MMSC 433 Final
MDS-RS-SLD (MDS with ringed sideroblasts, single lineage dysplasia)
-*1 dysplastic lineage* -1-2 cytopenias -*≥15% ringed sideroblasts* -BM <5% blasts -PB <1% blasts -no auer rods -cytogenetics: anything that does not cause MDS-5q-
MDS-SLD (MDS with single lineage dysplasia)
-*1 dysplastic lineage* -1-2 cytopenias -<15% ringed sideroblasts -BM <5% blasts -PB <1% blasts -no auer rods -cytogenetics: anything that does not cause MDS-5q-
MDS-RS-MLD (MDS with ringed sideroblasts, multilineage dysplasia)
-*2-3 dysplastic lineages* -1-3 cytopenias -*≥15% ringed sideroblasts* -BM <5% blasts -PB <1% blasts -no auer ords -cytogenetics: anything that does not cause MDS-5q-
MDS-MLD (MDS with multilineage dysplasia)
-*2-3 dysplastic lineages* -1-3 cytopenias -<15% ringed sideroblasts -BM <5% blasts -PB <1% blasts -no auer rods -cytogenetics: anything that does not cause MDS-5q-
MDS-U defining cytogenetic abnormality (MDS unclassifiable with defining cytogenetic abnormality)
-0 dysplastic lineages -1-3 cytopenias -<15% ringed sideroblasts -BM <5% blasts -PB <1% blasts -no auer rods -cytogenetics: must be some kind of MDS-defining abnormality
MDS-EB-2 (MDS with excess blasts subtype 2)
-0-3 dysplastic lineages -1-3 cytopenias -none or any ringed sideroblasts -*BM 10-19% blasts* -*PB 5-19% blasts* -*auer rods may be present* -cytogenetics: anything
MDS-EB-1 (MDS with excess blasts subtype 1)
-0-3 dysplastic lineages -1-3 cytopenias -none or any ringed sideroblasts -*BM 5-9% blasts* -*PB 2-4% blasts* -no auer rods -cytogenetics: anything
MDS-U with SLD and pancytopenia (MDS unclassifiable with SLD and pancytopenia)
-1 dysplastic lineage -*3 cytopenias* -none or any ringed sideroblasts -BM <5% blasts -PB <1% blasts -no auer rods -cytogenetics: anything
MDS-5q- (MDS with isolated 5q-/ MDS with isolated del(5q))
-1-3 dysplastic lineages -1-2 cytopenias -none or any ringed sideroblasts -BM <5% blasts -PB <1% blasts -no auer rods -cytogenetics: *5q-* (deletion of long arm of chromosome 5) alone, or with another abnormality such as -7 or 7q-
MDS-U refractory cytopenia of childhood (MDS unclassifiable refractory cytopenia of childhood)
-1-3 dysplastic lineages -1-3 cytopenias -*no ringed sideroblasts* -BM <5% blasts -PB <2% blasts -cytogenetics: anything
MDS-U 1% blood blasts (MDS unclassifiable with 1% blood blasts)
-1-3 dysplastic lineages -1-3 cytopenias -none or any ringed sideroblasts -BM <5% blasts -*PB = 1% blasts* -no auer rods -cytogenetics: anything
chronic myeloid leukemia (CML) treatments
-BM transplant or SCT= CURE -*gleevec* (imatnib mesylate) -sprycel, dasigna, bosulib, iclusig
pre-PMF criteria (WHO)
-Major: increased megakaryopoiesis, increased granulopoiesis, decreased erythropoiesis, NO reticulin fibrosis, hypercellular BM, JAK2, CALR, or MPL mutation present -minor: anemia not attributed to another condition, leukocytosis 11*10⁹/L, palpable splenomegaly, LDH increased
G6PD deficiency lab findings
-N/N anemia -decreased H/H -anisocytosis/ poikilocytosis -spherocytes, schistocytes and heinz bodies present in PB -increased retics, polychromasia -serum haptoglobin, LDH and indirect bili increased (hemolysis) -fluorescent spot test negative
MDS RBC morphology
-PB: oval macrocytes, hypochromic microcytes, dimorphic RBC population (some big, some small), poikilocytosis, basophilic stippling, Howell-Jolly bodies, siderocytes (prussian blue)/pappenheimer bodies (wright stain) -BM: multi-nucleated RBC precursors, abnormal nuclear shapes (lobes, buds, fragments, nuclear bridging), ringed sideroblasts, megablastoid cellular devleopment
hereditary pyropoikilocytosis (HPP)
