scholarly journals The role of genetic markers of thrombophilia in the structure of the causes of placenta-associated complications in pregnant women with thrombocytopenia

2021 ◽  
Vol 70 (1) ◽  
pp. 101-108
Author(s):  
Olga L. Mysik ◽  
Marina S. Zaynulina ◽  
Vladislav S. Baranov ◽  
Ksenia A. Klikunova ◽  
Aliya M. Zhivopistseva

Hypothesis/Aims of study: Disorders of the hemostatic system continue to occupy one of the leading places in the structure of the causes of infertility and miscarriage. While being associated with reproductive losses, hemostatic disorders are a significant link in the pathogenesis of placenta-associated pregnancy complications. The consumption of platelets and blood clotting factors can be a consequence of inherited thrombophilia and the cause of adverse clinical outcomes of pregnancy. Women with congenital and acquired thrombophilia are at high risk of developing both thrombotic and gestational complications of pregnancy. The aim of this study was to assess the frequency of genetic markers of thrombophilia in pregnant women with thrombocytopenia and to determine the risk of developing obstetric complications depending on thrombophilia gene polymorphisms in the examined women. Study design, materials and methods: This multicenter prospective study involved 299 pregnant women in the third trimester of pregnancy. Two groups of patients were included in the study: the main group (n = 249) consisted of individuals with thrombocytopenia, whereas the control group (n = 50) comprised women with normal platelet counts during physiological pregnancy. All patients underwent a complete clinical, anamnestic and laboratory examination. To identify thrombophilia gene polymorphisms, molecular genetic blood testing was conducted using a biochip developed jointly in the Laboratory of Prenatal Diagnostics of Congenital and Hereditary Diseases, the Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott, Saint Petersburg, Russia and the V.A. Engelhardt Institute of Molecular Biology, Moscow, Russia. Results: The data obtained from a comparative analysis of genetic markers of thrombophilia indicate that the incidence of mutations in the GPIa platelet receptor gene in pregnant women with thrombocytopenia was significantly higher than that in pregnant women with normal platelet counts and physiological pregnancy (42.5% vs. 14.7%; p = 0.003). The frequency of polymorphisms in genes responsible for disorders in the fibrinolytic system (PAI-1, FGB) was also significantly higher than that in the control group (76.4% vs. 47.0%, p = 0.001; 45.7% vs. 23.5%, p = 0.030, respectively). Conclusion: The revealed high frequency of polymorphisms in the platelet receptor genes and genes responsible for disorders of fibrinolysis system in pregnant women with thrombocytopenia may cause platelet hyperaggregation and hypercoagulation, while being a significant risk factor for placenta-associated complications during pregnancy. The variety of genetic defects that may lead to an unfavorable clinical outcome of pregnancy dictates the need for further study.

GYNECOLOGY ◽  
2019 ◽  
Vol 21 (2) ◽  
pp. 18-22
Author(s):  
Nataly I Frolova ◽  
Tatiana E Belokrinitskaya ◽  
Nataliya N Strambovskaya ◽  
Evgeniya P Belozertseva

Aim. To assess the association between polymorphisms of FVL-1691G>A, FII-20210G>A, MTHFR-677C>T, MTHFR-1298А>C, РАІ-1-6755G>4G and their combinations in patients with recurrent early pregnancy losses (RPL). Materials and methods. This study included two groups of women (age range 20-35 years): 50 currently non-pregnant women with a history of 2-5 unexplained recurrent early spontaneous abortion and unknown causes of miscarriages (RPL group), and 50 currently non-pregnant women with a history of having given birth to at least one live baby and without a history of spontaneous abortion, preterm labor, stillbirth, preeclampsia and other pregnancy complications (control group). Gene polymorphisms were detected by the technique of polymerase chain reaction-real time. We have analyzed the frequencies, Hardy-Weinberg equilibrium, V-Kramer test, χ2 test, odds ratio (OR) and its 95% confidence interval (95% CI). General (χ2 test, df=2) and multiplicative (χ2 test, df=1) models of inheritance have been used to assess the presence of gene polymorphisms. Results. Significant association between heterozygotes genotype PAI-1-5G4G (72% vs 32%, p=0.000; OR 5.46; 95% CI 2.32-12.87) and RPL was found. Heterozygous genotype FII-20210GA was detected only in RPL group (4% vs 0%). Combinations of genetic polymorphisms of FVL-1691G>A, FII-20210G>A, MTHFR-677C>T, MTHFR-1298А>C, РАІ-1-6755G>4G increase the risk of RPL by 2.4 times (56% vs 20%; χ2=29.20, р=0.000; OR 3.69, 95% CI 1.52-8.97; strong V-Kramer association). The combination of two heterozygotes variants of minor alleles was found to be a risk factor for RPL (34% vs 10%; χ2=8.73, р=0.004; OR 4.64, 95% CI 1.55-3.84). Combined PAI-1-5G4G + FVL-1691GA genotypes was detected only in RPL group of women (2% vs 0%). No significant association between the combination of three heterozygotes variants of minor alleles and RPL. Conclusion. Our data suggest significant gene-gene interaction of the heterozygotes variants of minor alleles of FVL-1691G>A, FII-20210G>A, MTHFR-677C>T, MTHFR-1298А>C, РАІ-1-6755G>4G polymorphisms in patients with recurrent miscarriage. Combined genotypes FVL-1691GA/PAI-1-5G4G can be considered as a genetic molecular predictor of recurrent early pregnancy losses.


