Characteristics of factor V and protein C based on results from Korean testing centers.

OBJECTIVE: The global incidence of thrombosis is increasing. However, research on thrombosis in the context of Korea is scarce. We aimed to analyze the relationship between factor V and protein C test results and thrombosis in Koreans through a domestic commissioned testing institution conducting mass examinations. METHODS: Results of factor V and protein C tests of 1386 individuals referred simultaneously to EONE Laboratories (Incheon, Republic of Korea) from January 2017 to July 2023 were analyzed retrospectively to identify the association with thrombotic disease. The tests were performed using a STAR MAX (Diagnostica Stago, Asnieres, France) automatic blood coagulation analyzer. The results were analyzed by age and sex. RESULTS: The inspection rate increased gradually from 2017 to 2022. Women (70.0%) demonstrated a higher test rate than did men (30.0%). Young women reported high test rates; the test rate and age distribution differed by sex. Women aged between 20 and 49 years reported lower factor V and higher protein C concentrations than did men between 20 and 49 years of age. CONCLUSIONS: The tests were more commonly performed in women than in men. Women aged between 20 and 49 years reported lower factor V concentrations and higher protein C concentrations than men between 20 and 49 years of age. This study will facilitate recognizing and preventing thrombotic diseases in women.

Anti-phospholipid syndrome in seven leprosy patients with thrombotic events on corticosteroid and/or thalidomide regimen: insights on genetic and laboratory profiles

Abstract INTRODUCTION Corticosteroids and/or thalidomides have been associated with thromboembolism events (TBE) in multibacillary (MB) leprosy. This report aimed to determine genetic and laboratory profiles associated with leprosy and TBE. METHODS Antiphospholipid antibodies (aPL), coagulation-related exams, prothrombin and Leiden's factor V mutations, and ß2-glycoprotein-I (ß2GPI) Val247Leu polymorphism were assessed. RESULTS Six out of seven patients with leprosy were treated with prednisone and/or thalidomide during TBE and presented at least one positive aPL. All patients presented ß2GPI polymorphism, and one showed prothrombin mutation. CONCLUSIONS Corticosteroid or thalidomide adverse effects and aPL and ß2GPI polymorphisms may cause TBE in patients with MB leprosy.

Fator V de Leiden na doença de Legg-Calvé-Perthes / Leiden's V-factor in Legg-Calvé-Perthes disease

Trobofilias hereditárias têm sido implicadas na patogênese da doenca de Legg-Calvé-Perthes. Uma investigação do fator de risco hereditário mais comum para hipercoagulabilidade - a mutação no gene do fator V (fator V de Leiden) - foi conduzida em 20 pacientes com Legg-Calvé-Perthes e 214 controles sadios. A prevalência do fator V de Leiden foi maior nos pacientes com Legg-Calvé-Perthes que no grupo controle (30 vs. 1,87 por cento). A razão de chances (odds ratio) para o desenvolvimento de Legg-Calvé-Perthes foi de 22,5 (p<0,05; intervalo de confiança: 5,68- 89.07). Estes dados sugerem, o fator V de Leiden como fator de risco hereditário para hipercoagulabilidade associada ao desenvolvimento da doença de Legg-Calvé-Perthes.

Inherited tendency to hypercoagulability has been suggested as a cause of vascular thrombosis resulting in Legg-Calvé-Perthes disease. An investigation of the most common inherited risk factor for hypercoagulability - the mutation in the V-factor gene (Leiden's V-factor) - was carried out among 20 Patients diagnosed with Legg- Calvé-Perthes disease. Patients were compared with 214 healthy controls. The prevalence of the Leiden's V-factor was higher in patients with Legg-Calvé-Perthes disease than in controls (30 percent vs. 1,87 percent). The odds ratio for the development of Legg-Calvé-Perthes disease in the presence of the Leiden's V-factor mutation was 22,5 (p<0,05; confidence interval: 5,68-89.07). These data suggest the Leiden's V-factor as an inherited risk factor for hypercoagulability associated with the development of Legg-Calvé-Perthes disease.

