DIC

Overview of Disseminated Intravascular Coagulation (DIC)

Definition: A complex and life-threatening acquired syndrome characterized by widespread activation of coagulation and fibrinolysis, leading to consumption of coagulation factors and platelets, and ultimately resulting in both thrombosis and bleeding
Key Features:
- Systemic Activation of Coagulation: Uncontrolled activation of the coagulation cascade, leading to the formation of microthrombi throughout the vasculature
- Consumption of Coagulation Factors and Platelets: Widespread clotting consumes coagulation factors and platelets, leading to deficiencies
- Activation of Fibrinolysis: Activation of the fibrinolytic system to break down the microthrombi, resulting in the generation of fibrin degradation products (FDPs)
- Bleeding and Thrombosis: The consumption of coagulation factors and platelets, combined with excessive fibrinolysis, leads to both bleeding and thrombotic complications
Always Secondary: DIC is never a primary disease; it is always secondary to an underlying disorder
High Mortality Rate: DIC is associated with significant morbidity and mortality

Sepsis:
- Severe bacterial, fungal, or viral infections
- Gram-negative bacteria are a common cause of DIC
Trauma:
- Severe tissue injury, burns, or crush injuries
- Release of tissue factor into the circulation
Obstetric Complications:
- Abruptio placentae (premature separation of the placenta)
- Amniotic fluid embolism
- Preeclampsia and eclampsia
- Septic abortion
Malignancy:
- Acute promyelocytic leukemia (APL): A specific subtype of AML associated with a high risk of DIC due to the release of procoagulant substances from leukemic cells
- Solid tumors (e.g., lung, breast, ovarian, prostate): Can release tissue factor or other procoagulant substances
Other Causes:
- Severe allergic or toxic reactions
- Transfusion reactions
- Snake bites
- Pancreatitis
- Liver disease
- Aortic aneurysm

The pathophysiology of DIC involves a complex interplay between the coagulation and fibrinolytic systems:

Triggering Event: The underlying disorder releases procoagulant substances into the circulation (e.g., tissue factor, inflammatory cytokines)
Activation of Coagulation: The extrinsic pathway of coagulation is activated by the release of tissue factor, leading to:
- Formation of Thrombin: Activation of the coagulation cascade leads to increased thrombin generation
- Fibrin Formation: Thrombin converts fibrinogen to fibrin, resulting in the formation of microthrombi throughout the vasculature
Consumption of Coagulation Factors and Platelets:
- Widespread clotting consumes coagulation factors (Factors V, VIII, fibrinogen) and platelets, leading to deficiencies
Activation of Fibrinolysis:
- Thrombin also activates the fibrinolytic system by releasing tissue plasminogen activator (tPA) from endothelial cells
- Plasminogen is converted to plasmin, which degrades fibrin clots into fibrin degradation products (FDPs), including D-dimer
Bleeding and Thrombosis: The consumption of coagulation factors and platelets, combined with excessive fibrinolysis, leads to:
- Microthrombi: Can cause organ ischemia and damage, leading to kidney failure, respiratory distress, and neurological dysfunction
- Bleeding: Due to the deficiency of coagulation factors and platelets

Bleeding:
- Oozing from IV sites, surgical wounds, and mucous membranes
- Petechiae (small, pinpoint hemorrhages)
- Purpura (larger areas of bleeding under the skin)
- Gastrointestinal bleeding
- Pulmonary hemorrhage
- Intracranial hemorrhage
Thrombosis:
- Microthrombi can cause organ damage and dysfunction
- Kidney failure (oliguria, anuria)
- Acute respiratory distress syndrome (ARDS)
- Neurological dysfunction (altered mental status, seizures, coma)
- Skin necrosis
- Limb ischemia
Other Symptoms:
- Hypotension (low blood pressure)
- Tachycardia (increased heart rate)
- Fever

Coagulation Studies:
- Prothrombin Time (PT): Prolonged
- Activated Partial Thromboplastin Time (aPTT): Prolonged
- Thrombin Time (TT): Prolonged
- Reptilase Time: Prolonged (may be normal in some cases)
- Mixing Studies: PT and aPTT typically do not correct on mixing with normal plasma
Fibrinogen Level:
- Decreased (often <100 mg/dL)
- Reflects consumption of fibrinogen
Platelet Count:
- Decreased (thrombocytopenia) - often <100 x 10^9/L
- Platelet count decreases as the patient’s condition worsen
Fibrin Degradation Products (FDPs):
- Elevated
- Latex agglutination assay is positive
D-dimer:
- Markedly Elevated
- D-dimer is a cross-linked fibrin degradation product and is a more specific marker for DIC than FDPs
Peripheral Blood Smear:
- Schistocytes (fragmented RBCs): Indicate microangiopathic hemolytic anemia (MAHA)
- Thrombocytopenia
Other Tests:
- Antithrombin Level: Decreased
- Protein C and S Levels: Decreased
- Factor Assays: Decreased levels of Factors V and VIII
- Reptilase Time: Reptilase time measures fibrin formation independent of thrombin so is used to evaluate fibrinogen function
  - Prolonged in the setting of dysfibrinogenemia or hypofibrinogenemia

Several scoring systems have been developed to aid in the diagnosis of DIC
The International Society on Thrombosis and Haemostasis (ISTH) scoring system is one of the most widely used
Scoring systems consider:
- Platelet count
- Prothrombin time (PT)
- Fibrinogen level
- D-dimer level

Treat the Underlying Cause: This is the most important step in managing DIC.
- Antibiotics for sepsis
- Surgical evacuation of retained products of conception in obstetric DIC
- Chemotherapy for acute promyelocytic leukemia (APL)
Supportive Care:
- Transfusions:
  - Platelet transfusions to maintain platelet count > 20-30 x 10^9/L (or higher if there is active bleeding)
  - Packed red blood cells (PRBCs) to maintain adequate oxygen delivery
  - Fresh Frozen Plasma (FFP): To provide coagulation factors
  - Cryoprecipitate: To increase fibrinogen levels (target fibrinogen > 100 mg/dL)
Anticoagulation:
- Heparin: May be considered in specific situations (e.g., APL-associated DIC or thrombosis-dominant DIC) to inhibit thrombin generation
  - Use is controversial and requires careful monitoring due to the risk of worsening bleeding
  - Low-molecular-weight heparin (LMWH) may be preferred over unfractionated heparin
Antifibrinolytic Therapy:
- Controversial and generally not recommended
- May be considered in rare situations with life-threatening bleeding and evidence of primary fibrinolysis (very low fibrinogen and elevated D-dimer)

Poor Prognosis: DIC is associated with a high mortality rate
Factors Influencing Prognosis:
- Severity of the underlying condition
- Rapid and effective treatment of the underlying cause
- Prompt recognition and management of DIC complications