Report of the ISTH registry on pregnancy and COVID-19-associated coagulopathy (COV-PREG-COAG).

Background: Concerns about COVID-19-associated coagulopathy (CAC) in pregnant individuals were raised in early pandemic. Methods: An ISTH-sponsored COVID-19 coagulopathy in pregnancy (COV-PREG-COAG) international registry was developed to describe incidence of coagulopathy, VTE, and anticoagulation in this group. Results: All pregnant patients with COVID-19 from participating centers were entered, providing 430 pregnancies for the first pandemic wave. Isolated abnormal coagulation parameters were seen in 20%; more often with moderate/severe disease than asymptomatic/mild disease (49% vs 15%; p < 0.0001). No one met the ISTH criteria for disseminated intravascular coagulopathy (DIC), though 5/21 (24%) met the pregnancy DIC score. There was no difference in antepartum hemorrhage (APH) with asymptomatic/mild disease versus moderate/severe disease (3.4% vs 7.7%; p = 0.135). More individuals with moderate/severe disease experienced postpartum hemorrhage (PPH) (22.4% vs 9.3%; p = 0.006). There were no arterial thrombotic events. Only one COVID-associated venous thromboembolism (VTE) was reported. Conclusions: Low rates of coagulopathy, bleeding, and thrombosis were observed among pregnant people in the first pandemic wave.

Hematologic characteristics and coagulopathy in pregnancy with COVID-19 succeeding the first wave: a multicenter retrospective cross-sectional study.

Background: Early reports have demonstrated an association of COVID-19 infection during pregnancy and postpartum period with coagulopathy and bleeding complications and indicated that pregnant people with COVID-19 are more likely to experience coagulopathy and venous thromboembolism. A recent report concerning such complications during the first wave of the pandemic was reassuring; however, no publications have evaluated these issues in the context of increased illness severity with the emergence of SARS-CoV-2 variants of concern. Objectives: We performed a retrospective, multinational cohort study in Canada, Romania, and the United Kingdom, aiming to provide a comprehensive analysis of the hematologic test characteristics of pregnancies affected by COVID-19 after the first wave of the pandemic. Results: Three-hundred-seventy patients were evaluated. Markers of inflammation and endothelial dysfunction were significantly elevated, in keeping with observations in the nonpregnant population. Reassuringly, despite more severe disease noted in succeeding waves of the pandemic, there was no significant evidence of COVID-19-associated coagulopathy, and overall, no association was demonstrated between isolated coagulation abnormalities and bleeding risk. Notably, fibrinogen below 2g/L was again linked with the risk of postpartum hemorrhage. Finally, venous thromboembolism risk was low but noted more frequently in those with severe illness despite thromboprophylaxis. Conclusion: Our findings add valuable insights into the nature of hematologic test characteristics, bleeding, and thrombotic complications for those affected with COVID-19 in pregnancy, reassuring readers of the low incidence of bleeding and thrombotic complications but inviting further debate as to the degree of thromboprophylaxis that may benefit the subgroup with severe disease.

Identification and treatment of iron-deficiency anemia in pregnancy and postpartum: A systematic review and quality appraisal of guidelines using AGREE II.

BACKGROUND: Several international guidelines provide recommendations for the optimal management of iron-deficiency anemia (IDA) in the pregnant and postpartum populations. OBJECTIVES: To review the quality of guidelines containing recommendations for the identification and treatment of IDA in pregnancy and postpartum using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument and to summarize their recommendations. SEARCH STRATEGY: PubMed, Medline, and Embase databases were searched from inception to August 2, 2021. A web engine search was also performed. SELECTION CRITERIA: Clinical practice guidelines that focused on the management of IDA in pregnancy and/or postpartum populations were included. DATA COLLECTION AND ANALYSIS: Included guidelines were appraised using AGREE II independently by two reviewers. Domain scores greater than 70% were considered high-quality. Overall scores of six or seven (out of a possible seven) were considered high-quality guidelines. Recommendations on IDA management were extracted and summarized. MAIN RESULTS: Of 2887 citations, 16 guidelines were included. Only six (37.5%) guidelines were deemed high-quality and were recommended by the reviewers. All 16 (100%) guidelines discussed the management of IDA in pregnancy, and 10 (62.5%) also included information on the management of IDA in the postpartum period. CONCLUSIONS: The complex interplay of racial, ethnic, and socioeconomic disparities was rarely addressed, which limits the generalizability of the recommendations. In addition, many guidelines failed to identify barriers to implementation, strategies to improve uptake or iron treatment, and resource and cost implications of clinical recommendations. These findings highlight important areas to target future work.

Planning Pregnancy and Birth in Women with Inherited Bleeding Disorders.

Inherited bleeding disorders are characterized by a diverse clinical phenotype within and across specific diagnoses. von Willebrand disease (VWD), hemophilia A, and hemophilia B comprise 95 to 97% of inherited bleeding disorders, with the remaining 3 to 5% attributed to rare bleeding disorders, including congenital fibrinogen disorders, factor deficiencies (affecting FII, FV, FV + FVIII, FVII, FX, FXI, and FXIII), and platelet function defects. The pregnancy, birth, and the puerperium may be adversely influenced in the setting of an inherited bleeding disorder depending on its type and clinical phenotype. Obstetric hemostatic challenges may sometimes also unmask the presence of a previously unknown inherited bleeding disorder. This review aims to address the approach to pregnancy and birth in the context of an inherited bleeding disorder and highlights the significance of multidisciplinary input into the care of these women.

