DIC Score Research Articles

Recombinant Human Thrombomodulin in the Treatment of Acute Myeloid Leukemia Patients Complicated By Disseminated Intravascular Coagulation: Results of a Multicenter, Retrospective Epidemiologic Study in Japan

Background: Thrombomodulin is a thrombin receptor that acts an important regulator of coagulation. Recombinant human thrombomodulin (rTM) is a promising anticoagulant that activates protein C, which leads to the inactivation of factor (F) Va and FVIIIa and decreased formation of thrombin. rTM has also been identified as a novel anticoagulant with a long half-life. When compared with heparin therapy, rTM therapy more significantly improves DIC and alleviates bleeding symptoms in DIC patients. However, it is unknown as to whether or not the treatment with rTM affects patient’s outcome. Therefore, we retrospectively analyzed 88 patients with acute myeloid leukemia (AML) (except adult acute promyelocytic leukemia), who suffered from DIC and compared the outcomes between the patients with low molecular weight heparin (LMWH) therapy and with rTM in multi-center.Methods: The diagnosis of de novo AML patients was based on the morphology, histopathology, cytogenetics, expression of leukocyte-differentiation antigens, and the French-American-British (FAB) classification. The patients examined in the current study (aged 18–84 years) were diagnosed with AML from January 2004 to March 2013. Patients younger than 65 years of age were treated with idarubicin (12 mg/m2 per day) for 3 days (days 1–3) and cytarabine (100 mg/m2 per day) by continuous infusion for 7 days (days 1–7). Patients 65 years of age or older were treated with daunorubicin (40 mg/m2 per day) for 3 days (days 1–3) and 200 mg/m2 per day behenoyl cytarabine for 8 days (days 1–8). The continuous infusion of dalteparin sodium (75 IU/kg per day) or recombinant human thrombomodulin (380 U/kg per day) was used to treat DIC.The diagnostic criteria for DIC previously proposed by the Japanese Ministry of Health and Welfare (JMHW) were employed in this study. The criteria are based on a scoring system including the presence of underlying disease (0 or 1 points), organ failure (0 or 1 points), and the results of coagulation tests of fibrinogen (0 to 2 points), fibrin/fibrinogen degradation products (FDP, 0 to 3 points), and the prothrombin time (0 to 2 points). DIC is diagnosed when the DIC score is greater than 4.Comparisons between the qualitative variables were carried out using the Chi-square test. The survival probabilities were estimated by the Kaplan-Meier method, and differences in the survival distributions were evaluated using the log-rank test. These statistical analyses were performed with the software package Stata version 11 (StataCorp LP, College Station, TX, USA). For all analyses, the P values were 2-tailed, and a P value less than.05 was considered to be significant.Results: DIC developed in 88 patients. Median age of patients was 60 years (from 15 to 85) and median duration was 699 days (from 15 to 2552 days). 30 patients were treated with dalteparin sodium and 58 patients were treated with recombinant human thrombomodulin. The FAB subtypes, age distribution, major laboratory data (CBC, LDH, and CRP) were not significantly different between two groups. The duration of DIC treatment with rTM was significant shorter than that with LMWH (6.3 days vs 15.1 days, p <0.0001). The overall survival was superior in the rTM group compared with dalteparin sodium group (P=0.0425).Discussion: Patients with DIC resulting from sepsis or hematological malignancies can be successfully treated if sufficient treatments are offered. However, additional anti-coagulant treatments may be required in many cases because of life-threatening abnormal coagulation states. In Japan, LMWH has been recommended by the Japanese Society of Thrombosis Hemostasis/DIC subcommittee for the treatment of DIC because patients were less likely to bleed when treated with LMWH than with unfractionated heparin (UFH) (Level 2b). On the other hand, a randomized controlled study reported that rTM therapy improved DIC and relieved bleeding complications in DIC patients more significantly than UFH therapy. To the best of our knowledge, very few institutes compared rTM with heparin as a therapy for DIC during AML induction therapy. Here, we demonstrate that if patients develop DIC, their prognosis will be improved by the administration of rTM.Conclusion: We conclude that treatment with rTM is safe and efficient, when compared with LMWH. Based on this retrospective study, randomized control study could be attempted in the future. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Evaluation of ISTH DIC Score to Predict Significant Bleeding and Thrombosis Events in Pediatric Acute Promyelocytic Leukemia; A Report from the Children’s Oncology Group AAML0631 Trial

