Disseminated Intravascular Coagulation (DIC)

Etiology

Infection

  • Sepsis (see Sepsis, [[Sepsis]])
    • Bacterial Infection
    • Fungal Infection
    • Parasitic Infection

Intravascular Hemolysis

Malignancy

  • Acute Promyelocytic Leukemia (APML) (see Acute Promyelocytic Leukemia, [[Acute Promyelocytic Leukemia]]): patient may present with DIC acutely or after initiation of chemotherapy
  • Brain Tumors
  • NK Cell Leukemia (aka Aggressive NK Cell Leukemia, ANKL) (see NK Cell Leukemia, [[NK Cell Leukemia]])
  • Mucinous Tumors

Obstetric Complications

Rheumatologic

Toxic

  • Amphetamine Intoxication (see Amphetamine, [[Amphetamine]])
  • Serotonin Syndrome (see Serotonin Syndrome, [[Serotonin Syndrome]])
  • Snake Bite
    • Rattlesnake Bite (see Rattlesnake Bite, [[Rattlesnake Bite]]): however, some consider this to be a coagulopathy/thrombotic microangiopathy that is distinct from DIC
    • Viper Bite

Other

  • Aortic Aneurysm
  • Anti-Phospholipid Antibody Syndrome (see Anti-Phospholipid Antibody Syndrome, [[Anti-Phospholipid Antibody Syndrome]])
  • Cardiopulmonary Bypass (CPB) (see Cardiopulmonary Bypass, [[Cardiopulmonary Bypass]]): the diagnosis of DIC post-cardiopulmonary bypass is difficult (since the identification of microthrombi is difficult and hemolysis and consumption of coagulation factors may be commonly seen following cardiopulmonary bypass)
  • Crush Injury
  • Cytokine Release Syndrome (see Cytokine Release Syndrome, [[Cytokine Release Syndrome]])
  • Fat Embolism (see Fat Embolism, [[Fat Embolism]])
  • Heat Stroke (see Heat Stroke, [[Heat Stroke]])
  • Kaposiform Hemangioendothelioma
  • Peritoneovenous Shunt (LeVeen Shunt) (see Peritoneovenous Shunt, [[Peritoneovenous Shunt]])
  • Protein C Deficiency (Hereditary) (see Protein C Deficiency, [[Protein C Deficiency]])
  • Solid Organ Transplant Rejection
  • Surgery
  • Trauma: especially to the central nervous system

Physiology

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Diagnosis

Clinical Differentiation of Hemolytic Syndromes

hemolyticsyndromes


Clinical Manifestations-Acute Disseminated Intravascular Coagulation (DIC)

Candidate Precipitating Etiology

  • Acute Hemolytic Transfusion Reaction (see Acute Hemolytic Transfusion Reaction, [[Acute Hemolytic Transfusion Reaction]])
  • Malignancy: especially the following
    • Acute Promyelocytic Leukemia (see xxxx, [[xxxx]])
  • Sepsis (see Sepsis, [[Sepsis]])
  • Trauma

Diagnosis

  • Platelet Count: decreased
  • INR: increased
  • PTT: increased
  • Thrombin Time: increased
  • Fibrinogen: decreased
  • Decreased Procoagulant Factors
    • Factor II (Thrombin): decreased
    • Factor V: decreased
    • Factor VIII: decreased (note: factor VIII is not synthesized by the liver and it is often high in liver disease, but is decreased in DIC)
    • Factor X: decreased
  • Decreased Coagulation Inhibitors
    • Antithrombin: decreased
    • Protein C: decreased
    • Protein S: decreased
  • Fibrin Degradation Products (FDP): increased (due to fibrinolysis)
  • D-Dimer: increased (due to fibrinolysis)
  • Peripheral Smear
    • Changes Consistent with Microangiopathic Hemolytic Anemia (MAHA): schistocytes, helmet cells, etc

Clinical

  • Hemorrhage: common in acute DIC (less common in chronic DIC) -> occurs in 64% of acute DIC cases
    • Hemorrhage from Wound/Trauma/Catheter/Drain Sites
    • Diffuse Alveolar Hemorrhage (DAH) (see Diffuse Alveolar Hemorrhage, [[Diffuse Alveolar Hemorrhage]]): due to damage to the pulmonary vascular endothelium
    • Ecchymoses
    • Intracranial Hemorrhage
    • Gastrointestinal Hemorrhage (see Gastrointestinal Hemorrhage, [[Gastrointestinal Hemorrhage]])
    • Mucosal Hemorrhage
  • Arterial/Venous Thromboembolism: more common in chronic DIC than in acute DIC -> occurs in 7% of cases
  • Organ Dysfunction
    • Acute Kidney Injury (AKI) (see Acute Kidney Injury, [[Acute Kidney Injury]]): occurs in 25% of cases
    • Acute Lung Injury-ARDS (see Acute Lung Injury-ARDS, [[Acute Lung Injury-ARDS]]): occurs in 16% of cases
      • Mechanism: pulmonary microthrombi
    • Adrenal Dysfunction/Waterhouse-Friderichsen Syndrome
      • Mechanism: adrenal hemorrhage or infarction
    • Central Nervous Involvement (Coma, Delirium, Transient Focal Neurologic Symptoms): occurs in 2% of cases
      • Mechanism: central nervous system microthrombi, hemorrhage, and/or hypoperfusion
    • Hepatic Dysfunction: occurs in 19% of cases
    • Shock: occurs in 14% of cases
  • Purpura Fulminans (see Purpura Fulminans, [[Purpura Fulminans]]): purpura associated with DIC

