Disseminated intravascular coagulation in infants and children
- Wendy Wong, MD
Wendy Wong, MD
- General Pediatrician
- Palo Alto Medical Foundation
- Bertil Glader, MD, PhD
Bertil Glader, MD, PhD
- Professor of Pediatrics
- Stanford University School of Medicine
Disseminated intravascular coagulation (DIC) is an acquired syndrome characterized by hemorrhage and microvascular thrombosis. Endothelial tissue damage from a variety of underlying disorders (eg, sepsis, trauma, and malignancy) activates the coagulation cascade, which promotes fibrin production and deposition, and consumption of clotting factors. The subsequent consumption of coagulation factors and platelets, enhanced fibrinolysis, and fibrin deposition result in the clinical picture of DIC of a bleeding diathesis accompanied by thrombosis that may lead to end organ damage (figure 1 and figure 2).
The etiology, clinical manifestations, diagnosis, and treatment of DIC in infants and children will be reviewed here. DIC in adults is discussed separately. (See "Clinical features, diagnosis, and treatment of disseminated intravascular coagulation in adults".)
The following is a summary of the pathogenesis of disseminated intravascular coagulation (DIC). A more complete discussion is found elsewhere. (See "Clinical features, diagnosis, and treatment of disseminated intravascular coagulation in adults", section on 'Pathogenesis'.)
DIC is a secondary process caused by the systemic activation of the coagulation system by tissue damage from a variety of underlying diseases (eg, sepsis, trauma, and malignancies) . The activation of the intravascular coagulation system initiates the following processes (figure 1):
●Exposure of blood to procoagulants — Tissue damage from the initiating primary disease releases procoagulants into the bloodstream.
- Levi M. Disseminated intravascular coagulation. Crit Care Med 2007; 35:2191.
- Abshire TC, Gold SH, Odom LF, et al. The coagulopathy of childhood leukemia. Thrombin activation or primary fibrinolysis? Cancer 1990; 66:716.
- Ribeiro RC, Pui CH. The clinical and biological correlates of coagulopathy in children with acute leukemia. J Clin Oncol 1986; 4:1212.
- Hunger SP. Chromosomal translocations involving the E2A gene in acute lymphoblastic leukemia: clinical features and molecular pathogenesis. Blood 1996; 87:1211.
- Barbui T, Falanga A. Disseminated intravascular coagulation in acute leukemia. Semin Thromb Hemost 2001; 27:593.
- Pegelow C, Goldberg R, Turkel S, Powars D. Severe coagulation abnormalities in Reye syndrome. J Pediatr 1977; 91:413.
- Andrew M. The relevance of developmental hemostasis to hemorrhagic disorders of newborns. Semin Perinatol 1997; 21:70.
- Kreuz W, Veldmann A, Fischer D, et al. Neonatal sepsis: a challenge in hemostaseology. Semin Thromb Hemost 1999; 25:531.
- Andrew M, Paes B, Milner R, et al. Development of the human coagulation system in the full-term infant. Blood 1987; 70:165.
- Andrew M, Paes B, Milner R, et al. Development of the human coagulation system in the healthy premature infant. Blood 1988; 72:1651.
- Veldman A, Fischer D, Nold MF, Wong FY. Disseminated intravascular coagulation in term and preterm neonates. Semin Thromb Hemost 2010; 36:419.
- Woods WG, Luban NL, Hilgartner MW, Miller DR. Disseminated intravascular coagulation in the newborn. Am J Dis Child 1979; 133:44.
- GAJL-PECZALSKA K. PLASMA PROTEIN COMPOSITION OF HYALINE MEMBRANE IN THE NEWBORN AS STUDIES BY IMMUNOFLUORESCENCE. Arch Dis Child 1964; 39:226.
- Buchanan GR. Coagulation disorders in the neonate. Pediatr Clin North Am 1986; 33:203.
- Bick RL. Disseminated intravascular coagulation current concepts of etiology, pathophysiology, diagnosis, and treatment. Hematol Oncol Clin North Am 2003; 17:149.
