Systemic activation of coagulation
D ISSEMINATED I NTRAVASCULAR C OAGULATION
MARCEL LEVI, M.D.,
Intravascular deposition of fibrin
Depletion of platelets and coagulation factors
ISSEMINATED intravascular coagulation is characterized by the widespread activation ofcoagulation, which results in the intravascular formation of fibrin and ultimately thrombotic occlusion of small and midsize vessels.1-3 Intravascular coagulation can also compromise the blood supply to organs and, in conjunction with hemodynamic and metabolic derangements, may contribute to the failure of multiple organs. At the same time, the use and subsequent depletion of platelets and coagulationproteins resulting from the ongoing coagulation may induce severe bleeding (Fig. 1). Bleeding may be the presenting symptom in a patient with disseminated intravascular coagulation, a factor that can complicate decisions about treatment.
ASSOCIATED CLINICAL CONDITIONS AND INCIDENCE
Thrombosis of small and midsize vessels and organ failure
Figure 1. TheMechanism of Disseminated Intravascular Coagulation. Systemic activation of coagulation leads to widespread intravascular deposition of fibrin and depletion of platelets and coagulation factors. As a result, thrombosis of small and midsize vessels may occur, contributing to organ failure, and there may be severe bleeding.
TABLE 1. COMMON CLINICAL CONDITIONS ASSOCIATED WITH DISSEMINATEDINTRAVASCULAR COAGULATION.
Sepsis Trauma Serious tissue injury Head injury Fat embolism Cancer Myeloproliferative diseases Solid tumors (e.g., pancreatic carcinoma, prostatic carcinoma) Obstetrical complications Amniotic-fluid embolism Abruptio placentae Vascular disorders Giant hemangioma (Kasabach–Merritt syndrome) Aortic aneurysm Reactions to toxins (e.g., snake venom, drugs, amphetamines) Immunologicdisorders Severe allergic reaction Hemolytic transfusion reaction Transplant rejection
Disseminated intravascular coagulation is an acquired disorder that occurs in a wide variety of clinical conditions, the most important of which are listed in Table 1. Infectious disease, in particular septicemia, is the most common clinical condition associated with disseminated intravascular coagulation.Although virtually all microorganisms can cause disseminated intravascular coagulation, bacterial infection is most frequently related to the development of the syndrome. Clinically overt disseminated intravascular coagulation may occur in 30 to 50 percent of patients with gram-negative sepsis.4-6 Contrary to widely held belief, clinically overt disseminated intravascular coagulation appears to beas common in patients with gram-positive sepsis as in those with gram-negative sepsis.7 Triggers of the activation of diffuse coagula-
From the Department of Vascular Medicine and Internal Medicine, Academic Medical Center, University of Amsterdam (M.L., H.C.), and the Department of Internal Medicine, Slotervaart Hospital (H.C.) — both in Amsterdam. Address reprint requests to Dr. Levi at theDepartment of Vascular Medicine and Internal Medicine, Academic Medical Centre F-4, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands, or at email@example.com. ©1999, Massachusetts Medical Society.
tion in patients with infections are cell-specific membrane components of the microorganism, such as lipopolysaccharide or endotoxin, or bacterial exotoxins (e.g., staphylococcal a hemolysin). Allthese components may induce a generalized inflammatory response, characterized by the activation of the cytokine network.
Augus t 19 , 19 9 9 Downloaded from www.nejm.org by BARBARA ALVARADO on June 17, 2009 . Copyright © 1999 Massachusetts Medical Society. All rights reserved.
C UR R ENT C ONC EP TS
Another clinical condition frequently...