Disseminated Intravascular Coagulation (DIC)

Topic Overview

Summary

Disseminated intravascular coagulation (DIC) is a life-threatening syndrome characterized by systemic activation of coagulation, leading to widespread intravascular fibrin deposition and formation of microthrombi. This consumptive process depletes platelets, fibrinogen, and other clotting factors, resulting in a paradoxical state of simultaneous microvascular thrombosis and severe bleeding. DIC is always secondary to an underlying disease process — most commonly sepsis, trauma, malignancy (particularly acute promyelocytic leukaemia), or obstetric emergencies. The hallmark laboratory findings are thrombocytopenia, prolonged PT/APTT, low fibrinogen, and markedly elevated D-dimer. The ISTH scoring system provides standardized diagnostic criteria. Management focuses on treating the underlying trigger while providing supportive blood product replacement. Mortality ranges from 30-80% depending on the underlying cause and severity. [1,2,3]

Key Facts

• Always secondary: DIC is never a primary diagnosis — identify and treat the underlying cause
• Pathophysiology: Uncontrolled thrombin generation → microthrombi formation → consumption of platelets and factors → bleeding
• Classic pentad: Thrombocytopenia + prolonged PT/APTT + low fibrinogen + elevated D-dimer + schistocytes
• ISTH score: Score ≥5 indicates overt DIC (platelet count, PT prolongation, fibrinogen, D-dimer)
• Treatment priorities: (1) Treat underlying cause, (2) Blood product support, (3) Monitor serial coagulation studies
• Most common causes: Sepsis (40-50%), trauma (30%), malignancy (APL 90-100%), obstetric emergencies
• Blood products: Platelets if less than 50 with bleeding; FFP if prolonged PT/APTT; cryoprecipitate if fibrinogen less than 1.0 g/L
• Red flag: Purpura fulminans = severe DIC with skin necrosis, often meningococcal sepsis
• Mortality: 30-40% in septic DIC; up to 80% with multi-organ failure

Clinical Pearls

DIC is a syndrome, not a disease — always search for the underlying trigger

"Consumptive coagulopathy" = activated coagulation consumes platelets and factors faster than production

Fibrinogen less than 1.0 g/L is critically low — replace urgently with cryoprecipitate (target > 1.5 g/L)

In APL, DIC develops in > 90% — start ATRA immediately to prevent fatal haemorrhage

D-dimer is almost always massively elevated in DIC — a normal D-dimer makes DIC unlikely

Platelet transfusion is NOT contraindicated in DIC (unlike TTP) — transfuse if less than 50 with bleeding

Serial coagulation studies (every 4-6 hours) are essential to monitor response to treatment

Never give tranexamic acid in DIC — may worsen microvascular thrombosis

Why This Matters Clinically

DIC is a haematological emergency that complicates numerous critical illnesses. Early recognition using the ISTH scoring system, prompt treatment of the underlying cause, and judicious blood product support are life-saving interventions. Delayed diagnosis or failure to identify the trigger significantly increases mortality. DIC is a high-yield topic for MRCP PACES (data interpretation stations), MRCS vivas, and ICU medicine examinations.

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Visual Summary

Visual assets to be added:

• DIC pathophysiology flowchart (TF expression → thrombin generation → fibrin deposition → consumption → bleeding)
• ISTH DIC scoring algorithm
• Blood film showing schistocytes and thrombocytopenia
• DIC management algorithm (treat cause + blood products)
• Comparison table: DIC vs TTP vs Liver failure
• Purpura fulminans clinical photograph
• Coagulation cascade highlighting consumed factors

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Epidemiology

Incidence and Prevalence

DIC is a relatively common complication in critically ill patients, with incidence varying by underlying disease:

• Severe sepsis/septic shock: 30-50% develop DIC [1,4]
• Major trauma: 20-30% (higher with traumatic brain injury) [5]
• Acute promyelocytic leukaemia (APL): 90-100% at presentation [6]
• Solid organ malignancy: 7-15% (pancreatic, prostate, gastric adenocarcinoma) [7]
• Obstetric emergencies: Placental abruption (10%), amniotic fluid embolism (80%), severe pre-eclampsia (5%) [8]
• Overall ICU population: 10-15% of critically ill patients [2]

The true incidence may be underestimated due to variability in diagnostic criteria and delayed recognition.

Mortality

Mortality in DIC is high and closely linked to the underlying disease and severity:

• Overt DIC: 30-40% overall mortality [1,3]
• Septic DIC: 40-60% (higher than sepsis without DIC) [4]
• Traumatic DIC: 30-50% [5]
• Malignancy-associated DIC: 50-80% (better prognosis in APL with ATRA) [6,7]
• DIC with multi-organ failure: 70-80% [2]
• Non-overt (compensated) DIC: 10-20% (if underlying cause controlled) [3]

Mortality is significantly higher when DIC is diagnosed late or when the underlying trigger is not identified and treated.

