Pathology of Red Blood Cells and Bleeding Disorders (Part 1 of 3) Flashcards
What is hemoglobin?
the main protein in the RBC, transports oxygen and carbon dioxide
what is hematocrit?
percentage of whole blood volume occupied by red cells
How do you calculate MCV?
HCT/RBC
how do you calculate MCH?
hgb/rbc
how do you calculate MCHC?
hgb/hct
what type of anemia is indicated if there is a low MCV?
microcytic
what type of anemia is indicated if there is a high MCV?
macrocytic
what type of anemia is indicated if there is a low MCH?
hypochromic
how do reticulocytes appear in a peripheral blood smear? and what stain can you use to highlight the presence of the RNA in the reticulocytes?
reticulocytes appear polychromatic with a purple grey tinge in larger cells; a supravital stain can be used
What does the RDW tell us?
it is a measure of the variability in size of circulating erythrocytes
what is the term used for increased variability in size of cell?
anisocytosis
How does anemia manifest in acute blood lost?
through low HGB/HCT 6-12 hours later; there will be a normal MCV/MCH; initially the retic count will stay low, and then 6-7 days later it will rise to compensate for anemia
When does chronic blood lose lead to anemia?
when the rate of loss exceeds the rate of replacement
what type of anemia will present with chronic blood loss?
iron deficiency anemia
What are the two common themes seen with hemolytic anemias?
peripheral destruction is the basis for anemia and the bone marrow will attempt to compensate
what is the main effect of hereditary spherocytosis?
mutations lead to unstable skeletal membrane proteins- so you don’t have stability in the membrane, and as cells are released into the circulation, little pieces get lost over time and as a result the cell has to contract down to form a sphere
what happens to the RBCs in hereditary spherocytosis when they go through the microvasculature of the spleen?
the spherocytes are destroyed because they have lost their ability to deform and move through that microvasculature
the spherocytes moving through the spleen results in what?
splenomegaly–> hypersplenism
In hereditary spherocytosis, a common treatment is to remove the patient’s spleen. Patients without a spleen typically have what in their RBCs?
they have increased “howell Jolly bodies”, which are just DNA inclusions that are typically removed by the spleen
what does the anemia of a patient with hereditary spherocytosis look like? (i.e. MCV, MCH, and MCHC)
MCV= decreased, MCH= same, and MCHC= increased
what is the typical presentation of a patient with hereditary spherocytosis? (3)
anemia, jaundice, and splenomegaly
what can parvovirus infection lead to in anyone with a hemolytic anemia?
an aplastic crisis with overdependence on erythropoiesis
what occurs in a parvovirus B19 infection?
there is destruction of erythroid precursors in the bone marrow
what is the inheritance pattern of G-6-PD deficiency?
x-linked recessive
what demographic is G-6-PD very common in?
sub-saharan africa, middle east, and mediterranean
under what conditions can we peroxidase free radicals?
whenever we have enough reduced glutathione
In order to have enough reduced glutathione, what must we have?
an electron from NADPH
what is the role of G6PD?
it must replace the electron lost from NADPH
When does G-6-PD deficiency present?
it is marked by episodic hemolysis due to oxidative stress–> certain drugs, stress, infection, and select foods such as fava beans
What does oxidative damage cause?
denaturation and precipitation of hemoglobin and other stromal proteins known as Heinz bodies
what happens to the cells with Heinz bodies?
they are less able to traverse the splenic red pulp and may be eliminated- bite cells are where the spleen has removed them
people with the G6PD deficiency actually have an advantage when exposed to what?
plasmodium falciparum
what is sickle cell anemia?
a mutation in the beta chain of hemoglobin can result in variant hemoglobins- like Hgb S; a point mutation that changes an adanine to a thiamine (changes the product from a glutamate to a valine residue)
what happens when a valine is present on the beta-hemoglobin?
it is going to create a polymerization prone molecule
populations with high incidence of HbS may have other variant hemoglobins such as what?
