Splanchnic vein thrombosis as a manifestation of latent myeloproliferative neoplasm associated with sticky platelet syndrome / Trombosis esplácnica como presentación de neoplasia mieloproliferativa latente asociada con síndrome de plaqueta pegajosa

Abstract Vein thrombosis of unusual sites such as the splanchnic region continues to be not only a diagnostic but also a therapeutic challenge for the clinician due to its manifestation and associated pathologies. Latent JAK2 (Janus kinase 2) positive myeloproliferative neoplasm associated with sticky platelet syndrome is unusual. We present a clinical case of a 38-year-old female patient who presented with sudden onset abdominal pain of a possible vascular origin. Splanchnic thrombosis was diagnosed in latent myeloproliferative neoplasm by identifying the JAK2V617F mutation and sticky platelet syndrome via platelet aggregometry. Off-label anticoagulation with rivaroxaban 20 mg/day was administered. During her outpatient follow-up, she did not suffer any new thrombotic episodes.

Resumen La trombosis venosa de sitios inusuales como la esplácnica continúa siendo un reto no solo diagnóstico sino también terapéutico para el clínico debido a su forma de presentación y las patologías asociadas. La neoplasia mieloproliferativa latente JAK2 (cinasa de Janus 2) positiva asociada con síndrome de plaqueta pegajosa es inusual. Se presenta un caso clínico de una paciente de 38 años de edad que debutó con dolor abdominal de inicio súbito que sugirió un posible origen vascular. Se diagnosticó trombosis esplácnica en relación con neoplasia mieloproliferativa latente por la identificación de la mutación de la JAK2V617F y síndrome de plaqueta pegajosa mediante agregometría plaquetaria. Se administró de manera off-label anticoagulación con rivaroxabán 20 mg/día. Durante su seguimiento ambulatorio no ha presentado nuevos episodios trombóticos.

Correlation between the Polymorphism of Coagulation-Related Genes and Lower Extremity Deep Venous Thrombosis / 法医学杂志

Objective To investigate the correlation between the polymorphism of 4 coagulation-related genes, rs1799963 （coagulation factor V gene Leiden）, rs6025 （prothrombin gene G20210A）, rs1042579 （thrombomodulin protein gene c.1418C>T） and rs1801131 （methylenetetrahydroflate reductase gene） and lower extremity deep venous thrombosis （LEDVT）. Methods The 4 genotypes mentioned above of 150 LEDVT patients and 153 healthy controls were detected by the kompetitive allele specific polymerase chain reaction （KASP）, then related blood biochemical indicators were collected, binary Logistic regression was established to screen the independent risk factors of LEDVT, and the correlation between polymorphism of 4 coagulation-related genes and LEDVT and its indicators under different genetic modes after adjusting confounding factors were analyzed. Results Five variables, D-dimer, fibrinogen degradation product, homocysteine, sex and age might be the risk factors of LEDVT. These variables were put into 4 genetic inheritance models, and adjusted in binary Logistic regression. The results suggested that the mutations of rs1042579 were correlated with LEDVT under dominant inheritance mode. Conclusion The gene polymorphism of rs1799963, rs6025 and rs1801131 has no significant correlation with the formation of LEDVT. The gene polymorphism of rs1042579 plays a role under dominant inheritance mode, and might be an independent risk factor for formation of LEDVT.

Genetic and Clinical Characteristics of A Family with Combined PROC and PROS1 Genetic Variants / 中国实验血液学杂志

OBJECTIVE@#To test the anticoagulation functions, perform the genetic diagnosis and analyze the clinical characteristics in a family with combined heterozygous genetic variants of PROC and PROS1.@*METHODS@#Peripheral blood was collected from all the family members. Hematological phenotypes and activity of anticoagulant factors were analyzed. Target genes were amplified by PCR from DNA isolated from peripheral blood, and then were analyzed by Sanger DNA sequencing.@*RESULTS@#Many members in the family displayed the combined genetic variants in protein C and protein S, and six family members accompanied by deep venous thrombosis (DVT). The influences of genetic and secondary factors on the incidence of venous thrombosis in the family members were analyzed. The results showed that in this family, carriers of combined protein C and protein S gene defects had a higher incidence of VTE, but acquired factors still played a key role in the eventual thrombotic symptoms.@*CONCLUSION@#Venous thromboembolism (VTE) is a multifactorial disease, the combined genetic heterozygous mutations of protein C and S is an important genetic factor, and the clinical phenotype show a high heterogenicity, the secondary factors contribute to the VTE incidence.

Epidemiological African Day for Evaluation of Patients at Risk of Venous Thrombosis in Acute Hospital Care Settings : Cardiovascular Topic

Introduction : This study aimed to identify patients at risk for venous thromboembolism (VTE) among all patients hospitalised; and to determine the proportion of at-risk hospital patients who received effective types of VTE prophylaxis in sub-Saharan Africa (SSA). Methods: A multinational; observational; cross-sectional survey was carried out on 1 583 at-risk patients throughout five SSA countries. Results: The prevalence of VTE risk was 50.4 overall; 62.3 in medical and 43.8 in surgical patients. The proportion of at-risk patients receiving prophylaxis was 51.5 overall; 36.2 in medical and 64 in surgical patients. Low-molecular weight heparin was the most frequently used prophylactic method in 40.2 overall; 23.1 in medical and 49.9 in surgical patients. Discussion: This study showed a high prevalence of VTE risk among hospitalised patients and that less than half of all at-risk patients received an American College of Clinical Pharmacy-recommended method of prophylaxis. Conclusion: Recommended VTE prophylaxis is underused in SSA

Prevalence of Janus kinase 2 mutations in patients with unusual site venous thrombosis / Prevalencia de las mutaciones del gen quinasa Janus 2 en pacientes con trombosis venosa en sitios poco frecuentes

We aimed to study patients with splanchnic vein thrombosis (SVT) and cerebral vein thrombosis (CVT) searching for JAK2 mutations. We evaluated 14 patients (median age: 41.5 years) with portal vein thrombosis (PVT) = 7; mesenteric vein thrombosis (MVT) = 3; and CVT = 4. JAK2 V617F was assessed by allele specific PCR of peripheral blood DNA. In addition, DNA was sequenced for other JAK2 mutations. Other inherited and acquired thrombophilia risk factors were evaluated. JAK2 V617F was positive in four out of seven patients with PVT and in one CVT patient. These five patients had a diagnosis of myeloproliferative disorder (MPD) at the moment of the occurrence of thrombosis (n = 2) or later (n = 2). Patients with MVT and CVT were negative for JAK2 V617F, except one patient with CVT and a diagnosis of essential thrombocythemia. No other JAK2 mutations were found in this cohort. Besides MPD, other thrombophilia risk factors were identified in five patients. One patient had MPD as well as thrombophilia risk factor. In this group, 4 out of 7 of the patients with PVT carried the JAK2 V617F mutation with or without overt MPD. However, the investigation of other JAK2 mutations may not be necessary in patients with thrombosis at unusual sites.

Nuestro objetivo fue estudiar pacientes con trombosis de las venas esplácnicas (TVE) o trombosis de las venas cerebrales (TVC) en búsqueda de mutaciones del gen quinasa Janus 2 (JAK2). Se estudiaron 14 pacientes (media de edad: 41.5 años) con trombosis de la vena porta (TVP n = 7), trombosis de la vena mesentérica (TVM, n = 3) y TVC (n = 4). La mutación V617F del gen JAK2 fue evaluada por reacción en cadena de la polimerasa (PCR) alelo-específica en muestras de sangre periférica. Además, se realizó secuenciación de ADN en búsqueda de otras mutaciones del gen JAK2 distintas de V617F. También se investigaron factores genéticos y adquiridos para trombofilia. JAK2 V617F fue positiva en 4 de 7 pacientes con TVP y en un paciente con TVC. Estos 5 pacientes con la mutación tuvieron diagnóstico de síndrome mieloproliferativo (SMP) en el momento de la detección de la trombosis (n = 2) o después (n = 3). Un paciente con TVP sufrió el episodio trombótico 18 años después del diagnóstico del SMP y la mutación JAK2 V617F fue negativa. No se encontraron otras mutaciones del gen JAK2 en este grupo d e pacientes. Además del diagnóstico de SMP, se identificaron otros factores de riesgo para trombofilia en 4 pacientes. Un paciente tuvo un factor de riesgo para trombofilia además del diagnóstico de SMP. La mutación JAK2 V617F se presentó en 4/7 de los pacientes con TVP con o sin un diagnóstico obvio de SMP. La investigación de otras mutaciones podría no ser necesaria en pacientes con trombosis en sitios poco frecuentes.

Asociación de variantes funcionales en genes del metabolismo de la homocisteína con riesgo de trombosis venosa profunda e hiperhomocisteinemia en individuos del Sur de Chile / Association of functional variants in homocysteine metabolism genes, deep venous thrombosis risk and hyperhomocysteinemia in Southern Chilean subjects

Introducción: La Trombosis Venosa Profunda (TVP) es un importante problema de salud en la sociedad moderna. Evidencia reciente sugiere una asociación entre variantes funcionales en genes del metabolismo de la homocisteína con TVP. Sin embargo, los resultados entre poblaciones son contradictorios. En este trabajo, evaluamos la potencial asociación entre la presencia de polimorfismos en genes del metabolismo de la homocis-teína y susceptibilidad a TVP e hiperhomocisteinemia en sujetos chilenos. Métodos: Un total de 231 individuos, 77 pacientes con diagnóstico de TVP y 154 controles fueron incluidos en el estudio. Polimorfismos en los genes Metilenotetrahi-drofolato reductasa (MTHFR) y Cistationina p-sintetasa fueron genotipificados por PCR-RFLP Las concentraciones de homocisteína basal fueron cuantificadas mediante Inmunoensayo de Fluorescencia Polarizada. Resultados: La distribución genotípica y frecuencias alélicas del polimorfismo MTHFR C677T fue significativamente diferente entre pacientes y controles (p<0.01). Odds Ratio para TVP asociada al genotipo homocigoto fue 3.68 (I.C. 95 por ciento: 1.628-8.337, p<0.01). Por el contrario, la distribución genotípica de la variante CBS 844ins68 fue similar en ambos grupos (OR=1.82, I.C. 95 por ciento: 0.636-5.234, p=0.257). Además, los portadores del genotipo homocigoto MTHFR 677TT presentaron niveles más elevados de homocisteína plasmática. Conclusiones: El polimorfismo MTHFR C677T constituye un biomarcador de riesgo de TVP en población chilena, y se relaciona a mayores niveles de homo-cisteína en sujetos homocigotos. Los resultados sugieren que la detección molecular de esta variante debería ser incluida en el estudio básico de Trombofilia en nuestra población.

Background: Deep Venous Thrombosis (DVT) is an important health problem in modern society. Recent evidence suggests an association between functional variants in homocysteine metabolism genes and DVT. However, findings in different populations have been contradictory. In this work, we evaluated the potential association between the presence of polymorphisms in homocysteine metabolism genes, DVT susceptibility and hyperhomocysteinemia in Chilean subjects. Methods: A total of 231 individuals, 77 patients with diagnosis of DVT and 154 controls were included in this study. Common variants in Metylenete-trahydrofolate reductase (MTHFR) and Cistationine p-synthetase (CBS) genes were genotyped by PCR-RFLP. Basal homocysteine was quantified by Fluorescence Polarization Immunoassay. Results: Genotype distribution and allelic frequencies of MTHFR C677T polymorphism were significantly different between patients and controls. Odds Ratio for DVT associated to homozygous status was 3.68 (95 percent C.I., 1.628-8.337, p<0.01). On the other hand, the genotype distribution of the CBS 844ins68 variant was similar in both groups (OR 1.82, 95 percent C.I.: 0.636-5.234, p=0.257). In addition, the individuals carrying the MTHFR 677TT homozygous genotype exhibited higher levels of homocysteine. Conclusion: The MTHFR C677T polymorphism constituted a molecular biomarker of DVT in Chilean population, and related to higher levels of homocysteine in homozygote subjects. The results suggest that the molecular detection of this polymorphism should be included in the basic screening for thrombophilia in our population.

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.