Outcomes of Pregnancy in Women With Bioprosthetic Heart Valves With or Without Valve Dysfunction.

BACKGROUND: Although pregnancy outcomes in women with normally functioning bioprosthetic valves (BPVs) are often good, structural valve dysfunction (SVD) may adversely affect pregnancy outcomes, but this has not been studied. OBJECTIVES: The aim of this study was to examine outcomes in pregnant women with BPVs and the association with SVD. METHODS: Pregnancy outcomes in women with BPVs were prospectively collected. Adverse maternal cardiac events (CEs) included cardiac death or arrest, sustained arrhythmia, heart failure, thromboembolism, and stroke. Adverse fetal events were also studied. Determinants of adverse events were examined using logistic regression. RESULTS: Overall, 125 pregnancies in women with BPVs were included, 27% with left-sided and 73% with right-sided BPV. SVD was present in 27% of the pregnancies (44% with left-sided BPVs vs 21% with right-sided BPVs; P = 0.009). CEs occurred in 13% of pregnancies and were more frequent in women with SVD compared with those with normally functioning BPVs (26% vs 8%; P = 0.005). CEs were more common in women with left-sided BPVs with SVD vs normally functioning BPVs (47% vs 5%; P = 0.01) but not in women with right-sided BPVs (11% in those with SVD vs 8% in those without SVD; P = 0.67). Left-sided SVD (P = 0.007), maternal age >35 years (P = 0.001), and a composite variable of "high-risk" features (P = 0.006) were predictors of CEs. Fetal events occurred in 28% of pregnancies. CONCLUSIONS: In this cohort of young women with BPVs, SVD was present in 27% at the first antenatal visit and negatively affected pregnancy outcomes. In particular, SVD of left-sided BPVs was associated with high rates of adverse outcomes.

Distinct maternal and fetal pregnancy outcomes in women with sickle cell disease can be predicted using routine clinical and laboratory data.

We aimed to identify risk factors for adverse outcomes in pregnancies of women with sickle cell disease (SCD) and develop risk prediction models. Models were derived from a retrospective cohort of pregnant women with SCD and constructed using generalised estimating equation logistic regression, with clustering by woman. Maternal event(s) consisted of acute anaemia; cardiac, pulmonary, hepatobiliary, musculoskeletal, skin, splenic, neurological or renal complications, multi-organ failure, venous thromboembolism, admission-requiring vaso-occlusive events (VOE), red cell transfusion, mortality or hypertensive disorder of pregnancy. Fetal events included preterm birth, small-for-gestational-age or perinatal mortality. Of 199 pregnancies, 71% and 45% resulted in adverse maternal and fetal outcomes respectively. Low first-trimester haemoglobin, admission-requiring VOE in the year before pregnancy, multiple transfusions before pregnancy, SCD genotype and previous cardiac complications predicted maternal risk. Younger age and SCD genotype allowed early prediction of fetal risk (model-F1). Adding maternal event(s) and high lactate dehydrogenase enabled re-assessment of fetal risk with advancing gestation (model-F2). Models were well calibrated and moderately discriminative for maternal outcome (c-statistic 0·81, cross-validated value 0·79) and fetal outcome (model-F1 c-statistic 0·68, cross-validated value 0·65; model-F2 c-statistic 0·72, cross-validated value 0·68). The models will allow early identification of women with SCD at high risk of adverse events, permitting early targeted interventions and ongoing fetal risk re-assessment enabling intensification of surveillance and optimisation of delivery timing.

Haemostatic and thrombo-embolic complications in pregnant women with COVID-19: a systematic review and critical analysis.

BACKGROUND: As pregnancy is a physiological prothrombotic state, pregnant women may be at increased risk of developing coagulopathic and/or thromboembolic complications associated with COVID-19. METHODS: Two biomedical databases were searched between September 2019 and June 2020 for case reports and series of pregnant women with a diagnosis of COVID-19 based either on a positive swab or high clinical suspicion where no swab had been performed. Additional registry cases known to the authors were included. Steps were taken to minimise duplicate patients. Information on coagulopathy based on abnormal coagulation test results or clinical evidence of disseminated intravascular coagulation (DIC), and on arterial or venous thrombosis, were extracted using a standard form. If available, detailed laboratory results and information on maternal outcomes were analysed. RESULTS: One thousand sixty-three women met the inclusion criteria, of which three (0.28, 95% CI 0.0 to 0.6) had arterial and/or venous thrombosis, seven (0.66, 95% CI 0.17 to 1.1) had DIC, and a further three (0.28, 95% CI 0.0 to 0.6) had coagulopathy without meeting the definition of DIC. Five hundred and thirty-seven women (56%) had been reported as having given birth and 426 (40%) as having an ongoing pregnancy. There were 17 (1.6, 95% CI 0.85 to 2.3) maternal deaths in which DIC was reported as a factor in two. CONCLUSIONS: Our data suggests that coagulopathy and thromboembolism are both increased in pregnancies affected by COVID-19. Detection of the former may be useful in the identification of women at risk of deterioration.