Hyperhomocysteinemia, obesity and cryptogenic stroke.

BACKGROUND: The pathogenic role of hyperhomocysteinemia in cryptogenic stroke is not well established. We aimed to determine homocysteine levels in patients with cryptogenic stroke considering the possible variables that may act as confounders and analyze the influence of obesity on this association. PATIENTS AND METHODS: We conducted a case-control study in 123 patients with cryptogenic stroke aged 42 ± 12 years and in 153 control subjects aged 42 ± 13 years. Serum homocysteine was determined by fluorescence polarization immunoassay. RESULTS: Patients showed statistically higher levels of homocysteine, creatinine and higher BMI than controls (p = 0.045, p = 0.014, p = 0.013), respectively. After multivariate adjustment the differences in homocysteine levels disappeared (p = 0.774). When subjects were classified according to the presence or absence of obesity, the differences in the prevalence of hyperhomocysteinemia (homocysteine >15 µM) were highly significant, being higher in patients than in controls (p = 0.009). Likewise, mean values of homocysteine in obese were higher in cases than in controls (16.9 ± 9.5 µM vs. 10.12 ± 2.5 µM; p = 0.020), remaining significant after adjusting for the above mentioned confounders. CONCLUSION: Although in general, hyperhomocysteinemia does not seem to constitute an independent risk factor for cryptogenic stroke, it significantly increases the risk in obese subjects; therefore it is convenient to decrease its levels in this sub-group to minimize the risk.

Enfermedad de Behçet en la Comunidad Valenciana. Estudio del estadopretrombótico y revisión de la enfermedad / Behçet’s disease in Valencia Community. Prothrombotic status

La enfermedad de Behçet (EB) es una enfermedad de base inflamatoria y etiología desconocida. Afecta por igual a ambos sexos. En España, su prevalenciaes baja, respecto a otras áreas. La clínica se caracteriza por la aparición de úlceras orales recurrentes, aftas genitales y afectación ocular y cutánea.Las manifestaciones gastrointestinales, neurológicas y vasculares asocian una elevada morbilidad.Con este trabajo, proponemos; por un lado, un acercamiento a las manifestaciones clínicas en estudios realizados en la Comunidad Valenciana; así como, una revisión sistemática de la enfermedad; ahondando particularmente, en el aspecto vascular y el estado protrombótico de la misma (AU)

Behcet´s disease (BD) is a rare inflammatory disease with unknown aetiology. It affects equally both sexes. The disease has oral and genital ulcers, ocular and cutaneous manifestations. Gastrointestinal, neurological and vascular manifestations are associated with a high morbidity.In this paper we present a disease review with special interest in vascular manifestations in view of our results in several studies realized in 74 patients from the Valencia Community (AU)

Erythrocyte membrane composition in patients with primary hypercholesterolemia.

There are conflicting results regarding the erythrocyte membrane cholesterol and phospholipid content in patients with primary hypercholesterolemia (PHC), due to methodological problems in obtaining haemoglobin-free ghosts. At the same time, the different units used and the fact that the cholesterol and phospholipids are not expressed in relation with integral protein membrane content, produces contradictory results. We have analysed in 33 patients with PHC (12 male, 31 female) aged 43+/-12 years and in 33 healthy normolipaemic volunteers (9 male, 24 female) aged 43+/-13 years plasma lipids, along with, erythrocyte membrane cholesterol, phospholipids and integral proteins. PHC patients showed increased erythrocyte membrane cholesterol: 0.36+/-0.15 mg/mg when compared with controls: 0.29+/-0.75 mg/mg; p=0.018. Phospholipid membrane content, although higher in the cases, did not reach statistical significance (PHC patients: 0.38+/-0.15 mg/mg vs. 0.33+/-0.72 mg/mg; p=0.098). The cholesterol/phospholipids ratio (Chol/Ph) was 0.99+/-0.22 in PHC patients versus 0.92+/-0.28 in controls; p=0.127. Our results suggest that there is a slight increase in erythrocyte membrane cholesterol in patients with PHC. Given the increasing importance of erythrocyte membrane cholesterol in the stability of the atheroma plaque due its possible contribution to the clinical signs of ischaemic heart disease, it seems relevant to determine this parameter in risk populations. Therefore, a simple and reproducible method needs to be standardised which would enable comparisons between laboratories and facilitate further studies aimed to it as a marker of acute coronary syndromes.

