Disseminated intravascular coagulation

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Disseminated intravascular coagulation is a secondary syndrome in which widespread thrombin generation and disordered fibrinolysis produce both clotting and bleeding. It ranges from compensated laboratory consumption in malignancy or vascular disease to explosive haemorrhage, microvascular thrombosis and organ failure during sepsis, trauma or an obstetric catastrophe. Diagnosis therefore requires a compatible cause, clinical assessment and repeated tests. A score can support the diagnosis of overt DIC, but it never replaces recognition of the precipitating emergency.

The typical screen shows thrombocytopenia, a prolonged PT, increased D-dimer or other fibrin-degradation marker and reduced fibrinogen. None is individually diagnostic. Fibrinogen is an acute-phase reactant and can remain normal or high early in sepsis; APTT can be normal, and fragmented cells are neither required nor usually as prominent as in TTP. Trends reveal consumption: falling platelets and fibrinogen, increasing PT and escalating fibrin markers. Repeat after a clinically meaningful interval determined by severity, sometimes every few hours during active haemorrhage.

Treating the cause is the intervention most likely to stop DIC. Cultures must not delay broad-spectrum antimicrobials and source control in sepsis. Obstetric teams must achieve uterine or placental source control. Trauma requires damage-control resuscitation and surgery or interventional radiology. Suspected acute promyelocytic leukaemia requires immediate haematology contact and ATRA while confirmation proceeds. Component therapy supports haemostasis but cannot overcome an uncontrolled driver.

Choose supportive therapy by phenotype. Clinically important bleeding or an urgent invasive procedure justifies targeted replacement; abnormal tests alone usually do not. Conversely, prolonged clotting tests do not protect against thrombosis. When clotting predominates, such as purpura fulminans, acral ischaemia or established VTE, specialist-selected heparin may be appropriate. Reassess after every intervention for bleeding, fluid burden, thrombosis and laboratory response rather than pursuing a normal coagulation screen.

Key points

DIC is an acquired systemic activation of coagulation caused by another disorder; a laboratory pattern without an appropriate clinical trigger is not sufficient.
First-line assessment is serial FBC and film, PT, APTT, fibrinogen and a fibrin-related marker such as D-dimer, interpreted with bleeding, thrombosis and organ function.
A falling platelet count and fibrinogen, prolonging PT and rising D-dimer are more informative than one isolated result; early sepsis-related DIC may have a normal fibrinogen.
Management priority is rapid control of the driver: antimicrobials and source control for sepsis, delivery or obstetric haemorrhage control, trauma haemostasis, or immediate ATRA for suspected APL.
Do not transfuse solely to normalise numbers in a non-bleeding patient; give platelets, plasma and fibrinogen replacement for significant bleeding or a high-risk procedure using clinical and laboratory guidance.
For active bleeding with platelets below 50 × 10⁹/L, platelet transfusion is generally considered; plasma provides multiple factors when PT or APTT is prolonged and bleeding is present.
If fibrinogen remains critically low during bleeding, use cryoprecipitate or fibrinogen concentrate according to the major-haemorrhage protocol and reassess promptly.
Therapeutic heparin is not routine for bleeding DIC, but may be used with specialist oversight when thrombosis predominates; prophylactic VTE prevention remains important when bleeding risk permits.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Sepsis and severe infection

Bacterial sepsis is common, but viral, fungal and parasitic infection can also trigger systemic tissue-factor expression, endothelial injury and loss of physiological anticoagulant control.

Obstetric and tissue injury

Placental abruption, amniotic-fluid embolism, retained dead fetus, major trauma, burns, pancreatitis and extensive surgery release procoagulant material and amplify inflammation.

Malignancy and vascular lesions

Acute promyelocytic leukaemia may cause severe hyperfibrinolytic bleeding, while mucinous adenocarcinoma, large vascular malformations and aortic pathology can produce chronic or thrombotic DIC.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Uncontrolled thrombin generation
Tissue factor and inflammatory signalling generate thrombin throughout the circulation, depositing fibrin in small vessels and consuming platelets and coagulation factors.
2
Failed natural anticoagulation
Antithrombin, protein C and endothelial thrombomodulin activity fall, so normal restraints on thrombin are overwhelmed and microvascular clotting continues.
3
Variable fibrinolysis
Fibrin breakdown raises D-dimer; sepsis often suppresses effective fibrinolysis, whereas obstetric emergencies and acute promyelocytic leukaemia may produce dominant hyperfibrinolysis and catastrophic bleeding.
4
Microvascular organ injury
Fibrin-rich microthrombi, endothelial leak, shock and haemorrhage combine to impair kidney, lung, liver, brain, skin and limb perfusion.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Diffuse bleeding

Persistent oozing from lines, wounds or mucosa, ecchymoses and disproportionate postoperative or obstetric blood loss suggest consumption.