Author(s):  
Mei-Lien Pan ◽  
Li-Ru Chen ◽  
Kuo-Hu Chen

Objective: To assess the risk of subsequent miscarriage in pregnant women with a prior diagnosis of polycystic ovarian syndrome (PCOS). Methods: Using a nationwide, population-based database (Taiwan National Health Insurance Research Database) during 1998–2012, the study retrieved 1,000,000 randomly-sampled insured citizens as research subjects. The women with a diagnosis of pre-pregnancy PCOS (n = 13,562) who had chromosomal anomalies, artificial abortion, inconsistent diagnoses, and who were initially diagnosed with PCOS at >45 or <15 year-old were excluded, respectively. The records of gynecologic ultrasonography and/or blood tests were checked to verify the accuracy of the diagnoses of both PCOS and miscarriage (ICD-9 CM codes). After pregnancy, every woman with prior PCOS was age-matched to four women without prior PCOS. Results: Pregnant women with prior PCOS (the case group; n = 1926) and those without prior PCOS (the control group; n = 7704) were compared. The incidence of subsequent miscarriage was much higher in the case group compared with the control group (33.80% vs. 4.09%, p < 0.0001). Logistic regression analysis revealed that the risk of subsequent miscarriage was significantly higher in the case group than the control group (odds ratio [OR] 11.98; 95% CI 10.34–13.87, p < 0.0001), and the result remained similar while adjusted with covariates (adjusted OR 11.97; 95% CI 10.27–13.95, p < 0.0001). In the case group, the patient who used metformin had a lower risk of subsequent miscarriage (adjusted OR 9.53; 95% CI 6.69–13.57) when compared with those who did not receive metformin treatment (adjusted OR 12.13; 95% CI 10.38–14.18). Conclusion: For pregnant women, a pre-pregnancy diagnosis of PCOS is an independent and significant risk factor for subsequent miscarriage. The risk of subsequent miscarriage is reduced by about 1/4 for the PCOS patients who undergo metformin treatment compared with those who do not.


Author(s):  
Suhail Iqbal ◽  
Aditi Sharma

Background: One of the most common and potential life-threatening complications of pregnancy is pregnancy induced hypertension. Though platelet count during pregnancy is within the normal non-pregnant reference values, there is a tendency for the platelet count to fall in late pregnancy. The frequency and intensity of maternal thrombocytopenia varies and is dependent on the intensity and severity of PIH.Methods: This prospective study was conducted in the Department of obstetrics and gynecology in Jhalawar medical college from January 2018 to April 2018.Total 120 pregnant women during third trimester (32-40 weeks) aged 18 to 35 years were selected. Among them 63 were preeclamptic patients and 63 were healthy normotensive control. Subjects and healthy pregnant women (control) visiting the Obstetrics and Gynecology department of Jhalawar Medical College were registered in the study and followed during their pregnancy. Both, subjects and control participants were subject to platelet count manually and MPV was determined by an automated analyser (sysmex XN-1000™) performed using standard methods on.Results: The mean platelet count of the subject group (131.4937±62.05999 lakh/mm3) was significantly lower than that of the control group (324.9683±230.78764 lakh/mm3). This shows that there is thrombocytopenia found in patients with P.I.H in their third trimester. On the other hand, the p value of “mean platelet volume” in patients with preeclampsia was (p<0.0001) which shows that there is no significant difference in MPV of cases (7.1438±2.62 femtolitre) and control (7.8976±3.08 femtolitre) (p>0.142), regular monitoring of platelet counts in women with Pregnancy Induced Hypertension must be subject of the management protocols.Conclusions: In present study we observed that the number of thrombocytopenic subjects was higher in cases of preeclampsia as compared to the control group. These extrapolations indicate that there might be some important mechanism which interferes with platelets life span thus reducing the number of functional platelets in circulation. The platelet count has an association at prediction of increasing grade of PIH. There is an inverse relationship between the severity of PIH and platelet count. The depleted platelet counts are concluded to be consistently associated with clinical groups of severe preeclampsia and the risk of consumptive coagulopathy.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4985-4985 ◽  
Author(s):  
Hemendra Mhadgut ◽  
Hadiza Galadima ◽  
Hassan Raymond Tahhan

