Consensus on hemophilia in Mexico.

Hemophilia is a hemorrhagic disorder with a sex-linked inherited pattern, characterized by an inability to amplify coagulation due to a deficiency in coagulation factor VIII (hemophilia A or classic) or factor IX (hemophilia B). Sequencing of the genes involved in hemophilia has provided a description and record of the main mutations, as well as a correlation with the various degrees of severity. Hemorrhagic manifestations are related to levels of circulating factor, mainly affecting the musculoskeletal system and specifically the large joints (knees, ankles, and elbows). This document is a review and consensus of the main genetic aspects of hemophilia, from the inheritance pattern to the concept of women carriers, physiopathology and classification of the disorder, the basic and confirmation studies when hemophilia is suspected, the various treatment regimens based on infusion of the deficient coagulation factor as well as innovative factor-free therapies and recommendations for the management of complications associated with treatment (development of inhibitors and/or transfusion-transmitted infections), or secondary to articular hemorrhagic events (hemophilic arthropathy). Finally, relevant reviews of clinical and treatment aspects of hemorrhagic pathology characterized by acquired deficiency of FVIII secondary to neutralized antibodies named acquired hemophilia.

La hemofilia es un trastorno hemorrágico con patrón de herencia ligado al sexo, caracterizado por una incapacidad en la amplificación de la coagulación ocasionada por la deficiencia del factor VIII (hemofilia A o clásica) o del factor IX (hemofilia B). La secuenciación de los genes involucrados en la hemofilia ha permitido la descripción y registro de las principales mutaciones, así como la correlación con los diversos grados de severidad. Las manifestaciones hemorrágicas se relacionan con los niveles de factor deficiente circulante, afectando principalmente al sistema musculoesquelético y en particular a las grandes articulaciones (rodillas, tobillos y codos). El presente documento hace una revisión y consenso de los principales aspectos genéticos de la hemofilia, desde el patrón de herencia y el concepto de mujeres portadoras, la fisiopatología y clasificación de la enfermedad, los estudios básicos y de confirmación ante la sospecha de hemofilia, y de los diversos esquemas de tratamiento basados en la infusión del factor de coagulación deficiente hasta las terapias innovadoras libres de factor, así como de las recomendaciones para el manejo de las complicaciones asociadas al tratamiento (desarrollo de inhibidores y/o infecciones transmitidas por transfusión) o secundarias a los eventos hemorrágicos a nivel articular (artropatía hemofílica). La parte final del documento revisa los aspectos clínicos y de tratamiento relevantes de una patología hemorragica caracterizada por la deficiencia adquirida del FVIII mediada por anticuerpos neutralizantes denominada hemofilia adquirida.

Consenso de hemofilia en México / Mexican Consensus in Haemophilia

resumen está disponible en el texto completo

Abstract Hemophilia is a hemorrhagic disorder with a sex-linked inherited pattern, characterized by an inability to amplify coagulation due to a deficiency in coagulation factor VIII (hemophilia A or classic) or factor IX (hemophilia B). Sequencing of the genes involved in hemophilia has provided a description and record of the main mutations, as well as a correlation with the various degrees of severity. Hemorrhagic manifestations are related to levels of circulating factor, mainly affecting the musculoskeletal system and specifically the large joints (knees, ankles and elbows). This document is a review and consensus of the main genetic aspects of hemophilia, from the inheritance pattern to the concept of women carriers, physiopathology and classification of the disorder, the basic and confirmation studies when hemophilia is suspected, the various treatment regimens based on infusion of the deficient coagulation factor as well as innovative factor-free therapies and recommendations for the management of complications associated with treatment (development of inhibitors and/or transfusion transmitted infections) or secondary to articular hemorrhagic events (hemophilic arthropathy). Finally, relevant reviews of clinical and treatment aspects of hemorrhagic pathology charachterized by acquired deficiency of FVIII secondary to neutralized antibodies named acquired hemophilia.

Preoperative recipient cytokine levels are associated with early lung allograft dysfunction.

BACKGROUND: Primary graft dysfunction (PGD) is a morbid complication after lung transplant (LTx). Recipient before and after cytokine and chemokine profiles may be associated with a recipient's propensity to have PGD. METHODS: Serum samples were obtained from adult (more than 17 years old) primary LTx recipients (2002 to 2007) at two time points: (1) pre-reperfusion of transplanted lungs, and (2) within 24 hours after reperfusion. Interleukin (IL)-6, IL-8, IL-10, chemokine ligand (CCL)-2, and matrix metalloproteinase (MMP)-9 levels were determined. A PaO2/FiO2 ratio less than 300 at 48 hours (International Society for Heart and Lung Transplantation PGD grade 2 or more) was used to stratify patients. Follow-up was obtained through August 2009. Cytokine levels at both time points and the change in levels were assessed for association with PGD grade 2 or more. Outcomes and clinical characteristics were analyzed. RESULTS: Of 28 patients, 8 (28.6%) had PGD grade 2 or more. Median follow-up was 23 months (interquartile range, 16 to 31). Demographics, clinical data, and pre-LTx diagnoses did not differ between the groups. Patients who had PGD grade 2 or more had higher baseline levels of IL-10, IL-8, IL-6, and CCL-2 (all p<0.05). Within 24 hours, PGD grade 2 or more patients had higher IL-10 (p=0.02) and CCL-2 (p=0.04) levels. The PGD grade 2 or more patients were more likely to have had cardiopulmonary bypass during LTx (p=0.002) and blood products administered: platelets (p=0.004), plasma (p=0.05), and packed red blood cells (p=0.03)]. The PGD grade 2 or more patients had longer length of stay, duration of mechanical ventilation, and total intensive care unit days. CONCLUSIONS: Higher before and after transplant cytokine/chemokine levels were found in LTx recipients who subsequently had PGD grade 2 or more. Our study demonstrates that the recipient's inflammatory state at the time of LTx may impact early allograft function. That could represent a potential target for pretransplant pharmacologic intervention.

Loss of types XV and XIX collagen precedes basement membrane invasion in ductal carcinoma of the female breast.

Ductal and lobular carcinomas comprise most malignancies of the female breast and the morbidity and mortality associated with breast cancer. During the progression from in situ to invasive stages, tumour cells penetrate the epithelial and vascular basement membranes (BM) to realize full metastatic potential. While the definition of these structures has primarily resulted from analysis of laminin and type IV collagen, characterization of newly discovered BM/BM zone (BMZ) proteins will further elucidate the interactions between tumour cells and the host stroma. We have studied the expression of two non-fibrillar BMZ collagens, the type XV proteoglycan and collagen XIX, in breast cancer where a linear, well-formed BM becomes fragmented and even lost in the progression of epithelial malignancy. In the normal breast, types XV and XIX were found in all BMZ: epithelial, muscle, neural, endothelial, and fat. In in situ lesions, these two collagens, and particularly type XV, were often absent from the BM/BMZ displaying a continuous or just focally disrupted type IV/laminin staining pattern. In contrast, infiltrating ductal carcinomas showed only rare traces of laminin and collagen IV reactivity adjacent to the glands and tumour nests, and similarly there was little if any evidence of types XV and XIX collagen. All four molecules were, however, detected in the interstitium associated with some of the invasive carcinomas. The data suggest that types XV and XIX collagen are lost early in the development of invasive tumours, prior to penetration and eventual dissolution of the epithelial BM. Disappearance of these proteins from the BM/BMZ may signal remodelling of the extracellular matrix to promote tumour cell infiltration.