Thrombotic microangiopathy, DIC-syndrome and COVID-19: link with pregnancy prothrombotic state.

For last months, humanity has faced a formidable unknown enemy, which is presented as a new coronavirus infection. Despite the fact that the causative agents of new diseases appear at a certain frequency and that the virus SARS-CoV-2 has certain common properties with its predecessors, at the moment we are dealing with a new unknown pathogenesis of the development of severe complications in patients with risk factors. A final understanding of pathological process mechanisms is the goal of the scientific community. Summarizing research data from different countries, it became obvious that in severe cases of viral infection, we are dealing with a combination of the systemic inflammatory response syndrome, disseminated intravascular coagulation and thrombotic microangiopathy (TMA). Thrombotic microangiopathy is represented by a group of different conditions in which thrombocytopenia, hemolytic anemia, and multiple organ failure occur. The article reflects the main types of TMA, pathogenesis and principles of therapy. The main participants in the process are described in detail, including the von Willebrand factor and ADAMTS-13. Based on the knowledge available, as well as new data obtained from patients with COVID-19, we proposed possible models for the implementation of conditions such as sepsis, TMA, and DIC in patients with severe new coronavirus infection. Through a deeper understanding of pathogenesis, it will be possible to develop more effective diagnosis and therapy.

Novel coronavirus infection and Kawasaki disease.

There is a global problem of increment of the number of children with clinical features that mimic Kawasaki Disease (KD) during the ongoing Coronavirus Disease 2019 (COVID-19) pandemic. The disease was first reported by Tomisaku Kawasaki, a Japanese pediatrician, in a four-year-old child with a rash and fever at the Red Cross Hospital in Tokyo in January 1961. Now Kawasaki disease is recognized worldwide. The complexity of symptoms was defined as an «acute febrile mucocutaneous lymphnode syndrome". At the moment, it is still unclear whether the coronavirus itself can lead to development of mucocutaneous lymph node syndrome. However, it is believed that COVID-19 virus infection worsens the course of Kawasaki disease, and in some cases, children affected by SARS-V-2 may develop a disease that has a clinical picture similar to Kawasaki disease.

Role of Doppler ultrasound at time of diagnosis of late-onset fetal growth restriction in predicting adverse perinatal outcome: prospective cohort study.

