Anemia Flashcards
DAT negative AIHA
- IgA mediated
- Antibody under the limit of detection
- Strongly adherent so coated cells rapidly cleared
List 5 factors that influence physiologic variation in hemoglobin level
Age Gender Race Altitude Heredity Degree of sexual maturation Physical activity
List 2 reasons for a falsely reduced and elevated hemoglobin using an automated counter
Falsely reduced: diluted sample, clot in sample
Falsely elevated: lipema or anything else that increases turbidity of the sample
Inaccurate device could cause either
PNH: Name genetic defect, classic presentation, diagnostic test, mechanism of hemolysis, treatment
- PIGA mutation
- Presents with hemoglobinuria (DAT neg), venous thrombosis, defective erythropoesis (macrocytosis, SAA)
- Test: Flow for CD55/59
- Unable to stop complement activation hence hemolysis
- Eculuzimab
List risks of splenectomy
- sepsis
- thrombosis (particularly for stomatocytosis)
- bleeding
Complications of chronic hemolytic anemia
- hemolytic crisis with infection
- Aplastic crisis with parvo
- Gallstones
- Iron overload
- Folate deficiency (rare in NA with supplementation in all foods)
- Iron loading
- splenic rupture (and need for splenectomy)
What are the causes of iron deficiency anemia?
1-Inadequate absorption
a) poor bioavailaibility: cows milk, eating inhibitors, high pH state
b) absorptive loss/dysfunction: duodenectomy, gluten sensitive enteropathy
2-Excessive loss-GI (parasites),GU, pulmonary
3-Functional inaccessibility
anemia of chronic disease/infection/inflam
IRIDA
What is the bioavailiabity of iron in cows milk vs breastmilk
breastmilk about 50%
cows milk 5-10%
What is IRIDA?
iron refractory iron deficiency anemia
caused by mutation in TMPRSS6-gene that encodes a transmembrane protease called serine 6; this inhibits the signaling pathway which activates hepcidin
What are the CBC features of IRIDA?
severe MCV 50-60 anemia not responsive to iron very low transferrin saturation borderline low ferritin high hepcidin levels diagnosis is made by genetic testing
in iron deficiency anemia when do you expect reticulocytosis to occur upon starting treatment with iron?
usually peaks between day 5-10 of treatment, and then a rise in Hb will be seen
what is transferrin?
it carries iron in the plasma to the transferrin receptors on surface of erythroid precursors
It carries 0.1% of the total body iron
what is ferritin?
stores iron within the cells, allows iron to be mobilized when needed. Ferritin carries about 25% of total body iron, especially in liver and RE system
How is iron distributed throughout the body?
transferrin 0.1%
ferritin 25%
tissues (ie myoglobin, cytochromes)7%
Hb-70%
where in the GI tract is iron absorbed?
duodenum, it can adjust and increase absorption by 10x if needed
What foods are inhibitors of iron absorption
vegetable fiber
cows milk
tea/tannins
egg yolk
what is hepcidin?
a regulatory hormone, made by liver, circulates in the plasma and excreted by kidney
it is a negative regulator of cellular iron export
ie in iron deficiency hepcidin is down regulated
iron overload hepcidin is up regulated
Hepcidin’s mechanism of action is to downregulate ferroportin, the only known iron transport channel-works by taking iron from duodenum into plasma, where then iron can be bound to transferrin
What are the stages of iron depletion in iron deficiency anemia?
Iron depletion: tissue iron stores decrease, see lower ferritin
Iron-deficient erythropoiesis: RE stores are depleted, ferritin drops an the TF saturation drops
Iron def anemia-see a drop in MCV and Hb
What does TIBC measure?
measures transferrin (pretty crude test)
how do you calculate the transferrin saturation?
Serum Fe/TIBC
in iron deficiency Tf is low
what is the difference between heme and non-heme iron?
Iron is absorbed as heme iron (from hemoglobin and myoglobin in meat) and nonheme iron (iron salts extracted from plant and dairy foods
non-heme iron is poorly absorbed compared to the bioavailable heme iron
What are indications to use parenteral iron?
1-Not responding to oral iron:
because of non-compliance
severe bowel disease preventing oral iron
chronic blood loss that oral iron can’t keep up as the replacement
2- Functional iron deficiency:
IRIDA
patients on dialysis that failed EPO
*for patients that for religious reasons can’t have blood transfusion
for lead poisioning what is seen on the peripheral smear?
basophilic stippling in the erythrocytes
What is the major function of B12 and folate?
both a required for DNA synthesis
what is a megaloblast?
red cell with reduced DNA replication due to either B12 or folate deficiency
see nuclear to cytoplasmic dyssynchrony where the cytoplasm is more developed than the nucleus
in megaloblastic anemia where are patients icteric?
due to ineffective erythropoiesis there’s more RBC precursors broken down in the bone marrow, releasing excess amounts of heme that is catabolized to bilirubin
Where in the GI tract is B12 and folate absorbed?
B12-is bound to IF and absorbed in the terminal ileum
folate absorbed in proximal jejunum
What are the causes of B12 deficiency?
1-Intake-vegetarians
2-IF deficiency-gastrectomy, autoimmune gastritis
3-Competition-tape worm, bacterial overgrowth due to intestinal stasis
4-Receptor deficiency (problems with absorption)-ileal resection, crohns, imerslund-grasbeck syndrome
5-Defective B12 transport-Transcobalamin II deficiency
6-disorders of B12 metabolism
what are the causes of folate deficiency?
