Path HO2 Flashcards
Anemias of diminished erythropoiesis are all characterized by…
low reticulocyte count
Microcytic anemias are due to…
decreased Hgb production
Is the problem of microcytic anemias in the cytoplasm or in the nuclear maturation?
cytoplasmic maturation defect
What are four causes of microcytic anemia?
- iron deficiency anemia
- anemia of chronic disease
- sideroblastic anemia
- thalassemia
What is the MCC of anemia WW?
iron deficiency anemia
What are some causes of Fe deficiency anemia?
inadequate intake
impaired absorption
increased requirement
chronic blood loss
Fe deficiency in post-menopausal women and adult men is due to…
chronic blood loss/cancer until proven otherwise
Where does absorption of Fe occur?
duodenum
What cells in the duodenum help transport Fe across their cell membrane?
enterocytes
What transporter do enterocytes use to transport Fe across their cell membrane and into the blood?
ferroportin
After Fe is inside an enterocyte, what transports the Fe through the blood so that it can reach liver and bone marrow?
transferrin
What is stored intracellular Fe bound to? Why does it need to be bound?
ferritin
prevents iron from forming free radiacals via the Phenton reaction
Fe absorption is regulated by plasma levels of …
How does this work?
hepcidin
inhibits Fe transfer from enterocytes to plasma by binding to ferroportin causing it to be endocytosed and degraded
What are specific PE findings of Fe deficiency anemia?
koilonychia
alopecia
atrophic glossitis
atrophic gastritis
intestinal malabsorption
pica
80% of functional Fe is found where?
in hgb
What are some morphologic findings on a peripheral blood smear of Fe deficiency anemia?
microcytic hypochromic
anisocytosis (increased RDW)
“pencil cells”
low reticulocyte count
mild thrombocytosis
In Fe deficiency anemia, what will the Fe labs look like?
low ferritin (marrow Fe)
increased TIBC (total iron binding capacity)
low serum iron
low % saturation
increased Serum soluble Transferrin Receptor
increased Free erythrocyte protoporphyrin (FEP)
Anemia of chronic disease is due to…
defective iron cycling between macrophages and developing RBCs, resulting decrease in erythropoiesis
no intrinsic defect of RBCs
mediate by cytokines
What is the MC type of anemia in hospitalized pts?
anemia of chronic disease
How does hepcidin sequester iron in storage sites?
limiting iron transfer from macrophages to erythroid precursors
suppressing erythropoietin production - prevent bacteria from accessisng iron needed for their survival
What are morphological characteristics of anemia of chronic disease?
NONE
reticulocyte count is low
What are the lab findings with anemia of chronic disease?
decreased serum Fe
decreased TIBC
decreased % saturation
normal serum soluble transferrin receptors
increased ferritin (marrow Fe)
increased Free erythrocyte protoporphyrin (FEP)
anemia caused by abnormal fe metabolism within the RBC itself is called what? Going a little bit more in depth, what is happening?
sideroblastic anemia
defective protoporphyrin synthesis
What causes the look of ‘ringed sideroblasts’ ?
iron is sequestered in the developing RBC mitochondria and can’t be used for heme synthesis
iron swells and distorts the mito (which is surrounding the nucleus) showing a ring of dark blue staining, Fe containing mito around the nucleus
What are the MCC of sideroblastic anemia?
acquired causes like myelodysplastic syndromes or secondary to toxic insults like lead, drugs, or alcohol
What will the lab findings be in sideroblastic anemia?
increased serum Fe
decreased or nl TIBC
increased % saturation
variable SS Transferrin receptor
increased ferritin (marrow Fe)
megaloblastic marrow can be caused by what three things?
folate deficiency
Vt B12 deficiency
drugs that interfere with DNA synthesis
How does Vit B12 or folate deficinecy cause macrocytic megaloblastic anemia?
they are coenzymes required for the synthesis of thymidine - without, DNA synthesis is impaired
results in defective nuclear maturation of rapidly proliferating cells
long standing, untreated B12 deficiency eventually results in …
subacute combined degeneration of the spinal cord by demyelination
what are some causes of vit B12 deficiency?
