ABSTRACT
Background: Inflammatory bowel disease (IBD) including Crohn's disease (CD) and ulcerative colitis (UC), is associated with higher thrombotic risk and enhanced thrombin generation (TG) in adults. IBD patients were underrepresented in SARS-CoV- 2 mRNA vaccine trials. Case reports indicated that adverse events post-vaccination, including IBD flare, were more common among children, and those with prior COVID-19. Aim(s): To find out whether TG is increased in children with IBD as compared to healthy controls and whether TG parameters show significant changes following SARS-CoV- 2 mRNA vaccination. Method(s): In this observational case-control study, 37 children with IBD (CD:16, UC: 21) aged 12-18 years and 55 healthy age-matched children were enrolled. Blood was collected before and 2-4 weeks after the second dose of BNT162b2 (Pfizer-BioNTech) vaccine dose. Whole blood count, fibrinogen, inflammatory markers (CRP, ferritin), anti-SARS- CoV- 2 antibody levels were investigated, TG assay was carried-out using platelet-poor plasma. Lag time, endogen thrombin potential (ETP), peak thrombin, time-to- peak were calculated. Detailed clinical parameters including post-vaccination symptoms, COVID-19 history, disease activity scores (PUCAI, Mayo score, PCDAI) were registered. Result(s): CRP was significantly elevated in children with IBD and showed a positive correlation with ETP (CD: R = 0.700;p = 0.003 and CU: R = 0.501;p = 0.020). TG parameters did not differ between patients and controls pre-or post-vaccination. TG parameters remained unaltered post-vaccination in both groups. IBD disease flare was not observed post-vaccination, but reduced anti-SARS- CoV- 2 antibody titers were found in 4 patients receiving immunosuppressive therapies. Previous COVID-19 infection had no effect on TG levels. Conclusion(s): Although TG parameters correlated with the level of inflammation in children with IBD, the extent of TG was not significantly different from healthy controls. TG parameters and IBD disease activity scores did not increase significantly following mRNA vaccination. Our results support the safety of SARS-CoV- 2 mRNA vaccination in children with IBD, highlighting observations of lower antibody titers in immunosuppressed children.
ABSTRACT
Background: Coronavirus disease-2019 (COVID-19) increases the risk of acute ischemic stroke (AIS). Hemostasis alterations and outcomes of reperfusion therapy (thrombolysis or thrombectomy) in COVID-19- positive AIS patients are not well studied, as yet. (Figure Presented) Aims: We aimed to test hemostasis alterations in COVID-19- positive AIS patients receiving intravenous (i.v.) thrombolysis as compared to non-infected AIS patients and to correlate results with therapy outcomes and safety. Method(s): In this prospective observational study, 110 AIS patients receiving i.v. thrombolysis (recombinant tissue plasminogen activator) with/without thrombectomy were enrolled (April 2020-December 2021). Blood samples were taken on admission (within 4.5h of symptom onset), at 1h and 24h post-event. SARS-CoV- 2 RT-PCR test performed on admission confirmed acute infection in 9 cases (COVID-19+ group). Anti-SARS- CoV- 2 antibody test proved convalescence and/or vaccination in 48 patients (post-COVID/ post-vaccination group). Markers of inflammation (CRP, ferritin, IL-6), D-dimer, fibrinogen, von Willebrand factor (VWF) antigen, factor VIII (FVIII) and factor XIII (FXIII) activity, clot-lysis assay, thrombin generation, ROTEM and angiotensin convertase enzyme (ACE)1, ACE2 activities were analyzed. Stroke severity was determined by NIHSS. Therapy-associated intracerebral hemorrhage was classified according to ECASSII criteria. Short-and long-term outcomes were defined at 7 days and 3 months post-event according to the change in NIHSS and the modified Rankin Scale, respectively. Result(s): Stroke severity was significantly greater in the COVID-19+ group. VWF antigen levels were markedly elevated in the COVID-19+ group as compared to non-infected and post-COVID/ post-vaccination groups (323 +/- 72% vs. 248 +/- 75% and 222 +/- 80%, respectively, p = 0.006). FVIII levels were parallel to VWF levels and showed significant elevation in the COVID-19+ group. Short-term outcomes of therapy and the occurrence of hemorrhagic transformation did not differ between groups. Conclusion(s): Elevated FVIII and VWF levels in COVID-19- associated AIS seem to be linked to endothelial cell injury and are associated with more severe stroke. Efficacy of thrombolysis in COVID-19+ AIS patients was similar to non-infected patients in this cohort.
ABSTRACT
Background: Coronavirus disease-19 (COVID-19) is associated with disturbed hemostasis balance. Little is known about COVID-19- associated hemostasis alterations in pregnancy and their associations with the clinical course. Aim(s): We aimed to test hemostasis alterations in COVID-19- positive pregnant women as compared to non-infected pregnancies and to correlate results with maternal and perinatal outcomes. Method(s): In this single-center observational case-control study, 80 women with acute COVID-19 infection at 24-40 gestational weeks (COVID-19+ group) and 80 healthy age-and gestational week-matched pregnant women (COVID-19- group) were enrolled. All women were outpatients with mild/no symptoms at admission. Acute infection was confirmed/ruled out using SARS-CoV- 2 RT-PCR and/or antigen test. Blood taken on admission was analyzed for markers of inflammation (CRP, ferritin, IL-6), D-dimer, fibrinogen, von Willebrand factor antigen, factor VIII (FVIII) and factor XIII (FXIII) activity, clot-lysis assay, thrombin generation, ACE1, ACE2 activity, and anti-SARS- CoV- 2 antibody levels. Detailed clinical parameters of pregnancy, labor and post-partum period were registered. Pregnancies were followed for 6 weeks after childbirth. Result(s): In the COVID-19+ group, APTT was significantly prolonged, while PT, fibrinogen, and D-dimer levels did not significantly differ from the non-infected group. FVIII activity was significantly lower in the COVID-19+ group as compared to COVID-19- group (183.7 +/- 55.9% vs. 201.7 +/- 49.2%, p = 0.03). Similarly, FXIII activity was significantly reduced in COVID-19+ pregnant women (80.6 +/- 23.5% vs. COVID-19- group: 91.6 +/- 22.5%, p = 0.04). Pregnancy-associated complications were observed in 5 COVID-19+ cases, with marked alterations of coagulation screening tests, clot-lysis assay, and increased D-dimer. Perinatal complications were observed in 6 cases and one newborn tested positive for SARS-CoV- 2. Two cases of severe post-partum hemorrhage were observed in the COVID-19+ group. No post-partum thrombotic events occurred. Conclusion(s): In this cohort, third-trimester COVID-19+ pregnancies were associated with reduced levels of FVIII and FXIII activity. In a few cases, marked alterations of hemostasis and fibrinolysis balance occurred, which were accompanied by pregnancy complications.