From: Elizabeth M. Van Cott, M.D., and Michael Laposata, M.D., Ph.D., “Coagulation.” In: Jacobs DS et al, ed. The Laboratory Test Handbook, 5th Edition. Lexi-Comp, Cleveland, 2001; 327-358.
Related Information
Activated Partial Thromboplastin Time
D-Dimers and Fibrin Degradation Products
Fibrinogen
Prothrombin Time
Synonyms Consumptive Coagulopathy Screen; DIC Screen; Screen for Disseminated Intravascular Coagulation
Applies to Fibrinolysis; Schistocytes
Abstract The most useful panel of tests to screen for disseminated intravascular coagulation (DIC) includes D-dimer or fibrin degradation products (FDP), prothrombin time (PT), activated partial thromboplastin time (PTT), platelet count, and fibrinogen. These tests are not, however, specific for DIC.
Specimen Plasma (and whole blood for platelet count and peripheral blood smear)
Container Blue top (sodium citrate) tube; lavender top (EDTA) tube for platelet count and peripheral blood smear
Collection Routine venipuncture. Draw blue top before lavender top (EDTA) tube. If a red top is drawn, draw red top tube before blue top tube. Immediately invert tube gently at least 4 times to mix. Blue top tubes must be appropriately filled. Deliver tubes immediately to the laboratory.
Storage Instructions Blue top tube: separate plasma from cells as soon as possible; plasma may be stored on ice for up to 4 hours; otherwise store frozen
Causes for Rejection Blue top tube received more than 4 hours after collection, blue top tube not filled, clotted specimens
Turnaround Time 1-2 hours (often less than 1 hour if requested stat)
Reference Interval See individual tests.
Use Diagnose DIC in patients with an underlying disorder known to cause DIC and/or with clinical suspicion of DIC
Limitations D-dimer and FDP are positive with physiologic clot formation and lysis, and they may be positive in liver disease because they are normally cleared by the liver. Therefore, DIC can be difficult to diagnose in the presence of liver disease in some cases. Results should be reviewed in relation to the clinical situation.
Methodology See individual tests.
Additional Information DIC is a common acquired coagulation disorder resulting from excessive activation of the coagulation system, usually due to massive tissue injury, sepsis, or certain pregnancy complications. The normal anticoagulant and fibrinolytic systems are overwhelmed and cannot contain the coagulation activation, which becomes systemic, resulting in disseminated microvascular thrombi. Thrombosis consumes platelets, coagulation factors, and the natural anticoagulants, which consequently become depleted. The decrease in coagulation factors causes PT and PTT prolongations, and may lead to bleeding. Depletion of platelets also contributes to the bleeding risk. The fibrinolytic system is activated to dissolve the fibrin thrombi, resulting in consumption of plasminogen as it is converted into plasmin, and the formation of fibrin degradation products (FDP) including D-dimers as plasmin degrades fibrin clots. FDP can contribute to bleeding, because they impair fibrin clot formation and interfere with platelet function. In acute DIC, the most obvious clinical symptom is bleeding, although the insidious underlying disseminated microvascular thrombosis may lead to tissue ischemia and consequently multiorgan failure. The key laboratory findings are elevated D-dimers or FDP, prolonged PT and/or PTT, and decreased or decreasing platelets and fibrinogen. Repeat testing may be needed to show that fibrinogen and/or platelets are decreasing over time. Fibrinogen is decreased in ~50% of acute DIC cases; the PT is prolonged in ~70%; and the PTT is prolonged in ~50% of acute DIC cases. Thus, it is important to note that these tests can be normal in a substantial percentage of DIC cases.1,2 D-dimer or FDP should be positive in DIC. See D-Dimers and Fibrin Degradation Products.
