Anemias Flashcards
What are the stages of iron deficient anemia
storage iron depletion - stored iron is used up as there is a decrease of available iron
storage iron/pool exhaustion - storage pools are completely used up and serum iron continues to be used until it is also exhausted
iron deficient anemia - all iron stores and pools have been used and there is very little iron for incorporation into new RBCs
What are the symptoms of IDA
spooning of nails, sore tongue, muscle dysfunction, fatigue, blue sclera, cravings for non-nutritional items
What are the causes of anemia of chronic infection/disease
impaired iron kinetics - during infection available iron is removed from the serum and stored as ferritin
impaired erythropoiesis - inflammatory cytokines hinder the action of EPO
decreased RBC survival - body and immune system is on high alert
What are the features of warm auto-immune hemolytic anemia
usually of unknown cause or secondary to disease
IgG, reacts at 37, DAT IgG positive C3D variable, Complement activation variable, EVH, pan reactive Rh complex antibody
sphero, poly, nRBC, retic
What are the features of cold agglutin disease
can be non-pathogenic (will not react aboe 30) or pathogenic (will react at 37) usually idiopathic or secondary to lymphoproliferative disorders
IgM, reacts at 4, DAT C3D positive, activates compliment, EVH, anti- I, -i, -pr
autoagglutination, poly
What are the features of paroxysmal cold hemoglobinuria
idopathic or secondary to infection. Biphasic - bind at 4 and partially activate compliment then when 37 is achieved it will dissociate but complement will fully activate
IgG, reacts at 4, DAT C3D positive, activates compliment, IVH, anti-P
What are the expected hemoglobin levels in Beta Thalassemia Major
decreased/absent HGB A
normal-increased HGB A2
70-90% HGB F
What are the expected hemoglobin levels in Sickle cell trait
> /= 60% HGB A
Normal/increased HGB A2
<1% HGB F
</= 40% HGB S
What are the expected hemoglobin levels in sickle cell disease
Normal/increased HGB A2
20% HGB F
>/= 80% HGB S
What are the expected hemoglobin levels in hemoglobin C trait
> /= 60% HGB A
Normal HGB A2
Normal HGB F
30% HGB C
What are the expected hemoglobin levels in hemoglobin C disease
2% HGB A2
< 7% HGB F
>90% HGB C
What are the lab findings in IDA
micro/hypo
decreased HGB
decreased MCV
normal WBC
increased or decreased PLT
targets, eliptos, tears
normoblasts with ragged edges in BM
decreased M:E
What are the confirmation tests for IDA
decreased iron stores in BM
decreased serum iron
decreased serum ferritin
decreased transferrin
increased TIBC
What are causes of sideroblastic anemia
enzyme deficiency - ALA synthase
drugs - chemo drugs, isoniazid and chloramphenical
lead poisoning - inhibits ALA dehydratase and inhibits incorporation of iron into the protoporphyrin ring
What are lab findings in sideroblastic anemia
micro/hypo and normo/normo
decreased HGB
normal WBC
normal PLT
increased RDW
basophilic stippling, pappenheimers
ringed sideroblasts in BM
decreased M:E
What are the confirmation tests for sideroblastic anemia
increased iron stores in BM
increased serum iron
increased serum ferritin
increased transferrin
decreased TIBC
What are lab findings for anemia of chronic infection
micro/hypo or normo/normo
decreased HGB
decreased MCV
normal/increased WBC
normal/increased PLT
suppressed EPO
no erythroid hyperplasia
normal/increased M:E
What are confirmation tests for anemia of chronic infection
increased CRP
normal/increased iron stores in BM
decreased serum iron
increased serum ferritin
increased transferrin
decreased TIBC
What are causes of megaloblastic anemia
B12/folate deficiency due to diet, malabsorption, increased need, increased loss
What are lab findings for megaloblastic anemia
macro ovalocytes
hyper-segmented neuts
erythroid hyperplasia
nuclear-cytoplasm asynchrony
large precursors
HJ, tears, schistos, BC, nRBCs
decreased reticulocytes
decreased HGB
decreased RBC
decreased PLT
decreased WBC
increased MCH
increased MCV
decreased M:E
What are confirmation tests for megaloblastic anemia
normal iron studies
What are causes of non-megaloblastic anemia
liver disease, chronic alcoholism, post-splenectomy, BM failure
What are lab findings for megaloblastic anemia
macrocytes
erythroid hyperplasia
nuclear-cytoplasmic asynchrony
large precursors
decreased HGB
increased MCV
normal WBC
decreased M:E
What are confirmation tests for megaloblastic anemia
normal iron studies
What are lab findings for aplastic anemia
decreased HGB
decreased WBC