Demographics

• Age: All age groups affected, but incidence increases with age due to higher rates of sepsis, malignancy, and comorbidities
• Sex: No gender predisposition except for obstetric DIC (females)
• Risk factors: Critical illness, sepsis, severe trauma, haematological malignancy, advanced solid tumours, complicated pregnancy

Causes of DIC

DIC is always secondary to an underlying disease. The most common triggers are:

Special note on APL: Acute promyelocytic leukaemia (M3 AML) causes DIC in > 90% of patients at presentation due to release of procoagulant granules from abnormal promyelocytes. This is a haematological emergency requiring immediate ATRA (all-trans retinoic acid) to differentiate blast cells and halt DIC progression. [6]

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Pathophysiology

Overview of Normal Haemostasis

Normal haemostasis maintains a balance between:

1. Procoagulant forces: Platelet activation, coagulation cascade, thrombin generation
2. Anticoagulant forces: Antithrombin, protein C/S, tissue factor pathway inhibitor (TFPI)
3. Fibrinolysis: Plasmin degrades fibrin clots

In DIC, this balance is lost, leading to uncontrolled systemic coagulation activation.

Molecular Mechanisms of DIC

1. Systemic Activation of Coagulation

The underlying disease triggers widespread activation of the coagulation system through multiple pathways:

Tissue Factor (TF) Expression: [1,2,3]

• TF is the primary initiator of DIC
• Expressed on monocytes, macrophages, and endothelial cells in response to inflammatory cytokines (TNF-α, IL-1, IL-6)
• Sepsis, trauma, and malignancy all increase TF expression
• TF binds Factor VIIa → activates Factor X → thrombin generation

Endothelial Damage:

• Direct injury (trauma, sepsis, toxins) exposes subendothelial collagen
• Loss of endothelial anticoagulant function (thrombomodulin, protein C receptor)
• Endothelial cells release TF and von Willebrand factor (VWF)

Cytokine Storm: [4]

• TNF-α, IL-1β, IL-6, IL-8 amplify coagulation
• Downregulate anticoagulant pathways (protein C, antithrombin)
• Upregulate plasminogen activator inhibitor-1 (PAI-1) → impaired fibrinolysis

2. Uncontrolled Thrombin Generation

• Massive thrombin generation overwhelms natural anticoagulants
• Thrombin cleaves fibrinogen → fibrin monomers → widespread fibrin deposition
• Microthrombi form in capillaries and small vessels throughout the body
• Platelet activation and aggregation further propagate thrombosis

3. Consumption of Clotting Factors and Platelets

• Ongoing coagulation consumes factors faster than hepatic synthesis
• Fibrinogen (most sensitive), Factor V, Factor VIII, Factor XIII depleted
• Platelets consumed in microthrombi → thrombocytopenia
• This is the "consumptive" phase of consumptive coagulopathy

4. Impaired Fibrinolysis

• PAI-1 is markedly elevated in DIC [2,3]
• Impairs plasmin generation → fibrin clots persist
• Paradoxically, secondary fibrinolysis also occurs → elevated fibrin degradation products (FDPs) and D-dimer
• FDPs have anticoagulant effects → worsen bleeding

5. Depletion of Natural Anticoagulants

• Antithrombin: Consumed by excess thrombin, further reducing anticoagulant capacity [9]
• Protein C and Protein S: Depleted and downregulated
• Loss of these natural brakes allows uncontrolled coagulation propagation

6. Microangiopathic Haemolytic Anaemia (MAHA)

• Fibrin strands in microvasculature create a "mesh"
• RBCs are sheared as they pass through → fragmented (schistocytes)
• Haemolysis releases free haemoglobin → LDH elevation, unconjugated hyperbilirubinaemia
• Distinguishes DIC from isolated coagulopathy [10]

Why Bleeding AND Thrombosis Occur Simultaneously

This paradox is central to understanding DIC:

Both occur at the same time in the same patient, which is pathognomonic for DIC.

Organ Dysfunction Due to Microthrombosis

• Kidneys: Acute tubular necrosis, cortical necrosis → AKI [2]
• Lungs: Pulmonary microthrombosis → ARDS
• Liver: Hepatocellular necrosis → transaminitis, hyperbilirubinaemia
• Brain: Microinfarcts, haemorrhagic stroke
• Skin: Purpura fulminans (acral necrosis), digital gangrene
• Adrenal glands: Adrenal haemorrhage → Waterhouse-Friderichsen syndrome (meningococcal sepsis)

DIC in Specific Conditions

Septic DIC [4]

• Endotoxin (LPS) triggers TF expression on monocytes
• Cytokine storm amplifies coagulation activation
• Mortality increased 2-3 fold compared to sepsis without DIC

APL-Associated DIC [6]

