Overview

• Definition: a syndrome characterized by thrombosis, hemorrhage, and organ dysfunction caused by systemic activation of the clotting cascade, which leads to platelet consumption and exhaustion of clotting factors

• Latent DIC: no overt symptoms (little to no bleeding, increased risk of thrombotic events, laboratory abnormalities)

• Overt DIC: clear signs and symptoms (e.g., bleeding, thrombosis) that depend on the balance of the deranged processes

• Acute DIC

  • Excess thrombin generation leading to the formation of microthrombi and, eventually, microangiopathic hemolytic anemia (MAHA)

  • Rapid consumption of coagulation factors and platelets

  • Common causes include septic shock, acute pancreatitis, burns, snake bites, transplant rejection

  • Often starts as a hypercoagulable state (organ failure type DIC)

• Chronic DIC

  • Small thrombin generation over prolonged periods of time

  • Slower consumption of coagulation factors and platelets

  • Common causes include malignancies, aneurysms, retroperitoneal hematomas, intrauterine fetal death

  • Often manifests as nonsymptomatic type DIC

  • Thrombosis is more common in symptomatic chronic DIC.

Definition: Hyperfibrinolysis, causing overt coagulopathy and bleeding, PLUS hypercoagulability, which causes consumption of platelets and clotting factors, resulting in even more blood loss

• Infections

  • Viral infection

  • Rickettsial infections

  • Malaria

  • Sepsis (more commonly with gram-negative organisms)

• Trauma

  • Acute traumatic coagulopathy

  • Traumatic brain injury

  • Crush injuries

  • Burns

  • Fat embolism

  • Surgery

  • Rhabdomyolysis

• Obstetric complications

  • Amniotic fluid embolism

  • Preeclampsia

  • HELLP syndrome

  • Abruptio placenta

  • Retained products of conception (e.g., intrauterine death, placenta)

• Organ failure

  • Acute pancreatitis

  • Fulminant hepatitis

  • Liver cirrhosis

  • Acute hepatic necrosis

  • Acute respiratory distress syndrome (ARDS)

• Malignancies

  • Hematological, e.g., acute promyelocytic leukemia (APL), acute myelocytic leukemia

  • Solid tumors, e.g.:

    • Pancreatic

    • Ovarian

    • Gastric

    • Non-small cell lung cancer

• Toxins

  • Snake bites

  • Amphetamine overdose

• Immunologic

  • Acute hemolytic transfusion reaction (AHTR)

  • Transplant reaction (e.g., graft-versus-host disease)

  • Extracorporeal procedures (e.g., dialysis)

• Vascular malformations

  • Aortic aneurysms

  • Vasculitis

• Dilution

  • Massive bleeding

  • Massive transfusion

  • Massive volume repletion/volume overload

• Drug reactions

• Other

  • Nephrotic syndrome

  • New thrombus formation

  • Hemolysis

  • Acidosis

The mnemonic “STOP Making Trouble!” helps to recall the etiology of DIC: S – Sepsis/Snakebites, T – Trauma (acute traumatic coagulopathy), O – Obstetric complications, P – Pancreatitis, M – Malignancy, T – Transfusion.

• There are 4 concurrent events involved:

  • Initiation and propagation of coagulation (loss of localized activation of coagulation)

  • A systemic inflammatory activation → impairment of physiological anticoagulant pathways (e.g., depression of antithrombin and impairment of protein C system) and endogenous fibrinolysis (due to a consistent rise in PAI-1)

  • Activation of tissue factor pathway → factor Xa and IXa generation → increased thrombin production

  • Impaired fibrin removal due to depression of the fibrinolytic system → microthrombi production and possible obstruction of the microvasculature

• Underlying disease → ↑ release of procoagulants (e.g., tissue factor) → ↑ activation of the extrinsic coagulation cascade and platelets → ↑ activation of thrombin → ↑ generation of fibrin → ↑ generation of microthrombi rich in fibrin and platelets → ↑ activation of fibrinolysis and other anticoagulant pathways that break down thrombi → ↑ fibrin degradation and consumption of natural anticoagulants → further clinical course and resulting type of DIC is determined by the dominance of hyperfibrinolysis and/or hypercoagulopathy

  • Nonsymptomatic type DIC: low-grade fibrinolysis and/or hypercoagulation

  • Bleeding type DIC: hyperfibrinolysis due to excessive plasmin activity → increased fibrin degradation → thrombi becoming unstable and dissolving shortly after formation

  • Massive bleeding type DIC: hypercoagulation and hyperfibrinolysis → consumption of platelets and all coagulation factors → bleeding diathesis

  • Organ failure type DIC: ↑ cytokines → ↑ plasminogen activator inhibitor-I (PAI-I) and ↑ neutrophil extracellular traps (NETs) → hypercoagulation with suppressed fibrinolysis → platelet and fibrin-rich microthrombi → impaired perfusion and tissue necrosis

• Hematemesis, hematochezia

• Hematuria

• Oozing of blood from surgical wounds or intravenous lines

• Petechiae, purpura, ecchymoses

• Massive hemorrhage: collection of blood in body cavities (hemoperitoneum, hemothorax)

• Organ failure: primarily due to hypercoagulation

  • Microangiopathic hemolytic anemia

  • 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

  • Signs of shock