Disseminated Intravascular Coagulation (DIC) Workup

Updated: Aug 23, 2022
  • Author: Marcel M Levi, MD; Chief Editor: Srikanth Nagalla, MD, MS, FACP  more...
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Approach Considerations

Diagnosis of disseminated intravascular coagulation (DIC) can be difficult, especially in cases of chronic, smoldering DIC, where clinical and laboratory abnormalities may be subtle. [56] No single routinely available laboratory test is sufficiently sensitive or specific to allow a diagnosis of DIC; however, several commonly available laboratory tests often yield abnormal results in DIC. Typically, moderate-to-severe thrombocytopenia is present. Furthermore, the peripheral blood smear can demonstrate evidence of microangiopathic pathology (schistocytes). Scoring systems have been developed to facilitate diagnosis of DIC.

Imaging studies are useful only to detect an underlying cause; the diagnosis of DIC is made by combining the clinical impression with any laboratory abnormalities noted.

No specific procedures help establish a specific diagnosis of DIC. However, a number of different procedures may help to diagnose the underlying causative condition.


Laboratory Studies

Patients with DIC can present with a wide range of abnormalities in their laboratory values. Typically, prolonged coagulation times, thrombocytopenia, high levels of fibrin degradation products (FDPs), elevated D-dimer levels, and microangiopathic pathology (schistocytes) on peripheral smears are suggestive findings.

Most individual laboratory tests demonstrate high sensitivity for DIC but very low specificity. [57] Furthermore, whereas acute DIC typically overwhelms compensatory anticoagulation mechanisms, resulting in depletion of factors and laboratory derangements, chronic or localized DIC may produce only minimal abnormalities in laboratory tests. [58]

It is essential to keep in mind that laboratory values may represent only a momentary glimpse into a very rapidly changing systemic process and that repeated tests may therefore be necessary in order to make a more clinically certain diagnosis. [4]

Standard tests

In clinical practice, a diagnosis of DIC can often be made by a combination of the following tests [42] :

  • Platelet count
  • Global clotting times (aPTT and PT)
  • One or two clotting factors and inhibitors (eg, antithrombin)
  • Assay for D-dimer or FDPs

Platelet count

Typically, moderate-to-severe thrombocytopenia is present in DIC. Thrombocytopenia is seen in as many as 98% of DIC patients, and the platelet count can dip below 50 × 109/L in 50%. [59] A trend toward decreasing platelet counts or a grossly reduced absolute platelet count is a sensitive (though not specific) indicator of DIC. [42] Repeated platelet counts are often necessary, as a single platelet measurement may indicate a level within the normal range, whereas trend values might show a precipitous drop from previous levels.

The peripheral blood smear can reveal schistocytes, though these are rarely seen to exceed 10% of red blood cells (RBCs). The presence of schistocytes is neither sensitive nor specific for DIC, but in certain instances, it may help confirm a chronic DIC diagnosis when the schistocytes are seen in concert with normal coagulation values and increased D-dimer levels. [59]

Clotting times and coagulation factors

Global clotting times (ie, activated partial thromboplastin time [aPTT] and prothrombin time [PT]) are typically prolonged. In as many as 50% of DIC patients, however, a normal or even an attenuated PT and aPTT may be encountered; consequently, such values cannot be used to exclude DIC. [60] This phenomenon may be attributed to certain activated clotting factors present in the circulation, such as thrombin or Xa, which may in fact enhance thrombin formation. [35]

It should be emphasized that serial coagulation tests are usually more helpful than single laboratory results in establishing the diagnosis of DIC. It is also important to note that the PT, not the international normalized ratio (INR), should be used in the DIC monitoring process; INR is recommended only for monitoring oral anticoagulant therapy. [42]

The prolongation of global clotting times may reflect the consumption and depletion of various coagulation factors, which may be further substantiated by the measurement of selected coagulation factors, such as factor V and factor VII. Measurement of coagulation factors may be helpful for detecting additional hemostatic abnormalities (eg, those caused by vitamin K deficiency).

Protein C and antithrombin are 2 natural anticoagulants that are frequently decreased in DIC. There is some evidence to suggest that they may serve roles as prognostic indicators. [61, 62] Nonetheless, the practical application of measuring these anticoagulants may be limited for most practitioners because the tests may not be generally available. [42]

DIC is associated with an unusual light transmission profile on the aPTT, known as a biphasic waveform. In one study, the degree of biphasic waveform abnormality had an increasing positive predictive value for DIC, independent of clotting time prolongation. [63] In addition, the waveform abnormalities are often evident before more conventionally used laboratory value derangements, [63] making this a quick and robust test for DIC. At present, however, the photo-optical analyzers necessary in clot formation analysis are not widely available.

