Analysis of Phenotype and Genotype of A Family with Hereditary Coagulation Factor Ⅴ Deficiency Caused by A Compound Heterozygous Mutation / 中国实验血液学杂志

OBJECTIVE@#To analyze the molecular pathogenesis by analysis of phenotype and gene mutation in families with hereditary coagulation factor V (FⅤ) defect caused by complex heterozygous mutation.@*METHODS@#Plasma pro-thrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), FⅤ procoagulant activity (FⅤ∶C), FⅤ antigen (FⅤ∶Ag), and other related coagulation indexes were detected in the proband and his family members (3 generations 10 people). Using DNA direct sequencing to analyze all exons, flanks, 5' and 3' untranslated regions of F5 genes and the corresponding mutation site regions of family members, the mutation site was confirmed by reverse sequencing．The conservation of mutant amino acids was analyzed by ClustalX-2.1-win software. The PROVEAN and MutationTaster online bioinformatics software were used to predict the effect of mutation on protein function. Protein model and amino acid interaction at mutation sites was analyzed by Swiss-pdbviewer software.@*RESULTS@#The PT and APTT of the proband were significantly prolonged compared with healthy controls (34.2 vs 13.2 s and 119.3 vs 36.0 s), while FⅤ∶C and FⅤ∶Ag extremely reduced (3% and 6%). The PT and APTT of the second-born, the third son, daughter, and grandson of the proband were slightly prolonged, and the FⅤ∶C and FⅤ∶Ag decreased to varying degrees. The related coagulant parameters of other family members were within normal range. Genetic analysis revealed that the proband had a c.911G>A heterozygous missense mutation on the exon 6 lead to p.Gly276Glu, and a c.5343C>G heterozygous missense mutation on the exon 16 lead to p.Ser1781Arg of the proband. The second-born, the third son, and grandson of the proband carry p.Gly276Glu heterozygotes, and the daughter carries p.Ser1781Arg heterozygotes, while the other family members were wild-type. The results of conservative analysis indicated that p.Gly276 and p.Ser1781 were highly conserved in homologous species. The two bioinformatics software predicted the same results, PROVEAN (score -6.214 and -12.79) indicated that the compound heterozygous mutation was a harmful mutation; MutationTaster (score 0.976 and 0.999) suggested that these mutations might cause corresponding disease. p.Gly276Glu protein model analysis showed that, the Glu side chain was prolonged and the molecular weight became larger, which would increase the steric hindrance between it and the surrounding amino acids, affect the normal local folding of the FⅤ protein, and eventually lead to the decrease of protein activity and content. This paper can not provide analysis of the spatial structure of p.Ser1781Arg mutant protein because of the lack of X ray 3 D structure file of FⅤ exon 16.@*CONCLUSION@#The new compound heterozygous mutations (p.Gly276Glu and p.Ser1781Arg) identified in this study are the main reasons for the decrease in the FⅤ level of the family, among which p.Ser1781Arg is rarely reported at home and abroad.

H1299R in coagulation Factor V and Glu429Ala in MTHFR genes in recurrent pregnancy loss in Sari, Mazandaran

Background: Recurrent pregnancy loss [RPL] is caused by different factors, including genetics and thrombophilia. Beside Factor V Leiden, another nucleotide change in a factor V [FV] gene [A4070G; His1299Arg] has been identified linking to hereditary thrombophilia. Also, two proposed MTHFR polymorphisms, C677T and A1298C [Glu429A] are linked with RPL

Objective: In this study, the effect of two factors, A4070G in FV and A1298C in MTHFR are evaluated in RPL patients from Mazandaran province, Iran

Materials and Methods: Sample population of 100 women with RPL and 100 controls with Mazandarani ethnics from northern Iran were consist. The factor V [A4070G] and MTHFR [A1298C] polymorphisms were genotyped by PCR-RFLP

Results: Molecular study showed 5 women from patients and 9 women from control group were heterozygous AG for A4070G. Frequency of "A" allele in patient and control groups was 97.5% [0.975] and 95.5% [0.955] respectively, and "G" allele frequency was 2.5% [0.025] and 4.5% [0.045] respectively. No significant association [p

Conclusion: Our finding showed that A4070G and A1298C polymorphisms cannot be considered as a cause of PRL in women from Mazandaran province, northern Iran

Genetic Confirmation of Congenital Factor V Deficiency in Korean Patients

No abstract available.

