Disseminated intravascular coagulation in cancer

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

Disseminated intravascular coagulation is a clinicopathological syndrome rather than a single laboratory result. Malignant cells, infection or tissue injury generate systemic thrombin, forming fibrin in small and large vessels while consuming platelets and clotting factors. Secondary fibrinolysis produces high D-dimer and contributes to bleeding. The phenotype depends on the driver: APL commonly causes severe hyperfibrinolytic bleeding; metastatic mucinous adenocarcinoma may produce slower thrombosis-dominant DIC; sepsis can create rapidly progressive microvascular organ failure.

Diagnosis requires a compatible cause and repeated tests. Platelets fall, PT commonly prolongs, fibrinogen may fall and D-dimer rises, but early fibrinogen can remain normal or high as an acute-phase reactant. APTT may be normal or shortened initially. The blood film can show schistocytes, although heavy fragmentation suggests thrombotic microangiopathy. The ISTH overt-DIC score combines platelet, PT, fibrin markers and fibrinogen and is useful when applied serially; it does not excuse treatment delay in a bleeding patient with a strong APL or sepsis picture.

Cause control is the decisive intervention. Suspected APL receives immediate all-trans retinoic acid while PML-RARA testing and intensive transfusion support proceed. Sepsis needs prompt antimicrobial and source control. Metastatic solid-tumour DIC may improve only with effective cancer therapy, so performance and goals matter. Support is phenotype-based: replace platelets and coagulation factors when bleeding or an urgent procedure creates a clinical need; avoid chasing normal tests in a stable patient because infused components are quickly consumed.

Thrombosis and bleeding can coexist. A patient with digital ischaemia, VTE or non-bacterial thrombotic endocarditis may need heparin despite thrombocytopenia and prolonged clotting, with close haematology control. In a bleeding-dominant presentation, anticoagulation is usually deferred while the trigger and haemostasis are treated. Repeated examination, coagulation trends and organ markers guide each change; the label DIC should never freeze management into one transfusion or anticoagulation rule.

Key points

DIC is an acquired systemic process of excessive coagulation activation with factor and platelet consumption, secondary fibrinolysis and variable bleeding, thrombosis and organ failure.
Cancer causes acute haemorrhagic DIC in APL, chronic thrombotic DIC in metastatic adenocarcinoma and mixed phenotypes intensified by sepsis, surgery or treatment.
First-line tests are serial platelet count, PT, APTT, fibrinogen and D-dimer with blood film, haemoglobin, renal, liver and haemolysis assessment; no single normal result excludes early DIC.
A falling platelet or fibrinogen trend and rising PT and fibrin markers are more useful than one static value; an ISTH score supports but does not replace clinical diagnosis.
Treat the cause first: give ATRA immediately when APL is suspected, treat sepsis and start tumour-directed therapy through haematology or oncology.
Do not transfuse solely to normalise laboratory values in a stable non-bleeding patient; use platelets, plasma and fibrinogen support for active bleeding or a high-risk invasive procedure.
BSH supports platelet transfusion when DIC with bleeding or high procedural risk has platelets below 50 × 10^9/L; plasma is guided by bleeding with prolonged coagulation, not PT alone.
When thrombosis clearly predominates, therapeutic heparin can be considered with haematology despite abnormal tests, using unfractionated heparin when rapid reversibility is important.

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

Acute promyelocytic leukaemia

APL blasts release potent procoagulant and fibrinolytic mediators, causing an especially haemorrhagic form that can deteriorate before marrow confirmation.

Metastatic adenocarcinoma

Mucinous pancreatic, gastric, prostate, lung and other disseminated tumours express tissue factor and mucins that drive chronic or acute coagulation activation.

Cancer-associated sepsis or shock

Infection and tissue hypoperfusion amplify endothelial tissue factor, cytokine release and impaired natural anticoagulants in an already prothrombotic host.

Treatment and tumour disruption

Systemic therapy, major surgery, transfusion and abrupt tumour breakdown can expose procoagulant material and convert compensated activation into overt DIC.

