The prothrombin time-INR and activated thromboplastin time (aPPT) are usually elevated in severe DIC but may be normal or shortened in chronic forms.9 One may also see a shortened aPTT in severe acute DIC due to large amounts of activated thrombin and factor X “bypassing” the contact pathway. An aPTT as short as 10 seconds has been seen in acute DIC. The platelet count is usually reduced but may be normal in chronic DIC. Serum fibrinogen and platelets are decreased in acute DIC but again may be in the “normal” range in chronic DIC.10 The most sensitive screening test for DIC is a fall in the platelet count, with low counts seen in 98% of patients and counts under 50,000 cells/μL in 50%.9,11 The least specific test is fibrinogen, which tends to fall below normal only in severe acute DIC.9
SPECIFIC TESTS
This group of tests allows one to deduce that abnormally high concentrations of thrombin are present.
Ethanol Gel and Protamine Tests
Both of these older tests detected circulating fibrin monomers, whose appearance is an early sign of DIC. Circulating fibrin monomers are seen when thrombin acts on fibrinogen. Usually the monomer polymerizes with the fibrin clot, but when there is excess thrombin these monomers can circulate. Detection of circulating fibrin monomer means there is too much IIa and, ergo, DIC is present.
Fibrin(ogen) Degradation Products
Plasmin acts on the fibrin/fibrinogen molecule to cleave the molecule in specific places. The resulting degradation product levels will be elevated in situations of increased fibrin/fibrinogen destruction (DIC and fibrinolysis). The FDP are typically mildly elevated in renal and liver disease due to reduced clearance.
D-Dimers
When fibrin monomers bind to form a thrombus, factor XIII acts to bind their “D” domains together. This bond is resistant to plasmin and thus this degradation fragment is known as the “D-dimer.” High levels of D-dimer indicate that (1) IIa has acted on fibrinogen to form a fibrin monomer that bonded to another fibrin monomer, and (2) this thrombus was lysed by plasmin. Because D-dimers can be elevated (eg, with exercise, after surgery), an elevated D-dimer needs to be interpreted in the context of the clinical situation.11 Currently, this is the most common specific test for DIC performed.
Other Tests
Several other tests are sometimes helpful in diagnosing DIC.
Thrombin time. This test is performed by adding thrombin to plasma. Thrombin times are elevated in DIC (FDPs interfere with polymerization), in the presence of low fibrinogen levels, in dysfibrinogenemia, and in the presence of heparin (very sensitive).
Reptilase time is the same as thrombin time but is performed with a snake venom that is insensitive to heparin. Reptilase time is elevated in the same conditions as the thrombin time, with the exception of the presence of heparin. Thrombin time and reptilase time are most useful in evaluation of dysfibrinogenemia.
Prothrombin fragment 1.2 (F1.2). F1.2 is a small peptide cleaved off when prothrombin is activated to thrombin. Thus, high levels of F1.2 are found in DIC but can be seen in other thrombotic disorders. This test is still of limited clinical value.
DIC scoring system.A scoring system to both diagnose and quantify DIC has been proposed (Figure).11,12
This system is especially helpful for clinical trials. A drawback of the score that keeps it from being implemented for routine clinical use is that it requires the prothrombin time, which is not standardized nor often reported by many clinical laboratories.
Thromboelastography (TEG). This is a point-of-care test that uses whole blood to determine specific coagulation parameters such as R time (time from start of test to clot formation), maximal amplitude (MA, maximum extent of thrombus), and LY30 (MA at 30 minutes, a measure of fibrinolysis).13 Studies have shown that TEG can identify DIC by demonstrating a shorter R time (excess thrombin generation) which prolongs as coagulation factors are consumed. The MA is decreased as fibrinogen is consumed and the LY30 shows excess fibrinolysis. TEG has been shown to be of particular value in the management of the complex coagulopathy of trauma.14
MIMICKERS OF DIC
It is important to recognize coagulation syndromes that are not DIC, especially those that have specific other therapies. The syndromes most frequently encountered are thrombotic thrombocytopenic purpura (TTP) and catastrophic antiphospholipid antibody syndrome (CAPS). One important clue to both of these syndromes is that, unlike DIC, there is no primary disorder (cancer, sepsis) that is driving the coagulation abnormalities.
TTP should be suspected when any patient presents with any combination of thrombocytopenia, microangiopathic hemolytic anemia (schistocytes and signs of hemolysis) plus end-organ damage.15–18 Patients with TTP most often present with intractable seizures, strokes, or sequelae of renal insufficiency. Many patients who present with TTP have been misdiagnosed as having sepsis, “lupus flare,” or vasculitis. The key diagnostic differentiator between TTP and DIC is the lack of activation of coagulation with TTP—fibrinogen is normal and D-dimers are minimally or not elevated. In TTP, lactate dehydrogenase is invariably elevated, often 2 to 3 times normal.19 The importance of identifying TTP is that untreated TTP is rapidly fatal. Mortality in the pre–plasma exchange era ranged from 95% to 100%. Today plasma exchange therapy is the foundation of TTP treatment and has reduced mortality to less than 20%.16,20–23Rarely patients with antiphospholipid antibody syndrome can present with fulminant multiorgan system failure.24–28 CAPS is caused by widespread microthrombi in multiple vascular fields. These patients will develop renal failure, encephalopathy, adult respiratory distress syndrome (often with pulmonary hemorrhage), cardiac failure, dramatic livedo reticularis, and worsening thrombocytopenia. Many of these patients have pre-existing autoimmune disorders and high-titer anticardiolipin antibodies. It appears that the best therapy for these patients is aggressive immunosuppression with steroids plus plasmapheresis, followed by rituximab or, if in the setting of lupus, intravenous cyclophosphamide monthly.27,29 Early recognition of CAPS can lead to quick therapy and resolution of the multiorgan system failure.
