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Congenital factor VII (FVII) deficiency is characterized by genotypic variability and phenotypic heterogeneity. Traditional screening and factor assays are unable to reliably predict clinical bleeding phenotype and guide haemorrhage prevention strategy. Global assays of coagulation and fibrinolysis may better characterize overall haemostatic balance and aid in haemorrhagic risk assessment. We evaluated the ability of novel global assays to better understand clinical bleeding severity in congenital FVII deficiency. Subjects underwent central determination of factor VII activity (FVII:C) as well as clot formation and lysis (CloFAL) and simultaneous thrombin and plasmin generation (STP) global assay analysis. A bleeding score was assigned to each subject through medical chart review. Global assay parameters were analysed with respect to bleeding score and FVII:C. Subgroup analyses were performed on paediatric subjects and subjects with FVII ≥ 1 IU dL(-1). CloFAL fibrinolytic index (FI2 ) inversely correlated with FVII:C while CloFAL maximum amplitude (MA) and STP maximum velocity of thrombin generation (VT max) varied directly with FVII:C. CloFAL FI2 directly correlated with bleeding score among subjects in both the total cohort and paediatric subcohort, but not among subjects with FVII ≥ 1 IU dL(-1) . Among subjects with FVII ≥ 1 IU dL(-1), STP time to maximum velocity of thrombin generation and time to maximum velocity of plasmin generation inversely correlated with bleeding score. These preliminary findings suggest a novel potential link between a hyperfibrinolytic state in bleeding severity and congenital FVII deficiency, an observation that should be further explored.

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In a workshop organized by NICHD and the AAP in January 2004, we addressed and discussed issues related to a Hispanic perspective in Training and Retaining of underrepresented minority physician scientists in the United States. A review of the literature related to training of underrepresented minority physicians in the United States (US) was performed, giving emphasis to those related to the Hispanic population. Success and failure in training and retention of Hispanic physician scientists and trainees was examined. An underrepresentation of Hispanic minorities in medical research workforce was found. This fact has recently resulted in efforts to increase their recruitment and there is a mandate by the National Institute of Health (NIH) for their inclusion. The Hispanic population in the US has increased rapidly, with diversity among the Hispanics in their personal and professional behavior. Significant disparities in health, health risk factors and access to health care manifested by an increased burden of illness and death have been documented. There in an undersupply of academic Hispanic neonatologist. Factors such as availability of academic employment, limited research funding in pediatrics, managed care and large debt burden of the US medical graduates interfere with recruitment of Hispanic trainees and academic physician scientist. Possible solutions, including recognition research awards, revision of NIH policies in awarding funds for neonatology, establishing strategies to improve minorities' acceptance, participation in research and increase accrual of Hispanic population in clinical trials should be given priority.

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Five unrelated families with Puerto Rican ancestry were identified as having at least one member with bleeding due to a prothrombin deficiency. Genetic prothrombin deficiencies are extremely rare, but at the University of Puerto Rico Hemophilia Center, prothrombin deficiency is the third most common congenital coagulation factor deficiency. Because Puerto Rico is relatively isolated, there was a reasonable expectation of a founder effect. Prothrombin genes from probands and their parents were directly sequenced from PCR amplified exons using forward and reverse primers. Four novel prothrombin mutations were identified. The first, a G-->A substitution at DNA position 10150 predicting an Arg457-->Gln (R457Q) replacement, is common to all five families. In two of the families, the proband children are homozygous for R457Q. In the other three families, the probands are compound heterozygotes for R457Q and one of the other three mutations, which include another point mutation (gamma16Q), a deletion and a splice junction mutation. The two point mutations have been designated Puerto Rico I and Puerto Rico II. The crystal structure of alpha-thrombin predicts that the R457Q mutation removes a salt bridge that links the A- and B-chains of thrombin. The primary effect of this defect appears to be destabilization of the circulating prothrombin, creating a moderate hypoprothrombinemia. However, prothrombin antigen/activity ratios indicate a dysprothrombinemia as well, most likely due to the inability of R457Q prothrombin to activate fully to thrombin.

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Neutropenia exists when the neutrophil counts is less than 1000/mm3 in infants between 2 weeks and 1 year of age and less than 1500/mm3 beyond 1 year of age (1). Severe infections occur when the absolute neutrophil count is below 500/mm3 with perirectal abscesses, pneumonia, and sepsis being common. Granulocyte Colony-Stimulating Factor (G-CSF) produces a sustained neutrophil recovery in patients with severe neutropenia, reduces the incidence and severity of infection, and improves the quality of life. Various cytopenias, including neutropenia, thrombocytopenia and pancytopenia, have been reported in association with inborn errors of branched aminoacid metabolism such as methylmalonic, propionic and isovaleric acidemia. We report an infant with methylmalonic acidemia who presented severe neutropenia

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The present cost of optimal care in haemophilia is very high. The paradigm of comprehensive care approach, including the essential elements of continuous integrated multidisciplinary health services and the provision of home care with early use of antihaemophilic products requires abundant economic resources that usually are not readily available in nonaffluent countries. A cost-effective comprehensive paediatric haemophilia programme has been operating in Puerto Rico during the last 15 years that provides quality care to over 90% of paediatric haemophiliacs, and is financed mainly by the local government health system. Efforts are also being made to provide and/or coordinate health care to all adult haemophilic patients through the Puerto Rico Pediatric Hemophilia Treatment Center. Information on the haemophilia care available in Latin American countries is scanty. The data available indicate that with a few exceptions, haemophilia care in this vast region is suboptimal. Apparently, early diagnosis is not common, there is lack of accessibility of services in most countries, comprehensive care is not the rule, safe high-purity AHF concentrates are used infrequently, and home care is used rarely. The main antihaemophilic products used are fresh frozen plasma and cryoprecipitate due to the high cost of modern antihaemophilic factor concentrates. The average per capita income of the main Latin American countries is about one-quarter of that of the USA and Canada. The existing economic situation of most Latin American countries would make it very difficult for them to purchase modern antihaemophilic products regularly and provide quality comprehensive care to their haemophilia patients, unless they make special efforts and get some type of external help. As a result of this study recommendations are made to improve the quality and accessibility of services to haemophilia patients in Latin America and other nonaffluent countries.