-a variant of HE that causes extreme poikilocytosis with a large number of schistocytes -EMA binding test: low fluorescence -increased thermal sensitivity (fragmentation at 41-45 C) -low MCV
G6PD deficiency
-decrase in G6PD enzyme causes underproduction of NADPH, leading to inability to reduce glutathione for detox of H2O2 -H2O2 oxidizes hemoglobin in the RBCs, leading to formation of *heinz bodies* -can be induced by oxidative drugs -symptoms: jaundice, anemia, hyperbilirubinemia -N/N anemia -anisocytosis, poikilocytosis -spherocytes and schistocytes in PB -*heinz bodies seen with crystal violet* -G6PD activity decreased -fluorescent spot test negative
disorders of ineffective erythropoiesis
-megaloblsatic anemia -aplastic anemia
DNA synthesis
-methionine synthase and its vitamin B12 cofactor transfer a methyl group from 5-methyl THF to homocysteine, generating methionine and THF -THF is converted to 5,10- methelene THF by gaining methyl groups from serine - 5,10-methylene THF is converted to dUMP -dUMP is converted to dTMP -dTMP is converted to *dTTP*, which is used in DNA synthesis
stage 3 iron deficiency (frank anemia)
-patient exhibits fatigue, weakness, pallor, glossitis, koilonychia and pica -*H/H decreased* -*hypochromic/ microcytic anemia* -FEP, TIBC and sTR increased -ferritin, hepcidin and serum iron decreased
vitamin B12 (cobalamin) absorption
-pepsin and HCL remove B12 from food products, B12 binds to haptochorrin -B12 is cleaved from haptochorrin by pancreatic protases -parietal cells release intrinsic factor, which binds to B12 and allows it to be taken up into enterocytes via cuban receptors -IF and B12 are separated in the enterocyte, and B12 binds to transcobalamin to be transported through portal circulation -B12 is used as a coenzyme in DNA synthesis
fanconi's anemia (FA) symptoms
-physical malformations present at birth in 2/3 of affected individuals -radial hypoplasia, microencephaly, hip dislocation, hyper/ hypopigmentation, short stature, low birth weight, *triphalangeal thumb* -bone marrow failure by age 40 -increased risk of cancers/ tumors
chronic myeloid leukemia (CML) accelerated phase criteria (WHO)
-poor response to therapy -anemia is increased (hemoglobin is decreased) -mature WBCs decreased -basophils increased -platelets decreased -micromegakaryocytes & megakaryocyte fragments present -WBC count increased >10*10⁹ and unresponsive to therapy -splenomegaly unresponsive to therapy -thrombocytosis OR thrombocytopenia -≥20% blasts in PB -10-19% blasts in BM -additional clonal chromosomal abnormalities (other than philadelphia chromosome) appear
hereditary spherocytosis (HS)
-proteins in the RBC membrane disrupt *vertical* interactions and destabilize the lipid bilayer, causing loss of membrane material that leads to formation of spherocytes -mutations in genes for *ankyrin*, alpha and beta spectrin or protein 4.2 lead to increased membrane permeability to Na+ and K+, leading to cellular dehydration -splenic conditioning: abnormal RBCs are targeted by macrophages and lead to anemia -HS triad: N/N anemia, jaundice and splenomegaly -*spherocytes* and polychromasia in PB -increased MCHC and RDW -increased osmotic fragility -EMA binding test: low fluorescence -autohemolysis test: 10-50%, decreased in presence of glucose
PK deficiency lab findings
-reticulocytosis -anisocytosis, poikilocytosis -increased bili and LDH -decreased haptoglobin -normal osmotic fragility -autohemolysis test does *not* correct itself in presence of glucose -fluorescent spot test increased
hereditary elliptocytosis (HE) treatment
-splenectomy -RBC transfusions to treat anemia
hereditary pyropoikilocytosis (HPP) treatment
-splenectomy and supportive transfusions
hereditary spherocytosis (HS) treatment
