mccarthy- heme Flashcards
what is anemia
reduction of the oxygen transporting capacity of blood.
3 ways anemia can come about
- bleeding, 2. increased red blood cell (RBC’s) destruction or 3. decreased RBC production.
healthy individual, anemia from acute bleed or increased RBC destruction will result in what?
compensatory hyperplasia of the erythroid (RBC) activity in the bone marrow.
- with appearance of increased reticulocytes in blood
what are reticulocytes?
immature erythrocytes (RBC) that still contain ribosomes
one to two days in the circulation reticulocytes will lose their _______ and become what?
ribosomes and become mature RBCs
stable conditions: normal reticulocyte count
1% (0.5-1.5).
normal retic. count with anemia, is this normal?
no, its inappropriately low
if your anemic and its normal- thats not good, it should be up to a bout 5% for “appropriate response for anemia”
define hematopoiesis
Multipotential stem cell gives rise to progenitor cells committed to a single line of cell development.
two types of WBC
granulocytes + monocytes
renal failure caused anemia is anemia without what?
an anemia w/out increase in reticulocyte count
it is anemia secondary to decrease erythropoietin production
RBC development requires what from the kidney? what type of environment prompts the kidney to produce this?
erythropoietin - this increases production secondary to hypoxia
how long is the lifespan of an RBC? where is it broken down at the end of this life? what parts of it are reused?
120 days- spleen
-Fe and amino acids
indirect bilirubin is a product of what? what does it go on to form?
product of :breakdown of RBCs transported to the liver-. Its then conjugated to direct bilirubin and secreted in bile
Increase RBC breakdown causes ______ indirect bilirubin and ___ LDH.
incr indirect bilirubin
increase LDH
FE from RBC breakdown transported on ________ to bone marrow to be used for what?
transferrin (transport protein)- (glycoprotein w/ two receptors for iron)
used again in RBC production
what is TBIC?
Receptor sites on transferrin represent total iron binding capacity (TIBC).
normal labe values Hgb/HCT ratio? what bout Hgb for females and males?
Hgb/HCT 1:3 ratio
Female Hgb > 12 gm
Male Hgb > 13.5 gm
microcytic vs normocytic vs macrocyctic ? (MCV levels)
Microcytic MCV < 80
Normocytic MCV 80-100
Macrocytic MCV > 100
what does MCV stand for?
Mean corpuscular volume (MCV) measures the average red blood cell volume, meaning the actual size of the cells themselves.
3 Ddx for microcytic anemia?
- FE deficiency
- pt w/ thalassemia gene
- anemia of chronic disease
what are microcytic anemias with normal iron, normal TIBC, normal to increased Ferritin, and normal to increased reticulocyte count?
Thalassemias (Thal)
what do you use to Dx thlassemia?
Hgb electrophoresis
normal values for Hgb electrophoresis? (A, A2 and F)
A>95% alph2 beta2.
A2 <3% alpha2 delta2
F<1% alpha2 gamma2
FE deficiency: lab values and treatment?
lab:
Beta Thal trait (AB0) what is the dx and txt?
Dx: asymptomatic: labs: mild increase in reticulocyte count
HgB electrophoresis: increase A2
Txt: none required
Beta Thal major (B0B0) what is the dx and txt?
Dx: symptomatic @ 6months
HgB electrophoresis:↑F, ↑A2. No A.
Txt: regular maintenance blood transfusions, plus iron chelators to avoid iron overload. (secondary hemochromatosis)
Alpha thal trait: dx and txt ?
Dx: asymptomatic: labs + HgB electrophoresis normal
*- CBC of one parents shows similar degree of microcytosis
Txt: none needed
Alpha thal major: dx and txt?
die in utero
*two bad genes- no alpha chain synthesis
anemia of chronic disease: dx and txt?
Dx: ↓ FE serum, ↓ TIBC, normal to incr. ferritin, normal to low retic. count
Txt: treat underlying disease
anemia of chronic disease: what are the 3 potential causes and what is the MCV?
(chronic infections, inflammation, or malignancy)
1/3 have mild microcytosis; 2/3 normocyte.
what is hemoglobin F?
Hemoglobin F is replaced by hemoglobin A (adult hemoglobin) shortly after birth; only very small amounts of hemoglobin F are made after birth. Some diseases, such as sickle cell disease, aplastic anemia, and leukemia, have abnormal types of hemoglobin and higher amounts of hemoglobin F
what is Hgb S vs Hgb C?
Hemoglobin S. This type of hemoglobin is present in sickle cell disease.
