Hematology-Oncology Board Review Manual
Disseminated Intravascular Coagulation
Thomas G. DeLoughery, MD, MACP, FAWM
In the normal person, the process of coagulation is finely controlled at many levels to ensure
the appropriate amount of hemostasis at the
appropriate location. Broadly defined, disseminated intravascular coagulation (DIC) is the
name given to any process that disrupts this fine
tuning, leading to unregulated coagulation.
Defined this way, DIC may be found in a variety
of patients with a variety of disease states, and
can present with a spectrum of findings ranging
from asymptomatic abnormal laboratory results
to florid bleeding or thrombosis. It is important
to remember that DIC is always a consequence
of an underlying pathological process and not a
disease in and of itself. This article first reviews
concepts common to all forms of DIC, and then
reviews the more common disease states that
lead to DIC.
At the most basic level, DIC is the clinical
manifestation of inappropriate thrombin activation.1– 5 Inappropriate thrombin activation
can be due to underlying conditions such as
sepsis and obstetric disasters. The activation of
thrombin leads to (1) conversion of fibrinogen
to fibrin, ( 2) activation of platelets (and their
consumption), ( 3) activation of factors V and
VIII, ( 4) activation of protein C (and degradation of factors Va and VIIIa), ( 5) activation of
endothelial cells, and ( 6) activation of fibrinolysis (Table 1). Thus, with excessive activation of
thrombin one can see the following processes:
1. Conversion of fibrinogen to fibrin, which
leads to the formation of fibrin monomers and
excessive thrombus formation. These thrombi
are rapidly dissolved by excessive fibrinolysis in
most patients. In certain clinical situations, especially cancer, excessive thrombosis will occur. In
patients with cancer, this is most often a deep
venous thrombosis. Rare patients, especially
those with pancreatic cancer, may have severe
DIC with multiple arterial and venous thromboses. Nonbacterial thrombotic endocarditis can
also be seen in these patients, leading to widespread embolic complications.
2. Activation of platelets and their consumption. Thrombin is the most potent physiologic activator of platelets, so in DIC there
is increased activation of platelets. These activated platelets are consumed, resulting in
thrombocytopenia. Platelet dysfunction is also
present. Platelets that have been activated and
have released their contents but still circulate
are known as “exhausted” platelets; these cells
can no longer function to support coagulation. The fibrin degradation products (FDP)
in DIC can also bind to GP IIb/IIIa and inhibit
further platelet aggregation.
3. Activation of factors V, VIII, XI, and XIII.
Activation of these factors can promote thrombosis, but they are then rapidly cleared by antithrombin (XI) or activated protein C (V and
VIII) or by binding to the fibrin clot (XIII). This
can lead to depletion of all the prothrombotic
clotting factors and antithrombin, which in turn
can lead to both thrombosis and bleeding.
4. Activation of protein C further promotes
degradation of factors Va and VIIIa, enhances
fibrinolysis, and decreases protein C levels.