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

Acquired factor V inhibitor: 3 cases report and literature review / 中华血液学杂志

<p><b>OBJECTIVE</b>To better understand the acquired factor V (FV) inhibitors.</p><p><b>METHODS</b>The clinical features, laboratory manifestations, treatment options and prognosis of 3 cases were reported and related literature were reviewed.</p><p><b>RESULTS</b>All the 3 patients were older than 50 years without family history and related disease. Their clinical manifestations included spontaneously mucous bleeding, hematuria, epistaxis and encephalic bleeding. Laboratory test showed prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT). The FV levels decreased and the presence of FV inhibitor was confirmed by Bethesda method. All patients were treated with glucocorticoid and immunosuppressive agents. The haemorrhages of two patients stopped but their coagulation test and FV level recovered slowly. One patient died from encephalic bleeding.</p><p><b>CONCLUSIONS</b>Acquired FV inhibitor is a rare coagulation disorder with variable clinical symptoms. Immunosuppressive agents are effective to eliminate the inhibitors. The prognosis of acquired FV inhibitors seemed to be strictly related to the basic disease.</p>

Coagulation inhibitors and activated protein C resistance in recurrent pregnancy losses in Indian women.

Background: Thrombophilias, both acquired and inherited, have been investigated in the etiopathogenesis of unexplained recurrent pregnancy loss. Aim: To study coagulation inhibitors and activated protein C resistance (APCR) in recurrent pregnancy losses (RPL) occurring in second and third trimesters. Materials and Methods: A total of 30 pregnant women (group A) with two or more recurrent unexplained fetal loses were evaluated for APCR, protein C deficiency, protein S deficiency, antithrombin deficiency, and antiphospholipid antibodies (APLA). Thirty age-matched controls were taken (group B) comprising of pregnant women with at least one live issue. Statistical Analysis: Comparisons between two group frequencies and group means were made using Chi square test and Student's t test, respectively. Results: Protein C and protein S levels were reduced in group A compared with group B and the difference was statistically significant (P=0.005 and P=0.032, respectively). The mean value of antithrombin was slightly reduced in group A compared with group B. APCR was observed in 16.6% cases and 3.3% controls. However, the difference was not statistically significant. APLA was observed in 20% cases and none of the controls. Of these, lupus anticoagulant was positive in 16.6% cases and anticardiolipin antibodies in 10% cases. Combined defects were seen in seven patients. Conclusion: There is a significant risk of RPL in pregnant women with thrombophilias. Therefore, screening for thrombophilias may be justified in pregnant women with unexplained recurrent fetal wastage, especially in second and third trimester.

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

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.

Constitutional deficits in coagulation factors

Hereditary deficit of coagulation factors is rare affection. This is a retrospective study which analyse the coagulation parameters of 25 patients with an hereditary deficit. Deficiency on factor V, VII and VIII were the most frequent. Generally without symptoms, hereditary deficiency of coagulation factors must to be diagnosing with a great prudence for prevention of hemorrhagie riskin surgery

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

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.

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

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 40.1ñ69 mg/L (Median 8.34 [3.0-47.5]) compared to 2.7ñ3.3 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 (29.5ñ43 mg/L and 49.4ñ83 mg/L respectively). Mean thrombin-antithrombin values in patients under antiplatelet agents were lower than in those without treatment (17.3ñ43 vs 66.8ñ127 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

Pacientes con trastornos de la hemostasia. Un grupo de riesgo en la atención estomatológica / Patients with hemostatic disorders: a risk group in dental care

Los pacientes con alteraciones de la hemostasia constituyen un grupo de riesgo en la atención estomatológica cuando tienen que ser sometidos a procederes que presuponen sangramiento. La hemostasia está determinada por una serie de eventos complejos que evitan que se pierda sangre del torrente circulatorio, y la falla de cualquiera de estos mecanismos provocará salida de sangre de los vasos sanguíneos, máxime si el proceder estomatológico que se va a aplicar conlleva sangramiento de tejidos. Por tal motivo se debe solicitar un estudio del caso antes de proceder, con el fin de diagnosticar qué tipo de trastorno presenta el paciente e indicar tratamiento específico en su caso. Es propósito de este trabajo incursionar en aquellos trastornos de la hemostasia que involucran a las plaquetas y alargan el tiempo de sangramiento, así como abordar las deficiencias de factores de la coagulación que afectan este importante mecanismo; por otro lado, dada su importancia, abarcaremos los efectos antiinflamatorios no esteroideos (AINES) y anticoagulantes en pacientes que necesitan un tratamiento quirúrgico estomatológico, de manera que se facilite la labor del profesional de la salud que a diario se enfrenta con problemas de esta índole y dotarlo de un conocimiento valioso en cada uno de los aspectos tratados(AU)

