Disseminated Intravascular Coagulation
Introduction And Definition
Acquired clinicopathologic syndrome characterized by widespread, unregulated pathologic activation of coagulation system. Process leads to microvascular thrombi, systemic fibrin deposition, and rapid consumption of platelets, procoagulant clotting factors, and anticoagulant proteins.
Pathophysiology Of Disseminated Intravascular Coagulation
Complex pathogenesis involves loss of localized hemostasis and excessive coagulation activation. Divided into three overlapping pathologic processes.
Initiation Of Fibrin Deposition
- Mediated primarily by extrinsic pathway.
- Endothelial injury or inflammatory cytokines prompt tissue factor expression.
- Tissue factor accumulates on activated platelets via P-selectin binding, driving initial thrombin generation.
Amplification Of Thrombin Generation
- Thrombin generation amplifies inflammation and clotting cascades.
- Activates platelets, factor V, factor VIII, and factor IX.
- Activated factor XIII cross-links fibrin clots, rendering them insoluble.
- Thrombin activatable fibrinolysis inhibitor (TAFI) further protects fibrin clots from physiologic fibrinolysis.
Propagation Of Fibrin Deposition
- Sustained increase in plasma levels of plasminogen-activator inhibitor 1 (PAI-1) suppresses fibrinolysis.
- Injury, infection, or triggers release tumor necrosis factor (TNF), interleukin-1 (IL-1), and interleukin-6 (IL-6).
- Cytokines convert endothelium from anticoagulant to procoagulant surface.
- Microvascular fibrin deposition mechanically injures traversing erythrocytes, causing erythrocyte fragmentation and microangiopathic hemolytic anemia.
Consumption And Bleeding
- Fibrinogen, prothrombin, platelets, and other clotting factors are consumed beyond compensatory synthesis capacity.
- Concurrent secondary fibrinolysis generates fibrin degradation products (FDPs), which inhibit platelet aggregation and further impair hemostasis.
Etiology And Triggers
Syndrome represents a secondary complication of severe underlying disorders.
| Disease Category | Associated Conditions |
|---|---|
| Infections | Bacterial sepsis (Meningococcemia, Streptococcal, Gram-negative, Salmonella), Viral (Cytomegalovirus, Herpes simplex, HIV, Hemorrhagic fevers, Ebola), Parasitic (Malaria), Fungal, Rickettsia. |
| Tissue Injury | Severe trauma, crush injuries, major operations, severe burns, heat stroke, snakebite venom. |
| Malignancy | Acute promyelocytic leukemia, neuroblastoma, solid tumors. |
| Obstetric/Perinatal | Abruptio placentae, amniotic fluid embolism, toxemia, fetal demise, necrotizing enterocolitis, meconium aspiration. |
| Vascular/Localized | Kasabach-Merritt syndrome (giant hemangioma), vascular aneurysms. |
| Immunologic | Acute hemolytic transfusion reactions, severe allograft rejection, systemic lupus erythematosus, Kawasaki disease. |
Clinical Manifestations
Severity ranges from subclinical laboratory derangements (nonovert) to fulminant, life-threatening disease.
- Hemorrhagic Features: Bleeding from venipuncture sites, surgical incisions, mucous membranes. Cutaneous signs include petechiae, purpura, ecchymoses.
- Thrombotic Features: Microvascular occlusion leading to tissue necrosis, massive skin/subcutaneous infarction. Compromised perfusion causes multiorgan failure (lungs, kidneys, liver, brain).
- Neonatal Purpura Fulminans: Rapidly spreading purpuric skin lesions due to dermal vessel thrombosis, often associated with homozygous protein C or S deficiency or severe sepsis.
Laboratory Evaluation And Diagnosis
No single test establishes diagnosis; relies on compatible clinical scenario and coagulation panel derangements.
Diagnostic Findings
- Peripheral Smear: Schistocytes, helmet cells, microspherocytes, burr cells indicative of microangiopathic hemolysis.
