Journal of Thrombosis and Thrombolysis

Postmenopausal hormone replacement therapy (HRT), such as estrogen with a progestin (E+P), is associated with an increased risk of myocardial infarction (MI), stroke, and venous thrombosis. Subgroups of susceptible women for these clinical outcomes have not been clearly identified, although women with a prior history of venous thrombosis and women with factor V Leiden are at higher risk of venous thrombosis on HRT than others. Effects of HRT on atherosclerosis, coagulation, and inflammation have been investigated, and might improve our understanding of the pathogenesis of this drug effect. In 2 trials E+P did not alter the progression of coronary atherosclerosis, while in a third trial unopposed estradiol retarded atherosclerosis progression in the carotid arteries. HRT is associated with an increase in high-sensitivity C-reactive protein (CRP), an inflammation marker associated with arterial disease risk, and an increase in activated protein C resistance, the biochemical defect associated with factor V Leiden. Given recent data, the only current indication for E+P is the short-term treatment of symptoms of estrogen deficiency, such as hot flashes. Testing for coagulation disorders or inflammatory factors, such as factor V Leiden or CRP, for use in decision-making about HRT use would be premature in unselected patients. Further research is needed to identify pathophysiological mechanisms of vascular harm from these hormones.

SARS-CoV-2 represents the causative agent of the current pandemic (COVID-19). The drug repurposing technique is used to search for possible drugs that can bind to SARS-CoV-2 proteins and inhibit viral replication. In this study, the FDA-approved antiplatelets are tested against the main protease and spike proteins of SARS-CoV-2 using in silico methods. Molecular docking and molecular dynamics simulation are used in the current study. The results suggest the effectiveness of vorapaxar, ticagrelor, cilostazol, cangrelor, and prasugrel in binding the main protease (Mpro) of SARS-CoV-2. At the same time, vorapaxar, ticagrelor, and cilostazol are the best binders of the spike protein. Therefore, these compounds could be successful candidates against COVID-19 that need to be tested experimentally.

Heparin-induced thrombocytopenia (HIT) causes thrombosis and thrombocytopenia, usually due to prior heparin exposure, so-called classical HIT. However, in the autoimmune form, the signs and symptoms of HIT occur without prior heparin exposure. Development of cerebral venous sinus thrombosis (CVST) secondary to HIT is a rare occurrence, with relatively few reports in the literature. There is a need to better understand the clinical presentation and treatment paradigms in these rare cases. Therefore, we present the first systematic review of CVST occurring in classical and autoimmune HIT. Cases of HIT-induced CVST were identified through a systematic search of Pubmed from the date of inception to March 2021. Literature search revealed 21 cases of HIT and associated CVST with six cases (28.6%) of autoimmune HIT. Patients presented with signs and symptoms consistent with increased intracranial pressure, intracerebral hemorrhage (ICH), and/or focal neurologic deficits. Headache was the most common symptom with 12 patients (60.0%) presenting as such. 10 patients (47.6%) included in the study developed ICH. Non-heparin anticoagulants, especially direct thrombin inhibitors, were the first-line treatment for the majority of patients (55.6%). Intravenous immunoglobulin (IVIG) was used as treatment for select patients (16.7%) with autoimmune HIT. Few patients received surgical intervention for CVST (14.3%) or ICH (30.0%). Four patients had a full recovery, four patients had residual deficits, and seven patients ultimately expired. Symptoms of HIT-induced CVST are often related to CNS dysfunction. Non-heparin anticoagulants are important to treat CVST, even when patients have concomitant ICH, and may be supplemented with IVIG if treating autoimmune HIT. Rapid identification and treatment of HIT-induced CVST is imperative in order to prevent morbidity and mortality.

To investigate whether the addition of left ventricular ejection fraction (LVEF) to the TIMI risk score enhances the prediction of in-hospital and long-term death in ST segment elevation myocardial infarction (STEMI) patients. 673 patients with STEMI were divided into three groups based on TIMI risk score for STEMI: low-risk group (TIMI ≤3, n = 213), moderate-risk group (TIMI 4–6, n = 285), and high-risk group (TIMI ≥7, n = 175). The predictive value was evaluated using the receiver operating characteristic. Multivariate logistic regression was used to determine risk predictors. The rates of in-hospital death (0.5 vs 3.2 vs 10.3 %, p < 0.001) and major adverse cardiovascular events (14.6 vs 22.5 vs 40.6 %, p < 0.001) were significantly higher in high-risk group. Multivariate analysis showed that TIMI risk score (OR 1.24, 95 % CI 1.04–1.48, P = 0.015) and LVEF (OR 3.85, 95 % CI 1.58–10.43, P = 0.004) were independent predictors of in-hospital death. LVEF had good predictive value for in-hospital death (AUC: 0.838 vs 0.803, p = 0.571) or 1-year death (AUC: 0.743 vs 0.728, p = 0.775), which was similar to TIMI risk score. When compared with the TIMI risk score alone, the addition of LVEF was associated with significant improvements in predicting in-hospital (AUC: 0.854 vs 0.803, p = 0.033) or 1-year death (AUC: 0.763 vs 0.728, p = 0.016). The addition of LVEF to TIMI risk score enhanced net reclassification improvement (0.864 for in-hospital death, p < 0.001; 0.510 for 1-year death, p < 0.001). LVEF was associated with in-hospital and long-term mortality in STEMI patients and had additive prognostic value to TIMI risk score.