strict vegetarianism
intrinsic factor deficiency
broad fish tape worm - diphyllobothrium latum
pregnancy
hyperthyroidism
Does it take longer for a deficiency in vit B12 or folate take longer to cause symptoms?
folate deficiency will be noticed within a few months
what is a particular form of megaloblastic anemia due to autoimmune gastritis, destruction of parietal cells and B12 deficiency d/t lack of intrinsic factor?
pernicious anemia (PA)
in peripheral blood smear, what morphologies will you see with megaloblastic macrocytic anemia?
anisopoikilocytosis
macro-ovalocytes
neutrophils larger with hypersegmented nuclei
rare tear drop cells
reticulocyte count is low
What are unique labs you might find elevated with Vit B12 deficiency anemia?
serum homocysteine and methylmalonic acid
Methylmalonic acid will be… in folate deficiency anemia
normal
chronic primary hematopoietic failure with pancytopenia is considered…
aplastic anemia
what will the morphology of aplastic anemia appear like?
blood: typically pancytopenia, no specific morph abnls
bone marrow: markedly hypocellular, largely devoid of hematopoietic cells; mainly contains fat and stromal cells
what is a primary marrow disorder in which only erythroid progenitors are suppressed?
pure red cell aplasia
What are some common etiologies of pure red cell aplasia?
neoplasms, esp thymoma and large granular lymphocytic leukemia
autoimmune diseases
parvovirus B19 (in bone marrow, rare giant erythroblasts are seen, with intranuclear inlcusions)
Space occupying lesions in the marrow replace hematopoietic tissue is called what?
what is this caused by?
myelophthisic anemia
caused by metastatic carcinoma
the only congenital disorder characterized initially by isolated and sustained (pure) red cell aplasia
diamond-blackfan anemia
What are clinical features of Diamond-Blackfan anemia? What does the CBC look like?
short stature, craniofacial and thumb skeletal abnls
CBC: macrocytic anemia with elevated HbF and increased RBC adenosine deaminase; markedly decreased reticulocyte count
hemolytic anemias are usually (intravascular/extravascular) meaning they take place…
extravascular
in the macrophages of the reticuloendothelial system
If bone marrow is appropriately responding to hemolytic anemia, what will happen?
erythroid hyperplasia and peripheral blood reticulocytosis
physiologic destruction of RBCs is …
this takes place where?
extravascular hemolysis
takes place within the macrophages of liver, spleen, and marrow
What breakdown products does extravascular hemolysis create?
heme ( to biliverdin and then bilirubin)
globin (degraded amino acid compounds)
iron (taken up by RE cells and recycled)
lactate dehydrogenase (LDH)
What are common clinical features of extravascular hemolytic anemia?
anemia
splenomegaly
jaundice
variable decreases in serum haptoglobin
Intravascular hemolysis is never physiological but is always…
pathological
What does intravascualr hemolysis release from RBCs?
free hemoglobin (into the plasma which then binds haptoglobin, normally is eaten by macrophages, but if overwhelmed, will cause hemosiderinuria and if even more overwhelmed will cause hemoglobinuria)
free hemoglobin could also bind to transferring and albumin resulting in methhemoglobin
Splenomegaly is NOT a feature of…
intravascular hemolysis
What are common clinical features of intravascular hemolysis?
anemia
hemoglobinemia
hemoglobinuria
hemosiderinuria
decreased plasma haptoglobin**
jaundice
In all hemolytic anemias, reticulocytes will be increasingly released into peripheral blood appearing as…
polychromasia on Wright-Giemsa stains (increased MCV and blue-tinted cytoplasm)
reticulocytosis on new methylene blue stain
In other organs, hemolytic anemias will cause:
hemosiderosis (esp within spleen, liver, and bone marrow
extrameduallary hematopoiesis
pigmanet gallstones and cholelithiasis
alpha thalassemia is mainly from…
gene deletions
beta thalassemia is mainly from …
point mutations that lead to defects in transcription, splicing or translation of beta globin mRNA
if all four alpha genes are deleted in alpha thalassemia, what results? What is this called hgb wise?
hydrops fetalis, fatal in utero
hgb barts, four gamma chains instead of alpha
how are beta thalassemias divided?
major
intermedia
minor
What is the predominant form of hgb in B thalassemia major? When is this disease apparent?