Abstract Background: Thrombocytosis can be a result of a reactive process such as acute blood loss, infections, iron deficiency anemia (IDA) or a clonal disorder such as Essential Thrombocythemia. The challenge of correctly identifying the etiology of thrombocytosis in an individual patient becomes particularly essential when the clinician is confronted with decisions regarding further workup, follow up as well as preventing future complications such as thrombotic events. Prior data linking iron deficiency anemia and thrombocytosis has been concluded from studies with small sample size, and to a large part, this association is based on anecdotal evidence. Our study examines the association between IDA and platelet counts and to the best of our knowledge is the largest study to do so. Methods: We performed a retrospective chart review of patients seen at our outpatient clinic from 1st January to 31st December 2017. We defined Iron deficiency as serum ferritin <30 mcg/dl, anemia in males as hemoglobin (Hb) <13.1 g/dl, anemia in females as Hb <11.7g/dl and thrombocytosis as platelet count >450,000/ul. Patient demographics, as well as hematological data, were collected and compared between three groups: Iron deficiency anemia, Iron deficiency without anemia, and control. We defined controls as subjects with neither iron deficiency nor anemia. Bivariate analysis using the Chi-square test for categorical variables, and a One-Way ANOVA for continuous variables were used to determine the association between the three groups of interest and the covariates. The relationship between platelet counts and other hematological parameters was evaluated using Pearson's correlation test. Results: Of the 4896 subjects included in our study, 1225 (25.02%) had iron deficiency anemia, 699 (14.28%) had iron deficiency without anemia, and 2972 (60.70%) were controls. The mean age of the cohort was 55.8 (SD = 18.31) years, and 73.9% of the subjects were females. In the IDA group, the mean hemoglobin was 10.21 (SD = 1.39) g/dl, the mean platelet count was 319.24 (SD = 106.92) k/uL, and 127 (10.37%) subjects had thrombocytosis whereas 1098 (89.63%) had normal platelet counts. When compared to the control group, 32 (1.08%) subjects had thrombocytosis, and 2940 ( 98.92%) had normal platelet counts. The difference in numbers of subjects with thrombocytosis between iron deficiency anemia, iron deficiency without anemia and control group was statistically significant as indicated by P<0.001 on the Chi-Square test. Furthermore, we found an inverse relationship between platelet count and ferritin as well as hemoglobin level with a p < 0.0001 across all groups. Conclusions: Our study demonstrated a significant association between iron deficiency anemia and thrombocytosis when compared to the control group however at a lower frequency than seen in the previously published studies. Further studies are needed to study causality and to elucidate the mechanism by which iron deficiency anemia leads to thrombocytosis. Table. Table. Disclosures No relevant conflicts of interest to declare.


2021 ◽  
Vol 18 (6) ◽  
pp. 57-62
Author(s):  
O. I. Dolgov ◽  
А. V. Gerasin ◽  
А. А. Shcherbakov ◽  
V. E. Pavlov ◽  
S. А. Karpishchenko ◽  
...  

The objective: to assess the incidence and influence of platelets level on the hemorrhagic complications during percutaneous dilated tracheotomy (PDT) in patients with thrombocytopenia.Subjects and Methods. The study included 85 consecutive patients with varying degrees of thrombocytopenia at the stages of hematopoietic stem cell transplantation. The control group included 56 patients who underwent classical tracheotomy. The study group included 29 patients who underwent PDT (Griggs method). The operations were performed for prolonged artificial pulmonary ventilation. When the platelets level was below 20 × 109/L, platelet concentrate transfusion was performed before the operation.Results. The incidence of hemorrhagic complications in patients with thrombocytopenia during PDT was 13.8% (95% CI 9.13–18.45%). In open tracheotomy, the bleeding rate was 3.8% (95% CI 2.65–4.49%). These results are comparable to the incidence of hemorrhagic complications in patients with normal platelet counts. The influence of the platelet level on the presence of hemorrhagic complications in both groups was not established.Conclusion. Thrombocytopenia is not a contraindication to performing PDT. However, platelet concentrate transfusion should be performed in patients with platelet counts less than 20 × 109/L. An experienced team of anesthesiologists and endoscopists can reduce the incidence of other complications.


