A 35-year-old woman with a lifelong history of easy bruising and menorrhagia is found to have a prolonged aPTT, normal PT, and normal platelet count. Mixing study corrects the aPTT. Which finding best distinguishes Factor V deficiency from Factor VIII deficiency?

Question

Accepted Answer

D. Prolonged thrombin time. ## Distinguishing Factor V from Factor VIII Deficiency

### The Critical Distinction: Thrombin Time

**Key Point:** Factor V is a cofactor in both the intrinsic (aPTT) and extrinsic (PT) pathways, as well as in the final common pathway (thrombin generation). Factor VIII participates only in the intrinsic pathway. A prolonged thrombin time (TT) indicates involvement of the final common pathway, which occurs in Factor V deficiency but not Factor VIII deficiency.

### Comparative Table

| Coagulation Test | Factor V Deficiency | Factor VIII Deficiency |
|------------------|-------------------|------------------------|
| **PT** | Prolonged | Normal |
| **aPTT** | Prolonged | Prolonged |
| **Thrombin Time (TT)** | Prolonged | Normal |
| **Platelet count** | Normal | Normal |
| **Bleeding time** | Normal | Normal |
| **Mixing study** | Corrects aPTT | Corrects aPTT |
| **Fibrinogen** | Normal | Normal |

### Pathophysiologic Basis

**Factor V Role:**
- Essential cofactor in prothrombinase complex (Factor Xa + Factor V + phospholipid + Ca²⁺ → thrombin)
- Participates in both extrinsic AND intrinsic pathways
- Required for thrombin generation from prothrombin

**Factor VIII Role:**
- Cofactor only in the intrinsic tenase complex (Factor IXa + Factor VIII + phospholipid + Ca²⁺ → Factor Xa)
- Does NOT participate in the extrinsic pathway or final common pathway
- Deficiency does NOT prolong PT or TT

**High-Yield:** The **prolonged PT in Factor V deficiency** is the most obvious discriminator, but since the stem specifies "normal PT," the next-best discriminator is **prolonged TT**, which reflects Factor V's role in the final common pathway.

**Mnemonic:** **"V is for Very versatile"** — Factor V participates in all three major pathways (intrinsic, extrinsic, common). Factor VIII is **"VIII = Intrinsic only"**.

Answer

A. Reduced fibrinogen level

Answer

B. Abnormal bleeding time

Answer

C. Normal prothrombin time (PT)

A 35-year-old woman with a lifelong history of easy bruising and menorrhagia is found to have a prolonged aPTT, normal PT, and normal platelet count. Mixing study corrects the aPTT. Which finding best distinguishes Factor V deficiency from Factor VIII deficiency?

Explanation

Distinguishing Factor V from Factor VIII Deficiency

The Critical Distinction: Thrombin Time

Comparative Table

Pathophysiologic Basis

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Coagulation Test	Factor V Deficiency	Factor VIII Deficiency
PT	Prolonged	Normal
aPTT	Prolonged	Prolonged
Thrombin Time (TT)	Prolonged	Normal
Platelet count	Normal	Normal
Bleeding time	Normal	Normal
Mixing study	Corrects aPTT	Corrects aPTT
Fibrinogen	Normal	Normal