HbF
first 6-9 months of life
In B thalassemia major, what will be seen on XRs?
crew cut appearance on skull
If there are three deletions of alpha globins in thalassemia, what occurs?
HbH disease, resembling beta thalassemia intermedia
What will Fe lab studies in thalassemia show?
increased serum Fe
decreased or nl TIBC
increased or normal % saturation
variable SS Transferrin receptor
increased or normal ferritin (marrow Fe)
reticulocyte count is …. in thalassemia
increased
Sickle cell anemia
single point mutation in gene for beta chain of hgb
glu 6 to val
may progress to functional asplenia, then more susceptible to infection by encapsulated organisms
osteomyelitis caused by salmonella species
heterozygotes for HbS is thought to confer protection against…
P. falciparum
hereditary spherocytosis
cytoskeleton defect
sphere shape causes them to get trapped in cords (erythrostasis) and then phagocytosed by macrophages
normochromic normocytic anemia and increased MCHC on CBC
How do you diagnose hereditary spherocytosis?
osmotic fragility test.
spherocytes rupture easily in a hypotonic solution
G6PD deficiency
susceptible to oxidative stress (hemolysis only after such stress)
X linked
may confer protection v Plasmodium falciparum
hemolysis is both extravascular and intravascular (Heinz bodies in cells, then taken out, now have bite cells)
can not do enzyme testing during an episode may yield false negative result
What are three types of antibodies that can cause immune hemolytic anemia?
autoantibodies (cold and warm)
alloantibodies
drug-related antibodies and MOA
Cold and warm agglutinins go with what immunoglobulins?
IgG - warm
IgM - cold
What is the only acquired stem cell defect to cause hemolytic anemia? (intrinsic to RBC)
Paroxysmal Nocturnal Hemoglobinuria
What is the pathogenesis behind PNH?
partial or complete loss of linkage of cell surface proteins to the membrane by GPI anchors due to mutations of the PIGA gene
How would I diagnose PNH?
loss of CD55 (DAF) and CD59 (MIRL) on flow cytometry
What may be causes of decreased extravastation of cells from the blood to the tissues, causing leukocytosis?
glucocorticoids
What is the number one cause of neutrophilia?
acute bacterial infections/sepsis
What is a leukemoid reaction?
severe, persistant, reactive neutrophilic leukocytosis above 50k/uL when the cause is not leukemia
often caused by severe infection, toxic reactions, malignancies, severe hemorrhage, or acute hemolysis
leukoerythroblastosis is… and is typically caused by …
immature myeloid and erythroid precursors in peripheral blood
myelophthisis (bone marrow disruption/inflitration by tumor and/or fibrosis)
Eosiniophilia is caused by
allergic disorders
drug hypersenstivities
parasitic infections
some neoplasms
Basophilia can be from neoplastic or non-neoplastic conditions, but it is most likely …
neoplastic
Monocytosis is often from…
chronic infections
bacterial endocarditis
some malignancies
recovery from bone marrow suppression (chemo)
In non-neoplastic causes of neutropenia, what happens in each?
- proliferation defect
- agranulocytosis
- myeloid hypoplasia
- maturation defect
- myeloid hyperplasia
- survival defect
- early destruction after maturation
- myeloid hyperplasia
- distribution abnormality
- sequestration in spleen
- bone marrow is variable
potenital consequence of severe neutropenia is..
infections, esp candida and aspergillus spp.