Potential Risk Factors Associated With Vascular Diseases in Patients Receiving Treatment for Hypertension

BACKGROUND: Currently, the hypertension (HTN) patients undergo appropriate medical treatment, and traditional risk factors are highly controlled. Therefore, potential risk factors of atherosclerotic vascular diseases (AVD) and venous thromboembolisms (VTE) in HTN should be reconsidered. We investigated thrombophilic genetic mutations and existing biomarkers for AVD or VTE in HTN patients receiving treatment. METHODS: A total of 183 patients were enrolled: AVD with HTN (group A, n=45), VTE with HTN (group B, n=62), and HTN patients without any vascular diseases (group C, n=76). The lipid profile, homocysteine (Hcy) levels, D-dimers, fibrinogen, antithrombin, lupus anticoagulant, and anti-cardiolipin antibody (aCL) were evaluated. Prothrombin G20210A, Factor V G1691A, and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C were analyzed. RESULTS: All patients revealed wild type prothrombin G20210A and Factor V G1691A polymorphisms. The frequency of MTHFR polymorphisms was 677CT (n=84, 45.9%); 677TT (n=46, 25.1%); 1298AC (n=46, 25.1%); and 1298CC (n=2, 1.1%). The MTHFR 677TT genotype tended to increase the odds ratio (OR) to AVD events in HTN patients (OR 2.648, confidence interval 0.982-7.143, P=0.05). The group A demonstrated significantly higher Hcy levels (P=0.009), fibrinogen (P=0.004), and platelet counts (P=0.04) than group C. Group B had significantly higher levels of D-dimers (P=0.0001), platelet count (P=0.0002), and aCL (P=0.02) frequency than group C. CONCLUSIONS: The MTHFR 677TT genotype and Hcy level could be potential risk factors associated with development of AVD in HTN patients receiving treatment. D-dimer and aCL might be useful to estimate the occurrence of VTE in them.

Dilataciones endoscópicas del tracto gastrointestinal / Endoscopic dilation of the gastrointestinal tract

Las dilataciones en el tracto gastrointestinal se llevan a cabo para aliviar la obstrucción sintomática, ya sea funcional u orgánica, secundarias a una variedad de patologías tanto benignas como malignas. Con el advenimiento de las nuevas tecnologías, virtualmente toda estenosis digestiva puede ser manejada en forma mínimamente invasiva. Pese a su amplia difusión en la práctica actual, existen pocos estudios controlados que comparen las diferentes modalidades de dilatación. En el presente artículo realizamos una revisión de esta técnica, así como de la evidencia disponible para su aplicación en los diferentes segmentos del tracto gastrointestinal. El futuro de la dilatación incluye el desarrollo de dilatadores que permitan evaluar la dilatación durante su realización. Estos advenimientos, así como la ejecución de estudios controlados prospectivos van a mejorar las indicaciones, beneficios y riesgos para cada uno de los sistemas de dilatación existentes.

The endoscopic dilation of the gastrointestinal tract is carried out to relieve either functional or organic disorders, secondary to a variety of both benign and malignant diseases. With the advent of new technologies, virtually all digestive stenosis can be managed in a minimally invasive way. Despite its wide dissemination in actual practice, there are few controlled studies comparing the different forms of endoscopic dilation. In this article, we review this technique and the evidence available for application in different segments of the gastrointestinal tract. The future of the dilations includes the development of dilators to assess dilation during the procedure. These advents and the implementation of prospective controlled studies will improve the indications, benefits and risks for each of the existing systems of dilations.

