[Colonic pseudotumoral involvement as an expression of severe plasminogen deficiency]. / Compromiso pseudotumoral colónico como expresión de déficit grave de plasminogéno.

Plasminogen deficiency is a very rare multisystem entity that affects different tissues of the economy through the deposition of fibrin-rich pseudomembrane and determines a heterogeneous and diverse clinical presentation. It is transmitted in an autosomal recessive manner by mutations of the PLG gene on chromosome 6 and can be divided into hypoplasminogenemia or type I and dysplasminogenemia or type II, the latter not related to clinical pathology. Severe plasminogen deficiency has a prevalence of 1.6 individuals per million inhabitants and although it can be diagnosed in adulthood, the most severe symptoms are observed in infants and children. The most common form of onset is the so-called woody conjunctivitis, characterized by fibrin membranes that are deposited on the eyelids since childhood, causing exophytic lesions that affect vision. It can also affect other mucous membranes such as the gingival, respiratory, oropharyngeal, digestive and genital mucosa, among others. We present a rare case of severe plasminogen deficiency with conjunctivitis and woody cervicitis who was admitted with clinical acute abdominal symptoms, associated with a tumor mass due to pseudomembranous deposition in the ascending colon that simulated inflammatory bowel disease and resolved spontaneously.

La deficiencia de plasminógeno es una entidad multisistémica, muy infrecuente, que afecta diferentes tejidos de la economía mediante el depósito de pseudo membranas ricas en fibrina y que determina una presentación clínica heterogénea y diversa. Se transmite en forma autosómica recesiva por mutaciones del gen PLG del cromosoma 6 y se puede dividir en hipoplasminogenemia o tipo I y displasminogenemia o tipo II, esta última no relacionada con patología clínica. El déficit grave de plasminógeno tiene una prevalencia de 1.6 individuos por millón de habitantes y si bien puede diagnosticarse en edad adulta, los síntomas más graves se observan en lactantes y niños. La forma de inicio más común es la denominada conjuntivitis leñosa, caracterizada por membranas de fibrina que se depositan en los parpados desde la infancia, provocando lesiones exofíticas que afectan la visión. También puede afectar otras mucosas como la gingival, respiratoria, orofaríngea, digestiva y genital entre otros. Presentamos un raro caso de deficiencia grave de plasminógeno con conjuntivitis y cervicitis leñosa que ingresó con un cuadro de abdomen agudo clínico, asociado a una masa tumoral por depósito de pseudomembranas en el colon ascendente que simuló una enfermedad inflamatoria intestinal y que se resolvió espontáneamente.

A Clot Twist: Extreme Variation in Coagulotoxicity Mechanisms in Mexican Neotropical Rattlesnake Venoms.

Rattlesnakes are a diverse clade of pit vipers (snake family Viperidae, subfamily Crotalinae) that consists of numerous medically significant species. We used validated in vitro assays measuring venom-induced clotting time and strength of any clots formed in human plasma and fibrinogen to assess the coagulotoxic activity of the four medically relevant Mexican rattlesnake species Crotalus culminatus, C. mictlantecuhtli, C. molossus, and C. tzabcan. We report the first evidence of true procoagulant activity by Neotropical rattlesnake venom in Crotalus culminatus. This species presented a strong ontogenetic coagulotoxicity dichotomy: neonates were strongly procoagulant via Factor X activation, whereas adults were pseudo-procoagulant in that they converted fibrinogen into weak, unstable fibrin clots that rapidly broke down, thereby likely contributing to net anticoagulation through fibrinogen depletion. The other species did not activate clotting factors or display an ontogenetic dichotomy, but depleted fibrinogen levels by cleaving fibrinogen either in a destructive (non-clotting) manner or via a pseudo-procoagulant mechanism. We also assessed the neutralization of these venoms by available antivenom and enzyme-inhibitors to provide knowledge for the design of evidence-based treatment strategies for envenomated patients. One of the most frequently used Mexican antivenoms (Bioclon Antivipmyn®) failed to neutralize the potent procoagulant toxic action of neonate C. culminatus venom, highlighting limitations in snakebite treatment for this species. However, the metalloprotease inhibitor Prinomastat substantially thwarted the procoagulant venom activity, while 2,3-dimercapto-1-propanesulfonic acid (DMPS) was much less effective. These results confirm that venom-induced Factor X activation (a procoagulant action) is driven by metalloproteases, while also suggesting Prinomastat as a more promising potential adjunct treatment than DMPS for this species (with the caveat that in vivo studies are necessary to confirm this potential clinical use). Conversely, the serine protease inhibitor 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF) inhibited the direct fibrinogen cleaving actions of C. mictlantecuhtli venom, thereby revealing that the pseudo-procoagulant action is driven by kallikrein-type serine proteases. Thus, this differential ontogenetic variation in coagulotoxicity patterns poses intriguing questions. Our results underscore the need for further research into Mexican rattlesnake venom activity, and also highlights potential limitations of current antivenom treatments.

von Willebrand Disease and other hereditary haemostatic factor deficiencies in women with a history of postpartum haemorrhage.

