1. This lecture was conducted during the Nephrology Unit Grand Ground by Medical Student rotated under Nephrology Division under the supervision and administration of Prof. Jamal Al Wakeel, Head of Nephrology Unit, Department of Medicine and Dr. Abdulkareem Al Suwaida. Nephrology Division is not responsible for the content of the presentation for it is intended for learning and /or education purpose only.

2. Disseminated Intravascular Coagulation (DIC) ABDULMJEED ALSHAIKH

3. Background: "An acquired syndrome characterized by the intravascular activation of coagulation with loss of localization arising from different causes. It can originate from and cause damage to the microvasculature, which if sufficiently severe, can produce organ dysfunction Guideline] Taylor FB Jr, Toh CH, Hoots WK, Wada H, Levi M, Scientific Subcommittee on Disseminated Intravascular Coagulation (DIC) of the International Society on Thrombosis and Haemostasis (ISTH). Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost. Nov 2001;86(5):1327-30.

6. *Franchini M, Lippi G, Manzato F. Recent acquisitions in the pathophysiology, diagnosis and treatment of disseminated intravascular coagulation. Thromb J. 2006;4:4. * Levi M, ten Cate H, Bauer KA, van der Poll T, Edgington TS, Büller HR, et al. Inhibition of endotoxin-induced activation of coagulation and fibrinolysis by pentoxifylline or by a monoclonal anti-tissue factor antibody in chimpanzees. J Clin Invest. Jan 1994;93(1):114-20 Pathophysiology widespread and ongoing activation of coagulation TF activates coagulation by the extrinsic pathway involving factor VIIa to activate thrombin. cleaves fibrinogen to fibrin while simultaneously causing platelet aggregation (TFPI) is another anticoagulant mechanism that is disabled in DIC.

9. Schafer AI. Hemorrhagic disorders: disseminated intravascular coagulation, liver failure, and vitamin K deficiency. In: Goldman L, Ausiello D, eds. Cecil Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 181. UPDATED 11-5-2009: Updated by: David C. Dugdale, III, MD, Professor of Medicine, Division of General Medicine, Department of Medicine, University of Washington School of Medicine; Yi-Bin Chen, MD, Leukemia/Bone Marrow Transplant Program, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc. Causes: Sepsis Blood transfusion reaction Cancer, especially acute promyelocytic leukemia Pregnancy complications ( retained placenta ) Recent surgery or anesthesia Severe liver disease Severe tissue injury (as in burns and head injury)

11. Schafer AI. Hemorrhagic disorders: disseminated intravascular coagulation, liver failure, and vitamin K deficiency. In: Goldman L, Ausiello D, eds. Cecil Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 181. UPDATED 11-5-2009: Updated by: David C. Dugdale, III, MD, Professor of Medicine, Division of General Medicine, Department of Medicine, University of Washington School of Medicine; Yi-Bin Chen, MD, Leukemia/Bone Marrow Transplant Program, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc. Symptoms: Bleeding, possibly from multiple sites in the body Blood clots Drop in blood pressure Sudden bruising

13. Siegal T, Seligsohn U, Aghai E, Modan M. Clinical and laboratory aspects of disseminated intravascular coagulation (DIC): a study of 118 cases. Thromb Haemost. Physical: Signs of spontaneous and life-threatening hemorrhage. Cardiovascular system Respiratory system Gastrointestinal system Dermatologic system

14. Clark, Michael; Kumar, Parveen J. (1998). Clinical Medicine: A Textbook for Medical Students and Doctors (4 ed.). Philadelphia: W.B. Saunders. Diagnosis: The blood film may show fragmented red blood cells (schistocytes).* Fibrin degradation products (FDP) OR (FSP)- high D-dimer – high * Prothrombin time (PT) - high Partial thromboplastin time (PTT) - high Platelet count - low Serum fibrinogen - low *

16. Schafer AI. Hemorrhagic disorders: disseminated intravascular coagulation, liver failure, and vitamin K deficiency. In: Goldman L, Ausiello D, eds. Cecil Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 181. UPDATED 11-5-2009: Updated by: David C. Dugdale, III, MD, Professor of Medicine, Division of General Medicine, Department of Medicine, University of Washington School of Medicine; Yi-Bin Chen, MD, Leukemia/Bone Marrow Transplant Program, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc. Possible Complications: Lack of blood flow to arms, legs, or vital organs Severe bleeding Stroke

17. Treatment: treatment of the underlying disorder Consultations Medication

18. Medication: (1)Anticoagulant agents (2) Recombinant human activated protein C (3) Blood components (4) Antifibrinolytic agents

19. Medication: (1)Anticoagulant agents: These agents are used when the patient continues to bleed Heparin: Prevents reaccumulation of a clot after spontaneous fibrinolysis. Antithrombin III (ATnativ, Thrombate III) inhibit coagulation.

20. (2) Recombinant human activated protein C: These agents inhibit factors Va and VIIIa and may also inhibit plasminogen activator inhibitor-1 (PAI-1) Drotrecogin alfa-activated (Xigris) Indicated for severe sepsis associated with acute organ dysfunction.

21. (3) Blood components used to correct abnormal hemostatic parameters. Packed red blood cells (PRBCs; washed) Preferred to whole blood since they limit volume, immune, and storage complications. Platelet concentrates Considered safe for use in acute DIC. Fresh frozen plasma (FFP) Contains coagulation factors as well as protein C and protein S. Cryoprecipitate or fibrinogen concentrates Not commonly recommended except when fibrinogen is needed. The theoretical concern that these blood products may "fuel the fire" and exacerbate the DIC has not been supported by clinical experience

22. (4) Antifibrinolytic agents These agents are used only after all other therapeutic modalities have been tried and deemed unsuccessful. Aminocaproic acid (Amicar) Inhibits fibrinolysis via inhibition of plasminogen activator substances and, to a lesser degree, through antiplasmin activity Tranexamic acid (Cyklokapron) Used as alternative to aminocaproic acid. Inhibits fibrinolysis by displacing plasminogen from fibrin. Baratto F, Michielan F, Meroni M, Dal Palu A, Boscolo A, Ori C. Protein C concentrate to restore physiological values in adult septic patients. Intensive Care Med. Sep 2008;34(9):1707-12

23. Thank you