• Abnormal promyelocytes release:
  • Tissue factor
  • Annexin II (enhances plasmin generation)
  • Elastase (degrades fibrinogen)
• Results in hyperfibrinolytic DIC with severe bleeding
• ATRA induces differentiation → halts procoagulant release

Traumatic DIC [5]

• Tissue injury releases massive TF
• Hypoperfusion and acidosis worsen coagulopathy
• Hypothermia impairs enzyme function in coagulation cascade
• "Lethal triad": Hypothermia, acidosis, coagulopathy

Obstetric DIC [8]

• Placental abruption: Thromboplastin release from placenta
• Amniotic fluid embolism: Amniotic fluid is highly procoagulant
• HELLP syndrome: Platelet activation, microangiopathy

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Clinical Presentation

Symptoms

DIC presentations range from asymptomatic laboratory abnormalities (non-overt DIC) to fulminant bleeding and organ failure (overt DIC).

Bleeding Manifestations

• Skin: Petechiae, purpura, ecchymoses, spontaneous bruising
• Mucosal: Gum bleeding, epistaxis, conjunctival haemorrhage
• Gastrointestinal: Haematemesis, melaena, haematochezia
• Genitourinary: Haematuria, vaginal bleeding
• Procedural sites: Oozing from venipuncture sites, IV lines, surgical wounds, drains
• Internal: Intracranial haemorrhage (ICH), retroperitoneal bleeding, intra-abdominal haemorrhage

Thrombotic Manifestations

• Acral ischaemia: Cool, cyanotic digits (fingers, toes)
• Purpura fulminans: Haemorrhagic skin necrosis with dermal vascular thrombosis [11]
• Venous thromboembolism: DVT, PE (less common than microthrombosis)
• Arterial thrombosis: Stroke, limb ischaemia

Organ Dysfunction (Due to Microthrombosis)

• Renal: Oliguria, anuria, acute kidney injury
• Respiratory: Dyspnoea, hypoxaemia (ARDS)
• Neurological: Confusion, delirium, focal deficits, seizures
• Hepatic: Jaundice, hepatomegaly
• Cardiovascular: Hypotension, shock

Signs on Examination

General Appearance

• Critically ill, often requiring ICU-level care
• Evidence of underlying disease (septic shock, trauma injuries, pregnancy)

Skin and Mucous Membranes

• Petechiae: Pinpoint haemorrhages, non-blanching
• Purpura: Larger areas of skin haemorrhage (> 3 mm)
• Ecchymoses: Large bruises, often spontaneous
• Purpura fulminans: Haemorrhagic bullae with skin necrosis (surgical emergency) [11]
• Acral cyanosis: Dusky, cool digits

Mucosal Bleeding

• Gum oozing
• Conjunctival haemorrhage
• Blood in nasogastric aspirate

Procedural Site Oozing

• Persistent bleeding from IV sites, arterial lines, central lines
• Surgical wound bleeding despite adequate haemostasis

Signs of Organ Dysfunction

• Respiratory: Tachypnoea, hypoxia, crackles (ARDS)
• Renal: Oliguria, anuria
• Neurological: Altered consciousness, focal neurology (ICH, microinfarcts)
• Cardiovascular: Hypotension, tachycardia (shock, bleeding)

Red Flags

Clinical Subtypes

Overt (Decompensated) DIC [1,3]

• Clinically apparent bleeding and/or thrombosis
• Laboratory abnormalities meet ISTH criteria (score ≥5)
• Requires urgent treatment

Non-overt (Compensated) DIC [3]

• Laboratory abnormalities without clinical bleeding
• ISTH score less than 5 but trending abnormal
• May progress to overt DIC if underlying cause not treated
• Serial monitoring essential

Bleeding-Predominant DIC

• Severe factor and platelet consumption
• Common in APL, obstetric emergencies, trauma

Thrombosis-Predominant DIC

• Microthrombi with less overt bleeding
• Organ dysfunction predominates
• May see purpura fulminans, digital gangrene

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Clinical Examination

Haematology PACES/Viva Examination Approach

Skin Examination

1. Inspect for bleeding:
   • Petechiae (platelet disorder)
   • Purpura (platelets + coagulation)
   • Ecchymoses (factor deficiency)
2. Distribution: Widespread vs localized
3. Look for purpura fulminans: Haemorrhagic necrosis (DIC red flag)
4. Acral changes: Cyanosis, gangrene (thrombotic DIC)

Mucosal Examination

• Gum hypertrophy/bleeding (consider APL)
• Conjunctival haemorrhage
• Oral petechiae

Procedural Sites

• Check all IV sites, surgical wounds for oozing

Lymph Node Examination

• Lymphadenopathy (haematological malignancy)

Organomegaly

• Hepatomegaly/splenomegaly (haematological disease, liver dysfunction)

Evidence of Underlying Cause

• Septic shock: hypotension, fever, rigors
• Trauma: injuries, burns
• Pregnancy: obstetric examination
• Malignancy: cachexia, masses

Viva Questioning (MRCP/MRCS)

Examiner: "This patient has DIC. What are the key features you would look for on examination?"

