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)

Current Pathological and Laboratory Considerations in the Diagnosis of Disseminated Intravascular Coagulation

Systemically sustained thrombin generation in vivo is the hallmark of disseminated intravascular coagulation (DIC). Typically, this is in response to a progressing disease state that is associated with significant cellular injury. The etiology could be infectious or noninfectious, with the main pathophysiological mechanisms involving cross-activation among coagulation, innate immunity, and inflammatory responses. This leads to consumption of both pro- and anticoagulant factors as well as endothelial dysfunction and disrupted homeostasis at the blood vessel wall interface. In addition to the release of tissue plasminogen activator (tPA) and soluble thrombomodulin (sTM) following cellular activation and damage, respectively, there is the release of damage-associated molecular patterns (DAMPs) such as extracellular histones and cell-free DNA. Extracellular histones are increasingly recognized as significantly pathogenic in critical illnesses through direct cell toxicity, the promotion of thrombin generation, and the induction of neutrophil extracellular trap (NET) formation. Clinically, high circulating levels of histones and histone–DNA complexes are associated with multiorgan failure, DIC, and adverse patient outcomes. Their measurements as well as that of other DAMPs and molecular markers of thrombin generation are not yet applicable in the routine diagnostic laboratory. To provide a practical diagnostic tool for acute DIC, a composite scoring system using rapidly available coagulation tests is recommended by the International Society on Thrombosis and Haemostasis. Its usefulness and limitations are discussed alongside the advances and unanswered questions in DIC pathogenesis.

Síndrome de Nicolau posterior a la inyección de penicilina intramuscular / Nicolau's syndrome after benzathine penicillin intramuscular injection

El síndrome de Nicolau se produce por la inyección intra-arterial accidental de sustancias de aplicación intramuscular. Se caracteriza por dolor inmediato en el sitio de la inyección, seguido de alteraciones cutáneas locales y posterior desarrollo de embolias en las extremidades que generan daño isquémico tisular pudiendo llevar a la necrosis. En general se ha adjudicado a la penicilina G benzatínica intrmuscular, aún con técnica de aplicación adecuada, como responsable de este síndrome. Este fármaco sigue siendo de elección en una gran cantidad de enfermedades infecciosas; dentro de sus efectos advesos no alérgicos se destacan las complicaciones vasculares como las más frecuentes. Reportamos un paciente con sífilis tratado con penicilina G benzatínica intramuscular que presentó efectos adversos neurovasculares.

Nicolau's syndrome occurs as a result of intra-arterial accidental injection of intramuscular drugs. The clinical presentation includes immediate pain followed by skin local changes and extremities embolism that may lead to necrosis. Intramuscular Benzathine penicillin has been associated with this syndrome, even with adequate injection technique. This drug is of choice for a wide variety of infectious diseases; the most common non-allergic adverse events are vascular. We report here a syphilitic patient who suffered neurovascular adverse effects after intramuscular penicillin G benzathine application.

Aetiological factors, diagnosis and treatment of disseminated intravascular coagulation - a study in a tertiary care hospital

Disseminated intravascular coagulation is a syndrome, characterized by a systemic activation of the blood coagulation system. It results in the generation and deposition of fibrin, leading to microvascular thrombi in various organs contributes to the development of multi organ failure. It is always secondary to or associated with an underlying disorder.1,2 The objectives of this study were to: describe the clinicopathological pattern of DIC, to find out the associated factors for DIC, and enlist different diagnostic tests and follow the therapeutic outcome and prognosis. It is a case series study. The study was carried out at Shaikh Zayed Hospital Lahore which is 750 bedded facility affiliated with FPGMI. Sociodemographic data like name, age, sex, address was collected. The history of the present illness was noticed with regard to severity of symptoms like fever, bleeding, cough, dyspnoea and altered consciousness. Patients were investigated for complete blood counts like Hb%, Platelet count, D-dimer, FDPs levels and fibrinogen level. Association factors for DIC were also noticed. In this study the most frequent association factor was found to be sepsis. Bleeding manifestations present in 90% of the patients, cough in 63.3% of the subjects. Patients with hypotension and altered consciousness were found to have a bad prognosis. Those treated with heparin infusion were not found to have a significant improvement in their clinical outcome. DIC is an important acquired coagulation abnormality most frequently associated with sepsis requiring vigorous treatment with blood products and anticoagulants

