Why anticoagulant studies on sepsis fail frequently --- start with SCARLET / 中华创伤杂志(英文版)

The Sepsis Coagulopathy Asahi Recombinant LE Thrombomodulin (SCARLET) trial has many defects, and thus cannot be the terminator of recombinant thrombomodulin (rTM). On the contrary, it provides sufficient evidence for further research. Based on analysis focusing on the failure of SCARLET and several previous anticoagulant studies, it is most important for new studies to grasp the following two points: (1) The enrolled cases should have sufficient disease severity and a clear standard for disseminated intravascular coagulation; (2) Heparin should not be used in combination with the investigated drugs. Multiple post-hoc analyses show that no combination of heparin will not increase the risk of thromboembolism. In fact, the combination of heparin can mask the true efficacy of the investigated drug. Due to the complexity of sepsis treatment and the limitations of clinical studies, the results of all treatment studies should be repeatedly verified, rather than be determined at one stroke. Some research conclusions contrary to disease physiology, pharmacology and clinical practice may be deceptive, and should be cautious rather than be simply accepted. On the other hand, the dissenting voices in the "consensus" scene are often well discussed by the authors and should be highly valued.

Coagulación intravascular diseminada y sepsis: tratamiento y criterios diagnósticos / Disseminated intravascular coagulation and sepsis: treatment and diagnostic criteria

Introducción: La sepsis es un proceso patológico que se caracteriza por un estado inflamatorio desmesurado que puede generar coagulopatías graves como la coagulación intravascular diseminada. Esta coagulopatía se caracteriza principalmente por la exposición del factor tisular que activa la cascada de coagulación y genera un estado protrombótico que puede empeorar la falla orgánica. Objetivo: Analizar criterios diagnósticos e implicación terapéutica con el fin de mostrar una actualización en el abordaje de un paciente con coagulación intravascular diseminada y sepsis. Métodos: Se realizó una búsqueda de artículos en la base de datos PubMed, Science direct y Scielo, utilizando los siguientes descriptores: coagulopatía, sepsis, coagulación intravascular diseminada, criterios diagnósticos y tratamiento. Conclusión: Se ha encontrado una mejora en la mortalidad de los pacientes tratados con anticoagulantes como la proteína C, la antitrombina, entre otros, sin embargo, estos hallazgos no han logrado la trascendencia necesaria para ser recomendados en las guías de tratamiento de coagulación intravascular diseminada(AU)

Introduction: Sepsis is a pathological process characterized by inordinate inflammation which may cause severe coagulopathies, such as disseminated intravascular coagulation. This coagulopathy is mainly characterized by exposure of the tissue factor, activating the coagulation cascade and generating a prothrombotic state which may worsen organ failure. Objective: Analyze diagnostic criteria and therapeutic implications to present an update on the management of patients with disseminated intravascular coagulation and sepsis. Methods: A search was conducted for papers published in the databases PubMed, Science Direct and SciELO, using the search terms coagulopathy, sepsis, disseminated intravascular coagulation, diagnostic criteria and treatment. Conclusion: Improvement was observed in the mortality of patients treated with anticoagulants such as protein C and antithrombin, among others. However, these findings have not achieved the relevance required to be recommended for inclusion in the treatment guides for disseminated intravascular coagulation(AU)

The effect of activated protein C in the experimental disseminated intravascular coagulation model formed by lipopolysaccharide infusion

Abstract Purpose: In this experimental study, activated protein C (APC), which has anticoagulant, antithrombotic, profibrinolytic, anti-inflammatory and antiapoptotic properties, was used to prevent coagulopathy in a disseminated intravascular coagulation (DIC) model formatted with lipopolysaccharide (LPS) infusion. Methods: Twenty-five Wistar albino rats weighting 280 - 320 g each were used. They were randomly divided into three groups: sham, control and study groups. To sham group (n = 5), only normal saline was infused. To control (n = 10) and study groups (n = 10), 30 mg/kg LPS was infused for 4 h from femoral vein. After LPS infusion, 100 µg/kg recombinant APC was given during 4 h in study group. Eight hours later, blood samples were taken from abdominal aorta and the animals sacrificed. From these samples, platelet, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and D-dimer levels were studied. Results: Platelet counts and fibrinogen levels were significantly lower in control and study groups than sham group (p < 0.05). The PT, aPTT and D-dimer levels were significantly higher in control and study groups than in sham group (p < 0.05). When comparing control and study groups, platelet counts were not statistically different (p = 0.36). However, the difference of the fibrinogen levels was significant between these groups (p = 0.0001). While PT and aPTT were longer in the study group compared to the control group (p < 0.05), D-dimer levels were lower in the study group than in control (p = 0.0001). Conclusion: Use of APC can prevent hypercoagulation and consumption coagulopathy in the DIC as a result of correcting hematological parameters other than prolongation of coagulation time.