INTRODUCTION: Postpartum haemorrhage (PPH) is the main cause of maternal morbidity and mortality globally, but it is far more important in non-developed countries. PPH represents 25% of all maternal deaths worldwide. Women with von Willebrand disease (VWD) and other inherited haemorrhagic disorders are at increased risk of PPH. Our aim was to establish a probable association of severe PPH in women with a history of haemostatic abnormalities. METHODS: An observational, controlled study of adult women with a one or more episodes of severe PPH requiring treatment in an intensive care unit or >10 units of blood products during the 24-hour period after diagnosis and their controls. The tests performed were blood cell count, blood group, renal, viral, liver function and haemostatic tests, fibrinogen, activity of the plasma factors and specific test to diagnose and classify VWD. RESULTS: We included 124 women with 133 PPH events and their controls. The median age at the first event was 25.5 years old. Results were significantly different between the groups in terms of fibrinogen concentration, VWF:Ag, VWF:RCo and FVIII. A specific diagnosis was established in 69 (55.6) and 4 (3.2%) patients in the PPH group and controls, respectively. Of 61 patients with VWD, 57 had type 1, two had type 2A, and another two had type 2B. CONCLUSION: Our results show a relationship between PPH and inherited haemostatic disorders. VWD was the most frequent diagnosis. Appropriate and opportune diagnosis before pregnancy of inherited haemostatic disorders may be important to effectively prevent and treat PPH.

Anticoagulação no paciente oncologico / Anticoagulation in the oncologic patient

A doença neoplásica associa-se a um aumento da incidência de eventos tromboembólicos. Os fatores associados a esses fenômenos englobam não apenas o estado pró-trombótico associado ao câncer, mas também os efeitos colaterais dos quimioterápicos, além da imobilidade associada a algumas situações, como intervenções cirúrgicas, por exemplo. De acordo com a American Cancer Society (ACS), que desenvolveu a mais recente diretriz sobre profilaxia e tratamento da TVP em pacientes oncológicos, somando os fatores de risco já existentes aos fatores intrínsecos dos pacientes oncológicos, esses pacientes são, quase sempre, classificados como de alto risco. A simplicidade de administração oral sem necessidade de monitorização laboratorial torna os novos anticoagulantes orais uma alternativa atrativa para a prevenção e o manejo de eventos tromboembólicos em pacientes oncológicos. Subgrupos de estudos maiores demonstram a eficácia e segurança dessa classe de fármacos nesse grupo de pacientes, porém, mais estudos estão sendo conduzidos, a fim de responder com mais clareza a esta questão. O estado pró-trombótico promovido pela doença neoplásica acarreta maior risco de fenômenos embólicos em pacientes oncológicos com fibrilação atrial (FA). Não existem recomendações específicas para terapia antitrombótica para pacientes com FA e câncer. Não há evidência que essa população apresente risco aumentado de acidente vascular cerebral embólico em comparação com os pacientes com FA sem neoplasia associada. Os pacientes portadores de FA e câncer concomitantemente são mais idosos do que os pacientes portadores apenas de FA. Ainda existem muitas controvérsias com relação à anticoagulação no paciente oncológico. Novos estudos com foco nessa temá- tica contribuirão muito para o manejo mais homogêneo e embasado nessa população

Neoplastic disease is associated with an increase in the incidence of thromboembolic events. Factors associated with these phenomena include not only the prothrombotic state associated with cancer, but also the side effects of chemotherapy, and the immobility associated with certain situations, such as surgical interventions. According to the American Cancer Society (ACS), which produced the latest guidelines on prophylaxis and treatment of DVT in cancer patients, adding the existing risk factors to the intrinsic factors of cancer patients, these patients are almost always classified as high risk. The simplicity of oral administration, without the need for laboratory monitoring, makes the new oral anticoagulants an attractive alternative in the prevention and management of thromboembolic events in cancer patients. Subgroups of larger studies demonstrate the efficacy and safety of this class of drugs in this group of patients. However, further studies are being conducted in order to answer this question more clearly. The prothrombotic state promoted by the neoplastic disease presents a higher risk of embolic phenomena in cancer patients with atrial fibrillation (AF). There are no specific recommendations for antithrombotic therapy in patients with AF and cancer. There is no evidence that this population presents an increased risk of embolic cerebrovascular event compared to patients with AF without associated neoplasia. It is known that cancer patients with concomitant cancer and AF are older than non-cancer patients. There is still much controversy regarding anticoagulation in cancer patients. New studies focusing on this theme will contribute to a more homogeneous and grounded management of this population

