Red Blood Cell Disorders II-Usera Flashcards
What are the five types of normocytic anemia?
- acute blood loss
- early iron deficiency and ACD
- aplastic anemia
- chronic renal failure
- malignancy
What are the intrinsic defect causes of normocytic anemia?
- membrane defect
- abnormal HB
- enzyme deficiency
What are the extrinsic defect causes of normocytic anemia?
trauma (e.g. aortic stenosis, prosthetic valves)
immune destruction
How come you get extravascular hemolysis?
RBC phagocytosis by splenic and hepatic macrophages due to IgG bound with or without complement, or abnormal shape (e.g. spherocytosis, sickling)
What are the laboratory findings of normoncytic anemia?
increase unconjugates bilirubin
increased serum LDH
How come you get intravascular hemolysis?
RBC phagocytosis by splenic and hepatic macrophages
-hemolysis occurs within blood vessels (enzyme deficiency G6PD, mechanical trauma, complement/immune destruction)
What are the lab findings in intravascular hemolysis?
- increase unconjugates bilirubin (minimal)
- increased serum LDH
- decreased serum haptoglobin
- hemosiderinuria
(Blank) is an acute phase reactant that complexes with Hb?
haptoglobin
Is herediatary spherocytosis autosomal dominant or recessive?
autosomal dominant
What causes hereditary spherocytosis?
intrinisic defect caused by mutation in ankyrin Howvere can have problems in Band 3, spectrins, protein 4.2
What are the clinical features of hereditary spherocytosis?
jaundice
gallstones
splenomegaly
aplastic crisis in children
What are the lab findings of hereditary spherocytosis?
normocytic anemia
increase MCHC
increase osmotic fragility (rupture in hypotonic solutions)
elevated LDH and Bili
Are all spherocytes due to genetic diseases?
no
What are 2 non genetic causes of sphereocytes?
warm autoimmune hemolytic anemia
ABO incompatibility
How do you treat spherocytosis?
splenectomy.
How come in spherocytosis, MCV may vary?
due to reticulocytosis
What is this: autosomal dominant defect in spectrin tetramers or 4.1 mild anemia splenomegaly
Hereditary ellipotcytosis
What can hereditary ellipotcytosis cause?
mild anemia
splenomegaly
What percent of your peripheral blood must be elliptocytes to be considered hereditary elliptocytosis?
greater than 25%
How do you get sickle cell anemia?
autosomal recessive missense mutation
What amino acid causes sickle cell?
valine substitution for glutamic acid in beta-globin chain
A lot of people (mainly A.A) are heterozygotes for sickle cell anemia but are not (blank)
anemic
If you have more (blank) HBS is threshold for sickle cell anemia
60%
(blank) concentrations prevent sickling in newborns for 5-6 months.
HbF
What are the clinical findings of sickle cell anemia?
dactyitis acute chest syndrome (most common cause of death) stroke gallstones priapism aseptic necrosis of femoral head aplastic crisis (ass. w/ parvovirus) autosplenectomy (splenomegaly by 2 years, then loses function)
Where do you see howel-jolly bodies?
sickle cell anemia
Why do you get suscpetibility to infections with sickle cell anemia?
due to dysfunctional spleen
What are some infections often associated with sickle cell anemia?
strep pneumonia, other encapsulated organisms
osteomyelitis by salmonella paratyphi
What are the renal findings in sickle cell anemia?
may occur in peritubular capillaries
microhematuria
renal papillary necrosis
What is the treatment for sickle cell anemia?
- infectious prophylaxis
- pain management
- transfusion- acute chest syndrome, aplastic crisis
What are some preventive measures for sickle cell anemia?
- hydroxyurea
- immunizations
- pneumococcal vaccine
- folic acid supplementation
How do you get G6PD deficiency?
recessive x linked pattern
In G6PD deficiency which RBCs appear normal and which dont?
Does it affect men or women more?
whites or blacks?
young RBCs-normal old-affected females-asymptomatic males-symptomatic affects 22% of blacks
There are over 100 genetic variations of G6PD deficiency but most represent (blank) substitutions
amino acid
(blank) protects RBCs and their membranes from oxidants
Glutathione (reduced state)
If you dont have G6PD (thus no glutathione) you will get (blank) and thus hemolysis
oxidative damage
What are some inciting causes of G6PD?
infection
drugs; primaquine, sulfas
If you have G6PD then you will have decreased (blank) throughout life span of RBCs
enzyme activity
In G6PD you get accumulation of (blank)
H202
What does accumulating H202 do?
injuries RBC and results in hemolysis
What will you see in G6PD mediterranean ?
heinz bodies-> oxidized hemoglobin precipitates
Bite cells-> macrophage removal of damaged membrane
What are the clinical and lab findings of G6PD?
