At a Glance

Disseminated intravascular coagulation (DIC) is a potentially life-threatening disorder that involves a pathological activation of coagulation system. This clinical syndrome can be triggered by a variety of disorders that lead to the formation of widespread intravascular thrombosis.

Depending on the underlying condition, two clinical forms of DIC have been described: acute (decompensated) and chronic (compensated). The acute form (e.g., sepsis) is usually developed after sudden exposure of the blood to excessive amount of tissue factor, which usually occurs via endothelial injury during massive tissue damage, inflammatory activation, or cancer cell lysis. This will cause massive generation of intravascular thrombin that will overwhelm the compensatory hemostatic mechanisms. Consequently, a severe consumptive coagulopathy will develop leading to serious internal and/or external bleeding complications.

DIC is most commonly seen in sepsis, massive tissue injury (e.g., trauma, burns, extensive surgery), malignancy (particularly acute promyelocytic leukemia – APML), severe transfusion reactions, infections (gram-negative sepsis), autoimmune disorders, obstetric complications (e.g., intrauterine death with retained fetus, retained placenta, and amniotic fluid embolism), snake bite, shock, heat stroke, vasculitis, vascular abnormalities, severe hepatic failure, and severe toxic reactions.

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The typical initial presentation of acute DIC may vary from minor bleeding (e.g., petechiae, ecchymoses, oozing from venipuncture sites, etc.) to serious, life-threatening bleeding (e.g., gastrointestinal bleeding, respiratory tract bleeding, oozing from surgical wound sites, etc.). The intravascular thrombosis will also cause a mechanical shearing of the bypassing red blood cells producing microangiopathic hemolytic anemia.

In addition, thrombosis can disrupt and compromise the blood supply to organs and may, along with the anemia, contribute to multiorgan dysfunction, shock, and death. Acute renal failure can develop in up to 40% of DIC patients. Liver dysfunction, pulmonary complications (e.g., hemorrhage, hemoptysis, dyspnea, and acute respiratory distress syndrome), and central nervous system dysfunction (e.g., coma, delirium, and transient focal neurologic symptoms) are often seen as well.

The rate of intravascular thrombosis formation in chronic DIC is much slower and balanced with the normal compensatory mechanisms. Therefore, other than the underlying condition symptoms, often cancer, chronic DIC patients may be completely asymptomatic, and DIC is usually diagnosed accidentally in these patients.

In the United States, DIC occurs in an estimated 1% of all hospitalized patients with no age or gender differences. This may rise to 30-50% in septic patients. Mortality rate varies from 10-50%, depending on the associated underlying disorder and the extent of the intravascular thrombosis with the highest rate also seen in septic patients.

Four different methods are effectively engaged in the hematologic abnormalities of DIC: excessive thrombin generation, suppressed anticoagulant pathways, impaired fibrinolysis, and inflammatory activation.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

In addition to the clinical findings of the underlying condition, diagnosis of acute DIC is suggested by a variety of laboratory tests that demonstrate evidence of both increased thrombin generation and increased fibrinolysis.

The former can be manifested by signs of coagulation factors consumption: prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT) and moderate to severe thrombocytopenia (<100 x 103/microL). The fibrinogen level is usually low in acute DIC but may be elevated as an acute phase reactant in certain chronic conditions.

The presence of microangiopathic changes (schistocytes) on the peripheral blood smear provides additional evidence of acute DIC. Elevated levels of fibrinogen degradation products (FDPs) and D-dimers are sufficient evidence of accelerated fibrinolysis in DIC.

Although evaluation is not recommended during acute DIC, all anticoagulants (i.e., antithrombin, protein C, and protein S) levels are depleted. Other tests that may be helpful in acute DIC, but are often not needed, are the prolonged thrombin time (TT) and reptilase time.

Because of the slower and balanced coagulation factors consumption, these laboratory findings are quite different in chronic DIC; PT and aPTT are often normal, fibrinogen level is normal or slightly elevated, and platelet count may be only slightly decreased.

In addition to the peripheral blood smear evidence of microangiopathy, elevated FDPs and D-dimers are basically the main diagnostic findings in chronic DIC.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

Significant hemolysis, presence of anticoagulant (therapeutic or contamination), and/or dilution factors (drawing from an IV line) may affect the lab results.

What Lab Results Are Absolutely Confirmatory?

In addition to the peripheral blood smear findings (schistocytes), D-dimers and FDPs are used to confirm both types of DIC.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

According to the International Society on Thrombosis and Haemostasis (ISTH), DIC is defined as “An acquired syndrome characterized by the intravascular activation of coagulation with loss of localization arising from different causes. It can originate from and cause damage to the microvasculature, which if sufficiently severe, and can produce organ dysfunction.” Table 1 shows a DIC scoring system developed by the ISTH to support DIC diagnosis.

Table 1.
Score 0 1 2 3
Platelet Count (x 103/microL) >100 <100 <50
Elevated FDPs or D-dimers No increase Moderate increase Strong increase
Prolonged PT (Seconds) <3 >3<6 >6
Fibrinogen level (mg/dL) >100 <100

Maximal score, 8; if greater than or equal to 5, compatible with DIC; if less than 5, not affirmative for DIC.

In addition to the tissue plasminogen activator (tPa) that has been released from the injured endothelial cells, thrombin also assists in the conversion of plasminogen to plasmin. This will produce compensatory thrombolysis and the release of large amount of FDPs, which will enhance bleeding by interfering with normal fibrin polymerization and by binding to the platelet surface glycoprotein IIb/IIIa fibrinogen receptor, interfering with platelet aggregation. Simultaneously, plasmin will also activate the complement and kinin systems causing the development of many of the DIC clinical symptoms: hypotension, increased vascular permeability, and shock.(Table 1)

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

The negative predictive value of D-dimers is significantly high; therefore, negative D-dimers can rule out DIC with 95% confidence. However, elevated D-dimers and FDPs are not specific for DIC, as they may be elevated in other conditions, such as venous thromboembolism, trauma, or recent surgery, limiting the specificity of these tests.

It is very important to differentiate between DIC and other medical conditions that exhibit similar findings but with different pathogenesis, as in liver disease, thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS), and Heparin-induced thrombocytopenia (HIT).

Synthesis of coagulation factors and inhibitors can be significantly decreased in severe liver diseases. Thrombocytopenia can also be induced by hypersplenism secondary to portal hypertension. Low fibrinogen, dysfibrinogenemia, and elevated levels of FDPs can be present in liver diseases as well. Hence, careful interpretation is required in these cases.

Thrombocytopenia and microangiopathic blood smear findings are also present in patients with TTP-HUS. However, coagulation screening tests (PT and aPTT) are usually normal or slightly elevated.

HIT is another clinical condition that may resemble DIC; however, HIT does not typically produce the consumptive coagulopathy seen in DIC and thrombocytopenia is often more prominent in HIT and usually pursues a history of a prolonged exposure to heparin.