**Question:** Which of the following is the only hemolytic anaemia caused by acquired intrinsic defect in the cell membrane:

A. Spherocytosis
B. Sickle cell anaemia
C. Hereditary spherocytosis
D. Thrombotic thrombocytopenic purpura (TTP)

**Correct Answer:** D. Thrombotic thrombocytopenic purpura (TTP)

**Core Concept:** Hemolytic anaemia refers to a group of disorders characterized by the premature breakdown of red blood cells (RBCs) in the body. These conditions can be primary (genetic) or secondary (acquired). Hemolysis can occur due to various factors, including intrinsic defects in the RBC membrane.

**Why the Correct Answer is Right:** Thrombotic thrombocytopenic purpura (TTP) is a rare acquired disorder characterized by the presence of microangiopathic haemolytic anaemia, thrombocytopenia, and renal failure. The defect lies in the intrinsic membrane of RBCs, specifically in the von Willebrand factor-cleaving protease (ADAMTS13) activity. This leads to the accumulation of large platelet-rich thrombi in the microcirculation, causing organ damage and symptoms.

**Why Each Wrong Option is Incorrect:**

A. Spherocytosis (Option A) is a primary (hereditary) disorder characterized by the presence of spherical RBCs due to intrinsic membrane defects. While some cases can be acquired, the correct answer is D (TTP), which is an acquired disorder.

B. Sickle cell anaemia (Option B) is a primary genetic disorder caused by a mutation in the beta-globin gene, leading to sickle-shaped RBCs. It is not caused by a defect in the RBC membrane.

C. Hereditary spherocytosis (Option C) is a primary disorder characterized by the presence of spherical RBCs due to intrinsic membrane defects. Similar to Option A, some cases can be acquired, but the correct answer is D (TTP), which is an acquired disorder.

**Clinical Pearl:** Hemolytic anaemia can have various causes, but always considering the correct answer (TTP), understanding the role of ADAMTS13 activity helps in distinguishing between primary and secondary hemolysis. In TTP, the absence or dysfunction of ADAMTS13 leads to a condition known as thrombotic microangiopathy, causing the clinical presentation of TTP.