Anemia 2- Krafts Flashcards
Hemoglobinopathies: Things you must know
Part of hemolytic anemias
- Qualitative hemoglobin abnormality
- Sickle cell is most important
- Sickle cells –>hemolysis, vaso-occlusion
- Usually just a point mutation in the beta chain
Hemoglobinopathies:
-Best lab test?
- structurally abnormal Hgb
- Best lab test: Hgb electrophoresis
- Hb chains will migrate to different areas depending on if they have normal, heterozygous, of homozygous traits.
Process of sickle cell formation
- point mutation in beta chain gene (val for glutamat) –>HgbS
- aggregates and polymerizes on deoxygenation –>cell becomes sickle shaped
- hemolyze and also clog up small vessels
Clinical findings in SC anemia
- African Americans (8% are heterozygous)
- variable severity
- Chronic hemolysis
- vaso-occlusive disease
- INCREASE infections (autosplenectomy) –especially encapsulated organisms
Morphology of SCA:
- Sickle cells —DUH
- “Post-splenectomy blood picture”
- nucleated red blood cells
- target cells
- Howell-Jolly bodies: pieces of nucleus left
- Pappenheimer bodies: pieces of iron
- increased platelet count
Tx of SCA:
- Prevent triggers: infection, fever, dehydration, hypoxemia
- Vaccinate against encapsulated bugs (S. pneumoniae & H.influenzae
- Blood transfusion
- Bone marrow transplant
Thalassemia: things you must know
weird size
- Quantitative defect in Hgb
- Can’t make enough alpha or beta chains
- severity varies
- Hypochromic, microcytic anemia with INCREASED RBCs and target cells
Type of Hgb as a fetus?
At birth?
Adult?
Hgb F = 2alpha and 2gamma
At birth you make a little delta (Hgb A2 =2 alpha and 2 delta) –always make a little bit of this.
After birth you start making beta chains for normal Hgb A =2 alpha & 2 beta
Beta Thalassemia is better than alpha. Why?
- can sometime make delta or gamma to make up for loss of Beta chains
- NO replacement for alpha chains :(
Normal globin genes?
4 alpha chain genes
2 beta chain genes
Alpha vs beta thal?
Alpha = DELETION of alpha chain gene Beta = DEFECTIVE beta chain gene (transcription, translation, or mRNA processing)
Beta thal severity?
Beta = normal gene Beta+ = produces some Beta chains Beta^0 = produces NO beta chains
beta-thal minor = asymptomatic
beta thal intermedia = less severe
beta-thal major =severe
Alpha thal problem
Alpha chain genes are ABSENT
- must be missing 3 of 4 genes to get severe disease
- missing all 4 = hydrops fetalis (incompatible with life)
What can cause anemia in alpha thalassemia?
- not enough alpha chains
- Excess unpaired beta, gamma, or delta chains
Newborns -gamma tetramers
Adults - beta tetramers –> eat up my macs
What can cause anemia in beta thal?
- not enough beta chains
- excess unpaired alpha chains
- -> cells get eaten up by macs.
Morphology of Thal?
Hypochromic, microcytic anemia (**MOST COMMON)
- some anisocytosis and poikilocytosis
- target cells
- basophilic stippling
How do you tell IDA from Thal?
- -don’t have as much anisocytosis
- -all cells will be about the same size in Thal
X-ray findings in thalassemia?
- Medually expansion –make bone marrow in places you usually don’t –>skull
- in severe cases only
Alpha Thal: clinical findings
- Asians and African Americans
- Carrier state and thal trait: asymptomatic
- HbH disease: moderate –> severe disease
- Hydrop fetalis: fatal in utero
Beta Thal: clinical findings
Mediterranean, Blacks, Asians
- Thal minor: usually asymptomatic
- Thal major: variable severity, usually presents in infancy.
Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD):
Things to know :)
- decreased G6PD –> increased peroxides –>cell lysis
- Oxidant exposure
- Bite cells (removal of Heinz bodies)
- Self-limiting!