- Complete Blood Count: Moderate to severe thrombocytopenia.
- Coagulation Assays: Prolonged prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin time (TT).
- Fibrinogen: Hypofibrinogenemia in severe disease. May appear normal early due to acute-phase reactant properties; rapidly declining levels strongly suggest consumption.
- Fibrin Markers: Markedly elevated D-dimers and FDPs reflect simultaneous clot formation and robust fibrinolysis.
- Specific Factor Assays: Reduced factor V, factor VIII, prothrombin. Factor VIII reduction crucially differentiates consumption from liver disease (where factor VIII remains normal or elevated).
Differential Diagnosis
| Clinical/Lab Feature | Disseminated Intravascular Coagulation | Severe Liver Disease | Vitamin K Deficiency |
|---|---|---|---|
| Red Cell Morphology | Schistocytes, helmet cells, fragmented | Target cells | Normal |
| PT And aPTT | Prolonged | Prolonged | Prolonged |
| Fibrin Split Products | Markedly increased | Normal or slightly increased | Normal |
| Platelet Count | Reduced (consumption) | Normal or reduced (hypersplenism) | Normal |
| Factor VIII Level | Decreased (consumed) | Normal or Increased | Normal |
| Factor V Level | Decreased | Decreased | Normal |
| Factor VII Level | Decreased | Decreased | Decreased |
[Data compiled from differentiating coagulopathies].
ISTH Diagnostic Scoring System
Validated algorithm for diagnosing overt disease. Prerequisite: Underlying disorder known to cause condition must be present.
| Parameter | Laboratory Result | Assigned Score |
|---|---|---|
| Platelet Count | >100,000/mm³ 50,000-100,000/mm³ <50,000/mm³ | 0 1 2 |
| Fibrin-Related Marker (D-Dimer/FDP) | No increase Moderate increase Strong increase | 0 2 3 |
| Prothrombin Time Prolongation | <3 seconds >3 but <6 seconds >6 seconds | 0 1 2 |
| Fibrinogen Level | >1 g/L <1 g/L | 0 1 |
Score interpretation:
Management Strategies
Primary Interventions
- Resolution of triggering underlying disorder remains paramount.
- Administer appropriate broad-spectrum anti-infectives for sepsis.
- Administer anti-snake venom, antineoplastic therapy, or remove triggering stimulus.
- Maintain tissue perfusion, correct hypoxia, reverse acidosis, and manage shock with intravenous fluids.
Hemostatic Support (Component Therapy)
Component replacement indicated exclusively for active hemorrhage or prior to invasive procedures. Prophylactic correction of laboratory values in non-bleeding patients is not recommended.
| Component | Indication / Target | Recommended Dosage |
|---|---|---|
| Fresh Frozen Plasma (FFP) | Replaces depleted coagulation factors (II, V, VII, X, XI) and natural anticoagulants | 10-15 mL/kg initial bolus; may repeat 5 mL/kg every 6 hours. |
| Cryoprecipitate | Severe hypofibrinogenemia (<100 mg/dL) | 1 bag per 5-10 kg (provides 150-200 mg fibrinogen per bag); raises level by 60-100 mg/dL. |
| Platelet Concentrates | Severe thrombocytopenia (<50,000/mm³) with active bleeding | 10-20 mL/kg or 1 unit per 10 kg. |
Anticoagulation Therapy
- Heparin: Routine use controversial and potentially harmful in active bleeding. Considered primarily for overt, progressive thromboembolic complications (arterial or large vessel venous thrombosis) and purpura fulminans.
- Contraindicated Agents: Activated prothrombin complex concentrates (aPCC) and recombinant factor VIIa risk exacerbating unregulated systemic thrombin generation. Systemic antifibrinolytics (aminocaproic acid, tranexamic acid) generally contraindicated, except in specific hyperfibrinolytic states like acute promyelocytic leukemia.