*2.2.1 Mechanism involved or pathophysiology of the drug-induced agranulocytosis (DIA)*

The exact reason for drug induced agranulocytosis is still not recognized but many mechanisms were put forward, nonetheless the recent studies revealed that medications may have a direct toxic effect on the bone marrow, neutrocytes or stem cells. The first mechanism involves the anti-thyroid drugs (ATD) such as methimazole and propylthiouracil which have been outlined to cause agranulocytosis. Apoptosis occur which activates inflammasomes (important for innate immune system). The following figure shows the direct toxicity of ATD-Induced agranulocytosis. In recent outline 7–23% of DIA cases occur due to anti-thyroid drugs. Higher dose of methimazole received by patient showed neutropenia.

The second kind of mechanism comprises antibodies, neutrophils, immunemediated medications, or drug metabolites. This process suggests that the medication is adsorbing through the neutrophile membrane. The drug-containing membrane functions as a hapten to promote the production of antibodies. As a result of the antibodies' binding to the drug-membrane complex, the phagocytic system activates

*Drug Induced Hematological Disorders: An Undiscussed Stigma DOI: http://dx.doi.org/10.5772/intechopen.109533*

**Figure 1.** *Antibody and complement system-based mechanism of toxicity.*

complement, which in turn causes the WBC to be destroyed. When medications like penicillin derivatives are administered at larger doses, this hapten-type response occurs as depicted in **Figure 1**.

There are also several other immune-mediated processes that have been identified. The culprit medicine reforms the neutrophil membrane through the autoantibodies forming to a membrane mechanism. This alteration triggers the production of autoantibodies, which kill cells.