Early deaths and morbidity due to coagulopathy (both hemorrhage and thrombosis) remain a significant problem in APL. Some studies have shown that various clinical and laboratory parameters (including elevated WBC count, low platelet count, decreased fibrinogen, and elevated PT) are associated with risk for hemorrhage and thrombosis, but individually these features are neither sensitive nor specific predictive tools. The ISTH DIC score was developed as a set of objective criteria for the diagnosis and severity of DIC with a score of ≥5 correlating with overt DIC (Taylor, et al, Thromb Haemost, 2001). When applied to coagulopathy in APL, one retrospective study showed that an ISTH DIC score of ≥6 independently correlated with hemorrhagic early death (Mitrovic, Med Onc, 2013). Here we evaluate the predictive value of the ISTH DIC score for pediatric patients with newly diagnosed APL treated on Children’s Oncology Group study AAML0631.The ISTH DIC score is calculated using platelet count (≥100,000 = 0; 50,000-99,999 = 1; <50,000 = 2), fibrinogen level (≥100 mg/dL = 0; <100 mg/dL = 1), prothrombin time prolongation above upper limit of normal (ULN) (<3 seconds = 0, 3-6 seconds = 1, >6 seconds = 2), and D-dimer (<2 times ULN = 0, 2-4 times ULN = 2, >4 times ULN = 3). Out of the 102 eligible patients on AAML0631, complete data on coagulation parameters and clinically significant adverse events (AEs) related to coagulopathy (grade III-V bleeding or thrombosis) during induction were available on 76 patients. Among 31 pts with ISTH DIC score ≥6, 10 patients had at least 1 AE related to coagulopathy in induction. Four of these were high risk patients (WBC >10,000 at diagnosis) who experienced grade V early deaths. Among 45 pts with ISTH DIC score <6, there were only 4 patients with at least 1 coagulopathy AE and no grade V events. The ISTH DIC score ≥6 was significantly associated with a higher rate of grade V events compared to score <6 (13% vs. 0%, P=0.025). When considering all AEs (grade III-V) due to coagulopathy, patients with ISTH DIC score ≥6 compared to those with score <6 also had a significantly increased rate of at least 1 AE (grade III-V) related to coagulopathy (32% vs. 9%, P=0.015). However, the sensitivity of the ISTH DIC score in predicting patients experiencing at least 1 coagulopathy event during induction was only 66.7% and the specificity was 65.6%.The coagulopathy of APL is unique as there is activation of the coagulation cascade due to expression of tissue factor and other procoagulants with concomitant increase in primary and secondary fibrinolysis due to expression of Annexin II on the APL blasts. Traditional coagulation tests such as those used to calculate the ISTH DIC score cannot measure the unique contribution of fibrinolysis or the balance between coagulation and fibrinolysis. The current study demonstrates that ISTH DIC score is significantly correlated with AEs related to coagulopathy, and yet it has low sensitivity and specificity as a predictive model in pediatric APL patients. Other biomarkers and coagulation assays such as thrombomodulin levels and thrombin generation ought to be studied for their predictive value and to inform potential intervention strategies. Such prospective studies are planned for the next APL clinical trial in the Children’s Oncology Group. DisclosuresOff Label Use: Idarubicin- labeled for use in AML/APL for adults (not pediatric patients).

Thrombotic events in acute promyelocytic leukemia

IntroductionThrombotic events (TE) appear to be more common in acute promyelocytic leukemia (APL) than in other acute leukemias, with reported prevalence ranging from 2 to10-15%. Materials and MethodsWe retrospectively analyzed the data on TE appearance in 63 APL patients. ResultsTE occured in 13 (20.6%) cases, four arterial (6.3%) and nine venous (14.3%). TE were more frequently diagnosed after initiation of weekly D-dimer monitoring (7 TE during 20months vs 6 during 76months, P=0.032). Patients with and without venous thrombosis were significantly different regarding female/male ratio (P=0.046), PT (P=0.022), aPTT (P=0.044), ISTH DIC score (P=0.001), bcr3 (P=0.02) and FLT3-ITD (P=0.028) mutation. The most significant risk factor for venous TE occurrence in multivariate analysis was FLT3-ITD mutation (P=0.034). PAI-1 4G/4G polymorphism was five times more frequent in patients with venous TE than without it (P=0.05). Regarding risk factors for arterial TE we failed to identify any. ConclusionsWe have demonstrated that APL-related TE rate is higher than previously reported and that weekly D-dimer monitoring might help to identify patients with silent thrombosis. Moreover, our study suggests a possible relationship between venous TE occurrence and several laboratory findings (PT, aPTT, ISTH DIC score, bcr3 isoform, FLT3-ITD mutation and PAI 4G/4G). Prophylactic use of heparin might be considered in patients with ISTH DIC score<5, bcr3 isoform, FLT3-ITD mutation and PAI 4G/4G.

Usefulness of shock indicators for determining the need for blood transfusion after massive obstetric hemorrhage.

Massive obstetric hemorrhage (MOH) requires prompt transfusion of red blood cells and coagulation factors. Because MOH has a diverse pathogenesis, the shock index (SI) alone may be insufficient for determining blood transfusion. Here, we retrospectively analyzed patients with MOH to determine usefulness of the indicators of shock including the SI in evaluating the need for blood transfusion. We reviewed records of 80 emergency referral patients who had received blood transfusions at our department between 1 January 2009 and 31 July 2011. The shock indicators for blood transfusion are estimated blood loss, fibrinogen level, hemoglobin concentration, the Japan Society of Obstetrics and Gynecology disseminated intravascular coagulation (JSOG DIC) score and the SI. The strength of the correlation of each shock indicator with the transfusion volume was ranked using Spearman's rank correlation coefficient-ρ and multivariate analysis. Although the SI showed significant positive correlation with blood transfusion volume for red blood cell concentrate (RCC) and fresh frozen plasma (FFP) in patients with dilutional coagulopathy, a stronger correlation was seen with the fibrinogen level and JSOG DIC score. In patients with consumptive coagulopathy, the strongest correlation was seen between RCC transfusion volume and fibrinogen level, and between FFP transfusion volume and JSOG DIC score followed by fibrinogen level. In multivariate analysis, only fibrinogen level was significantly associated with both RCC and FFP massive transfusion. Because MOH has a diverse pathogenesis, various indicators should be evaluated. Among shock indicators, fibrinogen level was the best indicator of the need for blood transfusion following MOH.