- sudden onset back pain and delayed hemoglobinuria
- suscpetibility to infections (impaired MPO-No NADHPH)
- normocytic anemia
- Heinz bodies
What is immunohemolytic anemia?
extrinisc hemolytic anemia with intra- or extravascular hemolysis
caused by antibody mediated destruction of RBCs (IgG or IgM)
What will you find in immunohemolytic anemia?
warm agglutinins (70% in IgG) cold agglutinins (30% in IgM) complement drug induced paroxysmal cold hemoglobinuria (PCH)
In immunohemolytic anemia (blank) mediated diseases usually involves extravascular hemolysis
IgG
What is the most common hemolytic anemia?
extravascular immunohemolytic anemia (IgG0
In immunohemolytic anemia IgG RBCs are phagocytosed by (blank)
splenic macrophages
(blank) percent of immunohemoytic anemias are idiotpathic (arise spontaneously)
50%
What diseases are immunohemolytic anemia associated with?
SLE
Collagen Vascular diseases (SLE)
CLL
Malignant lymphome (Esp hodgkins), viral infections etc
Where do you see cold agglutinins in immunohemolytic anemia?
IgM (30%) immunohemolytic anemia
What causes IgM immunohemolytic anemia?
mycopasma pneumoniae, infectious mononucleosis, CLL, drugs
Does IgM immunohemolytic anemia cause intravascular or extravascular hemolysis?
either or :)
What phenomenon do you commonly see in immunohemolytic anemia?
Raynauds phenomenon
What is complement mediated hemolysis caused by immunohemmolytic anemia?
- C3B coated RBC are phagocytosed by liver macrophages-extravascular
- RBCs coated by C5-C9 membrane attack complex-intravascular
What are the clinical findings of immune hemolytic anemia?
jaundice
hepatosplenomegaly
Raynauds phenomenon
What are the lab findings for immune hemolytic anemia?
Positive dat Positive indirect Unconjugated hyperbilirubinemia Hemoglobinuria Decreased haptoglobin Normocytic anemia Rbc agglutination (igm)
What is drug induced IHA?
antibody (IgG) to drug binds to RBC membrane
What is a drug that can induce IHA and what do you see in this?
penicilin
-extravascular hemolysis
-direct coombs positive
“innocent bystanders”
What are the drugs that can cause drug-antidrug immune complexes?
quinidine, quinine, INH, sulfonamides
Igm drug-antidrug immune complex results in (Blank) hemolysis
intravascular
IgG drug-anti-drug immune complex results in (blank) hemolysis
extravascular
How do you treat drug induced IHA?
discontinue offending drug
- corticosteroids/immunsuppresion
- splenectomy
- IVIG-IgG coated macrophages can not phagocytize RBCs
What is this:
acquired membrane defect in myeloid stem cells-mutation in Pig-A gene.
Paroxysmal nocturnal hemoglobinuria
What does the Pig A gene mutation in paroxysmal nocturanl hemoglobinuria cause?
loss of decay accelerating factor (DAF)
What happens if you lose DAF (when mutated)?
you cant destabilize compliment so you cant lyse blood cells and they end up in urine.
What does IVIG do?
Give IgG via IV which will coat macrophages so they are unable to phagocytize RBCs
In paraoxsmal nocturnal hemoglobinuria you cant activate the (blank)
membrane attack complex
Why do you call it paroxysmal NOCTURNAL hemoglobinuria?
because it happens in periods of acidosis which usually occurs during sleeping hence nocturnal
(blank) is a clonal stem cell disorder so there is increased risk for other clonal disorders such as AML
Paroxysmal nocturnal hemoglobinuria
What is this:
- episodic hemoglobinuria
- may lead to iron def
- increased risk of thrombosis
- increased risk of AML
Paroxysmal nocturnal hemoglobinuria
What do the labs look like in paroxysmal nocturnal hemoglobinuria?
- normocytic anemia with pancytopenia
- decreased haptoglobin
- increased serum/urin HB
(blank) are when you have a whole range of abnormal shaped cells
schistocytes
What will you see in traumatic hemolysis?
cell fragments: shcistocytes, burr cells, helmet cells
Why do you get disseminated intravascular coagulation (DIC)?
RBCs damaged by fibrin buildup or clots in small vessel lumen
What are some causes of traumatic hemolysis?
long distance running artificial heart valves thrombotic thrombocytopenia (purpura)
What is this: hypersplenism microangiopathic hemolytic anemia (MAHA) Common in patients with malignant hypertension microorganisms, i.e. malaria, babesia, Clostridium perfringens snake venoms, i.e. cobra venom chemical, i.e. plumbism (lead poisoning) physical, i.e. burns
non-immunologic hemolytic anemia
A transfusion reaction can cause (blank) hemolytic anemia
alloimmune
donor and recipient blood is incompatible
What are the lab findings of alloimmune hemolytic anemia?