-splenectomy: prevents targeting of RBCs by splenic macrophages and keeps cells in circulation longer
stage 2 iron deficiency (exhaustion of iron storage pool)
-subclinical symptoms -hemoglobin in retics is decreased, *hemogram appears normal still* -iron deficiency erythropoiesis is occurring -hepcidin decreased -serum iron and ferritin decreased -RDW, TIBC and sTRs increased -prussian blue stain of BM is negative for iron
MDS treatments
-supportive care: transfusions, pain meds -lealidomide, azacytidine, deitabine -growth factors: EPO/ erythropoietin, TPO/ thrombopoietin, G-CSF/ granulocyte colony stimulating factors -immunosupressive therapy -faresyltransferase inhibitors -hematopoietic stem cell transplant (cure)
aplastic anemia lab findings
-symptoms: insidious onset, pallor, fatigue, tachycardia, hypotension, cardiac failure, bleeding (petechiae, ecchymoses), fever-neutropenia -pancytopenia -low Hgb -retics decreased -serum iron and % transferrin saturation increased -neutropenia -increased adipocytes in bone marrow, severe hypocellularity of RBC precurors
hereditary hemochromatosis treatment
-therapeutic phlebotomy: 500 mL of blood is removed per week to decrease serum iron
polycythemia vera (PV) treatments
-therapeutic phlebotomy: bring Hct ≤45% -hydroxyurea -busulfan -JAK inhibitors: Ruxolitinib, Lestaurtinib
babesia
-tick transmitted disease -can be transmitted by transfusion of infected blood unit -symptoms: can be asymptomatic, fever, chills, headache, sweats, nausea, fatigue, jaundice, splenomegaly, hepatomegaly -H/H decreased -reticulocytosis -decreased serum haptoglobin -bilirubinemia -leukopenia, thrombocytopenia -hemoglobinuria, proteinuria
iron deficiency anemia treatment
-treat underlying cause of poor iron status (correct diet, bleeding, malabsorption, etc.) -oral or parenteral supplemental iron -BRC transfusion (extreme cases only)
hereditary xerocytosis (HX) treatment
-usually not necessary -supportive transfusions
G6PD class III
10-60% activity of G6PD
G6PD class IV
60-150% activity of G6PD -no clinical symptoms
G6PD class I
<1% activity of G6PD
G6PD class II
<10% activity of G6PD -*can be induced by fava beans*
G6PD class V
>150% G6PD activity -no clinical symptoms
polycythemia vera (PV) chromosomal abnormality
JAK2V617F mutation (most cases)
chronic myeloid leukemia (CML) chromosomal abnormality
Philadelphia chromosome (~95% of cases)
stomatocytes
RBC morphology associated with Rh null syndrome
250-400 (ug/dL)
TIBC reference range
pancytopenia
a decreased in all cell lines (WBC, RBC and PLT) -can be caused by deficiency of folate/ B12
myeloproliferative meoplasms (MPN)
clonal hematopoietic disorders caused by genetic mutations in hematopoietic stem cells taht cause expansion, excess production and accumulation of the cell lines (erythrocytes, granulocytes and platelets) -each MPN is characterized by the clonal expansion or one or more specific cell lines
5q-
deletion of the long arm of chromosome 5 -long arm of chromosome 5 contains genes to produce growth factor cytokines -without these cytokines, there is a lack of growth and differentiation of the cell lines leading to MDS
12-160 (ng/mL)
female serum ferritin reference range
auer rods
formed by granules fusing together -appear like lines that are branching off of the nucleus
Fanconi's anemia (FA) treatment
hematopoietic stem cell transplant in BM
plasmodium knowlessi
infects RBCs of all ages -ring forms can have multiple rings in same RBC -trophozoites visible on thin smears
plasmodium falciparum
infects RBCs of all ages, leading to high level of parasitemia -gametocytes cause crescent shaped RBC -most severe form of malaria, *leads to cerebral malaria*
plasmodium malariae
infects older RBCs -band form causes a thin, dark band to form across the RBC