Role of Presepsin (sCD14-ST) and the CURB65 scoring system in predicting severity and outcome of community-acquired pneumonia in an emergency department

CD14 is one of the leukocyte differentiation antigens, and is present in macrophages, monocytes, granulocytes and their cell membranes. Presepsin, namely soluble CD14-subtype (sCD14-ST) is produced by circulating plasma proteases activating cleavage of soluble CD14 (sCD14). The aim of this study is to investigate the role of Presepsin and the CURB65 scoring system in the evaluation of severity and outcome of CAP in an ED. A prospective, observational study was performed in an ED of an university teaching hospital from November 2011 to October 2012. A total of 359 patients with CAP and 214 patients with severe CAP (SCAP) were consecutively enrolled. Plasma Presepsin, lactate, serum PCT levels and leukocyte counts were measured and CURB65 score were calculated at admission enrollment. Plasma Presepsin levels were significantly higher in SCAP patients than in CAP patients (P < 0.0001), increasing correspondingly with the enhancement of CURB65 score. Patients with ARDS or DIC had obviously higher plasma Presepsin levels than those without ARDS or DIC (all P < 0.0001), and plasma Presepsin levels were significantly higher in non-survivors than in survivors at 28-day follow-up. In logistic regression analysis, CURB65 score was the independent predictor of ARDS, and Presepsin was the independent predictor of DIC, and Presepsin and CURB65 score were both the independent predictors of 28-day mortality. The AUCs showed Presepsin in combination with CURB65 score in predicting ARDS, SCAP and 28-day mortality was superior to Presepsin or CURB65 score alone ( all P < 0.01), Presepsin was better than CURB65 score and leukocyte in predicting DIC ( P < 0.01). Presepsin is a valuable biomarker in predicting severity and outcome in CAP patients in the ED and Presepsin in combination with CURB65 score significantly enhanced the predictive accuracy.

DIC score in pregnant women--a population based modification of the International Society on Thrombosis and Hemostasis score.

ObjectivesThe objectives of this study were: 1) To determine the component needed to generate a validated DIC score during pregnancy. 2) To validate such scoring system in the identification of patients with clinical diagnosis of DIC.Material and MethodsThis is a population based retrospective study, including all women who gave birth at the ‘Soroka University Medical Center’ during the study period, and have had blood coagulation tests including complete blood cell count, prothrombin time (PT)(seconds), partial thromboplastin time (aPTT), fibrinogen, and D-dimers. Nomograms for pregnancy were established, and DIC score was constructed based on ROC curve analyses.Results1) maternal plasma fibrinogen concentrations increased during pregnancy; 2) maternal platelet count decreased gradually during gestation; 3) the PT and PTT values did not change with advancing gestation; 4) PT difference had an area under the curve (AUC) of 0.96 (p<0.001), and a PT difference ≥1.55 had an 87% sensitivity and 90% specificity for the diagnosis of DIC; 5) the platelet count had an AUC of 0.87 (p<0.001), an 86% sensitivity and 71% specificity for the diagnosis of DIC; 6) fibrinogen concentrations had an AUC of 0.95 (p<0.001) and a cutoff point ≤3.9 g/L had a sensitivity of 87% and a specificity of 92% for the development of DIC; and 7) The pregnancy adjusted DIC score had an AUC of 0.975 (p<0.001) and at a cutoff point of ≥26 had a sensitivity of 88%, a specificity of 96%, a LR(+) of 22 and a LR(−) of 0.125 for the diagnosis of DIC.ConclusionWe could establish a sensitive and specific pregnancy adjusted DIC score. The positive likelihood ratio of this score suggests that a patient with a score of ≥26 has a high probability to have DIC.

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Introduction: Severe traumatic brain injury is generally associated with a poor functional prognosis. However, there are some patients who demonstrate a good functional prognosis. To evaluate the procedures associated with a better clinical outcome in severe traumatic a brain injury, we performed a retrospective review of our own hospital clinical data. Methods: Severe traumatic brain injury patients were transferred by the emergency medical system to Hokkaido University Hospital between January 1, 2001 and December 31, 2012, due to high energy injury. During this period, 205 patients were transferred, and 50 patients were treated by either craniotomy or craniectomy, and 80 patients underwent only medical treatment. Seventy patients were excluded because they had an Injury Severity Score (ISS) of less than 14. The Glasgow coma scale (GOS), ISS, JAAM DIC score, SOFA score, APACHE score, and Glasgow outcome scale were all obtained from the medical records. Results: Two hundred and five patients were identified. Fifty patients were surgically treated within 24 hours after admission. The overall mortality rate was 19.23%. The GOS was better in the surgery group than in the only medical treatment group (3.26 vs. 2.93). The mortality rate was lower in the surgery group than in the only medical treatment group (10.0% vs. 18.9%). A subgroup analysis found that the good recovery group (GOS 4 to 5) was younger than that of the poor recovery group (GOS 1 to 3), (33.7y vs. 39.1y), and the serum fibrinogen level of the good recovery group was higher than that of the poor recovery group (214.6mg/dl vs. 173.3mg/dl). Conclusions: Surgery was associated with a better GOS than medical treatment only. In a subgroup analysis, the good recovery group was younger than the poor recovery group, and the serum fibrinogen level of the good recovery group was higher than that in the poor recovery group.

