Summary
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. Common causes of DIC include sepsis, trauma, and malignancy. Depending on the underlying pathophysiological processes and subtype, patients present with signs of bleeding (e.g., purpura, petechiae, ecchymoses) and/or multiorgan failure. Laboratory studies can be highly variable. However, typical findings in overt decompensated DIC include thrombocytopenia, prolonged PT and aPTT, decreased fibrinogen levels, and elevated D-dimer levels. Treatment involves identification of the underlying cause and supportive therapy with transfusions of blood products (pRBCs, platelet concentrates, FFP, and/or cryoprecipitate) and, in select cases, anticoagulants (e.g., heparin) or antifibrinolytic therapy (tranexamic acid). Close monitoring and specialist consultation (e.g., critical care and hematology) are typically required.
Overview
Definition [1]
-
Disseminated intravascular coagulation (DIC): 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
- Consumption coagulopathy: hyperfibrinolysis, causing overt coagulopathy and bleeding, PLUS hypercoagulability, which causes consumption of platelets and clotting factors, resulting in even more blood loss.
Classification [2][3]
The 2014 International Society of Thrombosis and Haemostasis (ISTH) harmonized guidelines distinguish between DIC types based on clinical phenotype, characteristic laboratory abnormalities, and treatment targets.
Overview of DIC types [1][3][4][5] | |||
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Types | Description | Suggestive laboratory findings | Potential therapeutic targets |
Nonsymptomatic type DIC |
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Bleeding type DIC |
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Massive bleeding type DIC |
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Organ failure type DIC |
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TAT: Thrombin antithrombin complex, PPIC: Plasmin α2-plasmin inhibitor complex, PAI-1: Plasminogen activator inhibitor-1, PT: Prothrombin time, FDPs: Fibrin degradation products, FFP: Fresh frozen plasma, pRBC: Packed red blood cells |
Etiology
- Infections
- Trauma
-
Obstetric complications
- Amniotic fluid embolism
- Preeclampsia
- HELLP syndrome
- Abruptio placenta
- Retained products of conception (e.g., intrauterine death, placenta)
- Organ failure
-
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
-
Dilution
- Massive bleeding
- Massive transfusion
- Massive volume repletion/volume overload
- Drug reactions
- Other
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.
References:[1][4][6]
Pathophysiology
The pathophysiology of DIC is variable and depends on the underlying processes (see “Hemostasis and bleeding disorders” and “Acquired thrombophilia”). [3][4]
- Nonsymptomatic type DIC: mild fibrinolysis and/or mild hypercoagulation
- Bleeding type DIC: hyperfibrinolysis (excessive plasmin activity → increased fibrin degradation → thrombi become unstable and dissolve shortly after forming)
- Massive bleeding type DIC: hypercoagulation and hyperfibrinolysis → consumption of platelets and all coagulation factors → bleeding diathesis
- Organ failure type DIC: ↑ cytokines → hypercoagulation with hypofibrinolysis → microthrombi → impaired perfusion and tissue necrosis
DIC is an acquired coagulopathy that is most frequently seen in hospitalized individuals.
Clinical features
Clinical features are variable and depend on the predominant underlying mechanism. [7]
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Bleeding
- 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)
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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
The clinical features of DIC may appear acutely (e.g., following trauma, sepsis) or subacutely (e.g., DIC following malignancy).
Diagnostics
General principles [5][8]
- Suspect DIC based on clinical features and typical underlying diseases; especially in patients with clinical deterioration.
- Laboratory studies vary depending on the subtype, underlying disorders, and stage of DIC.
- Challenges
- No single test can reliably rule out DIC.
- Nonsymptomatic DIC may only become apparent after specific laboratory screening.
- DIC may already be irreversibly decompensated by the time diagnosis is made using scoring systems.
- Many conditions can manifest with similar laboratory abnormalities (see “Differential diagnoses of DIC by laboratory findings”).
Laboratory studies [3][5][9]
Routine laboratory tests
-
Coagulation panel: Monitor frequently (e.g., every 6–8 hours or until stable or improving).
- ↑ aPTT, ↑ PT
- ↓ Fibrinogen: indicative of associated hyperfibrinolysis
- Markers of fibrin breakdown: ↑ D-dimer or other FDPs
- ↑ Bleeding time
- Coagulation factors: ↓ factor V and ↓ factor VIII
-
CBC and blood smear
- ↓ Platelet count: due to consumption and/or bleeding
- ↓ Hct: occurs with bleeding
- Schistocytes: indicative of microangiopathic hemolytic anemia [10]
- Other tests of organ function (e.g., renal function tests, liver chemistries): Order depending on clinical picture and underlying conditions.