The anticoagulant properties of a novel RNA aptamer that binds FIXa depend collectively on the intensity of surface contact activation of human blood plasma, aptamer concentration, and its binding affinity for FIXa. Accordingly, anticoagulation efficiency of plasma containing any particular aptamer concentration is low when coagulation is strongly activated by hydrophilic surfaces compared to the anticoagulation efficiency in plasma that is weakly activated by hydrophobic surfaces. Anticoagulation efficiency is lower at hypothermic temperatures possibly because aptamer-FIXa binding decreases with decreasing temperatures. Experimental results demonstrating these trends are qualitatively interpreted in the context of a previously established model of anticoagulation efficiency of thrombin-binding DNA aptamers that exhibit anticoagulation properties similar to the FIXa aptamer. In principle, FIXa aptamer anticoagulants should be more efficient and therefore more clinically useful than thrombin-binding aptamers because aptamer binding to FIXa competes only with FX that is at much lower blood concentration than fibrinogen (FI) that competes with thrombin-binding aptamers. Our findings may have translatable relevance in the application of aptamer anticoagulants for clinical conditions in which blood is in direct contact with non-biological surfaces such as those encountered in cardiopulmonary bypass circuits.

Coronavirus disease 2019 (COVID-19) has been associated with an increased risk of thromboembolic complications due to systemic coagulation activation. Little is known about the role of direct anticoagulants (DOACs) in COVID-19 related thrombosis. In this audit we sought to distinguish COVID-19 hospitalised patients with a diagnosis of venous thromboembolism (VTE) and record their outcomes over a period of 3 months (01/02/2020–30/04/2020). A total of 1583 patients were diagnosed with laboratory proven COVID-19 disease. Amongst them, 38 patients (0.82%) suffered VTE (median age 68 years, male/female: 20/18). VTE was the presenting symptom on admission in 71%. Pulmonary embolism was diagnosed in 92% of patients; 5 patients required intensive care and 3 underwent thrombolysis. 27 patients received initial treatment with unfractionated heparin/low molecular weight heparin (LMWH) while 10 were treated with direct anticoagulants (DOACs). After a median follow up of 25 days, 29 (76%) patients were alive while 5 were still hospitalised. Most patients (83%) were discharged on DOACs, no VTE recurrence or bleeding was recorded post-discharge. Our results suggest that direct anticoagulants could be a safe and effective treatment option in selected COVID-19 positive patients who have suffered venous thromboembolism.

Acute coronary syndromes may be associated with a systemic acute pro-thrombotic condition, possibly involving inflammatory mechanisms as well, which are not confined to a single spot in the coronary circulation. Multivessel coronary thrombosis appears to be an exceptionally rare clinical finding. Here we present a case of anterior MI complicated by thrombi in circumflex and right coronary arteries.

Background: In epidemiologic studies, excessive body weight, independent of other risk factors, portends a poor prognosis among patients with coronary artery disease experiencing acute myocardial infarction (MI). At least one recent study has suggested that patients of excessive body weight when receiving thrombolytic therapy are often underdosed, potentially reducing early coronary arterial patency and adversely affecting in-hospital clinical outcome. Concern has also been raised that body weight may influence treatment utilization, delays, and complication rates. Despite these concerns, the association between body weight and patient outcome following coronary thrombolysis has received limited attention.Methods/Results: Demographic, procedural, and outcome data from patients with MI were collected at 1073 United States hospitals participating in The National Registry of Myocardial Infarction from 1990 through 1994. Among 350,755 patients with MI enrolled, 87,688 (25.1%) were treated with tissue plasminogen activator (t-PA). Divided into body weight tertiles, 23.5% of patients were less than 70 kg (low weight), 36.8% were 70–85 kg (modrate weight), and 37.5% were greater than 85 kg (high weight). Patients of low weight were older (p < 0.001), received treatment later (p < 0.001), and were less likely to undergo cardiac catheterization, coronary angioplasty, or bypass surgery (p < 0.001) than moderate- or high-weight patients. Low-weight patients also experienced minor bleeding, major bleeding, recurrent MI, and death more often (p < 0.001). Adjusted for age, low body weight was independently associated with in-hospital mortality. Despite receiving a lower dose of t-PA per kg body weight, high-weight patients had a low incidence of cardiogenic shock, recurrent MI, death, and hemorrhagic complications. When high-weight women and men were compared, several interesting observations emerged. Mortality was increased twofold in women (6.8% vs. 3.0; p < 0.001), even adjusting for their older age. Despite being at increased risk, women were less likely than their male counterparts to undergo cardiac catheterization (p=0.001) or bypass surgery (p=0.008).Conclusions: The National Registry of Myocardial Infarction provides a unique resource for assessing health care trends in the United States. Our findings suggest that low body weight is associated with increased in-hospital morbidity and mortality. They also suggest that current dosing strategies for t-PA administration are probably adequate for high-weight patients. The excessive mortality and limited use of in-hospital interventions among high-weight women deserve further study to address gender-related differences in disease processes, as well as potential bias or discrimination.