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Introducción: La enfermedad traumática grave es la sexta causa de muerte a nivel mundial, un elevado porcentaje de fallecidos se atribuye a hemorragias no controladas. En Cuba se carece de estudios sobre variables predictoras de mortalidad precoz en pacientes hospitalizados con trauma hemorrágico. Objetivo: Identificar variables predictoras de mortalidad precoz en pacientes hospitalizados con trauma hemorrágico. Métodos: Se realizó un estudio observacional, analítico, transversal, que incluyó 207 pacientes con trauma hemorrágico, en el Hospital General Provincial Camilo Cienfuegos de Sancti Spíritus, En el período comprendido entre los años 2012 y 2017. Las variables se agruparon en sociodemográficas, enfermedades crónicas, mecanismo lesional, tipo de trauma, localización topográfica, complicaciones precoces, tratamiento médico-quirúrgico y mortalidad precoz. Se elaboró un modelo de regresión logística binaria mediante el método hacia delante de Wald. Resultados: El porcentaje global del modelo de regresión logística mostró la relación entre lo pronosticado respecto a lo observado en un 94,6 por ciento. Los predictores explicaron el 83,8 por ciento de la variabilidad de la variable dependiente. Se determinaron cinco variables predictoras de mortalidad precoz, hipertensión arterial, enfermedad pulmonar obstructiva crónica, hepatopatía crónica, coagulopatía aguda e hipotermia. Conclusiones: Se concluye que las enfermedades crónicas como la hipertensión arterial, la enfermedad pulmonar obstructiva crónica y las hepatopatías crónicas, asociadas a la coagulopatía aguda e hipotermia fueron identificadas como variables predictoras de muerte precoz en pacientes hospitalizados por trauma hemorrágico(AU)

Introduction: Severe traumatic disease is the sixth leading cause of death worldwide, high percentage of deaths is ascribed to uncontrolled bleeding. There are no studies in Cuba on predictive variables of early mortality in hospitalized patients with hemorrhagic trauma. Objective: To identify predictive variables of early mortality in hospitalized patients with hemorrhagic trauma. Methods: An observational, analytical, cross-sectional study was carried out, which included 207 patients with hemorrhagic trauma, at Camilo Cienfuegos Provincial General Hospital in Sancti Spíritus, from 2012 to 2017. The variables were grouped into sociodemographic, diseases chronic, lesion mechanism, type of trauma, topographic location, early complications, medical-surgical treatment and early mortality. A binary logistic regression model was developed using the Wald forward method. Results: The global percentage of the logistic regression model showed the relationship between what was predicted with respect to what was observed in 94.6 por ciento. The predictors explained 83.8 por ciento of the variability of the dependent variable. Five predictors of early mortality, arterial hypertension, chronic obstructive pulmonary disease, chronic liver disease, acute coagulopathy, and hypothermia were determined. Conclusions: It is concluded that chronic diseases such as arterial hypertension, chronic obstructive pulmonary disease and chronic liver disease, associated with acute coagulopathy and hypothermia, were identified as predictors of early death in patients hospitalized for hemorrhagic trauma(AU).

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Snakebites are considered a major public health problem worldwide. In the Amazon region of Brazil, the snake Bothrops atrox (B. atrox) is responsible for 90% of the bites. These bites may cause local and systemic signs from acute inflammatory reaction and hemostatic changes, and present common hemorrhagic disorders. These alterations occur due the action of hemostatically active and immunogenic toxins which are capable of triggering a wide range of hemostatic and inflammatory events. However, the crosstalk between coagulation disorders and inflammatory reaction still has gaps in snakebites. Thus, the goal of this study was to describe the relationship between the consumption of fibrinogen and the profile of inflammatory molecules (chemokines and cytokines) in evenomations by B. atrox snakebites. A prospective study was carried out with individuals who had suffered B. atrox snakebites and presented different levels of fibrinogen consumption (normal fibrinogen [NF] and hypofibrinogenemia [HF]). Seventeen patients with NF and 55 patients with HF were eligible for the study, in addition to 50 healthy controls (CG). The molecules CXCL-8, CCL-5, CXCL-9, CCL-2, CXCL-10, IL-6, TNF, IL-2, IL-10, IFN-γ, IL-4, and IL-17A were quantified in plasma using the CBA technique at three different times (pre-antivenom therapy [T0], 24 h [T1], and 48 h [T2] after antivenom therapy). The profile of the circulating inflammatory response is different between the groups studied, with HF patients having higher concentrations of CCL-5 and lower IFN-γ. In addition, antivenom therapy seems to have a positive effect, leading to a profile of circulating inflammatory response similar in quantification of T1 and T2 on both groups. Furthermore, these results suggest that a number of interactions of CXCL-8, CXCL-9, CCL-2, IL-6, and IFN-γ in HF patients are directly affected by fibrinogen levels, which may be related to the inflammatory response and coagulation mutual relationship induced by B. atrox venom. The present study is the first report on inflammation-coagulation crosstalk involving snakebite patients and supports the better understanding of envenomation's pathophysiology mechanisms and guides in the search for novel biomarkers and prospective therapies.