Activated protein C resistance and lupus anticoagulant activity induced by plasma and purified monospecific human IgG anti-β2-glycoprotein-I antibodies / Resistencia a la proteína C activada y actividad de anticoagulante lúpico inducidas por plasma y por anticuerpos purificados humanos del IgG anti β2-glicoproteína I

ABSTRACT Introduction. We investigated the activated protein C resistance (APCR) phenotype and the lupus anticoagulant (LA), activity induced by anti-β2-glycoprotein-I (anti-β2GP-I) antibodies. Patients and methods. We studied plasma and sera samples from 29 patients with persistently positive anti-β2GP-I: 22 with thrombosis (12 with primary APS, 10 with APS secondary to SLE) and seven without thrombosis (all with SLE); 25 healthy subjects were studied as controls. We detected anticardiolipin antibodies (ACA); IgG (and its subclasses) and IgM anti-β2GP-I, on irradiated and non-irradiated plates by ELISA. APCR was assessed by the activated partial thromboplastin time (APTT)-based assay and by the modified test. The FV Leiden mutation was studied by PCR. LA determination included screening and confirmatory dRVVT. Serum anti-β2GP-I were affinity purified on sepharose columns and their isotype, subclass, and reactivity against various antigens were studied by ELISA. Results. We found that titers of IgG anti-β2GP-I on irradiated plates were higher than on non-irradiated plates (p = 0.002), IgG2 was the predominant subclass. Fifteen patients (13 with thrombosis) had LA and 15 (also 13 with thrombosis) induced the APCR phenotype. Eleven (all with thrombosis) had both. Two patients were heterozygous for the Leiden mutation. Two purified antibodies, monospecific for β2GP-I, induced an in vitro APCR phenotype and LA activity. Conclusions. Our results seem to indicate that the inhibition of the APC anticoagulant function by IgG2 anti-β2GP-I with LA activity may be one of the responsible mechanisms of thrombophilia in patients with APS.

Introducción. Investigamos la resistencia a la proteína C activada (RPCA) y la actividad de anticoagulante lápico (AL), inducidas por anticuerpos anti-β2-glicoproteína-I (anti-β2GP-I). Pacientes y métodos. Estudiamos los plasmas y sueros persistentemente positivos para anti-β2GP-I de 29 pacientes: 22 tuvieron trombosis (12 con síndrome de antifosfolípidos (SAF) primario y 10 con SAF secundario a lupus erítematoso generalizado (LEG)) y siete sin trombosis (todos con LEG). Como controles estudiamos 25 sueros de personas clínicamente sanas. Detectamos anticuerpos anticardiolipina, anti-β2GP-I IgG (y sus subclases) e IgM por ELISA en placas irradiadas y no irradiadas. Evaluamos la RPCA por medio del tiempo parcial de tromboplastina activada y por la prueba modificada. Estudiamos la mutación FV de Leiden por PCR y el anticoagulante lápico con el método de dRVVT screening y confirmatorio. Después de purificar los anti-β2GP-I séricos con una columna de antígeno unido a sefarosa, analizamos por ELISA sus isotipos, subclases y reactividad contra β2GP-I y algunos fosfolípidos. Resultados. Los títulos de anti-β2GP-I IgG fueron más altos en placas irradiadas que en no irradiadas (p = 0.002), predominó la subclase IgG2. Quince plasmas (13 de pacientes con trombosis) tuvieron AL y 15 (13 también de pacientes con trombosis) indujeron el fenotipo de RPCA. Once plasmas (todos de pacientes con trombosis) indujeron ambas actividades. Dos pacientes fueron heterocigotos para la mutación de Leiden. Dos anticuerpos purificados monoespecíficos para β2GP-I indujeron el fenotipo de la RPCA y la actividad de AL in vitro. Conclusiones. Nuestros resultados sugieren que la RPCA, inducida por los anti-β2GP-I que concomitantemente tienen actividad de AL, puede tener implicaciones patogénicas en la trombofílía del SAF.