Genotipos frecuentemente asociados a trombofilias / Frequently associated genotypes to thrombophilia

La enfermedad tromboembólica venosa es una entidad patológica importante debido a la morbilidad que causa, por sus complicaciones y por su alta incidencia en el mundo, la cual puede variar desde 1:100 en adultos mayores hasta 1:100.000 en niños. Existen múltiples factores de riesgo tanto genéticos como ambientales asociados a la enfermedad; los más ampliamente estudiados por su incidencia en la población mundial son el factor V de Leiden, la mutación G20210A en el factor II (protrombina) y las mutaciones en la metilen-tetrahidrofolato reductasa C677T y A1298C, que hasta hace poco se consideraban factores de riesgo. En la presente revisión se presenta de forma concisa qué es y cómo se produce un trombo a partir de la enfermedad tromboembólica, cuáles son las principales entidades nosológicas que involucra la enfermedad y los genotipos más frecuentemente asociados a la misma. Se enfatiza en las alteraciones genéticas epidemiológicamente más importantes y se muestran brevemente los estudios realizados en Colombia.

Venous thromboembolism is an important pathological entity that causes high morbidity due either to the disease or its complications. The incidence in the world ranges between 1:100 in adults and 1:100,000 in children. Risk factors for the disease include genetic as well as environmental factors. Among them, factor V Leiden (G1691A), prothrombin (G20210A) and MTHFR C677T and A1298C (which until recently were considered risk factors), have been widely studied given their impact in the world. This review presents in a clear and concise way what a thrombous is and how it is formed; how a clot is able to produce thromboembolic disease; what are the main nosological entities involved, and their main genetic causes. The most epidemiologically important genetic alterations and studies conducted in Colombia will be emphasized.

Evaluation the frequency of factor V leiden mutation in pregnant women with preeclampsia syndrome in an Iranian population

Role of genetic factors in etiology of preeclampsia is not confirmed yet. Gene defect frequency varies in different geographic areas as well as ethnic groups. In this study, the role of factor V Leiden mutation in the pathogenesis of preeclamsia syndrome among the pregnant population of northern shore of Persian Gulf in Iran, were considered. Between Jan. 2008 and Dec. 2009, in a nested case control study, pregnant women with preeclamsia [N=198] as cases and healthy [N=201] as controls were enrolled in the study. DNA were extracted from 10 CC peripheral blood and analyzed for presence of factor V Leiden mutation in these subjects. The maternal and neonatal outcomes of pregnancy according to the distribution of factor V Leiden were also compared among cases. In total, 17[8.6%] of cases and 2 [1%] of controls showed the factor V Leiden mutation. The incidence of factor V Leiden was typically higher in preeclamsia women than control group [OR: 9.34%95 CI: 21.12-41.01]. There was no difference in incidence rate of preterm delivery <37 weeks [OR: 1.23%95 CI: 0.38-4.02], very early preterm delivery <32 weeks [OR: 1.00%95 CI: 0.12-8.46], intra uterine fetal growth restriction [IUGR] [OR: 1.32%95 CI: 0.15-1130], and the rate of cesarean section [OR: 0.88%95 CI: 0.29-2.62] among cases based on the prevalence of factor V Leiden mutation. The pregnant women with factor V Leiden mutation are prone for preeclampsia syndrome during pregnancy, but this risk factor was not correlated to pregnancy complications in the studied women

Genetic polymorphisms and cerebrovascular disease in children with sickle cell anemia from Rio de Janeiro, Brazil / Polimorfismos genéticos e doença cerebrovascular em crianças com anemia falciforme do Rio do Janeiro, Brasil

The aim of the present work was to examine possible genetic risk factors related to the occurrence of cerebrovascular disease (CVD) in Brazilian population, the frequency of βS-globin gene haplotypes and co-inheritance with α-thalassemia (-α3.7kb) and single nucleotide polymorphism of methylenetetrahydrofolate reductase (MTHFR-C677T), Factor V Leiden (FV-G1691A) and prothrombin (PT-G20210A) genes in children from Rio de Janeiro. Ninety four children with sickle cell anemia (SCA) were included, 24 patients with cerebrovascular involvement and 70 patients without CVD as control group. The mean age of children at the time of the cerebrovascular event was similar to the control group. The frequency of -α3.7kb thalassemia was similar in both groups (p=0.751). Children with Bantu/Atypical βS-globin gene haplotype presented 15 times more chance (OR=15.4 CI 95 percent 2.9-81.6) of CVD than the other βS-globin gene haplotypes. The C677T polymorphism of MTHFR gene was similar in both groups (p=0.085). No mutation in the FV Leiden or PT genes was found. A large study seems necessary to establish the role of these genetic polymorphisms in Brazilian miscegenated population.