- Poralla C, Traut C, Hertfelder HJ, et al. The coagulation system of extremely preterm infants: influence of perinatal risk factors on coagulation. J Perinatol 2012; 32:869.
- Favaloro EJ. Laboratory testing in disseminated intravascular coagulation. Semin Thromb Hemost 2010; 36:458.
- Akca S, Haji-Michael P, de Mendonça A, et al. Time course of platelet counts in critically ill patients. Crit Care Med 2002; 30:753.
- Taylor FB Jr, Toh CH, Hoots WK, et al. Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost 2001; 86:1327.
- Bakhtiari K, Meijers JC, de Jonge E, Levi M. Prospective validation of the International Society of Thrombosis and Haemostasis scoring system for disseminated intravascular coagulation. Crit Care Med 2004; 32:2416.
- Toh CH, Hoots WK, SSC on Disseminated Intravascular Coagulation of the ISTH. The scoring system of the Scientific and Standardisation Committee on Disseminated Intravascular Coagulation of the International Society on Thrombosis and Haemostasis: a 5-year overview. J Thromb Haemost 2007; 5:604.
- Levi M, Toh CH, Thachil J, Watson HG. Guidelines for the diagnosis and management of disseminated intravascular coagulation. British Committee for Standards in Haematology. Br J Haematol 2009; 145:24.
- Williams MD, Chalmers EA, Gibson BE, Haemostasis and Thrombosis Task Force, British Committee for Standards in Haematology. The investigation and management of neonatal haemostasis and thrombosis. Br J Haematol 2002; 119:295.
- Franchini M, Manzato F. Update on the treatment of disseminated intravascular coagulation. Hematology 2004; 9:81.
- de Kleijn ED, de Groot R, Hack CE, et al. Activation of protein C following infusion of protein C concentrate in children with severe meningococcal sepsis and purpura fulminans: a randomized, double-blinded, placebo-controlled, dose-finding study. Crit Care Med 2003; 31:1839.
- Veldman A, Fischer D, Wong FY, et al. Human protein C concentrate in the treatment of purpura fulminans: a retrospective analysis of safety and outcome in 94 pediatric patients. Crit Care 2010; 14:R156.
- Nadel S, Goldstein B, Williams MD, et al. Drotrecogin alfa (activated) in children with severe sepsis: a multicentre phase III randomised controlled trial. Lancet 2007; 369:836.
- Martí-Carvajal AJ, Solà I, Lathyris D, Cardona AF. Human recombinant activated protein C for severe sepsis. Cochrane Database Syst Rev 2011; :CD004388.
- Hanada T, Abe T, Takita H. Antithrombin III concentrates for treatment of disseminated intravascular coagulation in children. Am J Pediatr Hematol Oncol 1985; 7:3.
- Ogawa E, Yagasaki H, Kato M, et al. Successful treatment of disseminated intravascular coagulation in a child with acute myelogenous leukaemia using recombinant thrombomodulin. Br J Haematol 2010; 149:911.
- Shirahata A, Mimuro J, Takahashi H, et al. Postmarketing Surveillance of Recombinant Human Soluble Thrombomodulin (Thrombomodulin α) in Pediatric Patients With Disseminated Intravascular Coagulation. Clin Appl Thromb Hemost 2014; 20:465.
- Saito H, Maruyama I, Shimazaki S, et al. Efficacy and safety of recombinant human soluble thrombomodulin (ART-123) in disseminated intravascular coagulation: results of a phase III, randomized, double-blind clinical trial. J Thromb Haemost 2007; 5:31.
- Older infants and children
- - Sepsis
- - Trauma and tissue injury
- - Malignancy
- - Miscellaneous
- - Sepsis
- - Perinatal conditions
- - Congenital disorders
- CLINICAL MANIFESTATIONS
- LABORATORY FINDINGS
- Fibrin formation
- Other studies
- Laboratory evaluation
- Scoring system
- - Neonates
- DIFFERENTIAL DIAGNOSIS
- Thrombocytopenia and normal coagulation tests
- - Neonate
- Abnormal coagulation tests and normal platelet count
- Normal coagulation tests and platelet count
- Replacement therapy
- - Heparin
- - Anticoagulant restoration
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS