Understanding Anemia: Types and Causes

• Anemia is a reduction in the total number of erythrocytes in the circulating blood, or a decrease in the quality or quantity of hemoglobin
• Erythrocytes are red blood cells
• Hemoglobin is the oxygen-carrying protein in red blood cells
• Erythropoiesis is the process of red blood cell production
• Hypoxemia is reduced oxygen-carrying capacity of the blood
• Macrocytic-normochromic anemia is characterized by large, abnormally shaped erythrocytes with normal hemoglobin concentrations
• Pernicious anemia is a megaloblastic anemia caused by vitamin B12 deficiency, typically due to intestinal malabsorption from absence of intrinsic factor (IF)
• Folate deficiency anemia stems from a lack of folate
• Microcytic-hypochromic anemia involves small erythrocytes and reduced hemoglobin content
• Iron deficiency anemia (IDA) results from insufficient iron for hemoglobin synthesis
• Thalassemia is characterized by impaired synthesis of globin chains of hemoglobin A
• Normocytic-normochromic anemia includes erythrocytes of normal size and hemoglobin content, but in decreased numbers
• Anemia of blood loss results from acute or chronic blood loss
• Anemias of diminished erythropoiesis are caused by impaired red blood cell production
• Anemias of increased destruction (hemolysis) result from a higher-than-normal rate of red blood cell destruction
• Sickle cell anemia is a hereditary disorder where abnormal hemoglobin synthesis leads to abnormal cell shape and destruction
• Hereditary spherocytosis is an inherited disorder characterized by destruction of mature erythrocytes with abnormal cell membranes and spherical shapes
• Aplastic anemia shows decreased RBCs, WBCs, and platelets(pancytopenia) due to hematopoietic cell destruction
• Anemia of inflammation (AI) is associated with chronic inflammatory conditions
• Renal failure anemia is due to erythropoietin deficiency in chronic kidney disease
• Anisocytosis refers to the varying sizes of erythrocytes
• Poikilocytosis signifies the varying shapes of erythrocytes
• Reticulocytosis indicates an increased number of immature red blood cells in the blood
• Koilonychia are concave, ridged, and brittle nails often seen in iron deficiency anemia
• Glossitis is the inflammation of the tongue, seen in various anemias
• Hypochromic means decreased hemoglobin content
• Normochromic means normal hemoglobin content
• Hyperchromic means increased hemoglobin content
• Macrocytic refers to large cell size
• Microcytic refers to small cell size
• Normocytic refers to normal cell size
• Mean Cell Volume (MCV) measures the average size of red blood cells
• Mean Corpuscular Hemoglobin (MCH) is the average amount of hemoglobin per RBC
• Mean Corpuscular Hemoglobin Concentration (MCHC) is the mean hemoglobin concentration per RBC
• Red Blood Cell Distribution Width (RDW) estimates the variation in red blood cell size
• Erythropoietin is a kidney-secreted hormone stimulating erythropoiesis
• Leukocytes are white blood cells
• Leukocytosis means increased numbers of leukocytes
• Leukopenia means decreased numbers of leukocytes
• Lymphocytes are a type of white blood cell
• Neutrophils are a type of white blood cell
• Lymphocytosis means increased number of lymphocytes
• Atypical lymphocytes are lymphocytes with altered morphology, often observed in infections like infectious mononucleosis (IM)
• Neutropenia means decreased number of neutrophils
• Leukemia refers to cancer of the blood-forming tissues, like bone marrow, with abnormal leukemic cells
• Acute leukemia: Undifferentiated/immature cells (blast cells) with abrupt, rapid onset
• Acute lymphocytic leukemia (ALL): Aggressive, too many lymphoblasts in marrow/blood, primarily affects lymphocyte precursors
• Acute myelogenous leukemia (AML): Aggressive, myeloid lineage, overproduction of neoplastic myeloid stem cells/myeloblasts
• Chronic leukemia: Differentiated predominant cell, abnormal function, relatively slow progression
• Chronic lymphocytic leukemia (CLL): Mature but immunologically immature lymphocytes accumulate, most common adult leukemia in the Western world
• Chronic myelogenous leukemia (CML): Myeloproliferative neoplasm, increased maturing granulocytic precursors in marrow, often involves the Philadelphia chromosome
• Myeloblasts are immature white blood cells that are not lymphoblasts
• Lymphoblasts are immature lymphocytes with altered morphology
• Philadelphia chromosome: Reciprocal translocation between chromosomes 9 and 22, t(9;22)
• BCR-ABL is the fusion gene from the Philadelphia chromosome translocation, creating a protein with unregulated tyrosine kinase activity
• Tyrosine kinase inhibitors (TKIs) block intracellular signals involved in cell growth
• Myeloproliferative neoplasms (MPNs): Diseases characterized by growth factor-independent proliferation in bone marrow
• Myelodysplastic syndrome (MDS) is a group of disorders in which bone marrow doesn't produce enough healthy blood cells
• Leukostasis is an intravascular clumping of leukemic cells leading to infarction/hemorrhage
• Auer rods are fused cytoplasmic granules forming rod-like structures, often seen in AML
• Cellular senescence: Stable cell cycle arrest contributing to a pro-tumorigenic microenvironment
• Minimal residual disease: Small numbers of cancer cells remaining after treatment, can lead to relapse
• Chimeric antigen receptor T cells (CAR-T cells): Genetically engineered T cells target cancer cells

