iMLS-HEMATOLOGY

Heme biosynthesis occurs in the mitochondria and cytoplasm of bone marrow erythroid precursors

Neutrophil development occurs in the BM and share common progenitor with monocytes (GM-). Neutrophil production is stimulated by G-CSF. Three pools of developing neutrophils in the BM exist: the stem cell pool, the proliferation pool, and the maturation pool. The stem cell pool consists of HSCs capable of self-renewal and differentiation; The proliferation (mitotic) pool consists of cells that are dividing in order of maturation include: Common myeloid progenitors (CFU-GEMMs), GM progenitors, myeloblasts; promyelocytes; and myelocytes. Maturation (storage) pool consist of cells undergoing nuclear maturation and are available for release: metamyelocytes, band neutrophils, and segmented neutrophils.

Iron deficiency anemia develops when the intake of iron is inadequate to meet a standard level of demand, when the need for iron expands without compensated intake, when there is impaired absorption, or when there is chronic loss of hemoglobin from the body.

Anemia of chronic inflammation only ranks behind Iron deficiency anemia found mostly in hospitalized patients, Associated with systemic diseases/chronic inflammation such as rheumatoid arthritis, chronic infections such as tuberculosis or HIV infection, and malignancies. Sideroblastic anemias result from diseases that interfere with the production of protoporphyrin. As in iron deficiency, the anemia may be microcytic and hypochromic. In contrast to iron deficiency, however, iron is abundant in the bone marrow. Iron overload may be primary, as in hereditary hemochromatosis, or secondary to chronic anemias and their treatments. In both cases the toxic effects of excess iron lead to serious problems as lipids, proteins, nucleic acids, and heme iron become oxidized.

The root cause of megaloblastic anemia is impaired DNA synthesis. When either folate or vitamin B₁₂ is deficient, thymidine nucleotide production for DNA synthesis is impaired. Megaloblastic anemia is one example of a macrocytic anemia.

The root cause of megaloblastic anemia is impaired DNA synthesis. When either folate or vitamin B₁₂ is deficient, thymidine nucleotide production for DNA synthesis is impaired. Megaloblastic anemia is one example of a macrocytic anemia..

Hemoglobinopathies are the most common genetic diseases, affecting approximately 7% of the world’s population. All hemoglobinopathies result from a genetic mutation in one or more genes that affect hemoglobin synthesis. Mutated gene may code for either globin chains or proteins involved in their synthesis. All hemoglobinopathies affect hemoglobin synthesis in one of two ways: Qualitatively or Quantitatively

Thalassemias are divided into β-thalassemias, which include all the disorders of reduced globin chain production arising from the β-globin gene cluster on chromosome 11, and α-thalassemias, which involve the genes for the α1 and α2 chains on chromosome 16. Deletional and non-deletional mutations can cause each of these disorders. 

Intrinsic hemolytic anemias comprise a large group of disorders in which defects in the red blood cells (RBCs) result in premature hemolysis and anemia. Intrinsic disorders can be divided into abnormalities of the RBC membrane, metabolic enzymes, or hemoglobin. Most of these defects are hereditary.

Intrinsic hemolytic anemias comprise a large group of disorders in which defects in the red blood cells (RBCs) result in premature hemolysis and anemia. Intrinsic disorders can be divided into abnormalities of the RBC membrane, metabolic enzymes, or hemoglobin. Most of these defects are hereditary.

Hereditary ovalocytosis or Southeast Asian ovalocytosis (SAO) is a condition caused by a mutation in the gene for band 3 that results in increased rigidity of the membrane and resistance to invasion by malaria. It is common in the malaria belt of Southeast Asia, where its prevalence can reach 30%. The inheritance pattern is autosomal dominant, and all patients identified are heterozygous.

Extrinsic hemolytic anemias comprise a diverse group of disorders in which RBCs are structurally and functionally normal, but a condition outside of the RBCs causes premature hemolysis. The extrinsic hemolytic anemias can be divided into conditions with nonimmune and immune causes.

A common feature in the nonimmune extrinsic hemolytic anemias is the presence of a condition that causes physical or mechanical injury to the RBCs. This injury can be caused by abnormalities in the microvasculature (microangiopathic) or the heart and large blood vessels (macroangiopathic), infectious agents, chemicals, drugs, venoms, or extensive burns.

In immune hemolytic anemia, hemolysis is mediated by antibodies, complement, or both.

Examination of a peripheral blood film (PBF) is important in suspected extrinsic hemolytic anemias, because observation of abnormal RBC morphology, such as schistocytes, spherocytes, or the presence of intracellular organisms, provides an important clue to the diagnosis.

This chapter concentrates on leukocyte disorders that are not caused by clonal or neoplastic changes in hematopoietic precursor cells.

Primarily a disease of childhood and adolescence peaks at 2-5 yrs of age. It is rare in adults, seen in >50, with risk increased with age. Adults get high complete remission (90%) but cure- rate is <40%.

The most common leukemia in adult and incidences increase with age. It is less common in children.

MPNs are clonal hematopoietic disorders caused by genetic mutations in the HSCs that result in expansion, excessive production, and accumulation of mature erythrocytes, granulocytes, and platelets.

It is an expansion of one or more myeloid cell lines, but one cell line dominates. MPNs can manifest in chronic with accelerated, subacute, or acute phases; and can be transformed into other MPNs or Acute leukemias.

Mature lymphoid neoplasms are a diverse collection of disease entities with varying clinical presentations and natural histories;

Lymphoproliferative disorders in which the primary site of disease is the blood or bone marrow are classified as leukemias; disorders in which the localization of disease is in the lymph nodes and spleen are considered lymphomas.

These categories are not mutually exclusive; there are disorders, such as chronic lymphocytic leukemia (CLL), in which the neoplastic cells are prominent in the blood yet also involve the spleen and lymph nodes. Likewise, lymphomas may have a leukemic phase in which the malignant cells are found in the peripheral blood.

MDS are a group of acquired clonal hematologic disorders characterized by progressive cytopenias in the peripheral blood, reflecting defects in erythroid, myeloid, and/or megakaryocytic maturation, and increased risk for the disease to transform into AML.

Median age of diagnosis is 76 years old. MDS rarely affect individuals younger than age 50 unless preceded by chemotherapy or radiation. However, De novo mutations (primary MDS) account for most of the cases in elderly people.

Platelet disorders are classified as quantitative (numerical) or qualitative (functional). Quantitative disorders are those in which the platelet count is either below (thrombocytopenia) or above (thrombocytosis) the reference interval. Qualitative disorders involve an abnormality of some aspect of platelet function. Characteristic manifestations of the hemostatic defect seen in patients with platelet disorders are petechiae and excess bleeding from superficial areas of the body such as the skin and mucous membranes.

Manual cell counts are performed using a hemacytometer, or counting chamber, and manual dilutions made with calibrated, automated pipettes and diluents. The principle for the performance of cell counts is the same for WBCs, RBCs, and platelets; only the dilution, diluting fluid, and area counted vary.