During a routine hematology clinic review, you are asked to identify the most common cause of pancytopenia globally among patients presenting with bone marrow hypoplasia. Which of the following is the most frequent etiology?

Explanation

## Most Common Etiology of Aplastic Anemia **Key Point:** Idiopathic aplastic anemia (immune-mediated, no identifiable cause) accounts for approximately 50–70% of all aplastic anemia cases, making it the single most common etiology. ### Epidemiology of Aplastic Anemia Causes | Etiology | Frequency | Notes | |----------|-----------|-------| | **Idiopathic** | 50–70% | No identifiable trigger; immune-mediated | | Drug-induced | 10–20% | Chloramphenicol, NSAIDs, anticonvulsants | | Viral hepatitis-associated | 2–5% | Seronegative hepatitis; more common in Asia | | Radiation-induced | 1–2% | Occupational or therapeutic exposure | | Other (infections, autoimmune) | 5–10% | EBV, CMV, parvovirus B19, SLE | **High-Yield:** In the absence of a clear causative agent (drugs, radiation, infection, autoimmune disease), the diagnosis is idiopathic aplastic anemia, which is the most common presentation. ### Mechanism of Idiopathic Aplastic Anemia 1. T-cell mediated immune destruction of hematopoietic stem cells 2. Cytokine-driven (IFN-γ, TNF-α) suppression of progenitor cells 3. Loss of hematopoietic reserve 4. Pancytopenia results from reduced production, not destruction **Clinical Pearl:** Seronegative hepatitis-associated aplastic anemia is more prevalent in Asia and the Middle East than in Western countries, but globally, idiopathic cases still predominate. **Mnemonic: DRAPE** — Drug-related causes of aplastic anemia: - **D**iclofenac / **D**isulfiram - **R**ifampicin (rare) - **A**ntibiotics (chloramphenicol, trimethoprim-sulfamethoxazole) - **P**henytoin / **P**rocainamide - **E**strogens / **E**thambutol **Warning:** Do not assume a drug or environmental exposure caused aplastic anemia without temporal correlation. Many patients with idiopathic aplastic anemia will have taken medications or had exposures, but causality cannot be established. The diagnosis of idiopathic aplastic anemia is one of exclusion. [cite:Robbins 10e Ch 12]