Actitud ante un paciente con calcifilaxia que precisa anticoagulación / Management of a Patient with calciphylaxis and requiring anticoagulation

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Fibrinogen, plasma viscosity and blood viscosity in obesity. Relationship with insulin resistance.

Plasma viscosity (PV) and blood viscosity (BV) have been scarcely evaluated in morbid obese patients with no other concomitant cardiovascular risk factors. Contradictory results have been published regarding the influence of insulin resistance on these rheological parameters in obesity. In 67 severe or morbid obese patients without other cardiovascular risk factors (51 women and 11 men, aged 34+/-11 years), fibrinogen, PV and BV at native (nBV) and corrected 45% hematocrit (cBV) have been determined, and insulin resistance has been calculated with homeostasis model assessment (HOMA) index, in basal conditions and after a three month diet period. The same determinations were performed in 67 healthy volunteers (45 women, 22 men, aged 32+/-10 years) at baseline and three months later. When cases and controls were compared, obese patients showed higher fibrinogen levels (P<0.001), PV (P=0.050) and cBV (P=0.035), and showed a higher insulin resistance than the control group (P<0.001). Differences in PV were maintained after adjusting for BMI (P=0.001), but disappeared after adjusting for HOMA (P=0.391) fibrinogen (P=0.367) and LDL-chol (P=0.097). Differences between obese patients and the control group for cBV disappeared after adjusting for BMI (P=0.739), HOMA (P=0.744), fibrinogen (P=0.907), LDL-chol (P=0.283) and PV (P=0.112). The achieved weight loss (8.7+/-3.53%) was not accompanied by any changes in these rheological parameters (P>0.050). Obese patients show increased fibrinogen levels, PV and cBV. These rheological disturbances seem to be associated with insulin resistance and the metabolic syndrome, and do not seem to improve with moderate weight loss.

Erythrocyte deformability in obesity measured by ektacytometric techniques.

Erythrocyte deformability (ED) has been scarcely evaluated in obese patients without other concomitant cardiovascular risk factors and contradictory results have been published regarding the influence of plasma lipids on the erythrocyte membrane lipid composition and insulin resistance on this rheological parameter. In 67 severe or morbid obese patients without other cardiovascular risk factors (51 women and 11 men, aged 34+/-11 years) and in 67 controls (45 women and 22 men, aged 32+/-10 years), ED has been determined by ektacytometric techniques in a Rheodyn SSD, the elongation index (EI) being measured at 12, 30 and 60 Pa, along with plasma lipids, red blood cell membrane lipids (cholesterol and phospholipids) and insulin resistance indexes in basal conditions and after a three month diet period. No significant differences were obtained in the EI between obese patients and the control group at any of the shear stresses tested (P>0.05). The cholesterol and phospholipid content of the red blood cell membrane did not significantly differ between cases and controls (P>0.05). Obese patients with metabolic syndrome showed lower EI at 30 and 60 Pa than those without metabolic syndrome (P=0.014 and P=0.031 respectively). Weight loss was not accompanied by any changes in these rheological parameters. Obesity itself does not seem to modify ED. However, metabolic syndrome seems to decrease ED, possibly through insulin resistance.

Platelet activation and red blood cell phosphatidylserine exposure evaluated by flow cytometry in patients with Behçet's disease: are they related to thrombotic events?

