Thus, in this study, we aimed to assess the efficacy of heparin administration in patients with sepsis.

Methods: A systematic review was conducted following the PRISMA guidelines. The searches included MEDLINE, Cochrane, and Japanese databases up to January 2023. The inclusion criteria consisted of randomized control trials (RCTs) involving adult sepsis patients receiving heparin. The risk of bias was assessed using RoB2, and the data extraction included 28-day mortality and bleeding complications.

Results: Out of 1733 initial articles, only three studies met the inclusion criteria. The analysis, which included 426 patients, showed no significant difference in 28-day and in-hospital mortality between the heparin and control groups (risk ratio [RR] = 0.86, 95% confidence interval [CI]: 0.60-1.24). Subgroup analysis of sepsis-associated disseminated intravascular coagulation (DIC) patients (n = 109) also did not show a significant reduction in mortality (RR = 0.84, 95% CI: 0.51-1.38). Heterogeneity was zero, and no publication bias was observed. Additionally, there was significant difference in bleeding complications (RR = 0.49, 95% CI: 0.24-0.99, p = 0.047).

Conclusions: This meta-analysis did not demonstrate a survival benefit of heparin administration in patients with sepsis and sepsis-associated DIC. Further investigation into the potential benefits of heparin is warranted. Moreover, the analysis revealed no increase in bleeding risks with heparin administration; instead, a significant reduction in the risk of bleeding was noted.

Trial registration: This review was preregistered with PROSPERO (registration: CRD42023385091).

Cardiac embolism plays a very significant role in acute ischemic strokes (AIS), constituting approximately one-third of cases. The origin of these emboli often stems from intracardiac thrombi in the left atrium or left ventricle. Utilizing the National Readmission Database from 2016 to 2019, we investigate the prevalence of cardiac thrombi in AIS patients and explore their potential correlation with endovascular thrombectomy (EVT) utilization, and mortality rates. Among 1,272,456 AIS patients, 0.6% had concurrent cardiac thrombus, with an increasing trend observed over the study period (P value < 0.001). The cardiac thrombus cohort showed a higher prevalence of comorbidities such as congestive heart failure and atrial fibrillation. After propensity-score matching, groups were well-balanced in terms of baseline characteristics. Patients within the cardiac thrombus cohort experienced a longer hospital stay (median 5 days vs. 3 days), but no significant difference in mortality was noted. Importantly, the cardiac thrombus cohort demonstrated a higher frequency of EVT utilization, suggesting a link to larger vessel occlusions. Despite matching based on atrial fibrillation, the EVT utilization in the cardiac thrombus cohort remained high, highlighting a significant association. While 30-day readmission rates were comparable, cardiac thrombus patients faced a higher risk of gastrointestinal bleeding and hemorrhagic stroke, likely attributed to anticoagulation use. Limitations include potential miscoding in the administrative database and a lack of detailed imaging findings. In conclusion, this study highlights the increased likelihood of EVT in AIS patients with cardiac thrombus, possibly indicative of larger vessel occlusion associated with cardiac thrombus.