Model Answer: "I would perform a systematic examination looking for evidence of both bleeding and thrombosis, as well as the underlying cause. For bleeding, I would inspect the skin for petechiae, purpura, and ecchymoses, check mucosal surfaces for bleeding, and examine all procedural sites for oozing. For thrombosis, I would look for acral cyanosis, purpura fulminans, and signs of organ dysfunction. I would also search for the underlying trigger — signs of sepsis, trauma, pregnancy complications, or haematological malignancy such as gum hypertrophy suggesting APL."

Examiner: "What is purpura fulminans?"

Model Answer: "Purpura fulminans is a catastrophic manifestation of DIC characterized by rapidly progressive haemorrhagic skin necrosis due to dermal vascular thrombosis. It typically affects the extremities and is associated with severe sepsis, particularly meningococcal septicaemia. It carries a high mortality and often requires surgical debridement."

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Investigations

Coagulation Studies — Diagnostic Hallmark

Key point: A normal D-dimer makes DIC highly unlikely. D-dimer is the most sensitive marker. [13]

ISTH DIC Scoring System [1,3]

The International Society on Thrombosis and Haemostasis (ISTH) provides standardized diagnostic criteria for overt DIC:

ISTH Overt DIC Score

Interpretation:

• Score ≥5: Compatible with overt DIC
• Score less than 5: Suggestive (repeat in 1-2 days if clinical suspicion high)

Clinical use: The ISTH score is used to diagnose overt DIC in patients with an underlying disorder known to be associated with DIC. It is not a screening tool for the general population.

Blood Film [10]

• Schistocytes (fragmented RBCs): Microangiopathic haemolytic anaemia (MAHA)
• Thrombocytopenia: Low platelet count
• Polychromasia: Reticulocytosis (haemolysis)
• Blasts (if APL): Abnormal promyelocytes with Auer rods

Full Blood Count

• Haemoglobin: Often low (bleeding + MAHA)
• MCV: Normal or slightly elevated (reticulocytosis)
• White cell count: Variable (elevated in sepsis, low in bone marrow failure)
• Reticulocyte count: Elevated (haemolysis)

Haemolysis Markers (MAHA)

• LDH: Elevated (RBC destruction)
• Unconjugated bilirubin: Elevated
• Haptoglobin: Low (binds free haemoglobin)
• Free haemoglobin: Elevated in severe haemolysis

Renal and Hepatic Function

• Urea and creatinine: Elevated (AKI from microthrombi)
• ALT/AST: Elevated (hepatic ischaemia)
• Bilirubin: Elevated (haemolysis + hepatic dysfunction)

Sepsis Work-Up (If Suspected)

• Blood cultures: Bacterial/fungal (before antibiotics)
• Lactate: Elevated in septic shock
• CRP/procalcitonin: Markers of infection
• Imaging: CT chest/abdomen/pelvis for source control

Malignancy Work-Up (If Suspected)

• Bone marrow aspirate/trephine: If APL or other haematological malignancy suspected
• ATRA-responsive APL: PML-RARA fusion gene (FISH, PCR)
• CT staging: Solid organ malignancy

Obstetric Work-Up (If Relevant)

• Ultrasound: Placental abruption, fetal status
• Kleihauer-Betke test: Feto-maternal haemorrhage

Differential Diagnosis — Laboratory Comparison

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Classification & Staging

By Clinical Presentation

Overt DIC (Decompensated)

• Clinically apparent bleeding and/or thrombosis
• ISTH score ≥5
• Requires immediate intervention

Non-overt DIC (Compensated)

• Laboratory abnormalities without overt clinical signs
• ISTH score less than 5
• Risk of progression to overt DIC
• Serial monitoring required

By Predominant Manifestation

Bleeding-Predominant DIC

• Severe factor and platelet consumption
• Common in APL, obstetric emergencies, massive trauma
• Mucosal bleeding, surgical site oozing, ICH risk

Thrombosis-Predominant DIC

• Microthrombosis with organ dysfunction
• Purpura fulminans, digital ischaemia
• AKI, ARDS, hepatic dysfunction

By Underlying Cause

By Fibrinolytic Activity

Hypofibrinolytic DIC

• Elevated PAI-1 suppresses fibrinolysis
• Microthrombosis predominates
• Common in sepsis

Hyperfibrinolytic DIC

• Excessive plasmin activity
• Severe bleeding
• Common in APL, prostate cancer, liver disease

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Management

General Principles

The cornerstone of DIC management is treating the underlying cause. Blood product support is essential but is only supportive — without treating the trigger, DIC will not resolve. [1,2,14]

Step 1: Treat the Underlying Cause — Most Critical

Critical point: In APL, start ATRA immediately upon clinical suspicion — do not wait for cytogenetic confirmation. Delay increases risk of fatal ICH. [6]

Step 2: Supportive Blood Product Replacement [1,2,14]

Blood products do not worsen DIC (this is a myth). They are essential to maintain haemostasis while the underlying cause is treated.

