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Disseminated Intravascular Coagulation, Pediatric

Basics

Description

- 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

- 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

- 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

  • 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. пїЅ

  • Sepsis/severe infectionBacterial: gram-negative and gram-positiveMalaria: Plasmodium falciparumFungal: AspergillusRickettsial: Rocky Mountain spotted feverViral
  • TraumaMultiple fractures with fat emboliMassive soft tissue injurySevere head traumaMultiple gunshot wounds
  • MalignanciesAcute promyelocytic leukemiaWidespread solid tumors (e.g., neuroblastoma, adenocarcinoma)
  • ObstetricRetained intrauterine fetal demisePreeclampsia/eclampsiaAmniotic fluid embolismAbruptio placentaePosthemorrhagic shock
  • NeonatalNecrotizing enterocolitisPerinatal asphyxiaAmniotic fluid aspirationObstetric complications (see above)Sepsis (bacterial and viral)Erythroblastosis fetalisRespiratory distress syndrome
  • Vascular malformationsKasabach-Merritt syndromeLarge vascular aneurysms
  • MiscellaneousAcute hemolytic transfusion reactionSnake biteHomozygous protein C/S deficiency (purpura fulminans)Transplant rejectionSevere collagen vascular diseaseRecreational drugsProfound shock or asphyxiaHypothermia or hyperthermiaExtensive burn injuriesFulminant hepatitis/hepatic failureSevere pancreatitis

Diagnosis

History

  • Presence of one of the underlying conditions (see "Etiology"пїЅ)
  • 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 prolongedProlonged PT in 50-75% of casesProlonged 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: increasedSensitivity 90-100% but low specificity
  • Soluble fibrin monomer complexes (D-dimers): increasedElevated D-dimer in 93-100% of patients with DIC but low specificityA normal D-dimer rules out DIC
  • Antithrombin, protein C or S levels: decreasedNot routinely sent to assess for DIC
  • Factor VIII: in the initial phase could be increased as an acute-phase reactant and then decrease with consumptionFactor 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 therapyCryoprecipitate: for fibrinogen replacementPlateletsFresh 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 пїЅM. Disseminated intravascular coagulation. Crit Care Med. 2007;35(9):2191-2195. пїЅ[View Abstract]
  • Levi пїЅM, Meijers пїЅJC. DIC: which laboratory tests are most useful? Blood Rev. 2011;25(1):33-37. пїЅ[View Abstract]
  • Montagnana пїЅM, Franchi пїЅM, Danese пїЅE, et al. Disseminated intravascular coagulation in obstetric and gynecologic disorders. Semin Thromb Hemost. 2010;36(4):404-418. пїЅ[View Abstract]
  • Veldman пїЅA, Fischer пїЅD, Nold пїЅMF, et al. Disseminated intravascular coagulation in neonates and preterm neonates. Semin Thromb Hemost. 2010;36(4):419-428. пїЅ[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)