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Introduction:Bothrops atrox snakebites are a major public health problem in the Amazon region and also cause hemostatic disorders. In this study, we assessed the recovery from hemostatic disorders in Bothrops snakebite patients after being given antivenom therapy.Methods: This is a prospective study of Bothrops snakebite patients (n = 100) treated at the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazilian Amazon, between January 2016 and December 2017. Blood samples were taken for the measurement of venom concentrations, platelets, clotting time and factors of patients on admission, 12, 24 and 48 h after antivenom therapy, and taken again on discharge. The presence of systemic bleeding was recorded during the follow-up.Results: On admission, systemic bleeding was observed in 14% of the patients. Thrombocytopenia was noted in 10% of the patients. A total of 54% of the patients presented unclottable blood with low levels of fibrinogen and alpha 2-antiplasmin, and high levels of fibrin/fibrinogen degradation product (FDP) and D-dimers. Unclottable blood and systemic bleeding were overcome in most patients 12 h after the antivenom therapy. Three patients developed systemic bleeding 48 h after antivenom therapy. Levels of fibrinogen and alpha 2-antiplasmin, FDP and D-dimer returned to normal around 48 h after the treatment or on discharge. The frequency of thrombocytopenia with high mean platelet volume increased in the first 24 h after antivenom therapy, and decreased on discharge. Bothrops venom levels in patients decreased 12 h after antivenom therapy and were not correlated with coagulation and fibrinolytic parameters. There were no deaths.Conclusion: Laboratorial parameters of coagulopathy returned to normal values within 48 h after the antivenom therapy until discharge. A few patients still presented bleeding signs within 48 h after beginning antivenom therapy. However, the Brazilian antivenom was able to overcome the hemostatic disorders in these cases of envenomation.

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Objective: to describe the haemostatic characteristics of the venom as well as the potency appraisal of the polyvalent antiophidic serum against haemotoxicity from Porthidium lansbergii hutmani experimental envenomation. Methods: Evaluation was performed of the venom's lethality, haemorrhagic activity, effects on coagulation and platelet aggregation, proteolytic activity, and neutralization by the commercial antivenom available in the country. Results: Several components with haemostatic activities were found in Porthidium l. hutmanni venom when a study of fibrinogenolytic, haemorrhagic and proteolytic activities was conducted of a pool of P.l.h venom. Porthidium l. hutmanni venom lacked the coagulant and defibrinating activities that are characteristic of bothropic venoms. Porthidium l. hutmanni venom showed very high haemorrhagic and anticoagulant activities. These findings could be related to the presence of multiple metalloproteases, which was evidenced in this study, and also the possible presence of phospholipases or other anticoagulant activity proteins that were not defined here. They inhibited platelet aggregation, suggesting that the venom had some proteins with marked effects on haemostasis. The commercial antivenom proved to be of little effectiveness in neutralizing the crude venom haemorrhagic activity. Conclusions: These toxins cause many physiopathological alterations in bitten patients, creating a clinical picture characterized by oedema, local and systemic haemorrhages, and even necrosis, comparable to that seen in bothropic envenomation. Porthidium l. hutmanni venom has no in vitro procoagulant activity, typical of bothropic venoms, suggesting there are variances in its protein conformation. Porthidium l. hutmanni venom is used for horse immunization. However, in order to preserve the patient's life, it is necessary to improve the immunization process to produce antivenom containing high avidity and specificity antibodies against the major toxins present in this venom. Porthidium l. hutmanni venom has demonstrated being a venom with high lethal, haemorrhagic, proteolytic and procoagulant activities, whose description will have enormous utility among clinicians who deal with these accidents in its geographical distribution areas(AU)