Clinical Manifestations-Chronic Disseminated Intravascular Coagulation (DIC)

Candidate Precipitating Etiology

  • Malignancy: especially the following
    • Brain Tumors
    • Gastric Cancer
    • Ovarian Cancer
    • Pancreatic Cancer

Diagnosis

  • Platelet Count: variable
  • INR: normal
  • PTT: normal
  • Thrombin Time: normal-slightly increased
    • Thrombin time is more sensitive than INR/PTT to the effects of increased D-dimers and fibrin degradation products in chronic DIC
  • Fibrinogen: normal-slightly increased
  • Factor V: normal
  • Factor VIII: normal
  • Fibrin Degradation Products (FDP): increased (due to fibrinolysis)
  • D-Dimer: increased (due to fibrinolysis)
  • Peripheral Smear: microangiopathic changes (schistocytes, helmet cells, etc)

Clinical

  • May Be Asymptomatic
  • Arterial/Venous Thromboembolism: more common in chronic DIC than in acute DIC
    • Especially without a clear precipitating factor
  • Hemorrhage: less common in chronic DIC (more common in acute DIC)
  • Non-Bacterial Thrombotic Endocarditis (Marantic Endocardiits, Libman-Sacks Endocarditis, Verrucous Endocarditis) (see Marantic Endocardiits, [[Marantic Endocardiits]])
  • Superficial Migratory Thrombophlebitis (Trousseau’s Syndrome) (see Superficial Migratory Thrombophlebitis, [[Superficial Migratory Thrombophlebitis]])

Treatment

Treat Underlying Etiology

  • Most Important Treatment Modality

Supportive Care

  • Hemodynamic Support (Pressors, Intravenous Fluids): as required
  • Mechanical Ventilation: as required

Treatment of Thrombotic Complications

  • Anticoagulation: as required to treat thrombotic complications

Treatment of Bleeding Complications

  • Antifibrinolytic Agents (Tranexamic Acid, Epsilon-Aminocaproic Acid, Aprotinin): contraindicated (since blockade of the fibrinolytic system may increase the risk of thrombosis)
    • However, these agents may be used in patients who have severe bleeding associated with a hyperfibrinolytic state
  • Antithombin: trials have shown this to be ineffective in DIC
  • Cryoprecipitate (see Cryoprecipitate, [[Cryoprecipitate]])
    • Indication: fibrinogen <100 mg/dL
    • One unit of cryoprecipitate (10-20 ml) contains the cold insoluble protein from one unit of FFP (contains vWF, factor VIII, factor XIII, fibrinogen, and fibrinonectin)
    • Some blood suppliers now provide one bag of pre-pooled cryoprecipitate which contains 5 (or more) units in 120-160 mL: use two bags of pre-pooled cryoprecipitate (ie: from 10 units of FFP)
  • Fresh Frozen Plasma (FFP) (see Fresh Frozen Plasma, [[Fresh Frozen Plasma]]): as required to treat coagulopathy in the setting of significant hemorrhage or need for invasive procedures
  • Packed Red Blood Cells (see Packed Red Blood Cells, [[Packed Red Blood Cells]]): as required to treat hemorrhage-related anemia
  • Platelet Transfusion (see Platelet Transfusion, [[Platelet Transfusion]])
    • Transfuse for Platelet Count <50k: in the setting of significant hemorrhage or need for invasive procedures
    • Transfuse for Platelet Count <10k: in all patients (due to the risk of spontaneous hemorrhage)
  • Prothrombin Complex Concentrates: likely contraindicated (due to risk of more thrombotic complications in the setting of an already hypercoagulable state)

Treatment of Purpura Fulminans (see Purpura Fulminans, [[Purpura Fulminans]])

  • Fresh Frozen Plasma (FFP) (see Fresh Frozen Plasma, [[Fresh Frozen Plasma]]): the administration of FFP as a source of protein C is problematic because of the short plasma half-life of protein C
    • Due to short plasma protein C half-life, FFP 2-3 units may be administered approximately every 6 hrs
  • Protein C Concentrate (see Protein C Concentrate, [[Protein C Concentrate]]): proven to decrease mortality rate in purpura fulminans

Expected Course of Resolution

  • Factors Impacting the Rate of DIC Resolution: DIC does not usually resolve immediately once the inciting factor is corrected
    • Resolution requires the synthesis of coagulant factors (which are synthesized at different rates)
    • Resolution requires hepatic clearance of anticoagulant factors and fibrin degradation products
    • Resolution requires bone marrow production of new platelets (which may take several days)
  • Resolution of DIC-Related Laboratory abnormalities: usually improve within a few days after the inciting stimulus is removed
  • Impact of Renal Failure on the Rate of DIC Resolution: does not impact the rate DIC resolution (unless there is a component of hepatorenal syndrome or if the kidneys are a major site of thrombosis)

References

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