Diagnóstico laboratorial de coagulopatías hemorrágicas en pacientes del Hospital Nacional de Itauguá / Laboratory diagnosis of hemorrhagic coagulopathies in patients of the National Hospital of Itauguá

Introducción: la hemostasia es el conjunto de sistemas que actúan coordinadamente para mantener la integridad de los vasos sanguíneos y la fluidez de la sangre; la alteración puede desencadenar trastornos trombóticos o hemorrágicos, dependiendo de la naturaleza de la falla. Objetivos: describir las coagulopatías hemorrágicas que se registraron en el departamento de laboratorio del Hospital Nacional de Itauguá, desde julio 2014 hasta diciembre 2015, obtener frecuencia y datos demográficos, edad, sexo, procedencia y clasificar las coagulopatías según deficiencias de factores de la coagulación, vía extrínseca, vía intrínseca y vía común final; sospecha de inhibidores adquiridos y enfermedad de von Willebrand. Material y Métodos: diseño observacional, descriptivo, retrospectivo de corte trasverso; incluyéndose pacientes de ambos sexos, todas las edades, derivados de médicos hematólogos. Resultados: se registraron 77 pacientes con coagulopatías hemorrágicas en el Laboratorio, 43 fueron del sexo masculino, de 1 a 75 años, mediana 18 años; 31% (24/77) con deficiencias del factor VII, todos leves, edades 7 a 75 años. En la vía intrínseca, la deficiencia del factor VIII o Hemofilia A, fue la más observada 29%(22/77), mayoría severas (13/22), mientras que déficit de factor IX, Hemofilia B, en 4 pacientes 5%(4/77). 85% Hemofilia A y 15% Hemofilia B, edades 1 y 64 años, mediana 13,5 años, todos del sexo masculino; no se registraron deficiencias de FXI y FXII en el periodo de estudio. De la vía común final, se encontraron 3 pacientes con hipofibrinogenemia, 1 con probable disfibrinogenemia, 1 con déficit de Factor II, 2 de Factor V y 2 de Factor X, 2 adultas, y el resto pediátricos; estas deficiencias son muy poco frecuentes, Factor I, V y X de 1/1.000.000 y FII 1/2.000.000 personas. Quince pacientes con sospecha de inhibidores, dos de ellas con inhibidor específico anti-FVIII, y probables inhibidores de interferencia. Se confirmó el primer déficit de factor Von Willebrand, en una mujer de 47 años. Conclusiones: entre las coagulopatías hemorrágicas de mayor frecuencia, se encuentran las Hemofilias A y B, seguida de deficiencias del factor VII y probables inhibidores de interferencia, los dos casos de inhibidores específicos anti Factor VIII fueron en pacientes con Hemofilia A severa. Fue relevante también el hallazgo de deficiencias de la vía común de la coagulación, a pesar de ser poco frecuentes. Algunos pacientes fueron diagnosticados en edad adulta, reflejando lo tardío que se llega al diagnóstico en el país.

Introduction: hemostasis is the set of systems that work in concert to maintain the integrity of blood vessels and blood flow; alteration can trigger thrombotic disorders or bleeding, depending on the nature of the fault Objective: describe hemorrhagic coagulopathy registered in the Medical Laboratory Department diagnosis at the National Hospital of Itauguá, from July 2014 to December 2015, obtain frequency and demographics, age, sex, origin and classify coagulopathy in to deficiencies of coagulation factors of the extrinsic pathway, intrinsic pathway, and common pathway; suspicion acquired inhibitors and von Willebrand's disease. Material and Methods: the design was an observational, descriptive, retrospective cross sectional study; being including patients of both sexes, all ages, referred by hematologists. Results: 77 patients with hemorrhagic coagulopathies, were female 43 male and 34 female, from 1 to 75 years, median age of 18 years; 31% (24/77) with factor VII deficiency, all mild, ages 7 to 75, 1 / 500,000 appears. In the intrinsic pathway, the factor VIII deficiency or hemophilia A, was the most observed 29% (22/77) severe majority (13/22), while Factor IX deficit, Hemophilia B, in 5% of patients (4/77). 85% Hemophilia A, and 15% Hemophilia B, ages 1 to 64 years, median age of 13.5 years, all male; no FXI and FXII deficiencies were recorded in the study period.Of the final common pathway, 3 patients with hipofibrinogenemia were found, 1 probable dysfibrinogenaemia, 1 deficiency of FII, 2 FV and FX 2, 2 were adult and the rest were pediatric; these deficiencies are rare, FI, V and X of 1 / 1,000,000 and FII 1 / 2,000,000 people. Fifteen patients with suspected inhibitors adquired, two of them with anti-FVIII specific inhibitor, and probable interference inhibitors. The first von Willebrand, factor deficiency was confirmed in a woman of 47 years. Conclusions: among the most frequent hemorrhagic coagulation disorders, we found hemophilia A and B, followed by deficiencies of factor VII and probable interference inhibitors both cases of specific inhibitors of factor VII were found in patients with severe Hemophilia A. Some patients were diagnosed in adulthood

