-Intrinsic Defects in the red cell membrane skeleton, they leave red cells spheroid and vulnerable to spleen destruction

-Autosomal Dominant b-spectrin

-Autosomal Rec- a-Spectrin

-Life span of cell is 10-20 days

-Ankyrin, Band 4.2, Spectrin mutations

-Frame Shift or Missense Mutation

-Cells appear small, dark, and no central zone of pallor

-Cells have increased mean cell hemoglobin concentration

-Main Clinical Features: Anemia, Splenomegaly, Jaundice

-Red Cell is vulnerable to injury by exogenous and endogenous oxidants

-Abnormalities in the hexose monophosphate shunt or glutathione metabolism from enzyme disfunction

-G-6-PD reduces NADP to NADPH which protect against H2O2

-X-linked Recessive

-G-6-PD (-) and Mediterranean 

-Cause misfolding of the protein

-Causes Hemolytic Anemia

-Heinz Bodies form

-Point Mutation in the sixth codon of Beta-Globin, is a replacement of Glutamate by Valine (HbS)

-Autosomal Recessive

-Major Pathogenesis: Chronic Hemolysis, Microvascular occlusions, Tissue Damage

-Inherited Defect in HbA formation on chromosome 11

-Beta-Thalassemia Major, Minor, intermedia

-Major: B+/B+, B+/B',B'/B'

-Minor:B/B+, B/B'

-Intermedia:B+/B+, B+/B'

-Major Path: Ineffective Erythropoiesis, Extravascular Hemolysis, Anemia, Skeletal Deformities, Systemic Iron overload

-Deletions on chromosome 16 that removes 1-4 Alpha-Globin Genes

-Barts Syndrome- Gamma-4

-HbH- Beta-4

-Silent Carrier- One Deletion

-a-T trait- (a/a,-/-) or (a/-,a/-)

-HbH Disease- Deletion of three genes

-Hydrops Fetalis-Deletion of all 4 genes

-Mutation in the PIGA gene, enzyme needed for formation of cell surface enzymes

-Acquired Genetic Defect

-PGI-linked proteins are deficient

-X-linked

-Causes susceptibility to the complement system

-Three proteins are messed up:CD59, CD55, C8

-Cells lyse more easily while asleep (decrease in pH of Blood)

-Caused by antibodies that bind to RBC's leading to there immature destruction

-Warm Antibody Type

    -IgG antibodies active at 37 degrees

    -Can be drug induced (drug binds to RBC)

-Cold Agglutinin Type

    -IgM antibodies

    -Bind to RBC in vascular beds

    -Leaves C3b attached(spleen breaks cell down)

-Cold Hemolysin Type

    -IgG antibody mediated

    -Bind to the P blood group antigen on RBC

    -Occurs in cold areas of the body (periphery)

-Some type of blockage or rough area causes red cells to fragment

-Leads to Schistocyte formation (helmet cells)

-Impairment of DNA synthesis that leads to morphologic changes in RBC's

-Pernicious Anemia (Autoimmune Gastritis and IF formation def, leads to b12 Deficiency)

-Folate Deficient Anemia (Due to Diet)

-Both are coenzymes for thymidine formation

-Path: Macrocytic and Oval RBC's, Larger Overly segmented nuetrophils, anisocytosis, poikilocytosis.

-Can be caused by diet, impaired absorption, blood loss, or increased need. 

-TMPRSS6- gene that silences hepcidin, if it is mutated then hepcidin will be two high

-Causes a hypochromic microcytic anemia

-Impaired red cell production due to chronic disease

1. Chronic Microbial Infection

2. Chronic Immune Disorders 

3. Neoplasms

-IL-6 stimulates an increase in hepcidin which causes decreased iron absorption and also causes a large amount if iron to be stored

-Bacteria need iron so body stops the absorption

-Lysine is substituted for Glutamate at the 6th amino acid in B-Globin

-Causes cells to crystalize and clog the microvascular system

-Causes mild hemolysis

-Hemolytic Anemia

-RBC's become echinocytes of blood smears

-Autosomal Recessive inheritance

-Excess PEP therefore this will cause an increase in 2,3-BPG

-Chronic Primary Hematopoietic failure

-Marrow suppression caused by autoimmunity, drugs, chemical agents, infection, radiation, or inherited defects.

-Marrow is not working properly, therefore the marrow will not contain cells of the hematopoietic lineage.

-Space occupying lesions replace normal marrow elements

-Cancer is a common cause