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. [9]
Specialized tests [3]
The following tests should be considered on a case-by-case basis in consultation with a specialist (e.g., intensivist, hematologist).
- Monitoring treatment: Anti-Xa activity can be used to monitor the anticoagulant effect of heparin. [5]
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Classifying DIC subtype: may be helpful in cases in which the subtype is uncertain [3][6]
- Soluble fibrin (SF)
- Thrombin-antithrombin complex (TAT)
- Plasminogen activator inhibitor-1 (PAI-1)
- Plasmin-plasmin inhibitor complex (PPIC)
- Other procoagulants and anticoagulants that may be consumed
- Coagulation factors: ↓ factor V and ↓ factor VIII [10]
- Coagulation inhibitors: ↓ protein C and ↓ antithrombin
International Society of Thrombosis and Haemostasis (ISTH) DIC score [3][9][11]
- Multiple scoring systems exist, each with advantages and disadvantages that depend on the underlying cause of DIC. [6]
- The ISTH DIC score identifies patients with a high likelihood of overt DIC. It can only be used in patients with a known predisposing disease.
ISTH DIC score [12] | ||
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Criteria | Level | Points assigned |
Platelet count | > 100,000/mm3 | 0 |
50,000–100,000/mm3 | 1 | |
< 50,000/mm3 | 2 | |
Increase in fibrin markers (D-dimer, soluble fibrin, other FDPs) | None | 0 |
Moderate | 2 | |
Strong | 3 | |
Prothrombin time prolongation | < 3 seconds | 0 |
3–6 seconds | 1 | |
> 6 seconds | 2 | |
Fibrinogen | ≥ 100 mg/dL | 0 |
< 100 mg/dL | 1 | |
Interpretation
|
Differential diagnoses
Differential diagnoses by laboratory findings [13]
Differential diagnoses of DIC by laboratory findings [5][13][14] | ||||||
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Condition | Platelets | Bleeding time | PT | aPTT | Fibrinogen | D-dimer/FDPs |
DIC | ↓ | ↑ | ↑ | ↑ | Typically low but can be variable [15] | ↑ |
Thrombotic microangiopathy (TTP, HUS, HELLP syndrome) | ↓↓ | ↑ | Normal | Normal | Normal | Normal or ↑ |
HIT | ↓ | ↑ | Normal or ↑ | Normal or ↑ | Normal | ↑ |
ITP | ↓ | ↑ | Normal | Normal | Normal | Normal or ↑ |
Liver disease | Normal or ↓ | Normal or ↑ | ↑ | ↑ | Normal or ↓ | Normal or ↑ |
Vitamin K deficiency or warfarin use | Normal | Normal | ↑ | Normal or ↑ | Normal | Normal |
Differential diagnoses by underlying process
-
Decreased production of platelets and clotting factors
- Severe hepatic dysfunction
- Vitamin K deficiency
- Bone marrow suppression
- Hemophilia
- Increased destruction of platelets and clotting factors [16]
-
Increased consumption of platelets and clotting factors
- DVT/pulmonary embolism
- Surgery
- Infections
-
Increased loss of platelets and clotting factors
- Massive blood transfusion causing dilutional coagulopathy
- Capillary leak syndrome
The differential diagnoses listed here are not exhaustive.
Treatment
General principles [3][9]
- First-line: treatment of the underlying disease (see “Etiology”)
- Additional treatment depends on the subtype and is complicated (see “Overview of DIC types”). Involve specialists early.
- Blood products as needed
- Anticoagulation: if hypercoagulability is the leading problem (e.g., in organ failure type DIC)
- Consider advanced treatment options (e.g., antithrombin) in consultation with a specialist.
- Supportive therapy
- Avoid invasive procedures if possible
- Vitamin K supplementation if deficiency is suspected [1]
- Initiate clinical and serial laboratory monitoring to assess response to treatment.
Treatment recommendations by type of DIC [1][3] | |||
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Type | Generally recommended | Generally discouraged | |
Nonsymptomatic type DIC | |||
Organ failure type DIC |
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Bleeding type DIC |
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Massive bleeding type DIC |
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Treatment of the underlying disease is the cornerstone of management.
