A 35-year-old woman presents with recurrent thrombosis and recurrent pregnancy loss. Investigations reveal prolonged aPTT that does not correct with 1:1 mixing study. What is the most common cause of acquired thrombophilia in this clinical presentation?

Question

Accepted Answer

C. Antiphospholipid syndrome. ## Diagnosis: Antiphospholipid Syndrome (APS)

**Key Point:** Antiphospholipid syndrome is the most common acquired thrombophilia, accounting for 5–15% of thrombotic events and 10–15% of recurrent pregnancy losses.

### Clinical Presentation
The triad of findings in this case is pathognomonic:
1. Recurrent thrombosis (venous or arterial)
2. Recurrent pregnancy loss (typically second/third trimester)
3. Prolonged aPTT that does NOT correct on mixing study (indicates presence of inhibitor)

**High-Yield:** The non-correcting aPTT is the hallmark laboratory finding. It occurs because antiphospholipid antibodies bind to phospholipids in the in vitro coagulation assay, prolonging the aPTT. In vivo, these antibodies promote thrombosis paradoxically.

### Diagnostic Criteria (Revised Sydney Criteria)
Diagnosis requires:
- Clinical criteria (thrombosis and/or pregnancy morbidity) AND
- Laboratory criteria (lupus anticoagulant, anticardiolipin antibodies, or anti-β2-glycoprotein-I antibodies) on ≥2 occasions ≥12 weeks apart

### Pathophysiology
Antiphospholipid antibodies bind to β2-glycoprotein-I and phospholipid complexes, activating tissue factor and platelets, leading to thrombosis.

**Clinical Pearl:** APS is the most common acquired cause of thrombophilia; inherited thrombophilias (Factor V Leiden, Prothrombin mutation) are more common overall but are inherited, not acquired.

### Comparison with Other Thrombophilias

| Feature | APS | Factor V Leiden | Prothrombin Mutation | Protein C Deficiency |
|---------|-----|-----------------|----------------------|----------------------|
| **Inheritance** | Acquired | Inherited (autosomal dominant) | Inherited (autosomal dominant) | Inherited (autosomal dominant) |
| **Prevalence** | 1–5% population | 3–7% Caucasians | 1–2% population | Rare |
| **Thrombotic Risk** | High (especially recurrent) | Moderate | Moderate | High |
| **Pregnancy Loss** | Yes (characteristic) | No | No | No |
| **aPTT** | Prolonged (non-correcting) | Normal | Normal | Normal |
| **Most Common Cause of Acquired Thrombophilia** | **YES** | No | No | No |

**Mnemonic: APS = Acquired Paradoxical Syndrome** — acquired (not inherited), paradoxical (prolongs aPTT but causes thrombosis), syndrome (multi-system involvement).

Answer

A. Prothrombin G20210A mutation

Answer

B. Factor V Leiden mutation

Answer

D. Protein C deficiency

A 35-year-old woman presents with recurrent thrombosis and recurrent pregnancy loss. Investigations reveal prolonged aPTT that does not correct with 1:1 mixing study. What is the most common cause of acquired thrombophilia in this clinical presentation?

Explanation

Diagnosis: Antiphospholipid Syndrome (APS)

Clinical Presentation

Diagnostic Criteria (Revised Sydney Criteria)

Pathophysiology

Comparison with Other Thrombophilias

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Feature	APS	Factor V Leiden	Prothrombin Mutation	Protein C Deficiency
Inheritance	Acquired	Inherited (autosomal dominant)	Inherited (autosomal dominant)	Inherited (autosomal dominant)
Prevalence	1–5% population	3–7% Caucasians	1–2% population	Rare
Thrombotic Risk	High (especially recurrent)	Moderate	Moderate	High
Pregnancy Loss	Yes (characteristic)	No	No	No
aPTT	Prolonged (non-correcting)	Normal	Normal	Normal
Most Common Cause of Acquired Thrombophilia	YES	No	No	No