Situación de salud oral de niños uruguayos portadores de coagulopatías hereditarias: Centro Hospitalario Pereira Rossell, Montevideo, Uruguay / Oral health in uruguayan children with inherited bleeding disorders: Pereira Rossell Hospital, Montevideo, Uruguay

Propósito: describir la situación de salud oral de los niños portadores de coagulopatías atendidos en el Servicio de Hemoterapia del Centro Hospitalario Pereira Rossell de Montevideo,Uruguay, entre febrero del 2008 y diciembre del 2009, y compararla con un grupo sin coagulopatías. Método: se realizó un estudio retrospectivo de casos y controles. El grupo deestudio estuvo conformado por 39 pacientes (edad: 8,62 ±4,20 años) y el grupo de control, por 78 (edad: 6,5 ± 2,88 años). El análisis de los hallazgos fue descriptivo. Resultados: enel grupo de niños con coagulopatías se encontró un índice ceo-d 2,85 ± 2,41 y un CPO-d 1,96 ±2,59, ambos ligeramente superiores al grupo control. Según la clasificación de lacoagulopatía se registró: hemofilia A en 17 pacientes, hemofilia B en 7, deficiencia de factor XII en un paciente y enfermedad de von Willebrand en 14. La adherencia al tratamientofue calificada como buena en 15 pacientes, mientras que fue mala en los 24 pacientes restantes. Conclusión: este es un primer reporte de salud oral en niños con coagulopatías en Uruguay. Es necesario hacer un seguimiento y aumentar la cobertura de este programa para mantener la salud oral de estos pacientes...

Aim: Describe the oral health status of children with inherited bleeding disorders who attended the Pereira Rossell Hospital in Montevideo Uruguay for dental care, between February 2008 and December 2009, and compare it with children without bleeding disorders. Methods:A retrospective case-control study was carried out. The study group consisted of 39 patients (age: 8.62 ± 4.20 years), while the control group had 78 patients (age 6.5 ± 2.88). Descriptive analysis was done to the data. Results: The study group had a dmf-s index 2.85± 2.41 and a DMF-s 1.96 ± 2.59, being slightly higher than in the control group. The bleeding disorder classification was: Hemophilia A, 17 patients; Hemophilia B, 7 patients; factor XII deficit, 1 patient; and Von Willebrand disease, 14 patients. Commitment to the treatmentwas determined as good in 15 patients and bad in 24 patients. Conclusion: This is the first oral health report on children with bleeding disorders from this program in Uruguay. It isnecessary to follow up the patients and increase the program coverage in order to maintain the oral health of this kind of patients...

Fulminant Epstein-Barr Virus-associated T-cell Lymphoproliferative Disorder in an Immunocompetent Middle-aged Man Presenting with Chronic Diarrhea and Gastrointestinal Bleeding

The World Health Organization (WHO) recently defined systemic Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disorders (LPD) of childhood as a life-threatening illness. However, this rare disease has not been extensively studied. Here we report a case of systemic EBV-positive T-cell LPD in a previously healthy middle-aged man with a chief complaint of chronic diarrhea. The initial colon biopsy showed focal infiltration of EBV-positive small lymphocytes without any atypia. However, the disease rapidly progressed and the patient required a total colectomy due to severe gastrointestinal bleeding. Three and half months after admission, the patient died from a complication of disseminated intravascular coagulation. The resected colon showed diffuse infiltration of EBV-positive atypical lymphocytes with ischemic change. Most atypical lymphocytes were CD3+ or CD5+. The monoclonality of EBV was demonstrated by sequence variation analysis of the latent membrane protein 1 (LMP1) gene in the colectomy specimen as well as in the initial biopsy.

Coagulação intravascular disseminada na gravidez - considerações, diagnóstico e manejo / Disseminated intravascular coagulation in pregnancy - considerations, diagnosis and manegement

A Síndrome de Coagulação Intravascular Disseminada (CIVD) é caracterizada por alteração das vias de ativação e controle da coagulação sanguínea gerando acúmulos de fibrina na micro-vasculatura, com consumo de plaquetas e fatores de coagulação. Pode resultar em falência orgânica múltipla e sangramento anormal. A gravidez caracterizase por estado de hipercoagulabilidade e por complicações como descolamento prematuro de placenta, pré-eclâmpsia e síndrome HELLP que representam algumas das condições associadas à CIVD. Seu diagnóstico é feito baseado na suspeita clínica, conhecendo-se os fatores de risco associados e apoiando-se na propedêutica sugestiva de coagulopatia. A abordagem terapêutica consiste principalmente em tratar a anormalidade obstétrica de base. Mas podem ser necessárias as medidas de suporte e de reposição de elementos sanguíneos para a normalização da função hemostática. A CIVD, apesar de rara, figura como complicação obstétrica grave, que pode cursar com hemorragia intensa e levar a paciente ao óbito. Esta revisão propõe-se a sistematizar o conhecimento da CIVD para ajudar em seu manejo eficiente e estratégico.

