05 disseminated intravascular coagulation

1. DISSEMINATED INTRAVASCULAR COAGULATION (DIC)

2. DEFINITION ETIOLOGY PATHOPHYSIOLOGY CLINICAL MANIFESTATIONS LABORATORY FINDINGS DIFFERENTIAL DIAGNOSIS TREATMENT

3. DEFINITION It is an acquired condition in which normal physiology of coagulation is disturbed leading to widespread intravascular coagulation process associated with injury to microvasculature which results in organ dysfunction, capillary leak & shock.

4. MECHANISMS Occurs due to simultaneous action of the following 4 mechanisms Increased thrombin generation Suppressed physiological anticoagulant pathways Activation & subsequent impairment of fibrinolysis Activation of inflammatory pathways

5. ETIOLOGY INFECTIOUS : Meningococcemia- purpura fulminans Bacterial sepsis- staphylococcal, streptococcal, E coli Rickettsia- Rocky Mountain spotted fever Viral- CMV, varicella, arboviruses Malaria, Candida, Aspergillus TISSUE INJURY : Multiple fractures with fat emboli, crush injury, head injury MALIGNANCY : Acute promyelocytic leukemia, acute myeloid leukemia, neuroblastoma VENOM OR TOXIN : Snake bites, insect bites

6. Contd … MICROANGIOPATHIC DISORDERS : TTP, HUS, Kasabach-Meritt syndrome GI DISORDERS : Fulminant hepatitis, Inflammatory bowel disease, Pancreatitis HEREDITARY THROMBOTIC DISORDERS : Antithrombin III deficiency, Homozygous protein C deficiency NEWBORN : Maternal toxemia, Abruptio placentae, Necrotizing enterocolitis, Erythroblastosis fetalis MISCELLANEOUS : Acute graft rejection, Acute hemolytic transfusion reaction, Collagen vascular disorders, Heparin induced thrombosis, hyperpyrexia

7. PATHOPHYSIOLOGY

8. CLINICAL MANIFESTATIONS DIC NON OVERT DIC OVERT DIC ACUTE DIC CHRONIC DIC CONTROLLED UNCONTROLLED

9. Non overt DIC : Stressed & compensated hemostatic system. Lab tests- abnormal but no clinical manifestations. Overt DIC : Stressed and decompensated hemostatic system. Lab tests- abnormal with clinical bleeding or micro vascular thrombosis and organ dysfunction. Further divided into controlled and uncontrolled based on whether the process will resolve when the underlying condition is removed.

10. Acute DIC : Bleeding from vein puncture site, surgical wound. Grayish discoloration of tips of fingers, toes & ears in a symmetrical distribution. Meningococcemia( PURPURA FULMINANS )- bleeding from GI tract, gingival bleeding, epistaxis, pulmonary hemorrhage, hematuria.

11. PURPURA FULMINANS

12. Chronic DIC : Superficial and extensive ecchymosis of extremities without petechiae which may be intermittent or can persist. Recurrent episodes of epistaxis or internal mucosal bleeding. Trousseau sign - Recurrent migratory thrombophlebitis in association with cancer. Impairment of renal function, confusion, repeated episodes of cerebral thrombosis.

13. CHRONIC DIC

14. Specific features of DIC in neonates and infants CAUSES : Transplacental passage of thromboplastin or other procoagulant substances in neonates born of mothers affected with DIC owing to abruptio placenta, eclampsia or septicemia Development of DIC in a twin fetus may be due to feto-fetal passage of thromboplastin. DIC secondary to hemangioma . PRECIPITATING FACTOR : Asphyxia, septicemia, eclampsia

15. CLINICAL FEATURES: Symmetric ecchymosis of lower extremities and buttocks. Later these lesions become necrotic ultimately forming blood filled bullae. Sharply circumscribed infarcts of skin and genitalia Gangrene of extremities involves digits symmetrically. Fever and prostration Mortality 40-70% TREATMENT: Heparin. Relapse common after cessation.

16. BULLAE SEEN IN DIC

17. LABORATORY FINDINGS COMPLETE BLOOD COUNT : Severe thrombocytopenia(50000-100000/µl) with or without anemia PERIPHERAL BLOOD SMEAR : Schistocytes- Microangiopathic hemolysis PROTHROMBIN TIME & aPTT : Prolonged in early cases but may be normal or short in chronic cases FIBRINOGEN LEVEL : Low

18. SCHISTOCYTES IN PERIPHERAL BLOOD SMEAR

19. D dimer, FIBRINOGEN / FIBRIN DEGRADATION PRODUCTS : Increased >25µg fibrinogen equivalents/ml PROTEIN C & S, ANTITHROMBIN : decreased MARKERS OF ENDOGENOUS THROMBIN GENERATION : Prothrombin fragment 1.2 and Thrombin-Antithrombin complexes(TATs) are elevated

20. Overt DIC Scoring System

21. DIFFERENTIAL DIAGNOSIS Primary fibrinogenolysis or Pathologic fibrinolysis : Platelet count is normal D dimer may be normal or minimally increased No hypoprothombinemia & No deficiency of coagulation factors (VII, IX, X, XI) Severe liver disease : D dimer test is normal

22. TREATMENT BLOOD COMPONENT THERAPY : INDICATIONS : Active bleeding Invasive procedure Risk of bleeding complication GOALS : To maintain Platelet count >50000/µl Fibrinogen concentration >1g/L Prothrombin values less than double the normal range

23. FRESH FROZEN PLASMA(FFP ) : Constituents : 0.7-1.0 U/ml of factors II,V, VII, VIII, X, XI, XII, XIII and 2.5mg/ml fibrinogen. Dosage : 15ml/kg CRYOPRECIPITATE : Constituents ; fibrinogen 150mg/bag factor VIII 80-120units/bag factor XIII & vWB Dosage : 1 bag/5kg body wt.

24. PLATELETS : Random donor platelets (RDP) : Constituents : 5.5×10¹° platelets Dosage : 1 unit/ 10 kg Single donor platelets : Constituents : 3×10¹¹ platelets FRESH BLOOD : Indicated in severe trauma to replace acute massive blood loss.

25. ANTICOAGULANT THERAPY: Heparin and other anticoagulant therapy to inhibit thrombin. Indicated in patients with clinically overt thromboembolism , chronic DIC and extensive fibrin deposition. Dosage: Weight < 30kg – 10U/kg/hr Weight > 30kg – 4U/kg/hr

26. REPLACEMENT OF NATURAL ANTICOAGULANT PATHWAY Recombinant human activated protein c 24µg/kg/hr. Adverse effects include bleeding. ANTI-THROMBIN INDEPENDENT INHIBITORS desirudin gabexate mesylate

27. COMPLICATIONS Respiratory failure Renal failure Stroke Cardiac tamponade Hemothorax