Disseminated Intravascular Coagulation (DIC)

A 64-year-old female is admitted with fever, confusion, and hypotension due to severe bacterial sepsis. Over the next several hours, she develops diffuse petechiae, ecchymoses, and persistent oozing from venipuncture sites. Her blood pressure is 85/55 mm Hg and heart rate is 120 beats per minute. Laboratory studies show a platelet count of 38 × 10⁹/L, prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT), markedly elevated D-dimer, and a fibrinogen level of 90 mg/dL. Peripheral blood smear shows occasional schistocytes. Serial testing demonstrates progressive thrombocytopenia and worsening coagulation abnormalities. Diagnosis?

Diagnosis is Disseminated Intravascular Coagulation (DIC) Secondary to Sepsis.

1. Definition

Disseminated intravascular coagulation (DIC) is an acquired, life-threatening disorder characterized by systemic activation of coagulation, dysregulated fibrinolysis, and endothelial injury, resulting in widespread microvascular thrombosis.

Progressive consumption of platelets and coagulation factors may lead to clinically significant bleeding.

DIC develops secondary to an underlying disorder rather than occurring as a primary disease.

2. Common Causes

Important causes include:

1.      Sepsis and severe infection

2.      Malignancy, particularly acute promyelocytic leukemia and some advanced solid tumors

3.      Major trauma, burns, and extensive tissue injury

4.      Obstetric complications, including:

o    Placental abruption

o    Amniotic fluid embolism

o    Severe postpartum hemorrhage

o    Intrauterine fetal demise

o    Severe hypertensive disorders of pregnancy

5.      Severe pancreatitis

6.      Severe hemolytic transfusion reactions

7.      Shock

Sepsis is a major cause of acute DIC.

3. Pathophysiology

1.      The underlying disorder causes systemic activation of coagulation

2.      Excessive thrombin generation produces widespread fibrin formation

3.      Microvascular fibrin thrombi impair tissue perfusion and contribute to organ dysfunction

4.      Platelets and coagulation factors are progressively consumed

5.      Physiologic anticoagulant pathways become impaired

6.      Fibrinolysis becomes dysregulated and may be suppressed or excessive depending on the underlying cause

7.      Consumption of platelets and coagulation factors may ultimately produce bleeding

DIC therefore produces a combination of:

Microvascular thrombosis + consumption coagulopathy + bleeding

4. Clinical Features

4.1 Bleeding Manifestations

1.      Petechiae and purpura

2.      Ecchymoses

3.      Oozing from venipuncture or catheter sites

4.      Mucosal bleeding

5.      Gastrointestinal bleeding

6.      Severe cases may develop intracranial or other major hemorrhage

4.2 Thrombotic and Organ Manifestations

1.      Digital or acral ischemia

2.      Purpura fulminans

3.      Acute kidney injury

4.      Respiratory failure

5.      Hepatic dysfunction

6.      Neurologic dysfunction

7.      Shock and multiorgan failure

Depending on the underlying cause, either bleeding or thrombosis may predominate.

5. Diagnostic Evaluation

DIC is a clinical and laboratory diagnosis. No single laboratory test confirms or excludes DIC.

5.1 Laboratory Findings

Typical findings include:

1.      Thrombocytopenia

2.      Prolonged PT

3.      Prolonged aPTT may occur, particularly in advanced DIC, but aPTT may be normal early and is not required for diagnosis

4.      Markedly elevated D-dimer

5.      Reduced fibrinogen, particularly in advanced or bleeding DIC

6.      Schistocytes may be present, but they are usually less prominent than in thrombotic microangiopathies such as TTP

In sepsis-associated DIC, fibrinogen may initially be normal or elevated because it is an acute-phase reactant. Therefore, a normal fibrinogen level does not exclude early DIC.

Serial measurements are important because platelet counts and coagulation parameters can change rapidly.

5.2 2025 ISTH Overt DIC Score

The updated ISTH overt DIC score uses:

1.      Platelet count

o    50 to <100 × 10⁹/L: 1 point

o    <50 × 10⁹/L: 2 points

2.      D-dimer

o    3 to ≤7 times the upper limit of normal: 2 points

o    7 times the upper limit of normal: 3 points

3.      PT prolongation

o    ≥3 to <6 seconds: 1 point

o    ≥6 seconds: 2 points

4.      Fibrinogen

o    <100 mg/dL or <1.0 g/L: 1 point

A total score of ≥5 is compatible with overt DIC.

aPTT is not included in the ISTH overt DIC score.

The 2025 ISTH framework also recognizes an early phase of DIC, for which diagnostic assessment may need to be tailored to the underlying disease. In sepsis, sepsis-induced coagulopathy (SIC) criteria may help identify earlier coagulation dysfunction.

5.3 Important Differential Diagnosis

DIC should be distinguished from thrombotic microangiopathies, particularly TTP.