Patients with hemostatic disorders are a risk group in dental care when they should undergo dental procedures that presupposes bleeding. Hemostasis is determined by a series of complex events that prevent the loss of blood, so, if any of these mechanisms fails, blood will come out of the blood vessels, especially if the dental procedure to be applied involves tissue bleeding. Before performing the procedure, one should request a study of the case to diagnose what type of disorder the patient might present with and give the specific treatment. This paper is aimed at studying those hemostatic disorders that involve platelets and extend the bleeding time and dealing with the coagulation factors defects affecting this important mechanism. On the other hand, we will address the effects of non-steroidal anti-inflammatory and anticoagulant agents in patients requiring a dental surgical treatment in order to facilitate the work of a health professional who daily faces problems of this kind and provide him with valuable knowledge on each of the analyzed issues(AU)

Monitoreo de la respuesta inflamatoria / Monitoring inflammatory answer

The ill patients present frequently a systemic inflammatory response; showing problems in differing if there is an aggregated infection; it means sepsis. The objective of this article is to revise the literature about parameter evaluation which are used for monitoring the inflammatory response and its capacity to predict sepsis. Mainly, European studies show comparisons between different markers as leucocytes count, C reactive protein (CRP), procalcitonin (PCT), a new parameter described in 1993 and the interleukins. These studies reveal that the determination of cytokines and other acute phase proteins are laborious, and they do not differ if there is infection. In contrast, CPR an specially PCT show in different studies to have a sensibility and specificity over 80 percent, being similar for both. In relation with corporal temperature, leucocyte count and erythrocyte sedimentation rate do not show utility. Therefore, actually the best inflammatory markers are CRP and the PCT. In my opinion I consider the first one (CRP) not replace in our environment for the monitoring of the inflammatory response

Defectos congénitos de antitrombina III y proteínas S y C durante el embarazo / Congenital defects of antithrombin III and proteins C and S during pregnancy: report of ten cases

We report 10 patients with congenital deficiencies of the natural anticoagulant proteins S, C and antithrombin III. Thirteen of a total of 30 pregnancies were managed at the perinatal branch of our department. We discuss the mechanism of action of these proteins and their role in thrombotic events. We analyze the most frequent thrombotic complications and we discuss the general guidelines for the investigation of a patient with a suspected congenital thrombophilia with special regard to its management during pregnancy, delivery and perinatal outcome

Cofactor II de la heparina (HCII), un inhibidor de trombina cuyo rol fisiologico no esta completamente esclarecido / Heparin cofactor II, a thrombin inhibitor with a still unclarified physiologic role

El Cofactor II de la Heparina (HCII) es una proteína perteneciente al sistema de coagulación que inhibe específicamente trombina, processo que es potenciado por acción de los glicosaminoglicanos dermatán sulfato y heparina. Hasta el momento las deficiencias congénitas de HCII encontradas en forma aislada no están asociadas con eventos trombóticos, sí desarollan eventos trombóticos cuando están asociadas a otros factores predisponentes. Se observó disminución en los niveles de HCII en hepatopatías, coagulación intravascular diseminada, en anemia drepanocítica, encontrándose niveles elevados en embarazo a término y por el uso de contraceptivos orales. En el laboratorio realizamos el dosaje del HCII en la población normal de la ciudad de Buenos Aires, en diversas patologías como sepsis, quemados , anticoagulados con dicumarínicos y con heparina, diabéticos, hiperhomocisteinemia, observándose valores disminuidos principalmente en sepsis y pacientes diabéticos. El HCII es una glicoproteína que participa en la inhibición de trombina pero cuyo rol fisiológico no está completamente esclarecido. Es probable que el HCII inhiba trombina en el espacio extravascular, y está relacionado con la regulación de procesos inflamatorios y de reparación tisular.