Soluble Recombinant Thrombomodulin Ameliorates Hematological Malignancy-Induced Disseminated Intravascular Coagulation More Promptly Than Conventional Anticoagulant Therapy Without Causing Severe Hemorrhagic Events

BackgroundDisseminated intravascular coagulation (DIC) is a lethal complication in patients with hematological malignancies. Although standard therapy against DIC remains to be established, soluble recombinant thrombomodulin (rTM), which serves as a receptor for thrombin, has been developed and its effectiveness for DIC was reported (Saito et al, J Thromb Haemost 2006). However, there is not enough evidence of rTM on DIC associated with hematological malignancy. Therefore we retrospectively compared outcome of hematological malignancy-related DIC treated with rTM or other conventional anticoagulant therapies. Patients and MethodsOne hundred and sixty-five consecutive DIC episodes in 146 patients with hematological malignancies (AML except for APL, 49; APL, 21; ALL, 19; NHL, 31; myeloma, 11; CML, 7; other; 8) hospitalized between January 2004 and May 2013 in University of Tsukuba Hospital were retrospectively analyzed. Diagnosis of DIC was based on DIC score of Japanese Ministry of Health and Labor Welfare criteria (Kobayashi et al, Bibl Haematol 1983). DIC was induced by hematological malignancy itself (h-DIC) or severe infection secondary to hematological malignancy (i-DIC) in 108 and 57 episodes, respectively. In 73 episodes, 380 units/kg/day of rTM was administered intravenously from the onset of DIC for median of 6 (range, 2-22) days. Other DIC episodes were treated with conventional anticoagulant therapy (low molecular weight heparin, 65; gabexate mesilate, 17; other anticoagulant, 10). Every anticoagulant therapy was accompanied by treatment for DIC-causing disease. We compared recovery time from DIC (the day when DIC score was decreased to 5 or less), overall survival, and severe hemorrhagic events related to the treatment, between rTM- and conventional anticoagulant-treated groups. ResultsFifty-three DIC episodes were accompanied by bleeding tendency at the onset. In h-DIC, recovery from DIC was significantly more prompt in rTM-treated group, with the recovery rates of 55% (95% CI: 40 - 68) in the rTM-treated group and 33% (95% CI: 21 - 45) in the conventional therapy group at day 7 after the therapy initiation (P = 0.03, Fig.1). On day 14, the recovery from h-DIC was seen in 72% (95% CI: 56 - 83) and 60% (95% CI: 47 - 71) with the rTM and conventional therapies, respectively (P = 0.2). By contrast, recovery from i-DIC was significantly worse than that from h-DIC, and was not influenced by anticoagulant therapies. Recovery rates from i-DIC at day 14 were 27% (95% CI: 12 - 45) in the rTM-treated group and 36% (95% CI: 19 - 52) in the conventional therapy group (P = 0.6). Day 60 overall survival rates in h-DIC were 82% (95% CI: 66 - 91) and 79% (95% CI: 65 - 88) in the rTM-treated and conventional therapy groups. In i-DIC, on the other hand, 33% (95% CI: 16 - 52) and 33% (95% CI: 18 - 50) survived with the rTM and conventional therapies, respectively (Fig.2). Severe hemorrhagic events that led to discontinuation of anticoagulant therapy was significantly less in the rTM-treated group (3%; 95% CI, 0.3 - 9) compared with that in the conventional therapy group (12%; 95% CI: 6 - 20; P = 0.04). [Display omitted] [Display omitted] Discussion and ConclusionThe recovery from h-DIC treated with rTM was more prompt compared to that with conventional anticoagulant therapy. Although the conventional anticoagulant therapy has fostered bleeding tendency, bleeding tendency was reduced after rTM administration in most of the DIC episodes. We emphasize that rTM can be an effective anti-DIC agent without causing adverse hemorrhagic event even in DIC cases with preexisting bleeding tendency. However, the outcome was still significantly worse in i-DIC secondary to hematological malignancies even after introduction of rTM. Further development of anticoagulant therapy is required for the control of i-DIC. Disclosures:Chiba:Asahi Kasei Pharma: Research Funding.

The effectiveness of XueBiJing injection in therapy of sepsis: a multicenter clinical study