What’s so great about G6PD?
Need G6PD so you have NADPH to keep glutathione in proper state.
Why do G6PD deficient red cells die?
- Can’t reduce nasties!
- ->Nasties attack Hbg bonds
- ->Heme breaks away from globin
- ->globin denatures, sticks to RBC membrane (Heinz body)
- ->Spleen bites out Heinz bodies
Where is highest incidence of G6PD?
-Areas with MALARIA
G6PD deficiency: Clinical Findings
- many asymptomatic
- Others have episodic hemolysis
- Usually you have enough G6PD to be a great person.
- Triggers: FAVA BEANS & DRUGS (antibiotics, aspirin)
- Spontaneous resolution
G6PD deficiency: Morphology
- Without exposure? no anemia
- Exposure to oxidating agent –> acute hemolysis
- -bite cells, fragments
- -Heinz bodies (need special stain)
Microangiopathic Hemolytic anemia (weird shape)
Things you musttttttt know, Morgan:
- physical trauma to RBCs
- Schistocytes (fragmented red cell)
- Find out why! –lots of different reasons that you can help with.
What are the causes of MAHA?
- Artificial heart valve
- Anything causing DIC, TTP, HUS –>get little blood clots all over the body.
(disseminated intravascular coagulation, thrombotic throbocytopenia purpura, hemolytic-uremic sydnrome) –but you don’t need to know these right now :)
How fragmented cells form:
RBC gets caught on fibrin and is ripped open.
Seals itself back up as a fragmented cell / microspherocyte
Schistocyte
in MAHA ONLY.
- Triangulocytes
- No central pallor
Anemias with Normal Shape and Sized RBCs
- Anemia of blood loss
- AOCD
- Anemia in kidney, liver disease
- Aplastic anemia
Anemia of blood loss:
Things to know!
- Cause: traumatic, acute blood loss
- At first, Hbg is NORMAL!!!
- 2-3 days, see reticulocytes (BM is kicking up output)
- Chronic blood loss is different (IDA)
Anemia of Chronic Disease (AOCD)
Things you must know:
- Infections, inflammation, malignancy
- Iron metabolism disturbed
- Normochromic, normocytic anemia
- Anemia usually mild
Pathogenesis of AOCD:
Disturbed iron metabolism–> hepcidin is over produced (ugh, can’t get iron out of storage)
- shortened RBC survival
- Impaired marrow response to anemia
Labs: AOCD vs IDA
ACD: increased ferritin and marrow storage iron. Decreased TIBC
IDA: *decreased ferritin. decreased iron stores. Increased TIBC.
Anemia of Renal Disease: things to know–>
- end stage renal failure
- cause: lack of erythropoietin
- May see echinocytes (bumps on red cell)
What causes anemia of renal disease?
Lack of erythropoietin :((((
Anemia of Renal Disease:
Clinical Features?
Tx?
-Anemia severity roughly == degree of renal failure
tx: mild=none
severe=replace erythropoietin.
Anemia of Liver Disease: things 2 know:
- Anemia is frequent in liver disease (75%)
- lots of causes
- cases are usually complicated
- Might see acanthocytes, targets
Red cell shape in kidney vs liver disease?
Kidney = echinocytes: small bumps on membrane
Liver-acanthocytes: more pointy bumps
Aplastic Anemia: Things to know!
- Pancytopenia (low # of RBC, WBC, platelets)
- Empty Marrow
- Most are idiopathic
Causes of aplastic anemia:
Idiopathic: most common
drugs, viruses, pregnancy, Fanconi anemia (congenital)
Aplastic anemia: Clinical findings?
- Pallor, dizziness, fatgue (anemia
- Recurrent infection (leukopenia)
- Bleeding, brusing (thrombocytopenia)
Tx of aplastic anemia?
- avoid further exposure
- give blood products
- Drugs: G-CSF, prednisone, ATG
- BM transplant as last resort
- 3 yr survival: 70%