Studies on the components of the contact phase system in patients with acute nonlymphoblastic leukemia

The objective of the present study was to evaluate factors of the plasma kallikrein system in patients with acute nonlymphoblastic leukemia (ANLL), and compare the results to a normal control group. A prospective study was performed in the Tertiary Health Care Institution, Hemocentro, Campinas State University, Campinas, Sao Paulo, Brazil. Thirty-five patients, diagnosed as ANLL between 1988 and 1991, were considered for participation. Eleven patients were not elegible, according to the exclusion criteria: infection/septicemia, previous treatment of blood transfusion. The study was performed with 24 ANLL patients, average age 34 years (16-69 years), 14 men and 10 women. Nineteen healthy volunteers, workers from the Hematology Center, average age 32 years (21-59 years), 11 men and 8 women, were the control group. Plasmatic prekallikrein, C1-inhibitor, alpha 2-macroglobulin, activated partial thromboplastin time, prothrombin time, factor XII, factor XI, factor V and prealbumin were measured. Plasmatic prekallikrein (p=0.02) and prealbumin (p=0.03) were significantly decreased, and prothrombin time increased (p=0.003) in the patient group when compared to the control. Significant correlation (r=0.49, critical value=0.43, p<0.05) between prekallikrein and prealbumin, and between prothrombin time and factor V (r=0.54, critical value=0.44, p<0.05) was demonstrated in the patient group. No correlation was found between parameters analysed and circulant blast count or leukemia subgroups. Statistical analysis was performed by the Willcoxon test. Correlation between the parameters was also verified. These results suggest activation of the contact system or impaired liver synthesis in patients with ANLL, and could contribute to disease complications.

Enfermedad tromboembólica venosa recurrente asociada a hiperhomocisteinemia. Una asociación a debate / On the association between recurrent venous thromboembolic disease and hyperhomocysteinemia

No disponible

No disponible

Trombofilia primaria: 41 nuevos casos / Primary thrombophilias: 41 new cases

Se presentan 37 casos de trombosis, en su mayoría jóvenes, con antecedentes trombóticos familiares y con diagnóstico de trombofilia primaria o hereditaria además de cuatro familiares de primer grado de estos pacientes en los cuales se confirmó la portación familiar de trombofilia. La anamnesis reveló que el 82 por ciento presentó la primera trombosis antes de los 45 años; tuvo más de una trombosis en un 59 por ciento y tenía antecedentes familiares en 49 por ciento. Los defectos trombofílicos determinantes encontrados fueron: deficiencia de proteína S (27 por ciento); resistencia a proteína C activada por factor V Leiden (24,3 por ciento); deficiencia proteína C (21,6 por ciento) y antotrombina III (16,2 por ciento); mutación G20210 A del gen protrombina (8,1 por ciento). Entre los defectos adquiridos estudiados simultáneamente, un 27,2 por ciento de los casos presentaron anticoagulante lupico y ninguno hiperhomocisteína. La existencia de mas de un factor de riesgo trombofílico se observó en el 24.3 por ciento de los pacientes. En el estudio de los 4 parientes de primer grado se encontró factor V Leiden en uno; factor V Leiden mas anticoagulante lupico en uno y deficiencia proteína S en dos. El trabajo anterior publicado en 2004 motivó a los pacientes que no se hicieron el estudio a tomar conciencia de su situación y de la necesidad de controlarse, lo que demuestra la importancia de difundir esta patología aún poco conocida.