OBJECTIVE: Pregnancies complicated by late-onset fetal growth restriction (FGR) are at increased risk of short- and long-term morbidities. Despite this, identification of cases at higher risk of adverse perinatal outcome, at the time of FGR diagnosis, is challenging. The aims of this study were to elucidate the strength of association between fetoplacental Doppler indices at the time of diagnosis of late-onset FGR and adverse perinatal outcome, and to determine their predictive accuracy. METHODS: This was a prospective study of consecutive singleton pregnancies complicated by late-onset FGR. Late-onset FGR was defined as estimated fetal weight (EFW) or abdominal circumference (AC) < 3rd centile, or EFW or AC < 10th centile and umbilical artery (UA) pulsatility index (PI) > 95th centile or cerebroplacental ratio (CPR) < 5th centile, diagnosed after 32 weeks. EFW, uterine artery PI, UA-PI, fetal middle cerebral artery (MCA) PI, CPR and umbilical vein blood flow normalized for fetal abdominal circumference (UVBF/AC) were recorded at the time of the diagnosis of FGR. Doppler variables were expressed as Z-scores for gestational age. Composite adverse perinatal outcome was defined as the occurrence of at least one of emergency Cesarean section for fetal distress, 5-min Apgar score < 7, umbilical artery pH < 7.10 and neonatal admission to the special care unit. Logistic regression analysis was used to elucidate the strength of association between different ultrasound parameters and composite adverse perinatal outcome, and receiver-operating-characteristics (ROC)-curve analysis was used to determine their predictive accuracy. RESULTS: In total, 243 consecutive singleton pregnancies complicated by late-onset FGR were included. Composite adverse perinatal outcome occurred in 32.5% (95% CI, 26.7-38.8%) of cases. In pregnancies with composite adverse perinatal outcome, compared with those without, mean uterine artery PI Z-score (2.23 ± 1.34 vs 1.88 ± 0.89, P = 0.02) was higher, while Z-scores of UVBF/AC (-1.93 ± 0.88 vs -0.89 ± 0.94, P ≤ 0.0001), MCA-PI (-1.56 ± 0.93 vs -1.22 ± 0.84, P = 0.004) and CPR (-1.89 ± 1.12 vs -1.44 ± 1.02, P = 0.002) were lower. On multivariable logistic regression analysis, Z-scores of mean uterine artery PI (P = 0.04), CPR (P = 0.002) and UVBF/AC (P = 0.001) were associated independently with composite adverse perinatal outcome. UVBF/AC Z-score had an area under the ROC curve (AUC) of 0.723 (95% CI, 0.64-0.80) for composite adverse perinatal outcome, demonstrating better accuracy than that of mean uterine artery PI Z-score (AUC, 0.593; 95% CI, 0.50-0.69) and CPR Z-score (AUC, 0.615; 95% CI, 0.52-0.71). A multiparametric prediction model including Z-scores of MCA-PI, uterine artery PI and UVBF/AC had an AUC of 0.745 (95% CI, 0.66-0.83) for the prediction of composite adverse perinatal outcome. CONCLUSION: While CPR and uterine artery PI assessed at the time of diagnosis are associated independently with composite adverse perinatal outcome in pregnancies complicated by late-onset FGR, their diagnostic performance for composite adverse perinatal outcome is low. UVBF/AC showed better accuracy for prediction of composite adverse perinatal outcome, although its usefulness in clinical practice as a standalone predictor of adverse pregnancy outcome requires further research. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Papel de la ecografía Doppler en el momento del diagnóstico de la restricción del crecimiento fetal de aparición tardía para la predicción de resultados perinatales adversos: estudio prospectivo de cohortes OBJETIVO: Los embarazos complicados por la restricción del crecimiento fetal (RCF) de aparición tardía tienen un mayor riesgo de morbilidad a corto y largo plazo. A pesar de ello, es difícil identificar los casos con mayor riesgo de resultados perinatales adversos en el momento del diagnóstico de RCF. Los objetivos de este estudio fueron dilucidar la fortaleza de la asociación entre los índices Doppler fetoplacentarios en el momento del diagnóstico de la RCF de aparición tardía y el resultado perinatal adverso, y determinar su precisión predictiva. MÉTODOS: Este fue un estudio prospectivo de embarazos consecutivos con feto único complicados por una RCF de aparición tardía. La aparición tardía de la RCF se definió como peso estimado del feto (PEF) o circunferencia abdominal (CA) <3er percentil, o PEF o CA <10o percentil junto con índice de pulsatilidad (IP) de la arteria umbilical (AU) >95o percentil, o una relación cerebroplacentaria (RCP) <5o percentil, diagnosticado después de las 32 semanas. El PEF, el IP de la arteria uterina (IP-AU), el IP de la arteria cerebral media fetal (ACM), la RCP y el flujo sanguíneo de la vena umbilical normalizado para la circunferencia abdominal fetal (UVBF/AC, por sus siglas en inglés) se registraron en el momento del diagnóstico de RCF. Las variables Doppler se expresaron como puntuaciones Z para la edad gestacional. El resultado perinatal adverso compuesto se definió como la ocurrencia de al menos una cesárea de emergencia por sufrimiento fetal, test de Apgar a los 5 minutos <7, pH de la arteria umbilical <7,10 y el ingreso a la unidad de cuidados especiales de recién nacidos. Se utilizó el análisis de regresión logística para dilucidar la fortaleza de la asociación entre los diferentes parámetros de la ecografía y el resultado perinatal adverso compuesto, y se empleó el análisis de la curva de características operativas del receptor (ROC, por sus siglas en inglés) para determinar su precisión predictiva. RESULTADOS: En total, se incluyeron 243 embarazos con feto único consecutivos complicados por RCF de aparición tardía. El resultado perinatal adverso compuesto se produjo en el 32,5% (IC 95%, 26,7-38,8%) de los casos. En los embarazos con resultados perinatales adversos compuestos, en comparación con los que no los tuvieron, la puntuación Z del IP de la arteria uterina media (2,23±1,34 vs 1,88±0,89, P=0,02) fue mayor, mientras que las puntuaciones Z de UVBF/AC (-1,93±0,88 vs -0,89±0,94, P≤0,0001), IP-ACM (-1,56±0,93 vs -1,22±0,84, P=0,004) y RCP (-1,89±1,12 vs -1,44±1,02, P=0,002) fueron más bajas. En el análisis de regresión logística multivariable, las puntuaciones Z del IP de la arteria uterina media (P=0,04), RCP (P=0,002) y UVBF/AC (P=0,001) estuvieron asociadas de forma independiente con el resultado perinatal adverso compuesto. La puntuación Z del UVBF/AC tuvo un área bajo la curva (ABC) ROC de 0,723 (IC 95%, 0,64-0,80) para el resultado perinatal adverso compuesto, demostrando una mejor precisión que la de la puntuación Z del IP de la arteria uterina media (ABC, 0,593; IC 95%, 0,50-0,69) y la de la puntuación Z de la RCP (ABC, 0,615; IC 95%, 0,52-0,71). Un modelo de predicción multiparamétrico que incluía las puntuaciones Z del IP-ACM, el IP de la arteria uterina y el UVBF/AC resultó en un ABC de 0,745 (IC 95%, 0,66-0,83) para la predicción de un resultado perinatal adverso compuesto. CONCLUSIÓN: Aunque la RCP y el IP de la arteria uterina evaluados en el momento del diagnóstico están asociados de forma independiente con un resultado perinatal adverso compuesto en embarazos complicados por una RCF de aparición tardía, la eficacia del diagnóstico para el resultado perinatal adverso compuesto es baja. El UVBF/AC mostró una mayor precisión para la predicción de un resultado perinatal adverso compuesto, aunque su utilidad en la práctica clínica como parámetro indicativo independiente del resultado adverso del embarazo requiere más investigación. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Role of first-trimester umbilical vein blood flow in predicting large-for-gestational age at birth.