decreased PLT
pancytopenia
normo/normo or macro
increased yellow tissue in BM (dry tap)
What are lab findings for Beta Thalassemia
decreased HGB
decreased MCV
increased/normal retic
hypo/micro
targets, tears, schisto, sphero, elipto, HJ, BS, papenheimer
Heinz bodies in major
nRBC
erythroid hyperplasia
decreased M:E
What causes Beta Thalassemia
decrease in beta globin chains due to deletion or silencing of one or both genes
1 gene: minor
2 genes: major
What are confirmation tests for Beta Thalassemia
HPLC
HGB electrophoresis
increased iron stores in BM
normal serum iron
normal/increased serum ferritin
molecular genetics
What are lab findings for Alpha Thalassemia
decreased HGB
decreased MCV
micro/hypo
tears, schistos, spheros, targets, HJ, BS
erythroid hyperplasia
What are confirmation tests for Alpha Thalassemia
HPLC
HGB electrophoresis
normal serum iron
normal/increased serum ferritin
What are lab findings for Hemoglobin S
sickle cells
increased iron stores
targets, sphero, schisto, poly, nRBC, JH, BS, pappenheimer
decreased M:E
What are confirmation tests for Hemoglobin S
HGB electrophoresis
HPLC
sickling test
solubility test
What are lab findings for hemoglobin C
short, thick crystals
increased iron stores
normo/normo
targets, sphero, schisto, nRBC
What are confirmation tests for Hemoglobin C
HBG electrophoresis
HPLC
What are lab findings for hemoglobin E
micro
target cells
increased iron stores
often another hemoglobinopathy
What are confirmation tests for hemoglobin E
HGB electrophoresis
HPLC
What are confirmation tests for Hemoglobin M
HGB electrophoresis
HPLC
What are lab findings for hemoglobin M
increased iron stores
What does G6PD deficiency effect
the hexose monophosphate shunt in the ebdimeyerhoff pathway causing cells to be more prone to oxidative damage under stress
X-linked inheritance
What are lab findings for G6PD deficiency
heinz bodies
bites, helmets, schistos
DAT neg
What is the confirmation test for G6PD deficency
decreased G6PD assay
What are lab findings for PK deficiency
poly
echinocytes
What causes PNH
acquired stem cell disorder missing the GPI protein (CD 55, 59) these proteins are responsible for preventing cell lysis from complement
What are lab findings of DIC
decreased HGB
thrombocytopenia
schistos
increased PT
increased PTT
decreased fibrinogen
increased D-dimers
poly
What causes TTP
decrease om ADAMTS-13 which is responsible for cleaving VWF multimers. Without ADAMTS-13 the long multimers cause thrombi formation and blockages in the vasculature
it can be inherited, idiopathic or acquired
What are lab findings in TTP
thrombocytopenia
schistos
increased LDH
poly
What causes HUS
toxins from ecoli O1:5:7 or shigella. The toxins cause endothelial cell damage which creates a pro-coagulative environment and thrombi formation
atypical HUS can cause spontaneous activation of the alternate complement system leading to vascular injury and subsequent activation of the coagulation system. Increased damage leads to large multimers of VWF despite normal ADAMTS-13 activity
What are the lab findings in HUS
thrombocytopenia
schistos
poly
What are the lab findings in HELLP
increased liver enzymes
decreased platelets
What is the confirmation test of PCH
donath-landsteiner test
What are causes of anemia
ineffective erythropoiesis
insufficient erythropoiesis
excessive blood loss
hemolysis
What are the microcytic anemias
IDA, Sideroblastic, ACI, Thalassemia
What are the macrocytic anemias
megaloblastic, non-megaloblastic
What are the normocytic anemias
hemolytic, aplastic, ACI
What do vitamin B12 and folate have to do with erythropoiesis
they are vital to the production of thymine, without them thymine cannot be produced and DNA replication is slowed down. A place holder is used but never replaced causing the DNA to be broken during proof reading making unstable cells
What is pernicious anemia
an autoimmune disorder that causes a lack of intrinsic factor due to destruction of parietal cells
What causes aplastic anemia
bone marrow failure and decrease in hematopoietic cells due to damage or injury to the marrow
acquired - idiopathic, exposure to toxic agents or viruses
inherited - fanconcis anemia, duskeratosis congenita. schwachman-diamond syndrome
What is fanconis anemia
an autosomal recessive disorder or X-linked that causes abnormal chromosomal fragility and a predisposition to leukemia and cancer
What is dyskeratosis congenita
X-linked autosomal dominant or autosomal recessive mutations that reduce telomerase activity
What is scheachman-diamond syndrome