1970 ◽  
Vol 24 (01/02) ◽  
pp. 010-016 ◽  
Author(s):  
D Green ◽  
H. C Kwaan ◽  
G Ruiz

SummaryCoagulation studies were performed in 52 patients with sickle cell disease during asymptomatic periods and during episodes of crisis and infection. Platelet counts averaged 473,000, 469,000, and 461,000 per mm3 in these 3 groups, and factor VIII concentrations were elevated in all. Fibrinogen was increased to the same extent in both sickle cell and non-sickle cell patients with infection. Fibrinolytic activity, as measured by euglobulin lysis times and zones of lysis on fibrin plates, was markedly reduced during periods of infection in sickle cell patients but not in non-sickle patients. Impairment of fibrinolysis in most patients was not on the basis of overutilization or consumption, since no decrease in the levels of clotting factors or plasminogen was observed. It was suggested that generalized intravascular sickling in these patients may have caused widespread endothelial damage, resulting in decreased production of plasminogen activator.In addition, several sickle cell patients with infection were found to possess elevated levels of an inhibitor directed against urokinase.


2017 ◽  
pp. 66-68
Author(s):  
V.I. Boyko ◽  
◽  
S.A. Tkachenko ◽  

The objective: depression of frequency of perinatal pathology at women with decompensation form of placental dysfunction by improvement of the main diagnostic and treatment-and-prophylactic actions. Patients and methods. 154 pregnant women in gestation term from 22 to 40 weeks were surveyed. Depending on features of course of pregnancy and families of all surveyed it was divided into 4 groups. The group of the retrospective analysis was made by 45 pregnant women with decompensation placental dysfuction, the group of prospective research included 109 pregnant women of whom the main group was made by 38 women with decompensation form of placental dysfunction, the group of comparison included 47 pregnant women with the compensated form of placental dysfunction. The control group was made by 24 pregnant women with the uncomplicated course of pregnancy and labors. The complex of the conducted researches included clinical, ehografical, dopplerometrical, laboratory, morphological and statistical methods. Results. Use of advanced algorithm of diagnostic and treatment-and-prophylactic actions allows to increase efficiency of diagnostics of decompensation form of placental dysfunction for 33.3%, and rational tactics of a delivery leads to depression of perinatal pathology for 22.7%. Conclusion. Decompensation placental dysfuction is one of the main reasons for perinatal mortality and a case rate at the present stage. Use of the algorithm of diagnostic and treatment-and-prophylactic actions improved by us allows major factors of risk of this complication and the indication for change of tactics and delivery times. Key words: decompensation placental dysfunction, diagnostics, delivery tactics.


2017 ◽  
pp. 68-73
Author(s):  
I.P. Polishchuk ◽  

The objective: was to examine the effectiveness of treatment of late miscarriage threat by micronized form of progesterone for 100 mg – 3 times a day in the form of gelatin pills and vaginal tablets with lactose. Patients and methods. Under our supervision there were 70 pregnant women with normocenosis of vagina (NCV) without extragenital pathology, which were not performed systemic or local treatment with antibacterial drugs in the last 4 weeks. Among them 25 pregnant women with TLSM treated by gelatin tablets of micronized progesterone (GTP) (group 1); 25 pregnant women with TLSM, treated by vaginal micronized progesterone tablets (VPT) (2nd group) and 20 healthy women with physiological pregnancy – PV (control group). The distribution of women in the group adhered to the principles of randomization. The age of examined women ranged from 19 to 32 years, most pregnant women were aged under 30 years (89.02%). General clinical examination was carried out according to the standard scheme according to the Order MH of Ukraine № 620. Results. During the research we have determined the colpocytologcal dynamics and state of vaginal microbiota in pregnant women with threatened late miscarriage with initial vaginal normocenosis before and after treatment whit vaginal forms of progesterone. Conclusion. The received results showed low efficiency of micronized progesterone gelatin dragee at threat of the late miscarriage that at small therapeutic effect has led to the development of vaginal dysbiosis in all surveyed. In contrast, the use of micronized progesterone vaginal tablets – the maximally rapid therapeutic effect without disturbance of vaginal normocenosis. Key words: the threat of a late miscarriage, vaginal micronized forms of progesterone.