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

1
Thrombin forms throughout the circulation
Widespread tissue-factor signalling generates fibrin and platelet-rich microthrombi beyond the site of the original tumour or infection.
2
Platelets and factors are consumed
Continuous clot formation uses platelets, fibrinogen and coagulation factors faster than marrow and liver can replace them, causing bleeding.
3
Fibrinolysis becomes dysregulated
Plasmin generation produces high fibrin-degradation products and may dominate in APL, while suppressed fibrinolysis favours microvascular organ injury in sepsis.
4
Microvascular perfusion fails
Fibrin deposition, endothelial injury and red-cell fragmentation impair renal, pulmonary, cerebral, hepatic and skin flow, producing organ dysfunction.

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

Diffuse bleeding phenotype

Oozing from lines, mucosal bleeding, haematuria, ecchymosis and operative-site bleeding with falling platelets or fibrinogen suggests active consumption.

APL emergency patternRed flag

Bruising, mucosal bleeding and abnormal coagulation with abnormal promyelocytes or pancytopenia requires immediate ATRA and haematology support.

Microvascular organ phenotypeRed flag

Oliguria, hypoxaemia, confusion, jaundice or skin mottling can reflect widespread fibrin deposition and endothelial injury.

Thrombosis-dominant malignancy

Recurrent VTE, digital ischaemia, migratory thrombophlebitis or embolic stroke can occur during slower tumour-driven DIC.

Compensated laboratory evolution

A progressive platelet fall and rising D-dimer may precede overt bleeding or PT prolongation in chronic cancer-associated activation.

Trigger-related acceleration

Sepsis, surgery or initial cancer treatment can abruptly worsen a previously modest coagulation abnormality.

Red flags requiring action

Headache, focal neurology, reduced consciousness or severe hypertension with coagulopathy requires urgent intracranial bleeding assessment.
Persistent venepuncture oozing, mucosal bleeding, haematuria, gastrointestinal bleeding or rapidly expanding bruising indicates clinically active consumption.
Cold painful cyanotic digits, skin necrosis, renal failure, respiratory deterioration or confusion may reflect microvascular thrombosis despite simultaneous bleeding.
Suspected APL with bleeding or abnormal coagulation requires immediate ATRA before genetic confirmation because early haemorrhagic death is preventable.
Sepsis, shock, transfusion reaction and tumour lysis can accelerate a compensated cancer DIC into fulminant organ failure.

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 serial DIC panelFirst stepFirst line
Why
Detect consumption and fibrin turnover and measure its direction over hours.
Interpretation and limitations
Repeat platelet count, PT, APTT, fibrinogen and D-dimer; trend is crucial because fibrinogen may initially be normal or raised from inflammation.
02
Blood film and haemolysis profile
Why
Assess red-cell fragmentation and alternative microangiopathic disease.
Interpretation and limitations
Schistocytes can occur in DIC, but prominent fragmentation with relatively normal coagulation raises TTP, HUS or drug-associated microangiopathy.
03
ISTH overt-DIC score
Why
Standardise probability and serial communication using platelet, PT, fibrin marker and fibrinogen.
Interpretation and limitations
A score meeting the validated threshold supports overt DIC; repeat when initially below threshold and never delay emergency cause treatment for score completion.
04
Renal, liver, lactate and blood gas
Why
Identify organ hypoperfusion and the effects of shock, liver failure and treatment.
Interpretation and limitations
Organ deterioration increases urgency and can itself alter coagulation; interpret renal and hepatic trends with the suspected trigger.
05
APL diagnostic pathway
Why
Confirm PML-RARA while immediate differentiation treatment and haemostatic support continue.
Interpretation and limitations
Send urgent molecular and cytogenetic testing from blood or marrow; do not wait for confirmation before ATRA when morphology and coagulopathy are strongly suspicious.
06
Bleeding and thrombosis imaging
Why
Locate intracranial or internal bleeding and confirm macrovascular thrombosis when symptoms require intervention.
Interpretation and limitations
Choose CT, ultrasound or angiography from the clinical emergency; abnormal coagulation does not make all symptoms laboratory-only.

