جستجوی مقالات مرتبط با کلیدواژه « Thrombophilia » در نشریات گروه « پزشکی »

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19) which is associated with nonspecific respiratory syndromes, varying from mild symptoms of upper airway to required mechanical ventilation hypoxemia. A unique feature of this disease is COVID-19-associated coagulopathy (CAC) that linked with disease severity and hospital mortality. These patients have a profound hypercoagulable state and in patients with severe type arterial and venous thrombotic events are frequent. Abnormal coagulation parameters such as activated partial thromboplastin time (aPTT) were observed in patients with COVID-19. Regarding the above finding it could be considered as a reason to avoid anticoagulation at the both doses of therapeutic and prophylactic. A prolonged aPTT may indicate a coagulation factor deficiency or inhibitor of coagulation, which can be specific (antibody to factor VIII) or nonspecific (lupus anticoagulant, LA). LA can affect laboratory tests of blood coagulation, but is not usually associated with bleeding; however, it can be associated with thrombotic risk as a part of the antiphospholipid syndrome. In a phospholipid concentration-dependent manner LA recognizes a type of antiphospholipid antibodies (aPLs) that prolong clotting tests. In patients with antiphospholipid syndrome (APS) LA is considered as one of the laboratory criteria representing a significant risk factor of both thrombosis and pregnancy morbidity. Similarities between some of the pathophysiological features of COVID-19 and APS has been focused in several reports particularly in the most severe form, catastrophic APS. This study aimed to evaluate the effect of LA on the incidence of thrombophilia in patients with COVID-19, as well as its impact on the inflammation and finally the mortality final rate.

Protein S (PS) is a vitamin K-dependent glycoprotein synthesized by endothelial and somatic cells that acts as an anticoagulant in its free form and an inhibitor of the complement system in its bound form. Deficiency of PS is a congenital thrombophilia that can have significant clinical consequences. This study aimed to report the clinical and genetic characterization of four Iranian patients with PS deficiency.

In this study, we investigated the genetic basis of PS deficiency in four Iranian patients from three unrelated families, including two females and two males with a mean age of 32.5(± 25.73) years. Whole blood was collected to measure PS total antigen levels and isolated genomic DNA, which was then amplified using polymerase chain reaction to direct sequencing of the PROS1 gene with the Sanger method. Each novel variation was subjected to in silico analysis.

Two novel variants in the PROS1 gene were identified: c.-196 C > G in exon 1 and c.198A > C in exon 2. In this setting, both variants were present in a heterozygous state in patient C1 and a homozygous state in patient C2. In addition, a silico analysis was conducted to assess the impact of the identified variants, showing that the c.198A > C variant was likely detrimental and the c.198A > C variant was likely pathogenic.

The results highlight the heterogeneity of PS deficiency and the need for further investigation to identify additional mutations and understand the genetic basis of this condition in the Iranian population.

Kawasaki disease is an acute self-limiting systemic vasculitis in childhood, resulting in arterial swelling or inflammation and eventually leading to cardiovascular problems, such as coronary artery aneurysms. Based on previous studies, serum sodium ≤133 mmol/L, albumin ≤3.2 g/dL, alanine transaminase ≥80 U/L, and neutrophil percentage ≥80% at diagnosis are risk factors for intravenous immunoglobulin (IVIg). However, the prevalence of resistance to Ig among children with Kawasaki disease varies among different countries due to diversity in evaluation, treatment, and diagnosis. Approximately, 10% to 20% of patients have IVIg-resistant Kawasaki disease. As the probability of coronary artery damage associated with IVIg-resistant Kawasaki disease is higher than that with IVIg-sensitive Kawasaki disease, the early detection and appropriate treatment of IVIg-resistant Kawasaki disease can decrease the probability of damage to coronary arteries and hospital lengths of stay and cost. Kawasaki disease in early infancy is uncommon, and sometimes it occurs with thrombosis and peripheral gangrene. A positive genetic background may play a role in susceptibility to thrombosis. We herein describe a patient suffering from an IVIg-resistant Kawasaki disease with severe coronary artery thrombosis and positive genetic mutation. Medical treatment resolved the thrombosis, but the coronary arteries remained dilated.

The role of anticoagulant medications in preventing placental mediated pregnancy complications in patients with and without thrombophilia has not been investigated well. One underlying cause is associated with adverse effects of anticoagulants in pregnancy including teratogenicity, complexities in dosing and management of anticoagulants during pregnancy and labor. We aimed to assess effects of prophylactic anticoagulant medications in pregnant women with history of the PMPCs who were tested for hereditary thrombophilia.