Do PT and APTT sensitivities to factors' deficiencies calculated by the H47-A2 2008 CLSI guideline reflect the deficiencies found in plasmas from patients?

INTRODUCTION: Prothrombin time (PT) and activated partial thromboplastin time (APTT) sensitivity for detecting isolated factor deficiencies varies with different reagents and coagulometers. The Clinical and Laboratory Standards Institute (CLSI) H47A2 guideline proposed a method to calculate these sensitivities, but some inconsistency has been reported. This study aimed to calculate factor sensitivities using CLSI guideline and to compare them with those obtained from single factor-deficient patients' data. METHODS: Different mixtures of normal pooled and deficient plasmas were prepared (<1IU/dL to 100 IU/dL) according to the CLSI H47A2 guideline. PT with rabbit brain (RB) and human recombinant (HR) thromboplastins, APTT and factors' activities were measured in an ACL TOP coagulometer. Sensitivities (maximum factor concentration that produces PT or APTT values out of the reference range) were calculated from mixtures and from patients with single-factor deficiencies: 17 factor FV, 36 FVII, 19 FX, 39 FVIII, 15 FIX 15 FXI and 24 FXII. RESULTS: PT sensitivity with RB was as follows: FV 38 and 59, FVII 35 and 58, FX 56 and 64 IU/dL; PT sensitivity with HR was as follows: FV 39 and 45, FVII 51 and 50, FX 33 and 61 IU/dL; and APTT sensitivity was as follows: FV 39 and 45, FX 32 and 38, FVIII 47 and 60, FIX 35 and 44, FXI 33 and 43, FXII 37 and 46 IU/dL, respectively. CONCLUSIONS: Reagent-coagulometer combination has adequate sensitivities to factor deficiencies according to guideline recommendations (>30 IU/dL). These should not be considered as actual sensitivities because those obtained by analysing patients' plasmas with single-factor deficiencies were higher for most factors and could induce misinterpretation of the basic coagulation test results.

Concentrado de complejo protrombínico para el tratamiento de deficiencias congénitas o adquiridas en factores de coagulación / Concentrate of prothrombin complex for the treatment of congenital or acquired deficiencies in coagulation factors