Avaliar o papel da talassemia alfa (-α3.7kb), dos haplótipos da globina βS, e mutações nos genes da metileno-tetrahidrofolato redutase (MTHFR-C677T), fator V de Leiden (FV-G1691A) e protrombina (PT-G20210A) como fatores de risco para a doença cerebrovascular em pacientes com anemia falciforme. Foi realizado um estudo de caso controle com 94 crianças portadoras de anemia falciforme, 24 com doença cerebrovascular (DCV) e 70 sem DCV como grupo controle. A frequência de talassemia -α3.7kb foi semelhante em ambos os grupos (p=0,751). Crianças portadoras do haplótipo Bantu/Atípico da globina βS apresentam 15 vezes mais chances de desenvolverem DCV (OR=15,4 IC 95 por cento 2,9-81,6) do que os outros haplótipos. A frequência do polimorfismo MTHFR-C677T foi semelhante em ambos os grupos (p=0,085) e não foi observada mutação nos genes fator V e protrombina. Estudos com maior número de casos são necessários para esclarecer o papel desses polimorfismos genéticos na nossa população.

Hemi-central retinal artery occlusion in young adults.

Amongst the clinical presentations of retinal artery occlusion, hemi-central retinal artery occlusion (Hemi-CRAO) is rarely described. This case series of four adults aged between 22 and 36 years attempts to describe the clinical profile, etiology and management of Hemi-CRAO. Case 1 had an artificial mitral valve implant. Polycythemia and malignant hypertension were noted in Case 2. The third patient had Leiden mutation while the fourth patient had Eisenmenger’s syndrome. Clinical examination and fundus fluorescein angiography revealed a bifurcated central retinal artery at emergence from the optic nerve head, in all cases. Color Doppler examination of the central retinal artery confirmed branching of the artery behind the lamina cribrosa. It is hypothesized that bifurcation of central retinal artery behind the lamina cribrosa may predispose these hemi-trunks to develop an acute occlusion if associated with underlying risk factors. The prognosis depends upon arterial recanalisation and etiology of the thromboembolic event.

Asociación de la RPCA con mutaciones Leiden y Cambridge del factor V de la coagulación en pacientes mexicanos con trombofilia primaria / Association of resistance to activated protein with the presence of Leiden and Cambridge Factor V mutations in Mexican patients with primary thrombophilia

Introducción: Las mutaciones Leiden y Cambridge del factor V de la coagulación y la resistencia a la proteína C activada (RPCA) son alteraciones que se relacionan con trombosis venosa y arterial. En este trabajo se analizó si la RPCA está asociada con las mutaciones Leiden y Cambridge, y la frecuencia de éstas en población mestiza mexicana. Material y métodos: Se incluyeron 150 pacientes mexicanos con trombofilia primaria y 100 sujetos sanos. Se determinó la RPCA empleando método comercial y los genotipos factor V Leiden y factor V Cambridge mediante PCR-RFLPs. Resultados: La RPCA fue positiva en cuatro pacientes y en un individuo control; sin embargo, no se encontró la mutación Leiden o Cambridge en la población estudiada, por lo que la RPCA no se correlacionó con ninguna de las mutaciones investigadas. Conclusiones: Los resultados indican que existen otras causas primarias o secundarias diferentes a las analizadas, que condicionan la RPCA. Además, la frecuencia obtenida para la RPCA en nuestra población trombofílica mestiza mexicana fue menor comparada con la obtenida en población caucásica, quizá por tratarse de poblaciones genéticamente diferentes.