OBJECTIVES: To describe umbilical vein (UV) hemodynamics at 11 + 0 to 13 + 6 weeks of gestation in pregnancies delivering a large-for-gestational-age (LGA) neonate, and to build a multiparametric model, including pregnancy and ultrasound characteristics in the first trimester, that is able to predict LGA at birth. METHODS: This was a matched case-control study, of singleton pregnancies that underwent ultrasound examination at 11 + 0 to 13 + 6 weeks for aneuploidy screening, at a single center over a 4-year period. Cases were women who delivered a neonate with birth weight (BW) > 90th centile for gestational age and sex, according to local birth-weight standards, while controls were those who delivered a neonate with BW ranging between the 10th and 90th centiles, matched for maternal and gestational age, at a ratio of 1:3. Each included case underwent Doppler assessment of the uterine arteries and UV, including measurement of its diameter, time-averaged maximum velocity (TAMXV) and UV blood flow (UVBF). UVBF and its components were expressed as Z-scores. Fisher's exact test and Mann-Whitney U-test were used to compare differences in maternal biomarkers and ultrasound characteristics between pregnancies complicated by LGA and controls. Logistic regression and receiver-operating-characteristics (ROC) curve analyses were carried out to identify independent predictors of LGA and to build a multiparametric prediction model integrating different maternal, pregnancy and ultrasound characteristics. Subgroup analysis was also performed, considering women who delivered a neonate with BW > 4000 g. RESULTS: In total, 964 pregnancies (241 with LGA at birth and 723 without) were included in the study. In LGA pregnancies compared with controls, UV-TAMXV Z-score (0.8 (interquartile range (IQR), 0.4-1.5) vs 0.0 (IQR, -0.3 to 0.5); P ≤ 0.001) and UVBF Z-score (1.3 (IQR, 0.8-1.9) vs 0.1 (IQR, -0.4 to 0.4); P ≤ 0.001) were higher, while there was no difference in median UV diameter Z-score (P = 0.56). Median uterine artery pulsatility index multiples of the median (MoM; 0.94 (IQR, 0.78-1.12) vs 1.02 (IQR, 0.84-1.19); P = 0.04) was significantly lower in LGA pregnancies. On multivariate logistic regression analysis, maternal body mass index (BMI; adjusted odds ratio (aOR), 1.2 (95% CI, 1.1-1.7); P < 0.001), parity (aOR, 1.4 (95% CI, 1.2-1.6); P < 0.001), pregnancy-associated plasma protein-A (PAPP-A) MoM (aOR, 1.1 (95% CI, 1.0-1.6); P = 0.04) and UVBF Z-score (aOR, 1.6 (95% CI, 1.1-1.9); P < 0.001) were associated independently with LGA. A multiparametric model integrating parity, BMI and PAPP-A MoM provided an area under the ROC curve (AUC) of 0.72 (95% CI, 0.67-0.76) for the prediction of LGA. The addition of UVBF Z-score to this model significantly improved the prediction of LGA provided by maternal and biochemical factors, with an AUC of 0.79 (95% CI, 0.75-0.83; P = 0.03). Similarly, the model incorporating UVBF Z-score predicted BW > 4000 g with an AUC of 0.83 (95% CI, 0.75-0.93). CONCLUSIONS: UVBF measured at the time of the 11-14-week scan is associated independently with, and is predictive of, LGA and BW > 4000 g. Adding measurement of UVBF to a multiparametric model that includes maternal (parity and BMI) and biochemical (PAPP-A) parameters improves the diagnostic accuracy of prenatal screening for LGA at birth. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Catastrophic antiphospholipid syndrome and pregnancy. Clinical report.

