Intracranial subarachnoid fat and hemorrhage secondary to sacral fracture with spondylopelvic dissociation. / Grasa y hemorragia en el espacio subaracnoideo intracraneal por fractura sacra con disociación espondilopélvica.

We describe a case of fat droplets and blood in the cerebral subarachnoid space secondary in a patient with a complex sacral fracture without associated cranial trauma, a few days after admission. To our knowledge, there is only one published case with similar findings and without any other underlying lesion as cause. We explain the differences in the mechanism of production between this direct fat embolism and brain fat embolism syndrome, which is an intravascular embolism with different radiological appearance. The most important features of sacral fracture with spondylopelvic dissociation are described. Finally, this entity should be taken into account in the differential diagnosis of the few causes of fat in the subarachnoid space. In the context of high-energy trauma fractures of the sacrum or spine must be ruled out as a potential cause of this uncommon intracranial finding.

Risk of venous thromboembolism associated with the insertion/deletion polymorphism in the angiotensin-converting enzyme gene.

The circulating levels of angiotensin I-converting enzyme (ACE) are linked with a 287-base pair insertion/deletion (I/D) polymorphism at intron 16 of the ACE gene. Thus, the homozygous deletion (D/D genotype) could cause chronic vasoconstriction, arterial hypertension and, possibly, coronary artery disease. Also, the increase in plasminogen activator inhibitor-1 level and impaired fibrinolysis were related with the D/D genotype. The D allele has been recently associated with venous thrombosis among African-American men as well as among patients that underwent elective total hip replacement. We assess the risk of venous thromboembolism (VTE) linked with each genotype of the I/D ACE gene polymorphism in a Caucasian population by means of a case-control study. We genotyped the ACE gene in a series of 148 patients aged 45.0 +/- 16.0 years (range, 11-80 years), objectively diagnosed in our centre of deep-vein thrombosis or pulmonary embolism, and in 240 thrombosis-free subjects (25-75 years) from the same geographic area. The observed difference in D allele frequencies between patients (0.56) and controls (0.62) was nonsignificant overall; however, statistical significance (P = 0.05) was found by considering the recessive hypothesis (D/D versus I/ D + I/I) [odds ratio (OR) = 0.64, 95% confidence interval (CI95) = 0.42-0.99]. The OR was 0.88 (CI95 = 0.51-1.53; P = 0.65) for the dominant hypothesis (D/D + I/D versus I/I genotypes). The relative risk for the D allele was close to 1 for the dominant hypothesis, both considering gender and recurrent tendency; however, it was protective in men regarding the recessive hypothesis (OR = 0.53, CI95 = 0.29-0.97, P = 0.04). The I/D ACE allele distribution was similar among the 46 thrombophilic patients (antithrombin, protein C or protein S deficiencies, factor V R506Q, factor II G20210A or lupus anticoagulant). In conclusion, among (Spanish) Caucasians, this study does not support the hypothesis that the deletion allele (D) of the ACE gene could be a significant risk factor for VTE, being protective in men.

[Lowering high levels of fasting total homocysteine with folic acid and vitamins B in patients with venous thromboembolism: relationship between response and the C677T methylenetetrahydrofolate reductase (MTHRF) genotype]. / Reducción de concentraciones elevadas de homocisteína con ácido fólico y vitaminas B en pacientes con tromboembolia venosa: relación entre respuesta y genotipo C677T de la metilén tetrahidrofólico reductasa (MTHFR).