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

Thrombotic microangiopathy

TTP, HUS and drug-associated microangiopathy cause thrombocytopenia and fragmentation but often have near-normal coagulation tests and require different urgent treatment.

Liver failure

Reduced factor synthesis prolongs clotting and lowers fibrinogen, but the clinical context, factor pattern, platelets and serial activation markers help identify overlap.

Massive bleeding and dilution

Haemorrhage and high-volume fluid or transfusion can dilute platelets and factors without primary systemic thrombin generation; both mechanisms can coexist.

Anticoagulant effect or HIT

Heparin, direct oral anticoagulants and heparin-induced thrombocytopenia alter tests and thrombosis risk; exposure history and targeted assays are essential.

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

01RecogniseConfirm a changing syndromeFirst stepCancer coexists with bleeding, thrombosis, falling platelets or abnormal coagulation.

1Assess ABCDE, bleeding sites, skin and limb perfusion, neurological state and infection and obtain serial DIC panel, film, haemolysis and organ tests.
2Identify the likely trigger and use the ISTH score as supporting structure while acting immediately on major bleeding, shock or limb and brain threat.
3Call haematology and the tumour team early and communicate whether bleeding, thrombosis or organ failure currently dominates.

02CauseStop the coagulation driverThe tumour, infection or treatment trigger is identified or strongly suspected.

1Give ATRA immediately for suspected APL and proceed with urgent PML-RARA confirmation and the risk-adapted leukaemia protocol.
2Treat sepsis with prompt antimicrobials and source control and correct shock, hypoxia and hypothermia that amplify coagulopathy.
3Start effective solid-tumour or lymphoma therapy when benefits and performance allow, recognising components cannot overcome continuing malignant tissue-factor release alone.

03BleedingReplace what active haemostasis needsClinically significant bleeding or an urgent high-risk procedure occurs during DIC.

1Control the anatomical source and give platelets when the count is below the bleeding or procedural threshold, commonly 50 × 10^9/L under BSH guidance.
2Use FFP for bleeding with prolonged coagulation and cryoprecipitate or fibrinogen replacement for severe persistent hypofibrinogenaemia according to transfusion guidance.
3Recheck clinical bleeding and laboratory response after each intervention and avoid fixed repetitive transfusion without evidence of benefit or cause control.

04ThrombosisAnticoagulate a clot-dominant phenotypeObjectively confirmed VTE, arterial thrombosis, acral ischaemia or severe fibrin deposition predominates over bleeding.

1Assess current bleeding, platelets, fibrinogen, procedures and reversibility with haematology and confirm the threatened vascular territory.
2Use therapeutic heparin when benefit outweighs bleeding; consider continuous unfractionated heparin when short half-life and reversibility are advantageous.
3Monitor bleeding, platelet and fibrinogen trends and organ perfusion closely while treating the malignant driver.

Key medicines and prescribing safety4 treatments · regimens, roles and cautions

Differentiates the malignant promyelocyte clone and begins reversing the uniquely dangerous APL coagulopathy before definitive genetic confirmation.

All-trans retinoic acid for suspected APL

Give tretinoin 45 mg/m² per day orally in two divided doses immediately when APL is suspected, continuing under the risk-adapted specialist protocol while urgent PML-RARA confirmation is obtained.

Monitor differentiation syndrome, leukocytosis, liver tests, headache and intracranial hypertension; give dexamethasone promptly for suspected differentiation syndrome and enforce pregnancy prevention because tretinoin is teratogenic.

Replaces multiple consumed coagulation factors when clinically important bleeding or an urgent procedure requires haemostatic support.

Fresh frozen plasma

For active bleeding with prolonged PT or APTT, use the current transfusion-guideline adult dose, commonly 12 to 15 mL/kg, then reassess bleeding and coagulation rather than transfusing to a laboratory number alone.

Risks include overload, allergic reaction and transfusion-associated lung injury; plasma does not treat the cause and is not routine for abnormal tests without bleeding or procedural need.