We have observed the development of a catastrophic antiphospholipid syndrome (CAPS) in a pregnant woman hospitalized at 28 weeks of gestation with a severe preeclampsia. On the same day, an eclampsia attack developed, and an emergency surgical delivery was performed. On the third day, multiorgan failure developed. Examination showed a persistent circulation of lupus anticoagulant, high level of antibodies to cardiolipin, b2-glycoprotein I, and prothrombin. The usual diagnosis of the severe preeclampsia masked a catastrophic antiphospholipid syndrome, exacerbated by the coincident presence of several types of antiphospholipid antibodies. The first pregnancy resulted in a premature birth at 25 weeks, possibly also due to the circulation of antiphospholipid antibodies. The trigger of the catastrophic form development was the pregnancy itself, surgical intervention, and hyperhomocysteinemia. CAPS is the most severe form of antiphospholipid syndrome, manifested in multiple microthrombosis of microcirculation of vital organs and in the development of multiorgan failure against the background of the high level of antiphospholipid antibodies. CAPS is characterized by renal, cerebral, gastrointestinal, adrenal, ovarian, skin, and other forms of microthrombosis. Thrombosis recurrence is typical. Thrombotic microvasculopathy lies at the heart of multiorgan failure and manifests clinically in central nervous system lesions, adrenal insufficiency, and ARDS development. CAPS is a life-threatening condition, therefore, requires an urgent treatment. Optimal treatment of CAPS is not developed. CAPS represent a general medical multidisciplinary problem.

Pregnancy and mesenchimal dysplasias (Marfan syndrome, Ehlers-Danlos syndrome, hereditary hemorrhagic telangiectasia).

The objective of this article is to attract the attention of clinical physicians to the rare but extremely relevant clinical pathology of mesenchymal dysplasias (Marfan syndrome, Ehlers-Danlos syndrome, hereditary hemorrhagic telangiectasia) and especially specific characteristics of such diseases during pregnancy. Connective tissue pathology can cover different organs and systems, symptoms of the same disease can vary in different patients thus making diagnostics significantly difficult. Here clinical diagnostic criteria and methods of molecular diagnostics of diseases are described. The pathogenesis of mesenchymal dysplasias is not currently well understood. For the patients with mesenchymal dysplasias pregnancy is fraught with high risk of life-threatening complications. The preferred delivery method for such patients is caesarean section.