Platelet Transfusion

• Dose: 1 adult therapeutic dose (ATD) = 4 units pooled platelets or 1 apheresis unit
• Expected increment: ~20-30 × 10⁹/L per ATD (but consumption is ongoing)
• Re-check: 15-60 minutes post-transfusion, then serial monitoring

Fresh Frozen Plasma (FFP)

• Dose: 15-20 mL/kg (typically 4-6 units for an adult)
• Contains: All coagulation factors, natural anticoagulants
• Re-check: Coagulation studies 30-60 minutes post-transfusion

Cryoprecipitate

• Dose: 2 pools (10 units) for adults
• Contains: Fibrinogen (high concentration), Factor VIII, VWF, Factor XIII
• Expected increment: Each pool raises fibrinogen by ~0.5-1.0 g/L
• Re-check: Fibrinogen 1-2 hours post-transfusion

Clinical pearl: Fibrinogen is the first factor to become critically depleted in DIC. Aggressive cryoprecipitate replacement is often required, especially in APL and obstetric DIC. [12]

Red Blood Cell Transfusion

• Transfuse to maintain oxygen delivery
• Avoid over-transfusion (fluid overload risk)

Step 3: Anticoagulation (Controversial) [9,15]

The role of anticoagulation in DIC is debated and must be individualized.

When to Consider Anticoagulation

• Thrombosis-predominant DIC: Purpura fulminans, digital ischaemia, VTE
• Non-bleeding patients: With evidence of ongoing thrombosis
• Severe protein C deficiency: Replacement protein C concentrate (if available) or FFP

Anticoagulation Options

• Low-dose heparin: UFH 5-10 units/kg/hour (without bolus) or LMWH prophylactic dose
• Antithrombin concentrate: If antithrombin level less than 70% (not routinely recommended) [9]
• Recombinant thrombomodulin: Used in Japan, not widely available elsewhere [16]

Contraindications to Anticoagulation

• Active bleeding
• ICH or high ICH risk
• Severe thrombocytopenia (less than 20 × 10⁹/L)
• Recent surgery

Recommendation: In most cases, treating the underlying cause and blood product support suffice. Anticoagulation should be discussed with haematology and only used in highly selected cases. [1,2]

Step 4: Avoid Tranexamic Acid

Tranexamic acid (TXA) is an antifibrinolytic agent that should generally be avoided in DIC because it may worsen microthrombosis by preventing fibrin clot breakdown. [1,2]

Exception: Some clinicians use TXA in hyperfibrinolytic DIC (e.g., APL) under haematology guidance, but this is controversial.

Step 5: Monitoring and Serial Assessment

Key principle: Serial trending is more important than absolute values. Improvement in platelet count, fibrinogen, and PT/APTT indicates DIC resolution.

DIC Management Algorithm

Patient with DIC (ISTH score ≥5)
         ↓
Identify and Treat Underlying Cause
         ↓
Sepsis → Antibiotics + source control
APL → ATRA + chemotherapy
Trauma → Surgery + "lethal triad" correction
Obstetric → Deliver fetus
         ↓
Blood Product Support
         ↓
Platelets: less than 50 with bleeding → transfuse
FFP: PT/APTT > 1.5× normal with bleeding → transfuse
Cryoprecipitate: Fibrinogen less than 1.0 g/L → transfuse
RBCs: Hb less than 70-80 g/L → transfuse
         ↓
Consider Anticoagulation (Specialist Guidance)
- If thrombosis-predominant
- No active bleeding
- Discuss with haematology
         ↓
Serial Monitoring (Every 4-6 Hours)
- Platelets, PT/APTT, fibrinogen, D-dimer
         ↓
Resolution of DIC
- Platelets rising
- PT/APTT normalizing
- Fibrinogen rising
- D-dimer falling

Special Considerations

DIC in APL [6]

• Start ATRA immediately (before cytogenetic confirmation)
• Aggressive cryoprecipitate: Target fibrinogen > 1.5 g/L, often requires repeated dosing
• Platelet transfusion: Maintain > 30-50 × 10⁹/L to prevent ICH
• Avoid anthracyclines alone: May worsen DIC transiently; ATRA is protective

DIC in Obstetrics [8]

• Deliver fetus/placenta: Definitive treatment for obstetric DIC
• Ergometrine/oxytocin: Uterine contraction to reduce bleeding
• Massive obstetric haemorrhage protocol: Involve obstetric, anaesthetic, haematology teams