Restores fibrin substrate when consumption and hyperfibrinolysis leave clot formation critically impaired.

Cryoprecipitate or fibrinogen replacement

Give the locally specified adult cryoprecipitate pool or fibrinogen concentrate when significant bleeding accompanies severe persistent hypofibrinogenaemia, with post-dose fibrinogen and clinical reassessment.

Use laboratory and clinical targets from the transfusion or APL protocol, account for thrombosis and volume, and repeat only while consumption and bleeding justify replacement.

Suppresses ongoing thrombin when acral ischaemia, VTE or another dominant thrombotic complication outweighs current bleeding.

Unfractionated heparin for thrombosis-dominant DIC

Use a specialist titrated intravenous regimen selected for the confirmed thrombotic phenotype, often without an initial bolus when bleeding risk is high, with protocol anti-Xa or APTT monitoring as interpretable.

Avoid uncontrolled bleeding and review severe thrombocytopenia, intracranial lesions and procedures; abnormal baseline APTT can make anti-Xa monitoring preferable and HIT remains possible.

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

Catastrophic haemorrhage

Intracranial, pulmonary, gastrointestinal or postoperative bleeding can progress rapidly when fibrinogen and platelets continue falling despite local control.

Microvascular organ failure

Diffuse fibrin deposition contributes to acute kidney injury, hypoxaemia, liver dysfunction, encephalopathy, adrenal injury and skin necrosis.

Macrovascular thrombosis

Cancer DIC may cause venous thromboembolism, arterial limb ischaemia, stroke or non-bacterial thrombotic endocarditis despite abnormal bleeding tests.

Transfusion and treatment burden

Repeated components create fluid, reaction and alloimmunisation risks while uncontrolled tumour continues consuming the replacement unless definitive therapy begins.

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

Repeat platelets, PT, APTT, fibrinogen and D-dimer at a frequency matched to clinical change, often several times daily in unstable APL or bleeding.
Monitor every visible and occult bleeding site, neurological state, limb perfusion, urine, respiratory status and lactate rather than treating laboratory values in isolation.
After components, document the clinical response and post-transfusion count or fibrinogen and reassess overload and transfusion reaction.
During ATRA, monitor differentiation syndrome, weight, oxygen need, renal function and leukocytosis and maintain the APL-specific fibrinogen and platelet targets.
During heparin, monitor bleeding, platelets, fibrinogen, renal and liver function and objective thrombosis response with an interpretable assay.
Track response to tumour or sepsis treatment; persistent DIC despite apparent cancer control requires a renewed trigger and differential review.

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

Fibrinogen can start normal

Inflammation raises fibrinogen production, so a downward trend can be clinically important before the concentration crosses a low threshold.

APL treatment starts on suspicion

Waiting for genetic confirmation exposes the patient to preventable early intracranial or pulmonary haemorrhage during a time-sensitive coagulopathy.

Bleeding and clotting coexist

Consumed factors do not protect against thrombosis because systemic thrombin generation continues in vessels while haemostatic reserve falls.

Components are temporary

Replacement supports active haemostasis but will be consumed again unless the leukaemia, tumour, infection or shock driver is controlled.

The phenotype determines heparin

Anticoagulation is not universally prohibited or required; the balance shifts when objective thrombosis and ischaemia dominate.

11Common pitfallsFrequent interpretation and management errors.

01
Excluding early DIC because fibrinogen or APTT is initially normal.
02
Waiting for PML-RARA confirmation before giving ATRA in a strongly suspected bleeding APL presentation.
03
Transfusing plasma solely to normalise PT in a stable non-bleeding patient.
04
Using platelet count alone without clinical bleeding and procedure risk to decide transfusion.
05
Calling all schistocytic thrombocytopenia DIC and missing TTP or treatment-associated microangiopathy.
06
Assuming abnormal coagulation prevents thrombosis and failing to image a compatible VTE or ischaemic limb.
07
Replacing components repeatedly without treating tumour, infection or shock.