Disseminated Intravascular Coagulation
Agnes Aysola, M.D., ITxM Fellow
Ileana Lopez-Plaza, M.D., Assistant Medical Director, CTS
DIC is an acquired coagulation disorder with uncontrolled intravascular activation of coagulation and secondary fibrinolysis. It is a multietiologic, life-threatening syndrome with a broad spectrum of clinical manifestation spanning from compensated subacute to decompensated acute and fulminant forms.1
Virtually any disorder associated with release of phospholipids and tissue factor can lead to DIC. Clinical disorders giving rise to DIC fall into categories of trauma, surgery, obstetric complications, malignancy, sepsis, liver disease, intravascular hemolysis, and a variety of inflammatory conditions2.
Once DIC is triggered, the inappropriate formation of thrombin is basically similar in all disorders.
Activation of Thrombin:
Thrombin causes the conversion of fibrinogen into fibrin and causes platelet aggregation. Effects of uncontrolled thrombin activation leads to the decrease of Factors I, II, V, VIII, XIII, and platelets. Activated thrombin is neutralized by antithrombin III (AT) and heparin cofactor II. The levels of these proteins decrease due to their consumption and allow the unregulated activity of thrombin with formation of thrombi in microvasculature, leading to microangiopathic hemolytic anemia and secondary consumptive thrombocytopenia.
Activation of Plasmin:
Plasmin generation increases with thrombin activation, and fibrinolysis develops. Circulating plasmin then cleaves fibrin and factors I, V, and VIII, with subsequent formation of fibrinogen degradation products (FDP) and D-dimers. This secondary fibrinolysis in combination with thrombocytopenia leads to a bleeding diathesis. Plasmin can also activate the complement and kinin systems, causing increased vascular permeability, hypotension, and shock.
Clinical manifestations of DIC are extremely variable. They not only depend on features of the underlying disease, but they also vary with the evolving clinical picture2. Presenting symptoms include:
Petechiae, purpura, acral cyanosis/gangrene, oozing from puncture sites. The microvascular thrombosis causes end-organ damage to the lungs, heart, kidneys, liver, and CNS.
Symptoms depend on the compensation capacity of the liver and bone marrow. The patient can be asymptomatic with only laboratory abnormalities or, can present with low grade bleeding, singular or multiple thrombotic events, including large vessel thrombi.
Routinely employed laboratory tests are neither sensitive nor specific, and will vary with the degree of activity (acute versus chronic). Serial measurements of PT, PTT, fibrinogen level, platelet count, and the presence of FDP, D-dimers and schistocytes in the peripheral blood smear give more information about the dynamics of the clinical situation.
Frequently, PT, PTT, and TT will be prolonged (heparin will give a similar effect). The fibrinogen level decreases, but since fibrinogen is an acute phase reactant, normal levels do not exclude the diagnosis of DIC. A sharp recent decrease of the platelet count is the most characteristic feature (seen in 98% of cases). Hence, the absence of thrombocytopenia excludes the diagnosis of DIC. Naturally occurring inhibitors (antithrombin, protein C, and protein S) are consumed and their levels decline as well. As the result of rapid fibrinolysis, the level of FDP and D-dimer increase. These findings are non-specific, since they can be increased in any thromboembolic events causing reactive fibrinolysis. Peripheral smears reveal the presence of schistocytes in 63% of the cases, along with large platelets, indicating increased platelet turnover.
This form is suspected when bleeding occurs in a predisposed setting. Unexpected, mild thrombocytopenia, low to borderline low fibrinogen and AT levels are seen. The FDP and D-dimers are usually elevated.
Because of diverse etiologies and clinical manifestations of DIC, proper management must be highly individualized. In general, the therapeutic goal is:
The patients PT, PTT, platelet count, fibrinogen level, and HCT should be monitored at 4 to 6 hour intervals and replacement therapy adjusted accordingly. An effective therapy is indicated by the slowing or cessation bleeding, normalization of PT, PTT, and decreased FDP and D-dimer levels.
In DIC the uncontrolled activation of coagulation causes thrombin formation in microvasculature, leading to multiple organ failure. Thrombocytopenia and depletion of plasma clotting factors create a serious bleeding tendency that is worsened by secondary fibrinolysis. The hallmark of therapy is treatment of the underlying disorder. Replacement of the consumed coagulation factors helps to control the bleeding tendency.
CORRECTION: The February 1999 TMU issue has the following revision: For patients with a mechanical heart valve, a target range INR of 2.5 to 3.5 is recommended and for patients with lupus anticoagulant, the target INR of 3.0 to 3.5.
Copyright © 1999, Institute For Transfusion Medicine
Copies of the Transfusion Medicine Update can be obtained by calling Deborah Small at (412)209-7320; or by e-mail: firstname.lastname@example.org