274
U N I T 3
Hematopoietic Function
evidence that the underlying cause of DIC is infection
or inflammation, and the cytokines (tumor necrosis fac-
tor, interleukin-1, and others) liberated in the process
are the pivotal mediators.
29,30
These cytokines not only
mediate inflammation, but can also increase the expres-
sion of tissue factor on endothelial cells and simulta-
neously decrease the expression of thrombomodulin.
Thrombomodulin is a glycoprotein, present on the cell
membrane of endothelial cells, that binds thrombin
(IIa) and acts as an additional regulatory mechanism in
coagulation. The net effect is a shift in balance toward a
procoagulant state.
28
Common clinical conditions that may cause DIC
include obstetric disorders, accounting for 50% of
cases; massive trauma; shock; sepsis; and malignant dis-
ease. Chart 12-2 summarizes the conditions associated
with DIC. The factors involved in the conditions that
cause DIC are often interrelated. In obstetric complica-
tions, tissue factors released from necrotic placental or
fetal tissue or amniotic fluid may enter the circulation,
inciting DIC. The hypoxia, shock, and acidosis that may
coexist also contribute by causing endothelial injury.
Gram-negative bacterial infections result in the release
of endotoxins, which activate both the extrinsic path-
way by release of tissue factor and the intrinsic pathway
through endothelial damage. Endotoxins also inhibit
the activity of protein C. Antigen–antibody complexes
associated with infection can activate platelets through
complement fragments.
Although coagulation and formation of microem-
boli characterize DIC, its acute manifestations usually
Thrombin
generation
Thrombosis
Intravascular
fibrin deposition
Plasminogen
activation
Platelet
consumption
Thrombocytopenia
Plasmin
generation
Clotting factor
degradation
Fibrinolysis
Fibrin degradation
products
(inhibit thrombin
and platelet aggregation)
Hemolytic
anemia
Tissue
ischemia
Bleeding
Intrinsic pathway
(Endothelial injury)
Extrinsic pathway
(Tissue injury)
Trauma
Burns
Gram-negative sepsis
Hypoxia
Acidosis
Shock
Vasculitis
Trauma
Obstetric complications
Complications of cancer
FIGURE 12-5.
Pathophysiology of disseminated
intravascular coagulation.
CHART 12-2
ConditionsThat Have Been Associated
with Disseminated Intravascular
Coagulation
Obstetric Conditions
Abruptio placentae
Dead fetus syndrome
Preeclampsia and eclampsia
Amniotic fluid embolism
Cancers
Metastatic cancer
Acute promyelocytic leukemia
Infections
Acute bacterial infections (e.g., meningococcal
meningitis)
Histoplasmosis, Aspergillosis
Rickettsial infections (e.g., Rocky Mountain spotted fever)
Parasitic infections (e.g., malaria)
Sepsis/septic shock
Trauma or Surgery
Burns
Massive trauma
Surgery involving extracorporeal circulation
Snake bite
Heatstroke
Hematologic Conditions
Blood transfusion reactions
