Anemia Flashcards
Anemia is classified either by …
retic count or MCV of red blood cells
Anemias caused by these… tend to have low retic count
defects in cell pathways and abnormal reproduction of RBCs
T or F. Anemia due to loss have decreased retics
F! INCREASED reticulocytes because body is trying to compensate by increasing production and also has the necessary components to do so
4 causes of anemia
- ineffective erythropoiesis
- insufficient erythropoiesis
- excessive blood loss
- hemolysis
describe ineffective erythropoiesis
- defective erythroid precursor production
- cells die before maturing
- increased stimulation by EPO leading to high RBC production but RBC are defective
- lack of critical molecules
anemia with ineffective erythropoiesis
- megaloblastic anemia
- thalassemia
- sideroblastic anemia
- IDA
lack of critical molecules
describe insufficient erythropoiesis
- decrease in # of erythroid precursors in BM so low # of RBCs produced
common causes of insufficient erythropoiesis
- IDA
- decreased EPO
- autoimmune diseases or infections
- replacement of normal hematopoietic cells with malignant cells
stain used for iron studies
Prussian blue
osmotic fragility test
- RBCs in 0.85 saline
- normal patients will reach certain normality before RBCs burst (hypotonic)
- spherocytes = increased fragility; don’t have excess membrane so hypotonic and burst FASTER
- targets = excess membrane = so take longer to lyse; decreased OF
these factors can lead to IDA
- inadequate intake
- increased need (pregnancy, rapid growth periods, etc.)
- impaired absorption (decreased stomach acid, inflam. bowel disease, gastrectomies)
- chronic blood loss (menstrual bleeds, ulcers, etc.)
iron studies in IDA
- decreased iron
- decreased ferritin
- increased TIBC
platelets in IDA
often increased esp. if IDA due to blood loss or in severe anemia; WBC usually normal
T or F. In IDA, normoblasts won’t be as blue
T! bc poorly hemoglobinized ; may also develop ragged cytoplasm
anemia due to sideroblasts
anemia results from ineffective production of heme
- protoporphyrin ring = failure to use iron
- or impaired insertion of iron to ring centre
without iron = cannot carry O2
cause of sideroblastic anemia
- deficiency in ALA or heme synthase
- decreased vit. B6 or interference by drugs
- deficiency in other enzymes necessary for synthesis of heme (congenital)
iron studies in sideroblastic anemia
- increased serum iron (may have enough, just can’t incorporate it)
- increased ferritin
- incr Tsat
PBS findings in sideroblastic anemia
- dimorphic
- basophillic (esp. w lead)
- normal indices, RDW increased
how is sideroblastic anemia acquired?
- hereditary
or acquired - primary = myelodysplastic syndrome (chromosmal damage overtime)
- secondary = more common; due to drugs (which inhibit ALA synthase, etc.)
BM findings for sideroblastic anemia
BM + Prussian Blue = siderocytes
anemia of chronic infection mechanisms
cytokines:
- disturb iron metabolism = incr hepcidin and decrease iron absorption and release; increase lactoferrin and serum ferritin
- diminished erythropoiesis = blunted response to EPO
- decreased red cell lifespan = macs clear minimally damaged RBCs quicker bc they’re on high alert
RBC indices for ACI
all decreased (MCV, MCHC, MCH)
BM findings for ACI
- M:E ratio normal or slightly increased due to HYPOprolifeation of RBCs
(BM suppressed due to inflammation)
iron studies for ACI
- serum iron = decreased
- serum ferritin = increased (sequestered in macs)
- TIBC = decreased
- Tsat = decreased
- BM iron = normal to increased due to sequestration
- elevated ESR and CRP bc of inflammation
If the anemia is caused by ineffective or insufficient erythropoiesis, there will be a __________in retics and the BM will show a _______ M:E ratio
decreased retics
decreased M:E ratio bc trying to ramp up RBC production
root cause of megaloblastic anemia
impaired DNA synthesis
without vitamin B12 or folate, we can’t make this
thymine, one of the nucleotide bases in DNA
vitamin B12 role in NA synthesis
it is the coenzyme necessary for homocysteine to turn into methionine
PBS findings fr megaloblastic anemia
- oval macrocytes
- ## HJ bodies
BM findings for megaloblastic anemia
- hypersegs
- hypercellular; erythroid hyperplasia
- megakaryocytes decreased lobulation
- N:C asynchrony
- pancytopenia
- increased serum iron
- enlarged precursors
clinical presentation megaloblastic anemia
- jaundice
- glossitis
- gastritis
- nausea
- ailments related to GI
anemia caused by _________ causes increased homocysteine levels
folate
- thrombosis
- CV disease
pernicious anemia
- impaired absorption of B12 due to lack of IF
- autoimmune (parietal cells destroyed), gastric bypass, chronic gastric issues
non-megaloblastic anemia
- normal newborn blood
- postsplenectomy
- liver disease
- reticulocytosis
- chronic alcoholism
- bone marrow failure (MDS/AA)
aplastic anemia results from…
bone marrow failure and subsequent decreased hematopoietic cells
causes of aplastic anemia
- acquired: idiopathic of secondary to toxic agents or viruses
- inherited: Fanconi’s, Dyskeratosis congenita Shwachman-Diamond syndrome
Damage to bone marrow can cause (4)
- increased destruction of hem. stem cells (drugs, viruses, autoimmunity)
- decreased self-renewal of hematopoietic stem cells
- infiltration with abnormal cells
- inadequate or impaired microenvironment (decreased growth factors, etc.)