1-intake: malnutrition or high requirement states pregnancy, hemolysis
2-Malabsorption- jejunal resection, gluten enteropathy, crohns, short gut, tropical sprue
3-other-anti-folate meds MTX
4-Disorders of folic acid metabolism-MTHFR deficiency
what are the non-heme complications of folate deficiency?
neural tube defects
thrombosis (theorectically) due to elevated homocysteine levels
what does methylmalonic acid test for?
if elevated indicated B12 deficiency, both urine and serum
what are other causes of megaloblastic anemia?
MDS AML (M6) congenital dyserythropoietic anemia hereditary orotic aciduria thiamine responsive megaloblastic anemia
Hemoglobinuria indicates what type of hemolysis
Intravascular
2) What is the composition of the RBC membrane?
Spectrin is the major component, alpha and beta spectrin that are vertically placed in the lipid bilayer through the intercession of smaller proteins (ankyrin, 4.2) to membrane spanning proteins-band 3, Rh antigen and glycophorin A
3) What is the inheritance pattern of HS?
Autosomal Dominant-makes up 75% of the cases
4) Mutation in which membrane protein is the most common in HS?
Ankyrin (about 60% cases), occurs in both dominant and recessive forms of the disease, and can vary in severity from mild-severe. Mutations in HS affect the vertical proteins, which causes a loss in membrane lipid and surface area-leading to the spherocyte shape-cells are less flexible and get stuck in the spleen
5) What two tests together are very specific for HS?
MCHC (elevated) and RDW (elevated)
6) What is the osmotic fragility test?
HS cells have increased osmotic fragility, spherocytes lyse in higher concentrations of sodium than normal RBCs do
7) In hereditary elliptocytosis which proteins are mutated?
Deficiency of Spectrin (alpha)-65%, spectrin (beta)-30%, protein 4.1, glycophorin C
8) What is hereditary pyropoikilocytosis (HPP)?
Have spectrin chain mutations, congenital hemolytic anemia, classified under HE
9) For HPP, what clinical test can confirm the diagnosis?
In vitro incubation for 10 mins at 45C will cause hemolysis, RBCs are very sensitive to heat
10) What are the two type of hereditary stomatocytosis?
Overhydrated stomatocytosis due to loss of membrane protein stomatin (subsequently have too much sodium inside RBC) and dehydrated stomatocytosis due to mutations in PIEZO1 (mechanotransduction protein) (lose too much K+ and not appropriately compensated for by gaining Na+)
11) What should be avoided in hereditary stomatocytosis?
Splenectomy, seems these patients have an increased risk of post splenectomy thrombosis
12) What is a differential diagnosis for acquired acanthocytosis?
Anorexia, renal failure, MAHA, thyroid disease, liver disease (there’s an imbalance in loading of cholesterol and phospholipid onto the RBC membrane, can cause an even more brisk hemolysis
Describe PNH
A clonal disorder, caused by a mutation in PIGA gene which encodes for the GPI anchor. This anchor is seen on all cell surfaces and is responsible for binding complement regulatory proteins-this increases sensitivity to complement mediated hemolysis
14) What two complement regulatory proteins are no longer present on the cell surfaces in PNH?
CD55 and CD59 are regulatory proteins that are not present, which leads to chronic hemolysis
15) What are the 3 major clinical presentations of PNH?
Aplastic anemia and bone marrow failure
Chronic hemolysis-paroxysmal intravascular hemolysis-causes back pain, usually comes in intervals every few weeks
Thrombosis
16) What is the inheritance of PK deficiency?
AR
17) In PK deficiency, what happens to the oxygen dissociation curve?
Due to the deficiency of PK, there’s upregulation of 2,3 DPG and other intermediaries, causing a right shift. This allows for better off-loading of oxygen to the tissues and allows for patients to better tolerate their anemia
18) What is the inheritance pattern of G6PD?
x-linked
19) What are the WHO classes of G6PD?
Class I-2% normal activity (patients have chronic non-spherocytic hemolytic anemia), Class II-3%, have intermittent hemolysis, class III-10-60% activity hemolysis with drugs/infection, class IV-100% no hemolysis
20) For warm Autoimmune hemolytic anemia what is the associated antibody type?
IgG
21) For the treatment of AIHA, in what time frame do you expect a response in the Hb?
Within 4-7 days there should be a response
22) What second line treatments should be used if AIHA is not responding to steroid?
IVIG, Rituximab, plasmapheresis, immune modulators-MMF, CSA and danazol, antimetabolites-Azathioprine and 6-MP, rarely cyclophosphamide and vincristine are used, splenectomy
23) Why is plasmapheresis not a very useful treatment for AIHA?
Most of the antibodies are extravascular, most of the antibody is bound to the RBC membrane and little is free in the plasma
24) What antibody is involved in cold AIHA?
IgM-occurs due to production of antibodies during mycoplasma pneumoniae infection (can also occur with mono, CMV) antibodies target the I/i system
25) For cold AIHA what result do you expect for the DAT?
Negative for IgG can be positive for Complement
26) What treatment should be considered for cold AIHA?
Keep patient warm, if transfusing blood use a warmer to 37C, plasmapheresis works very well since IgM is mostly intravascular due to its size, if needed could use cyclophosphamide or rituximab with plasmapheresis, steroids do not work
27) What is the antibody associated with Paroxysmal cold hemoglobinuria?
IgG with anti-P specificity, found in children after a viral infection
28) How do patients clinically present with PCH?
Usually have a severe illness then they will have a sudden drop of their hemoglobin and have hemoglobinuria, likely needing transfusion. Antibody is usually made only for a short period of time
30) How is PCH treated?
Keep patient warm, keep blood warm during transfusion, plasmapheresis may help