INTRODUCCIÓN: Los FII, FVII, FIX y FX son denominados como factores de coagulación dependientes de vitamina K. La deficiencia adquirida de estos factores comúnmente ocurre durante el tratamiento de antagonistas de la vitamina K. Estas situaciones pueden ser revertidas por la suspensión del tratamiento con antagonistas de vitamina K, la administración de vitamina K o la administración de plasma fresco congelado (PFC). Sin embargo, en pacientes con hemorragia severa espontánea o inducida por traumatismo, o pacientes con riesgo de hemorragia que requieran una intervención de emergencia, la administración de concentrado de complejo protrombínico parece ser una opción más adecuada. La Hemofilia A (deficiencia de FVIII), B (deficiencia de FIX) y la enfermedad de von Willebrand (deficiencia de factor von Willebrand) representan la mayor parte los desórdenes de la coagulación congénitos. El tratamiento consiste básicamente en la reposición de los FVIII y FIX en dos modalidades: a demanda o preventivo. En Uruguay se encuentra incluido en el FTM únicamente el FVIII, el cual está indicado para el tratamiento y profilaxis de hemorragias en pacientes con hemofilia A (deficiencia congénita del factor VIII) y deficiencia adquirida del FVIII. Adicionalmente se encuentra disponible en el mercado nacional, pero no incluidos en el FTM el FVIIa, FVIII con factor de Willebrand y FIX. Octaplex® es un concentrado de complejo protrombínico (CCP) de administración intravenosa conteniendo como principios activos Factor II, Factor VII, Factor IX, Factor X, proteína C, proteína S y heparina.OBJETIVOS: Evaluar la eficacia y seguridad del concentrado de complejo protrombínico (CCP) para el tratamiento deficiencias congénitas o adquiridas en factores de coagulación. MÉTODOS: Se realizó una revisión sistemática de la evidencia clínica y posterior análisis de las principales variables de eficacia y seguridad. RESULTADOS: Los 2 principales estudios de Octaplex® incluyeron pacientes en tratamiento con anticoagulantes con hemorragia grave o que requerían de una intervención quirúrgica o de un procedimiento diagnóstico invasivo urgente. El estudio LEX-201 incluyó solamente 10 pacientes con hemofilia B o deficiencia del FVII, por lo que no fue considerado. Fueron identificados otros 10 estudios, los cuales evaluaron otras marcas comerciales con similar composición a Octaplex®. Esto hace que los resultados deban ser considerados con cautela, principalmente los de seguridad. Los ensayos fueron mayormente no controlados y con bajo número de pacientes, por lo que la calidad de la evidencia no es óptima. Los pacientes tratados con CCP (Octaplex®) presentaron una reducción del INR a partir de los 10 a 15 minutos post-infusión, al igual que un aumento en las concentraciones de los factores de coagulación. En cuanto a seguridad, el tratamiento con CCP principalmente puede producir transmisiones virales como hepatitis A u otros (4 de 80 pacientes) y aumento en la incidencia de eventos tromboembólicos. DISCUSIÓN: El producto Octaplex® es utilizado desde hace varios años en distintos países, sin embargo cuenta con una reducida evaluación clínica. En particular, no tiene ningún ensayo clínico finalizado comparando Octaplex® versus PFC. La falta de evidencia no permite conocer la eficacia y seguridad de Octaplex® en el tratamiento de deficiencias congénitas en factores de coagulación dependientes de vitamina K, siendo los ensayos mayormente en población con deficiencias adquiridas. CONCLUSIONES: La inclusión del CCP al FTM puede presentar beneficios clínicos en el tratamiento de pacientes que requieren de profilaxis, reposición perioperatoria y tratamiento de hemorragias graves con deficiencia adquirida de factores de coagulación del complejo protrombínico, cuando sea requerida una corrección rápida de la deficiencia. No hay suficiente evidencia clínica que permita recomendar la utilización de CCP en otras indicaciones. Previo a la toma de decisión, es necesario contar con un impacto presupuestal de la inclusión de este medicamento desde la perspectiva del sistema de salud.(AU)

Hematoma after augmentation mammaplasty in a patient with von Willebrand's disease / Hematoma após mamaplastia de aumento em paciente portadora de doença de von Willebrand

We present the case of a patient submitted to augmentation mammaplasty who developed 2 hematoma episodes as a result of von Willebrand's disease, which was not previously diagnosed. As a routine part of preoperative evaluation, the patient should always be tested for von Willebrand's disease. This disease affects 1-3 percent of the population and occurs twice as often as hemophilia. In our case, the patient recovered quite satisfactorily. Preventive and therapeutic approaches are discussed in this paper.

Os autores relatam o caso de uma paciente submetida a mamaplastia de aumento, não diagnosticada previamente como portadora de doença de von Willebrand, que teve dois episódios de hematoma no pós-operatório. Entre os distúrbios de coagulação, a doença de von Willebrand deve ser considerada na avaliação pré-operatória, pois afeta cerca de 1 por cento a 3 por cento da população, não é diagnosticada na maioria das pessoas, além de ser duas vezes mais frequente que a hemofilia. A paciente evoluiu bem no pós-operatório e medidas preventivas e terapêuticas são discutidas neste artigo.

Trastornos de la hemostasia durante la gestación / Hemostasia disorders during pregnancy

Se realizó una revisión de la literatura en relación con los trastornos hemorrágicos durante la gestación y se mencionan los cambios hematológicos fisiológicos que ocurren durante el embarazo y el puerperio. La conocida teoría de la coagulación como un proceso en cascada no tiene vigencia en la actualidad, sino que esta ha dado paso a la moderna teoría celular de la coagulación. Se describen también los criterios diagnóstico y terapéutico en las hemorragias obstétricas por incoagulabilidad sanguínea (HOICS). Al analizar el cuadro clínico y los resultados de laboratorio, se puede realizar un diagnóstico seguro de la HOICS que se presenta. La disminución de las plaquetas en sangre, constituye con frecuencia en los casos de HOICS la alteración inicial, el factor V de la coagulación siempre está disminuido, mientras que el factor VIII de la coagulación, generalmente se encuentra elevado. El uso de heparina de alto y bajo peso molecular, y de factores de la coagulación para el tratamiento de las HOICS ha sido controvertido. Se ha recomendado en estos casos la administración de sangre fresca, plasma fresco, plasma homólogo, crioprecipitados y concentrado de plaquetas. Actualmente, se vienen remplazando estas conductas terapéuticas por el uso del FVIIa recombinante, el cual puede asociarse con el misoprostol. La evacuación de la cavidad uterina tan pronto como sea posible constituye una medida necesaria en algunas pacientes (AU)

