Disseminated intravascular coagulation

Disseminated intravascular coagulation (DIC) is a disorder characterized by systemic activation of the clotting cascade with microthrombi formation, platelet consumption, and subsequent exhaustion of all clotting factors. The most common causes of DIC include sepsis, trauma, and malignancy. Patients present with signs of bleeding (e.g., purpura, petechiae, ecchymoses) and/or multiorgan failure. Laboratory studies show thrombocytopenia, prolonged PT and aPTT, decreased fibrinogen levels, and increased D-dimer. Treatment involves identifying the underlying cause as well as supportive therapy with transfusions of platelet concentrates, FFP, and/or cryoprecipitate.

• Sepsis (more commonly with gram-negative organisms)
• Acute traumatic coagulopathy
• Obstetric complications
  • Amniotic fluid embolism
  • Pre-eclampsia
  • Abruptio placenta
  • Retained products of conception
• Acute pancreatitis
• Malignancies
  • Acute promyelocytic leukemia
  • Pancreatic, ovarian, or gastric adenocarcinomas
  • Non-small cell lung cancer
• Acute hemolytic transfusion reaction (AHTR)
• Extracorporeal procedures (e.g., dialysis)
• Toxins: snake bites, amphetamine overdose
• Traumatic brain injury
• Heatstroke
• Vascular malformations: aortic aneurysms

The mnemonic “STOP Making Trouble!”- helps recall the etiology of DIC. M - Malignancy, T - Transfusion, S - Sepsis/Snakebites, T - Trauma (acute traumatic coagulopathy), O - Obstetric complications, P - PancreatitisReferences:^[1][2]

Types of DIC	Bleeding (hyperfibrinolytic) type	Organ-failure (thrombotic) type	Massive bleeding (consumptive) type	Non-symptomatic DIC
Pathophysiology	Hyperfibrinolysis	↑ Cytokines → hypercoagulation with hypofibrinolysis → microthrombi → impaired perfusion and tissue necrosis	Hyperfibrinolysis and hypercoagulation → consumption of platelets and all coagulation factors	Mild fibrinolysis and mild hypercoagulation
Common causes	Leukemia (e.g., acute promyelocytic leukemia) Obstetric complications Aortic aneurysms Acute traumatic coagulopathy	Sepsis	Post-operative DIC Obstetric complications Pancreatic, ovarian, gastric, brain tumors	Any cause of DIC
Clinical features	Bleeding	Multi-organ failure Microangiopathic hemolytic anemia	Massive hemorrhage	Asymptomatic

DIC is an acquired coagulopathy that is frequently seen in hospitalized individuals!References:^[3][4]

• Manifestations of bleeding
  • Petechiae, purpura, ecchymoses
  • Oozing of blood from surgical wounds, intravenous lines
  • Hematuria
  • Hematemesis, hematochezia
  • Collection of blood in body cavities: features of hemoperitoneum, hemothorax
• Manifestations of thrombosis
  • Acute renal failure: oliguria
  • Hepatic dysfunction: jaundice
  • ARDS: dyspnea, rales
  • Pulmonary thromboembolism: dyspnea, chest pain, hemoptysis
  • Deep vein thrombosis: lower limb edema
  • Neurological dysfunction: altered mental status, stroke
  • Purpura fulminans: DIC with extensive skin necrosis
  • Waterhouse Friderichsen syndrome: adrenal infarcts → adrenal insufficiency

The clinical features of DIC may appear acutely (e.g., following trauma, sepsis), or may appear subacutely (e.g., DIC following malignancy)!
References:^[1][2]

Finding	Type of DIC
	Bleeding type	Organ failure type	Consumptive type	Non-symptomatic type
Thrombocytopenia → ↑ bleeding time	✓	✓	✓	✓
↑ Markers of fibrin breakdown (D-dimer, or FDP)	✓	✓	✓	✓
↑ PT and APTT	✓	✓	✓	×
↓ Fibrinogen levels	✓	×	✓	×
↓ Factor V and ↓ factor VIII	✓	✓	✓	×
↓ Antithrombin	×	✓	×	×
↓ Hematocrit	×	×	✓	×
Schistocytes	×	✓	✓	×

The diagnosis of DIC is not based on a single marker but on a combination of laboratory findings! Thrombocytopenia, elevated D-dimer, increased PT and aPTT, and low fibrinogen should immediately raise suspicion for DIC!

References:^[3][4][5]

• Severe hepatic dysfunction: clinical features, and/or laboratory findings of liver injury, normal factor VIII assay
• Thrombotic thrombocytopenic purpura/immune thrombocytopenic purpura: no consumption coagulopathy → normal PT, aPTT
• Heparin-induced thrombocytopenia: history of heparin use, heparin-PF4 (HIT) antibodies in serum

All coagulation factors would be decreased in patients with DIC!
References:^[1][2]

The differential diagnoses listed here are not exhaustive.

• Treatment of the underlying illness (e.g., antibiotics for infectious diseases, chemotherapy or surgery for malignant disease)
• Bleeding and consumptive types
  • Transfusion of blood products
    • Platelet concentrate if:
      • Platelet count < 10,000 in asymptomatic individuals
      • Platelet count < 50,000 in patients with active bleeding or if a surgical procedure is planned
    • Fresh frozen plasma if PT or APTT > 1.5 times the normal value
    • Cryoprecipitate if fibrinogen < 150 mg/dL
    • Packed RBCs if:
      • Massive hemorrhage without hemodynamic response to fluid therapy
      • Hb < 7 g/dL
    • If acute traumatic coagulopathy → transfuse packed RBC, FFP, and platelet concentrate in a 1:1:1 ratio
  • Synthetic protease inhibitor (e.g., Gabexate mesilate^®, nafamostat^®)
  • Antifibrinolytic therapy (e.g., tranexamic acid)
• Organ failure type: natural protease inhibitor (e.g., antithrombin, or rhTM administration)
• Non-symptomatic type: heparin

Treatment of the underlying disease forms the cornerstone of the management of DIC!

References:^[1][3][6]