Postoperative excessive blood loss after cardiac surgery can be predicted with International Society on Thrombosis and Hemostasis scoring system / A perda sanguínea excessiva no pós-operatório de cirurgia cardíaca pode ser prevista com o sistema de classificação da Sociedade Internacional de Trombose e Hemostasia (ISTH)

Abstract Background and objective Prediction of postoperative excessive blood loss is useful for management of Intensive Care Unit after cardiac surgery. The aim of present study was to examine the effectiveness of International Society on Thrombosis and Hemostasis scoring system in patients with cardiac surgery. Method After obtaining approval from the institutional review board, the medical records of patients undergoing elective cardiac surgery using Cardio-Pulmonary Bypass between March 2010 and February 2014 were retrospectively reviewed. International Society on Thrombosis and Hemostasis score was calculated in intensive care unit and patients were divided with overt disseminated intravascular coagulation group and non-overt disseminated intravascular coagulation group. To evaluate correlation with estimated blood loss, student t-test and correlation analyses were used. Results Among 384 patients with cardiac surgery, 70 patients with overt disseminated intravascular coagulation group (n = 20) or non-overt disseminated intravascular coagulation group (n = 50) were enrolled. Mean disseminated intravascular coagulation scores at intensive care unit admission was 5.35 ± 0.59 (overt disseminated intravascular coagulation group) and 2.66 ± 1.29 (non-overt disseminated intravascular coagulation group) and overt disseminated intravascular coagulation was induced in 29% (20/70). Overt disseminated intravascular coagulation group had much more EBL for 24 h (p = 0.006) and maintained longer time of intubation time (p = 0.005). Conclusion In spite of limitation of retrospective design, management using International Society on Thrombosis and Hemostasis score in patients after cardiac surgery seems to be helpful for prediction of the post- cardio-pulmonary bypass excessive blood loss and prolonged tracheal intubation duration.

Resumo Justificativa e objetivo A previsão de perda sanguínea excessiva no pós-operatório é útil para o manejo em Unidade de Terapia Intensiva (UTI) após cirurgia cardíaca. O objetivo do presente estudo foi examinar a eficácia do sistema de classificação da Sociedade Internacional de Trombose e Hemostasia (International Society on Thrombosis and Hemostasis - ISTH) em pacientes submetidos à cirurgia cardíaca. Método Após obter a aprovação do Comitê de Pesquisa Institucional, os prontuários de pacientes submetidos à cirurgia cardíaca eletiva com circulação extracorpórea (CEC) entre março de 2010 e fevereiro de 2014 foram retrospectivamente revisados. O escore ISTH foi calculado na UTI e os pacientes foram alocados em dois grupos: grupo com coagulação intravascular disseminada (CID) manifesta e grupo com CID não manifesta. Para avaliar a correlação com a Perda Estimada de Sangue (PES), o teste t de Student e as análises de correlação foram usados. Resultados Dentre os 384 pacientes submetidos à cirurgia cardíaca, 70 com CID manifesta (n = 20) ou CID não manifesta (n = 50) foram incluídos. As médias dos escores CID na admissão na UTI foram 5,35 ± 0,59 (Grupo CID manifesta) e 2,66 ± 1,29 (Grupo CID não manifesta) e induzida CID manifesta em 29% (20/70). O grupo CID manifesta apresentou PES superior durante 24 horas (p = 0,006) e um tempo maior de intubação (p = 0,005). Conclusão Apesar da limitação do desenho retrospectivo, o uso do escore ISTH para o manejo de pacientes após cirurgia cardíaca parece ser útil para prever a perda sanguínea excessiva pós-CEC e o prolongamento da intubação traqueal.