plasmodium ovale
infects reticulocytes -infected cells appear oval shaped with fringed edges -Schuffner's slipping present in trophozoite stage
plasmodium vivax
infects reticulocytes with *duffy antigens present* -trophozoites cause ring forms in RBCs -infected RBCs appear enlarged -schuffner's stippling and ameboid appearance in infected RBCs -schizonts visible in thin smears -merezoites cause formation of brown hemozoin pigment
ringed sideroblasts
iron congregates in the mitochondria of developing erythroblasts -*hallmark of sideroblastic anemia*
40-400 (ng/mL)
male serum ferritin reference range
20-55(%)
percent transferrin saturation reference range
transferrin
plasma carrier protein for ferrous iron
basophilic stippling
ribosomal RNA in reticulocytes breaks down -*hallmark of lead poisoning*
50-160 (ug/dL)
serum iron reference range
prussian blue stain
stain that is used to identify iron in tissues and bone marrow
polycythemia vera minor criteria (WHO)
subnormal serum EPO levels
schillings test
test that was once used to diagnose pernicious anemia -part 1: oral intake of radiolabeled B12 and IM dose of nonlabeled B12, 24 hour urine sample is assesed for absorption of vitamins (>5%= normal, <5%=impaired absorption) -part 2: if part 1 is impaired, test is repeated with addition of intrinsic factor to oral dose (>5%= pernicious anemia due to lack of IF, <5%= malabsorptive disorder)
ferrous iron
the form of iron that is able to be utilized in the body for developing red cells
hereditary xerocytosis (HX)
-inherited mutation of the PIEZ01 gene leads to defects in membrane permeability that allows K+ to leak out of the cell, leading to dehydrated RBCs -symptoms: mild to moderate anemia, hydrops fetalis, jaundice and splenomegaly -reticulocytosis -increased MCHC -decreased osmotic fragility -stomatocytes, target cells, burr cells -*puddled hemoglobin* (shown in picture)
sideroblastic anemia
-iron deposits in the mitochondria of erythroblast cells in the bone marrow interfere with biosynthesis of heme -caused by genetic inheritance, drugs/ bone marrow toxins (*lead*, antibiotics, chemotherapeutics) -*ringed sideroblasts* are highly indicative of the disease -basophillic stippling is common in lead poisoning -normocytic normochromic cells
overt PMF criteria (WHO)
-major: increased megakaryopoiesis with either reticulin or collagen fibrosis, presence of JAK2, CALR or MPL mutation present, no other WHO diagnosis availible -minor: anemia not due to another disease, leukocytosis < 11x10⁹/L, palpable splenomegaly, LDH increased, leukoerythroblastosis (immature Grans and RBCs in PB)
PNH pathophysiology
-acquired stem cell mutation that results in lack of GPI anchor proteins, so CD55 and CD59 are unable to stay on the surface of cells -lack of CD55 and CD59 regulatory proteins prevents shutting off complement cascade, MAC continues lysing cells -RBCs are lysed leading to intravascular hemolysis -hemoglobinuria is most pronounced in the mornings
anemia of chronic inflammation
-anemia occurring secondary to underlying condition (chronic inflammatory disease, chronic infection or malignancy) that causes release of cell products -hepcidin, lactoferrin and inflammatory cytokines cause decreased iron status and anemia -low Hgb -*low TIBC* (hepcidin is increased due to acute phase reaction) -normocytic normochromic anemia -serum iron decreased -ferritin (acute phase reactant) and FEP increased
stage 1 iron deficiency (progressive loss of storage iron)
-asymptomatic -RBCs develop normally -*serum ferritin low*
pernicious anemia (PA)
