Incidence of thrombotic complications in COVID-19

Journal of Thrombosis and Thrombolysis - A high incidence of thrombosis in hospitalised patients with COVID-19 was identified early during the pandemic. Accurately quantifying thrombotic risk may...     

Delayed catastrophic thrombotic events in young and asymptomatic post COVID-19 patients

Journal of Thrombosis and Thrombolysis -     

Whole blood viscosity and arterial thrombotic events in patients with systemic lupus erythematosus

OBJECTIVE: To determine if whole blood viscosity (WBV), a rheologic variable contributing to risk of myocardial infarction and stroke in the general population, is elevated in patients with systemic lupus erythematosus (SLE), particularly SLE patients with a history of thrombotic or atherothrombotic events. Because the high rates of arterial and venous thrombosis in lupus cannot be explained by traditional risk factors, elevated WBV may be an easily measurable nontraditional risk factor to identify SLE patients at high risk for thrombotic events. METHODS: Sixty SLE patients (30 with a history of a thrombotic event) and 20 matched controls were recruited into the study. The thrombosis group was further subdivided into an arterial thrombosis group (n = 17). WBV values were determined at 9 different shear rates (1, 2, 5, 10, 50, 100, 150, 300, and 1,000 seconds(-1)). WBV was then compared between groups by repeated-measures analysis of variance. RESULTS: SLE patients with a history of arterial events had significantly elevated WBV relative to either controls (P = 0.022) or SLE patients without arterial events (P = 0.014). WBV in the total SLE group did not differ from controls. Differences in WBV were most prominent at lower shear rates (1, 2, 5, 10, 50, and 100 seconds(-1)). Anticoagulation, prednisone dose, and antiphospholipid antibodies did not significantly impact WBV. CONCLUSION: Our study demonstrated that WBV is selectively elevated in patients with SLE with a history of arterial events. Although this association is striking, longitudinal studies are needed to assess the positive predictive value of WBV for atherothrombotic events in SLE.     

Diagnosis of venous and arterial thromboembolic events in COVID-19 virus-infected patients

Journal of Thrombosis and Thrombolysis -     

Rheological alterations and thrombotic events in patients with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is characterised by increased venous and arterial thrombotic risk. Nevertheless, how hemorheological alterations contribute to thrombotic risk remains a question of debate. We aimed to determine the rheological profile in 105 patients with SLE (24 with a thrombotic event) and 105 healthy controls. We determined blood viscosity and erythrocyte aggregation along with plasma lipids and fibrinogen. Although SLE patients showed lower blood viscosity at 230 s(-1) at a native hematocrit when compared with controls (p < 0.001), differences disappeared after adjusting the hematocrit to 45% (p = 0.095). When comparing SLE patients with and without thrombotic events, no differences in any rheological parameter were found (p > 0.05), except in fibrinogen which was higher in patients with thrombosis (p = 0.013). No differences in the rheological parameters were observed when venous and arterial thrombotic events were compared, although a tendency for higher fibrinogen was observed in patients with venous thrombosis (p = 0.053). Only hematocrit, fibrinogen and triglycerides were independent predictors of native blood viscosity in the multivariate regression analysis, even after adjusting for continuous variables and for tobacco and hypertension: beta coefficient: 0.727 p < 0.001; beta coefficient: 0.152 p = 0.003 and beta coefficient: 0.133 p = 0.015, respectively. The logistic regression analysis revealed that neither increased native blood viscosity (BVn > 4.33) nor increased erythrocyte aggregation (EA1 > 7.85) increased thrombotic risk: OR 0.636, CI 0.313-3.12, p = 0.578 and OR 2.01, CI 0.77-5.20, p = 0.152, respectively. However, hyperfibrinogenemia (Fbg > 342 mg/dL) increased thrombotic risk by around three times: OR 3.44 CI 1.32-8.96, p = 0.011. Our results suggest that the role of blood viscosity and erythrocyte aggregation in thrombotic risk in SLE patients fails to demonstrate any association.     