This retrospective cohort study was done in obstetric clinics of Tehran University of Medical Sciences on medical records of 148 pregnant women with history of poor obstetric outcome due to placental complications. Pregnant women with both positive and negative thrombophilia test results were included in the study. They were divided into two group according to receiving anticoagulants. 

148 patients were analyzed over 1.5 years. Among them, 85 women received anticoagulant medications and 63 did not receive these treatments for the next pregnancy. Moreover, 58 out of 148 pregnant women were thrombophilic according to positive tests. Successful pregnancy outcomes were significantly higher in treated groups. The risk of abortion and unsuccessful pregnancy was significantly reduced in the treated groups. The occurrence of intrauterine fetal death (IUFD), intrauterine growth retardation (IUGR), and preeclampsia were not reduced. The use of anticoagulant during pregnancy did not have any adverse effects. The results in thrombophilia group and non-thrombophilia group demonstrated the benefit of anticoagulant therapy in improvement of pregnancy outcomes.

Testing for inherited thrombophilia in women who have experienced placental mediated pregnancy complications is not recommended. Anticoagulant therapy can be useful in women without thrombophilia and with poor obstetric history because of placental mediated pregnancy complications.

Vascular access thrombosis increases the risk of mortality and morbidity in end-stage renal disease (ESRD) patients on hemodialysis (HD). This study aimed to evaluate hereditary thrombophilia factors in HD patients and its association with tunneled cuffed catheters’ thrombosis.

In this cross-sectional study, 60 consecutive patients with ESRD on HD with tunneled cuffed catheters were selected. Inherited thrombophilia factors (Anti-thrombin III, Protein C, Protein S, and Factor V Leiden) were measured and the patients were followed for 3 months to evaluate the incidence of catheter-related thrombosis. The association between these factors and catheter thrombosis was assessed.

The mean age of patients was 60.30 ± 8.69 years. Forty-seven patients (78.30%) were female and thirteen patients (21.70%) were male. The most common cause of ESRD was diabetes mellitus (41.67%). The most catheter site was the right internal jugular vein (55%). There were 22 (36.67%) and 8 (13.33%) cases of thrombosis and mortality, respectively. The association between hereditary thrombophilia factors and catheter thrombosis was not statistically significant (P > 0.05).

In this small group of our patients, the frequency of hereditary thrombophilia was not significantly different between those with and without thrombosis of tunneled HD catheter.

To date, several factors have been reported in recurrent miscarriage. Genetic mutations are the most important causative factors in women. Fetal thrombotic vasculopathy is a new described placental alteration with varying degrees of involvement and often associated with adverse prenatal outcomes. The diagnosis is made histologically and so is postnatal, which makes it a challenge in clinical practice. The aim of the present study is investigation of the common mutations in women with recurrent miscarriage. A cross-sectional study was conducted on 100 women with a history of recurrent miscarriage fetus in 2018. In these patients, several genes such as MTHFR, F2, F5 Leiden, PAI1, F13 and FGB were analyzed by sequencing techniques. The most common mutations in these genes were sequenced and analyzed. According to statistical results obtained, MTHFR gene (C677T, A1298C) has the highest rate (50 %) of common mutations (p=0.001). After that F2 (G20210A) and F5 Leiden (G1691A) have the highest statistical values (each one 20%). In addition to these genes, there are other unknown mutations which have not been studied in terms of pathogenicity. Other genes have a smaller percentage of aborted fetus infrequently. Common polymorphisms in the thrombophilic system are likely to result in abortion in these subjects, due to impaired coagulation of the mother and the fetus. Investigating the presence of common mutations and examining their association with other mutations in the thrombophilia as a prognostic in patients with recurrent miscarriage is necessary.