Objetivo: Describir las características hemostáticas del veneno y evaluar la potencia del suero polivalente antiofídico contra la hemotoxicidad provocada por el envenenamiento experimental por Porthidium lansbergii hutmanni. Métodos: Se realizó una evaluación de la letalidad, actividad hemorrágica, efectos en la coagulación y agregación plaquetaria, actividad proteolítica y neutralización por el antiveneno disponible comercialmente en el país. Resultados: Se encontraron varios componentes con actividad hemostática en el veneno de Porthidium l. hutmanni al realizarse un estudio de la actividad fibrinogenolítica, hemorrágica y proteolítica de una muestra de veneno de Porthidium l. hutmanni. El veneno de Porthidium l. hutmanni no mostró la actividad coagulante o defibrinante característica de los venenos botrópicos. El veneno de Porthidium l. hutmanni mostró una elevada actividad hemorrágica y anticoagulante. Estos resultados podrían estar relacionados con la presencia de múltiples metaloproteasas, la que quedó demostrado en el estudio, y también a la posible presencia de fosfolipasas u otras proteínas de actividad anticoagulante que no se definen en el mismo. La inhibición de la agregación plaquetaria sugiere que el veneno contiene algunas proteínas con un marcado efecto sobre la hemostasis. El antiveneno comercial mostró poca efectividad en la neutralización de la actividad hemorrágica del veneno crudo. Conclusiones: Estas toxinas provocan muchas alteraciones fisiopatológicas en las víctimas de mordeduras, creando un cuadro clínico caracterizado por edema, hemorragias locales y sistémicas e incluso necrosis comparable con la que ocurre en el envenenamiento botrópico. El veneno de Porthidium l. hutmanni no tiene la actividad procoagulante in vitro típica de los venenos botrópicos, lo que apunta a variaciones en su conformación proteica. El veneno de Porthidium l. hutmanni de utiliza en la inmunización de los caballos. Sin embargo, para preservar la vida del paciente, es necesario mejorar el proceso de inmunización con vistas a producir un antiveneno que contenga anticuerpos de elevada avidez y especificidad contra las principales toxinas presentes en el veneno. El veneno de Porthidium l. hutmanni ha mostrado ser un veneno de elevada actividad letal, hemorrágica, proteolítica y procoagulante, cuya descripción tendrá una enorme utilidad para los médicos que atienden esos accidentes en sus áreas de distribución geográfica(AU)

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Background: Hemostatic alterations are commonly detected in canine cancer patients. However, few studies have described hemostatic dysfunction in dogs with different tumor subtypes. In Veterinary Medicine, the state of hypercoagulability is hardly diagnosed alive, since laboratory exams for evaluate hemostatic function are not always requested. Due to importance of homeostatic disorders in cancer patients, this study aimed to evaluate hemostatic alterations such as platelet count, activated partial thromboplastin time (aPTT), prothrombin time (PT) and fibrinogen in tumor-bearing dogs.Materials, Methods & Results: From the 55 dogs evaluated, 30 had mammary carcinoma, 6 visceral hemangiosarcoma, 9 high-grade cutaneous mast cell tumor and 10 multicentric lymphoma. The results were compared to a control group composed by 10 Beagle dogs. Thrombocytosis was observed in 26.6% (8/30) of mammary carcinoma group and thrombocytopenia in 10% (3/30). The patients with hemangiosarcoma and mast cell tumor did not reveal thrombocytosis, however, thrombocytopenia was present in 16.6% (1/6) and 33% (3/9), respectively. Three dogs with multicentric lymphoma showed thrombocytopenia and other three showed thrombocytosis. From patients with thrombocytosis, one was classified as severe thrombocytosis (1077 x 10³/µL). Therefore, there were no statistically significant associations between neoplasia group with control group (P > 0.05). Regarding the aPTT and PT evaluation, mammary carcinoma (P = 0.0005), hemangiosarcoma (P = 0.033) and mast cell tumor (P = 0.012) patients showed statistical difference for aPTT, while the evaluation for PT was not significant (P > 0.05). We grouped all patients as a “tumor group” and compared to the control group. It was possible to observe increased aPTT and PT in 89% (49/55) and 50.90% (28/55) respectively, in tumor group compared to normal.[...](AU)

