05 disseminated intravascular coagulation

DISSEMINATED INTRAVASCULAR COAGULATION (DIC)

DEFINITIONETIOLOGYPATHOPHYSIOLOGYCLINICAL MANIFESTATIONSLABORATORY FINDINGSDIFFERENTIAL DIAGNOSISTREATMENT

DEFINITIONIt 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.

MECHANISMSOccurs due to simultaneous action of

the following 4 mechanisms1) Increased thrombin generation2) Suppressed physiological anticoagulant

pathways3) Activation & subsequent impairment of

fibrinolysis4) Activation of inflammatory pathways

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

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

PATHOPHYSIOLOGY

CLINICAL MANIFESTATIONS

DIC

NON OVERT DIC OVERT DIC ACUTE DIC CHRONIC DIC

CONTROLLED UNCONTROLLED

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.

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.

PURPURA FULMINANS

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.

CHRONIC DIC

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

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.

BULLAE SEEN IN DIC

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

SCHISTOCYTES IN PERIPHERAL BLOOD SMEAR

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 andThrombin-Antithrombin complexes(TATs) are elevated

Overt DIC Scoring SystemOvert DIC Scoring System

DIFFERENTIAL DIAGNOSIS

Primary fibrinogenolysis or Pathologic fibrinolysis:Platelet count is normalD dimer may be normal or minimally increasedNo hypoprothombinemia & No deficiency of coagulation factors (VII, IX, X, XI)

Severe liver disease:D dimer test is normal

TREATMENTBLOOD COMPONENT THERAPY:

INDICATIONS:Active bleedingInvasive procedureRisk of bleeding complication

GOALS: To maintainPlatelet count >50000/µlFibrinogen concentration >1g/LProthrombin values less than double the normal range

FRESH FROZEN PLASMA(FFP):

Constituents:

0.7-1.0 U/ml of factors II,V, VII, VIII, X, XI, XII, XIII and2.5mg/ml fibrinogen.

Dosage: 15ml/kg

CRYOPRECIPITATE:

Constituents; fibrinogen 150mg/bagfactor VIII 80-120units/bagfactor XIII & vWB

Dosage: 1 bag/5kg body wt.

PLATELETS: Random donor platelets(RDP):• Constituents: 5.5×10¹° plateletsDosage: 1 unit/ 10 kg Single donor platelets:Constituents: 3×10¹¹ plateletsFRESH BLOOD:

Indicated in severe trauma to replace acute massive blood loss.

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/hrWeight > 30kg – 4U/kg/hr

REPLACEMENT OF NATURAL ANTICOAGULANT PATHWAYRecombinant human activated protein c 24µg/kg/hr.Adverse effects include bleeding.

ANTI-THROMBIN INDEPENDENT INHIBITORS

desirudingabexate mesylate

COMPLICATIONS Respiratory failureRenal failureStrokeCardiac tamponadeHemothorax