2019 ◽  
pp. 50-54
Author(s):  
V.O. Golyanovskiy ◽  
◽  
Ye.O. Didyk ◽  

Pregnant women with intrauterine growth restriction (IUGR) have an increased risk of adverse perinatal and long-term complications compared with the birth of children with normal body weight. Thus, IUGR is one of the main challenges for the global health system, especially in poor and developing countries. Morpho-functional studies of the placentas help in determining the causes of IUGR, and therefore, timely prevent complications in pregnant women with IUGR. The objective: The purpose of this study is to investigate various morphometric and pathomorphological changes in the placenta, including inflammatory, in cases of IUGR, and to establish a correlation of these results with the etiology and complications for the fetus. Materials and methods. In the current study, 54 placentas of the fetuses with IUGR (the main group) were compared with 50 placentas of the fetuses with normal development (control group). The criteria for the inclusion of IUGR were gestational age more than 30 weeks and all fetuses with a weight less than 10th percentile for this period of pregnancy. The placenta material was studied pathomorphologically with laboratory screening for infection and inflammation. Similarly, the results were determined for placentas of the fetuses with normal development compared to placentas with IUGR. Results. The placenta study showed the presence of calcification in the case of IUGR, as well as in the case of prolonged pregnancy. However, calcification of the placenta in the case of IUGR was more progressive compared with placenta in the normal pregnancy. In addition, the presence of intrauterine infection and inflammation was observed, which could also lead to an adverse outcome for the further progression of pregnancy with IUGR. Conclusion. A comparative macro- and microscopic pathomorphological study of the placentas in the two groups has shown a significant increase in the pathological changes in all the anatomical structures of the fetuses with IUGR. Key words: Intrauterine growth restriction (IUGR), fetal weight, pathomorphological changes of the placenta.


2016 ◽  
pp. 160-164
Author(s):  
D.N. Maslo ◽  

The objective: frequency decrease perinatal pathologies at women after ART on the basis of studying clinical-ehografical, endocrinological, biochemical, dopplerometrical, cardiotokografical and morphological researches, and also improvement of algorithm of diagnostic and treatment-and-prophylactic actions. Patients and methods. The work basis is made spent by us from 2012 on 2015 by complex inspection of 300 pregnant women from which 250 were after ART and 50 – firstlabours which pragnency without ART, and also their newborns. For the decision of an object in view of research spent to two stages. At 1 stage spent prosperctive research which included 150 pregnant women: з them 100 women pregnancy at which has come out ART (1 group) and 50 healthy women (control group). At 2 stage spent prospective randomization in which result of patients after ART have divided on two equal groups by therapy principle: 2 basic group - 75 pregnant women after ART at which used the algorithm improved by us; 3 group of comparison - 75 pregnant women after ART which have been spent on the standard treatment-and-prophylactic actions. Results. The results suggest that women after using ART is a high frequency of reproductive losses in the first trimester (10.0%), 3.0% of spontaneous abortion from 16 to 22 weeks, and 3.0% "early" premature delivery (22 to 28 weeks of pregnancy). The frequency of violations of the functional state of placenta in women after using IVF is 63.0%, which is the main cause of high levels of perinatal losses (40.0 ‰), and delivery by cesarean section (96.0%). Placental dysfunction in women after using ART characterized by retrohorialnyh hematoma (21.0%); size mismatch fruit (30.0%) and hypertonicity of the uterus (73.0%) against changes in fruit-placental blood flow - increased resistance index in umbilical artery and increased vascular resistance in the uterine arteries. Endocrinological and biochemical changes in placental dysfunction in women after using IVF starting from 28 weeks of pregnancy and are in significant reduction in progesterone, placental b1-microglobulin, B2-microglobulin of fertility and trophic в-glycoprotein. Conclusion. The received results: use of the algorithm of diagnostic and treatment-and-prophylactic actions improved by us allows to lower frequency of spontaneous interruption of pregnancy till 22 weeks – from 13.0% to 5.7%; «early» premature birth – from 3.0% to 1.0%; placentary dysfunction from 63.0% to 40.6%; cesarean sections – from 96.0% to 56.5%, and also perinatal losses – from 40.0‰ to 16.2‰. Key words: pregnancy, childbirth, auxiliary reproductive technologies.


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