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Background: Hemostatic alterations are commonly detected in canine cancer patients. However, few studies have described hemostatic dysfunction in dogs with different tumor subtypes. In Veterinary Medicine, the state of hypercoagulability is hardly diagnosed alive, since laboratory exams for evaluate hemostatic function are not always requested. Due to importance of homeostatic disorders in cancer patients, this study aimed to evaluate hemostatic alterations such as platelet count, activated partial thromboplastin time (aPTT), prothrombin time (PT) and fibrinogen in tumor-bearing dogs.Materials, Methods & Results: From the 55 dogs evaluated, 30 had mammary carcinoma, 6 visceral hemangiosarcoma, 9 high-grade cutaneous mast cell tumor and 10 multicentric lymphoma. The results were compared to a control group composed by 10 Beagle dogs. Thrombocytosis was observed in 26.6% (8/30) of mammary carcinoma group and thrombocytopenia in 10% (3/30). The patients with hemangiosarcoma and mast cell tumor did not reveal thrombocytosis, however, thrombocytopenia was present in 16.6% (1/6) and 33% (3/9), respectively. Three dogs with multicentric lymphoma showed thrombocytopenia and other three showed thrombocytosis. From patients with thrombocytosis, one was classified as severe thrombocytosis (1077 x 10³/µL). Therefore, there were no statistically significant associations between neoplasia group with control group (P > 0.05). Regarding the aPTT and PT evaluation, mammary carcinoma (P = 0.0005), hemangiosarcoma (P = 0.033) and mast cell tumor (P = 0.012) patients showed statistical difference for aPTT, while the evaluation for PT was not significant (P > 0.05). We grouped all patients as a “tumor group” and compared to the control group. It was possible to observe increased aPTT and PT in 89% (49/55) and 50.90% (28/55) respectively, in tumor group compared to normal.[...]

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Patients envenomed by Lonomia sp caterpillars initially experience a mild burning pain, headache, nausea, vomiting, and skin and mucosal hemorrhages. Some patients can rapidly progress to a severe coagulopathy that presents as visceral or intracerebral hemorrhaging. We studied the hemostatic alterations that occurred in 14 patients who were envenomed by Lonomia obliqua in Southern Brazil and presented at the Hospital São Vicente de Paulo (Passo Fundo, RS), Brazil during the summers of 1993 and 1994 when Lonomia antivenom was not yet available for treatment. The patients were classified into to 4 clinical groups: 0 (two patients), I (eight patients), II (two patients), and III (two patients). The patients were admitted to the hospital between 4 hours and five days after contact with the caterpillars. In this study, the coagulation parameters of the patients were followed up for up to 172 hours after the accidents. The patients received no treatment with the exceptions of two patients who received blood transfusions and antifibrinolytic treatment. The observed abnormalities related to blood coagulation and fibrinolytic factors were similar regardless of the severity of the bleeding symptoms. These findings suggest that alterations in hemostatic parameters without thrombocytopenia are not predictors of the seriousness of such accidents. Thus, consumptive disorder and reactive fibrinolysis are not proportional to mild coagulopathy. Furthermore, these patients recovered. The hemostatic parameters of most of the patients normalized between 96 and 120 h after the accident.