Analysis of factors affecting hemorrhagic diathesis and overall survival in patients with acute promyelocytic leukemia

BACKGROUND/AIMS: This study investigated whether patients with acute promyelocytic leukemia (APL) truly fulfill the diagnostic criteria of overt disseminated intravascular coagulation (DIC), as proposed by the International Society on Thrombosis and Haemostasis (ISTH) and the Korean Society on Thrombosis and Hemostasis (KSTH), and analyzed which component of the criteria most contributes to bleeding diathesis. METHODS: A single-center retrospective analysis was conducted on newly diagnosed APL patients between January 1995 and May 2012. RESULTS: A total of 46 newly diagnosed APL patients were analyzed. Of these, 27 patients (58.7%) showed initial bleeding. The median number of points per patient fulfilling the diagnostic criteria of overt DIC by the ISTH and the KSTH was 5 (range, 1 to 7) and 3 (range, 1 to 4), respectively. At diagnosis of APL, 22 patients (47.8%) fulfilled the overt DIC diagnostic criteria by either the ISTH or KSTH. In multivariate analysis of the ISTH or KSTH diagnostic criteria for overt DIC, the initial fibrinogen level was the only statistically significant factor associated with initial bleeding (p = 0.035), but it was not associated with overall survival (OS). CONCLUSIONS: Initial fibrinogen level is associated with initial presentation of bleeding of APL patients, but does not affect OS.

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...

Evaluation of the Diagnostic Performance of Fibrin Monomer in Disseminated Intravascular Coagulation / 대한진단검사의학회지

BACKGROUND: Fibrin-related markers (FRM) such as fibrin monomer (FM) and D-dimer (DD) are considered useful biological markers for the diagnosis of disseminated intravascular coagulation (DIC). However, no studies on the diagnostic performance of different FRMs have been published in Korea. The aim of this study was to evaluate the diagnostic performance of FM for DIC in comparison with DD. METHODS: The reference limit of FM was determined based on plasma sample data obtained from 210 control individuals. To evaluate diagnostic performance, FM data from the plasma samples of 139 patients with DIC-associated diseases were obtained for DIC scoring. FM was measured by immunoturbidimetry using STA-LIATEST FM (Diagnostica Stago, France). Patients were classified according to the DIC score as non-DIC, non-overt DIC, or overt DIC. ROC curve analyses were performed. RESULTS: The reference limit in the control individuals was determined to be 7.80 microg/mL. Patients with DIC-associated diseases were categorized as non-DIC (N=43), non-overt DIC (N=80), and overt DIC (N=16). ROC curve analyses showed that the diagnostic performance of FM was comparable to DD in both non-overt DIC and overt DIC (P=0.596 and 0.553, respectively). In addition, FM had higher sensitivity, specificity, positive predictive value, and negative predictive value than DD for differentiating overt DIC from non-DIC. CONCLUSIONS: This study demonstrated that the diagnostic performance of FM for DIC was comparable to DD. FM might be more sensitive and more specific than DD in the diagnosis of overt DIC, but not non-overt DIC.

Evaluation of the Diagnostic Performance of Fibrin Monomer in Disseminated Intravascular Coagulation / 대한진단검사의학회지

BACKGROUND: Fibrin-related markers (FRM) such as fibrin monomer (FM) and D-dimer (DD) are considered useful biological markers for the diagnosis of disseminated intravascular coagulation (DIC). However, no studies on the diagnostic performance of different FRMs have been published in Korea. The aim of this study was to evaluate the diagnostic performance of FM for DIC in comparison with DD. METHODS: The reference limit of FM was determined based on plasma sample data obtained from 210 control individuals. To evaluate diagnostic performance, FM data from the plasma samples of 139 patients with DIC-associated diseases were obtained for DIC scoring. FM was measured by immunoturbidimetry using STA-LIATEST FM (Diagnostica Stago, France). Patients were classified according to the DIC score as non-DIC, non-overt DIC, or overt DIC. ROC curve analyses were performed. RESULTS: The reference limit in the control individuals was determined to be 7.80 microg/mL. Patients with DIC-associated diseases were categorized as non-DIC (N=43), non-overt DIC (N=80), and overt DIC (N=16). ROC curve analyses showed that the diagnostic performance of FM was comparable to DD in both non-overt DIC and overt DIC (P=0.596 and 0.553, respectively). In addition, FM had higher sensitivity, specificity, positive predictive value, and negative predictive value than DD for differentiating overt DIC from non-DIC. CONCLUSIONS: This study demonstrated that the diagnostic performance of FM for DIC was comparable to DD. FM might be more sensitive and more specific than DD in the diagnosis of overt DIC, but not non-overt DIC.