Objective To evaluate the effectiveness and safety of Xuebijing (XBJ) injection in therapy of sepsis.Methods It is a prospective,randomized controlled trial conducted in multicenter.Totally 731 patients with sepsis were enrolled from January to December 2011 at 37 centers and randomly (random number) separated into the XBJ group (n =392) and the control group (n =339).Basic therapy was adoptd in the both groups,but XBJ injection was additionally used in the XBJ group.The effectiveness of XBJ injection was evaluated by comparing the differences of MEDS score,APACHE Ⅱ score,DIC score,SOFA score,coagulation parameters,duration of mechanical ventilation and antibiotic therapy between the two groups.The influence on the outcome of XBJ injection was assessed by mortalities of 28-day and 90-day.The side-effects of XBJ injection were recorded.Results The score of each system and the abnormal rates of coagulation parameters were significantly higher in the XBJ group than in the control group at admission (P ＜ 0.05).After combined treatment of XBJ injection and basic therapy,the score values of the XBJ group decreased distinctly,and the differences of pre-therapy and post-therapy in the two groups had statistical significance (P＜0.01).The abnormal rates of coagulation parameters in the XBJ group decreased after therapy.The 90-day mortality of the XBJ group was lower than the control group (P ＜ 0.05).No severe side-effects were found during study.Conclusions This study proved that the severity of sepsis can be alleviated by XBJ injection.Meanwhile,the organ function and the coagulation status can be protected,and then the prognosis can be improved.The safety of XBJ injection was good. Key words: Sepsis; Xuebijing injection; Therapy; Score system; Coagulation; Prognosis; RCT; Multicenter

International Society of Thrombosis and Hemostasis Scoring System for disseminated intravascular coagulation ≥6: a new predictor of hemorrhagic early death in acute promyelocytic leukemia

High-hemorrhagic early death (ED) rate is a major impediment in the managing of acute promyelocytic leukemia (APL). In our group of 56 newly diagnosed APL patients, ED occurred in 12 subjects, due to endocranial bleeding (8/12), differentiation syndrome (2/12), or infection (2/12). Predictors of hemorrhagic ED were as follows: white blood cells count ≥ 20 × 10(9)/L (P = 0.002337), Eastern cooperative oncology group performance status ≥ 3 (P = 0.00173), fibrinogen level <2 g/L (P = 0.004907), prothrombin time <50% (P = 0.0124), and International Society of Thrombosis and Hemostasis Scoring System for disseminated intravascular coagulation (ISTH DIC score) ≥ 6 (P = 0.00741). Multivariate analysis indicated ISTH DIC score ≥ 6 to be the most significant predictor for hemorrhagic ED (P = 0.008). The main finding of this study is that simple coagulation-related tests, performed on hospital admission and combined in the ISTH DIC score, might help to identify patients at high risk for fatal bleeding needing more aggressive supportive measures.

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Introduction: Coagulopathy is commonly found in cardiac arrest and was suggested to be associated with prognosis. It’s been reported that tissue hypoperfusion plays major role in coagulation activation and subsequent coagulopathy in trauma, sepsis and cardiac arrest. Hypothesis: It is possible that factors other than tissue hypoperfusion can also significantly influence the initial coagulation process. We sought to investigate other possible determinants of severity of initial coagulopathy in cardiac arrest. Methods: A single center emergency department out-of-hospital cardiac arrest registry was analyzed to identify witnessed sudden cardiac arrest (SCA) patients between 2008 and 2011. Patients were assessed for prehosptial factors and initial laboratory results. The severity of initial coagulopathy was measured with ISTH DIC score. Linear regression modeling using best subset method was used to identify and assess the relative importance of each significant independent variable. The relative importance was calculated with leave-one-out method based on the residual sum of squares provided by SPSS 19.0 (SPSS Inc., IL) Results: Among 124 witnessed SCA patients, DIC score was available in 106 patients. Increased DIC score was associated with lower rate of achieving survival discharge (odds ratio [OR], 0.43 per unit; 95% confidence interval [CI], 0.27-0.69; p<.001) and good neurologic outcome (6-month CPC 1-2; OR, 0.38 per unit; 95% CI, 0.21-0.67; p=.001). The linear regression modeling identified four major predictors including serum albumin and lactic acid level, age and male sex with their beta coefficients of -0.575 (95% CI, -0.934 - -0.215; p=0.002), 0.089 (95% CI, 0.025 - 0.153; p=0.007), 0.022 (95% CI, 0.007 - 0.037; p=0.004) and -0.503 (95% CI, -1.004 - -0.003; p=0.049), respectively. The calculated relative predictor importance was 0.277, 0.210, 0.241 and 0.109, respectively. Conclusions: In addition to lactic acid, serum albumin, age and sex were also significant factors determining early coagulopathy in cardiac arrest. Future study is needed to investigate the possible roles of serum albumin and other factors in the disease process of initial coagulopathy in cardiac arrest.

Abstract 51: Prognostic Implication of Initial Coagulopathy in Out-of-Hospital Cardiac Arrest