Disseminated Intravascular Coagulation (DIC) is a syndrome characterized by altered activation and control of blood coagulation pathways causing accumulation of fibrin in the micro-vasculature, consumption of platelets and coagulation factors, which may result in organ failure and abnormal bleeding. Pregnancy is known to be a hypercoagulable state and complications such as placental abruption, pre-eclampsia and HELLP syndrome are some of the conditions associated to the onset of DIC. The diagnosis is based on clinical suspicion and investigation of associated risk factors and supported by lab tests results suggestive of coagulopathy. Primary therapeutic management includes addressing the underlying obstetric disorder. However, additional supportive treatment and blood transfusion may be necessary to repair haemostatic function. Therefore, despite its rare incidence, DIC figures as a very serious obstetric complication that can cause massive bleeding and lead to patient´s death. This review aims to systematize the knowledge of this entity to allow an efficient and strategic management.

Rare presentation of a common disease of tropics.

A 19 years male presented with fever, oliguria and purpuric lesions involving both hands. The patient was diagnosed as a case of purpura fulminans with disseminated intravascular coagulation due to complicated falciparum malaria. The case is presented to sensitize the physicians to keep malaria as a differential in cases of fever with purpura fulminans.

Disseminated intravascular coagulation: current concepts.

Disseminated intravascular coagulation (DIC) is an acquired disorder in which normal hemostatic balance is disturbed. There is excessive thrombin formation leading to fibrin deposition in microcirculation and consequent ischemic organ damage. The etiology is multifactorial. A number of medical, surgical, oncological and obstetrical conditions can cause DIC. The diagnosis is essentially clinical supported by laboratory parameters and a scoring system based on these. The mainstay of treatment is correction of underlying cause and hemostatic support with replacement of coagulation factors. The role of heparin therapy and other therapeutic options including activated protein C, antithrombin III etc. have also been discussed.

Purpura fulminans in a complicated Falciparum malaria.

A 19-year-old male presented with fever, oliguria and purpuric lesions involving both hands. The patient was diagnosed as a case of purpura fulminans with disseminated intravascular coagulation due to complicated Falciparum malaria. The case is presented to sensitize the physicians to keep malaria as a differential in cases of fever with purpura fulminans.

Enfermedad de Võn Willebrand y embarazo gemelar: a propósito de un caso / Von Willebrand disease and pregnancy twins: a purpose of a case

Durante el embarazo ocurren alteraciones importantes en varios órganos y sistemas particularmente el mecanismo hemostático expresado por episodios hemorrágicos trombóticos o ambos, con una marcada influencia en la morbimortalidad materna. Las mujeres con coagulopatías presentan durante el embarazo, parto y puerperio, un riesgo mayor de hemorragia, por lo que es necesario una adecuada evaluación y un manejo multidisciplinario del embarazo. La enfermedad Võn Willebrand es una coagulopatía poco común. Con el objetivo de revisar el manejo intraparto de pacientes con coagulapatías hereditarias. Se presenta el caso clínico de una mujer con embarazo gemelar portadora de Enfermedad de Võn Willebrand tipo 1, recomendando al final, un protocolo de estudio de las pacientes y sus hijos.

Embolia de líquido amniótico: Criterio diagnóstico en dos casos fatales / Amniotic fluid embolism: Diagnostic criteria in two fatal cases

La embolia de líquido amniótico continúa siendo una causa importante de mortalidad materna. Presentamos la información obtenida por medio de la cateterización cardíaca derecha y la ecocardiografía, en dos pacientes que desarrollaron embolia de líquido amniótico y fallecieron por shock y coagulación intravascular diseminada a pesar del tratamiento intensivo. Aunque la fisiopatología continúa siendo discutida, la embolia por líquido amniótico se puede diagnosticar y manejar a partir de los valores hemodinámicos y el ecocardiograma.