DIC in Trauma [5]

• Damage control resuscitation:
  • Permissive hypotension (SBP 80-90 mmHg) until haemorrhage controlled
  • "Balanced blood product ratio: RBCs:FFP:platelets = 1:1:1"
  • Correct hypothermia (warm fluids, warming blanket)
  • Correct acidosis (adequate resuscitation)
• Tranexamic acid: May be considered in trauma (within 3 hours), but DIC is a relative contraindication

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Complications

Complications of DIC Itself

Complications of Treatment

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Prognosis & Outcomes

Mortality Rates [1,2,3,4]

Prognosis in DIC is heavily dependent on the underlying cause and severity:

Prognostic Factors

Poor Prognosis

• Multi-organ failure (renal, respiratory, hepatic)
• Severe thrombocytopenia (less than 20 × 10⁹/L)
• Fibrinogen less than 0.5 g/L
• Delayed diagnosis or treatment
• Uncontrolled underlying cause (refractory sepsis, advanced malignancy)
• ICH
• Age > 70 years

Good Prognosis

• Early diagnosis and treatment
• Reversible underlying cause (e.g., APL with ATRA, obstetric DIC with delivery)
• Non-overt DIC (caught early)
• Good response to blood products
• Single-organ involvement

Long-Term Outcomes

Survivors May Experience:

• Chronic kidney disease: If AKI progressed to cortical necrosis
• Digit/limb amputations: From purpura fulminans or gangrene
• Neurological deficits: From ICH or microinfarcts
• Psychological sequelae: PTSD from critical illness

Follow-Up

• Haematology review: Assess for underlying haematological disorders
• Renal function monitoring: If AKI occurred
• Rehabilitation: Physiotherapy, occupational therapy for amputations or neurological deficits

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Evidence & Guidelines

Key Guidelines

1. ISTH Guidance on Diagnosis and Management of DIC [1,3]

   • Standardized diagnostic criteria (ISTH DIC score)
   • Recommendations for blood product support
   • Evidence-based approach to anticoagulation

2. British Committee for Standards in Haematology (BCSH) Guideline on DIC [14]

   • UK-specific guidance
   • Emphasis on treating underlying cause
   • Blood product thresholds

3. Japanese Association for Acute Medicine (JAAM) DIC Criteria [16]

   • Alternative diagnostic scoring system
   • Includes recombinant thrombomodulin (not widely used outside Japan)

Key Evidence

Treating Underlying Cause is Most Effective [1,2,6]

• APL + ATRA: Landmark studies showed ATRA reduced early haemorrhagic death in APL from 70% to less than 10% [6]
• Sepsis + antibiotics: Early antibiotic administration reduces DIC incidence and mortality [4]
• Obstetric DIC + delivery: Delivery of fetus/placenta resolves DIC in most obstetric cases [8]

Blood Product Replacement [12,14]

• Fibrinogen replacement: Maintaining fibrinogen > 1.5 g/L reduces bleeding complications [12]
• Platelet transfusion: No evidence that platelet transfusion worsens DIC; should be used if less than 50 × 10⁹/L with bleeding [14]

Anticoagulation is Controversial [9,15]

• Antithrombin concentrate: Large RCT (KyberSept) showed no mortality benefit in severe sepsis [9]
• Heparin: Limited evidence; may reduce microthrombosis but increases bleeding risk [15]
• Recommendation: Reserve for thrombosis-predominant DIC under specialist guidance [1,2]

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Examination Focus

MRCP PACES / Data Interpretation

Scenario

"A 68-year-old man is admitted with septic shock secondary to pneumonia. He develops bleeding from venipuncture sites and a petechial rash. Coagulation studies are shown."

Question: What is the diagnosis and how would you manage this patient?

Model Answer: "This patient has overt DIC secondary to septic shock. The key features are thrombocytopenia, prolonged PT and APTT, low fibrinogen, and markedly elevated D-dimer — classic for consumptive coagulopathy. The ISTH DIC score is 7 (platelets less than 50 = 2 points, strong D-dimer elevation = 3 points, PT prolonged > 6 seconds = 2 points), confirming overt DIC.

Management priorities are:

1. Treat underlying sepsis: Broad-spectrum antibiotics, source control, sepsis resuscitation
2. Blood product support: Platelet transfusion (target > 50), FFP (normalize PT/APTT), cryoprecipitate (fibrinogen less than 1.0 g/L — urgent replacement to > 1.5 g/L), RBC transfusion if anaemic
3. Serial monitoring: Coagulation studies every 4-6 hours to guide ongoing replacement
4. ICU-level care: Close monitoring for organ dysfunction

The prognosis depends on control of sepsis. Without treating the underlying infection, DIC will not resolve despite blood product support."

