How I Treat In Brief: Managing Disseminated Intravascular Coagulation

Recently, Marcel Levi, MD, and Marie Scully, MD, wrote about their strategies for the management of patients with disseminated intravascular coagulation (DIC). Below, we summarize their approach.

This material was repurposed from “How I Treat Disseminated Intravascular Coagulation,” published in the February 22, 2018, edition of Blood.

  • Disseminated intravascular coagulation (DIC) is systemic activation of coagulation in its most extreme form and is characterized by organ failure and profuse bleeding from various sites.
  • DIC is not a disease in itself, but is always secondary to an underlying condition that causes the activation of coagulation, including sepsis, malignancy, and trauma.
  • There is no single laboratory test that can diagnose DIC, but reliable diagnosis can be made through a simple scoring algorithm based on routine hemostatic parameters.
  • The cornerstone of supportive treatment of DIC is management of the underlying condition. Therapeutic interventions to treat DIC are mostly supportive and only partially effective.
  • Adjunctive supportive treatment aimed at the coagulation system (i.e., prothrombin complex or coagulation factor concentrates) may be required even after adequate treatment of the underlying condition.

Understanding DIC 

A variety of disorders, including severe sepsis, systemic inflammatory conditions, trauma, and malignant disease, can lead to activation of the coagulation system, which will rarely result in clinical complications. Disseminated intravascular coagulation (DIC) is systemic activation of coagulation in its most extreme form.

DIC is characterized by thrombotic obstruction of small and midsize vessels, thereby limiting blood supply to various organs and contributing to organ failure. Ongoing activation of the coagulation system and other factors may exhaust patients’ factors and platelets, potentially causing profuse bleeding from various sites.

DIC is not a disease in itself, but is always secondary to an underlying condition that causes the activation of coagulation. Sepsis, systemic inflammatory conditions, cancers, and the other disorders most frequently associated with DIC are listed in TABLE 1.

Clinical Conditions Most Frequently Associated With DIC

The development of DIC is often related to a strong immune response and the releases of cytokines (in the setting of DIC related to infections), the expression of procoagulant factors by tumor cells (in the setting of DIC in hematologic and solid-tumor malignancies), and release of tissue material and endothelial disruption (in the setting of DIC related to trauma).

For other underlying conditions, DIC is a relatively infrequent complication. In most situations, the severity of the associated systemic inflammatory response will determine whether severe systemic coagulation activation will occur.

While DIC is marked by certain laboratory abnormalities, the overlap between abnormalities associated with DIC and other coagulopathies complicates its diagnosis. The following cases illustrate the difficulties in identifying and managing DIC.

Case #1: Diagnosing DIC 

A 68-year-old man was admitted to the intensive care unit because of respiratory failure three days after a hemicolectomy. Laboratory analysis showed hemoglobin (Hb) level of 11.0 g/dL, leukocyte count of 9.2×109/L (with neutrophils at 7.7×109/L), some schistocytes in the blood smear, creatinine concentration of 2.4 mg/dL, bilirubin concentration of 1.2 mg/dL, lactic acid concentration of 30 mg/dL, and bicarbonate concentration of 18 mmol/L.

Routine coagulation tests showed a low platelet count (98×109/L), prolonged prothrombin time (PT; 17 seconds), prolonged activated partial thromboplastin time (aPTT; 43 seconds), high concentration of D-dimer (7.5 μg/mL), high fibrinogen concentration (3.5 g/L), and an international normalized ratio (INR) of 1.4.

Commentary: This patient presented with multiple organ failure and a clinical suspicion of sepsis. Although he showed clear signs of a coagulopathy, which may be compatible with DIC, some differential diagnostic considerations need to be taken into account, including thrombotic microangiopathy and heparininduced thrombocytopenia (HIT).

All the patient’s laboratory results taken together suggest that DIC is the most probable explanation for the coagulopathy in this patient. Patients with DIC have:

  • a low or rapidly decreasing platelet count
  • prolonged global coagulation tests
  • low plasma levels of coagulation factors and inhibitors
  • increased markers of fibrin formation and/or degradation (i.e., D-dimer or fibrin degradation products)

Proteins that are acute-phase reactants are usually not decreased, or may even increase. Therefore, fibrinogen, one of the laboratory tests used to diagnose DIC, is not a very good marker for DIC, except in severe cases.