In TTP:

1.      Thrombocytopenia and microangiopathic hemolytic anemia are prominent

2.      Schistocytes are typically more prominent

3.      PT and aPTT are usually normal

In overt DIC, abnormalities of PT, D-dimer, fibrinogen, and platelet count reflect systemic activation and consumption of coagulation factors.

6. Management

The cornerstone of DIC treatment is rapid treatment of the underlying cause.

In this patient, management requires aggressive treatment of sepsis and septic shock, including appropriate antimicrobial therapy, source control, hemodynamic support, and organ support.

6.1 Platelet Transfusion

Platelet transfusion should not be given routinely solely to normalize the platelet count.

It should be considered particularly in patients with:

1.      Active clinically significant bleeding

2.      Need for an invasive procedure

3.      High risk of bleeding

In patients with DIC who are bleeding or at high risk of bleeding, platelet transfusion should be considered when the platelet count is <50 × 10⁹/L.

Routine prophylactic platelet transfusion is generally avoided in nonbleeding patients unless the risk of bleeding is considered high.

6.2 Fresh Frozen Plasma

Fresh frozen plasma (FFP) may be used when there is:

1.      Active clinically significant bleeding

2.      Prolonged PT and/or aPTT indicating coagulation factor depletion

3.      Need for an urgent invasive procedure in a patient with clinically important coagulation abnormalities

FFP should not be administered solely to correct abnormal coagulation tests in a nonbleeding patient.

6.3 Fibrinogen Replacement

In patients with significant bleeding and severe hypofibrinogenemia, fibrinogen replacement may be required.

If fibrinogen remains <1.0 g/L or <100 mg/dL despite appropriate FFP replacement, treatment may include:

1.      Cryoprecipitate, or

2.      Fibrinogen concentrate, where available

Higher fibrinogen targets may be used in specific major hemorrhage protocols, but a universal target of ≥1.5 g/L is not a DIC-specific requirement.

6.4 Anticoagulation

1.      Therapeutic anticoagulation is not routinely indicated in all patients with DIC

2.      Heparin may be considered when thrombosis predominates, including:

o    Venous thromboembolism

o    Arterial thrombosis

o    Purpura fulminans with acral ischemia or vascular skin infarction

3.      Critically ill patients with DIC who are not actively bleeding should generally receive standard venous thromboembolism prophylaxis with unfractionated or low-molecular-weight heparin unless contraindicated

Anticoagulation should be individualized according to the balance between thrombosis and bleeding.

6.5 Antifibrinolytic Therapy

Tranexamic acid and other antifibrinolytic agents are generally avoided in DIC because inhibition of fibrinolysis may worsen pathologic thrombosis.

They may occasionally be considered in selected patients with severe bleeding due to a predominant hyperfibrinolytic phenotype, under specialist hematology guidance.

7. Monitoring

Serial monitoring should include:

1.      Platelet count

2.      PT/INR

3.      aPTT

4.      Fibrinogen

5.      D-dimer

6.      Hemoglobin

7.      Clinical evidence of bleeding, thrombosis, and organ dysfunction

DIC is a dynamic process, so laboratory abnormalities may change rapidly as the underlying disease improves or deteriorates.

8. Complications

1.      Major hemorrhage

2.      Microvascular thrombosis

3.      Digital ischemia and tissue necrosis

4.      Acute kidney injury

5.      Respiratory failure

6.      Neurologic dysfunction

7.      Multiorgan failure

8.      Death

9. Key Clinical Insight

Thrombocytopenia + prolonged PT + markedly elevated D-dimer + low or falling fibrinogen in a patient with sepsis, malignancy, trauma, or an obstetric emergency strongly suggests DIC.

A normal fibrinogen level does not exclude early sepsis-associated DIC.

DIC causes both thrombosis and bleeding because systemic coagulation activation produces microvascular fibrin deposition while simultaneously consuming platelets and coagulation factors.

Treat the underlying cause first. Blood products are used primarily for clinically significant bleeding, high bleeding risk, or invasive procedures rather than simply to normalize abnormal laboratory values.

References

1.      Iba T, Levy JH, Maier CL, et al. Updated definition and scoring of disseminated intravascular coagulation in 2025: communication from the ISTH SSC Subcommittee on Disseminated Intravascular Coagulation. J Thromb Haemost. 2025;23(7):2356-2362. doi:10.1016/j.jtha.2025.03.038.

2.      Iba T, Helms J, Connors JM, Levy JH. The pathophysiology, diagnosis, and management of sepsis-associated disseminated intravascular coagulation. J Intensive Care. 2023;11(1):24. doi:10.1186/s40560-023-00672-5.

3.      Levi M, Toh CH, Thachil J, Watson HG. Guidelines for the diagnosis and management of disseminated intravascular coagulation. Br J Haematol. 2009;145(1):24-33. doi:10.1111/j.1365-2141.2009.07600.x.