Acute infection as a trigger for incident venous thromboembolism: Results from a population‐based case‐crossover study

Abstract

Essentials There is a bidirectional relation between acute infections and immobilizationWe studied the impact of infection and immobilization on risk of VTE in a case‐crossover designAcute infection was a strong trigger for VTE independent of concomitant immobilizationInfection and immobilization had a synergistic effect on the VTE‐risk BackgroundA bidirectional relation exists between acute infection and immobilization, and both are triggers for venous thromboembolism (VTE). To what extent the association between infection and VTE‐risk is explained by immobilization is unknown.AimsTo investigate the impact of hospitalization with acute infection on the VTE‐risk in patients with and without concomitant immobilization, and to explore the differential impact of respiratory‐ (RTI) and urinary‐ (UTI) tract infections on the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE).MethodsWe conducted a case‐crossover study of VTE‐patients (n = 707) recruited from a general population. Hospitalizations and VTE‐triggers were registered during the 90 days before a VTE (hazard period) and in four preceding 90‐day control periods. Conditional logistic regression was used to estimate odds ratios (ORs) for VTE according to triggers.ResultsAcute infection was registered in 267 (37.8%) of the hazard periods and in 107 (3.8%) of the control periods, corresponding to a high VTE‐risk after infection (OR 24.2, 95% CI 17.2‐34.0), that was attenuated to 15‐fold increased after adjustment for immobilization. The risk was 20‐fold increased after infection without concomitant immobilization, 73‐fold increased after immobilization without infection, and 141‐fold increased with the two combined. The risk of PE was apparently higher after RTIs (OR 48.3, 95% CI 19.4‐120.0) than UTIs (OR 12.6, 95% CI 6.4‐24.7), but diminished in sensitivity analyses excluding uncertain RTI diagnoses.ConclusionsOur findings suggest that hospitalization with infection is a strong VTE‐trigger also in non‐immobilized patients. Infection and immobilization had a synergistic effect on the VTE‐risk.

Clinical and Imaging Findings in COVID-19 Patients Complicated by Pulmonary Embolism

“…Two out of 11 patients had lower-limb ultrasonography performed and no lower extremity deep vein thrombosis was found. Acute infection was reported to be a strong trigger for venous thromboembolism independent of concomitant immobilization [20], and there was higher risk estimates for infection preceding pulmonary embolism (PE) than deep vein thrombosis, and respiratory tract infection had a greater impact on venous thromboembolism than non-respiratory infections [21]. In our study, all the patient developed pulmonary embolism after severe COVID-19 pneumonia without major risk factors for PE including underlying cardiopulmonary diseases, oncologic disease history, past deep vein thrombosis, or prolonged immobility more than 3 days, which may further confirm the role of infection as an independent trigger for thromboembolism.…”

Plasma levels of mannose‐binding lectin and future risk of venous thromboembolism

“…First, MBL deficiency is a predisposing factor for the incidence and severity of systemic lupus erythematosus, as well as the frequency of infectious complications. Systemic lupus erythematosus and acute infectious diseases are associated with increased risk of VTE and may therefore counterbalance the beneficial effect of low MBL levels. Second, although mainly determined by the MBL2 genotype, there is no stringent relationship between MBL2 genotypes tested in previous studies and plasma MBL levels.…”

“…Mannose-binding lectin-deficient individuals are susceptible to other diseases, such as various types of infectious disease, autoimmune disorders, and arterial CVD. 35,55 These diseases are known to be associated with VTE risk 40,41,56,57 and could thereby counterbalance the potential beneficial effect of MBL deficiency. Mannosebinding lectin deficiency has been associated with advanced atherosclerosis 58,59 and a higher risk of myocardial infarction, independent of other traditional risk factors.…”

Complement component 5 does not interfere with physiological hemostasis but is essential forEscherichia coli-induced coagulation accompanied by Toll-like receptor 4

“…Eculizumab significantly reduced the E. coli-induced PTF1·2 when three, but not seven, groups were compared by one-way repeated-measures anova. As bacteria-induced thromboembolic events are significantly increased in PNH and catastrophic anti-phospholipid syndrome, two diseases indicative for eculizumab treatment, the putative protective effect of eculizumab on bacteria-induced thrombosis should be further examined [34]. When E. coli with and without eclizumab were compared using a paired Student's t-test, the effect on PTF1·2 was statistically significant in all experiments.…”

“…Patients treated with eculizumab may possibly have a reduced risk of E. coli-induced coagulation. As bacteria-induced thromboembolic events are significantly increased in PNH and catastrophic anti-phospholipid syndrome, two diseases indicative for eculizumab treatment, the putative protective effect of eculizumab on bacteria-induced thrombosis should be further examined [34].…”