Amniotic fluid embolism still remains an important cause of maternal mortality. We present information obtained by echocardiography and right cardiac catheterization of two patients who developed amniotic fluid embolism and died from shock and disseminated intravascular coagulation despite intensive medical treatment. Although the pathophysiology remains controversial, amniotic fluid embolism can be presumptively diagnosed and managed with hemodynamic values and echocardiography.

Coagulação intravascular disseminada no paciente crítico / Coagulation intravascular disseminated in critical patient

Coagulação intravascular disseminada é uma síndrome caracterizada por ativação sistêmica da coagulação, com conseqüente deposição intravascular de fibrina, trombose vascular e disfunção de órgão. O consumo de plaquetas e fatores de coagulação provoca trombocitopenia e sangramentos. O principal fator etiológico no paciente grave é a sepse. O tratamento consiste em tratar a causa e repor hemoderivados se houver sangramento ou algum procedimento cirúrgico for programado.

Overt disseminated intravascular coagulation in obstetric patients.

OBJECTIVE: To determine the incidence, etiology and outcome of treatment in obstetric patients complicated by overt disseminated intravascular coagulation (DIC). MATERIAL AND METHOD: Medical records of 25 obstetric patients with a diagnosis of DIC in Songklanagarind University Hospital from January 1993 to December 2005 were reviewed RESULTS: The incidence of overt DIC was I per 1,355 deliveries. Median maternal age was 30 years (range 17-44 years). Median duration of hospital stay was 10 days (range 0-32 days). The main associated conditions included abruptio placentae in 6 patients (24%), pregnancy-induced hypertension (PIH) in 5 (20%), amniotic fluid embolism in 4 (16%), acute fatty liver of pregnancy (AFLP) in 4 (16%), and HELLP syndrome in 3 (12%). A definite diagnosis ofDIC was made in 8 patients (32%) with a median DIC score of 6 (range 5-7) and the remainder were clinically diagnosed with incomplete work-up. All patients received blood component replacement. Cesarean section was performed in 10 patients (40%) and hysterectomy in 9 patients (36%). Six patients died, giving a case mortality rate of 24%. Three were associated with amniotic fluid embolism and one of each with fulminant hepatitis, ALFP and HELLP syndrome. Thirteen of 24 fetuses (54%) died, most related to abruptio placentae (6/6, 100%), PIH (4/5, 80%), and amniotic fluid embolism (2/4, 50%). CONCLUSION: Various pregnancy-related conditions will predispose to DIC development. Early diagnosis with prompt treatment, including a quick decision for surgical intervention, and eradication of predisposing conditions would minimize maternal morbidity and mortality.

Diagnosis of Overt Disseminated Intravascular Coagulation: A Comparative Study Using Criteria from the International Society Versus the Korean Society on Thrombosis and Hemostasis

PURPOSE: Since 1993, Koreans have used diagnostic criteria set by the Korean Society on Thrombosis and Hemostasis (KSTH) in the diagnosis of overt disseminated intravascular coagulation (DIC). In 2001, the Scientific and Standardization Committee (SCC) of the International Society on Thrombosis and Hemostasis (ISTH) proposed new diagnostic criteria for the diagnosis of overt DIC. We wanted to compare the use of the ISTH versus KSTH criteria in the diagnosis of overt DIC. MATERIALS AND METHODS: We enrolled 131 patients over the age of 15 years, who had been admitted and diagnosed as having DIC from May 2000 to April 2005 at the Youngdong Severance Hospital, Seoul, Korea. Of the 131 patients, there were 71 males and 60 females, with a median age of 61 years. Hemostatic tests, including platelet counts, PT, aPTT, fibrinogen level and D-dimer, were evaluated based on the respective scoring systems. To assess the concordance between the two diagnostic systems, we used the Student's t-test and the K-coefficient. RESULTS: There were 79 patients compatible with the ISTH criteria and 63 patients with the KSTH criteria. Sixty-one patients were compatible with both diagnostic systems. The grade of agreement, or concordance rate, was 84.7% and the K-coefficient, or interrater reliability, was as low as 0.6 without significance. However, if we scored 1 point for a fibrinogen level of 100-150mg/dL, and 2 points for a level below 100mg/dL, for the ISTH criteria, then 63 patients were compatible with both diagnostic systems, and the concordance rate increased to 85.5% and the K-coefficient to 0.71 with significance. CONCLUSION: To achieve good agreement between the ISTH and KSTH diagnostic systems for overt DIC, we highly recommend changing the plasma fibrinogen cut-off value in the ISTH criteria from 100mg/dL to 150mg/dL and scoring up to 2 points for a level below 100 mg/dL.