A literature review was performed in relation to hemorrhagic disorders during pregnancy signaling the physiologic and hematologic changes occurring at pregnancy and the puerperium. The well-known theory of coagulation as a cascade process has not validity at present time, but that this one gave way to the modern cellular theory of coagulation. The diagnostic and therapeutical in blood incoagulability obstetrics hemorrhages (BIOH). Analyzing the clinical picture and the lab results, it is possible to make an accurate diagnosis of present BIOHs. The blood platelet decrease, frequently in BIOH cases is the first alteration, the V coagulation factor, in general is always decreased, whereas the VIII coagulation factor is in general increased. The high and low weight heparin use and of coagulation factors for treatment of BIOHs has been controversial. In such cases it is recommended the administration of fresh blood, fresh plasma, the homologous plasma cryoprecipitates and platelet concentrates. Nowadays these therapeutical behaviors have been replaced by the use of recombinant FVIIa, which may be associated with the Misoprostol. The uterine cavity evacuation as soon as possible is a needed measure in some patients.(AU)

Trastornos de la hemostasia durante la gestación / Hemostasia disorders during pregnancy

Se realizó una revisión de la literatura en relación con los trastornos hemorrágicos durante la gestación y se mencionan los cambios hematológicos fisiológicos que ocurren durante el embarazo y el puerperio. La conocida teoría de la coagulación como un proceso en cascada no tiene vigencia en la actualidad, sino que esta ha dado paso a la moderna teoría celular de la coagulación. Se describen también los criterios diagnóstico y terapéutico en las hemorragias obstétricas por incoagulabilidad sanguínea (HOICS). Al analizar el cuadro clínico y los resultados de laboratorio, se puede realizar un diagnóstico seguro de la HOICS que se presenta. La disminución de las plaquetas en sangre, constituye con frecuencia en los casos de HOICS la alteración inicial, el factor V de la coagulación siempre está disminuido, mientras que el factor VIII de la coagulación, generalmente se encuentra elevado. El uso de heparina de alto y bajo peso molecular, y de factores de la coagulación para el tratamiento de las HOICS ha sido controvertido. Se ha recomendado en estos casos la administración de sangre fresca, plasma fresco, plasma homólogo, crioprecipitados y concentrado de plaquetas. Actualmente, se vienen remplazando estas conductas terapéuticas por el uso del FVIIa recombinante, el cual puede asociarse con el misoprostol. La evacuación de la cavidad uterina tan pronto como sea posible constituye una medida necesaria en algunas pacientes

A literature review was performed in relation to hemorrhagic disorders during pregnancy signaling the physiologic and hematologic changes occurring at pregnancy and the puerperium. The well-known theory of coagulation as a cascade process has not validity at present time, but that this one gave way to the modern cellular theory of coagulation. The diagnostic and therapeutical in blood incoagulability obstetrics hemorrhages (BIOH). Analyzing the clinical picture and the lab results, it is possible to make an accurate diagnosis of present BIOHs. The blood platelet decrease, frequently in BIOH cases is the first alteration, the V coagulation factor, in general is always decreased, whereas the VIII coagulation factor is in general increased. The high and low weight heparin use and of coagulation factors for treatment of BIOHs has been controversial. In such cases it is recommended the administration of fresh blood, fresh plasma, the homologous plasma cryoprecipitates and platelet concentrates. Nowadays these therapeutical behaviors have been replaced by the use of recombinant FVIIa, which may be associated with the Misoprostol. The uterine cavity evacuation as soon as possible is a needed measure in some patients.

Coagulación intravascular diseminada / Disseminated intravascular coagulation

Se describe la coagulación intravascular diseminada (CID), es un síndrome clínico patológico adquirido resultante de la activación y estimulación excesiva del sistema de coagulación.

High prevalence of bleeders of unknown cause among patients with inherited mucocutaneous bleeding. A prospective study of 280 patients and 299 controls.

