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
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.
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.
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.
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
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
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