Assessment of hemostatic risk factors in predicting arterial thrombotic events

Arterial thrombosis results from endovascular injury and, to a lesser extent, alterations in hemostatic equilibrium. Although multiple hereditary and acquired hemostatic risk factors have been described in the pathophysiology of venous thrombosis, the degree and type of abnormalities that contribute to arterial thrombosis are less well understood. Endothelial cell injury with the elaboration of proinflammatory mediators stimulates the process of arterial thrombosis. Although this is most often the result of endovascular injury attributable to atherosclerotic disease, other disease states can elicit a similar response as well. Similarly, once thrombosis has been initiated, variations in the activity of coagulation proteins and endogenous anticoagulants, as well as the kinetics of platelet aggregation, may alter the effectiveness of thrombus formation. Epidemiological studies have identified several acquired or inherited states that may result in endothelial damage or altered hemostatic equilibrium, thereby predisposing patients to arterial thrombosis. These include hyperhomocysteinemia, elevated C-reactive protein, antiphospholipid antibodies, elevated fibrinogen, Factor VII, plasminogen activator inhibitor-1 (PAI-1), hereditary thrombophilias, and platelet hyper-reactivity. This review explores our present understanding of these risk factors in the development of arterial thrombotic events. At present, the literature supports a role for hyperhomocysteinemia, elevated C-reactive protein, and elevated fibrinogen as risk factors for arterial thrombosis. Similarly, the literature suggests that lupus anticoagulants and, to a lesser extent, elevated titers of cardiolipin IgG antibodies predispose to arterial vascular events. In certain subsets of patients, including those with concomitant cardiac risk factors, <55 years of age, and women, hereditary thrombophilias such as carriership of the factor V Leiden and the prothrombin G20210A mutations may confer a higher risk of arterial thrombosis. However, the data on Factor VII, PAI-1, and platelet receptor polymorphisms are contradictory or lacking.     

Venous and arterial thromboembolic disease in COVID-19

Journal of Thrombosis and Thrombolysis -     

Spatiotemporal Analysis of COVID-19 Incidence Data

(1) Background: A better understanding of COVID-19 dynamics in terms of interactions among individuals would be of paramount importance to increase the effectiveness of containment measures. Despite this, the research lacks spatiotemporal statistical and mathematical analysis based on large datasets. We describe a novel methodology to extract useful spatiotemporal information from COVID-19 pandemic data. (2) Methods: We perform specific analyses based on mathematical and statistical tools, like mathematical morphology, hierarchical clustering, parametric data modeling and non-parametric statistics. These analyses are here applied to the large dataset consisting of about 19,000 COVID-19 patients in the Veneto region (Italy) during the entire Italian national lockdown. (3) Results: We estimate the COVID-19 cumulative incidence spatial distribution, significantly reducing image noise. We identify four clusters of connected provinces based on the temporal evolution of the incidence. Surprisingly, while one cluster consists of three neighboring provinces, another one contains two provinces more than 210 km apart by highway. The survival function of the local spatial incidence values is modeled here by a tapered Pareto model, also used in other applied fields like seismology and economy in connection to networks. Model’s parameters could be relevant to describe quantitatively the epidemic. (4) Conclusion: The proposed methodology can be applied to a general situation, potentially helping to adopt strategic decisions such as the restriction of mobility and gatherings.     

系统性红斑狼疮患者动脉僵硬度及其相关危险因素的研究

目的 评价系统性红斑狼疮(SLE)患者动脉僵硬度,并探讨其相关危险因素.方法 本研究为横断面研究,共纳入中国系统性红斑狼疮研究协作组(CSTAR)的SLE患者135例.利用动脉僵硬度检测仪测定患者臂踝脉搏波传导速度(baPWV),同时采集心血管相关的传统危险因素以及SLE相关因素.利用SAS软件进行统计分析.结果 (1)动脉僵硬度增高的SLE患者其年龄、心血管疾病家族史、平均动脉压和糖化血红蛋白与动脉僵硬度正常的SLE患者比较差异有统计学意义(P均＜0.05).动脉僵硬度增高的SLE患者其肌酐清除率低于动脉僵硬度正常的SLE患者,病程和羟氯喹使用疗程长于动脉僵硬度正常的SLE患者(P均＜0.05),静脉使用环磷酰胺的比例高于动脉僵硬度正常的SLE患者[OR =3.04,95％ CI:1.230 ～7.514,P=0.013].(2)对上述混淆因素进行调整后,年龄[OR=4.56,95％ CI:1.863 ～ 11.130,P=0.000]、平均动脉压[OR=1.12,95％CI:1.055～1.196,P=0.000]、SLE病程[OR=1.20,95％ CI:1.050 ～1.367,P =0.007]以及静脉使用环磷酰胺比例[OR=2.86,95％ CI:1.364 ～5.979,P=0.005]是SLE患者动脉僵硬度增高的独立危险因素.结论 传统心血管危险因素及SLE特异性相关因素均与SLE患者动脉僵硬度增高相关.     