-autoimmune destruction of parietal cells by CD4+ T cells leads to lack of intrinsic factor, which inhibits B12 absorption -B12 deficiency inhibits DNA synthesis, leading to anemia and megaloblastic RBCs -symptoms: usually appear in 6th decade of life, fever, glossitis, lack of appetite, neurologic abnormalities (pins and needles, numbness, hallucinations, paranoia/ megaloblastic maddness) -*serum B12 decreased* -achlorhydria: lack of H+ in stomach -increased gastrin -decreased H/H -*blocking antibodies to IF and parietal cells -macrocytosis -pancytopenia -hypersegmented neutrophils -treatment: intramuscular injection of B12
iron deficiency anemia (IDA)
-caused by inadequate intake, increased need or malabsorption of iron, poor diet or chronic blood loss -symptoms: fatigue, weakness, pallor, spooning of the nails (koilonychia) and pica -*H/H decreased* -microcytic, hypochromic cells -marked poikilocytosis (target cells, spherocytes, tear drop cells and schistocytes) -FEP, sTR and TIBC increased -ferritin, hepcidin and serum iron decreased
fanconi's anemia (FA) lab findings
-chromosome instability testing: increased breakage when exposed to DNA cross-linked agents (diepoxybutane or mitomycin C) -lymphocytes have increased chromosomal fragility -pancytopenia -reticulocytopenia -hypocellular BM -macrocytic RBCs (increased MCV)
chronic myeloproliferative disorders
-chronic myeloid leukemia (CML) -polycythemia vera (PV) -essential thrombocythemia (ET) -primary myelofibrosis (PMF) -chronic neutrophilic leukemia (CNL) -chronic myelomonocytic leukemia (CMML) -juvenile myelomonocytic leukemia (JMML)
fanconi's anemia (FA) etiology
-congenital form of aplastic anemia due to inherited bone marrow failure -inheritance of *FANCA* or FANCB gene leads to chromosome instability and increased breakage when exposed to DNA cross linking agents
anemia of chronic inflammation treatment
-erythropoietin (EPO) hormone treatment -iron supplements
chronic myeloid leukemia (CML)
-etiology: a single genetic translocation in a pluripotent hematopoietic stem cell causes clonal overproduction of immature neutrophils, usually diagnosed between age 45-55 -chromosomal abnormality: Philadelphia chromosome -morphology: myeloblasts, promyelovytes, bands, segmented neutrophils (all stages of neutrophil development) seen in the peripheral blood, nRBCs present, *gaucher-like macrophages present*, very small megakaryocytes present -symptoms: infections with Strep pneumoniae, anemia, bleeding, splenomegaly -PB: RBCs normal to inc, retics normal, total WBCs increased, granulocytes increased (neutrophils, basophils, eosinophils), PLTs normal to inc, *LAP stain decreased* -BM: hypercellular, increased granulopoiesis, decreased erythropoiesis, megakaryopoiesis increased, reticulin fibers increased
juvenile myelomonocytic leukemia (JMML)
-etiology: aggressive hematopoietic disorder that presents in childhood (~2 years old) -chromosomal abnormality: 1. PTPN-11, K-RAS, N-RAS, CBL or NF1 mutations seen in ~90% of cases, Philadelphia chromosome *NOT* implicated -morphology: dysplsatic/ abnormal monocytes -symptoms: splenomegaly, anemia -PB: leukocytosis, monocytosis (≥ 1*10⁹/L), thrombocytopenia, >20% blasts -BM: increase of myeloid and monocytic cells (hypercellular), >20% blasts
essential thrombocythemia (ET)
-etiology: clonal myeloproliferative neoplasm leading to increased megakaryopoiesis and thrombocytosis -chromosomal abnormality: JAK2V617F most common, CALR and MPL mutations also common (others possible: MPL W515L/K, TET2, ASX1, LNK, IDH1/2) -morphology: giant, agranular platelets, platelet clusters, RBCs are N/N -symptoms: vascular occlusion in digits, veins & arteries, splenomegaly, erythromyelalgia (throbbing/ burning in hands and feet) -PB: *increased PLT count* (≥450*10⁹/L) , Hgb/Hct slightly decreased, RBC count normal, total WBCs normal to inc, segmented neutrophils increased, *platelet function decreased* -BM: hypercellular, increased megakaryocytes, large/ variably sized megs with hyperlobulated/ dense nuclei, clusters of megs, mainly proliferation of megakaryocytes is seen, erythropoiesis increased, *reticulin fibers normal to mildly inc.*