- DAT
- anemia depending on severity
- total and indirect bilirubin elevated
- haptoglobin decreased
- increased LDH
How can newborns get an alloimmune anemia (called hemolytic disease of the newborn)?
What does this result in?
maternal antibodies greater than babys RBCs
Anemia and hyperbilirubinemia
What are the lab findings hemolytic disease of the newborn?
- positive DAT
- increased total and indirect bilirubin
- increased LDH
- initially hematocrit and hemoglobin may be within normal limits
Renal disease is associated with anemia. What will the RBCs look like with renal disease?
Normochromic, normocytic
mild anisocytosis
sometimes hypochromic, microcytic
burr cells – shrunken RBCs with irregular projections (echinocytes)
When do you usually see anemia with renal disease?
when BUN is twice the normal
What are the possible mechanisms for anemia occurring in renal disease?
- bone marrow suppression
- hemolysis from impaired renal excretion
- coagulation defects (in severe disease) leading to blood loss
- impaired erythropoietin production from renal endocrine failure
WHat do the RBCs look like with anemia with neoplasia?
normochromic and normocytic UNLESS there is blood loss, hemorrhage, a myelopthisic process (affects the bone marrow)
There is a mild (blank) component often present with neoplasia
anemic
THe hemolytic component associated with neoplasm can be severe with (blank) possibly due to the altered endothelium of malignant tissues (a set up for DIC)
lymphomas
(blank) can be associated with infection
hemolytic anemia
What are some infections that can cause hemolytic anemia?
bacterial toxins (c. perfringens) malaria
WHat are the 2 types of macrocytic anemias?
megaloblastic (folate or B12 deficiency)
Nonmegaloblastic (alcoholism)
What is this:
large nucleus in erythroid precursors (have a more mature cytoplasm than the nucleus i.e nuclear cytoplasmic dysynchrony
megaloblastic
What are the causes of B12 deficiency?
Pernicious anemia (autoimmune destruction of parietal cells ) Pure vegan diet Malnutrition Malabsorption ↓ Intrinsic factor ↓ Gastric acid ↓ Intestinal absorption (chrone’s disease)
(blank) cells in the stomach release intrinsic factor (and HCL) which is required for B12 absorption in the terminal (blank)
parietal
ileum
Folate is absorbed in the (blank) which can be affected by celiac disease
jejunum
What can cause folate deficiency?
decreased intake
malabsorption
durg inhibition
What are the reasons for decreased intake in folate deficiency?
Malnutrition
Etoh (inhibits absorption of folate)
Goat milk
Infants/elderly
What are the reasons for malabsorption in folate deficiency?
celiac
bacterial overgrowth
What are the reasons for drug inhibition in folate deficiency?
5-FU-chemotherapy MTX-chemotherapy Tpm-sfx Phenytoin Ocp’s etoh
What is the pathogenesis of megaloblastic anemia?
Delayed nuclear maturation
Affects all rapidly dividing cells
Cellular RNA and protein synthesis unabated
If you dont have folate or vit B12 what will you have increase of?
homocysteine
What happens if you have elevated homocysteine?
damaged to vascular endothelial cells
How can you get pernicious anemia?
Type II hypersensitivity, Blood group A individuals, Achloryhydria (decreased/no production of HCL)
What is this:
Autoimmune destruction of parietal cells (85-90%)
Antibodies that block B12-if binding (60-75%)
pernicious anemia
What are signs of pernicious anemia?
smooth/sore tongue
peripheral neuropathy
dementia
decreased vibratory and proprioception
Peripheral neuropathy is associated with (B12/folate) deficiency
B12 ONLY!!!!! (due to demyleination of dorsal columns affecting propioception and TVP)
What is this:
decreased serum and RBC folate (best test)
folate deficiency
What is the treatment of folate deficiency?
Intramuscular injections of b12 (to cure B12 def. not folate)
Oral administration of monoglutamic folic acid
WHat is this: Mcv 105 ±10 Anemia may not necessarily be present Etoh most common cause Liver disease (increased cholesterol)
Nonmegaloblastic macrocytosis
Does nonmegaloblastic macrocytosis have a problem with maturation of bone marrow?
no just have large cells
Why does nonmegaloblastic have large cell size?
due to increased cholesterol in the membrane because of liver disease-target cell appearance due to presence of more membrane (due to cholesterol)