The role of acquired thrombophilia has been accepted as an etiology of recurrent miscarriage (RM); however, the contribution of specific inherited thrombophilic genes to this disorder has remained controversial. An increased incidence of RM has been suggested in women with inherited thrombophilia.  In this prospective study, assisted women with RM or repeated implant failure (RIF) were subjected to Thromboincode analysis, in order to identify 12 genetic variants for Factor V Leiden, Factor V Hong Kong, Factor V Cambridge, FII, FXIII, FXII, and A1 carriers. Patients included in this study were separated in RM cases (n=43), RIF cases (n=36) and RIF+RM (n=76). As a control group, patients undergoing IVF treatment (n=34) were used and a previously described 249 cases population as a representative sample of Spanish population were selected. Level of statistical significance was p<0.05 and groups were compared by Fisher test, except for age that was compared by t-test. Regarding FXIII, higher values were observed in RM (69.76%), RIF (70%) and in RM+RIF (68.42%) group when compared with our control group (52.94%) and general Spanish population (56.5%), but these differences were statistically significant only in RIF group (p=0.043, p=0.01). Concerning our findings, both RM and RIF patients had a very similar panel of thrombophilia polymorphisms, suggesting that, in both, thrombophilia might have an important contribution. High frequency of Val34Leu polymorphism in RM/RIF presumably speaks in favor of a multifactorial RM genesis, wherean altered thrombophilia status plays a role.

Pregnancy represents a physiologic hypercoagulable state. The presence of inherited thrombophilias (factor V Leiden, prothrombin G20210A mutation, deficiencies of protein C, protein S and antithrombin) or acquired thrombophilias (antiphospholipid syndrome) increases the risk for venous thromboembolism, which represents one of the most common causes of direct maternal death. The clinical diagnosis of thrombosis can be difficult because of the overlap of symptoms with pregnancy-related manifestations. Antiphospholipid syndrome is correlated with early and late pregnancy complications whereas the association between the inherited thrombophilias and adverse pregnancy outcomes is still controversial. The psychological impact of thrombophilia in pregnancy should be also taken into consideration to prevent the negative effects of anxiety and stress on mother’s health and on birth outcomes. Thrombophilia testing in pregnancy is recommended only in cases in which the result is likely to influence the therapeutic decision. Low-molecular-weight heparins are the preferred anticoagulant for prophylaxis and therapy of thromboembolic events in pregnancy, presenting a low incidence of side effects. Future research is required to establish the optimal therapeutic strategy in pregnant women with thrombophilia, based upon a better stratification, in order to prevent thromboembolism and to improve pregnancy outcomes.

The purpose of this study was to detect the protective effects of adiponectin on coagulation dysfunction and its mechanism in sepsis of rats.
The experimental samples were composed of sham group, model group that was underwent cecal ligation and puncture (CLP) and three adiponectin treatment groups that treated by adiponectin with different dose (72 μg/kg, 96 μg/kg and 120 μg/kg) after CLP. The prothrombin time (PT), activated partial thromboplastin time (APTT) was measured, respectively, the level of malondialdehyde (MDA), tissue factor (TF), activated coagulation factor VIIa and Xa, p-selectin were detected, the histology structure of vascular was observed, the expressions of Caspase 9, Caspase 3, Bax, Bcl-2 and vWF in vascular were measured.
The results demonstrated that adiponectin treatment lengthened PT and APTT, reduced the expression of MDA, TF, activated coagulation factor VIIa, Xa and p-selectin in plasma of septic rats. Additionally, adiponectin treatment alleviated endothelial cell apoptosis and oxidative stress, down-regulated the levels of Caspase 3, Caspase 9, Bax, Bcl-2 and vWF in vascular.
These findings suggest that adiponectin treatment might be a promising therapeutic strategy for relieving septic endothelial cell injury and coagulation dysfunction via inhibiting endothelial cell apoptosis in septic rats.

Maternal thrombophilia has been identifed as a risk factor for recurrent pregnancy loss (RPL). The aim of this study was to investigate the association between prothrombin G20210A and factor V Leiden (FVL) polymorphisms in women with RPL and a control group of parous women in Isfahan province of Iran.
We studied 250 women with idiopathic RPL and 116 control cases. Prothrombin and FVL different genotypes were determined using polymerase chain reaction and reverse hybridization technique.
The frequencies of heterozygous mutation prothrombin G20210A were 6% and 0.9%, respectively (P = 0.025), in cases compared to the control group. The frequencies of homozygous mutation prothrombin G20210A were 0.4% and 0%, respectively, in cases compared to controls (P = 0.02). The prothrombin mutation was signifcantly higher in cases compared to the control group (odds ratio 8.81; 95% confdence interval: 1.16–66.62). There was no signifcant difference between the FVL mutation and pregnancy loss.
The results indicated a signifcant higher frequency of prothrombin G20210A in women with RPL in comparison with controls. Our data suggest that the prothrombin G20210A mutation, but not the FVL mutation, may be an unrecognized cause of RPL in our population.

