Disseminated intravascular coagulation (DIC) Dr. Mohamed Haseen Basha Assistant professor ( Paediatrics) Faculty of Medicine Al Maarefa College of Science and Technology

Definition Disseminated intravascular coagulation (DIC) is an acquired disorder, it occurs when the normal hemostatic balance is disturbed primarily by excessive thrombin formation. It is a dynamic process triggered by a variety of conditions causing activation of the clotting cascade and generation of excess thrombin within the vascular system, which in turn leads to deposition of fibrin in the micro circulation. This definition implies that microclot formation and consequent ischemic organ failure and/or a hemorrhagic diathesis may occur.

Types of DIC Acute DIC This is the most common form of DIC seen in clinical practice. Bleeding manifestations predominate Presents with sudden bleeding from multiple sites

Chronic DIC Develops over a period of months, maybe subclinical, eventually evolves into an acute DIC pattern This occurs from a weak or intermittent activating stimulus. The destruction and production of clotting factors and platelets is balanced, so that the DIC is considered to be compensated. Patients may have recurrent episodes of ecchymosis or mild bleeding and thrombophlebitis at unusual sites. Trousseau’s sign is a form of chronic DIC.

Diseases Causing Acute or Chronic DIC Causes Acute DIC Chronic DIC Medical Septicemia / Infections Fulminant Hepatic failure Allergic reactions Transplantation Heat Stroke Hypothermia Leukemia Homozygous protein C deficiency Solid tumors Liver cirrhosis Vasculitis Kasabach-Merritt syndrome Adult respiratory distress syndrome Surgical Poly trauma Major operations Brain injury Extracorporeal circulation Thermal injury Fat embolism Cardiac Bypass surgery Peritoneovenous shunt Organ transplantation Aortic aneurysm Vascular tumors

Causes Acute DIC Chronic DIC Obstetrics and Gynaecology Amniotic fluid embolism Abruptio placentae Septic abortion Acute fatty liver Uterine rupture Toxemia of pregnancy Septicemia Late gestation HELLP syndrome Retained dead fetus Transfusion Medicine Acute haemolytic transfusion reaction Massive Transfusion Artificial surfaces

Pathophysiology of DIC Activation of Blood Coagulation Suppression of Physiologic Anticoagulant Pathways Impaired Fibrinolysis Cytokines

Activation of Blood Coagulation Tissue factor/factor VIIa mediated thrombin generation via the extrinsic pathway complex activates factor IX and X Tissue Factor endothelial cells monocytes Extravascular: lung kidney epithelial cells

Suppression of Physiologic Anticoagulant Pathways reduced antithrombin III levels reduced activity of the protein C-protein S system Insufficient regulation of tissue factor activity by tissue factor pathway inhibitor (TFPI) inhibits TF/FVIIa/Fxa complex activity

IL-6, and IL-1 mediates coagulation activation in DIC TNF- Impaired Fibrinolysis Relatively suppressed at time of maximal activation of coagulation due to increased plasminogen activator inhibitor type 1. Cytokines IL-6, and IL-1 mediates coagulation activation in DIC TNF- mediates dysregulation of physiologic anticoagulant pathways and fibrinolysis modulates IL-6 activity IL-10 may modulate the activation of coagulation

Clinical features The diagnosis of DIC is mainly clinical. Hemorrhage is the commonest presentation characterized by spontaneous bruising, muscle oozing, bleeding from venipuncture sites, and secondary hemorrhage into surgical wounds. Bleeding is associated with varying degrees of shock, which is often out of proportion to the degree of blood loss. Shock is probably due to activation of contact factor XII that leads to production of bradykinin, and interaction between cytokines like TNF and IL-1.

Evidence of major organ dysfunction is common, usually involving the pulmonary, renal, hepatic and central nervous systems. These features are due to a combination of factors, namely microvascular thrombi, shock and cytokine effects. Anemia caused by hemolysis may develop rapidly, owing to microangiopathic hemolytic anemia.

Most common sign of DIC is bleeding - Manifested by ecchymosis, petechiae and purpura - Bleeding from multiple sites either oozing or frank bleeding - Cool and or mottled extremities may be noted - Dyspnea and chest pain if pleura and pericardium involvement - Hematuria

ORGAN ISCHEMIC HEMORRAGIC Skin Purpura Fulminans Gangrene Acral cyanosis Petechiae Echymosis Oozing CNS Delirium/Coma Infarcts Intracranial bleeding Renal Oliguria/Azotemia Cortical Necrosis Hematuria Cardiovascular Myocardial Dysfunction   Pulmonary Dyspnea/Hypoxia Infarct Hemorrhagic lung GI Endocrine Ulcers, Infarcts Adrenal infarcts Massive hemorrhage

Factors Accelerating DIC Shock Chronic renal insufficiency Acidosis Chronic hepatic insufficiency Hypoxemia Malnutrition Stasis Impaired anti-coagulation activity Dehydration Impaired fibrinolytic activity Hyperthermia Phagocytic dysfunction

Diagnosis The blood film may show fragmented red blood cells (schistocytes). Fibrin degradation products (FDP) - high D-dimer – high Prothrombin time (PT) - high Partial thromboplastin time (PTT) - high Platelet count - low Serum fibrinogen - low Low levels of coagulation inhibitors AT III, protein C Low levels of coagulation factors Factors V,VIII,X,XIII

Treatment The most critical steps in the treatment of DIC are : (a) Treat the trigger that caused DIC and (b) Restore normal homeostasis by correcting the shock, acidosis, and hypoxia that usually complicate DIC. If the underlying problem can be controlled and the patient stabilized, bleeding quickly ceases, and there is improvement of the abnormal laboratory findings.

Blood components are used for replacement therapy in patients with hemorrhage and may consist of Platelet infusions (for thrombocytopenia), Cryoprecipitate (for hypofibrinogenemia), and/or Fresh-frozen plasma (for replacement of other coagulation factors and natural inhibitors). The role of heparin In DIC is limited to patients who have vascular thrombosis in association with DIC or who require prophylaxis because they are at high risk for venous thromboembolism.