Disseminated intravascular coagulation (Consumptive coagulopathy)

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, which causes hemorrhagic manifestations. The most common causes are sepsis, trauma, and malignancy. Patients present with bleeding manifestations (e.g., purpura), and/or signs of multiorgan failure. Laboratory studies show thrombocytopenia, prolonged PT and aPTT, decreased fibrinogen levels, and increased D-dimer. Treatment of DIC involves treatment of the underlying cause, and supportive therapy with transfusions of platelet concentrates, FFP, and/or cryoprecipitate.

• Sepsis (more commonly with gram-negative organisms)
• Malignancies
  • Acute promyelocytic leukemia
  • Pancreatic, ovarian, or gastric adenocarcinomas
  • Pulmonary cancer
• Surgery on thrombokinase-rich organs (e.g., lung, prostate, pancreas)
• Acute traumatic coagulopathy
• Acute hemolytic transfusion reaction (AHTR)
• Traumatic brain injury
• Fat embolism
• Crush injuries
• Obstetric complications
  • Amniotic fluid embolism
  • Pre-eclampsia → HELLP syndrome
  • Abruptio placenta
  • Retained products of conception (e.g., dead fetus, placenta)
• Acute pancreatitis
• Heat stroke
• Intravascular hemolysis (e.g., acute transfusion reaction)
• Extracorporeal procedures (e.g.,, dialysis)
• Toxins: snake bites, amphetamine overdose
• Vascular malformations: aortic aneurysms; large hemangiomas (Kasabach-Merrit syndrome)
• Nephrotic syndrome

Thrombokinase-rich organs: Pulmonary, Prostate, Pancreas, Placenta

References:^[1][2]

Types of DIC	Bleeding (hyperfibrinolytic) type	Organ-failure (thrombotic) type	Massive bleeding (consumptive) type	Non-symptomatic DIC
Pathophysiology	Hyperfibrinolysis	↑ Cytokines → ↑ Plasminogen activator inhibitor-I (PAI-I) and ↑ neutrophil extracellular traps (NETs) → hypercoagulation with hypofibrinolysis → platelet and fibrin-rich 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 manifestation	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]

• Bleeding manifestations
  • Petechiae, purpura, ecchymoses
  • Oozing of blood from surgical wounds, intravenous lines
  • Hematuria
  • Hematemesis, hematochezia
  • Collection of blood in body cavities: features of hemoperitoneum, hemothorax
• Thrombotic manifestations
  • 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]

ISTH criteria	Score
	0	1	2	3
Platelet count	> 100,000 /mm3	50,000–100,000 /mm3	< 50,000 /mm3	×
Increase in fibrin markers (D-dimer, or FDP)	None	×	Moderate	Strong
Prothrombin time	< 3 seconds	3–6 seconds	> 6 seconds	×
Fibrinogen	> 1 g/dL	< 1 g/dL	×	×
Presence of an underlying disorder and ISTH score ≥ 5: DIC likely → monitor daily Presence of an underlying disorder and ISTH score < 5: probable DIC → repeat monitoring in 1–2 days

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!

Finding	Type of DIC				Differential diagnosis
	Bleeding type	Organ failure type	Consumptive type	Non-symptomatic type
Thrombocytopenia → ↑ bleeding time	✓	✓	✓	✓	Bone marrow suppression Thrombotic thrombocytopenic purpura
↑ Markers of fibrin breakdown (D-dimer, or FDP)	✓	✓	✓	✓	DVT, pulmonary embolism
↑ PT and APTT	✓	✓	✓	×	Hepatic dysfunction Vitamin K deficiency Massive blood transfusion → dilutional coagulopathy
Biphasic APTT waveform	×	✓	×	×	Infection
↓ Fibrinogen levels	✓	×	✓	×	Hepatic dysfunction
↓ Antithrombin	×	✓	×	×	Hepatic dysfunction Capillary leak syndrome
↑ Soluble fibrin, ↑ Thrombin-antithrombin complex	✓	✓	✓	✓	DVT, pulmonary embolism Surgery
↑ Plasmin α2-plasmin inhibitor complex (PPIC)	✓	×	✓	×	DVT, pulmonary embolism Surgery
↓ Hematocrit	×	×	✓	×	Acute hemolytic anemia
Schistocytes	×	✓	✓	×	Thrombotic thrombocytopenic purpura

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., tranexemic 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]