Blood products [2][3][5][9][9]
The decision to transfuse blood products should primarily be based on the presence or risk of bleeding. Laboratory parameters can be used as a treatment goal but should not be considered the sole rationale for transfusion. Involve specialists early.
- pRBCs: indicated for patients with active bleeding or Hb ≤ 7 mg/dL (see “Packed red blood cells” for specific transfusion thresholds and goals)
-
Platelets: [17]
-
Indications
- Active bleeding or high risk of bleeding (e.g, planned invasive procedure): platelet count < 50,000/mm3
- No bleeding: platelet count < 10,000–20,000/mm3
- Goals
- Active bleeding or at high risk of bleeding: platelet count > 20–50,000/mm3.
- If receiving massive transfusion: platelet count > 50,000/mm3.
-
Indications
-
Fresh frozen plasma (FFP) [10][18]
-
Indications
- PT or aPTT > 1.5 times the normal value if patient is bleeding or will undergo an invasive procedure
- Consider if bleeding and fibrinogen < 150 mg/dL
- As part of a massive transfusion protocol
- Goals
- PT < 3 seconds prolonged
- Fibrinogen > 100–150 mg/dL
-
Indications
-
Cryoprecipitate [19]
- Indication: bleeding and fibrinogen levels < 150 mg/dL despite FFP or when FFP transfusion is not possible [2]
- Goal: fibrinogen level of > 100–150 mg/dL
-
Prothrombin complex concentrate (PCC) [2][10][18]
- Individual decision in patients with active bleeding when FFP transfusion is not possible (e.g., due to volume overload)
- Cautions [8]
- May only partially correct coagulopathy
- Can tip the procoagulant-anticoagulant balance towards thrombosis.
- Monitoring of antithrombin activity and protein C levels is recommended.
Antifibrinolytic therapy [2][3]
-
Tranexamic acid: : not routinely recommended [9]
- Indication: Consider in patients with severe bleeding and hyperfibrinolysis (especially after trauma). [2]
- Contraindications [3]
- Not recommended in patients with nonsymptomatic type DIC or organ failure type DIC
- Avoid in patients with APL undergoing ATRA treatment.
- If indicated, administer early.
Aminocaproic acid is generally contraindicated in DIC.
Anticoagulation [2][3][9][11][20]
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Prophylactic heparin: indicated as DVT prophylaxis in critically ill patients in the absence of bleeding [21]
- LMWH (e.g., enoxaparin )
- UFH
-
Therapeutic heparin: indicated for clinically overt thromboembolic events
- LMWH (e.g., enoxaparin) : sometimes preferred over UFH [2]
- UFH : Consider in patients with high bleeding risk due to its short half-life and reversibility.
-
Other coagulation inhibitors: Consider in individual cases in consultation with a specialist. [2][3]
- Antithrombin (AT): Not routinely recommended due to a lack of supporting evidence.
- Plasma-derived activated protein C (APC)
- Recombinant human thrombomodulin (rhTM) [2][8]
- Synthetic inhibitors of serine proteases [20]
Patients receiving anticoagulants require careful monitoring of bleeding events and dosage adjustment for BMI and kidney function.
Warfarin is ineffective and possibly harmful in DIC, as it inhibits production of protein C and protein S, which can worsen coagulopathy. [22][23]
Fibrinolytic therapy (e.g., tPA) should be avoided in all types of DIC. [1][3]
Acute management checklist
All patients [2][3]
- Consider DIC in patients with an associated underlying condition and clinical deterioration.
- Order CBC and serial coagulation tests (including PT, aPTT, fibrinogen, D-dimer and other FDPs).
- Consider calculating the ISTH DIC score to support the diagnosis.
- Rule out differential diagnoses.
- Consult hematology and intensive care as needed.
- Consider ordering specialized tests according to DIC type.
- Identify and treat the underlying cause.
- Monitor coagulation parameters frequently.
- Avoid invasive procedures if possible.
- Supplement vitamin K if there is a suspected deficiency.
Bleeding type DIC or massive bleeding type DIC
- Transfusion of blood products as needed (e.g., pRBCs, FFP, platelets, cryoprecipitate)
- Consider massive transfusion.
- Consider tranexamic acid.
Nonsymptomatic type DIC and organ failure type DIC
- Transfusion of blood products as needed (e.g., FFP, platelets)
- VTE prophylaxis unless contraindicated
- Provide therapeutic anticoagulation for thromboembolic events.