Primary thrombophilia in Mexico. II. Factor V G1691A (Leiden), prothrombin G20210A, and methylenetetrahydrofolate reductase C677T polymorphism in thrombophilic Mexican mestizos.

We have shown that in Mexican mestizo patients with clinical features of primary thrombophilia, 39% have activated protein C resistance phenotype, 5% protein C deficiency, and 2% protein S deficiency. In the present study, in a group of 37 thrombophilic Mexicans and 50 normal controls, we assessed the factor V G1691A (Leiden), the prothrombin G20210A, and the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphisms. Four patients were found to be heterozygous for factor V Leiden, 5 heterozygous for the prothrombin 20210, 16 heterozygous, and 6 homozygous for the MTHFR 677. There were four individuals with co-segregation of alleles: two heterozygotes for the factor V Leiden/prothrombin 20210, one heterozygote for prothrombin 20210/MTHFR 677, and one heterozygote for prothrombin 20210/homozygote for MTHFR 677. For factor V Leiden, prothrombin 20210, and MTHFR 677 mutations, the allele frequencies were respectively 1% (+/-0.2%, alpha = 0.05), <1% and 51% (+/-5%, alpha = 0.05), with calculated relative risks for thrombosis of 5.94 (P = 0.08), >7.66 (P < 0.05), and 0.44 (P NS), respectively. In Mexican mestizo thrombophilic patients, the low prevalence of the factor V Leiden mutation (10.8%) and the high prevalence of the prothrombin 20210 mutation (13.5%) contrast with those identified in Caucasian thrombophilic patients (21% and 6%, respectively; P < 0.01). On the other hand, the high prevalence of the MTHFR 677 mutation gene both in normal controls (78%) and thrombophilic patients (61%) does not support a role of this mutation in the thrombogenesis of Mexican mestizo patients.

Diminished morbidity and mortality in portal hypertension surgery: relocation in the therapeutic armamentarium.

Although several effective therapeutic options are available for bleeding from portal hypertension, surgery has a well-defined role in the management of patients with good liver function who are electively operated. The aim of this investigation was to evaluate the operative mortality and morbidity of portal blood flow-preserving procedures in a highly select patient population. The records of 148 patients operated on between 1996 and 2000 using one of two techniques (selective shunts or a Sugiura-Futagawa operation [complete portoazygos disconnection]) were analyzed with particular attention to operative mortality, postoperative rebleeding, and encephalopathy. Survival was calculated according to the Kaplan-Meier method. Sixty-one patients had distal splenorenal shunts placed, and 87 patients had a devascularization procedure. Operative mortality for the group as a whole was 1.2%. In the group with selective shunts, the rebleeding rate was 4.9%, the encephalopathy rate was 9.8%, and the shunt obstruction rate was 1.6%. Survival at 24 months was 94% and at 48 months was 92%. In those undergoing devascularization, the encephalopathy rate was 5% and the rebleeding rate was 14%. Survival at 24 months was 90% and at 48 months was 86%. Portal blood flow-preserving procedures have very low morbidity and mortality rates at specialized centers. In addition, a low rebleeding rate is associated with a good quality of life. Low-risk patients with bleeding portal hypertension should be considered for surgical treatment.

Analysis of HFE-codon 63/282 (H63D/C282Y) gene variants in mexican mestizos. Blood donors and patients with hereditary hemochromatosis.

BACKGROUND: The prevalence of hereditary hemochromatosis (HH) (H63D/C282Y) gene variants in Mexico is unknown. METHODS: Using amplification refractory mutation system polymerase chain reaction, an analysis of HFE-codon 63/282 (H63D/C282Y) gene variants was performed in a group of 153 Mexican mestizo blood donors and six individuals with familial iron overload. RESULTS: In normal blood donors, three heterozygotes for the C282Y mutation (2.0%) were found, whereas 18 heterozygotes and one homozygote for the H63D mutation (11.8% and 0.6%, respectively) were identified; there was one compound heterozygote for the C282Y/H63D mutation. These data resulted in allele frequencies of 0.013 (+/-0. 2%, alpha = 0.05) and 0.062 (+/-0.9%, alpha = 0.05), respectively, for these two mutations, results similar to those found in whites. In the six patients with the HH phenotype, two were found to be heterozygous for C282Y and one heterozygous for H63D; three individuals with HH had no gene mutations. Two heterozygous HH individuals were found to have iron overload associated with other conditions: one heterozygous for C282Y infected with HIV, and another heterozygous for H63D with heterozygous beta-thalassemia. CONCLUSIONS: The prevalence of C282Y and H63D HFE gene mutations in Mexican mestizos is similar to that found in other populations. In addition, other gene mutations responsible for HH in the Mexican mestizo population should be investigated, because, in three of six individuals with the HH phenotype, neither of the two mutations was recorded.