Objective: We sought to investigate the prognostic implication of early coagulopathy represented by initial DIC score in out-of-hospital cardiac arrest (OHCA). Methods: OHCA registry was analyzed to identify patients with ROSC without recent use of anticoagulant between 2008 and 2011. Patients were assessed for prehosptial factors, initial laboratory results and therapeutic hypothermia. Outcome variables were survival discharge, 6-month CPC and survival duration within the first week after ROSC. Logistic regression and Cox-proportional hazards model were used for both univariate and multivariate analysis. Results: Among 273 eligible patients, initial DIC score was available in 252 (92.3%). Higher DIC score was associated with increased inhospital death (odds ratio [OR], 1.89 per unit; 95% confidence interval [CI], 1.48-2.41) and unfavorable long-term outcome (6-month CPC 3-5; OR, 2.21 per unit; 95% CI, 1.60-3.05). The adjusted ORs for both outcomes were 1.61 (95% CI, 1.17-2.22) and 1.84 (95% CI, 1.26-2.67), respectively. We categorized DIC score in five groups as &lt;3, 3, 4, 5 and &gt;5 and analyzed differential mortality risk using Cox- proportional hazards model. Compared with reference group (DIC score &lt;3), the adjusted HR for early mortality in each remaining group was 1.96 (95% CI, 1.13-3.40), 2.26 (95% CI, 1.27-4.02), 2.77 (95% CI, 1.58-4.85) and 4.29 (95% CI, 2.22-8.30), respectively (p-trend &lt;.001). The area under the receiver operating characteristic of DIC score for prediction of unfavorable long-term outcome was 0.79 (95% CI, 0.69-0.88). Conclusion: Increased initial DIC score in OHCA was an independent predictor for poor outcomes and early mortality risk. Uploaded image: Kaplan-Meier plots for cumulative 1-week survival of five DIC score groups; Log-rank test for difference (p &lt;.001, p-trend &lt;.001)

Prognostic Implication of Initial Coagulopathy in Out-of-hospital Cardiac Arrest

Abstract Objective We sought to investigate the prognostic implication of early coagulopathy represented by initial DIC score in out-of-hospital cardiac arrest (OHCA). Methods OHCA registry was analyzed to identify patients with ROSC without recent use of anticoagulant between 2008 and 2011. Patients were assessed for prehosptial factors, initial laboratory results and therapeutic hypothermia. Outcome variables were survival discharge, 6-month CPC and survival duration within the first week after ROSC. Logistic regression and Cox proportional hazards models were used for both univariable and multivariable analysis. Results Among 273 eligible patients, initial DIC score was available in 252 (92.3%). Higher DIC score was associated with increased inhospital death (odds ratio [OR], 1.89 per unit; 95% confidence interval [CI], 1.48–2.41) and unfavorable long-term outcome (6-month CPC 3–5; OR, 2.21 per unit; 95% CI, 1.60–3.05). The adjusted ORs for both outcomes were 1.61 (95% CI, 1.17–2.22) and 1.84 (95% CI, 1.26–2.67), respectively. We categorized DIC score in five groups as 5 and analyzed differential mortality risk using Cox proportional hazards model. Compared with reference group (DIC score p -trend Conclusion Increased initial DIC score in OHCA was an independent predictor for poor outcomes and early mortality risk.

O1-012 - The Efficacy of R-Thrombomodulin in Comparison with Dalteparin NA in 26 Patients with Hematological Malignancy Complicated by DIC

ABSTRACT Introduction Hematology malignancy is often complicated by many critical diseases including DIC. The resolution of DIC safely is one of the most important aspects in getting over hematological malignancy. We would like to report our comparative review of the administration of Recombinant Thrombomodulin (Recomodulin) versus Dalteparin Na (Fragmin) and this time, we would also report the possibility of reducing blood products such as fresh frozen plasma (FFP). Patient Thirteen patients (mean age 57.0 years, men/women 5/8, AML 7, APL 4, ALL 2) were administered recombinant thrombomodulin and 13 patients (mean age 50.5 years, men/women 8/5, AML 6, APL 4, ALL 3) were administered Dalteparin Na. Result The mean duration of therapies was 3.8 and 11.3 days, respectively. All patients has achieved DIC resolution, and the mean resolution time was 5.5 and 11.6 days (P = 0.020). The mean administration of FFP was 7.5 and 16.9 units (P = 0.091). The average of FDP, Fib, and JMHW DIC score has improved in both therapies. On the other hand, there were no changes in PT-INR and AT3. No bleeding and other adverse events were reported during both administration. Conclusion Recombinant thrombomodulin adminisitration is effective therapy rather than Dalteparin Na administration for patients with hematological malignancy and also tends to reduce the use of FFP.

Prognostic implication of initial coagulopathy in out-of-hospital cardiac arrest

ObjectiveWe sought to investigate the prognostic implication of early coagulopathy represented by initial DIC score in out-of-hospital cardiac arrest (OHCA). MethodsOHCA registry was analyzed to identify patients with ROSC without recent use of anticoagulant between 2008 and 2011. Patients were assessed for prehosptial factors, initial laboratory results and therapeutic hypothermia. Outcome variables were survival discharge, 6-month CPC and survival duration within the first week after ROSC. Logistic regression and Cox proportional hazards models were used for both univariable and multivariable analysis. ResultsAmong 273 eligible patients, initial DIC score was available in 252 (92.3%). Higher DIC score was associated with increased inhospital death (odds ratio [OR], 1.89 per unit; 95% confidence interval [CI], 1.48–2.41) and unfavorable long-term outcome (6-month CPC 3–5; OR, 2.21 per unit; 95% CI, 1.60–3.05). The adjusted ORs for both outcomes were 1.61 (95% CI, 1.17–2.22) and 1.84 (95% CI, 1.26–2.67), respectively. We categorized DIC score in five groups as <3, 3, 4, 5 and >5 and analyzed differential mortality risk using Cox proportional hazards model. Compared with reference group (DIC score<3), the adjusted HR for early mortality in each remaining group was 1.96 (95% CI, 1.13–3.40), 2.26 (95% CI, 1.27–4.02), 2.77 (95% CI, 1.58–4.85) and 4.29 (95% CI, 2.22–8.30), respectively (p-trend<0.001). The area under the receiver operating characteristic of DIC score for prediction of unfavorable long-term outcome was 0.79 (95% CI, 0.69–0.88). ConclusionIncreased initial DIC score in OHCA was an independent predictor for poor outcomes and early mortality risk.