Behçet's disease (BD) is associated with an increased risk of venous and arterial thromboses that are associated with morbidity and mortality increase, although the mechanisms are not well established. In the present study, we used whole blood cytometry to determine the exposure of CD62 on the surface of platelets and the expression of phosphatidylserine (PS) on the surface of circulating red blood cells. Microparticle and microaggregate formation from platelets were also determined in a well-classified group of 72 patients (39 males, 33 females, aged 46.5 +/- 12.5 years) with BD, in comparison with a well-matched control group of 72 healthy volunteers. Results showed no differences in the above-mentioned parameters when BD patients and controls were compared. However, when we compared BD patients with/without thrombosis using these parameters, there were significant differences between both groups. BD patients with previous thrombosis had a higher percentage of circulating CD62-positive platelets and a higher number of circulating microaggregates than those without thrombosis, suggesting that platelet activation may be involved in the development of thrombotic events in these patients.

Complicaciones tromboembólicas en el buceo / Thromboembolic complications in the diving

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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)

Pseudotrombocitopenia EDTA-dependiente ¿indicador de enfermedad severa en pacientes de edad avanzada? Caso Clínico / EDTA-dependent pseudothrombocytopenia, indicator of severe illness in old patients?; a case report

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Erythrocyte aggregability and disaggregability in thalassemia trait carriers analyzed by a laser backscattering technique.

Erythrocyte aggregability was determined by a laser backscattering light technique in 23 beta minor thalassemia carriers and in 36 age and sex matched controls. The aggregation time (Ta) was statistically higher in cases than in controls (2.8 +/- 1.0 vs 2.3 +/- 0.4, p < 0.05) and the aggregation index at 10 sec (AI10) was statistically lower (25.1 +/- 5.7 vs 28.2 +/- 3.8, p < 0.05), suggesting both parameters a statistically lower erythrocyte aggregability tendency. However, the total disaggregation threshold (gammaD) was statistically higher in cases than in controls (134.4 +/- 34.1 vs 105.1 +/- 33.1, p < 0.05), indicating that once aggregates are formed a higher shear rate is needed to break them up. No differences were observed in plasmatic factors, i.e., fibrinogen, total cholesterol and triglycerides, that could have influenced erythrocyte aggregation. A negative statistically significant correlation was found between erythrocyte indexes and the total disaggregation threshold. The lower erythrocyte aggregation found in minor thalassemia carriers could be attributed in part to the morphological alterations, although others mechanisms such as modifications in the membrane structure of the RBC can not be ruled out.

Evaluación de un nuevo sistema automático para la determinación de la velocidad de eritrosedimentación (test 1) / Evaluation of a new automated system for measuring erythrocyte sedimentation rate (Test 1)

La determinación de la velocidad de eritrosedimentación (VS) es una de las pruebas más utilizadas en la práctica clínica, útil para indicar la presencia de enfermedad, seguir el curso evolutivo de procesos inflamatorios y comprobar la respuesta a tratamientos. La determinación de la VS conlleva la extracción de un tubo exclusivo de sangre con citrato, seguida de un ensayo de laboratorio que precisa de un tiempo prolongado. Sería deseable la aparición de un nuevo test de medición de la VS que posibilitara la integración de la medida de VS con la hematología automatizada, empleando microvolúmenes de sangre anticoagulada con EDTA, y que permitiera una determinación rápida y de forma continua. El objetivo de este estudio es valorar la aplicabilidad del nuevo analizador Test 1 (Sire Analytical Systems, Udine, Italia), que emplea una tecnología basada en la fotometría capilar cuantitativa, evaluando su reproducibilidad y estabilidad y comparando los resutados obtenidos para la VS con los obtenidos mediante el analizador Ves-MAtic (Diesse, Milán, Italia) y con los valores de las medidas de viscosidad plasmática. Para ello, se determinaron las VS de 375 pacientes, emplando muestras anticoagulantes con K3-EDTA para el Test 1 y con citrato sódico para el Ves-Matic. Además, se ha valorado la viscosidad plasmática en 39 de los 375 pacientes. La reproducibilidad intra-ensayo del Test 1 fue satisfactoria y su estabilidad fue aceptable durante las primeras 24 horas, manteniendo las muestras a 4ºC. Sin embargo, al comparar los valores de VS obtenidos mediante el analizador Test 1 y el sistema Ves-MAtic, mediante el coeficiente de correlación de Pearson y el análisis de Bland-Altman, se llegó a la conclusión de que los dos métodos presentan diferencias significativas, por lo que no son intercambiables. Por otra parte, las medidas de viscosidad plasmática se correlacionan mejor con las determinaciones del VS obtenidad con el Test 1 que con las obtenidas con el Ves-Matic. El Test 1 tiene numerosas ventajas operativas evidentes. Sin embargo, al basarse en principios físicos completamente diferentes a los sistemas habituales de medida de la VS, la variable física que se determina no es completamente equivalente a ésta. Serían necesarios estudios más profundos acerca del significado clínico de las determinaciones realizadas mediante el analizador Test 1, antes de su introducción en el laboratorio clínico como sustituto de los actuales analizadores de VS (AU)