Incidence of acute pulmonary embolism in COVID-19 patients: Systematic review and meta-analysis.

BackgroundAcute pulmonary embolism (PE) has been described as a frequent and prognostically relevant complication of COVID-19 infection.AimWe performed a systematic review and meta-analysis of the in-hospital incidence of acute PE among COVID-19 patients based on studies published within four months of COVID-19 outbreak.Material and MethodsSystematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in abstracting data and assessing validity. We searched Medline, Scopus and Web of Science to locate all articles published up to August 1, 2020 reporting the incidence of acute PE (or lung thrombosis) in COVID-19 patients. The pooled in-hospital incidence of acute PE among COVID-19 patients was calculated using a random effects model and presenting the related 95% confidence interval (CI). Statistical heterogeneity was measured using the Higgins I² statistic.ResultsWe analysed data from 7178 COVID-19 patients [mean age 60.4 years] included in twenty-three studies. Among patients hospitalized in general wards and intensive care unit (ICU), the pooled in-hospital incidence of PE (or lung thrombosis) was 14.7% of cases (95% CI: 9.9–21.3%, I²=95.0%, p<0.0001) and 23.4% (95% CI:16.7–31.8%, I2=88.7%, p<0.0001), respectively. Segmental/sub-segmental pulmonary arteries were more frequently involved compared to main/lobar arteries (6.8% vs18.8%, p<0.001). Computer tomography pulmonary angiogram (CTPA) was used only in 35.3% of patients with COVID-19 infection across six studies.ConclusionsThe in-hospital incidence of acute PE among COVID-19 patients is higher in ICU patients compared to those hospitalized in general wards. CTPA was rarely used suggesting a potential underestimation of PE cases.     

D-dimer and platelet aggregability are related to thrombotic events in patients with peripheral arterial occlusive disease.

AIMS: To evaluate the frequency of arterial thrombotic events in patients with peripheral arterial occlusive disease during 3-5 years of follow-up and to determine whether baseline levels of haemostatic factors were related to the risk of future thrombotic events. METHODS AND RESULTS: One hundred and twenty-three patients, mean age 56 years, with peripheral arterial occlusive disease and intermittent claudication were followed prospectively for an average of 4.2 years. Fibrinogen, prothrombin fragment 1+2, D-dimer, tissue plasminogen activator, plasminogen activator inhibitor type I antigen and activity, plasmin-alpha(2)-antiplasmin complex, beta thromboglobulin and ADP-induced platelet aggregation were measured at the recruitment. Thirty-eight new vascular events (15 fatal) were identified. Age- (and other clinical and laboratory variables) -adjusted relative risks (RR) of thrombotic events were significantly elevated (P<0.05) per higher value of D-dimer (RR: 14.1, 95% CI 1.7;115.8) and platelet aggregation was low (RR: 4.6, 95% CI 1.3;16.3). Diabetes mellitus, cerebrovascular disease, and continuing deterioration of intermittent claudication at the recruitment were also independently associated with risk of thrombotic events in the multiple regression model (RR: 5.2, 95% CI 1.5;17.5; RR: 8.6, 95% CI 2.7;27.4; RR: 2.6, 95% CI 1.2;5.7 respectively). CONCLUSION: Elevated level of D-dimer and low platelet aggregation are independent haemostatic predictors of thrombotic events in patients with peripheral arterial occlusive disease.     

A case of thrombotic thrombocytopenic purpura associated with COVID-19

Journal of Thrombosis and Thrombolysis - Acquired thrombotic thrombocytopenic purpura (TTP) is an autoimmune disease that can be triggered by different events, including viral infections. It...