Drug induced monocytosis

Monocytes are the largest leukocytes in the circulation.
These are agranulocytes
Largest cells of normal blood
Body's second line of defense against infection

1. DRUG INDUCED MONOCYTOSIS By : AYESHA ASIF ALI PHARM-D SULTAN-UL-ULOOM COLLEGE OF PHARMACY, HYDERABAD GUIDED BY: Dr.S.P.SRINIVAS NAYAK, ASSISTANT PROFESSOR , DEPT. OF PHARMACY PRACTICE, SUCP , HYD.

2. What are monocytes? Monocytes are the largest leukocytes in the circulation. These are agranulocytes Largest cells of normal blood Body's second line of defense against infection. 2

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4. Differentiation of Monocytes Monocytes are white blood cells that differentiate into macrophages and dendritic cells in the immune system Histiocytes, which are large macrophagic phagocytes, are classified as monocytes in a differential leukocyte count. Histiocytes and monocytes are capable of reversible transformation from one to the other. These monocytic/dendritic cells are derived primarily from bone marrow hematopoietic stem cells They are highly versatile with capacity to migrate to sites of inflammation, differentiate into tissue macrophages and specialized dendritic cell subtypes 4

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6. Role of Monocytes Circulating peripheral blood monocytes are key players in the innate immune system. Secrete cytokines and chemokines to attract other inflammatory cells. Phagocytose tissue debris and microorganisms. They participate in the initiation of adaptive immunity by presenting antigens to antigen‐specific lymphocytes. The effector functions and roles played by these cells are in mediating acute and chronic inflammation, antimicrobial defense, and tissue repair and wound healing , vital to the maintenance of a healthy steady state. 6

7. What is Monocytosis? Monocytosis is an increase in the number of monocytes circulating in the blood. with a level above 950/microLiter usually considered elevated. In patients with a normal leukocyte count, differentials with equal to or greater than 10% monocytes can also be considered monocytosis. In humans, monocytosis occurs when there is a sustained rise in monocyte counts greater than 800/mm3 to 1000/mm3A high monocyte count is indicative of chronic infection or inflammation. 7

8. Causes of Monocytosis Monocytosis often occurs during chronic inflammation. Diseases that produce such a chronic inflammatory state: Infections : tuberculosis, brucellosis, listeriosis, subacute bacterial endocarditis, syphilis, and other viral infections and many protozoal and rickettsial infections (e.g. kala azar, malaria, Rocky Mountain spotted fever). Blood and immune causes : chronic neutropenia and myeloproliferative disorders. Autoimmune diseases and vasculitis: systemic lupus erythematosus, rheumatoid arthritis and inflammatory bowel disease. Malignancies : Hodgkin's disease and certain leukaemias, such as chronic myelomonocytic leukaemia (CMML) and monocytic leukemia.Recovery phase of neutropenia or an acute infection. Miscellaneous causes : sarcoidosis and lipid storage disease. During these stages of extreme inflammation, monocytosis can damage tissues because it increases the activation of the immune response and prevents the inflammation from subsiding which is seen in cases where sepsis occurs. 8

9. Diagnosis Confirm the presence of monocytosis by blood smear review Blood test checking for monocytosis (Abnormal ranges: >10%) If monocytosis is sustained, unexplained, and/or features concerning for a hematologic neoplasm are present then further clinicopathologic workup should be considered including bone marrow examination with cytogenetic analysis flow cytometry Immunohistochemistry cytochemical stains special stains molecular genetic studies. 9

10. Drugs can induce almost the entire spectrum of hematologic disorders, affecting white cells, red cells, platelets, and the coagulation system. Drugs can induce toxicities spanning many hematologic syndromes, mediated by a variety of mechanisms. Physicians need to be alert to the potential for iatrogenic drug-induced hematologic complications. 10

11. Drugs that induce monocytosis Monocytosis may be seen in patients receiving cytokines (GM-CSF, M-CSF) TNF-alpha or drugs that increase levels of IL- 3, IL-6, or IL-1. It has also been described in patients taking Olanzapine, allopurinol, corticosteroids, Griseofulvin etc 11

12. TNF ALPHA Excess TNF-α in the blood activates monocytes with the potential to directly form lipid-laden ‘foam’ cells, a hallmark of atherosclerosis from stable to unstable state. These data demonstrate that excess TNF-α in the blood is the primary trigger for the development of atherosclerosis and CHD. The chronic inflammation or nonresolving inflammation involving monocyte increase , contributes to the pathophysiology of atherosclerosis. 12

13. Allopurinol Immune cells of the monocyte/macrophage cell lineage play a pivotal role in gouty inflammation. These cells are involved in all stages of disease progression, from triggering MSU crystal-induced inflammation in an acute attack . Based on clinical data , monocytes from gout patients with hyperuricaemia produce significantly less proinflammatory cytokines compared to monocytes from healthy volunteers. These differences indicated that hyperuricaemia may directly alter monocyte function. Allopurinol resulted in increased production of monocytes thereby increased production of proinflammatory cytokines (e.g. TNFa and IL-12) 13

14. Cortecosteroids The corticosteroid may stimulate interleukin-1 and granulocyte-macrophage colony stimulating factor to induce proliferation of colony forming unit i.e. granulocytesmacrophages These increase monocyte production. Olanzapine and Ziprasidone Infrequent and rarely , monocytosis was observed on higher doses of olanzapine and ziprasidone. 14

15. False-positive values may be caused by: Alprazolam Ampicillin Carbenicillin Chlorpromazine Granulocyte-colony stimulating factor (G-CSF) Griseofulvin Haloperidol Lomefloxacin Methsuximide Paroxetine Penicillamine Piperacillin Prednisone Propylthiouracil Quazepam. 15

16. Management of Monocytosis Management of Clinical Problem Monocytosis. Monocytosis itself is a sign only and does not require treatment. Treatment of the underlying etiology will cause resolution of this condition. 16

17. THANK YOU 17