Hemoglobin C. This type of hemoglobin does not carry oxygen well.
most common cause of death in sickle cell adult? what do you need to give them ?
acute chest syndrome - pulmonary infiltrates and atrial hypoxemia
-need abx for pneumonia + probably transfusion
anemia of renal failure: Dx and Txt
normocytic anemia
Dx: ↑BUN/creatinine
Txt: erythropoietin, monitor Fe stores.
what is your target Hgb for txt of renal failure?
Target hemoglobin of 11 if patient on dialysis. Pre-dialysis patient target hemoglobin of 10.
what is macrocytic anemia? what 2 things are in your differential?
MCV > 100
- megaloblastic - DNA maturation defect- B12 deficient or folate deficiency
- myelodysplastic syndrome
Dx of both B12 deficiency and Folate deficiency will show up with what lab results? (peripheral smear, LDH, indirect bili, retic count) ?
Dx: megaloblastic changes on peripheral smear (hyper-segmented PMN’s (aka granulocytes).
↑LDH ↑ indirect bilirubin; normal retic. count
_______- macrocytic megaloblastic anemia WITH neurological manifestations
__________- macrocytic megaloblastic anemia WITHOUT neurological manifestations
B12 deficiency- WITH
folate deficiency- WITHOUT
txt for B12 deficiency
IM B12 replacement therapy. Daily for one week; weekly until anemia corrected then monthly for life (1 mg or 1000 mcg.). Maintenance therapy can be with 1 mg po qd.
txt for folate deficiency
folic acid 1 mg., po qd.; if secondary to malabsorption 5 mg. P. qd.
what happens if you txt someone with B12 deficiency with folic acid?
Folic acid given to patients with B12 deficiency will partially correct the anemia but will worsen to neurologic disease.
what is myelodysplastic syndrome ?
an MSC (multipotent stem cell) defect that can present with anemia or any combination of cytopenia secondary to ineffective hematopoiesis (hypercellular bone marrow with peripheral cytopenia).
what causes myelodysplastic syndrome in those younger and older than 50?
older than 50yo: MSC defect
younger- radiation or chemo drug
Bone marrow evaluation in patient with macrocytic anemia with normal B12 and RBC folate level. What would this be for?
myelodysplastic syndrome
what 2 things causes B12 deficiency?
- Most commonly: pernicious anemia (an autoimmune disease) creating a deficiency of intrinsic factor
- Total gastrectomy or ileal resection
what does intrinsic factor do?
intrinsic (from parietal cells of stomach) binds b-12 and prevents it from being broken down. Isn’t absorbed until the terminal ileum. without stomach acid you cant remove b12 from food
what causes folate deficiency?
secondary to poor P.O. intake (alcoholic); malabsorption;
what is aplastic anemia caused by?
autoimmune medicated destruction of hematopoietic stem cells by T-cells.
(normocytic anemia)
lab values for severe Aplastic anemia (AA)? (absolute neutrophil, plts, retic count)
absolute neutrophil count: < 500
platelets: < 20,000
reticulocyte count: low (less than 1 %) with accompanying anemia.
Hgb electrophoresis for sickle cell disease vs sickle cell trait?
disease: (Example: S-90%, A2-2%, F-8%,)
trait: (Example: S- 40%, A2- 2%, A-57%, F-1% ).
what is AIHA (autoimmune hemolytic anemia) ?
Autoantibody directed against own RBC surface antigen.
Antibody coated RBC are destroyed in the spleen by macrophages
what are the symptoms and lab results of AIHA?
Clinical symptoms of anemia
LAB: anemia; ↑reti count, ↑LDH; ↑indirect bilirubin; ↓haptoglobin (protein that complexes with free hemoglobulin)
autoantibody vs alloantibody
Autoantibody: an antibody against self
alloantibody : an antibody against foreign antigens
Dx of AIHA?
positive direct and indirect coombs test
direct vs indirect coombs test
direct Coombs test: measures IgG or C3 (compliment) on RBC SURFACE
Indirect Coombs test: measures antibodies in the SERUM; could be an autoantibody or alloantibody.
what if you have a positive indirect but negative direct coombs test?
alloantibody from prior transfusion or pregnancy; not AIHA.
txt for AIHA
Prednisone; would also place patient of folic acid because of increase demand.
what is G6PD deficiency?
Glucose-6-Phosphate Dehydrogenase Deficiency:
self-limited hemolysis - RBCs are destroyed faster than they can be replaced = decreased O2 perfusion to tissues.
most don’t develop symptoms until exposed to
- infection or drugs - (an Oxidative stress)
what population gets G6PD ?
