Disseminated intravascular coagulation

1. Disseminated intravascular coagulation Disseminated intravascular coagulation (DIC) is a state/syndrome which is characterized by accelerated intravascular coagulation associated with increased consumption of platelets and plasma clotting factors.

2. ETIOLOGY • Bacterial (septic shock) : menningococcus, S. aureus, E. coli, protease, salmonella • Viral : measles, CMV, acute hepatitis • Fungal : Candida, histoplasmosis • Others : malaria, rickettsial • Tissue injury : head injury, multiple fracture, crush injury, shock, hypothermia, burns • Toxins: snake bite, insect bites

3. Cont.. • Hematological : incompatible blood transfusion, sickle cell anemia, acut iron toxicity • Neonatal causes: septicemia, RDS, birth asphyxia, necrotising enterocolitis, hypothermia • Obstetric complication: pre – eclampsia, septic abortion, maternal toxemia, retained fetus • Collagen vascular disease: JRA, SLE, acute vasculitis • Miscellaneous: major surgery, heat stroke, graft reaction, acute pancreatitis

4. Pathogenesis • There is intravascular activation of platelet adhesion, and the extrinsic and intrinsic systems of coagulation, initiated by any of the three major mechanism : - • 1. direct activation of factor V or X by proteolytic enzymes; • 2. activation of factor XII and • 3. activation of extrinsic pathway by release of tissue thromboplastin

7. Cont… • Continuation of this clotting process is dependent upon consumption of clotting factors and platelets, thrombin formation, activation of fibrinolytic system. • Thrombin activates the fibrinolytic system by activating the plasminogen by splitting peptides A and B from fibrinogen to soluble fibrin monomers and D dimers. • Fibrin monomers and polymers along with fibrin are degraded to fibrin split products (FSP) by plasmin.

8. Fibrinolytic system • Thrombin --------------- plasminogen -------- fibrinogen peptides A and B -------- soluble fibrin monomers and D dimers ---------- fibrin split products (FSP) Activates split plasmin

9. Cont.. • Increased levels of D – dimers and FSP are the pathognomonic of DIC Thrombin functions : • activates fibrinolytic system • activates factor XIII which acts on the fibrin polymers to form fibrin split products. • induces platelet adhesion and aggregation, leading to platelet consumption and thrombocytopenia.

10. Cont.. Course of DIC is determined by : • 1. platelet production versus platelet destruction; • 2. fibrin deposition versus fibrinolysis and • 3. synthesis of coagulation factor versus their depletion

11. Cont.. Process of DIC results in : • 1. increased thromboembolic phenomenon causing tissue ischemia and necrosis of multiple organs; • 2. depletion of clotting and antihemostatic effects of FSP resulting in bleeding and hemorrhages at multiple sites; • 3. red cell fragments

12. Clinical features • Purpura, ecchymosis, easy bruising, and bleeding from gums and mucous membranes. • Shock • Hematuria, oliguria leading to acute renal failure, abdominal pain, vomiting and respiratory distress

13. Differential diagnosis • Acute fulminant liver failure • Hemolytic uremia syndrome • Renal failure

14. Lab investigation • Low platelet count • Low levels of fibrinogen, factor II, V, X, VIII and XIII • Prolonged PT, APTT and TT • Low levels of antithrombin III, heparin cofactor II, protein C • Increased level of fibrin split products and • Microangiopathic hemolytic anemia as indicated by the presence of red cell fragmentation.

15. Treatment • Management of: • Acidosis, electrolyte disturbances, hypoxia, shock • Anemia (packed cells) • Hydrocortisone • Vitamin K

16. Cont… Replacement therapy : • Fresh frozen plasma (FFP) : • Fibrinogen level should be raised to over 150 mg/dL • 10 – 15 mL/kg of FFP along with ½ to 1 unit of platele concentrates every 12 – 24 hours • Platelat count should be maintained above 50,000/microL while fibrinogen level should be maintained above 75mg/dL.

17. Cont…. Exchange transfusion : • Double volume exchange transfusion helps by providing the replacement factors and removing the • A. circulating fibrin split products (FSP) • B. activated procoagulant: and • C. toxins • Platelet concentrates should be administered after the exchange for the successful management of DIC.

18. Cont… Heparin : • Inhibits number of proteolytic enzymes and factors such as thrombin, IXa and Xa • Dose : 15 – 20 units/kg hour as continuous drip or 50 – 70 units/kg/6 hourly Mortality : • Prolongation of PT (>1.5 times) and • APTT (>2,5 times) indicates poor prognosis.