BACKGROUND AND OBJECTIVES: Mucocutaneous bleeding (MCB) is the main expression of inherited disorders of primary hemostasis. However, the relative prevalence of these disorders, their clinical differential diagnosis, and the proportion of patients with MCB of unknown cause (BUC) after an initial comprehensive laboratory testing are unknown. DESIGN AND METHODS: We studied prospectively 280 consecutive patients with MCB and 299 matched controls, using strict inclusion and exclusion criteria. A single physician recorded the clinical data in a bleeding score and estimated the severity of bleeding in clinical categories. Laboratory criteria for the diagnosis of von Willebrand's disease (VWD) and platelet function defects were established from reference values derived from controls. RESULTS: Fifty patients (17.9%) had VWD (type 1VWD=45, type 2=5). Platelet function defects and mild clotting factor deficiencies were found in 65 (23.2%) and 11 (3.9%) patients, respectively. Thirteen (11.5%) patients had combined defects. The remaining 167(59.6%) patients had BUC, with prolonged bleeding time in 18.6% as their only abnormality. All these disorders, including BUC, were clinically undistinguishable. Moreover, no relationship was found between the severity of bleeding and VWF/platelet function variables. INTERPRETATION AND CONCLUSIONS: The diagnostic efficacy of a first laboratory testing in patients with hereditary MCB is 40.4%. Most patients have a disease(s) of high prevalence but unknown pathogenesis. Concurrent bleeding disorders in the same patient are frequent. Our results support the proposal that low plasma VWF levels, but also platelet function defects, should be considered risk factors rather than unequivocal causes of hemorrhages.

Nuevos abordajes en cáncer dirigiendo el Factor tisular a blancos vasculares tumorales / New approaches in cancer therapies targeting tissue factor to tumor vessels

La presente revisión se basa en el hecho de que el factor Tisular, la proteina humana inductora de la coagulación sanguínea, es el principal iniciador de la coa-gulación sanguínea. El objetivo de este trabajo fue revisar la literatura en angiogenesis , como nuevo abordaje en las terapias en cáncer y así también la factibilidad de tratar tumores sólidos dirigiendo el Factor Tisular humano contra blancos vasculares endometriales del tumor, como nuevas terapias en cáncer. Mostrando en un modelo animal la efectividad del factos Tisular, que en el abordaje generaron trombosis selectiva en tumores sólidos e inhibición del crecimiento celular, con la subsiguiente regresión, necrosis e infarto del tumor, usando para ello diferentes líneas celulares tumorales xenotransplantadas en ratones. Analizando la caracterización del factor tisular recombinante(rTF) fusionado con anticuerpos, fragmentos de anticuerpos y péptidos que reconecen y hacen blanco en los marcadores naturales de vasos tumorales y que son altamente expresados en las células endoteliales tumorales y, no así en tejidos normales. Conclusión: este trabajo trata de mostrar la inhibición efectiva del crecimiento de tumores humanos en vivo dirigiendo el rTF fusionado, contra marcadores naturales de la angiogenesis tumoral con el objetivo de generar coagulación intraluminal sanguínea selectiva de los vasos tumorales

Nuevos abordajes en cáncer dirigiendo el Factor tisular a blancos vasculares tumorales / New approaches in cancer therapies targeting tissue factor to tumor vessels

La presente revisión se basa en el hecho de que el factor Tisular, la proteina humana inductora de la coagulación sanguínea, es el principal iniciador de la coa-gulación sanguínea. El objetivo de este trabajo fue revisar la literatura en angiogenesis , como nuevo abordaje en las terapias en cáncer y así también la factibilidad de tratar tumores sólidos dirigiendo el Factor Tisular humano contra blancos vasculares endometriales del tumor, como nuevas terapias en cáncer. Mostrando en un modelo animal la efectividad del factos Tisular, que en el abordaje generaron trombosis selectiva en tumores sólidos e inhibición del crecimiento celular, con la subsiguiente regresión, necrosis e infarto del tumor, usando para ello diferentes líneas celulares tumorales xenotransplantadas en ratones. Analizando la caracterización del factor tisular recombinante(rTF) fusionado con anticuerpos, fragmentos de anticuerpos y péptidos que reconecen y hacen blanco en los marcadores naturales de vasos tumorales y que son altamente expresados en las células endoteliales tumorales y, no así en tejidos normales. Conclusión: este trabajo trata de mostrar la inhibición efectiva del crecimiento de tumores humanos en vivo dirigiendo el rTF fusionado, contra marcadores naturales de la angiogenesis tumoral con el objetivo de generar coagulación intraluminal sanguínea selectiva de los vasos tumorales

[Thrombophilic disorders in children and adolescents with portal vein thrombosis]. / Distúrbios trombofílicos em crianças e adolescentes com trombose da veia porta.

