Myeloid cells: Granulocytes (neutrophils, eosinophils, basophils) Neutrophils maturation in BM: 7-10 days, circulates in blood: 1 day, duration in tissue: 2-3 days Monocytes Macrophages Gaucher’s Disease: Autosomal recessive lysosomal storage disorder Caused by a deficiency of the enzyme glucocerebrosidase (GBA gene) Cells accumulate in the liver, spleen, and bone marrow Classic “crumpled tissue paper” appearance (Buzz word) Dendritic cells Mast cells Lymphocytes: B cells T
Hemoglobinopathy Sickle Cell Disease (discussed below) Thalassemia (discussed below) Hemoglobin C Substitution of lysine for glutamic acid in 6th position of the beta globin chain Subtypes: Hb AC (Hb C trait): No symptoms Hb CC (Hb C disease): Causes HbC crystals Symptoms: anemia, mild hemolytic anemia (prone to gallstone), splenomegaly Hb SC: less sickling and vaso-occlusive events compared to Hb SS More retinopathy, priapism and ischemic necrosis of bones Hemoglobin E Su
Qualitative: Defects in membrane glycoproteins Bernard-Soulier Syndrome (GPIb/IX/V) Glanzmann Thrombasthenia (GPIIB/IIIa) Collagen Defects (GPVI and GPIa/IIa) Defect in platelet granules Storage Pool Deficiency Gray Platelet Syndrome Quebec Platelet Disorder Hermanksy Pudlak syndrome Defects in platelet secretion and signaling Defects in platelet coagulant activity Defects of transcription factors RUNX1 Defects of cytoskeletal/structural proteins Wiskott-Aldrich Syndrome B1-T
Iron Metabolism: ~ 4000 mg of iron per person Mostly stored in the erythrocytes ( ~ 2700 mg) and liver ( ~ 1000 mg) Homeostasis is balance between absorption vs. loss Absorption is regulated Intestinal absorption can fluctuate in response to Iron status Erythropoietic demand Hypoxia Inflammation Normally absorb 1-2 mg iron/day Loss is unregulated Physiologic exfoliation (hair, skin) Bleeding (physiologic, hemorrhage) Reproductive (iron needed to make a new human) Transferrin
Major components of hemostasis: Primary hemostasis (platelet plug) Defects lead to mucosal bleeding (petechiae, purpura, epistaxis)...
Types of transplant: Allogeneic HCT: Infusion of hematopoietic cells ( CD34⁺ ) from a HLA-compatible donor after cytotoxic conditioning to eradicate disease and enable engraftment. Used in order to deliver high doses of chemotherapy + “graft vs. tumor” (GVT) effect GVT affect: immune-mediated cytotoxic effect exerted by donor-derived immune cells against the recipient’s neoplastic cells following allo-HCT ~30-50% of allo-HCT develops with acute GVHD (aGVHD) Most commonly used
Bone marrow failure: Disrupted hematopoietic stem and progenitor homeostasis → Inadequate WBC, RBC, Plt Pancytopenia differential diagnosis: Autoimmune: HLH, TTP, Lupus, Evan’s syndrome Malignancy: Leukemia, lymphoma, metastatic tumors (myelophthistic), myelofibrosis Infectious Metabolic/Toxins: B12/folate deficiency, excess zinc, storage diseases, alcoholism Bone marrow failure (least common cause) Acquired Bone Marrow Failure: Rapid onset, no family history, usually associa
Anemia of chronic disease: Mediated by IL-6 Promotes hepcidin expression → decreased intestinal absorption and storage of ferritin in macrophages Transferrin downregulated Erythropoiesis becomes iron restricted (since iron not accessible) May eventually lead to iron deficiency due to lack of GI absorption Hemolytic anemia (Separate section below) Iron deficiency anemia (Separate post " Iron Metabolism and Diseases ") Iron refractory iron deficiency anemia (IRIDA): Inherit