BACKGROUND: High levels of plasma total homocysteine (tHcy) are involved in arterial or venous occlusive diseases. It essentially depends on the nutritional status of folic acid (FA) and vitamins B12 or B6, but also on the methylenetetrahydrofolate reductase (MTHFR) enzymatic activity. We aim to evaluate the response of the hyperhomocysteinemia (HHcy) to a standard schedule of vitamin supplementation, according with the MTHFR genotype. PATIENTS AND METHODS: 227 patients, diagnosed with venous thromboembolism (VTE) were analysed for tHcy (in fasting conditions), and for the MTHFR-C677T gene polymorphism. When the tHcy exceeded the cut-off point (men = 16, women = 15 mumol/l), the patients were supplemented with a dose equivalent to 1 mg FA, 0.2 mg B12 and 100 mg of B6, daily by 6 weeks. Afterwards they were reanalysed and the reduction was stratified by MTHFR genotype, looking for any difference in the response. RESULTS: The mean fasting tHcy was 12.3 mumol/l (SD = 8). The 51 hyperhomocysteinemic patients (22%) were older (65.1 y) than the normal ones (55.0 y) (p = 0.0001). The treatment was carried out properly in 46 patients (90%). The pre-treatment mean Hcy was 23.2 (SD = 10.5) mumol/l, and it was reduced to 13.0 (SD = 5.9) (p = 0.0001) (mean reduction = 42.1%). By genotype, the C/C reduced from 21.0 to 13.2 mumol/l (37%) (n = 18), the C/T from 25.0 to 12.6 mumol/l (46%) (n = 24), and the abnormal homozygotes T/T from 22.7 to 14.5 mumol/l (39%) (n = 4), although no statistical significant differences were found. In 80% of cases (37/46), tHcy values normalised. A negative correlation (r = -0.471) (p = 0.005) was observed between age and response. CONCLUSIONS: The FA/B6/B12 based therapy reduces in a simple, quick and effective way (> 40% in 6 weeks) the pathologic tHcy levels on a VTE population and this is not influenced by the MTHFR genotype. As HHcy seems related with recurrences of venous thrombosis, we could speculate if it would be useful to analyse routinely the tHcy, attempting reduction in selected cases.

[20210A mutation of the prothrombin and venous thromboembolism gene]. / Mutacion 20210A del gen de la protrombina y tromboembolismo venoso.

PURPOSE: Various genetic disorders interact with environmental factors to cause thrombotic diseases. Recently, a G to A transition at nucleotide 20210 in the prothrombin gene, has been described in association with venous thromboembolism, in Dutch population. Currently, several reports want to know the frequence of this mutation in other ethnic groups and populations. The aim of this work was to assess the prevalence rates of prothrombin mutation in both, thrombotic and healthy Spanish populations, and to estimate the associated relative risks. We described the clinical features in our series of thrombotic carriers and moreover, we compared a routine clotting test versus DNA analysis in the diagnosis of this anomaly. POPULATION, MATERIAL AND METHODS: The design was a non-matched case-control study. The involved populations were: 187 patients of venous thromboembolic diseases and 200 healthy controls. Patients and controls were genotyped and both, carriers and non-carrier patients, were analyzed by a routine prothrombin clotting assay, to determine the sensibility and specificity and optimal cut off level of the test. RESULTS: The 20210 A allele was identified in 17 patients (9.1%) and in 7 controls (3.5%), with a 2.76-fold increased risk (OR 2.76, 95% CI = 1.12-6.81), in carriers. One patient and none of the controls were homozygous. The clinical characteristics (first manifestation age or thrombotic recurrence) are similar in both, carriers and non-carriers, patient groups. The prothrombin level by a routine coagulometric method was 1.31 +/- 0.14 U/ml (95% CI = 1.24-1.38) for the 20210 A carriers, whereas for the non carrier-patients was significantly lower, 1.06 (95% CI = 1.03-1.08) (p < 0.00001). With a cut off level of 1.25 U/ml, 12/16 (75%) carriers and 14/132 (10.6%) non-carriers were positive. Therefore, the sensibility was 75% and the specificity 89.4%. With a cut off level of 1.40 U/ml the diagnostic efficiency was even worse. CONCLUSIONS: 3.5% of healthy subjects and 9.1% of thromboembolic patients carried this prothrombin mutation with a relative risk of 2.76 (95% CI = 1.12-6.81). The relevant clinical features are similar to the rest of the series. The mean prothrombin level was higher (1.31 U/ml) than in the normal patients (1.06 U/ml), but the clotting test seems inappropriate for a diagnostic purpose.