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March, 1999

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 Diagnosis

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.

Laboratory Diagnosis

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:

1. Treatment of the underlying disease without delay

2. Replacement of deficient clotting components

3. Control of the coagulation disorder

Vigorous treatment of the underlying disease and aggressive support measures are the cornerstones of therapy. This may include fluid replacement, oxygenation, antibiotics for infections, removal of necrotic tissue, evacuation of retained products of conception, removal of malignant tumors, etc.

Substitution of coagulation components:

In seriously bleeding patients, packed red cells are transfused to improve the blood oxygen carrying capacity. A platelet count below 20,000/microL, (or below 50,000/microL in a bleeding patient), is indication for platelet transfusion. Generally, 1 unit of random platelets per 10 kgs of body weight will increase circulating platelets above hemostatic levels while providing 50 ml of plasma with each unit used. Fresh frozen plasma (FFP) contains all the components of the coagulation and fibrinolytic system; the recommended dose is 15-20 ml/kg (4-6 units for adults). If the fibrinogen level is below 100 mg/dL, cryoprecipitate is the treatment of choice. It provides an approximate 200 mg of fibrinogen per unit, along with Factor VIII, Factor XIII, and von Willebrand factor, all of which improve hemostasis. Each unit of cryoprecipitate increases the plasma fibrinogen level by 5-10 mg/dL; the usual adult dose is 6-10 units. Because antithrombin III is consumed along with other inhibitors, replacement with heat treated pooled plasma concentrates of AT may be beneficial (Thrombate IIIā and AT-nativā ). Multiple clinical trials have demonstrated shortened duration of DIC with high doses (2.0-4.0 units/ml) AT transfusion without clearly improved survival.3 The advantage of AT concentrate over the antithrombin effect of heparin, is that there is no bleeding risk associated with AT concentrate. Recombinant AT concentrate is currently under investigation.

Administration of Heparin:

This is controversial in acute DIC, because clinical studies yield conflicting results with no conclusive evidence that heparin treatment reduces morbidity and mortality. Anticoagulant therapy is generally accepted in chronic DIC, when progressive thrombin formation occurs. Heparin may also be beneficial in patients with large vessel thrombosis. The recommended heparin dose in low grade DIC is 100 units/kg subcutaneous ever 4 to 6 hours.

Monitoring Response

The patient’s 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.


1. MG Vervloet, LG Thijs, CE Hack Derangements of coagulation and fibrinolysis in critically ill patients with sepsis and septic shock. Semin Thromb Hemostas. 1998;24:33-44.

2. RL Bick. Disseminated intravascular coagulation: objective clinical and laboratory diagnosis, treatment, and assessment of therapeutic response. Semin Thromb Hemostas. 1996;22:69-88.

3. M Riewald, H Riess, Treatment options for clinically recognized disseminated intravascular coagulation. Semin Thromb Hemostas. 1998;24:53-59.

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


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