Lymphocytopenia could be caused by…
congenital deficiency
infectious disease
iatrogenic
malnutrition
Monocytopenia causes include
aplastic anemia
hairy cell leukemia
corticosteroids
acute infections with endotoxemia
Reactive plasmacytosis DOES NOT mean…
plasma cell neoplasm
MCC of reactive lymphoid aggregates are
infections, drug therapy, immune disorders
Pelger-Huet anomaly
nuclear hyposegmentation of neutrophils and other granulocytes
autosomal dominant
inherited form is not clinically relavent since neutrophils are still functional
acquired is often non-functional and hypogranular
May-Hegglin anomaly
asymptomatic (mostly). autosomal dominant
MYH9RD
large platelets
thrombocytopenia in spite of adequate numbers of bone marrow megakaryocytes, normal morphology
sensorineural hearing loss
large dohle body-like inclusions in neutrophils
Chediak- Higashi syndrome
severe anomaly with giant granules in neutrophils, eosinophils, monocytes, and lymphocytes
autosomal recessive
children have neutropenia, thrombocytopenia, and recurrent infections, esp to staph aureus
most die in childhood from infections or bleeding
Alder-Reilly anomaly
morphologic result of a type of lysosomal storage disease (LSD)
deficiency of any one of several lysosomal enzymes, resulting in accumulation of mucopolysaccharides, glycosphinglipids or glycoproteins within lysosomes
autosomal recessive
coarse facies, cardiac abnl, skeletal abnl, developemental delay, hepatosplenomegaly, corneal clouding
cytopenias may be present
prominent azurophilic granules are seen in leukocytes NOT related to infection
Bernard- Soulier syndrome
mutations in GPIb cause decreased membrane GP Ib-IX, a receptor for vWF
bleeding due to defective adhesion of platelets to subendothelial collagen after vascular injury
similar to May-Hegglin with large platelets, but here they actually have impaired function
Thrombocytopenia with absent radii (TWAR)
autosomal recessive
normal platelet morphology but abnl function
decreased megakaryocytes in bone marrow
absent radii, abnormal thumbs?
GI or skeletal anomalies at birth
Wiscott-Aldrich Syndrome
X linked
thrombocytopenia with small platelets
immunodeficiency due to failure of lymphocyte maturation
often involves IgM deficiency
Glanzman thrombasthenia
thrombasthenia “lazy” platelets
normal platelet count and morph but abnl function
dysfunction of glycoprotein IIb-IIIa causing defective platelet aggregation
thrombathenic platelets react only to ristocetin and failr to aggregate in response to ADP from collagen
rarely acquired as autoimmune disorder
primary immune thrombocytopenia
acquired, otherwise asymptomatic adults
insidious with mucocutaneous bleeding
absense of systemic symptoms and absence of splenomegaly help make the dx
bone marrow (if done) is normal, with plenty of megakaryocytes with normal morph
largely a dx of exclusion
Secondary ITP is associated with…
autoimmune diseases, lymphomas, viral infections, and drugs
formation of widespread microvascular thrombi after activation of coagulation cascade by tissue factor a mimic, resulting in microangiopathic hemolytic anemia and thrombocytopenia
DIC
What are coagulation factors and other things like in labs of DIC pts?
fibrinogen is low
D-dimer and FDP are high
PT, PTT, and TT may be prolonged or somestimes normal in early stages
schistiocytes are seen on peripheral blood smear
Thrombotic thrombocytopenia purpura/ hemolytic uremic syndrome
related disorders characterized by diffuse microvascular occlusion of arterioles and capillaries by thrombi mainly composed of platelets, not fibrin
no perivascular inflammation
clinical ssx overlap with DIC, preeclampsia, HELLP, malignant HTN, and vascultiis
COAGULATION SCREENING TESTS ARE USUALLY NORMAL
What kind of treatment does TTP require?
NOT PLATELETS
emergent plasma apheresis with FFP or cryo-poor plasma
What is the MCC of secondary HUS?
infection - shiga like toxin
How do you treat HUS?
supportive with dialysis
What type of heparin induced thrombocytopenia occurs immediately after heparin admin?
type 1
How does type 2 HIT work?
occurs within 5- 14 days after beginning heparin
caused by autoantibodies to a complex of heparin and LMW proteins, such as platelet factor 4
What are two clinical clues to HIT?
fall in platelet count around 1-2 weeks after starting heparin
unexpected shortening of the APTT in those receiving therapeutic concentrations of heparin
What are the affects of asa on platelet function?
impairs txa2 dependent platelet aggregation bc of inhibiting COX (1>2)
asa has no affect on the coagulation cascade
platelets return to normal within 5-6 days after last ASA dose
Pseudothrombocytopenia
platelet aggregates from traumatic blood draw or inadequate mixing the MCC
could be due to EDTA induced aggregation, draw in heparinized tube to get accurate platelet count