Clinical Usefulness of Plasma Interleukin-6 and Interleukin-10 in Disseminated Intravascular Coagulation / 대한진단검사의학회지

BACKGROUND: Disseminated intravascular coagulation (DIC) is a syndrome characterized by a systemic activation of coagulation leading to the intravascular deposition of fibrin and the simultaneous consumption of coagulation factors and platelets. Inflammatory cytokines can activate the coagulation system. This study investigated the diagnostic and prognostic usefulness of the plasma level of interleukin-6 (IL-6) and interleukin-10 (IL-10) for predicting DIC. METHODS: The study populations were 15 healthy controls and 81 patients who were clinically suspected of having DIC and were requested to perform DIC battery tests. The presence of overt DIC was defined by the International Society on Thrombosis and Haemostasis Subcommittee cumulative score of 5 or above. The 28 day mortality was used to assess the prognostic outcome. The plasma levels of the cytokines were measured by ELISA. RESULTS: The plasma levels of IL-6 and IL-10 in patients (N=81) were higher than those of control (N=15). IL-6 and IL-10 levels of overt DIC group (N=31) were 3 times and 1.5 times higher than those, respectively, of non-overt DIC group (N=50). In infection group (N=48), IL-6 and IL-10 levels of overt DIC group (N=18) were 5 times and 3 times higher than those, respectively, of non-overt DIC group (N=30). The diagnostic efficiency of IL-6 (optimal cut off >40.4 pg/mL) and IL-10 (>9.7 pg/mL) for the diagnosis of overt DIC were 67% and 69%, respectively, which were similar to that of D-dimer. Plasma levels of IL-6 and IL-10 were also higher in non-survivors than in survivors. The patients with higher levels of IL-6 and IL-10 showed a poorer prognosis. CONCLUSIONS: The proinflammatory cytokine, IL-6 and anti-inflammatory cytokine, IL-10 were useful for the diagnosis of overt DIC and the prediction of its prognosis. These results also showed the evidence of a close interaction between coagulation and inflammation.

Fibrinolytic markers and neurologic outcome in traumatic brain injury.

AIMS: To determine the usefulness of fibrinolytic markers as early prognostic indicators in patients with isolated head trauma. MATERIALS AND METHODS: Sixty-two consecutive patients (26 women and 36 men; mean age 61 years, range 2-76 years) with isolated head trauma seen within the first three hours of the trauma were included in the study. The Glasgow Coma score (GCS), platelet counts (Plt), prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, fibrin degradation products (FDP) and D-dimer levels were measured. Head computerized tomography (CT) findings were categorized as brain edema, linear fracture, depressed fracture, contusion and bleeding. Plt counts, PT, PTT, fibrinogen, FDP, D-dimer levels and CT findings were compared with both GCS and mortality in the first week. Statistical significance was accepted at P <or=0.05. RESULTS: A marked negative relationship was found between GCS and PT, PTT, FDP and D-dimer levels (P < 0.001). Plt levels did not correlate with GCS. Mortality was most strongly related to GCS, PT, FDP and D-dimer levels (P < 0.001, P < 0.001, P < 0.001 and P < 0.001, respectively). We found no relationship between mortality and CT findings, nor was there any significant relationship between Plt, PTT and fibrinogen levels. CONCLUSION: GCS and fibrinolytic markers measured within the first three hours were useful in determining the prognosis of patients with isolated head trauma.

Plasma Factor XIII Activity in Patients with Disseminated Intravascular Coagulation