T or F. The majority of AA cases is inherited
F! acquired mostly - idiopathic
Fanconi’s
- AA
- aut recessive
- defect in DNA repair
- increased fetal Hb (macros)
- renal probs, absent/hypoplastic thumb
Dyskeratosis Congenita
- X-linked or autosomal dominant
- abn skin, nail malformation, oral leukoplakia
- dyskerin protein lacking = inability to assemble ribosomes and maintain telomeres
Schwachman-Diamond syndrome
- aut recessive
- SBDS mutation = defect in ribosomal assembly
- affects BM - neuts predominantly so prone to infections
- pancreatic functions affected, skeletal abnormalities, etc.
Pure Red Cell Aplasia
- ACQUIRED through exposure to harmful substances
- no ribosomal assembly and function
- leads to Bm failure
AA CBC and PBS
- pancytopenia
- neuts and PLTs critically low
- low retics despite increased EPO
- normo/mormo or macrocytossis
- no poly or nRBCs
AA BM findings
- hypocellular
- trephine biopsy needed
- iron stores normal to increased
- Tx: BM transplants or continued transfusions
RBC indices in hemolytic anemia
usually N; can be increased due to reticulocytosis
T or F. Iron stores in hemolytic anemia is decreased
F! it is increased due to recycling!!
alpha thalassemia genetics
large deletion that removes one or more alpha genes; chr 16
Hemoglobin H
alpha thal; 3 gene deletion; alpha thal major
- does not precipitate right away but is unstable
- when leave the BM = Heinz bodies
- leads to decreased RBC lifespan and EVH
- still not as severe as B thal
Hb Barts
complete alpha deletion
excess gamma = incompatible with life
Hb S
- sickle cells
- Glu replaced with Val at 6th
- aut co-dom inheritance
- HbS less soluble than HbA
> polymerizes under deoxygenated conditions
> elongate/sickle
> RBCs less deformable
> vasculature occluded; sticky
> deformed RBCs hemolyzed; lifespan 10-20 days
Screens for sickle
HbS solubility test: patient sample with alkaline buffer = Hb precipitates out; HbS = insoluble = turbid
Sickling test: blood + alkaline solution to slide = real time sickling observed under mic
HbC
- Glu to lysine at 6th of B chain
- also polymerizes under low O2 = but less splenic sequestration and hemolysis, milder than HbS
- crystals (in/extracellular), spheros, targets
HbE
- Glu to Lys at 26th
- no clinical symptoms, mild anemia
- problem when co-dom with other Hbinopathies
HbM
- predisposition to form methemoglobin (Fe 3+)
- methemoglobin reductase CANNOT correct this oxidation
G6Pd deficiency tests
- negative DAT
- blister cells
- IVH indicators (incr LD, bili, hemoglobinuria, decrease hapto) or EVH
- decreased G6PD activity
what causes echinocytes in PK deficiency?
- less ATP formed
- Na/K pump fails
- K+ and water leak out
- cells rigid, shrink
RBC indices in HE
normal
T or F. In HE, the elliptos are made in the BM
F! they form like that overtime as they pass through vasculature
T or F. 80-95% of HE are asymptomatic
T!
three clinical findings of HS
- jaundice
- anemia
- splenomegaly
** symptoms often appear early in life**
screens vs confirmatory testing for HS
- EMA (binds to band 3; HS is decreased fluorescence) and osmotic fragility test
- molecular testing
hereditary acanthocytosis
- pts w liver disease may develop HA with acanthocytosis
- excess free cholesterol; mutation in MTP; decreases fluidity in cells
- spleen remodels cells into acanthocytes
- low Hb; normal indices
- EVH
- autosomal recessive
CBC for PNH
- low Hb
- decreased WBcs and PLTs
- elevated MCV due to retics
- loss of iron in urine => IDA?
PNH
red cells lack GPI-anchored proteins = susceptible to spontaneous lysis by complement; also found in WBCs and PLTs
T or F. PNH can lead to BM failure or AA
T
tests for PNH
- IVH tests
- flow cytometry for CD55, CD59
hemolysis markers
- increased LDH (intravascular)
- increased bilirubin (shows increased turnover of heme rings
- decreased haptoglobin
- decrease methemalbumin (occupied by Hb to transport to liver)
