Basics
Description
- Disseminated intravascular coagulation (DIC) is an acquired syndrome that is always secondary to an underlying etiology.
- It is a systemic life-threatening process characterized by an uncontrolled activation of the coagulation and fibrinolytic systems with excessive thrombin generation and the consumption of coagulation factors and platelets.
- Widespread deposition of microthrombi can compromise perfusion and lead to organ failure.
- Ongoing activation and consumption of coagulant factors and platelets can result in diffuse and profuse bleeding.
Epidemiology
- Most commonly secondary to infections
- Overall incidence is difficult to determine secondary to the many conditions that cause DIC.
Pathophysiology
- Not a disorder in itself; occurs as a result of various initiating events
- Characterized by microvascular thrombosis and hemorrhage
- May be acute (e.g., meningococcemia) or chronic (e.g., malignancy/leukemia)
- There is a systemic intravascular deposition of fibrin as a result of increased thrombin generation, suppression of anticoagulant pathways, impaired fibrinolysis, and activation of inflammatory pathways.
- The initiation of coagulation activation leading to thrombin formation in DIC is mediated via the tissue factor/factor VIIa pathway.
- The tissue factor/factor VIIa pathway is activated via tissue factor expression from damaged endothelial cells.
- Anticoagulant pathways are diminished because of a decrease in the plasma levels of antithrombin and the protein C system through impaired production and increased destruction.
- The increase in fibrinolytic activity is likely secondary to the release of plasminogen activators from damaged endothelial cells.
Etiology
Most common causes are sepsis (particularly gram-negative), hypotensive shock, and trauma. �
- Sepsis/severe infection
- Bacterial: gram-negative and gram-positive
- Malaria: Plasmodium falciparum
- Fungal: Aspergillus
- Rickettsial: Rocky Mountain spotted fever
- Viral
- Trauma
- Multiple fractures with fat emboli
- Massive soft tissue injury
- Severe head trauma
- Multiple gunshot wounds
- Malignancies
- Acute promyelocytic leukemia
- Widespread solid tumors (e.g., neuroblastoma, adenocarcinoma)
- Obstetric
- Retained intrauterine fetal demise
- Preeclampsia/eclampsia
- Amniotic fluid embolism
- Abruptio placentae
- Posthemorrhagic shock
- Neonatal
- Necrotizing enterocolitis
- Perinatal asphyxia
- Amniotic fluid aspiration
- Obstetric complications (see above)
- Sepsis (bacterial and viral)
- Erythroblastosis fetalis
- Respiratory distress syndrome
- Vascular malformations
- Kasabach-Merritt syndrome
- Large vascular aneurysms
- Miscellaneous
- Acute hemolytic transfusion reaction
- Snake bite
- Homozygous protein C/S deficiency (purpura fulminans)
- Transplant rejection
- Severe collagen vascular disease
- Recreational drugs
- Profound shock or asphyxia
- Hypothermia or hyperthermia
- Extensive burn injuries
- Fulminant hepatitis/hepatic failure
- Severe pancreatitis
Diagnosis
History
- Presence of one of the underlying conditions (see "Etiology"�)
- Abrupt onset of bleeding
- Prolonged bleeding from venipuncture sites
- Bleeding from multiple sites, especially venipunctures, cutdown sites, mucous membranes, skin, GI tract, and genitourinary tract
- Pulmonary or intracranial hemorrhage
- Major organ dysfunction: pulmonary, renal, hepatic
Physical Exam
- Signs of underlying disease
- Generally, a very toxic-appearing patient
- Ecchymosis and petechiae
- Bleeding from previously intact venipuncture sites or surgical wounds
- Skin infarctions (purpura fulminans) secondary to thrombosis of dermal vessels
Diagnostic Tests & Interpretation
Lab
- There is no single test that can reliably diagnose DIC.
- Laboratory testing for DIC should be followed closely because results can change rapidly.
- CBC: Decreased platelet count is often the earliest abnormality, but this finding is nonspecific.