Protrombina mutante em indivíduos sob investigação de trombofilia / Mutant prothrombin in individuals under thrombophilia investigation

INTRODUÇÃO: A doença tromboembólica é bastante freqüente, com incidência anual na população de 1 caso por mil indivíduos. Os fatores de risco para trombose incluem condições hereditárias e adquiridas. Uma mutação de ponto no fator II da coagulação, a protrombina G20210A (PTCR), constitui o segundo defeito genético mais comum associado à predisposição para trombose ou trombofilia. No Brasil, o estudo desse fator de risco é relativamente recente e se dispõe de poucos dados na literatura especializada. OBJETIVO: Este trabalho teve como objetivo determinar a freqüência da PTCR em 285 indivíduos sob investigação de trombofilia na Fundação de Hematologia e Hemoterapia de Pernambuco (HEMOPE/PE). MATERIAL E MÉTODO: A técnica molecular utilizada foi a enzima de restrição/reação em cadeia da polimerase (RE/PCR), com primers específicos e a enzima Hind III. RESULTADOS: A freqüência encontrada da PTCR foi de 6 por cento em heterozigose. A presença da mutação foi semelhante em indivíduos com idades tanto inferiores quanto superiores a 45 anos. DISCUSSÃO: A presença da PTCR pode ter sido determinante para o surgimento dos quadros trombóticos, e a baixa mediana de idade do grupo estudado sugere que outras causas genéticas de trombofilia devem ser investigadas, pois a maioria dos trabalhos associa a presença de fator de risco genético a eventos trombóticos em indivíduos com idade inferior a 45 anos. CONCLUSÕES: Os resultados da pesquisa mostraram que a freqüência da PTCR na população estudada é semelhante à descrita na literatura científica para indivíduos selecionados com tromboembolismo e confirmam a importância do estudo molecular em diferentes faixas etárias.

BACKGROUND: Thromboembolic disease is very common, with a yearly incidence in the general population of approximately 1 case per a thousand individuals. The risk factors for thrombosis include both hereditary and acquired conditions. A point mutation in coagulation factor II, prothrombin G20210A (PTCR), constitutes the second most prevalent genetic defect associated with the predisposition to thrombosis or thrombophilia. In Brazil, the study of this risk factor is relatively recent and there is little available data in medical literature. OBJECTIVE: The aim of this study was to determine the frequency of PTCR in 285 individuals being investigated for thrombophilia at Fundação de Hematologia e Hemoterapia de Pernambuco (HEMOPE/PE). MATERIAL AND METHOD: The molecular biology technique used was restriction enzyme/polymerase chain reaction (RE/PCR), using specific primers and the Hind III enzyme. RESULTS: The frequency of PTCR was 6 percent in heterozygosis. The presence of the mutation was similar among individuals under and over 45 years old. DISCUSSION: The presence of PTCR may have been a relevant factor for the episodes of thrombosis, and the low median age of the group suggests that other genetic causes of thrombophilia must be investigated inasmuch as most publications associate the presence of genetic risk factor with thrombotic events in individuals under 45 years old. CONCLUSIONS: Our findings showed that the frequency of PTCR in the studied population is similar to the results published in medical literature for selected patients with thromboembolism and they confirm the importance of molecular testing at different age groups.

Evaluación del impacto de la variante genética C677T de la enzima metilentetrahidrofolato reductasa en el pronóstico de trombosis venosa profunda / Impact of the C677T genetic variant of metilentetrahydrofolate reductase on the prognosis of deep venous thrombosis

Introducción: Diversos estudios han relacionado diferentes factores trombofílicos al desarrollo de trombosis venosa profunda (TVP). Entre las alteraciones adquiridas y hereditarias asociadas a trombofilias destacan las relacionadas al metabolismo de la homocisteína. Sin embargo, los resultados observados son contradictorios e influenciados por diversos factores, entre ellos la etnia. Objetivo: Considerando la escasa información sobre las bases genéticas de la TVP en Chile, el objetivo del presente estudio fue investigar la posible asociación entre la mutación C677T del gen de la metilentetrahidrofolato reductasa (MTHFR) y TVP en individuos de nuestra región. Métodos: Fueron evaluados 60 pacientes con TVP (17 a 87 años) y 120 controles (21 a 81 años), de ambos sexos, todos provenientes a la IX Región de La Araucanía. La presencia de TVP fue confirmada mediante ecografía Doppler. La genotipificación de la mutación C677T fue realizada mediante la técnica de PCR-RFLP. Resultados: El genotipo homocigoto TT para la mutación C677T del gen MTHFR fue más frecuente en los individuos con TVP (28 por ciento vs. 15 por ciento, p=0.047). Similarmente, el alelo mutado 677T fue también más frecuente en los pacientes con TVP (0.53 vs. 0.39, p=0.018). La Odss ratio (OR) asociada a la variante 677T confirma la interacción encontrada(OR= 2.0, IC 95 por ciento 1.06 – 3.79, p<0.05). Conclusión: Los datos sugieren que la mutación C677T del gen MTHFR contribuye para el desarrollo de TVP en la población analizada. Sin embargo, hasta que más antecedentes sean reunidos, nosotros no recomendamos incluir la genotipificación de esta mutación en el screening de rutina de trombofilias.