Recombinant Human Thrombomodulin in the Treatment of Acute Myeloid Leukemia Patients Complicated by Disseminated Intravascular Coagulation: Retrospective Analysis of the Outcomes Between the Patients with Heparin and with Recombinant Human Thrombomodulin Therapy

Abstract 1247 Introduction:Thrombomodulin is a thrombin receptor on the endothelial cell surface that plays an important role as a regulator of coagulation. Recombinant human thrombomodulin (rTM) is a promising anticoagulant that activates protein C, which leads to inactivation of factor (F) Va and FVIIIa and decreased thrombin formation. In addition, rTM is a novel anticoagulant with a long half-life. When compared with heparin therapy, rTM therapy more significantly improves DIC and alleviates bleeding symptoms in DIC patients. However, it is unknown as to whether or not the treatment with rTM affects patient's outcome. Therefore, we retrospectively analyzed 103 patients with acute myeloid leukemia (AML) (except adult acute promyelocytic leukemia), and compared the outcomes between the patients with heparin therapy and with rTM. Methods:The diagnosis of de novo AML patients was based on the morphology, histopathology, cytogenetics, expression of leukocyte-differentiation antigens, and the French-American-British (FAB) classification. The patients examined in the current study (aged 18–84 years) were diagnosed with AML from January 2004 to March 2010. Patients younger than 65 years of age were treated with idarubicin (12 mg/m2 per day) for 3 days (days 1–3) and cytarabine (100 mg/m2 per day) by continuous infusion for 7 days (days 1–7). Patients 65 years of age or older were treated with daunorubicin (40 mg/m2 per day) for 3 days (days 1–3) and 200 mg/m2 per day behenoyl cytarabine for 8 days (days 1–8). The continuous infusion of dalteparin sodium (75 IU/kg per day) or recombinant human thrombomodulin (380 U/kg per day) was used to treat DIC.The diagnostic criteria for DIC previously proposed by the Japanese Ministry of Health and Welfare (JMHW) were employed in this study. The criteria are based on a scoring system including the presence of underlying disease (0 or 1 points), organ failure (0 or 1 points), and the results of coagulation tests of fibrinogen (0 to 2 points), fibrin/fibrinogen degradation products (FDP, 0 to 3 points), and the prothrombin time (0 to 2 points). DIC is diagnosed when the DIC score is greater than 4.Comparisons between the qualitative variables were carried out using the χ2 test. The survival probabilities were estimated by the Kaplan-Meier method, and differences in the survival distributions were evaluated using the log-rank test. These statistical analyses were performed with the software package Stata version 11 (StataCorp LP, College Station, TX, USA). For all analyses, the P values were 2-tailed, and a P value less than.05 was considered to be significant. Results:DIC developed in 45 patients. 31 patients were treated with dalteparin sodium and 14 patients were treated with recombinant human thrombomodulin. The FAB subtypes, age distribution, major laboratory data (CBC, LDH, and CRP) were not significantly different between two groups. No patient died within 4 weeks after diagnosis who were treated with rTM. On the other hand, 3 patients died within 4 weeks after diagnosis who were treated with dalteparin sodium because of bleeding. The DIC resolution rates for the rTM and dalteparin sodium groups were 85.7 %( 12/14) and 67.7 %( 21/31). The overall survival was worse in the DIC group compared with the non- DIC group on the log-rank test (P=0.003). The overall survival was superior in the rTM group compared with dalteparin sodium group (P=0.016). Conclusion:We conclude that treatment with rTM is safe and efficient, when compared with dalteparin sodium. Based on this retrospective study, randomized control study could be attempted in the future. Disclosures:No relevant conflicts of interest to declare.

Clinical Features and Outcomes of Elderly Patients with Acute Promyelocytic Leukemia (APL) - the Japan Adult Leukemia Study Group APL97 Study.