- Peripheral smear: schistocytes, microspherocytes (50% of cases)
- Prothrombin time (PT) and activated partial thromboplastin time (aPTT): normal to prolonged
- Prolonged PT in 50-75% of cases
- Prolonged aPTT in 50-60% of cases
- Fibrinogen: in the initial phase is increased as an acute-phase reactant and then decrease with consumption
- Fibrin degradation products or fibrin split products: increased
- Sensitivity 90-100% but low specificity
- Soluble fibrin monomer complexes (D-dimers): increased
- Elevated D-dimer in 93-100% of patients with DIC but low specificity
- A normal D-dimer rules out DIC
- Antithrombin, protein C or S levels: decreased
- Not routinely sent to assess for DIC
- Factor VIII: in the initial phase could be increased as an acute-phase reactant and then decrease with consumption
- Factor VIII is normal in coagulopathy associated with liver disease.
- Multiple scoring systems using common laboratory results have been developed to help determine if a patient is in DIC. These scoring systems have not been validated in pediatric patients.
Differential Diagnosis
- Coagulopathy of liver disease
- Vitamin K deficiency
- Pathologic fibrinolysis
- Other microangiopathic diseases, for example, thrombotic thrombocytopenic purpura or hemolytic uremic syndrome
Treatment
Additional Treatment
General Measures
- The most important therapy for DIC is to treat the underlying disorder.
- Supportive therapy may be required to treat symptomatic coagulation abnormalities.
- Hemostatic therapy should not be used to treat isolated laboratory abnormalities.
- Correction of the coagulopathy should only occur to treat bleeding or prior to an invasive procedure.
- Replacement therapy
- Cryoprecipitate: for fibrinogen replacement
- Platelets
- Fresh frozen plasma: contains all pro and anticoagulant proteins
- The role of heparin for DIC is controversial. It has been used in chronic DIC, arterial thromboses, or large vessel venous thromboses.
- Antithrombin at supraphysiologic dosing has been studied with mixed results.
- Antithrombin is currently not recommended for the treatment of DIC in pediatric patients.
- In pediatric DIC, recombinant activated protein C has not been shown to be beneficial and was associated with an increased risk of bleeding.
- Off-label use of recombinant activated factor VII has been reported for patients with severe bleeding that is refractory to replacement therapy. There are significant concerns about the prothrombotic potential of this medication.
- Antifibrinolytic agents (aminocaproic acid or tranexamic acid) have been used for patients with intense fibrinolysis (e.g., Kasabach-Merritt, acute promyelocytic leukemia, or trauma). These medications are not routinely recommended for the treatment of DIC.
- Supportive care: Manage other organ system failure.
Ongoing Care
Prognosis
- Poor unless underlying disease is treated
- The intensity and duration of DIC depend on the degree of activation of the coagulation system, liver function, blood flow, and ability to reverse underlying etiology that has led to DIC.
Complications
- Hemorrhage
- Thrombosis
- Multiorgan system failure
Additional Reading
- Levi �M. Disseminated intravascular coagulation. Crit Care Med. 2007;35(9):2191-2195. �[View Abstract]
- Levi �M, Meijers �JC. DIC: which laboratory tests are most useful? Blood Rev. 2011;25(1):33-37. �[View Abstract]
- Montagnana �M, Franchi �M, Danese �E, et al. Disseminated intravascular coagulation in obstetric and gynecologic disorders. Semin Thromb Hemost. 2010;36(4):404-418. �[View Abstract]
- Veldman �A, Fischer �D, Nold �MF, et al. Disseminated intravascular coagulation in neonates and preterm neonates. Semin Thromb Hemost. 2010;36(4):419-428. �[View Abstract]
Codes
ICD09
- 286.6 Defibrination syndrome
- 776.2 Disseminated intravascular coagulation in newborn
ICD10
- D65 Disseminated intravascular coagulation
- P60 Disseminated intravascular coagulation of newborn
SNOMED
- 67406007 Disseminated intravascular coagulation (disorder)
- 34417008 Disseminated intravascular coagulation in newborn (disorder)