Factor V Leiden y trombosis de arteria central de retina (réplica) / Factor V Leiden and retinal central artery thrombosis (reply)

No disponible

No disponible

Factor V Leiden y trombosis de arteria central de retina / Factor V Leiden detected through thrombosis of central artery of the retina

No disponible

Riesgos del tratamiento estrogénico en trastornos de identidad sexual: a propósito de un caso / Risks of estrogen treatment in gender identity disorders: apropos of a case

Los riesgos potenciales del tratamiento estrogénico se deben tener en cuenta al tratar a los pacientes transexuales de varón a mujer con estos fármacos. Presentamos el caso de una paciente transexual de varón a mujer que estaba siendo tratada con etinilestradiol y sufrió un episodio de trombosis venosa profunda en el miembro inferior tras inmovilización por un esguince. Dicha paciente fue sometida posteriormente a un estudio de trombofilia y se detectó que era portadora heterocigota del factor V Leiden, por lo que se contraindicó el tratamiento con estrógenos de por vida. Debemos valorar, en los pacientes con mayor riesgo de trombosis venosa profunda, la realización de un estudio de trombofilia previo al tratamiento, así como la necesidad de profilaxis tromboembólica en caso de coexistir un reto trombótico (AU)

The potential risks of estrogen treatment when the male-to-female (M-to-F) transsexual patients are treated with estrogens should not be forgotten. We report the case of a M-to-F transsexual patient undergoing treatment with ethinyl estradiol who developed deep vein thrombosis of the lower extremity after a period of immobility because of a sprain. Thrombophilia study revealed that she was a heterozygous carrier of factor V Leiden. Estrogens were therefore contraindicated. We recommend screening for thrombophilic defects in patients at high risk for deep vein thrombosis before starting estrogen therapy. In addition, these patients require thromboembolic prophylaxis if there are concomitant triggering factors (AU)

Múltiples factores de riesgo trombofílicos identificados en un lactante con accidente vascular cerebral / The identification of multiple thrombophilic risk factors in an infant with cerebrovascular accident

Introducción. La frecuencia del accidente vascular cerebral (AVC) neonatal ha aumentado de manera significativa en los últimos años. Ello puede deberse no tanto a un aumento real del número de casos, como a una mayor certeza en su diagnóstico. Actualmente, su incidencia se ha calculado en un caso por cada 4.000 nacimientos. Caso clínico. Lactante con AVC en el área de la arteria cerebral media izquierda, del cual se disponía de información documentada sobre factores de riesgo (FR) tromboembólicos hereditarios y adquiridos, tanto en el niño (factor V de Leiden y sepsis neonatal) como en la madre (factor V de Leiden, lupus anticoagulante y preeclampsia). Conclusiones. Este caso apoya la evidencia, progresivamente observada en la literatura, de que el AVC neonatal es el resultado de una asociación de diversos FR trombótico (maternos y fetales). En este sentido, los autores consideran importante la investigación sistemática del niño y de su madre, teniendo en cuenta la identificación de una posible enfermedad trombofílica, incluso cuando se haya identificado un factor de riesgo exógeno

Introduction. Neonatal stroke (NNS) incidence appears to be increasing over the last years. This is believed to be a consequence of diagnostic accuracy rather than a real amplification of this entity. Nowadays, NNS incidence is estimated to be 1:4000 full newborns. Case report. Child with left middle cerebral artery territory infarction in which several thrombo-embolic risk factors were documented both in the child (neonatal sepsis and factor V Leiden) and his mother (lupus anticoagulant, pre-eclampsy and factor V Leiden). Conclusions. This case supports the increasing evidence in recent reports that association of multiple prothrombotic risk factors (maternal and foetal) is present in NNS genesis. This way the authors agree that wide prothrombotic study may be of crucial interest in identifying subjacent thrombophilic disease, even when an exogenous risk factor is present

Infarto isquémico cerebral provocado por factor V de Leiden, esferocitosis hereditaria y tabaquismo / Ischemic cerebral infarction due to factor V Leiden, hereditary spherocytosis and smoking