Assessment of residual disease in acute leukemia by means of polymerase chain reaction.

Along a 5-year period in a single institution, specific molecular markers were prospectively looked for in consecutive patients with acute leukemia, by means of polymerase chain reaction (PCR): In patients with acute lymphoblastic leukemia (ALL), the BCR/ABL and TEL-AML1 fusion transcripts as well as clonotypic immunoglobulin gene rearrangements were investigated, whereas in patients with acute myelogenous leukemia (AML) the PML-RAR alpha, AML1-ETO and CBF beta-MYH11 fusion proteins were assessed. Specific molecular markers were identified in 15/75 patients: Four with ALL (three with clonotypic IgG rearrangements and one with BCR/ABL) and 11 with AML (nine with the PML/RAR alpha fusion protein--M3 AML-, and two with the AML1/ETO fusion protein--M2 AML-). During follow-up periods ranging from 1 to 60 months, seven patients cleared the residual disease assessed by PCR (RD-PCR), whereas eight patients had either persistence of RD-PCR or a molecular relapse. For patients without or with RD-PCR, the 30-month survival (SV) was 86% and 14%, respectively, whereas median SV was > 60 and two months, also respectively (p < 0.01). Six of eight patients with detectable RD-PCR died, all of them within three months after the detection of the RD-PCR, whereas two of the patients that relapsed were rescued with treatment and entered a second molecular remission. Two of the three molecular relapses were detected without an overt morphological relapse. It is concluded that PCR is a valuable method for assessing residual disease and that early diagnosis of relapses may lead into effective salvage treatment in some instances.

Waldenström's macroglobulinemia is infrequent in Mexican Mestizos: experience of a hematological diseases referral center.

Along a 17-year period 7,373 patients were prospectively studied in a private practice Health facility; of these 11 were patients with Waldenström's macroglobulinemia; calculations from these data and previous publications show that this lymphoid malignancy represents in Mexico 0.18% of all hematologic malignancies, a figure 11 times lower than that described from caucasians. The median age was 65 years (range 31 to 84); there were 6 males and 5 females. Ten individuals were mexican mestizos, whereas one had a caucasian phenotype. The clinical features of the patients afflicted by the disease in Mexico were similar to those reported from caucasian populations. The median survival (SV) of the group of patients was 40 months, whereas the 42-month survival was 49%; the prognosis of the disease was relatively good despite the fact that complete remissions were unfrequent as a result of the treatment.

[Glycosilphosphatidylinositol-anchored cell surface protein deficiency in Mexican mestizo patients with aplastic anemia]. / Deficiencia de proteínas de superficie ancladas por glucosilfosfatidilinositol en células de pacientes mestizos mexicanos con hipoplasia medular.

The peripheral blood cells of ten patients with biopsy-proven aplastic anemia were studied by means of flow-cytometry in order to assess the expression of two phosphatidylinositol-anchored surface proteins: CD55/DAF (decay accelerating factor) and CD59/MIRL (membrane inhibitor of reactive lysis). An abnormal expression was found in five of these ten patients, whereas the "traditional" tests for paroxysmal nocturnal hemoglobinuria (PNH) were positive only on two of these five individuals. Five of the aplastic patients were treated with anti-thymocyte globulin and cyclosporin-A and three entered a complete remission; of the latter, one had CD55/CD59 deficiencies whereas two did not. Along the study period one patient with a hemolytic pattern of PNH was identified. It is concluded that CD55 and/or CD59 abnormalities are frequent in Mexican mestizo patients with aplastic anemia, that the aplastic presentation of PNH is more frequent in Mexico than the hemolytic presentation, that the flow-cytometric identification of CPI-anchored proteins is more sensitive than the "traditional" PNH tests, and that some patients with PNH-aplasia may respond to intensive immunosuppressive treatment. The flow-cytometric identification of GPI-anchored cell surface proteins should replace the "traditional" tests in the identification of patients with PNH.