Tests for fibrinogen, D-dimer, and FDPs

Because fibrin activation is a central component of DIC, it would seem logical to assume that if soluble fibrin is elevated, the diagnosis of DIC can be made with confidence. [64] However, soluble fibrin levels are not available to most clinicians within a relevant time frame. Likewise, laboratory assays aimed at differentiating between cross-linked fibrin, fibrinogen, and soluble fibrin have been developed but are not routinely available to the clinician.

The massive fibrin deposition in DIC suggests that fibrinogen levels would be decreased. Accordingly, measurement of fibrinogen has been widely advocated as a useful tool for the diagnosis of DIC; however, it is in fact not very helpful. Fibrinogen, as a positive acute-phase reactant, is increased in inflammation, and whereas values may decrease as the illness progresses, they are rarely low. [18, 65] One study demonstrated that in up to 57% of DIC patients, the levels of fibrinogen may in fact remain within normal limits. [59]

In a consecutive series of patients, the sensitivity of a low fibrinogen level for the diagnosis of DIC was only 28%, and hypofibrinogenemia was detected in a very small number of severe cases of DIC only. Sequential measurements of fibrinogen might be more useful and might be more likely to provide diagnostic clues.

Fibrinolysis is an important component of DIC; thus, there will be evidence of fibrin breakdown, such as elevated levels D-dimer and FDPs. D-dimer elevation means that thrombin has proteolyzed fibrinogen to form fibrin that has been cross-linked by thrombin-activated factor XIIIa. When fibrin becomes cross-linked insoluble, a unique D-D domain neoepitope forms. This cross-linked insoluble fibrin is then proteolyzed uniquely by plasmin to liberate the soluble D-D dimer. Thus, the D-dimer measures prior thrombin and plasmin formation. On the other hand, FDPs only inform that plasmin has been formed and it cleaved soluble fibrinogen, fibrin, or insoluble cross-linked fibrin. D-dimer is the better test for DIC.

Accordingly, testing for D-dimer or FDPs may be helpful for differentiating DIC from other conditions that may be associated with a low platelet count and prolonged clotting times, such as chronic liver disease. Most laboratories have an operational test for D-dimer. In the United States, FDPs are not used as often.

D-dimer or FDPs may be detected by means of specific enzyme-linked immunosorbent assay (ELISA) or latex agglutination assay, allowing rapid and bedside determination in emergency cases. However, some of the available assays for FDPs cross-react with fibrinogen degradation products, and this cross-reactivity may cause spuriously high results. The specificity of high levels of D-dimer and FDPs is therefore limited, and many other conditions (eg, venous thromboembolism, trauma, inflammation, and recent surgery) may be associated with elevated FDP levels. [18, 66]

Specialized tests

In a specialized setting, molecular markers for activation of coagulation or fibrin formation may be the most sensitive assays for DIC. [67] A number of clinical studies show that the presence of soluble fibrin in plasma has a 90-100% sensitivity for DIC but, unfortunately, a relatively low specificity. As noted (see above) a reliable test for quantifying soluble fibrin in plasma is not available, and one study showed a wide discordance among various assays.

The dynamics of DIC can also be judged by measuring activation markers that are released upon the conversion of the coagulation factor zymogen to an active protease, such as prothrombin activation fragment F1+2 (F1+2). Indeed, these markers are markedly elevated in patients with DIC, but again, the specificity is a problem.

In addition to the known limitations in specificity, many of the more sensitive and sophisticated tests described above are not available to general hematology laboratories. Although these tests may be very helpful in clinical trials or other research, they often cannot be used in a routine setting.

Evidence also suggests that serum levels of thrombomodulin, a marker for endothelial cell damage, correlate well with the clinical course of DIC, the development of multiple organ dysfunction syndrome (MODS), and mortality in septic patients. Thrombomodulin is elevated in DIC, and such elevation and not only correlates well with the severity of DIC but also can serve as a marker for early identification and monitoring of DIC. [68]

Regardless of the discussion above, most hospitals of all sizes in the developed world have available PT, aPTT, fibrinogen, platelet count, and D-dimer. These tests alone are sufficient to make or exclude a clinical diagnosis of DIC in the practice of medicine.


DIC Scoring Systems

The diagnosis of DIC relies on multiple clinical and laboratory determinations. The International Society on Thrombosis and Haemostasis (ISTH) developed a simple scoring system for the diagnosis of overt DIC that makes use of laboratory tests available in almost all hospital laboratories (see the image below, and the DIC Score calculator.) [4] The presence of an underlying disorder known to be associated with DIC (see Etiology) is a sine qua non for the use of this diagnostic algorithm.

Diagnostic algorithm for the diagnosis of overt di Diagnostic algorithm for the diagnosis of overt disseminated intravascular coagulation.