La hemorragia obstétrica en el servicio de Anestesiología del Hospital Dr. Agostinho Neto / Obstetric Hemorrhage in Anesthesia Service at Dr. Agostinho Neto Hospital

Introducción: La hemorragia obstétrica es una de las complicaciones más temidas y una de las principales causas de mortalidad materna. Objetivo: Caracterizar la hemorragia obstétrica en el servicio de Anestesiología y Reanimación del Hospital Dr. Agostinho Neto de Guantánamo. Métodos: Se realizó un estudio descriptivo, longitudinal y prospectivo en el mencionado servicio de salud desde 2015 - hasta 2017. De un universo de 388 pacientes que tuvieron diagnóstico de morbilidad materna extremadamente grave, la muestra quedó constituida por las diagnosticadas con hemorragia obstétrica (n= 71). Para el procesamiento estadístico se utilizó el porcentaje, la media y la desviación estándar. Resultados: La hemorragia obstétrica se precisó en 18,2 por ciento de las pacientes; de ellas, 0,7 por ciento fallecieron. La edad media de las pacientes fue de 24,2 ± 6,2 años. La edad gestacional fue de 34,2 ± 6,2 años y la estadía en días fue de 5,9 ± 4,2 [IC 95 por ciento 5,3 - 6,5]. La atonía uterina (50,8 por ciento) fue la causa más común de la hemorragia. El 91,5 por ciento de las pacientes presentó inestabilidad hemodinámica, lo que condicionó el uso de altos volúmenes de fluidos y hemoderivados para su reanimación. La coagulación intravascular diseminada fue la causa de muerte fundamental. Conclusiones: La hemorragia obstétrica continúa una causa importante de morbilidad y mortalidad en el mencionado servicio de salud(AU)

Introduction: Obstetric hemorrhage is one of the feared complications and it is one of the main causes of maternal mortality. Objective: To characterize obstetric hemorrhage in the service of Anesthesiology and Reanimation at Dr. Agostinho Neto Hospital in Guantanamo, Cuba from 2015 to 2017. Methods: A descriptive, longitudinal and prospective study was carried out in the aforementioned health service from 2015 to 2017. Three hundred eighty eight (388) patients that had diagnostic of extremely serious maternal morbidity were the universe of this study. The sample was constituted by those diagnosed with obstetric hemorrhage (n = 71). Percentage, mean and standard deviation were used for the statistical analysis. Results: Obstetric hemorrhage occurred in 18.2 percent of the patients. 0.7 percent died. The mean age was of 24.2 ± 6.2 years; the pregnancies age was of 34.2 ± 6.2 years and hospital stay was of 5.9 ± 4.2 [IC 95 percentage 5.3 - 6.5]. Uterine atony (50.8 percent) was the most common cause of the hemorrhage. 91.5 percent of the patients had hemodynamic unsteadiness that conditioned the use of high volumes of fluids and hemoderivates for reanimation. Clotting intravascular was the main cause of death. Conclusions: Obstetric hemorrhage constitutes an important cause of morbidity and mortality in the mentioned health service(AU)

Haematologic parameters in acute promyelocytic leukemia patients treated with ALL trans- retinoic acid

