Low-molecular-weight heparin use in coronavirus disease 2019 is associated with curtailed viral persistence: a retrospective multicentre observational study.

AIMS: Anticoagulation was associated with improved survival of hospitalized coronavirus disease 2019 (COVID-19) patients in large-scale studies. Yet, the development of COVID-19-associated coagulopathy (CAC) and the mechanism responsible for improved survival of anticoagulated patients with COVID-19 remain largely elusive. This investigation aimed to explore the effects of anticoagulation and low-molecular-weight heparin (LMWH) in particular on patient outcome, CAC development, thromboinflammation, cell death, and viral persistence. METHODS AND RESULTS: Data of 586 hospitalized COVID-19 patients from three different regions of Austria were evaluated retrospectively. Of these, 419 (71.5%) patients received LMWH and 62 (10.5%) received non-vitamin-K oral anticoagulants (NOACs) during hospitalization. Plasma was collected at different time points in a subset of 106 patients in order to evaluate markers of thromboinflammation (H3Cit-DNA) and the cell death marker cell-free DNA (cfDNA). Use of LMWH was associated with improved survival upon multivariable Cox regression (hazard ratio = 0.561, 95% confidence interval: 0.348-0.906). Interestingly, neither LMWH nor NOAC was associated with attenuation of D-dimer increase over time, or thromboinflammation. In contrast, anticoagulation was associated with a decrease in cfDNA during hospitalization, and curtailed viral persistence was observed in patients using LMWH leading to a 4-day reduction of virus positivity upon quantitative polymerase chain reaction [13 (interquartile range: 6-24) vs. 9 (interquartile range: 5-16) days, P = 0.009]. CONCLUSION: Time courses of haemostatic and thromboinflammatory biomarkers were similar in patients with and without LMWH, indicating either no effects of LMWH on haemostasis or that LMWH reduced hypercoagulability to levels of patients without LMWH. Nonetheless, anticoagulation with LMWH was associated with reduced mortality, improved markers of cell death, and curtailed viral persistence, indicating potential beneficial effects of LMWH beyond haemostasis, which encourages use of LMWH in COVID-19 patients without contraindications.

Long-term follow-up after successful treatment of vaccine-induced prothrombotic immune thrombocytopenia.

BACKGROUND: Cases of ChAdOx1 nCoV-19 (AstraZeneca) vaccinated patients with thrombocytopenia, elevated D-dimer, and elevated platelet factor 4 (PF4) antibody levels with- and without thrombosis have been reported. No recommendations regarding the duration of anticoagulation have been made, because data on the long-term course beyond the first weeks is lacking. OBJECTIVE: To report on the treatment, medical course, and longitudinal follow-up of laboratory parameters in patients with vaccine-induced prothrombotic immune thrombocytopenia (VIPIT). PATIENTS: We followed VIPIT patients with- (n = 3) and without (n = 3) venous thromboembolism fulfilling the aforementioned laboratory criteria. RESULTS: Elevated D-dimer (median: 35.10 µg/ml, range: 17.80-52.70), thrombocytopenia (42 G/l, 20-101), and strong positivity in the platelet factor 4 (PF4)/heparin-enzyme-immunoassay (2.42 optical density [OD], 2.06-3.13; reference range < 0.50) were present in all patients after vaccination (10 days, 7-17). Routine laboratory parameters rapidly improved upon initiation of treatment (comprising therapeutic non-heparin anticoagulation in all patients and high dose immunoglobulins ± corticosteroids in 5 patients). PF4 antibody levels slowly decreased over several weeks. Patients were discharged in good physical health (8 days, 5-13). VIPIT did not recur during follow-up (12 weeks, 8-17). Five of 6 patients fully recovered (in 2 patients thrombosis had resolved, in 1 patient exertional dyspnea persisted). CONCLUSIONS: Remissions without sequelae can be achieved upon rapid initiation of treatment in patients with VIPIT. Platelet factor 4 antibody levels slowly decreased over several weeks but VIPIT did not recur in any of our patients. Continuation of anticoagulation in VIPIT patients at least until PF4 antibody negativity is reached seems reasonable.

Successful treatment of vaccine-induced prothrombotic immune thrombocytopenia (VIPIT).

