Disseminated intravascular coagulation is a pathologic process in
which coagulation and fibrinolysis are inappropriately initiated in
the microvasculature, resulting in systemic generation of thrombin.
Generation of thrombin produces widespread thrombosis (the earliest
and often unrecognized manifestation of DIC) which eventually leads
to hemorrhage (from consumption of platelets and consumption and cleavage
of coagulation factors). Inhibitors such as antithrombin and protein
C are depleted when the body attempts to limit the over-activated hemostatic
system. Plasmin and other proteases (e.g. neutrophil elastase in sepsis-induced
DIC) lyse the formed clots, liberating excessive amounts of FDPs and
D-dimer. Fibrinolysis contributes to hemorrhage by clot lysis, plasmin-mediated
cleavage of coagulation factors, and the anticoagulant effect of FDPs
(FDPs bind to platelets and fibrin monomers [only when FDPs are in high
concentration], inhibiting platelet function and fibrin polymerization).
The consumption of inhibitors allows unchecked activation of coagulation.
The main clinical manifestation of DIC is bleeding which is due to depletion
of coagulation factors and platelets, fibrinolysis, and the anticoagulant
effect of FDPs. However, every animal in DIC is also experiencing diffuse
microvascular thrombosis which directly contributes to the high morbidity
and mortality of DIC.
Disseminated intravascular coagulation is always a secondary
hemostatic disorder, that is initiated by an underlying disease.
Many conditions, including sepsis, heat stroke, intravascular hemolysis,
burns, shock, pancreatitis, neoplasia, or trauma can initiate DIC. Most
animals with acute or overt DIC are very ill and many show evidence
of a long-standing, serious disease.
It is now believed that the main trigger for DIC in nearly all disease
states is the pathologic exposure, expression, or release of tissue
factor. In certain conditions, e.g. snake bites, pancreatitis (trypsin
release) or certain neoplasms, the coagulation cascade can be activated
directly. Tissue factor expression on monocytes/macrophages and possibly
endothelial cells is upregulated by cytokines (particularly IL-6). Tissue
factor initiates coagulation through the extrinsic pathway of coagulation,
which is then amplified by excessive thrombin generation (as described
in the section on secondary hemostasis). At
the same time, tissue plasminogen activator is released from endothelial
cells and initiates systemic fibrinolysis. Other factors (such as platelet
hyperaggregability [e.g. from the release of ADP, a platelet agonist,
in intravascular hemolysis] or hyperfibrinogenemia) facilitate the development
of DIC. In some conditions, e.g. sepsis, the fibrinolytic pathway is
actually downregulated by TNFA-mediated release
of plasminogen activator inhibitor. This aggravates widespread thrombosis.
Although DIC is not a primary event, if left unchecked it can cause
death of the patient primarily due to hypoxic injury of vital organs
because of thrombosis.
There is no single diagnostic test for DIC. The diagnosis of acute or
overt DIC (the most commonly recognized form of DIC in animals) requires
identification of an appropriate underlying disease, recognition of
clinical signs of hemorrhage or thrombosis, and documentation of the
constellation of laboratory abnormalities consistent with DIC.
- Clinical signs: Overt
DIC is most readily recognized in the dog, because this species demonstrates
excessive hemorrhage, which is often clinically obvious and dramatic.
In other species, such as horses and cats, clinical diagnosis of DIC
is more difficult because they rarely manifest signs of excessive
hemorrhage, but are suffering from diffuse thrombosis. In these patients
(and in dogs with DIC that are not actively bleeding) DIC is often
called "sub-clinical". This is not due to the fact that
the disease is truly not clinical, but because thrombosis is so difficult
to detect by clinical criteria and current imaging techniques.
- Laboratory tests:
In overt DIC, there are defects/abnormalities in all aspects of hemostasis,
including platelets (especially number), factors/enzymes of the coagulation
cascade, inhibitors and fibrinolytic components. Typical laboratory
findings include thrombocytopenia (or a sequentially decreasing platelet
count), prolonged APTT (and possibly ACT if factor deficiencies are
severe enought) and PT, low fibrinogen, low antithrombin activity,
and positive FDP and/or D-dimer results. Of these tests, a prolonged
APTT, low antithrombin activity and high FDP/D-dimer results are the
most sensitive for the diagnosis of DIC in dogs and horses. Fibrinogen
concentrations are often normal or even high as fibrinogen acts as
an acute phase reactant with increased production occurring secondary
to the underlying disease. This increased production offsets or balances
the increased consumption occurring in DIC. A normal PT does not rule
out DIC, as for unknown reasons, this test is not as sensitive as
the APTT for diagnosis of DIC in dogs or horses. Cats with DIC may
have a prolonged aPTT and/or PT but may not have increased FDPs/D-dimer.
They usually do not have low antithrombin activity or low fibrinogen
Patients in non-overt (early) DIC are even more difficult to recognize.
Patients more commonly have diffuse thrombosis rather than the acute
fulminant life-threatening thrombosis/hemorrhage seen in acute overt
DIC. These patients are often described as having "compensated" DIC,
as increased production of coagulation factors and platelets by the
liver and bone marrow result in normalization of many of the coagulation
screening tests and the activated coagulation system is kept in check
by inhibitors. Often the only routine laboratory test that is abnormal
in non-overt DIC is a positive FDP/D-dimer result.
Therapy for DIC is quite controversial and no authors agree on appropriate
treatment regimes. All authors agree, however, that treatment for DIC
should primarily be centered on the identification and treatment of
the underlying disease. Supportive therapy including intravenous fluids
to maintain fluid volume and organ perfusion is vital. When it comes
to treating the coagulation defects, opinions diverge. Currently, most
authors recommend administration of heparin (especially low-molecular
weight forms) in patients with evidence of thrombosis, although few
controlled studies have been done to determine the benefit of such treatment.
Aspirin is contra-indicated due to its effect on platelet function,
as platelet function is inhibited in DIC by FDPs already and platelet
hyperaggregability is not usually a cause for thrombosis in DIC. In
hemorrhaging patients, most authors recommend the use of fresh or fresh
frozen plasma or whole blood (for platelets) to replace depleted clotting
factors. The early concept that such treatment will "fuel the fire"
is now recognized as myth. Some authors have suggested that heparin
be injected into bags of fresh or fresh frozen plasma (to activate antithrombin)
prior to transfusion, however this approach has not been substantiated
by well-controlled studies. Recent studies in human patients indicate
that administration of inhibitors, particularly protein C, are beneficial
in treating DIC in sepsis. However, this product is not available in