The objective of this study was to investigate the correlation between factor XIII (FXIII) activity and disseminated intravascular coagulation (DIC) parameters and also to evaluate the clinical usefulness of DIC diagnosis. Citrated plasma from eighty patients with potential DIC was analyzed for FXIII activity. The primary patient conditions (48 male and 32 female, mean age, 51 years) were malignancy (n = 29), infection (n = 25), inflammation (n = 6), heart disease (n= 3), thrombosis (n = 2), injury (n = 2), and other miscellaneous conditions (n = 13). FXIII testing was performed using the CoaLinkTM FXIII Incorporation Assay Kit (PeopleBio Inc.). Among 80 patients who were suspected to have DIC based on clinical analysis, 46 (57.5%) fulfilled the overt DIC criteria (DIC score > = 5) according to the International Society of Thrombosis and Haemostasis. FXIII levels in the plasma were significantly decreased in overt DIC compared to non-overt DIC patients (mean 75.1% and 199.7% respectively, p < 0.0001). Interestingly, we found a significant inverse correlation between DIC scores and FXIII activity. In addition, FXIII activity significantly correlated with other hemostatic markers that included platelet count, prothrombin time, activated partial thromboplastin time, fibrinogen, and D-dimer. FXIII levels were significantly lower in patients with liver or renal dysfunction. In conclusion, FXIII cross-linking activity measurements may have differential diagnostic value as well as predictive value in patients who are suspected to have DIC.

Comparative evaluation of whole blood D-dimer test to plasma D-dimer test for diagnosis of disseminated intravascular coagulation.

Three rapid D-dimer test methods were compared for the diagnosis of acute disseminated intravascular coagulation (DIC). These were (a) SimpliRED, an autologous red cell agglutination assay. (b) DIMERTEST latex agglutination assay, containing monoclonal antibody DD-3B6/22(6), and (c) D-DI latex agglutination assay containing mouse anti-human D-dimer monoclonal antibodies. The D-DI latex method having higher sensitivity (100%) and specificity (81%) in clinically acute DIC was postulated as the gold standard and compared with the other two methods. The results suggest that D-DI latex agglutination assay containing mouse anti-human D-Dimer monoclonal antibodies are the better assay methods amongst all the three kits analyzed. It is advisable to look for the nature of the antibody used to coat the latex particles in plasma based kits. In emergency setting RBC kits may be of some use as rapid diagnosis is advantageous.

Antithrombin III assay using thrombin in disseminated intravascular coagulation (DIC), other thromboembolic disorders and hepatic diseases.

Fifty cases comprising 11 cases of disseminated intravascular coagulation (DIC), 16 cases of venous thromboses and 23 cases of hepatic diseases were studied for AT III levels using clotting assay. Twelve samples were subjected to ATIII estimation by the commercially available synthetic chromogenic assay. Twenty age and sex matched controls were also analysed to find out the reference value for the techniques. Low AT III levels, if present, were correlated with other markers of DIC, viz FDP and D-dimer assays. There was a decrease in the AT III levels in all the three disease categories with a significant difference between the AT III levels of the three disease categories. In DIC, lowest levels were observed which correlated well with FDP and D-dimer levels. There was no significant difference between the average AT III levels measured by both the clotting and synthetic chromogenic assay with the former procedure being relatively inexpensive.

D-dimer test: diagnostic role in clinical and sub-clinical DIC.

D-dimer test is used as a diagnosis test for acute disseminated intravascular coagulation (DIC). This study was undertaken to find out its sensitivity and specificity in the diagnosis of acute DIC and its role in diagnosis of sub-clinical DIC, as there is limited data available on the subject. Of the 29 patients of clinically acute DIC, all had positive D-dimer test, and markedly prolonged PT, APTT and TT were seen in 24 (83%) of these patients. D-dimer test was found to be highly specific but less sensitive for the diagnosis of acute DIC. Of the 29 patients predisposed to sub-clinical DIC. D-dimer was positive is 26 (90%) patients and PT, APTT and TT were mildly prolonged in 11 patients. It is suggested that D-dimer positivity for the diagnoses of sub-clinical DIC need to be considered with caution and to be supplemented by other coagulation test including serial follow up with d-dimer and coagulation tests.

Disseminated intravascular coagulation findings in 100 patients.