Lymphomas

• Lymphoma: Neoplasms developing from proliferation of malignant lymphocytes in the lymphoid system
• Hodgkin lymphoma (HL): Progresses contiguously, characterized by Hodgkin and Reed-Sternberg (HRS) cells
• Reed-Sternberg (RS) cells: Large, multinucleated cells from B lymphocytes, necessary for HL diagnosis
• Non-Hodgkin lymphoma (NHL): Heterogeneous group lacking HRS cells, diverse biologic and clinical patterns
• Burkitt lymphoma (BL): Aggressive NHL, often involves translocations of the MYC gene
• Diffuse large B-cell lymphoma: Common type of aggressive NHL
• Lymphoblastic lymphoma: Aggressive NHL, more common in children
• Mantle cell lymphoma: A type of B-cell NHL
• Follicular lymphoma: A type of B-cell NHL
• Marginal zone lymphoma: A type of B-cell NHL
• Lymphadenopathy is the enlargement of lymph nodes
• Splenomegaly is the enlargement of the spleen
• Mediastinal mass refers to a tumor in the mediastinum
• Lugano classification: Staging system for lymphomas
• B symptoms: Systemic symptoms like fever, weight loss, and night sweats
• Immunotherapy stimulates or directs the individual's immune system to target cancer cells

Plasma Cell Malignancy

• Plasma cell malignancy: Cancers originating from plasma cells
• Multiple myeloma (MM): Malignancy of plasma cells, abnormal immunoglobulins (M protein) and osteolytic lesions
• M protein: Abnormally large amount of one class of immunoglobulin
• Bence Jones protein: Free light chains of immunoglobulins in urine or serum
• Osteolytic lesions are bone destruction, common in multiple myeloma

Hemostasis and Hemorrhagic Disorders

• Hemostasis refers to the process of stopping bleeding
• Platelets (thrombocytes) are blood cells involved in blood clotting
• Coagulation factors are proteins in the blood that help with blood clotting
• Thrombocytopenia is a low platelet count
• Thrombocythemia (thrombocytosis) is a high platelet count
• Essential thrombocythemia (ET) A chronic myeloproliferative neoplasm with excessive platelet production
• Hemorrhage indicates copious or heavy discharge of blood from blood vessels
• Disseminated intravascular coagulation (DIC): Thrombohemorrhagic disorder, widespread clotting and bleeding due to depletion of factors and platelets
• Traumatic coagulopathy: Coagulation abnormalities from trauma
• Hemolytic uremic syndrome (HUS): Red blood cell destruction, kidney failure, and low platelet count
• Thrombotic thrombocytopenic purpura (TTP): Blood clots in small vessels, low platelet count, and red blood cell destruction
• von Willebrand disease is a genetic disorder affecting blood clotting
• Heparin-induced thrombocytopenia (HIT): Decreased platelet count from heparin treatment
• Immune thrombocytopenia (ITP): Thrombocytopenia due to immune system destroying platelets
• Hypersplenism: Splenomegaly and reduced blood cell count (cytopenias)