Background: Several studies relate the presence of diverse thrombophilic factors to the development of deep venous thrombosis (DVT). Alteration of homocisteine metabolism has been associated to hereditary and acquired forms of thrombophilia. However, several factors may modify this relationship, among them the subject’s ethnic origin. Aim: To investigate a possible association of the C677T mutation of metilentetrahydrofolate reductase (MTHFR) to DVT. Methods: Sixty patients with DVT, aged 17 to 87 years, and 120 control subjects (21 to 81 years old), males and females, all residents of the Araucania region were evaluated. DVT was confirmed by duplex ultrasonography. PCR-RFLP was used to determine de presence of the C677T mutation Results: The homozygous TT genotype for C677T was more frequent in DVT subjects (28 percent) as compared to controls (15 percent, p=0.047). The mutated alelle of C677T was also more frequent in the DVT group (53 percent vs 39 percent, p=0.018). The OR for DVT associated to C677T was 2.0 (95 percent CI 1.06 – 3.79, p<0.05) Conclusion: The data suggest that the C677T mutation of MTHFR is associated to DVT. However, more information is needed before making a recommendation for use of gene characterization of this mutation in screening for thrombophilia.

Factor V Leiden and prothrombin gene G20210A mutations are uncommon in portal vein thrombosis in India.

BACKGROUND: Extra-hepatic portal vein obstruction due to portal vein thrombosis (PVT) is an important cause of portal hypertension in several regions including India. The cause of thrombosis in these patients remains unclear. We studied the frequency of mutations in genes for coagulation factors V and II (prothrombin) in 61 Indian patients with PVT and 49 healthy control subjects. METHODS: The presence of factor V Leiden mutation and of G20210A prothrombin gene mutation was determined using polymerase chain reaction followed by restriction fragment length polymorphism. Chi-squared test was used to compare patients and controls. RESULTS: Of the 61 patients (median age 11 years; 47 male) studied, 49 were children. One of 61 (1.6%) patients with PVT was heterozygous for factor V Leiden mutation and none had the G20210 prothrombin gene mutation. The frequencies of these mutations were not different from those in control subjects (2/49 and 0/46, respectively). CONCLUSION: Factor V Leiden and G20210 prothrombin gene mutations are infrequent in Indian patients with PVT. Thus, these mutations are unlikely to be responsible for PVT in the Indian population.

Factor V Leiden is not commonly associated with idiopathic portal vein thrombosis in southern India.

BACKGROUND: Factor V Leiden has been reported in 2%-30% of patients with portal vein thrombosis. This wide variation makes it difficult to assess the importance of factor V Leiden as a predisposing factor. METHODS: Factor V Leiden was determined by restriction fragment length polymorphism in 112 patients with portal vein thrombosis, 104 with deep vein thrombosis and 98 control subjects. RESULTS: Only 3/112 (3%) patients with portal vein thrombosis had factor V Leiden, compared to 1/98 (1%) controls and 16/104 (15%) with deep vein thrombosis; of these, 3, 1 and 15, respectively, were heterozygous for this mutation. CONCLUSION: Factor V Leiden contributes little, if at all, to the development of portal vein thrombosis in southern India.

