Etiology

Infection

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

Intravascular Hemolysis

• Acute Hemolytic Transfusion Reaction (see Acute Hemolytic Transfusion Reaction, [[Acute Hemolytic Transfusion Reaction]])
• Malaria (see Malaria, [[Malaria]])

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
  • Breast Cancer (see Breast Cancer, [[Breast Cancer]])
  • Gastric Cancer (see Gastric Cancer, [[Gastric Cancer]])
  • Ovarian Cancer (see Ovarian Cancer, [[Ovarian Cancer]])
  • Pancreatic Cancer (see Pancreatic Cancer, [[Pancreatic Cancer]])
  • Prostate Cancer (see Prostate Cancer, [[Prostate Cancer]])

Obstetric Complications

• Acute Fatty Liver of Pregnancy (see Acute Fatty Liver of Pregnancy, [[Acute Fatty Liver of Pregnancy]])
• Amniotic Fluid Embolism (see Amniotic Fluid Embolism, [[Amniotic Fluid Embolism]])
• HELLP Syndrome (see HELLP Syndrome, [[HELLP Syndrome]])
• Pre-Eclampsia/Eclampsia (see Pre-Eclampsia,Eclampsia, [[Pre-Eclampsia,Eclampsia]])
• Retained Dead Fetus

Rheumatologic

• Adult-Onset Still’s Disease (see Adult-Onset Still’s Disease, [[Adult-Onset Stills Disease]])

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
  • Abdominal Aortic Aneurysm (AAA) (see Abdominal Aortic Aneurysm, [[Abdominal Aortic Aneurysm]])
  • Thoracic Aortic Aneurysm (see Thoracic Aortic Aneurysm, [[Thoracic 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
  • Liver Transplant Rejection (see Liver Transplant, [[Liver Transplant]])
• Surgery
• Trauma: especially to the central nervous system

Physiology

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Diagnosis

Clinical Differentiation of Hemolytic Syndromes

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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