chronic myelomonocytic leukemia (CMML)
-etiology: malignant hematopoietic stem cells lead to bone marrow dysplasia and monocytosis, may transition to AML -chromosomal abnormality: deletion of chromosome 7, trisomy 8 -morphology: monocytes make up ≥10% total WBCs in PB -symptoms: hepatoplenomegaly -PB: ≥20% blasts, persistent monocytosis >1*10⁹/L, increased monocytes -BM: ≥20% blasts, BM dysplasia
polycythemia vera (PV)
-etiology: neoplastic clonal stem cells mature independently of EPO stimulation, causing panmyelosis with a predominate increase in erythrocytes (grans and PLTs can be increased too) -Chromosomal abnormality: JAK2V617F mutation -morphology: N/N RBCs, teardrop cells (dacrocytes) present -symptoms: triad of BM fibrosis, splenomegaly and anemia w/ teardrop cells (dacrocytes) -lab findings: Hgb/ Hct/ RCM increased, low serum EPO levels -PB: RBCs increased, total WBCs increased, granulocytes increased, PLTs increased, *LAP stain normal to inc.* -BM: hypercellular, normoblasts (immature RBCs) increased, granulocytes increased, megakaryocytes increased, reticulin fibers increased
chronic neutrophilic leukemia (CNL)
-etiology: rare clonal disorder that causes hyperproliferation of neutrophilic cells in the bone marrow, may progress to AML -chromosomal abnormality: +8, +9, +21, Del(20q), Del(11q), del(12p), philadelphia chromosome *NOT * implicated -morphology: *extreme neutrophilia*, increased neutrophil precursors (segmented neutrophils, bands), neutrophils containing toxic granules, decreased monocytes, RBCs and PLTs are normal -symptoms: hepatosplenomegaly, mucocutaneous bleeds, gout, pruritis (itching) -PB: extreme neutrophilia (<70% of cells), WBC count increased >25x10⁹/L, monocytes decreased < 1x10⁹/L -BM: hypercellular, increased neutrophils, myeloblasts >5% of nucleated cells
essential thrombocythemia (ET) criteria (WHO)
-major: platelet count ≥ 450x10⁹/ L, BM biopsy showing mainly enlarged megakaryocytes with hyperlobulated nuclei, no significant increase in reticulin fibers, presence of JAK2, CALR or MPL mutations, does not meet requirements for different diagnosis -minor: presence of clonal marker OR absence of reactive thrombocytosis
primary myelofibrosis (PMF)
-etiology: splenomegaly and ineffective hematopoiesis caused by hypercellularity, fibrosis and increased megakaryocytosis of the bone marrow -chromosomal abnormality: JAK2V617F most common (also possible: MPL W515L/K, CBL, TET2, ASXL1, LNK, EZH2, IDH1/2) -morphology: tear drop cells (dacrocytes), nRBCs, anisocytosis, poikilocytosis, polychromasia, abnormal platelets and micromegakaryocytes present -symptoms: fatigue, pruritis (itching), bone pain, palpitations, night sweats, splenomegaly, hepatomegaly -Lab findings: Hgb normal to decreased -PB: normoblasts (immature RBCs) increased, immature granulocytes increased, total WBCs variable, PLT count variable, megakaryocytes present, LAP stain variable -BM: *INTENSE fibrosis* (lots of reticulin and collagen fibers), hypercellular, increased granulocytes and megakaryocytes, erythropoiesis and myelofibrosis increased, sinuses increased, dysmegakaryopoiesis and dysgranulopoiesis present -*dry tap on bone marrow aspiration due to extent of fibrosis*
iron absorption
-ferric iron is taken in from diet -ferric iron is reduced by duodenal cytochrome B to become ferrous iron -ferrous iron is absorbed into enterocytes by DMT 1 -absorbed iron is stored as ferritin, or sent into portal hepatic circulation and carried by transferrin to developing RBCs
