Anemia & Erythrocytosis

anemia - symptoms
weakness, fatigue, SOB on exertion, angina (not enough O2 to heart muscle to meet its needs)
low Hg, low HCT
normal hematocrit (HCT), males & females
hematocrit: RBCs/(RBCs+plasma)
36-42 females
41-47 males (higher b/c androgens stim EPO)
normal hemoglobin males & females
12-14 females
14-16 males
mean corpuscular volume, avg RBC cell size
= volume/cell = hematocrit/ (red cell number)
- 83-102
- tells whether you have microcytic (<83), normocytic, or macrocytic (>102) anemia
microcytic (hypochromic) anemia
2/3 anemias. Of microcytic anemias, iron deficiency is most common.
- Diff dx: Iron deficiency (95%), Beta thalassemia trait, anemia of chronic disease, Refractory anemia w/ ringed sideroblasts (MDS), Lead poisoning, Alpha thalassemia trait, Hypocupremia
- treat: ferrous sulfate TID until hct is normal, then 3-6 mo to replete marrow stores
iron, folate, B-12 absorption
duodenum, jejunum, ileum
iron overload due to genetic error in iron absorption (mucosa absorbs iron even when not needed)
- treat: phlebotomy
macrocytic anemia
likely megaloblastic anemia
- megaloblastic: production of RBCs requires hemoglobulinization and maturation of nucleus. DNA maturation lags behind in folate and B12 def, so RBC precursors show immature (megaloblastic) nuclei
- increased MCV
- other causes: MDS, aplastic anemia, inc reticulocytes
folate deficiency
- causes: inadequate diet (alcoholism), malabsorption (GI diseases), inc need (pregnancy)
- body stores last a few months (B12 - a few years). thus if see macrocytic anemia, likely due to folate, not B12, deficiency
- histo: macrocytic periph smear w/ multilobed polyps
- treat: folic acid
B-12 deficiency
- body stores last a few years (folate - a few months). thus if see macrocytic anemia, likely due to folate, not B12, deficiency
- clinical: DANGER, can cause neurologic deficiencies!
- a diagnosis of B12 def is FOREVER!
- causes: pernicious anemia (cannot absorb b/c lose gastric IF (nec for absorb) due to autoimmune damage), vegan diet, loss/def of terminal ileum
- clinical: palor w/ yellow skin, beefy red tongue, neuropsychiatric: paresthesias, sens loss, dmentia
- treat: Vit B-12 daily, then weekly until HCT is normal. then monthly for life!
anemias of bone marrow failure
normocytic anemias associated with low reticulocyte count
- ddx (6): aplastic anemia, pure red cell aplasia, myelofibrosis, myelodysplasia, myelophthisic anemia, anemia of chronic disease
- get BM biopsy, aspirate, and cytogenetics
6 anemias of BM failure
1. aplastic anemia
2. pure red cell anemia
3. myelofibrosis
4. myelodysplasia*
5. myelophthisic anemia
6. anemia of chronic disease*
* 2 most common
aplastic anemia
anemia of bone marrow failure
a pancytopenia, with HCT<20, neutropenia, thrombocytopenia
- majority acquired
- idiopathic - immune (most common - T cells attack BM precursors)
- secondary - drugs, chemotherapy, toxins (benzene)
- therapy: 1) BM transplant (can normalize blood counts; for younger pts) 2) immune therapy (partial responses; for older pts)
pure red cell aplasia (PRCA)
anemia of BM failure
pure anemia (WBC and platelet counts are normal)
- recticulocytes 0.0-0.2% (really really low!)
- an autoimmune B cell process. most acquired, idiopathic
- drug related (dilantin), post inf (parvovirus), or thymoma related
- treatment: immune therapy, transfusions (deal w/ Fe overload)
- prognosis: survival 10+ yrs
anemia of BM failure (underprod in this case)
clonal myeloproliferative disorder, clonal SC grows in spleen --> massive splenomegaly and reactive BM fibrosis
- tear drop RBCs, nucleated RBCs (can also see these in metastatic tumor replacing BM)
- BM biopsy shows fibrosis; diagnostic
- treat: observation, transfusion support, BMT (young pts)
anemia of BM failure
- erythroid hyperplasia with ineffective erythropoiesis
group of clonal disorders, variable risk of dev leukemia
- determines prognosis: % blasts, cytogenetics, # of dysplastic cell lines
- refractory anemia, ring sideroblasts
- cytogenetics: can be normal
- treat: supportive, maybe EPO/G-CSF, BMT (young pts only)
myelophthisic anemia
anemia due to BM replacement by tumor/ fibrosis/ granuloma/ cells containing storage product (mphages, Gaucher's disease -- rare!)