No disponible

Infarto renal, infarto cerebral y factor V Leiden / Renal infarction, cerebral infarction and Leiden factor V

No disponible

Actividad procoagulante y comportamiento tromboelastográfico en pacientes ateroscleróticos / Procoagulating activity and thromboelastographic behavior in atherosclerotic patients

Con los objetivos de determinar los niveles de los factores I, V y X de la coagulación sanguínea y algunos indicadores tromboelastográficos en una muestra de pacientes con aterosclerosis en los miembros inferiores, y comparar los resultados con los obtenidos en una muestra de controles para saber si están significativamente alterados en favor de un estado de hipercoagulabilidad evocador de trombosis incipiente, se realiza un estudio en una muestra de pacientes ateroscleróticos compuesta de 14 hombres (edad promedio 69,5 años) y en una muestra de controles senecentes (60-74 años) compuesta de 11 hombres (edad promedio 69,5 años) y 15 mujeres (edad promedio 71 años), considerados sanos desde el punto de vista angiológico clínico. En ambas muestras, se dosificaron los factores I, V y X y se hallaron indicadores tromboelastográficos de sangre total; en plasma pobre en plaquetas. Se comprobó que no existía diferencia significativa en los niveles de los factores I y X en los indicadores tromboelastográficos entre ateroscleróticos y controles, mientras que los pacientes manifestaran niveles de factor V significativamente más bajos que los controles estudiados

Coagulation changes during the steady state in homozygous sickle-cell disease in Jamaica

Coagulation studies were carried out in 117 Jamaicans with homozygous sickle-cell disease in the steady state, and 40 local controls. The patients had significantly higher factor-VIII levels, higher platelet counts, lower factor-V and plasminogen levels, shorter thrombin times and higher serum fibrinogen degradation products(FDP) than the control group. The low factor-V and plasminogen levels, and high FDP levels, might be explained by activation of the coagulation system and continuous clot lysis even in the absence of painful crisis. The high factor-VIII levels and short thrombin times found in these patients could not be explained.(Summary)

Resistencia a la proteína C activada / Resistence to protein C activation

La trombosis es la causa más frecuente de muerte en el mundo occidental, en EUA por tromboembolismo pulmonar, trombosis coronaria y accidentes cerebrovasculares mueren 1.990.000/año. Aparecen 398.000 trombosis venosas profundas en paciente/año y abortos o pérdidas fetales por trombosis de la placenta. El sistema inhibidor de la coagulación está compuesto por la Antitrombina III(ATIII) cofactor II de la Heparina (CIIIHep), inhibudor de la vía del factor tisular (TFPI), la vía fibronolítica y el sistema anticoagulante de la proteína C, que posee el mayor número de trastornos genéticos asociados con trombosis venosa (TV). La trombina activa a la proteína C; (proteína C activada) (PCA) con la finalidad de clivar a los cofactores VIIIa y la Va.La proteína c recibe la potenciación de la proteína S. El factor V (FV) sinérgicamente con la S como cofactor de la PCA en la degradación del VIIIa. La PCA produce un efecto anticoagulante medible por APTT. La falla de éste, es la resistencia a la proteína C activada (RPCA) común en la población caucasiana. Se hereda en forma autosómica dominante. Algunos portadores nunca desarrollan trombosis, en otros el cuadro es recurrente a tempbrana edad. Se agrava la situación por la coexistencia de otros factores de riesgo congénitos o adquiridos : ingestión de anticonceptivos, embarazo, cáncer, traumas y cirugías. La mutación se describió en el síndrome HELLP , y en la preeclampsia con un 22 por ciento de positividades. El estudio de la anomalía por el test RPCA es de utilidad clínica pero solo el estudio del factor V LEIDEN por PCR permite el conocimiento de la alteración genética. No hay pautas firmes sobre tratamiento. Si la trombosis es recurrentes, puede llegarse a la terapéutica profiláctica por vida

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)...