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.
ABSTRACT
The new coronavirus infection (COVID-19) is associated with significant changes in hemostasis parameters, however, little is known about COVID-19-associated coagulopathy in pregnancy. In this observational case-control study, 39 women with acute COVID-19 infection at 36-40 gestational weeks of their pregnancy (COVID-19+ group) and 21 healthy age-and gestational week-matched pregnant women were enrolled (COVID-19-group). All women were outpatients and acute infection was confirmed or ruled out using SARS-CoV-2 RT-PCR or antigen test. In addition to screening tests of coagulation, D-dimer, fibrinogen, von Willebrand factor antigen, chromogenic factor VIII (FVIII) activity, factor XIII (FXIII) activity, in vitro clot-lysis, angiotensin convertase enzyme (ACE) activity, and anti-SARS-CoV-2 antibody levels were measured. In the COVID-19+ group, APTT was significantly increased, while PT, TT, fibrinogen and D-dimer were not significantly different as compared to the COVID-19-group. FVIII activity was significantly lower in the COVID-19+ group (183.7±47.7%) as compared to COVID-19-group (226.7±62.5%, p=0.01). Similarly, FXIII activity was reduced in the COVID-19+ group (82.3±23.5% vs. COVID-19-group: 96.2±26.6%, p=0.04). Pregnancy-associated complications including HELLP syndrome were observed in 2 cases of COVID-19+ group, with marked alterations of coagulation screening tests, clot-lysis and D-dimer levels. Conclusion: Pregnancy associated with SARS-CoV-2 infection in the third trimester leads to reduced levels of FVIII and FXIII activity, most likely as a result of increased coagulation activation and consumption.