- treatment: treat primary disorder
anemia of chronic disease
anemia of BM failure
chronic condition (renal failure, liver disease, cancer, RA, endocrine) associated w/ anemia for NO SPEC REASON!
- levels of EPO are lower than expected for degree of anemia
- body behaves as if it has better things to do than make RBCs. mild anemia (HCT > 30)
BM biopsy - 6 anemias of BM failure
1. aplastic anemia - hypoplasia
2. pure red cell anemia - no RBCs
3. myelofibrosis - fibrosis
4. myelodysplasia - ineffective RBC production
5. myelophthisic anemia - infiltration by tumor or other process
6. anemia of chronic disease - normal!!
hemolytic anemia - features
1. high reticulocyte count (though this can be caused by bleeding)
- cresyl blue: stain for ribonucleoprot in retics
- large, grayish on periph blood
2. bilirubin will be elevated and unconjugated (indirect).
- liver disease: elevated bilirubin = conjugated/direct
4. INTRAVASCULAR hemolysis - Hb will bind to haptoglobin, haptoglobin levels DOWN
- extravascular (splenic) hemolysis - normal haptoglobin
- transfusion: drops haptoglobin (some IV hemolysis)
5. abnormal blood smear
hemolytic anemia - causes
1. outside the cell
- antibodies IgG (warm), IgM (cold) --> spherocytes! rouleaux! schistocytes!
- hypersplenism
- microangiopathy/TTP
2. in RBC membrane
- hereditary spherocytosis, elliptocytosis
- paroxysmal nocturnal hemoglobinuria
3. RBC enzymes
- G6Pd deficiency
4. hemoglobin
- SS anemia
- hemoglobin C dis (crystals, target cells)
- hemoglobin M (oxidant sensitive)
- thalassemias
autoimmune hemolytic anemia
acquired disorder, RBC destruction mediated by immunoglobulin (Ig) with or w/o complement
- warm ab: IgG -- fixes on RBCs, binds mphs in spleen, alters RBC surf --> spherocytes (rigid) --> dec survival (though haptoglobin normal b/c extravasc destruction). therapy: corticosteroids (block phagocytosis), splenectomy
- cold ab: IgM -- fixes complement. intravascular lysis -- haptoglobin falls. therapy: keep warm, plasmapheresis, chemo
- test: Coombs test
microangiopathic hemolytic anemia
most common type: thrombotic thrombocytopenic purpura (TTP)
- endothelial damage leads to fibrin deposition which destroys platelets and damages RBCs as they pass thru
- untreated: most die. treated (plasmapheresis) most cured
hereditary spherocytosis
hemolytic anemia
hereditary defect in membrane --> RBCs become spheres --> destroyed in spleen.
- can cause bilirubin gallstones
- splenectomy is curative
- osmotic fragility
paroxysmal nocturnal hemoglobinuria
hemolytic anemia
cells have enhanced susceptibility to complement due to missing surf prots, esp during acidosis (sleeping)
- dx: flow cyt for missing prots
G6Pd deficiency
hemolytic anemia
enzyme problem, X linked, african americans
sensitivity to oxidative stress
sickle cell disease
hemolytic anemia
most common hemoglobinopathy in US
mutant Hb - sickles - deoxygenation -->
pain crisis, aplastic crisis, splenic pooling crisis
- acute chest syndrome
- SS disease, SS trait (no sickle cells on smear)
hemolytic anemia
unbalanced synthesis of alpha and beta chains of hemoglobin
- clinical problem: iron overload (secondary hemochromatosis)
high HCT b/c plasma vol is decreased
HCT = RBC vol/(RBC + plasma vol)
- due to diuretics
- treat: volume repletion
secondary erythrocytosis
reactive condition caused by resetting the erythropoietin mechanism (ie the problem isn't in the BM!)
- physiologic elevation of EPO: chronic lung disease (hypoxia), smoking (CO - hypoxia), high altitude (hypoxia), abnormal Hb (hypoxia)
- abnormal elevation of EPO: renal disease (cysts, tumors), CNS disease, hepatoma, Cushing's, uterine fibroids
- treat: treat underlying disorder, phlebotomy
polycythemia vera
a MPN disorder - clonal myeloprolif disorder, trilineage hyperplasia, but major clinical manifestation is inc red cell mass
- splenomegaly, leukocytosis, thrombocytosis
- prod of RBCs independent of EPO (EPO NOT elevated!)
- JAK2 mutation
- treat: phlebotomy (though high risk for dehydration, stroke in elderly - use for younger pts), hydrea (oral chemo) for older pts