How to Approach Neutropenia PDF

How to approach Neutropenia Supervised by Assist.Prof. Dr.Hind Shaker Presented by Dr. Noor Saad / 3rd year hamatopathology student 2024/2025 1  By the end of this lecture we will be able to : De ne neutropenia. Know how neutropenia is classi ed ?...

How to approach Neutropenia Supervised by Assist.Prof. Dr.Hind Shaker Presented by Dr. Noor Saad / 3rd year hamatopathology student 2024/2025 1  By the end of this lecture we will be able to : De ne neutropenia. Know how neutropenia is classi ed ? What are the primary and secondary causes of neutropenia ? How to approach such a case ? 2 fi fi  Introduction Neutropenia is a common laboratory nding in adults and children. Its underlying causes are extremely heterogeneous and include benign conditions, autoimmune disorders, infections, and malignancies. The clinical laboratory plays a central role in the diagnosis of these disorders, including data derived from hematology, microbiology, molecular biology/ cytogenetics, and clinical chemistry. The purpose of this review is to (a) highlight the clinical, hematologic, and molecular genetic features of the major entities resulting in neutropenia. (b) outline an algorithm-based approach to permit the classi cation of neutropenias 3 fi fi  the absolute neutrophil count (ANC) of normal adults ranges from 1.5 to 7.0×109/L. the lower limit of the ANC can vary depending on the age and race of the patient. In normal neonates and infants, the lower limit of normal is ~2.5×109/L. In up to ~25% of African American children/adults, the absolute neutrophil count ranges from 1.0 to 1.5×109/L, so it is important to be aware of the age and ethnicity-related di erences in the ANC, to avoid unnecessary testing. 4 ff  HOW IS NEUTROPENIA CLASSIFIED? most laboratories would de ne neutropenia in infants with an ANC < 2.5 × 109/L and in adults with an absolute neutrophil count < 1.5 × 109 5 fi The classi cation of neutropenia on the basis of absolute count into three groups : 6 fi AGE-RELATED CAUSES OF Neutropenia Neonate 1. Infection —by far the most common cause. 2. Maternal hypertension and/or drug treatment. 3. Maternal antibody production. 4. Constitutional disorders, eg, cyclic neutropenia, Kostmann syndrome, Chediak-Higashi syndrome. 7  Infant / child 1. Infection —common. 2. Autoimmune neutropenia. 3. Neoplasms replacing the BM. 4. Idiosyncratic drug reactions. 5. Secondary autoimmune neutropenia in collagen vascular disorders Immunode ciency disorders. 6. Megaloblastic anemia. 7. Myeloablative therapies. 8. Constitutional neutropenia disorders—rare. 9. Copper de ciency—rare. 8 fi fi  Adults 1. Idiosyncratic drug reactions—most common cause in ambulatory patients. 2. Infections—common. 3. Neoplasms replacing the BM—common. 4. Myeloablative therapies—common. 5. Secondary autoimmune neutropenia in collagen vascular disorders. 6. Autoimmune disorders including white blood cell aplasia. 9 Classi cation of Neutropenia on basis of bone marrow reserve It is necessary to have a basic overview of the features of normal granulocyte maturation. Brie y, neutrophils are derived from BM stem cells, which undergo proliferation and di erentiation in the BM. The neutrophils are released into the blood where they have a survival time of ~5-135 hours. It is important to note the circulating neutrophils represent only ~5% of the total number of neutrophils in the body. The remaining 95% of neutrophils are present as maturing granulocytes in the BM and the storage pool, which is de ned as a body of mature neutrophils held by the body in reserve in the marrow. Neutropenia, then, can be a result of failure of any step in this process. 10 fi fl ff fi Neutropenia due to a defect involving the stem cell/maturing granulocyte/storage pool phases is classi ed as : Neutropenia with decreased BM reserve : which are sub classi ed into : -Primary : defect in granulopoises -secondary : suppress in normal granulopoises Neutropenia with normal BM reserve 11 fi fi NEUTROPENIA WITH DECREASED BM RESERVE 12  Inheritance Clinical Disorder Mechanism Characteristic Diagnostic Frequency Sever Apoptosis of AR (kostmann Sever BM: congenital precursors syndrom) neutropenia in Promyelo and Primary neutropenia cells AD ; S ; X linke newborn myeloctes (kostmann ELA2 Rare ~2% progress arrest syndrom) mutations 1-2/million to MDS /AML Infections Hypoplastic Fas mediated steatorrhea BM. granulocyte exocrine Normal sweat Shwachman AR ; S mediated pancreas chloride;; diamond extremly apoptosis defeciency Increase in syndrom rare SBDS ~33% fecal mutation progress fat ;; to MDS/AML Short stature 13 Morphology of marrow sample from patient with severe congenital neutropenia showing maturation arrest at level of promyelocyte 14  Inheritance Clinical Diagnostic Disorder Mechanism Characteristics Frequency Recurrent fever Precursors every 21days , apoptosis;; skin and AD ; S otolaryngeal CBC 2-3 time Cyclic some cases Periodic infections /week for 8 neutropenia with No increase in 1-2/million week ELA2 (ELAN) risk of mutation haematological malignancies Recurrent pyogenic Chediac infections as Mutation in AR oculocutaneous Giant granules higashi albinism due to in many cells LYST gene Rare syndrom decreased in microbcidal activity 15 Chediac-Higashi Syndrome with giant cytoplasmic granules are pathognomonic 16  Large Clonal granular Increase in Common Recurrent fever proliferations of lymphocytes : lymphocytic apoptosis due Up to 80% ;mouth ulcers ; Secondary CD3+/- leukemia and to Of patient with splenomegaly ; CD8+ or related FAS ligand TLGL arthritis CD16/CD56 disorders Or CD57 Severity of BM biopsy Direct toxicity neutropenia indicated when to depend on neutropeniais Chemotherapy Common neutrophils agent ; usually precursors high risk of prolonged infections and severe Comprises 70% Clinical history Direct of cases of Empirical Drug induced suppresion Not neutropenia discontinuation (non immune) of uncommon Fatal in up to 25% of myelopoieses of cases drugs 17 Adult patient with T cell large granular lymphocytic leukemia and neutropenia 18  Protien-calore malnutrition Clinical history Ine ective Nutritional Uncommon Folate; copper; BM. Biopsy if myelopoieses B12 necessary defeciency Viral infection most Direct e ect or Degree of Clinical history commonly immune uncommon neutropenia Viral study if (EBV,CMV,HIV, mediated variable necessary Hepatitis , measles v ) Severe Neutropenia Low birth wt neutropenia Clinical history of infant Not with high risk and neonate- Decreased in uncommon of Antenatal care hypertensive production of infections are important mother neutrophils Self limited 19 ff ff  Infection-related neutropenia in a 3-year-old girl: (A) peripheral blood smear demonstrating neutropenia and (B) BM aspirate smear demonstrating maturation arrest in myeloid lineage 20 21 There are many other congenital conditions associated with neutropenia. In these conditions, the degree of neutropenia is often mild and is not universally identi ed in all cases. These include myelokathexis/neutropenia with tetraploid nuclei, reticular dysgenesis, and dyskeratosis congenita. 22 fi NEUTROPENIA WITH NORMAL BM RESERVE 23  Inheritance Clinical Disorders Mechanism Diagnostic Frequency Characteristic 90% detected Chronic benign before BM. Normal or neutropenia of Antineutrophil 14th month of age increased in common infancy and antibody ANC usually