Recurrent pregnancy loss (RPL) is a common problem among couples, and acquired thrombophilia is the well-known etiology of RPL. The aim of this study was to establish the association between inherited thrombophilic gene polymorphisms and RPL.
This case-control study was conducted on 50 women with unexplained RPL and 50 parous women with no history of miscarriage (age range: 17–48 years). The data were collected during 2013–2015 in Sarem Hospital, Tehran, Iran. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for glycoprotein IIIa (PLA1/PLA2), KDR (Q472H), and β-fibrinogen (-455G/A); tetra-primer amplification refractory mutation system (ARMS)-PCR for glycoprotein Ia (807c/t) and vascular endothelial growth factor (VEGF) (2578c/a), and ins/del PCR for angiotensin I-converting enzyme (ACE) (intron 16 I/D). The association between the frequency of the genotypes and RPL was determined by Chi-square and Fisher’s exact tests.
The results of the present study revealed a significant relationship between glycoprotein Ia (807C/T), VEGF (2578C/A), and ACE (intron 16 I/D) polymorphisms and RPL (P=0.00, 0.02, and 0.00, respectively). In contrast, no relationship was observed between β-fibrinogen (-455G/A), KDR (Q472H), and glycoprotein IIIa (PLA1/PLA2) polymorphisms and increased risk of RPL (P>0.05).
This study demonstrated that glycoprotein Ia (807C/T), VEGF (2578C/A), and ACE (intron 16 I/D) polymorphisms may be a risk factor for the women with a history of RPL.

Prepartum or postpartum right ventricular thrombosis (RVT) is an exceedingly rare and potentially lethal phenomenon in pregnancy. We here report a case of a pregnant patient with near term pregnancy admitted for dyspnea, amniotic fluids discharge and labor pain in a gynecology center that an eight-month dead fetus was diagnosed and delivered vaginally by induction. A post delivery period was complicated by aggravation of her dyspnea and pleuritic chest pain that she referred for further evaluation in our cardiac center. Physical exam revealed normal head and neck exam, and history taking revealed that her fetus had intra-uterine growth failure as reported by her gynecologist. Chest exam except to left lung crackle was normal. Lower and upper left extremities were normal. However, acrocyanosis was found in tips of 4 and 5th right-hand digits. Chest x-ray revealed some linear consolidation in left lower lung lobes, and the precordial exam was normal. ECG was normal. Post delivery transthoracic echocardiography (TEE) showed a 1.5×1.5 cm mobile right ventricular clot. C-T angiography revealed obstruction of left upper lung pulmonary artery branches. Complete thrombophilia assay showed the presence of high titer of antiphospholipid, anticardiolipin antibody, and β1 glycoprotein antibody. However, others test were normal. The patient was scheduled for cardiac surgery, and her hemodynamic was monitored by left radial artery line and central pressure venous line, and thrombus was removed from the right ventricle (RV), and subsequent anticoagulation therapy constituted. Six-month follow-up revealed no recurrence of thrombus and recovery of patient’s symptoms.

Budd-Chiari syndrome (BCS) is an obstruction of hepatic venous flow at any level, from small hepatic veins to the junction of the inferior cava vein and the right atrium. Studies report that BCS is associated with prothrombosis. The authors present a review of the topic based on a case report of BCS where several risk factors are involved. These factors were genetic, such as mutation of the plasminogen activator inhibitor with 4G polymorphism and acquired, such as ulcerative colitis and oral contraceptives.

Warfarin-induced skin necrosis (WISN) is a rare complication of anticoagulant therapy associated with a high incidence of morbidity and mortality requiring immediate drug cessation. At particular risk are those with various thrombophilic abnormalities, especially when warfarinisation is undertaken rapidly with large loading doses of warfarin. Cutaneous findings include petechiae that progress to ecchymosis and hemorrhagic bullae. With the increasing number of patients anticoagulated as out-patients for thromboprophylaxis, we are concerned that the incidence of skin necrosis may increase. We present a case of WISN with low protein C level. He was a 50-year-old male who came to our department because of acute infarction in irrigation area of the superior cerebellar artery. He had intermittent atrial fibrillation and was started on anticoagulant therapy. After few day of therapy, he developed skin necrosis, and his level of protein C was low. Warfarin-induced skin necrosis is a rare but serious complication that can be prevented by routine screening for protein C, protein S or antithrombin deficiencies or for the presence of antiphospholipid antibodies before beginning warfarin therapy.