BACKGROUND: Leiden and Cambridge factor V coagulation mutations and activated protein C resistance (RaPC) are alterations related with vein and artery thrombosis. In this study we aimed to determine whether RaPC is associated with the presence of Leiden and Cambridge mutation and the frequency of these mutations in the racially mestizo Mexican population. METHODS: We included 150 Mexican patients with primary thrombophilia and 100 healthy subjects in this study. RaPC was determined using commercial methods and genotypes FV Leiden and FV Cambridge with PCR-RFLPs. RESULTS: RaPC was positive in four patients and in one control individual; however, there was no presence of Leiden or Cambridge mutation in the studied group; thus, RaPC was not correlated with the presence of any of the studied mutations. CONCLUSIONS: These results indicate that there are other primary or secondary causes different from those studied, which condition the presence of RaPC. Furthermore, the frequency obtained for RaPC in our thrombophilic population of racially mixed Mexicans is lower compared to that obtained in the Caucasian population, most probably because they are genetically different populations.

Resistência à proteína C ativada e doença arterial isquêmica em jovem / Resistance to activated protein C and ischemic arterial disease in a young man

A avaliação da resistência à ação da proteína C ativada (rPCA), causada por mutação no fator V (fator V de Leiden), é fator de risco importante para tromboembolia venosa, cujo papel como geradora de obstruções arteriais in situ é um tema ainda controverso. O caso clínico de um jovem com história de coronariopatia, múltiplas lesões cerebrovasculares e doença arterial periférica é relatado. A investigação diagnóstica apontou a rPCA como possível etiologia.

The assessment of activated protein C resistance (APCR) caused by mutations in factor V (factor V Leiden) is an important risk factor for venous thromboembolism, of which role as the originator of arterial obstructions in situ is still a controversial subject. The clinical case of a young patient with history of coronariopathy, multiple cerebrovascular lesions and peripheral artery disease is reported. The diagnostic investigation showed APCR as the possible etiology.

Factor V Leiden and prothrombin G20210A gene mutations in women with a history of thrombosis during pregnancy relation to pregnancy outcomes for mother and fetus

To investigate the presence of factor V Leiden [FVL], and prothrombin gene mutations [PRT], protein C and protein S in pregnant women with a previous history of thromboembolism, and evaluate their impact on maternal and fetal outcomes. This study was carried out at Ain Shams University Hospital, Cairo, Egypt between January 2006 to March 2008. The study included 15 pregnant females without a history of thromboembolism [control group], and 25 pregnant females with a history of previous thromboembolism during pregnancy, and puerperium [patient group]. Identification of FVL and PRT mutations by real-time quantitative polymerase chain reaction, and estimation of protein C and S activity by functional clotting assay were performed. Regarding the control group; one patient had FVL mutation [6.6%], and one had decreased protein C activity [6.6%]. As regard the patient group 13/25 [52%] bad normal genotype, and 12/25 [48%] expressed abnormal genotype either FVL or PRT G20210A, or both. Also 3/25 [12%] patients had decreased protein C activity, and 2/25 [8%] had decreased protein S. The intrauterine growth retardation [IUGR] less than the tenth percentile was more in the patients group [48%] compared to the control group [33%], while there was no statistically significant difference between both groups on preeclampsia, placental abruption, abortion, or IUGR less than the fifth percentile. The FVL was not associated with any adverse outcomes, while the PRT mutation was significantly associated with IUGR less than the fifth percentile. The results of this study shows that good monitoring of fetal growth is mandatory for all carriers of the PRT gene mutation

Mutação G20210A no gene da protrombina, fator V de Leiden e anticorpos anticardiolipina não influenciam a sobrevida do enxerto renal após o transplante / Prothrombin G20210A gene mutation, factor V Leiden and anticardiolipin antibodies do not influence renal graft survival after transplantation