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Background: Snake venoms are a complex mixture of proteins, organic and inorganic compounds. Some of these proteins, enzymatic or non-enzymatic ones, are able to interact with platelet receptors, causing hemostatic disorders. The possible therapeutic potential of toxins with antiplatelet properties may arouse interest in the pharmacological areas. The present study aimed to purify and characterize an antiplatelet DC protein from Bothrops alternatus snake venom. Methods: The protein, called BaltDC (DC protein from B. alternatus snake venom), was purified by a combination of ion-exchange chromatography on DEAE-Sephacel column and gel filtration on Sephadex G-75. The molecular mass was estimated by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS-PAGE). The amino acid sequence of the N-terminal region was carried out by Edman degradation method. Platelet aggregation assays were performed in human platelet-rich plasma (PRP). Infrared (IR) spectroscopy was used in order to elucidate the interactions between BaltDC and platelet membrane. Results: BaltDC ran as a single protein band on SDS-PAGE and showed apparent molecular mass of 32 kDa under reducing or non-reducing conditions. The N-terminal region of the purified protein revealed the amino acid sequence IISPPVCGNELLEVGEECDCGTPENCQNECCDA, which showed identity with other snake venom metalloproteinases (SVMPs). BaltDC was devoid of proteolytic, hemorrhagic, defibrinating or coagulant activities, but it showed a specific inhibitory effect on platelet aggregation induced by ristocetin and epinephrine in PRP. IR analysis spectra strongly suggests that PO 3 2 − groups, present in BaltDC, form hydrogen bonds with the PO 2 − groups present in the non-lipid portion of the membrane platelets. Conclusions: BaltDC may be of medical interest since it was able to inhibit platelet aggregation.(AU)

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ABSTRACT Patients envenomed by Lonomia sp caterpillars initially experience a mild burning pain, headache, nausea, vomiting, and skin and mucosal hemorrhages. Some patients can rapidly progress to a severe coagulopathy that presents as visceral or intracerebral hemorrhaging. We studied the hemostatic alterations that occurred in 14 patients who were envenomed by Lonomia obliqua in Southern Brazil and presented at the Hospital São Vicente de Paulo (Passo Fundo, RS), Brazil during the summers of 1993 and 1994 when Lonomia antivenom was not yet available for treatment. The patients were classified into to 4 clinical groups: 0 (two patients), I (eight patients), II (two patients), and III (two patients). The patients were admitted to the hospital between 4 hours and five days after contact with the caterpillars. In this study, the coagulation parameters of the patients were followed up for up to 172 hours after the accidents. The patients received no treatment with the exceptions of two patients who received blood transfusions and antifibrinolytic treatment. The observed abnormalities related to blood coagulation and fibrinolytic factors were similar regardless of the severity of the bleeding symptoms. These findings suggest that alterations in hemostatic parameters without thrombocytopenia are not predictors of the seriousness of such accidents. Thus, consumptive disorder and reactive fibrinolysis are not proportional to mild coagulopathy. Furthermore, these patients recovered. The hemostatic parameters of most of the patients normalized between 96 and 120 h after the accident.

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Background: Snake venoms are a complex mixture of proteins, organic and inorganic compounds. Some of these proteins, enzymatic or non-enzymatic ones, are able to interact with platelet receptors, causing hemostatic disorders. The possible therapeutic potential of toxins with antiplatelet properties may arouse interest in the pharmacological areas. The present study aimed to purify and characterize an antiplatelet DC protein from Bothrops alternatus snake venom. Methods: The protein, called BaltDC (DC protein from B. alternatus snake venom), was purified by a combination of ion-exchange chromatography on DEAE-Sephacel column and gel filtration on Sephadex G-75. The molecular mass was estimated by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS-PAGE). The amino acid sequence of the N-terminal region was carried out by Edman degradation method. Platelet aggregation assays were performed in human platelet-rich plasma (PRP). Infrared (IR) spectroscopy was used in order to elucidate the interactions between BaltDC and platelet membrane. Results: BaltDC ran as a single protein band on SDS-PAGE and showed apparent molecular mass of 32 kDa under reducing or non-reducing conditions. The N-terminal region of the purified protein revealed the amino acid sequence IISPPVCGNELLEVGEECDCGTPENCQNECCDA, which showed identity with other snake venom metalloproteinases (SVMPs). BaltDC was devoid of proteolytic, hemorrhagic, defibrinating or coagulant activities, but it showed a specific inhibitory effect on platelet aggregation induced by ristocetin and epinephrine in PRP. IR analysis spectra strongly suggests that PO 3 2 − groups, present in BaltDC, form hydrogen bonds with the PO 2 − groups present in the non-lipid portion of the membrane platelets. Conclusions: BaltDC may be of medical interest since it was able to inhibit platelet aggregation.(AU)

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