A score of 5 or higher indicates overt DIC, whereas a score of less than 5 does not rule out DIC but may indicate DIC that is not overt. [4] Prospective validation studies show this scoring system to be highly accurate for the diagnosis of DIC. The sensitivity of the DIC score for a diagnosis of DIC is 91-93%, and the specificity is 97-98%. [67, 69]

Other analyses show that the DIC scoring system is a strong independent predictor of a fatal outcome in intensive care unit (ICU) patients. In these studies, mortality was higher than 40% in patients with sepsis and DIC (according to the scoring system), compared with about 25% in patients without DIC. For each DIC point in the system, the odds ratio for mortality is 1.29, whereas for each Acute Physiology and Chronic Health Evaluation (APACHE) classification system point, the odds ratio for mortality is 1.07.

Despite the demonstrable utility of the ISTH scoring system for diagnosing overt DIC, concerns have been expressed about its validity for identifying nonovert DIC. In response to these concerns, the Japanese Association for Acute Medicine (JAAM) developed a diagnostic algorithm and scoring system designed for use in critically ill patients (see Table 4 below). [70]

Table 4. Japanese Association for Acute Medicine (JAAM) Scoring System for DIC (Open Table in a new window)

Clinical conditions that should be ruled out


Dilution and abnormal distribution

Massive blood loss, massive infusion


Disorders of hematopoiesis

Liver disease


Spurious laboratory results

Diagnostic algorithm for SIRS

Temperature >38°C or < 36°C

Heart rate >90 beats/min

Respiratory rate >20 breaths/min or PaCO2< 32 mm Hg (< 4.3 kPa)

WBC count >12,000 cells/µL, < 4000 cells/ µL, or 10% immature (band) forms

Diagnostic algorithm

SIRS criteria






Platelet count (× 109/L)


< 80 or >50 % decrease within 24 hours


>80 and < 120 or >30% decrease within 24 hours




Prothrombin time (value of patient/normal value)




< 1.2


Fibrin/FDPs (mg/L)




>10 and < 25


< 10



4 points or more


DIC = disseminated intravascular coagulation; FDP = fibrin degradation product; HELLP = hemolysis, elevated liver enzymes, low platelet count; HIT = heparin-induced thrombocytopenia; HUS = hemolytic uremic syndrome; ITP = idiopathic thrombocytopenic purpura; PaCO2 = partial pressure of carbon dioxide in arterial blood; SIRS = systemic inflammatory response syndrome; TTP = thrombotic thrombocytopenic purpura; WBC = white blood cell.

This system has been prospectively validated and has been found to be capable of diagnosing DIC earlier than previous methods could. Furthermore, evidence suggests that early identification of DIC using this scoring system, as well as early and aggressive treatment of DIC and the underlying disorder, can lead to improvements in patient outcome and reductions in mortality. [70]

In a study of the JAAM DIC criteria in 79 patients with severe sepsis or septic shock, Umemura et al reported that the addition of two hemostatic endothelial molecular markers—protein C activity and plasminogen activator inhibitor 1—measured within 12 hours of admission, provided greater prognostic value, predicting mortality with a sensitivity of 84.6% and a specificity of 80.3%. Protein C activity correlated best with mortality, followed by plasminogen activator inhibitor 1. Using those criteria, DIC-positive patients also had significantly higher disease severity. [44]

The Japanese Society on Thrombosis and Hemostasis (JSTH) has developed diagnostic criteria for DIC based on the underlying pathology (basic, hematopoietic, or infectious). [71] The JSTH criteria are shown in Table 5, below. 

Table 5. Japanese Society on Thrombosis and Hemostasis (JSTH) Diagnostic Criteria for DIC (Open Table in a new window)

            Test Results



Platelet count (×103/μl)*







Fibrin degradation products (FDP; μg/ml)**







Fibrinogen (mg/dl)





Prothrombin time ratio





Antithrombin (%)



TAT, SF, or F1+2

≥2-fold upper limit of normal


Liver failure

Acute: Prothrombin time activity 40% or International Normalized Ratio ≥1.5)

Chronic: Cirrhosis with Child-Pugh B or C (≥7 points)


F1+2= prothrombin fragment 1 + 2; SF=soluble fibrin; TAT=thrombin-antithrombin complex

*For a platelet count of >50 × 103/μL, add 1 point if the count decreases ≥30% within 24 h. The maximum score for the platelet count is 3 points.

**For institutions that do not measure FDP, a D-dimer increase of ≥2-fold the upper limit of normal scores 1 point.

With the JSTH system, diagnostic scoring for DIC is as follows:

  • Basic: ≥6 points
  • Hematopoietic (note that the platelet count is not included in the score calculation): ≥4 points
  • Infectious: (note that the fibrinogen level is not included in the score calculation)  ≥5 points

Histologic Findings

Grossly, hemorrhage into all tissues (eg, brain, adrenal, lung, kidney) can develop in acute hemorrhagic DIC.

Histologic studies in patients with DIC show the presence of ischemia and necrosis due to fibrin deposition in small and medium-sized vessels of various organs. The presence of these intravascular thrombi appears to be clearly and specifically related to the clinical dysfunction of the organ. Specific thrombotic complications that are sometimes seen in the framework of DIC are acral cyanosis, hemorrhagic skin infarctions, and limb ischemia.