Acute Promyelocytic Leukemia [APL] is commonly associated with disseminated intravascular coagulation [DIC] and early correction of coagulopathy is of vital importance. All Trans-Retinoic Acid [ATRA] is considered to be the drug of choice in the treatment of APL. The work was conducted to: 1- Identify patients with APL who show laboratory evidence of DIC. 2- Study the serial changes in haemostatic parameters in APL patients treated with ATRA and to compare their results with those treated with conventional chemotherapy without ATRA. In this prospective study [from October 2003 to October 2005], 44 newly diagnosed, untreated APL patients were included. ATRA plus chemotherapy - treated patients were 24 while 17 patients were treated with chemotherapy other than ATRA. For each patient, a full clinical evaluation was done and hematological investigations were accomplished at time of diagnosis and repeated on day 3 and 7 of therapy. Diagnosis of DIC was based on finding a positive D- dimer test with hypofibrinogenaemia with or without pathologically prolonged [PT and/or APTT]. In 44 newly diagnosed, untreated APL patients studied, the age ranged between 6-81 years with a median of 27 years. Male to female ratio was 1.3:1. Before treatment all patients had anemia, thrombocytopenia, and elevated level of D - dimer. DIC was present in all patients at time of diagnosis. All parameters that showed abnormal level at time of diagnosis had returned to normality within one week in ATRA treated group, indicating that DIC has essentially resolved. By contrast, those parameters remained abnormal even on day 7 in the chemotherapy treated group, indicating that DIC was ongoing. ATRA therapy in APL patients is associated with rapid improvement of coagulopathy therefore, it is justified to be used from day one of the treatment

Ketoconazole and Flutamide in the treatment of disseminated intravascular clotting from prostate cancer: a case report and review.

Disseminated intravascular clotting (DIC) is a well-recognized complication of malignancy. Prostatic cancer can produce chronic DIC as well as acute severe DIC. Treatment of DIC are general supportive measures including heparin, transfusion of blood, platelets and clotting factors, but the most important aspect is correction of underlying malignant diseases i.e. cancer of the prostate gland. For metastatic prostatic cancer presenting with an emergency oncologic condition, the treatment of choice is surgical orchiectomy, but surgery may not be possible in the presence of severe DIC. Ketoconazole and Flutamide are drugs with different mechanisms for hormonal manipulation of this cancer. Due to severe DIC, we combined both drugs trying to put maximum therapeutic effect on this life threatening profound DIC patient.

Síndrome de Kasabach-Merritt: actualización diagnóstica y terapéutica / Kasabach-Merritt syndrome: diagnostic and therapeutic update

Se presenta el caso de un paciente de sexo masculino, de un mes y medio de edad, con anemia hemolítica microangiopática y coagulopatía de consumo asociada a un hemangioma de rápido crecimiento (síndrome de Kasabach-Merritt). Se realiza una actualización diagnóstica y terapéutica de esta patología considerada de diferentes formas por otros autores

Sepsis: estudio comparativo en el tratamiento de las alteraciones de coagulación con concentrados de Antitrombina III o Heparina / Sepsis: Antitrombin III or Heparine therapy in disseminated intravascular coagulation, comparative study

Se efectuó el estudio en 48 pacientes con diagnóstico de sepsis, el mismo se hizo en todos los casos por el cuadro clínico y la confirmación bacteriológica, con aislamiento del germen por hemocultivo o cultivo de otras localizaciones. Se dividieron los pacientes en dos grupos distribuidos al azar, 24 pacientes fueron tratados con concentrados de AT III a las dosis de 1000 unidades cada 12 hs en infusión endovenosa durante 30 minutos, durante las primeras 48 hs. 24 recibieron heparina, 150 unidades por Kg por día en perfusión contínua durante 2 días, en el grupo con heparina si el paciente no mejoraba se mantenía la terapéutica más tiempo y si aparecían manifestaciones trombóticas (trombosis venosa profunda o tromboembolismo de pulmón) se aumentó la dosis a 500 unidades por Kg por día. A los pacientes se les efectuaron los siguientes controles de coagulación a las 0, 12, 24 y 48 hs: Tiempo de Quick, KPTT, Tiempo de Trombina, prueba de sulfato de protamina, recuento de plaquetas, determinación del factor II, V, VII-X y VIII, Pdf, D-Dimero, fibrógeno y AT III. Durante 7 días se siguió la evolución de los pacientes observando las complicaciones trombóticas, hemorrágicas y la mortalidad. En los resultados se pudo observar una mejoría en el grupo tratado con AT III en todos los parámetros de coagulación estudiados (P < 0,01), reducción de las hemorragias, trombosis y mortalidad, en este último caso cabe destacar que en el grupo tratado con AT III hubo 3 muertos contra 6 del grupo tratado con heparina, a pesar de ser el doble no es estadísticamente significativo, pero de aumentar el número de casos y mantenerse igual la proporción si llegaría a serlo