MRCS / FRCS Viva

Examiner: "A trauma patient develops DIC intra-operatively. What are your management priorities?"

Model Answer: "Traumatic DIC is part of the 'lethal triad' of hypothermia, acidosis, and coagulopathy. My management priorities are:

1. Damage control surgery: Abbreviate the operation, achieve temporary haemorrhage control, and plan re-look laparotomy when physiology corrected
2. Correct the lethal triad:
   • Hypothermia: Warm IV fluids, forced-air warming, warm blood products
   • Acidosis: Adequate resuscitation, bicarbonate if severe
   • Coagulopathy: Massive transfusion protocol with balanced RBCs:FFP:platelets (1:1:1), cryoprecipitate if fibrinogen low
3. Blood product support: Transfuse to maintain platelets > 50, fibrinogen > 1.5 g/L, normalize PT/APTT
4. Avoid over-resuscitation: Permissive hypotension until bleeding controlled
5. ICU transfer: Post-operative monitoring, serial coagulation studies

The key is damage control resuscitation and surgery — DIC will not resolve until haemorrhage is controlled and physiology is normalized."

MRCOG / FRANZCOG Viva

Examiner: "You are called to the labour ward for a woman with placental abruption and DIC. How do you manage her?"

Model Answer: "Placental abruption with DIC is an obstetric emergency. My approach is:

1. ABCDE assessment: Stabilize haemodynamics (large-bore IV access, fluid resuscitation, cross-match 6 units RBCs minimum)
2. Urgent delivery: DIC will not resolve until the placenta is delivered — expedite delivery (vaginal if imminent, otherwise emergency caesarean section)
3. Activate massive haemorrhage protocol: Request platelets, FFP, cryoprecipitate
4. Blood product replacement:
   • Platelets: Target > 50 × 10⁹/L
   • FFP: Normalize PT/APTT
   • Cryoprecipitate: Fibrinogen > 1.5 g/L (critical — obstetric DIC rapidly depletes fibrinogen)
5. Uterotonic agents: Oxytocin, ergometrine, carboprost to reduce uterine bleeding post-delivery
6. Monitor fetus: Continuous CTG (if viable gestation), but maternal resuscitation is priority
7. Involve MDT: Obstetric consultant, anaesthetist, haematology, ICU

The definitive treatment is delivery — this removes the source of tissue factor from the placenta."

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Patient & Family Information

What is DIC? (Layperson Explanation)

DIC stands for "disseminated intravascular coagulation." It is a serious condition where the blood clotting system becomes overactive throughout the body. Normally, blood clots only form when you are injured to stop bleeding. In DIC, tiny blood clots form in small blood vessels all over the body, even though there is no injury.

Why Does It Happen?

DIC is always caused by another serious illness or injury, such as:

• Severe infection (sepsis)
• Major trauma or burns
• Pregnancy complications (such as placental abruption)
• Certain types of cancer (especially blood cancers)

These conditions trigger the blood clotting system to become overactive.

What Are the Symptoms?

DIC causes two main problems at the same time:

1. Bleeding: Because clotting factors and platelets are "used up" forming clots, there are not enough left to stop bleeding. You may notice:

   • Bruising easily
   • Bleeding from gums, nose, or IV sites
   • Blood in urine or stool

2. Clotting: Tiny clots can block small blood vessels, which can damage organs such as the kidneys, lungs, or brain.

How is DIC Diagnosed?

Doctors use blood tests to diagnose DIC:

• Low platelet count: Platelets help blood clot
• Low fibrinogen: A protein needed for clotting
• Prolonged clotting times (PT and APTT): Blood takes longer to clot
• High D-dimer: Shows that clots are forming and breaking down

How is DIC Treated?

Treatment focuses on two things:

1. Treating the underlying cause: DIC will not go away unless the condition causing it is treated. For example:

   • Antibiotics for infection
   • Surgery for trauma
   • Delivery of the baby in pregnancy complications
   • Chemotherapy for certain cancers

2. Replacing blood components: You may need transfusions of:

   • Platelets (to help blood clot)
   • Fresh frozen plasma (contains clotting factors)
   • Cryoprecipitate (contains fibrinogen)
   • Red blood cells (if you have lost blood)

What is the Outlook?

The outlook for DIC depends on the underlying cause and how quickly treatment is started. DIC is a serious condition with a high risk of complications, but many people recover if the underlying disease is treated successfully.

