**Question:** A 35-year-old lady with normal PT and increased aPTT. Two years ago, she underwent cholecystectomy without any bleeding episode. What is the next investigation for clinical diagnosis -

A. Heparin-induced thrombocytopenia (HIT) test
B. Coagulation profile (PT, APTT, INR)
C. Factor V Leiden mutation testing
D. Vitamin K deficiency

**Correct Answer:** C. Factor V Leiden mutation testing

**Core Concept:**

In this question, we are dealing with a patient presenting with normal prothrombin time (PT) and an increased activated partial thromboplastin time (aPTT). The patient's history of cholecystectomy without a bleeding episode implies that the bleeding diathesis is not due to liver dysfunction or vitamin K deficiency, which would affect both PT and aPTT. The increased aPTT alone indicates a specific coagulation abnormality.

**Why the Correct Answer is Right:**

The correct answer (C) is Factor V Leiden mutation testing because the patient exhibits an isolated aPTT prolongation without a direct effect on PT. Factor V Leiden mutation is a common genetic thrombophilia (increased risk of blood clot formation) that primarily affects the intrinsic pathway of coagulation, causing an increased aPTT without affecting PT.

**Why Each Wrong Option is Incorrect:**

A. Heparin-induced thrombocytopenia (HIT) test: This test is used to diagnose HIT, a thrombocytopenia (decreased platelet count) caused by immune response to heparin administration. In this case, the patient doesn't have a history of heparin exposure, so HIT can be ruled out.

B. Coagulation profile (PT, APTT, INR): While this test is essential for assessing the overall coagulation status, the patient already has a normal PT, indicating no effect on the common pathway of coagulation. Hence, this test doesn't address the patient's specific concern of isolated aPTT prolongation.

D. Vitamin K deficiency: As mentioned earlier, the patient's PT is normal, ruling out vitamin K deficiency affecting both PT and aPTT.

**Clinical Pearl:**

In clinical practice, remember that isolated aPTT prolongation is often indicative of Factor V Leiden mutation or other intrinsic pathway abnormalities, whereas normal PT suggests the extrinsic pathway is not involved. Always consider the specific coagulation pathway affected when interpreting coagulation profile results, as this helps guide appropriate further testing and management.