Dynamic changes in coagulation factors and platelets may add important information. A significant drop in platelet counts (as illustrated in this case), a lengthening duration of clotting assays, or an increase in fibrin split products can indicate an early stage of DIC.

There is no single laboratory test with sufficient accuracy for the diagnosis of DIC. Instead, the International Society on Thrombosis and Haemostasis developed a simple scoring system that can be calculated with readily available, routine hemostatic parameters (TABLE 2). Notably, the severity of DIC according to this scoring system is a strong predictor for mortality in sepsis.

Case #2: Ruling Out Organ Failure–Related Coagulopathies 

A 63-year-old woman with long-standing alcohol abuse presented with decompensated liver cirrhosis. Laboratory test results showed an Hb concentration of 11.3 g/dL, leukocyte count of 9.2×109/L, and platelet count of 88×109/L. Coagulation tests revealed a prolonged PT (17 seconds), prolonged aPTT (52 seconds), high D-dimer concentration (1.0 μg/mL), and normal fibrinogen concentration (2.1 g/L). Are these coagulation abnormalities due to liver failure–related coagulopathy or DIC secondary to an infection?

Scoring Algorithm for the Diagnosis of DIC

Commentary: The differential diagnosis between the coagulopathy of liver disease and DIC is challenging, as many laboratory abnormalities point in the same direction. For example, more than 75 percent of patients with cirrhosis present with a platelet count of <150×109/L.

In most cases, the coagulopathy of liver disease can eventually be distinguished from the presence of DIC. In contrast to patients with DIC, those with severe liver disease have a stable low platelet count and only mildly elevated fibrin degradation products (due to the simultaneous presence of fibrinolytic activation and impairment in liver failure). In addition, clinical signs, such as the presence of splenomegaly and ascites, may indicate that liver disease, rather than DIC, is the cause of the coagulopathy. In the case presented, the DIC score was 4 (suggestive of no DIC) and, in combination with the clinical signs and symptoms, a diagnosis of coagulopathy due to severe liver failure was made.

Case #3: Managing Complications of DIC 

A 63-year-old man presented with severe cholangiosepsis due to an obstructive stone in the common bile duct. He was in shock, was respiratory-insufficient, and developed acute renal failure. Coagulation analysis showed a low platelet count (48×109/L), prolonged PT (19 seconds), prolonged aPTT (39 seconds), a high D-dimer concentration (5.5 μg/mL), normal fibrinogen concentration (2.8 g/L), and an INR of 1.6.

After the diagnosis of DIC was established, the patient was awaiting endoscopic retrograde cholangiopancreatography and restoration of bile-duct patency. He was treated with vasopressors, intubation, and mechanical ventilation, and antibiotics were started. What would be the most appropriate supportive treatment of the patient’s coagulopathy?

Commentary: A proposed algorithm for the diagnostic and therapeutic management of DIC, based on whether a patient has active bleeding, overt thromboembolism, or neither clinical symptom, is presented in the FIGURE.

Available therapeutic interventions for DIC are mostly supportive and only partially effective, at best resulting in an amelioration of coagulation derangement or more rapid resolution of DIC. However, these approaches have not been proven to result in an improvement of clinically relevant outcomes, such as organ function or survival.

The cornerstone of supportive treatment of this coagulopathy, then, is proper management of the underlying condition (i.e., bile-duct drainage and antibiotics in the case detailed above). If successfully undertaken, the coagulopathy will spontaneously resolve.

Therefore, in some situations, adjunctive supportive treatment aimed at the coagulation system will be required, because the coagulopathy may proceed even after adequate treatment of the underlying condition has been initiated.

Flowchart for the Diagnostic and Therapeutic Management of DIC

Future Directions 

Important questions about the proper management of this coagulopathy remain. For instance, a randomized controlled trial of heparin in patients with DIC is urgently needed because there is increasing circumstantial evidence that heparin may be beneficial in this setting.

Better supportive treatment of DIC also may stem from advances in early patient identification and risk stratification. Hypothetically, assays specifically aimed at the assessment of endothelial cell perturbation, in combination with early-stage systemic coagulopathy, would help identify high-risk patients to facilitate faster – and potentially more efficacious – interventions.

A better understanding of the influence of genomics in the host response leading to DIC will help determine a person’s risk of developing DIC and identify patients who are more susceptible to severe coagulopathy, with the eventual goal of tailoring treatment to the most vulnerable patients.