Recurrent pregnancy loss (RPL) defined by two or more failed pregnancies before 20 weeks of gestation. Several factors play a role in RPL including thrombophilic conditions which can be influenced by gene polymorphisms. Plasminogen activator inhibitor-1 (PAI-1) and angiotensin converting enzyme (ACE) genes are closely related to fibrinolytic process, embryonic development and pregnancy success.

The aim of this study was to investigate the relationship between RPL and common polymorphisms in ACE and PAI-1 genes.

In this case control study, 100 women with recurrent abortions (at least two) were selected as cases and 100 healthy women with two or more normal term deliveries without a history of abortion as controls. Total genomic DNA was isolated from blood leukocytes. The status of the PAI-1 4G/5G and ACE (D/I) polymorphism was determined by PCR-RFLP.

Homozygosity for PAI-1 4G polymorphism was seen in 17 cases (17%), and 5 controls (5%) (p=0.006) so patients with homozygote 4G mutation were significantly more prone to RPL in contrast to control group (OR: 4.63, % 95 CI: 1.55-13.84). In addition, 7 patients (7 %), and no one from the control group, were homozygote (I/I) for ACE polymorphism (p=0.034), suggesting no significant associations between ACE D allele or DD genotype and RPL.

Considering these results, because 4G/4G polymorphism for PAI-1 gene could be a thrombophilic variant leading to abortion, analysis of this mutation and other susceptibility factors are recommended in patients with RPL.

Methylenetetrahydrofolate reductase (MTHFR) single-nucleotide polymorphisms (SNPs) C677T and A1298C have been described as strong risk factors for idiopathic recurrent miscarriage (RM). However, very few studies have investigated the association of paternal MTHFR SNPs with RM. The aim of the present study was to evaluate the prevalence of paternal C677T and A1298C SNPs among Iranian RM couples. The study subjects comprised 225 couples with more than three consecutive pregnancy losses, and 100 control couples with no history of pregnancy complications. All females in the case group had MTHFR polymorphisms; and genotype SNPs were analyzed by PCR-RFLP. Groups were statistically compared using Mann Whitney U-test and Chi-square statistical tests. The p<0.05 were considered significant. Statistically significant difference was detected in the frequency of MTHFR SNPs in male partners of the two groups (p=0.019). Combined heterozygosity of MTHFR polymorphisms was a common phenomenon in the males; 52 (23.1%) and 14 14%) of males in RM and control groups, respectively. Absence of combined homozygosity for both SNPs in all studied groups/genders was observed. The MTHFR gene composition of male partners of RM couples may contribute to increased risk of miscarriage.

The aim of this study was to investigate the possible role of multiple inherited thrombophilic gene variations in women with unexplained spontaneous abortions. For this purpose, the Factor V Leiden (FVL) (rs6025), Prothrombin G20210A (rs1799963), MTHFR C677T (rs1801133), PAI-1 4G/5G (rs1799889), ACE I/D (rs1799752), eNOS E298D (rs1799983), and Apo E E2/E3/E4 (rs429358) polymorphisms were genotyped and correlated in spontaneously aborted fetal materials, their mothers and fertile women. Twenty three abortion materials, 22 women with ≥1 unexplained fetal loss, and 22 control subjects with at least two healthy term infants as a control group were studied. Target SNPs for each gene were analyzed by real time-PCR technique after genomic DNA isolation from maternal blood-EDTA, control group blood-EDTA and spontaneously aborted fetal tissues. Some cases had a single thrombophilic polymorphism, but the rest of the patients and fetal materials had combined thrombophilic polymorphisms. The PAI-1 4G/5G+4G/4G (P= 0.0017), 4G/4G (P= 0.0253), eNOS 894GT+894TT (P=0.0011) genotypes and T allele (P=0.0185), Apo E E3/E4+E3/E2+E2/E4 (P<0.0001) genotypes, E2 (P<0.0001) and E4 (P<0.0001) alleles were higher in spontaneously aborted fetal materials when compared to their mothers and control group. The Factor V Leiden rs6025, Prothrombin G20210A, MTHFR C677T, ACE I/D genotypes were different for each group but not statistically significant due to relatively small size of the samples (P>0.05). Our results indicated that combined thrombophilic gene variations may be associated with increased risk for spontaneous abortions and results need to be confirmed by larger sample size.