Resources

• Blood Cancer UK
• NHS — Disseminated Intravascular Coagulation
• Leukaemia Care

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References

Primary Guidelines

1. Wada H, Matsumoto T, Yamashita Y. Diagnosis and treatment of disseminated intravascular coagulation (DIC) according to four DIC guidelines. J Intensive Care. 2014;2:15. DOI: 10.1186/2052-0492-2-15. PMID: 25520831

2. Levi M, Scully M. How I treat disseminated intravascular coagulation. Blood. 2018;131(8):845-854. DOI: 10.1182/blood-2017-10-804096. PMID: 29255070

3. Taylor FB Jr, Toh CH, Hoots WK, et al. Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost. 2001;86(5):1327-1330. PMID: 11816725

Key Reviews

4. Gando S, Levi M, Toh CH. Disseminated intravascular coagulation. Nat Rev Dis Primers. 2016;2:16037. DOI: 10.1038/nrdp.2016.37. PMID: 27250996

5. Brohi K, Cohen MJ, Davenport RA. Acute coagulopathy of trauma: mechanism, identification and effect. Curr Opin Crit Care. 2007;13(6):680-685. DOI: 10.1097/MCC.0b013e3282f1e78f. PMID: 17975390

6. Tallman MS, Altman JK. How I treat acute promyelocytic leukemia. Blood. 2009;114(25):5126-5135. DOI: 10.1182/blood-2009-07-216457. PMID: 19797519

7. Levi M. Cancer-related coagulopathies. Thromb Res. 2014;133 Suppl 2:S70-S75. DOI: 10.1016/S0049-3848(14)50012-6. PMID: 24862149

8. Erez O, Mastrolia SA, Thachil J. Disseminated intravascular coagulation in pregnancy: insights in pathophysiology, diagnosis and management. Am J Obstet Gynecol. 2015;213(4):452-463. DOI: 10.1016/j.ajog.2015.03.054. PMID: 25840271

Specific Treatments

9. Warren BL, Eid A, Singer P, et al. Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial. JAMA. 2001;286(15):1869-1878. DOI: 10.1001/jama.286.15.1869. PMID: 11597289

10. George JN. How I treat patients with thrombotic thrombocytopenic purpura. Blood. 2010;116(20):4060-4069. DOI: 10.1182/blood-2010-07-271445. PMID: 20686117

11. Johansen ME, Jensen JU. Purpura fulminans: a review of pathophysiology and management. Acta Derm Venereol. 2017;97(3):275-283. DOI: 10.2340/00015555-2521. PMID: 27605184

12. Innerhofer P, Fries D, Mittermayr M, et al. Reversal of trauma-induced coagulopathy using first-line coagulation factor concentrates or fresh frozen plasma (RETIC): a single-centre, parallel-group, open-label, randomised trial. Lancet Haematol. 2017;4(6):e258-e271. DOI: 10.1016/S2352-3026(17)30077-7. PMID: 28569485

13. Levi M, Toh CH, Thachil J, Watson HG. Guidelines for the diagnosis and management of disseminated intravascular coagulation. Br J Haematol. 2009;145(24):24-33. DOI: 10.1111/j.1365-2141.2009.07600.x. PMID: 19222477

14. Levi M. Disseminated intravascular coagulation. Crit Care Med. 2007;35(9):2191-2195. DOI: 10.1097/01.CCM.0000281468.94108.4B. PMID: 17855836

15. Gando S, Saitoh D, Ogura H, et al. A multicenter, prospective validation study of the Japanese Association for Acute Medicine disseminated intravascular coagulation scoring system in patients with severe sepsis. Crit Care. 2013;17(3):R111. DOI: 10.1186/cc12783. PMID: 23787004

16. Saito H, Maruyama I, Shimazaki S, et al. Efficacy and safety of recombinant human soluble thrombomodulin (ART-123) in disseminated intravascular coagulation: results of a phase III, randomized, double-blind clinical trial. J Thromb Haemost. 2007;5(1):31-41. DOI: 10.1111/j.1538-7836.2006.02267.x. PMID: 17059423

Additional Evidence

17. Iba T, Levy JH, Wada H, et al. Differential diagnoses for sepsis-induced disseminated intravascular coagulation: communication from the SSC of the ISTH. J Thromb Haemost. 2019;17(2):415-419. DOI: 10.1111/jth.14354. PMID: 30387557

18. Wada H, Thachil J, Di Nisio M, et al. Guidance for diagnosis and treatment of DIC from harmonization of the recommendations from three guidelines. J Thromb Haemost. 2013;11(4):761-767. DOI: 10.1111/jth.12155. PMID: 23379279

19. Iba T, Di Nisio M, Levy JH, et al. New criteria for sepsis-induced coagulopathy (SIC) following the revised sepsis definition: a retrospective analysis of a nationwide survey. BMJ Open. 2017;7(9):e017046. DOI: 10.1136/bmjopen-2017-017046. PMID: 28963294

20. Schmitt FCF, Manolov V, Morgenstern J, et al. Acute fibrinolysis shutdown occurs early in septic shock and is associated with increased morbidity and mortality: results of an observational pilot study. Ann Intensive Care. 2019;9(1):19. DOI: 10.1186/s13613-019-0499-6. PMID: 30680501

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