Chronic DIC may develop when the activation of the coagulation system is low-grade and prolonged, as occurs with malignancy, retained dead fetus, aneurysm,3 or hemangioma. The clinical features and laboratory findings in chronic DIC can be much more subtle than with acute DIC. Fibrinogen and platelet levels are commonly elevated, because they can increase during acute phase reactions in response to illness (including malignancy), injury, or other conditions. The PT and PTT may actually be short, possibly due to increased circulating activated coagulation factors. Large-vessel thrombosis can occur in chronic DIC of malignancy. The main laboratory abnormality for acute or chronic DIC is positive D-dimers or FDP, neither of which are specific for DIC.
Schistocytes are present on the peripheral blood smear in 50% or more of acute DIC cases.4,5 Schistocytes are generated by microangiopathic hemolysis of red blood cells severed by flowing through fibrin strands. A large number of other coagulation tests may be abnormal in acute or chronic DIC, but their clinical utility for DIC diagnosis remains uncertain. These include decreases in the natural anticoagulant proteins antithrombin, protein C, and protein S; prolonged thrombin time; elevated markers of coagulation activation (eg, prothrombin fragment 1.2, fibrinopeptide A, fibrinopeptide B, fibrin monomers,6 thrombin-antithrombin complexes6), and the appearance of markers of fibrinolysis (plasmin-antiplasmin complexes,6 decreased plasminogen, and antiplasmin) (see Hypercoagulation Panel). The thrombin time is often prolonged because of decreased fibrinogen and/or elevated FDP. Elevated FDP interfere with fibrin polymerization, prolonging the thrombin time. Plasma markers of platelet activation, such as platelet factor 4 and beta-thromboglobulin, may also be detected. None of these markers are specific for DIC.
Treatment of the underlying condition is the primary treatment of DIC, along with supportive care including transfusions if needed for bleeding. Heparin use is controversial. New strategies, such as antithrombin concentrates or recombinant activated protein C, are under investigation.7
Footnotes
1. Spero JA, Lewis JH, and Hasiba U, “Disseminated Intravascular Coagulation: Findings in 346 Patients,”Thromb Haemost, 1980, 43:28-33.
2. Siegal T, Seligsohn U, Aghai E, et al, “Clinical and Laboratory Aspects of Disseminated Intravascular Coagulation (DIC): A Study of 118 Cases,”Thromb Haemost, 1978, 39(1):122-34.
3. Sakakibara Y, Takeda T, Hori M, et al, “Disseminated Intravascular Coagulation in Aortic Aneurysms: Assessment of Consumption Site Using Labeled-Platelet Scintigraphy,”Thorac Cardiovasc Surg, 1999, 47(3):162-5.
4. Chuansumrit A, Hotrakitya S, Sirinavin S, et al, “Disseminated Intravascular Coagulation Findings in 100 Patients,”J Med Assoc Thai, 1999, 82(Suppl 1):S63-8.
5. Gilbert JA and Scalzi RP, “Disseminated Intravascular Coagulation,”Emerg Med Clin North Am, 1993, 11(2):465-80.
6. Wada H, Sakuragawa N, Mori Y, et al, “Hemostatic Molecular Markers Before the Onset of Disseminated Intravascular Coagulation,”Am J Hematol, 1999, 60(4):273-8.
7. Eisele B and Lamy M, “Clinical Experience With Antithrombin III Concentrates in Critically Ill Patients With Sepsis and Multiple Organ Failure,”Semin Thromb Hemost, 1998, 24(1):71-80.
References
Baglin T, “Disseminated Intravascular Coagulation: Diagnosis and Treatment,”BMJ, 1996, 312(7032):683-7.
Levi M and ten Cate H, “Disseminated Intravascular Coagulation,”N Engl J Med, 1999, 341(8):586-92.
Marder VJ, Feinstein DI, Francis CW, et al, “Consumptive Thrombohemorrhagic Disorders,”Hemostasis and Thrombosis: Basic Principles and Clinical Practice, 3rd ed, Chapter 52, Colman RW, Hirsh J, Marder VJ, et al, eds, Philadelphia, PA: Churchill Livingstone, 1994, 1023-63.
