Type Type of Mutation/ Cause Pathogenesis Clinical picture and findings
hemolysis Sickle cell Extravascular Point mutation in beta-globin chain-glu On deoxygenation-polymerizaton and reversible Homozygous: severe anemia, HCT 18-30%, anemia hemolysis replaced by val- S Hb sickling, continued exposure-ireversible – reticulocytosis, hyper-bilirubinemia, crisis Can be homozygous- all chains have mononuclear phagocytosis & microvascular Hetero: asymptomatic until exposure to severe mutation or heterozygous- abt half obstructions. hypoxia chains have mutation Hypospleenism in adults, spleenomegaly in Particularly predisposed with salmonella children- infections. osteomyelitis Thalasemia intravascular α- thalasemia: 4 genes on ch 16 Excessive β- & γ- chains- form stable tetramers Major: hemolysis deletions- 1- silent carries, 4- hydrops (Hb H, Hb bart) low damage, ineffective in O2 Microcytic hypochromic + poikilocytosis fetalis, 3- disease delivery Failure of normal development β- thalasemia: 2 genes on ch 11 Decrease in β-chains – decreased Hb Skeletal deformities, reticulocytosis. point mutations on certain regions of More imp: increase in free α-chains that aggregate, Iron overload – leads to cardiac failure (need gene: in promoter & unsplicing region form inclusion in RBC (reduce plasticity of RBC, iron chelators) of intron- β+ (reduced β-chains) becomes more susceptible to mononuclear Minor In exon & splicing region of intron- β0 phagocytosis) destruction also of blasts – Mild microcytic hypochromic (absence of β-chains) ineffective erythropoisis - iron overload Normal life expectancy G6PD Intra- & extra- G6PD gene on ch X forms G6PD Exposure to drugs, toxins or infections increases H No symptoms unless exposure oxidative injury. deficiency vascular enzyme that regenerates GSH after its peroxide so increases oxidation of GSH to GSSG, In males severe oxidant injury hemolysis oxidation GSH regeneration is impaired so – accum. of H In females asymptomatic Mutation causes more rapid decay of peroxide which denatures Hb. This ppts causing Heinz bodies (precipitated Hb) and bite cells enzyme (A- variant) IVhemolysis and also EVhemolysis in spleen (phagocytosis by splenic phagocytes) Paroxysmal intravascular Acquired membrane defect secondary PIGA deficient BM cells are present in normal PIG-tailed proteins (3 that prevent activation of nocturnal hemolysis to a mutation that involves myeloid individuals, when there is immune-mediated complement on normal RBC’s) cannot be hemoglobinuria stem cells. Mutation in X-linked PIGA destruction or suppression of BM cells by expressed so RBC sensitive to lytic activity of (synthesis of intramembranous recognition of sp. PIG-tailed antigens the PIGA complement, also not expressed on granulocytes glycoprotein anchor – PIG) deficient cells do not express the targets and so and platelets – susceptibility to infections and escape the attack and replace BM IVthrombosis Immuno- Warm: IgG or (rarely) IgA active at 37 Opsonization by IgG and subsequent phagocytosis +ve direct/ indirect coombs test for both hemolytic deg. 60% idiopathic and 40 % by splenic macrophages. Attempts of phagocytosis Chronic mild anemia with moderate anemia underlying disease (SLE) or drugs (a- leads to injured bits of CM – decreased SA:V ratio spleenomegaly methyl dopa, penicillin) – spheroidal cells – sequestration Extravascular Cold: IgM binds to CM below 30 deg. Complement most active at 37 deg. so no Acute during recovery from Mycoplasma hemolysis (in distal parts) IVhemolysis, when cells go to warmer regions pneumonia and infectious mononucleosis or IgM is not well bound but leaves behind C3b chronic resulting in transient mild anemia with opsonin causing phagocytosis by kupffer cells often Raynaud phenomenon (EV) Resulting from Intravascular Valve prostheses and microangiopathic Valves cause abnormal pressure gradient and Burr, hemlet and triangle cells trauma hemolysis (caused by DIC, malignant HT, SLE or turbulent blood flow, and RBCs are squeezed thru disseminated cancer) narrowed vessels, results in mechanical damage in both malaria Intravascular Plasmodium vivax, malariea, ovale & After infecting hepatocytes, merozites infect Spikes of shaking, chills and fever at intervals hemolysis falciparum (most fatal causing cerebral erythrocytes forming trophozites (characteristic to which coincide with merozite release from RBC. malaria and blackwater fever) each specie) which divides giving rise to new Brown discoloration of spleen, liver, lymph merozites that destroy RBCs upon escape nodes & BM, massive spleenomegaly (hyperplasia of mononuclear phagocytes) Anemias of Diminished Erythropoiesis Type Cause Pathogenesis Clinical picture Diagnosis Iron Deficiency Low dietary intake (rare), Starts with decline in serum ferretin and Mostly asymptomatic with weakness Low: Hb, HCT, MCV, serum malabsorption (e.g. gastrectomy), stainable amounts of iron in BM. Followed and pallor in severe cases. Long-term ferretin, iron levels, transferring increased demands (pregnancy, by decrease in circulating iron and rise in severs anemia – thinning, flattening saturation, microcytic hypochromic infants), chronic blood loss (from transferrin iron-binding capacity – impact and spooning of fingernails, pica, RBCs. HIGH total iron-binding GIT – peptic ulcer, hemorrhoids - on Hb, myoglobin and other iron increase in platelet count. Sometimes capacity or female genital tract) compounds. When more severe – impaired develops plummer-vinson syndrome work performance, brain function and immunocompetence Anemia of Occurs in chronic microbial Sequestration of iron from cells from the __ Normocytic normochromic, or chronic disease infections (osteomyelitis, storage compartment (mononuclear hypocytic hypochromic, low serum bacterial endocarditis, lung phagocyte storage pool) and suppression of Treatment: iron, (similar to iron deficiency) abcess), chronic immune erythropoiesis due to inflammatory erythropoietin administration may but: Increased storage iron in disorders (rheumatoid arthritis, mediators (IL-1, TNF, interferon-alpha) that improve but only treatment of marrow macrophages, increased regional enteritis) and neoplasms are released from the underlying disease. underlying condition is reliable serum ferretin, decreased total iron- (Hodgkin, lung & breast cancer) binding capacity Megaloblastic Deficiency of folic acid from vit B12 required for regeneration of Non-specific symptoms relating to Smear of peripheral blood and bone anemia poor diet or increased metabolic tetrahydrofolate, Folic acid provides pancytopenia (weakness, pallor, easy marrow. To differentiate between needs. Or inhibition of folate tetrahydrofolate (carrier of a carbon group) fatigability, petechia, easy infection). vit B12 – serum folate and vit B12 metabolism by methotrexate, so both required for DNA synthesis. Alimentary tract related symptoms are levels and RBC folate levels acidic foods & beans, phenytoin. Deficiency – delay in nuclear maturation common e.g. sore tonge (rapid dividing Low serum vit B12 levels, normal pernicious anemia Impaired and cell division of erythroid precursors GIT cells). In vit B12 deficiency only or elevated folate, histamine-fast absorption of vitamin B12 by: producing megaloblasts (also granulocyte neurological symptoms may take place gastric achlohydria, anti IF *malabsorption (lack of vit B12 precursors produce giant megakaryocytes) e.g. symmetric numbness, tingling, antibodies, megaloblastic anemia uncommon), *autoimmune some megaloblasts have very defective burning in feet or hands, unsteadiness findings, leucopenia, schilling test reaction against parietal cells or DNA that they undergo apoptosis in BM, of gait, loss of position sense (unable to absorb an oral dose of vit IF, others give mature RBC’s but output is *Cellular morphology: hypercellular B12 but when administered with IF *surgery and gut disorders diminished. The enlarged RBCs are prone BM, nuclear-cytoplasmic asynchrony, absorption takes place) (gastrectomy regional enteritis) to premature destruction by mononuclear megaloblasts – delicate finely or *aging (gastric atrophy & phagocyte system leading to accumulation reticulated nuclear chromatin, achlohydria) of iron (in mononuclear phagocytes) megakaryocytes – bizarre multi-lobed nulei Aplastic Suppression of multipotent Autoreactive T-cells (patients respond to Symptoms relating to pancytopenia Differential diagnosis to myeloid stem cells caused by: immunosuppressive therapy aimed at T (weakness pallor, dyspnea, differentiate between it and *idiopathic, *myelotoxic agents cells) where viral antigens, drug-drived petechiae,frequent persistant minor myelophthisic (or other (irradiation or myelotoxic druds), haptens and genetic damage create infections or sudden onset of chills or pancytopenias) – hypocellular BM *drugs and chemicals neoantigens within stem cells that are fever) owing to stem cell failure (antineoplastic drugs, benzene, targets for autoreactive T cells Normocytic, normochromic, *Treatment: BM transplantation v. chloramphenicol, or sensitivity to sometimes slight macrocytic. effective in patients nontransfused sulfonamides, phenylbutazone Reticulocytosis is absent and younger than 40. other patients etc.), *viral infection Spleenomegaly is absent – immunosuppressive therapy Myelophthisic Associated with metastasis Bone marrow failure caused by extensive Anemia and thrombocytopenia Peripheral blood smear shows arising from breast, lung, replacement of BM by tumors or other (pancytopenia) immature RBCs (teardrops) , prostate or thyroid 1ry lesion or lesions slightly elevated WBC count, with myelofibrosis leukoerythroblastosis