An X linked genetic disorder:
Females carries; males have the disease. Black males most commonly
Dx of G6PD deficiency
G-6-PD level, if normal repeat in 3 months.
you do this b/c if you got this right after an attack (O2 stress) - it would show normal
what is a hemolytic transfusion rxn?
intravascular hemolysis: when someone is given the wrong blood type in transfusion- their immune system destroys the new RBCs
clinical symptoms + labs of hemolytic transfusion rxn
Clinical: fever; chills; chest pain
Lab: serum and urine free hemoglobin (hallmark of intravasc. hemolysis- marker for transfusion rxn).
↑indirect bilirubin; ↓haptoglobin.
Txt of hemolytic transfusion rxn
repeat Type and Cross
Stop transfusion, IV fluids
what is “type and cross”
tests before blood transfusion:
a. Type/screen: recipients blood type A, B, or O and Rh antigen
b. Crossmatch: tests recipient’s serum for antibodies against donors: RBC antigen
incubate your blood with donor to make sure theres no rxn
two types of Microangiopathic hemolytic anemias
disseminated intravascular coagulation (DIC)
thrombotic thromocytopenia purpura (TTP)
what is microangiopathic hemolytic anemia?
small blood vessels become partially obstructed or narrowed by lesions that predispose passing red cells to mechanical damage causing schistocytes (fragmented RBCs)
what is DIC
dissemintated intravasc. coag:
vessels are narrowed by intravascular deposition of fibrin.
–>Tissue factor released into the circulation resulting in thrombi in microcirculation and activation of the fibrinolytic system
major causes of DIC
major causes: Sepsis, trauma, malignancy, obstetric complications.
labs for DIC (4)
Schistocytes on peripheral smear and …
prolonged PT, prolonged a PTT
decreased platelets
decreased fibrinogen, increased fibrin split products (FSP)
along with increased D-Dimer.
what are schistoytes?
fragmented RBCs that take on different shapes
-their presence indicates microangiopathic hemolytic anemia
DIC txt
replacement therapy + txt underlying disease
- fresh frozen plasma
- platelets
what is TTP?
Thrombotic Thrombocytopenia Purpura: a deficiency of a protease that cleaves large vWF multimers into normal size multimers (vWF – cleaving protease). These large multimers cause agglutination of platelets in the circulation =diffuse platelet thrombi in the microcirculation.
Dx of TTP
schistocytes on smear and …
thrombocytopenia + increased LDH
**normal PT, PTT
txt of TTP
immediate plasma exchange therapy.
what is the Diagnostic approach to patient with normocytic anemia and ↑retic count?
what would suggest hemolyses? …what would suggest its microangiopathic hemolytic anemia?… what would tell you its hereditary spherocytosis?
LDH and indirect bilirubin elevated suggest hemolyses
- schistocytes on peripheral smear suggest microangiopathic hemolytic anemia.
- negative direct Coombs test and normal hemoglobin electrophoresis. Osmotic Fragility is increased (a reflection of spherocytes).
what is LDH?
lactate dehydrogenase- is an intracellular enzyme released from RBC when they are destroyed. Increase RBC destruction (hemolysis) results in an elevation of the serum LDH level. Increase LDH level is not specific for RBC destruction
what is hereditary spherocytosis?
A group of inherited disorders of the RBC cytoskeleton resulting in the progressive loss of membrane surface area.
RBC: changes from biconcave disc to a rigid spherocyte which causes premature destruction of circulatory erythrocytes in the spleen
lab findings for hereditary spherocytosis? (9)
- Normocytic anemia
- Hyperchromic RBCs (increased MCHC-mean corpuscle Hgb conc.)
- increased retic count (reticulocytosis)
+ hemolysis lab indicators
- Decreased haptoglobin
- increased indirect bilirubin
- increased LDH
+ 7. negative direct Coombs test 8. normal hemoglobin electrophoresis 9. Osmotic Fragility is increased
what does “increased osmotic fragility” mean?
indicates spherocytes- RBCs are subject to hypotonic solution- fluid moves into RBC: doesn’t have excessive membrane so they quickly hemolyze
clinical presentation of hereditary spherocytosis?
Splenomegaly. Patients have increased risk for gallstones. (THINK IF YOU HAVE A THIN FEMALE WITH GALLSTONES)
txt of hereditary spherocytosis?
Folic Acid (to help make RBCs) 1mg PO/day + Consider Splenectomy
what is the fxn of haptoglobin? (kinda weeds)
bind free plasma hemoglobin, which allows degradative enzymes to gain access to the hemoglobin.
increased free Hgb = decreased haptoglobin b/c it is binding the free Hgb
what does low haptoglobin mean?
When red blood cells are actively being destroyed, haptoglobin disappears faster than it is created. As a result, the levels of haptoglobin in the blood drop
