A 38-year-old woman with acute promyelocytic leukemia (APL) presents with fever, petechiae, and gum bleeding. Laboratory investigations reveal PT 18 s (control 12 s), aPTT 45 s (control 28 s), platelet count 45,000/μL, fibrinogen 85 mg/dL, and D-dimer 10 μg/mL. All of the following are mechanisms contributing to DIC in this patient EXCEPT:

Question

A 38-year-old woman with acute promyelocytic leukemia (APL) presents with fever, petechiae, and gum bleeding. Laboratory investigations reveal PT 18 s (control 12 s), aPTT 45 s (control 28 s), platelet count 45,000/μL, fibrinogen 85 mg/dL, and D-dimer >10 μg/mL. All of the following are mechanisms contributing to DIC in this patient EXCEPT:

Accepted Answer

B. Increased production of antithrombin III and protein C, overwhelming the coagulation cascade. ## Pathophysiology of DIC in Acute Promyelocytic Leukemia

**Key Point:** APL is the most common malignancy-associated cause of DIC. The pathophysiology involves release of procoagulant substances from abnormal promyelocytes, not activation of natural anticoagulants.

### Mechanisms of DIC in APL

| Mechanism | Role in DIC | Comment |
|-----------|-------------|----------|
| Tissue factor (TF) release | ✓ Initiates extrinsic pathway | Promyelocytes contain abundant TF |
| Cancer procoagulant | ✓ Activates Factor X directly | Independent of TF pathway |
| Microvesicles | ✓ Carry TF and phosphatidylserine | Amplify coagulation |
| Platelet consumption | ✓ Trapped in microthrombi | Leads to thrombocytopenia |
| Antithrombin/Protein C | ✗ Decreased, not increased | Consumed during DIC |

### Why Option 3 is Wrong

**High-Yield:** In DIC, antithrombin III and protein C are **CONSUMED** and therefore **DECREASED**, not increased. These are natural anticoagulants that are overwhelmed by the massive procoagulant stimulus, not the cause of DIC.

**Clinical Pearl:** The hallmark of DIC is an imbalance favoring coagulation activation over anticoagulation. Antithrombin and protein C levels are actually useful prognostic markers — very low levels indicate severe DIC with poor prognosis.

### Cascade of Events in APL-Associated DIC

```mermaid
flowchart TD
  A[Acute Promyelocytic Leukemia]:::outcome --> B[Release of TF & Cancer Procoagulant]:::action
  B --> C[Extrinsic Pathway Activation]:::action
  C --> D[Massive Thrombin Generation]:::urgent
  D --> E[Platelet Consumption & Microthrombi]:::action
  D --> F[Fibrin Deposition in Microvasculature]:::action
  E --> G[Thrombocytopenia]:::outcome
  F --> H[Tissue Ischemia & Bleeding]:::urgent
  D --> I[Secondary Fibrinolysis]:::action
  I --> J[Elevated D-dimer & FDP]:::outcome
  J --> K[Hypofibrinogenemia]:::outcome
  L[Antithrombin & Protein C]:::outcome --> M[Consumed & Depleted]:::urgent
```

**Mnemonic: PROMYELOCYTE PROCOAGULANTS** — **P**rocoagulant **R**elease **O**verwhelms **M**ultiple **Y**pathways **E**xtrinsic **L**eads **O**ver **C**oagulation **Y**ield **T**hrombi **E**verywhere

Answer

A. Release of tissue factor and cancer procoagulant from leukemic promyelocytes

Answer

C. Activation of the extrinsic pathway via tissue factor-bearing microvesicles

Answer

D. Platelet activation and aggregation leading to consumption in microthrombi

Explanation

Pathophysiology of DIC in Acute Promyelocytic Leukemia

Mechanisms of DIC in APL

Why Option 3 is Wrong

Cascade of Events in APL-Associated DIC

Practice similar questions

Join our NEET PG community

Mechanism	Role in DIC	Comment
Tissue factor (TF) release	✓ Initiates extrinsic pathway	Promyelocytes contain abundant TF
Cancer procoagulant	✓ Activates Factor X directly	Independent of TF pathway
Microvesicles	✓ Carry TF and phosphatidylserine	Amplify coagulation
Platelet consumption	✓ Trapped in microthrombi	Leads to thrombocytopenia
Antithrombin/Protein C	✗ Decreased, not increased	Consumed during DIC