A retrospective study of 100 patients with disseminated intravascular coagulation from 1993 to 1997 is reported. Forty-five patients were neonates with a mean age of 12.6 days and 55 patients were infants, children and adolescents with a mean age of 6 years and 3 months. Most of them (91.5%) had complicated underlying conditions which included congenital anomalies, prematurity, malignancy, hematological and various diseases. Additionally, every patient had triggering conditions commonly identified as gram-negative septicemia. Bleeding and thromboembolic manifestations were found in 59.4 per cent and 19.8 per cent, respectively. The laboratory findings revealed red blood cell fragmentation, 89.6 per cent and thrombocytopenia, 85.8 per cent. Natural anticoagulants were studied in a few cases and revealed low levels of antithrombin III and protein C. The prompt effective management included treatment of underlying diseases, identification and relief of triggering conditions, correction of thrombocytopenia and coagulopathy, and fully supportive care. The overall case-fatality rate was 41.6 per cent which was not correlated with age, underlying diseases, triggering conditions, manifestation of bleeding, thromboembolism or shock, and exchange transfusion. However, a significant lower case-fatality rate was found in patients with positive culture (25%) as compared to those with sepsis and negative culture (51.7%) (p = 0.044). In addition, the febrile neutropenic patients, who showed good response to the administrated granulocyte-colony stimulating factor (G-CSF), survived from the DIC.

Incidence and possible reasons for discordant results between positive FDP and negative D-dimer latex assays in clinical specimens

In general, FDP and D-dimer values have a correlation in clinical conditions associated with disseminated intravascular coagulation(DIC) or coagulation activation. However, there are some patients with discordant results who demonstrate elevated FDP and negative D-dimer results by latex agglutination assays. The incidence and possible reasons for the discordance between FDP and D-dimer results were investigated through simultaneous measurements (n = 763) from clinical patients with suspected DIC or coagulation activation. 24.8% (189/763) of samples with elevated FDP were negative for D-dimer assays by the latex agglutination method. Further detailed analysis on randomly-selected discordant samples (n = 41) revealed that the most common reason for the discordance was the lower sensitivity of the semiquantitative latex agglutination method for D-dimer, compared with quantitative enzyme or other latex immunoassay. The other contributing factors to the discordance were accelerated fibrinogenolysis without secondary fibrinolysis, elevated soluble fibrin monomer and rheumatoid factor.

Dosagem da antitrombina III usando o substrato cromogênico Tos-Gly-Pro-Arg-NAN, em diversas situaçöes patológicas / Antithrombin III dosage using the chromogenic substrate Tos-Gly-Pro-Arg-NAN, in several pathological situations

O uso de método funcional para dosagem de antitrombina III (ATIII) é fundamental para o diagnóstico de deficiência deste inibidor da coagulaçao. OBJETIVO. Padronizar metodologia para dosagem da ATIII no plasma, utilizando-se microplacas, em diferentes situaçoes clínicas. MÉTODOS. A dosagem de ATIII foi feita utilizando-se o substrato cromogênico Tos-Gly-Pro-Arg-NAN, específico para trombina, e sintetizado no Departamento de Biofísica da Escola Paulista de Medicina. RESULTADOS. Dos 21 pacientes com trombose venosa (TV-P), 20 apresentaram valores superiores a 70 por cento (ll3 ñ 22 por cento), dos quais uma paciente de 22 anos apresentava deficiência congênita, com ATIII de 56 por cento e história de TVP recorrente, além de história familiar de TVP. O nível de ATIII em seis pacientes portadores de doença de von Willebrand foi normal (lO9 ñ 28 por cento), como esperado. Em 20 pacientes com insuficiência hepática foi observada reduçao importante do nível de ATIII (42 ñ 19 por cento), pois este inibidor é produzido no hepatócito, sendo bom parâmetro para avaliar a funçao hepática. Os três pacientes portadores de sepse com CIVD apresentaram níveis reduzidos de ATIII (45 + 5 por cento), que é consumida durante processo de ativaçao intravascular da coagulaçao. Os níveis de ATIII mostraram correlaçao significante com o TP e os níveis de fator V, ambos bons parâmetros para avaliaçao da funçao hepática e para monitorizaçao da CIVD. Houve correlaçao significante entre as dosagens realizadas com o substrato Tos-Gly-Pro-Arg-NAN, sintetizado na EPM, e o substrato S-2238 do laboratório Kabi. CONCLUSOES. A medida da ATIII usando substrato cromogênico Gly-Pro-Arg-NAN é de fácil execuçao e é sensível para o diagnóstico da deficiência deste inibidor em pacientes com insuficiência heopática, coagulaçao intravascular disseminada e trombofilia.