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Cancer during pregnancy is infrequent. It presents an ethical dilemma--remission may be obtained with chemotherapy, but it has potential harmful effects to the fetus. We report a case of a very low birth weight preterm female infant born to a 21-year-old mother diagnosed with leukemia and given chemotherapy up to 1 week before delivery. In the laboratory, initial findings included severe pancytopenia, and bone marrow aspiration demonstrated complete aplasia. She was given blood product transfusions, erythropoietin, and granulocyte colony stimulating factor. The hematologic derangement was resolved without documented infections. The second case is a preterm male infant whose 30-year-old mother was diagnosed with lymphoma and had received chemotherapy during the third trimester. The infant presented with moderate leukopenia. He had an uneventful course without documented infection. Exposure of the fetus to transplacental chemotherapy must be considered when evaluating therapy options and timing of delivery in hematologic malignancies diagnosed during pregnancy.

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PURPOSE: Hemoglobin Hotel Dieu (HbHD) is a high-oxygen affinity variant of HbA never before reported in a Hispanic patient. This Hb variant was first reported in 1981 by Blouquit et al. in a white person with erythrocytosis with a substitution in the beta 99 aspartic acid residue by glycine. METHODS: A 13-year-old Puerto Rican boy had pain in his chest, headaches, easy fatigability, and high Hb (as high as 19.1 g/dl). Protein analysis was performed by cellulose acetate, citrate agar, and isoelectric focusing electrophoresis and high-pressure liquid chromatography (HPLC), polymerase chain reaction (PCR) amplification, and DNA sequencing of the second exon of the beta gene in samples obtained from the mother, father, and the patient, and DNA fingerprinting to determine paternity. RESULTS: The variant found in the patient migrated on cellulose acetate electrophoresis to a cathodic position relative to HbF, and a band cathodal to HbA and close to HbF on isoelectric focusing electrophoresis. The patient showed an abnormal well-resolved peak on HPLC with a retention time slightly shorter than that for HbS. DNA analysis by direct sequencing of the PCR product demonstrated heterozygosity for codon 99 (GAT-->GGT) in the patient but not in either parent. DNA fingerprinting by multiplex PCR amplification of three simple tandem repeat loci showed that the patient shared alleles in all three loci with both parents, ruling out nonpaternity. CONCLUSIONS: The protein and DNA analysis indicate that the erythrocytosis is caused by the presence of HbHD in this Hispanic adolescent.

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Factor VIII (FVIII) response to desmopressin (deamino-8-D-arginine vasopressin, abbreviated DDAVP) was studied in patients with mild Hemophilia A and von Willebrand Disease (vWD) who attend our Hemophilia Clinic. Thirty eight children and 9 adults had their F VIII components assayed 60 minutes after intravenous (IV) administration of DDAVP, 0.35 microgram/kg. Among 27 hemophiliacs, F VIII coagulant activity (F VIII: C) increased from a mean of 16.8 to 59.2 u/dL; with an average 3.2-fold increase. In 20 vWD patients, the mean F VIII:C and von Willebrand Factor increased from a mean of 50.1 to 136%; and from 22.6 to 75.6%; with an average 3.0 and 5.7-fold increase, respectively. The overall F VIII:C response was good or excellent in 81.5% of the hemophiliacs, and in 89.5% of the vWD patients tested. No significant side effects were observed. This study has demonstrated that IV DDAVP can cause an increase of F VIII:C and vWF to hemostatic levels, and thus it may be useful for the control of bleeding episodes in most of the patients tested in our clinic.

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Cinco mil cuatrocientos setenta y tres personas, incluyendo neonatos, adolescentes, mujeres embarazadas y varones adultos de San Juan y pueblos cercanos fueron examinados para detectar hemoglobinopatias por electroforesis en 1977-78. Se encontraron 210 casos (3.90 por ciento) de hemoglobinas anormales, incluyendo 190 (3.5 por ciento) de Hb S y 20 (0.4 por ciento) de Hb C. La prevalencia de Hb S y C entre los adolescentes del area de San Juan fue de 4.2 por ciento. Pero la prevalencia en adolescentes del pueblo de Loiza fue de 8.7 por ciento. Los datos indican que la prevalencia de Hb AS y AC en la poblacion cercana, excluyendo a Loiza, es de 3.1 por ciento, la cual es claramente distinta a la prevalencia en la comunidad de Loiza (8.7 por ciento). El hallazgo de 210 casos de hemoglobinas anormales incluyendo dos de Hb SS entre 5,473 personas cernidas y 177 de Hb AS entre 512 personas referidas indican que hay una necesidad para continuar proveyendo educacion deteccion y consejeria sobre hemoglobinopatias en la poblacion puertorriquena

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