Comparación de las frecuencias de los alelos factor V Leiden (G1691A) y protrombina-G20210A entre pacientes con trombosis venosa profunda y población general mediterránea española / Factor V Leiden (G1691A) and prothrombin-G20210A alleles among patients with deep venous thrombosis and in the general population from Spain

Background: Factor V leiden and the -G20210A variant of prothrombin gene are associated to a higher risk of deep venous thrombosis. Aim: To assess the frequency of factor V Leiden (G1691A) and prothrombin -G20210A alleles in patients with deep venous thrombosis (DVT) and in the general population from Spain. Material and methods: Factor V Leiden (g1691a) and prothrombin-g20210a alleles were genotyped in 493 individuals from the Spanish general populations and in 131 patients with DVT. The presence of DVT was confirmed by phlebography. Allelic frequencies and the DVT risk associated with these variants were estimated. Results: Allelic frequencies for the factor V Leiden (G1691A) allele were 0.019 in patients with DVT and 0.010 in the general population (p=0.235). The frequencies for the prothrombin-G20210A allele were 0.027 and 0.026 (p=0.975). After adjustment for age and gender, the odds ratio for DVT, associated with the presence of G1691A allele was 2.41, but not statistically significant (95% confidence intervals 0.63-9.19). Conclusions: Prothrombin-G20210A allele was more prevelant than factor V Leiden (G1691A) allele in the Spanish population. However, the magnitude of the association between the G20210A and DVT risk is very low. On the contrary, the G1691A allele is associated by itself with a two fold increase in DVT risk in this population although without reaching statistical significance due to its low frequency.

Factor V Kuwait: a novel mutation in the coagulation factor V gene discovered in Kuwait

It was the aim of this study to report a new point mutation in the clotting factor V gene in the general Arab population. The HR2 haplotype was tested in 288 Arabs living in Kuwait - 188 patients with venous thromboembolic disorders [VTE] and 100 healthy subjects - using polymerase chain reaction and restriction fragment length polymorphism techniques. The presence of the new mutation was verified by DNA sequencing. Two [1.06%] VTE patients had guanine instead of the wild-type adenine at nucleotide number 3935 [A3935G] of the factor V gene. This mutation caused a histidine to arginine change in amino acid number 1254 of the factor V molecule. The new mutation is termed 'factor V Kuwait' [His1254Arg] and was absent in the 100 healthy subjects. It appears that factor V Kuwait could be a risk factor for developing VTE in Arabs. A larger study is needed to confirm this observation

Factor V Leiden mutation and deep venous thrombosis in a patient with hypereosinophilic syndrome

Idiopathic hypereosinophilic syndrome is a rare condition characterized by extremely high peripheral blood eosinophil counts. Patients with idiopathic hypereosinophilic syndrome are at increased risk for thrombosis. The coexistence of idiopathic hypereosinophilic syndrome with other thrombotic disease is rare. We present an additional case of idiopathic hypereosinophilic syndrome and factor V Leiden mutation, which lead to deep vein thrombosis

Factor V Leiden y mutación de la protrombina G20210A en pacientes con trombosis venosa y arterial / Factor V Leiden and prothrombin G20210A among Chilean patients with venous and arterial thrombosis

Background: Factor V Leiden and G20210A mutation of prothrombin gene are two important genetic polymorphisms associated with an increased risk for thrombosis. Aim: To establish the prevalence of factor V Leiden and prothrombin G20210A mutation in the Chilean population and their association to venous and arterial thromboembolism. Material and methods: A case-control study was conducted where 149 patients with thrombosis (87 with arterial and 62 with venous thrombosis) confirmed by CAT-scan, electrocardiogram and cardiac enzymes or Doppler depending on the case, and 160 healthy blood donors were genetically analyzed for the presence of both polymorphisms. Results: Factor V Leiden mutation was found in 5.4% of patients and in 1.3% of healthy controls (p=0.04). Heterozygosity for G20210A prothrombin mutation was found in 5.4% of patients and in 2.5% of the control group (p=NS). When arterial and venous thrombosis were considered as separate entities, 4.6% of patients with arterial thrombosis and 6.5% with venous thrombosis presented factor V Leiden (p=NS). Likewise, 8.1% of patients with venous thrombosis and 3.5% of patients with arterial thrombosis had G20210A prothrombin mutation (p=NS). Conclusions: In non selected consecutive Chilean patients with arterial and venous thrombosis the frequency of factor V Leiden and prothrombin G20210A is less than we could expect from their prevalence in the general population.