Thrombotic skin pattern

Mottling, retiform purpura, painful blue digits or symmetrical peripheral ischaemia reflects microvascular or macrovascular thrombosis.

Organ dysfunction

Confusion, oliguria, hypoxaemia, jaundice and shock may result from the precipitant, DIC or both and demand parallel treatment.

Laboratory evolution

A downward platelet and fibrinogen trajectory with longer PT and increasing D-dimer supports active consumption more strongly than a single panel.

APL phenotypeRed flag

Promyelocytes, bruising, mucosal bleeding and profound fibrinogen depletion require immediate ATRA discussion before molecular confirmation.

Red flags requiring action

Hypotension, altered consciousness, oliguria, hypoxaemia or rising lactate indicates organ hypoperfusion and requires immediate source control and critical-care escalation.
Diffuse oozing from venepuncture sites, gastrointestinal bleeding, intracranial symptoms or rapidly expanding postoperative bleeding requires the major-haemorrhage pathway alongside DIC treatment.
Painful cyanotic digits, retiform purpura, symmetrical peripheral gangrene or new venous or arterial occlusion indicates clinically important thrombosis despite prolonged clotting tests.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
First-line: FBC and peripheral filmFirst stepFirst line
Why
Measure platelet consumption, anaemia and alternative cell abnormalities.
Interpretation and limitations
Track change from baseline. Schistocytes may occur but heavy fragmentation with relatively normal coagulation suggests thrombotic microangiopathy; abnormal promyelocytes demand an APL emergency pathway.
02
First-line: PT, APTT, fibrinogen and D-dimerFirst line
Why
Identify consumption and fibrin formation or breakdown and establish a trend.
Interpretation and limitations
Prolonged PT, low fibrinogen and markedly raised D-dimer support overt DIC, but normal APTT or fibrinogen does not exclude early disease. Repeat according to clinical tempo.
03
Organ and cause assessment
Why
Find the driver and quantify harm that changes resuscitation.
Interpretation and limitations
Use cultures, lactate, renal and liver profile, calcium, blood gas, urinalysis, imaging and pregnancy or malignancy-specific tests selected by presentation; do not delay source control.
04
Validated overt-DIC score
Why
Combine platelet count, PT prolongation, fibrin marker and fibrinogen in a compatible setting.
Interpretation and limitations
A threshold score supports overt DIC and should be recalculated serially; poor timing, missing data or an absent trigger limits its value.
05
Blood bank and procedural preparation
Why
Make component support available safely during bleeding or urgent intervention.
Interpretation and limitations
Send group and screen or crossmatch early, communicate ongoing losses and use viscoelastic testing only where validated within a major-haemorrhage protocol.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Massive haemorrhage and dilution

Large-volume blood loss, crystalloid and component replacement can prolong clotting times and lower platelets and fibrinogen without systemic intravascular coagulation.

Severe liver dysfunction

Reduced synthesis and clearance can mimic DIC; clinical context, trend, factor pattern, fibrin markers and evidence of active consumption help interpretation.

Thrombotic microangiopathy

TTP and complement-mediated HUS cause thrombocytopenia, fragmentation and organ injury, but coagulation tests are often near normal and disease-specific urgent treatment differs.

Primary hyperfibrinolysis

Advanced liver disease, prostate procedures or selected malignancy can cause marked fibrinolysis without the complete thrombin-consumption phenotype of DIC.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01Suspected DICConfirm syndrome while treating causeFirst stepA recognised trigger coexists with bleeding, thrombosis, organ dysfunction or evolving coagulation abnormalities.

1Perform ABCDE assessment, obtain blood before treatment when this causes no delay, and contact the relevant source-control team.
2Send serial platelet count, film, PT, APTT, fibrinogen and D-dimer and document sites of bleeding and thrombosis.
3Use a validated overt-DIC score as supporting evidence, repeat it with clinical change and actively test important mimics.

02Bleeding phenotypeReplace what is being consumedThere is significant active bleeding or an urgent invasive procedure with haemostatic deficiency.

1DefinitiveActivate the local major-haemorrhage protocol when loss is severe and use balanced resuscitation while achieving definitive haemostasis.
2Use platelets, plasma and cryoprecipitate or fibrinogen concentrate according to bleeding, count, clotting times, fibrinogen and local protocol.
3Recheck clinical haemostasis, temperature, ionised calcium, FBC and coagulation promptly and avoid unnecessary fluid-heavy transfusion.

03Thrombotic phenotypeBalance anticoagulation against bleedingDocumented VTE, arterial thrombosis, purpura fulminans or acral ischaemia dominates the presentation.