a mutation in the SBDS gene similar to Fanconies anemia with additional pancreaticfunction and malabsorption
What is pure red cell aplasia
a severe decrease of RBC precursors with no other bone marrow abnormalities
What are lab findings for pure red cell aplasia
low HGB
low PLT
low WBC
normo/normo or macro
increased yellow tissue in the marrow
What causes alpha thalassemia
defects in alpha globin chain production
minor - deletion of two genes
intermedia (hemoglobin H) - deletion of three genes
major (hemoglobin barts) - deletion of all four genes (not compatible with life)
What are the clinical complications of hemoglobin S
oxidative damage to RBC membrane which induces adherence of RBCs to the surface of capillaries and arterioles as well as RBC aggregation
adhesion of RBCs could activate the coagulation cascade
What is the benefit of sickle cell trait
malarial resistance
What causes hemoglobin S
a substitution in the 6th position of the beta chain causing replacement of glutamic acid with valine
What causes hemoglobin C
a substitution in the 6th position of the beta chain causing replacement of glutamic acid with lysine
What causes hemoglobin E
a substitution in the 26th position of the beta chain causing lysine to be replaced by glutamic acid
What causes hemoglobin M
different mutations in any chain that causes the formation of methemoglobin that has a structural abnormality in the globin portion. This causes heme iron to oxidize and cannot transport oxygen
What does pyruvate kinase deficiency effect
the embden-meyerhof pathway causing the cell to not produce enough ATP. This effects membrane permeability and causes the cell to become rigid and less deformable
autosomal recessive inheritance
What is hereditary eliptocytosis
autosomal dominant disorder with defects in the spectrin and protein 4.1 genes
RBC lack horizontal structural protein interactions causing them to form elliptocytes
What are the variants of hereditary elliptocytosis
hereditary pyropoikolocytosis - sever form with increased poik (sphero, micro, schisto, ellipto) and increased thermal sensitiivity
southeast asian ovalocytosis - band 3 gene mutation causing increased rigidity of membrane. Causes resistance to malaria. Looks like pig nose
What is hereditary spherocytosis
defects in vertical interactions of transmembrane protiens and cytoskeleton
mutations may occur in ankyrin. protein 4.3, band 3 or spectrin
due to lack of support RBC lose lipid membrane leading to formation of spherocytes as well as higher concentrations of Na and lower concentrations of K inside the cell
What is hereditary acanthocytosis
autosomal recessive disease caused by mutations in the microsomal triglyceride transfer protein
causes an absence of VLDL, LDL and chylomicrons decreasing membrane fluidity
severe liver disease can be an acquired form of the disease
What is the malaria lifecycle
- female anopheles mosquito acquires malaria from an infected source
- malaria reproduces and the zygote enters the stomach lining of the mosquito forming a cyst
- new parasites are produced and travel to the salivary gland of the mosquito
- malaria enters new host when bitten and travels to the liver
- parasites mature in the liver and then enter the blood stream and infect RBCs
How does malaria cause anemia
lysing infected cells, inhibited/ineffective erythropoiesis, causing immune cells to attack infected cells
What is the most severe form of malaria
plasmodium falciparum
Why is plasmodium falciparum the most severe form of malaria
it can affect all stages of the RBC and adheres to endothelial cells in organs and microvasculature to avoid removal via spleen
How is malaria confirmed once seen in smear
PCR
What are differentiating features of falciparum
small delicate ring forms with two chromatin dots, banana shaped gametes, multiple rings in a single cell
What is babesiosis
a parasite that is transmitted by Ixodes scapularis (tick)
What is the presentation of babeiosis
extracellular or as a maltese cross in RBCs
How does clostridium effect RBCs
releases alpha-toxins and phospholipase C as well as sphingomyelinase activity that all work together to alter the membrane causing spherocytes
What is seen in blood smears of burn patients
schistocytes and spherocytes for ~24 hours after incident
What are the methods of drug induced hemolytic anemias
autoimmune, drug adsorption, immune complex, drug induced non-immunologic protein adsorption
What is seen in blood smears of drug-induced hemolytic anemias
spherocytes and poly