Investigation of Hemostatic Changes in Patients with Sepsis / 대한진단검사의학회지

BACKGROUND: It is known that severe infection and inflammation lead to hemostatic abnormalities. Recently, much attention is focused on the mechanisms of infection or inflammation and on how it plays a central role in effecting the coagulation system. Disseminated intravascular coagulation in particular, is a common phenomenon in patients with sepsis, but the clinical implications of this condition are not clear. Therefore we attempted to evaluate the changes of the coagulation system in patients with sepsis and studied the factors that lead to such changes. METHODS: One hundred one patients diagnosed with sepsis were enrolled in this study. The patients were clinically evaluated for underlying disease and data for inflammatory status and coagulative changes were evaluated retrospectively. RESULTS: The WBC count increased in 76% and decreased in 6% of sepsis patients in comparison to the reference interval. The platelet count decreased in 65.3%. Changes in coagulative tests such as prothrombin time, activated partial thromboplastin time, antithrombin III, and D-dimer were observed in 70.4%, 52.7%, 87.2% and 100% of the patients, respectively. Correlation between ESR and fibrinogen was the highest in relation to the other coagulation factors. CRP also showed the highest correlation with fibrinogen in contrast to the other coagulation factors. CONCLUSIONS: This study confirmed the clear activation of coagulation in patients with sepsis. Of the evaluated factors involved in coagulation and fibrinolysis, fibrinogen showed the highest correlation to indices representing the inflammatory state. However further studies on the anticoagulant pathway are necessary in elucidating this matter.

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

Disseminated intravascular coagulation in a patient with HELLP syndrome

HELLP [Hemolysis Elevated Liver enzyme Low Platelet] syndrome an atypical form of severe preeclampsia, and if not treated is potentially fatal for both mother and fetus. Mostly presentation of HELLP syndrome is after 34 weeks of gestation but presentation may be between 20 weeks of gestation to few days after delivery. It is estimated that up to 10% of pregnancies are affected by HELLP syndrome. Only treatment option available to date is delivery of fetus and products of conception. In this case report patient was diagnosed having HELLP syndrome with DIC while initial presentation being thrombocytopenia and hypoxia

Diagnosis of disseminated intravascular coagulation in sepsis scoring system of a thrombosis-hemostasis center.

BACKGROUND: Disseminated intravascular coagulation (DIC) is a septic complication that is not easily diagnosed. The purpose of the study is to obtain a scoring system to diagnose DIC in sepsis. SUBJECT AND METHODS: An observational study with a cross-sectional design was performed at the Department of Internal Medicine, University of Indonesia, Dr. Cipto Mangunkusumo General Hospital from February to August 2002. Subjects were septic patients in the emergency unit or inpatient ward of the Department of Internal Medicine, and were taken consecutively. The criteria of sepsis, severe sepsis and septic shock were based on ACCP/SCCM Consensus 1991. The evaluation conformed to the Thrombosis Hemostasis Center (THC) scoring system, compared with modified Bick scoring system as a gold standard. RESULTS: There were 34 subjects ranging from 19 to 78 years old, 32.4% were septic patients, 41.2% with severe sepsis and 26.5% with septic shock. The most common source of infection was pneumonia, where bacterial pathogens were found in 35.2% of blood aerobic culture and 17.7% in pus or urine culture. Gram negative bacteria was the most common pathogen found. According to a modified Bick and THC scoring system, DIC was found in all subjects, consisting of mild and moderate DIC. No severe DIC was found. There was no difference between both scoring systems, with a p value of 0.125 based on the Mc Nemar test. There was no difference found in mild and moderate DIC in sepsis, severe sepsis and septic shock of modified Bick scoring systems (p value of 0.987) and THC scoring system (p value of 1.000). CONCLUSION: No difference was found between THC and modified Bick scoring system in diagnosing DIC in septic patients. In sepsis, severe sepsis and septic shock, mild and moderate DIC complications can be diagnosed with THC scoring system, which are of the same potency with the modified Bick, with the assumption that the modified Bick scoring system was the same as the Bick scoring system.