Introdução: Complicações tromboembólicas são importantes fatores de risco para perda do enxerto e pior evolução após o transplante renal. pacientes com defeito trombofílico apresentam maior risco de complicações tromboembólicas. Foram analisados, entre receptores de transplante renal, a prevalência de defeito trombofílico e o risco atribuído a esta condição para a perda do enxerto e para o desenvolvimento de tromboses intravasculares. Métodos: estudo do tipo coorte incluindo 388 receptores adultos analisados quanto à presença de trombofilia de acordo com a pesquisa de anticorpos anticardiolipidina (aCL) por ELISA e das mutações G1691A no gene do fator V (FV) e G20210A no gene da protrombina (PT) por PCR multiplex. Resultados: Defeito trombofílico foi identificado em 25,8% dos pacientes. As taxas de sobrevida de 2 anos do enxerto foram semelhantes entre os pacientes com e sem defeito trombofílico (94%, p=0,53), bem como a sobrevida dos enxertos livres de tromboses intravasculares (97% versus 97%, p=0,83). pacientes com defeito trombofílico apresentaram prevalência de tromboses intravasculares semelhante à do grupo-controle (3% versus 3,5%, p=0,82). O transplante renal anterior foi associado a maior risco de perda de enxerto (OR 20,8, p<0,001) e de ocorrência de trombose intravasculares (OR 6,8, p=0,008). Conclusões: As prevalências das mutações FVG1691A e PTG20210A na população estudada foram semelhantes às da população geral não transplantada, e a prevalência de anticorpos aCL superou a observada entre os indivíduos sadios. Não houve associação entre os marcadores de trombofilia estudados e a sobrevida em médio prazo do transplante renal.

Introduction: Thromboembolic complications are important risk factors for graft loss and poor outcome after renal transplantation. patients with thrombophilic defects are at increased risk of thromboembolic complications. Were analyzed, among kidney transplant recipients, the prevalence of thrombophilic defects and the risk attributed to this condition for graft loss and the development of intravascular thrombosis. Methods: A cohort study including 388 adult recipients analyzed for the presence of thrombophilia according to anticardiolipidina antibodies (aCL) by ELISA and gene mutations G1691A in factor V (FV) and prothrombin gene G20210A (PT) by multiplex PCR. Results: thrombophilic defect was identified in 25.8% of patients. The survival rates of two years of the graft were similar between patients with and without thrombophilic defect (94%, p = 0.53), and the survival of free grafts of intravascular thrombosis (97% versus 97%, p = 0 , 83). patients with an increased prevalence of thrombophilic defect intravascular thrombosis similar to the control group (3% versus 3.5%, p = 0.82). Previous renal transplantation was associated with increased risk of graft loss (OR 20.8, p <0.001) and intravascular thrombosis (OR 6.8, p = 0.008). Conclusions: The prevalence of mutations and FVG1691A PTG20210A in this study were similar to those of the general population not transplanted, and the prevalence of aCL antibodies exceeded that observed among healthy individuals. There was no association between markers of thrombophilia studied and medium-term survival in renal transplantation.

Trombose venosa em criança / Venous thrombosis in children

A incidência de trombose venosa profunda (TVP) em crianças (0 a 18 anos) é baixa. O objetivo desse trabalho é estudar uma criança de 12 anos que, após um trauma, apresentou TVP. Atividades de proteína C, proteína S, antitrombina e resistência à proteína C ativada (RPCA) foram analisadas em coagulômetro. O fator V de Leiden (FVL) foi pesquisado. O paciente e seu pai (assintomático até o momento) foram heterozigotos para FVL e sua mãe foi homozigota normal. Concluímos que o FVL associado a outras condições clínicas tende a ser multiplicativo para a ocorrência de trombose, que é multifatorial.

The incidence of deep venous thrombosis (DVT) in children (0-18 years old) is low. The aim of this study was to investigate the case of a 12 year-old child that had DVT after a trauma. Protein C and protein S activities, antithrombin and resistance to activated protein C were analyzed in coagulometer. Factor V Leiden (FVL) was studied. The patient and his father were heterozygotes for FVL. His mother was normal homozygote. We concluded that the presence of FVL associated with other medical conditions tends to multiply the occurrence of thrombosis, which is a multifactorial disease.

Placental histomorphology in unexplained foetal loss with thrombophilia.