AbstractAbstract 1077 (Background)Studies focused on elderly APL are limited. The European APL study group reported in their APL 93 trial that lower survival rate in elderly APL was mainly due to an increase of early deaths and toxicity of chemotherapy (Ades et al, 2005). On the other hand, PETHEMA group reported in their LPA96 and 99 studies that ATRA combined with anthracycline monochemotherapy resulted in low toxicity and high compliance, and that survival rate is similar to younger patients (Miguel A et al, 2004). We analyzed clinical features and outcomes of elderly APL patients with APL who were treated with ATRA and intensive chemotherapy and compared with those of younger patients in long term follow-up of the JALSG-APL97 Study. (Methods)Patients with newly diagnosed APL were continuously registered from May 1997 to June 2002, and induction therapy was composed of ATRA and chemotherapy including idarubicin and cytarabine. The dose and duration of chemotherapy were based on initial leukocyte count. After completion of 3 courses of consolidation chemotherapy, patients negative for the PML-RARA transcript were randomly allocated either to receive 6 courses of intensified maintenance chemotherapy or to observation. Elderly patients were treated with the same schedule to younger patients (Asou et al, 2007). Clinical features as well as relapse rate (RR), overall survival (OS) and disease-free survival (DFS) were assessed in elderly group with aged 60 or more in comparison with younger group. Clinical outcomes were updated on January, 2009 and the median follow up period is 7.3 years. (Results)Of 302 patients registered in this study, 283 patients were assessable. The median age was 48 years (range, 15–70 years), with 237 patients in younger group (median age, 44 years) and 46 patients in elder group (median age, 63 years). Significantly lower platelet count (less than 10 × 109/L), higher incidence of ECOG performance status 3 to 4, lower albumin level (< 3.5g/dl) were observed in elderly group compared to younger group (P = 0.04, P = 0.02 and P < 0.001, respectively), while clinical characteristics including gender, initial leukocyte count, APL cells in peripheral blood, DIC score, frequency of variant type (M3v), expression of CD-phenotype, past history of chemotherapy and/or radiotherapy and number of infectious complications at diagnosis, did not differ between two groups. The CR rates and early mortality during induction therapy including to hemorrhagic complications were similar between two groups (89% vs. 96%, P = 0.06; 11% vs. 4%, P = 0.08), whereas induction death due to differentiation syndrome in elderly group is higher compared with younger group (4% vs. 0%, P = 0.03). The cumulative incidence of non relapse mortality (NRM) during the third consolidation chemotherapy was significantly higher in elderly group (9% vs. 1%., P = 0.04). All of the mortality occurred during consolidation therapy was associated with infection. Although OS was lower in elderly groups at 10 year compared with younger group (65% vs. 87%, P < 0.001), DFS and RR were similar between two groups (65% vs. 67%, P = 0.70; 13% vs. 26%, P = 0.15, respectively). (Conclusion)The present study demonstrated that efficacy of ATRA combined with chemotherapy in elderly APL was similar to younger APL. Nevertheless, lower OS at 10 year in elderly APL was observed in this study. One of the reasons was an increase of NRM, especially induction death due to differentiation syndrome and infection death during consolidation chemotherapy. Thus, reduction of intensity of post remission chemotherapy should be considered in elderly patients. Non-myelosuppressive agents such as arsenic trioxide and/or tamibarotene should be incorporated into the post remission therapy for elderly patients with APL. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

DIC score predicts mortality in massive clot coagulopathy as a result of extensive pulmonary embolism: reply to a rebuttal

See also Levi M. Disseminated intravascular coagulation or extended intravascular coagulation in massive pulmonary embolism. This issue, pp 1475–6; Leitner JM, Jilma B, Spiel AO, Sterz F, Laggner AN, Janata KM. Massive pulmonary embolism leading to cardiac arrest is associated with consumptive coagulopathy presenting as disseminated intravascular coagulation. This issue, pp 1477–82; Thachil J. DIC score predicts mortality in massive clot coagulopathy as a result of extensive pulmonary embolism: a rebuttal. This issue, pp 1657–8.

Coagulation studies in patients with orthopedic trauma

Background:Head injury, severe acidosis, hypothermia, massive transfusion and hypoxia often complicate traumatic coagulopathy. First line investigations such as prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen level, platelet count and D-dimer levels help in the initial assessment of coagulopathy in a trauma victim.Aim:To study the coagulation profile in patients of orthopedic trauma.Settings and Design:Prospective study.Patients and Methods:Patients with head injury, severe acidosis, massive transfusion and severe hypoxia were excluded from the study. Coagulation parameters were evaluated at three intervals, at the time of admission, intra operatively and in the postoperative period.Statistical Analysis:Chi-square test was used for analysis of categorical variables. For comparison between groups, two- way ANOVA was used.Results and Conclusions:Of the 48 patients studied, 38 (80%) had normal DIC scores upon admission and only 10 (20%) had mild DIC scores at the time of admission. The median Injury Severity Score was 34 and they did not correlate with DIC scores. Fibrinogen levels alone were significantly different, increased progressively (mean pre op, intra op and post op levels 518 ± 31,582 ± 35 and 643 ± 27 respectively; P ≤ 0.02) since the time of admission in these patients. All the other parameters remained unchanged. Further large scale prospective studies would be required to correlate elevated fibrinogen levels with the type of trauma or surgery.

Coagulopathy in patients who experience snakebite

Background/AimsCoagulopathy is a common complication of snakebite, but there is little information on the clinical importance of coagulopathy. We analyzed the characteristics of coagulopathy after envenomation.MethodsNinety-eight patients who experienced snakebite were enrolled in this study. We divided all the patients into three groups by the ISTH DIC scoring system: the normal, simple coagulopathy and DIC groups. The coagulopathy group included both the simple coagulopathy and DIC groups. We then conducted a case-control study.ResultsThere was a significant decrease in the Hct, protein, albumin, ALP and cholesterol levels in the coagulopathy group, and only the cholesterol level was deceased in the DIC group (p<0.05). Leukocytosis and rhabdomyolysis were significantly associated with coagulopathy, and hemolysis and rhabdomyolysis were associated with DIC (p<0.05). The presence of rhabdomyolysis was considered a risk factor for coagulopathy (p<0.05). These conditions continued for up to six to seven days after the snakebite.ConclusionsEvaluation of coagulopathy with using these characteristics is helpful to properly manage the patients who experience snakebite.