Critical Care Medicine, Volume 34 (2), February 2006, pp 314-320 D ate: 2006/2/20

1. New disseminated intravascular coagulation score: A useful tool to predict mortality in comparison with Acute Physiology and Chronic Health Evaluation II and Logistic Organ Dysfunction scores Critical Care Medicine, Volume 34 (2), February 2006, pp 314-320 Date: 2006/2/20

2. Background • Disseminated Intravascular Coagulation • A complex systemic thrombohemorrhagic disorder • Fibrin deposition in microcirculature  Ischemic tissue damage • Consumption of coagulantion factor and PLTs  Diffuse bleeding • Most often associated with sepsis, shock, major trauma, malignancy (adenocarcinoma, leukemia), obstetric complications (abruptio placenta) • May occur in 30-50% of patients with sepsis

3. Pathophysiology • Tissue / endothelial injury / tumor / endotoxin Release of tissue factors / cytokines  Deposition of small thrombi in microvasculature  Consumption of coagulation factors and secondary fibrinolysis  Procoagulants and PLT deletion, FDP antihemostasis

5. Clinical Presentation • End organ infarction • Altered consciousness • Circulatory collapse, hypotension • ARDS • Acute renal failure, oliguria, hematuria • Diffuse or localized thrombosis • Acrocyanosis • Pregangrenous change • Hemorrhage • GI bleeding • Petechiae, mucosa bleeding • Microangiopathy • Hemolysis, Hematuria

6. Clinical Presentation • Lab examination • Thrombocytopenia • Prolonged PT, aPTT • Reduced fibrinogen level • Elevated FDP • Presence of D-dimer • Blood smear: schistocyte • Treatment • Treat the primary disease state • Control the major symptoms: thrombosis / bleeding • Heparin, FFP, Cryoprecipitate, platelets

7. Introduction • Scoring system for organ dysfunction • Acute Physiology and Chronic Health Evaluation (APACHE) II • Logistic Organ Dysfunction (LOD) score • DIC / coagulation abnormalities plays only a minor role in these scoring system. • However, multiple organ failure may involve DIC due to consumption coagulopathy or microvascular thrombosis.

8. Neurologic System Glasgow Coma Score Cardiovascular System Heart Rate (beats/min) Systolic Blood Pressure Renal System Serum Urea Serum Urea Nitrogen Creatinine Urine Output (L/day) Pulmonary System PaO2 (mm Hg)/FiO2 Hematologic System White Blood Cell Count Platelets (10^9/L) Hepatic System Bilirubin Prothrombin Total LODS Score Probability of Death (%) Logistic Organ Dysfunction (LOD) score JAMA, 1996, 276(10), p.802-10

9. Scoring system for diagnosing DIC Prothrombin Index: the percentage of the present prothrombin complex to its normal level

10. DIC scoring system • The DIC subcommittee of the International Society on Thrombosis and Haemostasis, Jul 2001 • 4 variables: prothrombin time (prothrombin index), platelet count, fibrinogen level, and a fibrin-related marker (D-dimer, FDP, soluble fibrin) • Compare with APACHE II and LOD score to predict mortality

11. Methods • Design: Single-center retrospective study • Setting: Medical intensive care unit of the University of Munich • Patients: A total of 797 patients admitted to the ICU between January 1, 1996, and January 1, 2001. • Inclusion Criteria: the coagulation variables D-dimer, platelet count, fibrinogen, and prothrombin indexwere available within the first 12 hrs after admission. • Exclusion criteria: missing values, missing admission diagnosis, fibrinolytic treatment before admission, vasculitis, unknown outcome due to transfer to other hospitals. • Survival: defined as survival at day 28 after admission • LOD score: counted by the worst value within the first 24 hrs • Stastics: SPSS version 1.0

13. An increasing DIC score was associated with an increasing mortality, especially in patients with serious infections. DIC score < 2 : low mortality (<20%) DIC score > 6 : high mortality (>80%) DIC score: Survivor / Non-survivor = 2.2 / 3.8, p<.001 Results

14. Survival time correlated with the scoring system for DIC in patients with sepsis Results

15. Scoring system for DIC correlated well with APACHE II score (r=0.36) and LOD score (r=0.35)

16. The performance of the different scoring systems concerning mortality was similar according to the ROC (receiver operating characteristic) curves

17. Results • In a Cox regression analysis using age, sex, coagulation variables, APACHE II, LOD, and DIC score as variables, only the scoring system for DIC and the APACHE II score remained as independent variables influencing the survival time in patients with sepsis (p<.001 [odds ratio, 1.524; 95% CI, 1.226 –1.894] and p<.001 [odds ratio, 1.101; 95% CI, 1.054 –1.149], respectively)

18. Results

19. In patients of cardiovascular disease (not prone to DIC) Increasing coagulation score was associated with increasing mortality, decreasing survival time, and with increasing APACHE II score or LOD score Results

20. Discussion • In patients with sepsis, the DIC scoring system and the established APACHE II and LOD scores show a positive correlation, and the diagnostic accuracy of the three scoring systems to predict mortality seems to be similar • The Cox regression analysis showed that the DIC and APACHE II scores correlated independently with survival time, with a greater effect of the DIC score than the APACHE II or the Logistic Organ Dysfunction score • Any state of shock, including septic or cardiogenic shock, leads to macrocirculatory and microcirculatory failure, activating coagulation and fibrinolysis, and becoming evenly prone to cause DIC

21. Discussion • A large randomized controlled trial showed a reduced mortalitywithactivated protein C treatment, especially in patients with highAPACHE II scores, coagulationabnormalities and in overt DICstatus. • The combination of APACHE II and DIC score may help to predictpatients who may potentially benefit more from this treatment option. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001; 344(10):699-709.

22. Discussion • Limitation of this studies • The study design is the retrospective analysis at a single center • The limited number of patients in the high range of scores • These results should be confirmed in a prospective study

23. Conclusion • The scoring system for DIC had an independent and higher impact on survival time than the APACHE II score • Retrospective data suggest that a combination of (APACHE) II score and the scoring system for DIC predicts mortality in critically ill patients better than the APACHE II score alone, especially in patients with infections.

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