1Image a suspected macrovascular event when this will not delay limb- or life-saving action and involve haematology and the relevant vascular specialty.
2Use specialist-selected UFH or LMWH when therapeutic anticoagulation benefit exceeds haemorrhage risk, favouring controllability when physiology is unstable.
3Provide ordinary pharmacological VTE prophylaxis to critically ill non-bleeding patients when platelet count and procedural risk permit.

04Failure to improveRevisit driver and mimicBleeding, thrombosis or consumption persists despite initial cause-directed and supportive treatment.

1Search for incomplete source control, occult haemorrhage, ongoing obstetric tissue, APL, malignancy or an unrecognised vascular lesion.
2Review transfusion dilution, liver failure, TTP, HIT and medicine effects with repeat film and appropriately timed specialist tests.
3EscalationEscalate to critical care and haematology and individualise further components or anticoagulation from phenotype and response.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

Replaces multiple consumed coagulation factors when bleeding or a high-risk procedure makes correction clinically necessary.

Fresh frozen plasma

For clinically significant bleeding with abnormal coagulation, give a typical initial dose of 15 mL/kg intravenously under the local transfusion protocol, then reassess bleeding, PT, APTT and fluid status before further doses.

Do not use simply to correct laboratory values in a non-bleeding patient. Consider circulatory overload, allergic reaction and the time and volume needed for effect; arrange urgent haemostasis rather than repeated empirical plasma.

Provides concentrated fibrinogen in bleeding DIC when plasma has not produced an adequate level or rapid replacement is required.

Cryoprecipitate

Give two pooled adult doses intravenously for clinically significant bleeding with low fibrinogen under the local major-haemorrhage protocol, then repeat fibrinogen and assess haemostasis before redosing.

Thresholds vary with major-haemorrhage and obstetric protocols; avoid number-driven use without bleeding, and record component exposure, response and thrombotic risk.

Provides rapidly adjustable anticoagulation for selected thrombotic DIC, including threatened acral ischaemia or established VTE.

Unfractionated heparin

When thrombosis clearly predominates, use the hospital weight-based intravenous UFH treatment protocol with an initial bolus omitted if bleeding risk is high, titrating the infusion by the locally validated anti-Xa or APTT method.

This is a specialist decision, not routine DIC treatment. Review active bleeding, platelets, recent surgery, neuraxial procedures and HIT history; UFH effect and baseline APTT can be difficult to interpret in DIC.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Major haemorrhage

Consumption, hyperfibrinolysis, endothelial injury and procedural trauma can produce intracranial, gastrointestinal, pulmonary, obstetric or postoperative bleeding.

Macrovascular thrombosis

Venous thromboembolism, arterial occlusion, catheter thrombosis and acral ischaemia may occur even when PT and APTT are prolonged.

Multiorgan dysfunction

Microthrombi and shock contribute to acute kidney injury, respiratory failure, hepatic dysfunction, encephalopathy and adrenal or pituitary injury.

Purpura fulminans

Rapid dermal-vessel thrombosis with haemorrhagic necrosis can follow severe sepsis and profound protein-C pathway failure, threatening limbs and life.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Record physiological observations, urine output, skin and limb perfusion, neurological state and every site of bleeding at a frequency matched to instability.
Repeat FBC, PT, APTT, fibrinogen and D-dimer after major intervention and serially while consumption is evolving; record trends graphically where possible.
During major transfusion, monitor temperature, ionised calcium, acid-base state, potassium, haemoglobin and fluid balance as well as coagulation.
Review source control repeatedly: persistent consumption may be the earliest sign that infection, retained tissue, bleeding or malignant disease remains active.
After recovery, stop unnecessary components or anticoagulation, document the trigger and thrombosis, and arrange condition-specific follow-up rather than labelling DIC as a primary disease.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Fibrinogen may mislead

Because it rises during inflammation, a normal absolute fibrinogen can still represent substantial consumption when the expected level would be high.

Trend beats snapshot

Serial change in platelets, PT and fibrinogen often recognises evolving DIC earlier than waiting for a textbook combination.

Bleeding tests do not prevent clot

Prolonged PT and APTT describe laboratory clot initiation and do not exclude dangerous microvascular or macrovascular thrombosis.

Components buy time

Plasma, platelets and fibrinogen support haemostasis, but DIC continues until the biological trigger is controlled.

APL is time critical

A coagulopathy with abnormal promyelocytes warrants immediate ATRA discussion because early haemorrhage can precede definitive molecular confirmation.

11Common pitfallsFrequent interpretation and management errors.

01
Diagnosing DIC from a raised D-dimer alone.
02
Excluding DIC because the first fibrinogen is normal.
03
Waiting for a score before treating sepsis or haemorrhage.
04
Transfusing a non-bleeding patient solely to normalise PT.
05
Assuming prolonged coagulation tests exclude thrombosis.
06
Using tranexamic acid routinely in unselected DIC without specialist assessment.