folate absorption
-folate polyglutamate is taken in from the diet, and converted to folate monoglutamate -folate monoglutamate is taken up into enterocytes and converted into 5-methyl THF - 5-methyl HF is released into circulation and is taken up by cells to catalyze reactions needed for DNA synthesis
polycythemia vera major criteria (WHO)
-hemoglobin >16.5 g/dL (men), >16 g/dL (women) -Hct >49% (men), >48% (women) -increased RCM >35 mL/kg (men), >31 mL/kg (women) -BM biopsy with hypercellularity and panmyelosis -presence of JAK2V617F or JAK2 Exon 12 mutations
low iron level regulation
-hepcidin is down regulated by hepatocytes -ferroportin becomes activated and transports iron out of the enterocytes and into circulation
high iron level regulation
-hepcidin is released from hepatocytes -ferroportin is inactivated, leading to decreased iron being transported into circulation
cytokines in anemia of chronic inflammation
-hepcidin: inflammation causes release of hepcidin as acute phase reactant (not due to adequate iron levels), inactivating ferroportin and inhibiting iron release into circulation -lactoferrin: activated neutrophils release lactoferrin to compete with bacteria for iron, lactoferrin will out-compete body cells for iron -cytokines: TNF alpha, INF gamma, IL1, etc. interfere with ferrokinetics and erythropoiesis, leading to anemia
autohemolysis test (HS vs. PK deficiency)
-hereditary spherocytosis: 10-50% hemolysis, corrected by adding glucose -PK deficiency: adding glucose to system does NOT decrease hemolysis
primary myelofibrosis (PMF) treatments
-hydroxyurea -JAK2 inhibitors: Ruxolitinib, Lestaurtinib -CYT387 -TG101348
essential thrombocythemia (ET) treatments
-hydroxyurea -JAK2 inhibitors: Ruxolitinib, Lestaurtinib -low dose aspirin (prevents thromboses)
megaloblastic anemia
-impaired DNA synthesis due to deficiency of Vitamin B12 and/ or folate leads to decreased number of cell divisions -produces large macrocytes with immature nuclei -symptoms: fever, glossitis, loss of appetite, neurologic abnormalities (pins and needles, numbness, hallucinations and paranoia/ megaloblastic madness) -pancytopenia -decreased H/H -macrocytosis -increased MCV, high RDW -hypersegmented neutrophils -nuclear cytoplasmic asynchrony _M:E ratio 1:1 to 1:3 -teardrop cells, schistocytes and microspherocytes in PB -Howell jolly bodies (DNA remnants) and cabot rings (figure 8) -increased bilirubin and LDH
methylmalonic acid
-in the absence of vitamin B12, the activity of methyl malonyl CoA reductase is inhibited -high serum levels of methylmalonic acids build up -common in B12 deficiencies (i.e. pernicious anemia)
hereditary hemochromatosis (HH)
-inheritance of mutated HFE gene inhibits production of hepcidin, leading to constant activation of ferroportin -increased levels of iron in circulation are exposed to oxygen and produce damaging superoxide ions -symptoms: begin between 30-40, iron deposits on organs (pancreas), bronzed diabetes, cell death, release of lysosomal enzymes -increased serum ferritin and transferrin saturation -genetic testing reveals mutated HFE gene
hereditary elliptocytosis (HE)
-inherited hemolytic anemia caused by defective *alpha* / beta spectrin, or protein 4.1 that disrupts *horizontal* interactions in the RBC cytoskeleton -mutations in *SPTA1*, SPTB and EP41 genes disrupt interactions of the spectrin dimer and destabilize the cytoskeleton, forming elliptocytes -symptoms: usually asymptomatic, mild compensated anemia -*cigar shaped elliptocytes* -increased osmotic fragility
< 40 (ug/dL)
FEP reference range