Urgências em hematologia / Hematological emergencies

Seräo abordados nesta revisäo apenas alguns dos quadros hematológicos com os quais o clínico se depara mais comumente em uma sala de urgência, como as crises vaso-oclusivas dos pacientes com doenças falciformes, a coagulaçäo intravascular disseminada e a febre no paciente neutropênico

Heparin therapy in Russell's viper bite victims with disseminated intravascular coagulation: a controlled trial.

A controlled clinical trial of low dose heparin was carried out in confirmed cases of Russell's viper bite. Twenty patients with systemic envenoming were included in the study. They were randomized to receive low dose heparin in an initial dose of 50 units/kg body weight intravenously immediately after antivenom followed by a continuous infusion of 10 unit 3 kg/hour in isotonic saline for 24 hours, or antivenom alone. Response to treatment was assessed clinically as well as by serial measurements of coagulation factors and biochemical values. No significant difference was observed in the outcome among two groups, the recovery rate from the clotting defect being similar in both. The mean serum creatinine values of the two groups were also not statistically different. The results indicated that there is no beneficial effect of adding heparin to the standard treatment by antivenom.

Prolongación exitosa de gestación gemelar de pretérmino complicada con un feto muerto y coagulación intravascular diseminada / Succesfully prolongation of twin preterm gestation complicated with one fetal death and disseminated intravascular coagulation

Se presenta un caso clínico de embarazo gemelar con coagulación intravascular diseminada y un feto muerto in utero en la semana 24, en el cual se utilizó heparina para prolongar la gestación. Se describe el uso de heparina y su efecto en el perfil hemostático de la paciente y su importancia en la resolución del caso

Emergency treatment with ketoconazole in disseminated intravascular coagulation due to metastatic prostatic carcinoma.

We report the use of ketoconazole to control disseminated intravascular coagulation due to prostatic carcinoma. Clinical improvement in the condition of the patient was noted in 48 hours and coagulation profile became normal in 10 days.

Effect of heparin and antiplasmin on platelet level in dengue haemorrhagic fever.

A study was carried out to determine the effect of heparin and antiplasmin in dengue haemorrhagic fever. The results shows that heparin and synthetic antiplasmin therapy could accelerate the restoration of platelet level which might reflect amelioration of disseminated intravascular coagulation in dengue haemorrhagic fever.

Evolución de la coagulación intravascular diseminada con microdosis de heparina / Course of disseminated intravascular coagulation with low doses of heparin

A 34 lactantes infectados graves se les midió tiempo de protrombina (TP), tiempo de tromboplastina parcial (TTP), plaquetas, fibrinógeno y productos líticos de fibrina (PLF). Todos se consideraron portadores de coagulación intravascular diseminada (CID). Se clasificaron en tres grupos: grupo I (6 pacientes) con fibrinógeno alto, plaquetas normales o altas y PLF elevados (considerado en fase de hipercoagulabilidad); grupo II (16 pacientes) con fibrinógeno normal, plaquetas bajas o normales y PLF elevados (en fase de compensación o "encubrimiento") y grupo III (12 pacientes) con fibrinógeno bajo, plaquetas bajas y PLF elevados (en fase de consumo). Después del tratamiento de fondo y utilización de heparina a 100 U/kg/24h, en infusión continua, se observó que en el grupo I el fibrinógeno, plaquetas y PLF disminuyeron a cifras normales; en el grupo II, el fibrinógeno y las plaquetas se mantuvieron normales y los PLF disminuyeron y en el grupo III, el fibrinógeno y las plaquetas se elevaron y los PLF disminuyeron. En los tres grupos el TP y TTP presentaron cambios sin importancia. Se concluye que la heparina en microdosis y a infusión continua frena la CID en cualquiera de las tres fases de evolución