Chapter 45: Disseminated Intravascular Coagulation

The differential diagnosis includes the following:

• Thrombotic thrombocytopenic purpura

• Idiopathic thrombocytopenic purpura

• Disseminated intravascular coagulation

• Heparin-induced thrombocytopenia

The most likely diagnosis in this clinical setting is disseminated intravascular coagulation (DIC). DIC is a syndrome, not a diagnosis. It is an acquired state that occurs as a result of a number of underlying conditions (Table 45-1). For the purpose of this review, we will focus on acute DIC. In the setting of DIC, there is global activation of the coagulation system with formation of fibrin within the circulation. Fibrin deposition leads to thrombosis and occlusion of small vessels, with subsequent end-organ damage. At the same time, depletion of platelets and clotting factors can also lead to bleeding.¹

In the clinical scenario described above, DIC may be due to his traumatic brain injury as well as his sepsis. The brain has a high concentration of tissue thromboplastin, which has a tendency to become prothrombotic when released into systemic circulation.² He is also bacteremic. Sepsis may cause marked activity of the inflammatory system, and inflammation-induced activation of coagulation is a well-recognized phenomenon.³ Severe sepsis may be complicated by DIC in about 35% of cases.⁴

DIC is a clinical diagnosis of a syndrome. Clinical manifestations include⁵:

• Thrombosis

• Bleeding

• Renal dysfunction

• Hepatic dysfunction

• Shock

On physical examination one may note cool, mottled extremities; petechiae; ecchymoses; or hemorrhages at the site of invasive procedures. From a laboratory standpoint, there is not one single laboratory test in isolation that can determine the diagnosis of DIC. Instead, DIC is a clinical syndrome, and laboratory data help support clinical suspicion (Table 45-2).

It is important to remember to monitor the trend in these parameters. As fibrinogen is an acute-phase reactant, it can be elevated in the setting of sepsis or inflammation. Therefore, evaluating serial measurements and analyzing the trend are essential. A review of the peripheral smear may reveal the presence of microangiopathic changes.

The subcommittee on DIC of the Scientific and Standardization Committee of the International Society of Thrombosis and Haemostasis (ISTH) has developed a scoring system based on the outcome of a combination of several laboratory tests (Table 45-3). A score of greater than or equal to 5 is compatible with the diagnosis of overt DIC.⁶ Prospective studies have validated this scoring system.⁴

The first step is to treat the underlying diagnosis. Supportive care for DIC includes infusion of fresh-frozen plasma 10 mL/kg, platelet and blood transfusion,⁷ and cryoprecipitate in order to improve abnormal coagulation and reduce active bleeding (Figure 45-1). Therapy is indicated in patients who are actively bleeding or who are at high risk of bleeding, but should not be used merely to "treat" abnormal laboratory values.

Heparin has been used in patients with thrombotic manifestations of DIC based on anecdotal evidence. Experimental studies have shown that heparin can at least partly inhibit the activation of coagulation in DIC.⁸ There are no randomized controlled trials to demonstrate the use of heparin in patients with DIC leading to any improvement in clinical outcomes. Small uncontrolled studies have reported limited benefits with heparin use and have demonstrated that heparin infusion may improve laboratory abnormalities associated with DIC.^9,10,11 If it is used, a bolus is usually not needed and it should be initiated at 500 units/h as a starting dose. Patients must be monitored carefully for any bleeding.

Given the association of abnormal coagulation with systemic inflammation, substitution of coagulation products such as antithrombin III and protein C has been attempted in the setting of sepsis and DIC. However, results have been conflicting. The largest study using antithrombin III in patients with DIC demonstrated no benefit. Activated protein C has been shown in some studies to have a possible mortality benefit in patients with severe sepsis.^12,13,14,15

The overall prognosis of acute DIC is poor, with reported mortality rates ranging from 40% to 80% in patients with severe sepsis, trauma, or burn injuries.^16,17,18 Mortality is thought to be affected by the magnitude of underlying disease processes causing the DIC, rather than DIC per se. However, in a recent study of traumatic brain injury, patients with higher DIC scores were found to have increased likelihood of death or persistent vegetative state compared to patients with lower DIC scores, irrespective of their Glasgow Coma Scale scores.¹⁹ In any event, early and prompt treatment of the underlying disease and providing hemodynamic support are the mainstays of DIC management.