HbC and beta-thalassemia
what exactly happens when you have that beta-globin S variant?
the variant hemoglobin polymerizes and forms a chain of hemoglobin polymers that extends and extends; the polymer chain is growing within the cell and is stretching it out
what makes the polymerization of the variant hemoglobin in sickle cell anemia more likely?
hypoxia, intracellular dehydration, low pH (decreased O2 affinity) and sluggish blood flow
due to the increased fragility of sickled cells, what can occur?
intravascular hemolysis
what is the hallmark presentation of patients with sickle cell anemia?
vaso-occlusive effects (acute respiratory distress, acute chest syndrome, autosplenectomy and infections, aseptic bone necrosis and osteomyelitis)
How is the diagnosis of SS disease made?
hemoglobin electrophoresis
what hemoglobin is present for sickle cell anemia?
S hemoglobin
what hemoglobin is present for SC disease and what are the characteristics?
C hemoglobin; milder than SS, Hgb C can crystalize but it does not polymerize
what do the RBCs look like in SC disease?
you are more likely to see target cells rather than true sickle cells
what are three ways you can treat sickle cell anemia?
hydroxyurea, supportive care, and CRISPR
how do you make beta-globin?
you need one gene per chromosome–> so 2 genes total
how do you make alpha-globulin?
2 genes per chromosome–> so 4 genes total
what causes beta-thal triat/minor?
a mutation on one of the two beta-globin genes
what causes beta-thal major?
with mutations on both of the beta-globin genes- so no beta-globin
what is the effect of beta-thal major?
not only hemolytic anemia but also ineffective erythropoiesis as well (hypoproliferative)
what two effects does ineffective erythropoiesis have?
causes anemia and there is a suppression of hepcidin
what is the effect of suppression of hepcidin?
increased iron absorption by gut enterocytes–> systemic iron overload
in beta thal major, what happens when the erythropoietin is increased but there is still ineffective erythropoiesis?
marrow expansion–> causes skeletal deformities
what are the 3 final outcomes of beta-thal major?
severe anemia, preferential switch to Hgb F, and dramatic medullary and extramedullary hematopoiesis
what is the clinical presentation of beta-thal minor?
microcytic anemia, mild and often asymptomatic
why is it important to differentiate between beta-thal minor and iron-deficiency?
you can pass beta-thal minor down to your kids
what do you get if 3 genes of alpha-globin are hit?
HbH disease
what is HbH/ what are the characteristics of HbH?
it is a tetramer of beta-globin, it has a high affinity for O2- so it is a poor oxygenator
what is the result of HbH disease?
anemia and splenomegaly
what do you get if four alpha genes are hit in alpha-thalassemia?
Hb Bart’s disease (Hydrops fetalis)
what happens when you don’t have any alpha-globin?
you are going to rely on very very immature hemoglobins in the embryonic fetal stagers, and the embryonic fetal hemoglobin is terrible at delivering oxygen
what is the outcome of not having any alpha-globin genes?
anemia and tissue hypoxia, which leads to heart failure and extramedullary erythropoiesis
the heart failure seen in hydrops fetalis leads to what?
edema, ascites, pleural effusion, large heart, and pericardial effusion
what are the anchored membrane proteins that are missing in patients with paroxysmal nocturnal hemoglobinuria?
CD55 and CD59
what is the result of not having CD55 and CD59?
you get complement settling on your RBCs and the MAC forms and the cell lysis
what mutation typically causes paroxysmal nocturnal hemoglobinuria?
mutation on the PIGA gene
what are the characteristics of PIGA mutations?
they are acquired (somatic), they affect a HSC- thus all derived cells are affected
what is PNH a risk factor for?
MDS/AML
How do you treat PNH?
turn off complement: eculizamab is a targeted therapy that blocks C5–> C5a
what happens when you block complement?
prone to getting neisserial infections like meningitis
how can immunohemolytic anemia be categorized?
autoimmune or drug induce and alloimmune
what would you perform to detect the presence of antibody bound to the red cell surface?
Direct antiglobulin test (DAT) aka Coombs test
what would you perform to detect antibodies in the plasma?
indirect antiglobin test (IAT) aka the indirect Coombs test
When you have hemolytic anemias from this autoimmune or drug induced source, they are broadly classified into what?
warm and cold hemolytic anemias
Which Ig subtype is most typically bound at warm temperatures?
IgG
which Ig subtype is most typically bound at cold temperatures?
IgM
where are cold hemolytic anemias more likely to manifest?
in the nose and fingertips
What does a peripheral smear look like in a patient with auto immune hemolytic anemia (AIHA)?
microspherocytes and polychromasia
What could cause hemolysis due to read cell trauma?
mechanical shear like from a prosthetic heart valve