BACKGROUND & OBJECTIVES: Acquired and genetic thrombotic conditions, both organ and non organ specific, are associated with increased foetal wastage. This study was carried out to examine the placenta from women with abnormal pregnancies and a history of unexplained foetal loss, and to associate with maternal thrombophilia status. METHODS: Placentas from eight women with history of unexplained foetal loss were analyzed for histopathological characteristics. All the women were simultaneously screened for the common acquired and genetic thrombophilia markers i.e., lupus anticoagulants ( LA), IgG / IgM antibodies for anticardiolipin (ACA), beta2 glycoprotein 1 (beta2GPI) and annexin V, protein C (PC), protein S (PS), antithrombin III (AT III), factor V Leiden ( FVL) mutation, prothrombin (PT) gene G20210A, methylene tetrahydrofolate reductase (MTHFR) C 677T, endothelial protein C receptor (EPCR) 23 bp insertion and plasminogen activator inhibitor ( PAI-1 4G/5G) polymorphisms RESULTS: Six of eight women were positive for one or more thrombophilia markers. The placenta in all the cases except one, showed the characteristic features of infarct fibrin deposition and calcification. Among two women who were negative for thrombophilia, one showed clear evidence of thrombus in the placental sections while the other did not show any characteristic infarcts in the placental sections. INTERPRETATION & CONCLUSION: Our findings showed that the histopathological examination of the placentas confirmed thrombophilia as the aetiological cause of thrombosis in 6 of the 8 women. The presence of thrombus in a negative thrombophilia woman suggests yet unidentified thrombophilia markers or probably non-haemostatic factors causing thrombosis.

Venous thromboembolism: the intricacies.

Venous thromboembolism (VTE) has been a subject of great interest of late. Since Rudolph Virchow described the famous Virchow's triad in 1856, there have been rapid strides in the understanding of the pathogenesis and factors responsible for it. Discovery of various thrombophilic factors, both primary and acquired, in the last 40 years has revolutionized prognostication and management of this potentially life-threatening condition due to its associated complication of pulmonary thromboembolism. Detailed genetic mapping and linkage analyses have been underlining the fact that VTE is a multifactorial disorder and a complex one. There are many gene-gene and gene-environment interactions that alter and magnify the clinical picture in this disorder. Point in case is pregnancy, where the risk of VTE is 100-150 times increased in the presence of Factor V Leiden, prothrombin mutation (Prothrombin 20210A) and antithrombin deficiency. Risk of VTE associated with long-haul air flight has now been well recognized. Thrombotic events associated with antiphospholipid syndrome (APS) are 70% venous and 30% arterial. Deep venous thrombosis and pulmonary embolism are the most common venous events, though unusual cases of catastrophes due to central vein thrombosis like renal vein thrombosis and Budd-Chiari syndrome (catastrophic APS) may occur.

Hypercoagulable state in idiopathic ulcerative colitis: role of hyperhomocysteinemia and hyperfibrinogenemia.

BACKGROUND: Previous reports on hypercoagulable factors in inflammatory bowel diseases involve heterogeneous populations and patients on various medications. AIMS: To determine the frequency of thrombotic complications in ulcerative colitis (UC); to evaluate for hyperhomocysteinemia and its relationship to vitamin B12 and folate levels and methylene tetrahydrofolate reductase (MTHFR) mutation; and to evaluate for hyperfibrinogenemia and factor V Leiden mutation. METHODS: Eighty-six adult patients with UC were seen during the study period; 28 of them underwent blood tests and constituted the study population. Patients who received medications that affect these factors were among the 58 excluded. Tests were obtained at baseline and after 2 months during remission. Patients received folic acid in addition to treatment for UC. RESULTS: Vascular thrombotic events were noted in 4 patients during follow up. Hyperhomocysteinemia was detected in 11 (39.3%) patients (controls 15/100, p=0.007). Heterozygous state for MTHFR C677T mutation was found in 5 (17.9%) patients (controls: 0.2% homozygous, 13.6% heterozygous, p>0.05). Plasma homocysteine did not correlate with extent, severity or duration of disease, or with MTHFR C677T heterozygous state, but correlated with serum folic acid level (p=0.003) and BMI (p=0.03). With folate supplementation, homocysteine decreased significantly in patients who had hyperhomocysteinemia at baseline. Hyperfibrinogenemia was detected in 3 patients (none in 100 controls). Plasma fibrinogen was not affected by duration, extent or severity of UC and did not decrease with remission of disease. Only one patient had heterozygous factor V Leiden mutation. CONCLUSION: Vascular thrombosis occurred in less than a fifth of the UC population studied. Hyperhomocysteinemia reversible by folate supplementation and hyperfibrinogenemia were observed, but their contribution and that of factor V Leiden mutation appear to be insignificant.