OBJECTIVE: To determine the frequency of protein C, protein S and antithrombin deficiency, and factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations in children and adolescents with portal vein thrombosis, as well as assessing the hereditary character of this disorders. METHODS: A two-year study was carried out to determine the frequency of thrombophilic disorders in children and adolescents with portal vein thrombosis (n = 14), their parents (n = 24), and two control groups, one age-matched children and adolescents free of liver disease (n = 28) and another group with cirrhosis (n = 24). The portal vein thrombosis patients were investigated by clinical and laboratory means, esophagogastroduodenal endoscopy and liver biopsies. The presence of portal vein thrombosis was assessed by Doppler ultrasonography and/or angiographic analysis. RESULTS: The frequency of protein C, protein S and antithrombin deficiency was 6/14 (42.9%) (p < 0.05 versus controls), 3/14 (21.4%) (p > 0.05) and 1/14 (7.1%) (p > 0.05) of children and adolescents with portal vein thrombosis, respectively. The frequency of protein C, protein S and antithrombin deficiency in cirrhotic patients was 14/24 (58.3%), 7/24 (29.2%) and 11/24 (45.8%), respectively (p < 0.05 versus controls free of liver disease). None of the portal vein thrombosis parents or controls presented protein C, protein S or antithrombin deficiency. One portal vein thrombosis patient and one control (p = 0.999) presented prothrombin G20210A mutation. The homozygous form of methylenetetrahydrofolate reductase C677T mutation was observed in 3/14 (21.4%) patients with portal vein thrombosis and in 5/28 (17.9%) (p = 0.356) controls. None of the patients or controls presented the factor V Leiden. CONCLUSION: Half of the children and adolescents with portal vein thrombosis presented deficiency of one or more coagulation inhibitor proteins, mainly protein C, but this deficiency does not seem to be an inherited condition. The hereditary prothrombotic disorders do not seem to play a vital role in thrombosis in patients with portal vein thrombosis of this study. In the cirrhotic patients, there was a higher frequency of protein deficiency when the disease was more intense.

Tratamiento de fractura de femur en paciente hemofilico: caso clínico del servicio de Ortopedía y Traumatología del Hospital General / Treatment of fracture of femur in hemofilico patient

La hemofilia siendo un trasntorno de coagulación por deficiencia de factores como el factor VIII de la hemofilia clásica o A, o el factor IX de la hemofilia B o enfermedad de Chistmas, ambos solo diferenciados en el análisis de la actividad de factores. Enfermedad que solo afecata varones por su transmisión ligada al cromosoma X. La predisposión de ocurrencias de fracaturas en pacientes hemofilicos aun por lesiones minimas es ocasionado por la osteoporosis, limitación articular y atrofia muscular patologicos. No esta recomendado uso de tracción esquelética debido a riesgo de hemorragia en sitio de inserción de los clavos, pese a existir trabajos con resultados adecuados, cuando obtienen niveles de facatores plasmaticos. Se debe iniciar de forma inmediata al trauma la repòsición de factores para así disminuir el hematoma resultante. Debido a que la velocidad de consolidación es el mismoq ue pacientes normales, y cuando se consigue niveles de facatos adecuado las indicaciones de fijación interna son las mismas que para otros pacientes, ya en los trabajos de Fiel se recomienda la fijación interna para así evitar desplazamientos con hemooragias a repetición.

[Hypercoagulability in atrial fibrillation and its relationship with risk factors for systemic embolism]. / Hipercoagulabilidad en fibrilación auricular y su relación con factores de riesgo para embolia sistémica.

BACKGROUND: Atrial fibrillation is associated to a high risk of systemic embolism and to hypercoagulability. AIM: To evaluate the activation of the coagulation cascade through determinations of the thrombin-antithrombin complex in patients with atrial fibrillation and to correlate this data with the clinical and echocardiographic risk factors for systemic embolism. PATIENTS AND METHODS: In 53 patients with atrial fibrillation plasma levels of the thrombin-antithrombin complex were determined on admission to a coronary care unit and 30 days later. Using a univariate and multiple regression analysis, the association basal thrombin-antithrombin with the duration of the arrhythmia, age over 70 years, previous use of antiplatelet agents, history of hypertension, mitral valve disease, diabetes, heart failure, previous systemic embolism, left atrial diameter and the presence of spontaneous contrast echo or thrombus in the left atrial appendage, was studied. RESULTS: Basal thrombin-antithrombin values were 40.1 +/- 69 mg/L (Median 8.34 [3.0-47.5]) compared to 2.7 +/- 3.3 mg/L in healthy controls (p < 0.001). No significant correlation was found between activation of the coagulation cascade and risk factors for systemic embolism. There were no significant differences in thrombin-antithrombin values between patients with chronic or paroxysmal atrial fibrillation (29.5 +/- 43 mg/L and 49.4 +/- 83 mg/L respectively). Mean thrombin-antithrombin values in patients under antiplatelet agents were lower than in those without treatment (17.3 +/- 43 vs 66.8 +/- 127 mg/L; p = 0.018). CONCLUSIONS: The activation of the coagulation cascade in patients with atrial fibrillation was confirmed. However, no association of this activation with well known clinical and echocardiographic risk factors for systemic embolism, was found. Previous antiplatelet treatment prevented a higher activation of the coagulation cascade.