Cases of unusual thrombosis and thrombocytopenia after administration of the ChAdOx1 nCoV-19 vaccine (AstraZeneca) have been reported. The term vaccine-induced prothrombotic immune thrombocytopenia (VIPIT) was coined to reflect this new phenomenon. In vitro experiments with VIPIT patient sera indicated that high-dose intravenous immunoglobulins (IVIG) competitively inhibit the platelet-activating properties of ChAdOx1 nCoV-19 vaccine induced antibodies. Here, we report a case of a 62-year-old woman who had received this vaccine and developed VIPIT. She visited the emergency ward because of petechiae and hematomas. In the laboratory work-up, thrombocytopenia, low fibrinogen, elevated D-dimer, and positivity in the platelet factor 4/heparin-enzyme-immunoassay were present. Signs and symptoms of thrombosis were absent. Upon immediate therapy with non-heparin anticoagulation, high-dose IVIG, and prednisolone, laboratory parameters steadily improved and the patient was discharged from hospital without thrombotic complications. We conclude that early initiation of VIPIT treatment results in a swift response without thrombotic complications.

Risk of venous thromboembolism in patients with COVID-19: A systematic review and meta-analysis.

Background: Venous thromboembolism (VTE) is frequently observed in patients with coronavirus disease 2019 (COVID-19). However, reported VTE rates differ substantially. Objectives: We aimed at evaluating available data and estimating the prevalence of VTE in patients with COVID-19. Methods: We conducted a systematic literature search (MEDLINE, EMBASE, World Health Organization COVID-19 database) to identify studies reporting VTE rates in patients with COVID-19. Studies with suspected high risk of bias were excluded from quantitative synthesis. Pooled outcome rates were obtained within a random effects meta-analysis. Subgroup analyses were performed for different settings (intensive care unit [ICU] vs non-ICU hospitalization and screening vs no screening) and the association of d-dimer levels and VTE risk was explored. Results: Eighty-six studies (33,970 patients) were identified and 66 (28,173 patients, mean age: 62.6 years, 60.1% men, 19.4% ICU patients) were included in quantitative analysis. The overall VTE prevalence estimate was 14.1% (95% confidence interval [CI], 11.6-16.9), 40.3% (95% CI, 27.0-54.3) with ultrasound screening and 9.5% (95% CI, 7.5-11.7) without screening. Subgroup analysis revealed high heterogeneity, with a VTE prevalence of 7.9% (95% CI, 5.1-11.2) in non-ICU and 22.7% (95% CI, 18.1-27.6) in ICU patients. Prevalence of pulmonary embolism (PE) in non-ICU and ICU patients was 3.5% (95% CI, 2.2-5.1) and 13.7% (95% CI, 10.0-17.9). Patients developing VTE had higher d-dimer levels (weighted mean difference, 3.26 µg/mL; 95% CI, 2.76-3.77) than non-VTE patients. Conclusion: VTE occurs in 22.7% of patients with COVID-19 in the ICU, but VTE risk is also increased in non-ICU hospitalized patients. Patients developing VTE had higher d-dimer levels. Studies evaluating thromboprophylaxis strategies in patients with COVID-19 are needed to improve prevention of VTE.

Pulmonary embolism during the COVID-19 pandemic: Decline in diagnostic procedures and incidence at a university hospital.

BACKGROUND: The COVID-19 pandemic has focused medical attention on treating affected patients and protecting others from infection. However, concerns have been raised regarding the pandemic´s impact and associated containment measures (eg curfew, lockdown) on non-coronavirus disease 2019 (COVID-19)-related acute medical diseases. OBJECTIVES: To investigate changes in the incidence of pulmonary embolism (PE) during the COVID-19 pandemic compared to the period before the pandemic and reference periods in previous years. METHODS: In this single-center study, we explored all diagnostic imaging tests performed for suspected PE between weeks 1 and 17 of the years 2018, 2019, and 2020. Incidence of PE (ie, primary outcome) was analyzed. Secondary outcomes included number of imaging tests for suspected PE. RESULTS: Compared to weeks 1 to 11, 2020, an abrupt decline in PE diagnosis (mean weekly rate, 5.2; 95% confidence interval [CI], 3.8-6.6 vs 1.8; 95% CI, 0.0-3.6) and imaging tests (mean weekly rate, 32.5; 95% CI, 27.5-37.6 vs. 17.3; 95% CI, 11.6-23.1) was observed from week 12, with beginning of the containment measures and public lockdown in Austria. Compared to weeks 12 to 17 of 2018 and 2019, PE incidence and imaging tests were similarly decreased from 5.3 (95% CI, 3.6-7.1) to 1.8 (95% CI, 0.0-3.6) and 31.5 (95% CI, 27.1-35.9) to 17.3 (95% CI, 11.6-23.1), respectively. The median simplified pulmonary embolism severity index (sPESI) score of PE patients during the pandemic was higher than in all other PE patients (3; interquartile range, 1-3 vs 1; interquartile range, 0-2; P = .002). CONCLUSION: Our study demonstrates that the COVID-19 pandemic has an impact on non-COVID-19-related acute diseases as shown by the decline in incidence of PE and imaging procedures for diagnostic workup. Further studies from other hospitals are needed to confirm our findings.