A 52-year-old man with a history of metastatic pancreatic cancer presents with acute onset of severe bleeding from the gums and nose. He is on palliative chemotherapy. Laboratory findings: PT 28 s (normal 12–14 s), aPTT 58 s (normal 25–35 s), Platelet count 45,000/μL, Fibrinogen 95 mg/dL (normal 200–400 mg/dL), D-dimer 8.5 μg/mL (markedly elevated). Prothrombin time corrects after mixing study. What is the most likely diagnosis?

Explanation

## Clinical Diagnosis: Disseminated Intravascular Coagulation (DIC) ### Pathophysiology and Diagnostic Criteria **Key Point:** DIC is a life-threatening syndrome of widespread intravascular activation of coagulation, leading to consumption of platelets and clotting factors, and generation of fibrin and thrombin. It is triggered by tissue factor release in malignancy, sepsis, trauma, and obstetric emergencies. ### Why DIC Fits This Case 1. **Prolonged PT and aPTT** — Reflects consumption of factors II, V, VII, X, and VIII. 2. **Thrombocytopenia** — Platelets consumed by microthrombi formation. 3. **Low fibrinogen** — Consumed in fibrin formation; also degraded by plasmin. 4. **Markedly elevated D-dimer** — Reflects massive fibrin formation and breakdown; highly sensitive for DIC. 5. **Clinical context** — Metastatic malignancy is a potent trigger of DIC via tissue factor release. 6. **Acute bleeding manifestations** — Mucosal bleeding reflects both thrombocytopenia and coagulation factor depletion. ### DIC Scoring and Diagnosis The International Society on Thrombosis and Haemostasis (ISTH) DIC score incorporates: - Platelet count - D-dimer/fibrinogen degradation product elevation - PT prolongation - Fibrinogen level **High-Yield:** A score ≥5 is compatible with overt DIC in the appropriate clinical context. This patient's findings (low platelets, prolonged PT/aPTT, low fibrinogen, very high D-dimer) are highly suggestive. ### Differential Diagnosis Table | Feature | DIC | Vitamin K Deficiency | Lupus Anticoagulant | HIT | | --- | --- | --- | --- | --- | | PT | Prolonged | Prolonged | Normal | Normal | | aPTT | Prolonged | Normal | Prolonged (corrects on mixing) | Normal | | Platelets | Low | Normal | Normal | Low | | Fibrinogen | Low | Normal | Normal | Normal | | D-dimer | Very high | Normal | Normal | Normal | | Mixing study | Corrects (factor consumption) | Corrects (factor deficiency) | Does NOT correct (inhibitor) | N/A | | Clinical trigger | Sepsis, malignancy, trauma, OB | Antibiotic use, malabsorption | Autoimmune, antiphospholipid | Heparin exposure | **Clinical Pearl:** The mixing study corrects in DIC because the patient's plasma lacks clotting factors (consumption), and adding normal plasma restores them. In contrast, mixing study does NOT correct in lupus anticoagulant because an inhibitor is present. ### Mechanism Flowchart ```mermaid flowchart TD A[Malignancy/Sepsis/Trauma]:::outcome --> B[Tissue factor release]:::action B --> C[Thrombin generation]:::action C --> D[Platelet activation & consumption]:::action C --> E[Fibrin formation & consumption]:::action D --> F[Thrombocytopenia]:::outcome E --> G[Low fibrinogen]:::outcome E --> H[Elevated D-dimer]:::outcome C --> I[Factor consumption]:::action I --> J[Prolonged PT/aPTT]:::outcome F --> K[Bleeding]:::urgent J --> K ``` ### Management Approach 1. **Treat the underlying cause** — Chemotherapy adjustment, infection control, delivery in obstetrics. 2. **Supportive transfusion** — Fresh frozen plasma (FFP) for factor replacement; cryoprecipitate for fibrinogen; platelet transfusion for severe thrombocytopenia. 3. **Anticoagulation** — Heparin may be considered in chronic DIC with thrombosis, but is contraindicated in acute bleeding DIC. 4. **Monitoring** — Serial PT, aPTT, fibrinogen, D-dimer, and platelet count to assess response.