Disseminated Intravascular Coagulation - DIC

Dx
Background
Lab Tests

Diagnosis

Indications for Testing

Patient with risk factors for DIC along with bleeding or thrombocytopenia
Underlying disorder with known DIC association

Criteria for Diagnosis

Score global coagulation test results based on the following scoring system proposed by the International Society on Thrombosis and Hemostasis (ISTH)
- Platelet count (x10⁹/L)
  - (>100 = 0, 50-100 = 1, <50 = 2)
- PT prolongation (seconds)
  - (<3 = 0, >3 but <6 = 1, ≥6 = 2)
- Fibrinogen (g/L)
  - (>1 = 0, <1 = 1)
- Fibrin-related markers (increase)
  - No increase = 0; moderate increase = 2; strong increase = 3
  - Cutoffs for scoring fibrin-related markers must be established for the specific assay
- TOTAL
  - If ≥5, compatible with overt DIC – repeat scoring daily
  - If <5, suggestive of non-overt DIC – repeat scoring after 1-2 days

Laboratory Testing

CBC – thrombocytopenia usually present (may be normal in early DIC)
Clotting times
- Prothrombin time (PT) – prolonged (may be normal in early or chronic DIC)
- Partial thromboplastin time (PTT) – prolonged (may be normal in early or chronic DIC)
- Thrombin time (TT) – may be increased due to consumption of fibrinogen
Fibrin-related marker
- D-dimer – increased in acute and chronic DIC (best single test)
  - Largely replaced fibrin degradation products (FDP) as a marker of coagulation
  - D-dimer measurements alone have excellent negative predictive value for DIC
  - Normal d-dimer essentially rules out DIC
  - Elevated d-dimer levels are seen in a number of conditions in addition to DIC (eg, pregnancy, acute thrombosis)
Coagulation factors
- Fibrinogen – decreased
  - As an acute phase reactant, fibrinogen might not decrease until DIC is severe

Differential Diagnosis

Idiopathic thrombocytopenic purpura
Hemolytic uremic syndrome
Thrombotic thrombocytopenic purpura
Severe liver disease
Malignancy
Drug-induced thrombocytopenia
Splenic sequestration
Heparin-induced thrombocytopenia

Clinical Background

Disseminated intravascular coagulation (DIC) is a disorder characterized by massive systemic activation of coagulation with consumption of platelets and coagulation proteins.

Epidemiology

Incidence – >18,000 cases annually in U.S.

Risk Factors

Sepsis (bacterial, viral, fungal)
Trauma (polytrauma, fat embolism, burns)
Malignancy (solid tumors, acute leukemia)
Obstetric complications (abruptio placentae, placenta previa, amniotic fluid embolus)
Toxic reactions (eg, venomous snake bite)
Immunologic reactions (hemolytic transfusion reaction, transplant rejection)
Organ destruction (pancreatitis, hepatic failure)

Pathophysiology

Activation of coagulation pathways
- Generation of thrombin and formation of fibrin in circulating blood
- Consumption of coagulation factors and platelets
Activation of inflammatory pathways via cytokines
Suppression of physiologic anticoagulant pathways
Activation and/or impairment of fibrinolysis

Clinical Presentation

Generally occurs in the setting of a risk factor listed above
Hemorrhage – petechiae, purpura, epistaxis, mucous membrane bleeding
Thrombosis – may lead to organ failure
Chronic DIC – occurs in cancer patients
- Thrombosis is primary symptom
- Referred to as Trousseau syndrome

Treatment

Treat underlying disorder causing DIC
Replacement therapy until underlying disorder resolved
- Platelets
- Fresh frozen plasma/cryoprecipitate
Patients with chronic DIC and thrombosis may require heparin therapy

Indications for Laboratory Testing

Tests generally appear in the order most useful for common clinical situations
Click on number for test-specific information in the ARUP Laboratory Test Directory

Test Name and Number	Recommended Use	Limitations
CBC with Platelet Count 0040002 Method: Automated Cell Count	Screen for coagulation disorder; order concurrently with PT, PTT, TT, and fibrinogen	Normal result does not rule out DIC
Prothrombin Time 0030215 Method: Electromagnetic Mechanical Clot Detection	Screen for coagulation disorder; order concurrently with CBC, PTT, TT, and fibrinogen	Normal result does not rule out DIC
Partial Thromboplastin Time 0030235 Method: Electromagnetic Mechanical Clot Detection	Screen for coagulation disorder; order concurrently with CBC, PT, TT, and fibrinogen	Normal result does not rule out DIC
Thrombin Time with Reflex to Thrombin Time 1:1 Mix 0030260 Method: Clotting	Screen for coagulation disorder; order concurrently with CBC, PT, PTT, and fibrinogen	Normal result does not rule out DIC
Fibrinogen 0030130 Method: Electromagnetic Mechanical Clot Detection	Screen for coagulation disorder; order concurrently with CBC, PTT, and TT	Normal result does not rule out DIC
D-Dimer 0030057 Method: Immunoturbidimetry	Aid in diagnosing DIC	Presence of rheumatoid factor, pregnancy, acute thrombosis may lead to false-positive results

Additional Tests Available

Click the plus sign to expand the table of additional tests.

Test Name and Number	Comments
Soluble Fibrin Monomer 0030126 Method: Qualitative Hemagglutination	Not recommended; order d-dimer test instead
Inhibitor Assay, PT with Reflex to PT 1:1 Mix 2003260 Method: Electromagnetic Mechanical Clot Detection
Inhibitor Assay, PTT with Reflex to PTT 1:1 Mix, with Reflex to 1-Hour Incubation 2003266 Method: Electromagnetic Mechanical Clot Detection
Fibrinogen Panel 0030137 Method: Electromagnetic Mechanical Clot Detection/Radial Immunodiffusion
Fibrin/Fibrinogen Degradation Split Products, Plasma 2006491 Method: Latex Agglutination	For fibrin degradation products (FDP) testing, this plasma test is the recommended test For evaluating coagulopathies (eg, disseminated intravascular coagulation), D-dimer is the preferred test
Fibrin/Fibrinogen Degradation Split Products 0030140 Method: Latex Agglutination	Not recommended for FDP testing or for evaluating coagulopathies (eg, DIC); for FDP testing, the plasma FDP test is recommended For evaluating coagulopathies (eg, DIC), D-dimer is the preferred test