Disseminated Intravascular Coagulation - DIC

Disseminated intravascular coagulation (DIC) is defined by the International Society of Thrombosis and Haemostasis (ISTH) as an acquired syndrome characterized by the intravascular activation of coagulation without a specific localization and arising from different causes. It can originate from and cause damage to the microvasculature; if the damage is sufficiently severe, organ dysfunction can result.  The activation of coagulation pathways results in extensive formation of intravascular fibrin, especially in small and midsize vessels. In addition to this fibrin formation, DIC is characterized by excessive thrombin generation with widespread microvascular thrombosis, which can lead to multiorgan ischemia and consumption of platelets and coagulation factors. Additionally, cross-talk via cytokines promotes activation of inflammatory and complement activation pathways.  DIC is associated with numerous illnesses and conditions such as sepsis and trauma. Diagnosis of DIC involves a combination of laboratory tests and clinical evaluation. Laboratory findings suggestive of DIC include a low platelet count, elevated D-dimer concentration, decreased fibrinogen concentration, and prolongation of clotting times such as prothrombin time (PT). 

Quick Answers for Clinicians

What is the association between COVID-19 and disseminated intravascular coagulation?

Elevated D-dimer concentrations have been described in patients with COVID-19 infection who require intensive care unit (ICU) admission, but the concentrations are not always at the very high level expected with DIC. DIC may evolve over time in critically ill patients as the illness worsens.    In one single-center study from Wuhan, China, approximately 70% of patients who died as a result of COVID-19 met current diagnostic criteria for DIC as set forth by the International Society of Thrombosis and Haemostasis (ISTH). 

Which conditions are associated with disseminated intravascular coagulation?

Disseminated intravascular coagulation (DIC) does not occur in isolation, but rather arises in the presence of many different underlying severe clinical disorders. These include sepsis, malignancy (eg, acute leukemia), trauma, liver disease, vascular anomalies, toxic reactions (eg, as a result of a venomous snake bite), immunologic reactions (eg, transplant rejection), and obstetric complications.  Sepsis-induced coagulopathy (SIC) may precede overt DIC in patients with sepsis; there is a separate scoring system for SIC. 

Indications for Testing

Laboratory testing for DIC is appropriate in patients with bleeding or microthrombi in combination with an associated DIC risk factor, including sepsis, obstetric disease, malignancy, and liver disease.

Criteria for Diagnosis

Overt Disseminated Intravascular Coagulation

The ISTH has developed a scoring system to aid in the diagnosis of overt DIC using laboratory testing results. This scoring system is appropriate for patients with an underlying disorder known to be associated with DIC. A score of ≥5 is compatible with overt DIC.  Repeat testing is important to monitor the dynamic progression of DIC. 

ISTH Overt DIC Scoring System
Score 0 1 2 3
Platelet count (k/µL) >100 50-100 <50
D-dimer (µg/mL FEU) No increase Moderate increase Strong increase
Fibrinogen (g/L) >1 <1
PT (increase in seconds) <3 3-6 >6
Source: Toh, ISTH, 2007 

Nonovert Disseminated Intravascular Coagulation

There are also nonovert (chronic) forms of DIC that have more subtle coagulopathy. The nonovert DIC scoring system described below is appropriate for patients with an underlying disorder known to be associated with DIC; use repeat testing to determine a patient’s evolving score.

ISTH Nonovert DIC Scoring System
Score -1 0 1
Platelet count (k/µL) >100 <100
Trend in platelet count Increasing over time Stable Decreasing over time
D-dimer, (µg/mL FEU) Normal Elevated
Trend in D-dimer Decreasing over time Stable Increasing over time
PT (increase in seconds) <3 >3
Trend in PT Decreasing over time Stable Increasing over time
Source: Toh, ISTH, 2007 

Laboratory Testing

Platelets

Low platelet count is a key laboratory finding in DIC; however, it is not a specific feature of DIC and may be seen in other conditions. Moderate to low thrombocytopenia (platelet count of 50-100 k/µL) is observed in the majority of patients with DIC, although severe thrombocytopenia (platelet count of <50 k/µL) may also occur.  In the early stages of DIC, or when there is significant acute phasing of platelets due to illness, the platelet count may be normal.

D-Dimer

D-dimer is a product of the plasmin degradation of fibrin cross-linked by factor XIIIa (FXIIIa); D-dimer is only produced if thrombin, FXIIIa, and plasmin are active.  D-dimer measurement is the best single laboratory test for DIC diagnosis but is not used in isolation. D-dimer concentrations are increased in patients with overt and nonovert (chronic) DIC; however, D-dimer elevation may also occur with trauma, venous thromboembolism, or other conditions.   In these conditions, the elevations are usually milder than those seen in DIC. A normal D-dimer level has excellent negative predictive value and generally excludes a diagnosis of DIC. Repeated, sequential measurement of D-dimer concentrations, to capture evolving illness, may provide additional diagnostic information in patients when there is a high clinical suspicion for DIC but the initial D-dimer value is normal or not elevated to the DIC range.

Fibrinogen

Fibrinogen is an acute phase reactant and, despite its ongoing consumption, can remain at normal concentrations for a long time after DIC onset.  Repeated, sequential measurement of fibrinogen concentrations may provide additional diagnostic information.  Fibrinogen remains a component of the ISTH scoring system and can contribute to the overall clinicopathologic picture. 

Clotting Times

Because of the consumption of coagulation factors, PT and activated partial thromboplastin time (aPTT) are prolonged in most cases of DIC , although normal or shortened PT and aPTT may also be observed in patients with DIC because of circulating activated clotting factors early in the course of DIC or in chronic DIC. The ISTH scoring system includes evaluation of PT prolongation.   Clotting times may also be prolonged in the presence of anticoagulant drugs. Refer to the Anticoagulants and Possible Coagulation Test Interferences table for possible interferences with coagulation assays based on the specific drug administered.

ARUP Laboratory Tests

Medical Experts

Contributor

Moser

Karen A. Moser, MD
Associate Professor of Clinical Pathology, University of Utah
Medical Director, Hemostasis/Thrombosis, ARUP Laboratories
Contributor
Contributor

Smock

Kristi J. Smock, MD
Professor of Clinical Pathology, University of Utah
Medical Director, Hemostasis/Thrombosis, ARUP Laboratories

References