Anemias

• Anemia: Reduction in erythrocytes or hemoglobin, reduces oxygen-carrying capacity, leading to tissue hypoxia
• Macrocytic-Normochromic Anemias: Large, abnormal erythrocytes with normal hemoglobin, often from vitamin B12 or folate deficiencies
• Pernicious Anemia: Vitamin B12 deficiency due to lack of intrinsic factor (IF)
• Folate Deficiency Anemia: Lack of folate, similar mechanisms to B12 deficiency, no nervous system manifestations
• Microcytic-Hypochromic Anemias: Small, abnormal erythrocytes with reduced hemoglobin
• Iron Deficiency Anemia (IDA): Lack of iron for hemoglobin synthesis
• Sideroblastic Anemia: Dysfunctional iron uptake and defective porphyrin/heme synthesis
• Normocytic-Normochromic Anemias: Normal size and hemoglobin, but reduced numbers
• Posthemorrhagic Anemia: Acute blood loss
• Aplastic Anemia (AA): Insufficient erythropoiesis, depressed stem cell proliferation
• Hemolytic Anemia: Premature destruction of mature erythrocytes in circulation
• Anemia of Inflammation (AI): Diminished erythropoiesis and impaired iron utilization associated with chronic diseases

Thrombocytopenias

• Heparin-Induced Thrombocytopenia (HIT): Immune reaction to heparin, leading to platelet activation and thrombosis
• Immune Thrombocytopenic Purpura (ITP): Autoimmune destruction of platelets
• Thrombotic Thrombocytopenic Purpura (TTP): Deficiency of ADAMTS13 enzyme, causing excessive platelet adhesion

Essential Thrombocythemia (ET)

• ET is a chronic myeloproliferative neoplasm characterized by excessive platelet production due to a defect in bone marrow megakaryocyte progenitor cells.

Impaired Hemostasis and Lymphomas

• Vitamin K Deficiency causes decreased synthesis of clotting factors
• Liver Disease diminishes production of clotting factors
• Hodgkin Lymphoma (HL) involves Reed-Sternberg cells
• Non-Hodgkin Lymphoma (NHL) is a diverse group without Reed-Sternberg cells

Comparison of Non-Hodgkin Lymphomas

• NHL in adults is more common and B-cell origin, associated with age and exposures
• NHL is less common in children than acute leukemias, subtypes differ with specific translocations and viral infections and is rapid and aggressive

Comparison of Acute and Chronic Leukemias

• Feature | AML | ALL | CML | CLL
• :------------------ | :----------------------| :-------------------------- | :-------------------------- | :--------------------------
• Cell Line | Myeloid | Lymphoid | Myeloid | Lymphocytes
• Onset | Abrupt, rapid | Abrupt, rapid | Slow, insidious | Slow, insidious
• Age | Older adults | Children | Adults | Older adults
• Bone Marrow | Myeloblasts | Lymphoblasts | Hypercellular | Increased number Lymphocytes
• Peripheral Blood | Leukocytosis/penia, blasts | Lymphoblasts | Marked leukocytosis | Lymphocytosis
• Lymphadenopathy | Less common | More common | Rare | Common
• Splenomegaly/Hepatomegaly | May occur | More common | spleen | liver/spleen
• Key Pathophysiology | Differentiation | Dysregulation | BCR-ABL1 | Transformation
• Clinical Manifestations | Fatigue | Fatigue | Fatigue | Asymptomatic