Familial homocystinuria

Two cases of siblings diagnosed as cases of familial homocystinuria are reported. Both the cases have classical presentation of familial homocystinuria including history of dislocation of lens of the right eye. Brother had history of psychomotor retardation while sister had a significant history of deep vein thrombosis. Levels of plasma homocysteine were elevated and urinary homocysteine was positive in both the cases

Acute superior mesenteric vein thrombosis associated with factor V 'Leiden' gene mutation.

OBJECTIVES: To study thrombophilia states in Indian patients with acute spontaneous superior mesenteric vein thrombosis (SMVT). METHODS: Two men with this condition, a 56 year old and a 31 year old presenting with acute SMVT, demonstrated on CT scan, were subjected to a thrombophilia screen consisting of Protein C, S, antithrombin levels, lupus anticoagulant, anticardiolipin antibodies, fibrinogen levels, factor VIII levels, factor V 'Leiden' gene mutation, and paroxysmal nocturnal hematuria screen. RESULTS: A thrombophilia screen showed factor V 'Leiden' gene mutation (heterozygous) in both cases. Additionally, the first patient had high fibrinogen levels and the second high factor VIII levels. Both patients are currently on long-term anticoagulation. CONCLUSION: Factor V 'Leiden' gene mutation in association with other thrombophilic factors may predispose to spontaneous superior mesenteric vein thrombosis.

Trombose venosa profunda e câncer: análise das mutações em fatores trombofílicos hereditários / Prevalence of factor V Leiden, FII G2002100 A, FXIII Val34Leu and MTHFR C6777T polymorfisms in cancer patients with or without venous trombosis

Trombose venosa é uma complicação comum em pacientes com neoplasias. Estudou-se a prevalência das mutações do FV, FII, FXIII e MTHFr em 211 pacientes oncológicos, 64 com tromboembolismo venoso. Detectou-se a prevalência do fator V Leiden em 1.5 por cento no grupo com trombose e 2.7 por cento no grupo sem trombose (O.R.= 0.586, I.C.= 0.064-5.352); mutação da protrombina em 1.5 por cento versus 1.3 por cento (O. R.= 1.169, I. C. = 0.104-13.135); mutação do fator XIII em 29.6 por cento versus 28.5 por cento (O. R. =1.056, I. C. =0.554-2.011) e mutação na MTHFr em 53.1 por cento versus 60.5 por cento (O. R. = 0.764, I. C. = / Thrombosis is a common complication in patients with cancer. We prospectivelly investigated the prevalence of FVL, FII, FXIII and MTHFr mutations in 211 cancer patients, 64 presenting VTE. We detected a prevalence of FVL in 1.5 per cent (1 of 64) in the thrombosis group and 2.7 per cent (4 of 147) in non DVT group(O.R.= 0.586, C.I.= 0.064-5.352); prothrombin mutation in 1.5 per cent versus 1.3per cent(O.R.=1.169, C.I.= 0.104-13.135); FXIII mutations in 29.6 per cent versus 28.5 per cent (O.R.=1.056, C.I.=0.554-2.011) and MTHF mutations in 53.1 per cent versus 60.5 per cent (O.R.=0.764, C.I.=0.421-1.386)...

Detection of an Ala601Thr Mutation of Plasminogen Gene in 3 out of 36 Korean Patients with Deep Vein Thrombosis

Plasminogen is a key proenzyme in the fibrinolytic and thrombolytic systems. Congenital deficiency of plasminogen and molecular abnormality of plasminogen (dysplasminogenemia) have been reported in association with the thrombotic tendency in human. In dysplasminogenemia, the level of immunoreactive plasminogen is normal, although the functional activity is reduced. Human plasminogen gene spans about 52.5 kb of DNA and consists of 19 exons. Three types of mutations (Ala601Thr, Val355Phe, and Asp676Asn) have been described in dysplasminogenemia. In this study, we measured the plasminogen activity in patients with deep vein thrombosis and analyzed the DNA sequence to detect three point mutations (Ala601Thr, Val355Phe and Asp676Asn) in patients with hypo/dysplasminogenemia. Dysplasminogenemia was identified in 3 (8.3%) of unrelated 36 patients with deep vein thrombosis and the Ala601Thr mutation was detected in all three patients with dysplasminogenemia. In conclusion, dysplasminogenemia is not rare in deep vein thrombosis, which suggests a risk factor for the thrombosis in Korean population.