Plasma lipids and blood fluidity in patients with polygenic hypercholesterolaemia treated with fluvastatin.

The clinical benefit brought about by HMG-CoA reductase inhibitors (statins) may not entirely be due to their lipid-lowering effect. Further investigation is necessary in order to determine the significance of ancillary effects to the clinical benefit of statin treatment. We studied 27 polygenic hypercholesterolaemia (PHC) patients before and 3 and 6 months after fluvastatin treatment. A control group of 38 normal, sex and age matched, subjects were also studied. The following parameters were measured: haematimetry, serum lipids and general biochemistry, apo-A/B and lipoproteins, fibrinogen, blood filterability, red blood cell aggregation, blood and plasma viscosity. PHC patients showed lower blood filterability (16.00+/-0.99 vs 19.90+/-2.90 microl/s), higher plasma fibrinogen (274.8+/-41.5 vs 241.6+/-43.2 mg/dl), increased erythrocyte aggregation at low shear stress (8.10+/-1.15 vs 7.19+/-1.29) and increased plasma viscosity (1.26+/-0.06 vs 1.23+/-0.05 mPa.s). Notable lipid changes after 6 months fluvastatin treatment were not accompanied by measurable changes in the haemorheological alterations of the PHC patients.

Factor V Leiden and prothrombin G20210A in relation to arterial and/or vein rethrombosis: two cases.

The factor V Leiden (FV Leiden) and prothrombin G20210A mutations, are the most common established genetic risk factors for deep vein thrombosis (DVT). However, the relationship between these mutations and arterial thrombotic syndromes (coronary heart disease, myocardial infarction, stroke) has not been established. Some studies have suggested a relationship between them, but other authors have considered it unlikely that these anomalies are a major risk factor for arterial thrombosis. From the clinical point of view, a question arises concerning the risk of repeated thrombosis in patients carrying one of these two mutations. The question is whether the recurrence is attributable to the mutations or to the presence of additional circumstantial risk factors. As the risk of repeated thrombosis varies considerably from one patient to another, decisions about long-term treatment require weighing the persistence of risk factors for vascular disease (venous and arterial), especially in selected cases such as young patients or patients with thrombosis of unusual localization.

The effect of acenocoumarol on hemorheological parameters.

The effect of acenocoumarol on hemorheological variables was measured in 35 non-valvular chronic atrial fibrillation patients before starting oral anticoagulant therapy (basal) and one and two months after beginning treatment (INR-2,3). Fibrinogen increased significantly from the basal situation: 332+/-99 mg/dl to 386+/-96 mg/dl in the second month (p<0.05). However, this small increase in fibrinogen is not large enough to mediate other rheological changes, and whole blood filterability, blood viscosity, plasma viscosity and erythrocyte deformability and aggregability remained unchanged after treatment. These results suggest that acenocoumarol does not affect rheological parameters and can therefore be used as a "neutral drug" for rheological studies in cardiovascular patients under oral anticoagulant therapy.