hematologic pathophysiology of anemias Flashcards
erythrocyte
primary function
produced in
RBC
transport HGB aka transport O2 to tissues
produced in bone marrow
reticulocyte
immature erythrocyte (day 1 or 2 in blood stream) can increase r/t infections
anemia
deficient number of RBC’s
mean corpuscle volume
size of RBC’s
normocytic
normal sized cells
microcytic
smaller than normal sized cells
macrocytic
larger than normal sized cells
HGB definition
four folded globin chains (2 alpha 2 beta)
hemolytic anemia
abnormal hemolysis of RBC’s
RBC and carbonic anhydrase
RBC contains carbonic anhydrase, enzyme that catalyzes reaction between CO2 and H2O to form carbonic acid and H2CO3 (transport CO2 in the form of HCO3- to lungs for removal)
any condition that decreases oxygen transport to tissues will stimulate
erythropoietin, a glycoprotein formed in the kidneys (hence why HD patients need EPO)
erythropoiesis
pluripotent hematopoietic stem cell to pro erythroblast (pronormoblast) to erytheoblast (normoblast) to reticulocyte (3 days in marrow, 1 day in blood) to erythrocyte
what percent of circulating RBC’s are reticulocytes
~1%
anemia main adverse effect
HGB concentration women
HGB concentration men
pregnancy
decreased oxygen carrying capacity
anemia is <12g/dL for women and
<13g/dL for men
pregnancy: physiologic anemia (dilution) due to decreased HCT in relation to increased plasma volume
polycythemia
increase in circulating RBC’s. main adverse effect is increased blood viscosity. cancers, resp deficiency, not enough O2 getting to tissues, so make more trucks
causes of anemia (3)
blood loss
decreased production
increased destruction
acute blood loss anemia
body replaces fluid portion of plasma in 1-3 days leaving a low concentration of RBC’s
RBC concentration usually returns to normal within 3-6 weeks
chronic blood loss anemia
cannot absorb enough iron from the gut to make HGB as rapidly as it is lost
RBC’s are then produced much smaller and have little HGB inside- microcytic hypo chromic anemia
transfusion triggers
10/30 rule, transfuse if HGB <10g/dL or HCT <30% (take comorbidities, risk of bleeding, risk of end organ dysfunction into consideration. if healthy then meh)
Hb levels below 6g/dL benefit from transfusion
RBC transfusions can transmit (3)
hep b
hep c
HIV
risks associated with transfusion: immunomodulatory effects (4)
cancer recurrence
bacterial infections
transfusion related acute lung injury (TRALI)
hemolytic transfusion reactions
general EBL and transfusion thresholds EBL <15% EBL 30% EBL 30-40% EBL 50%
EBL <15%: rarely requires transfusion
EBL 30%: replacement with crystalloids/albumins
EBL 30-40%: RBC transfusion
EBL 50%: massive transfusion, may need accompanied FFP and platelets at a ratio of 1:1:1
types of anemia based on mechanisms: decreased production examples (2)
iron deficiency
autoimmune
types of anemia based on mechanisms: increased destruction (life span of RBC <120 days)
thalassemia
hemolytic anemia
sickle cell
types of anemia based on mechanisms: blood loss
acute
chronic
types of anemia based on mechanisms: infectious
malaria parasite destroys RBC’s
babes (parasite usually spread by ricks) causes RBC hemolysis
parvovirus (fifth disease) virus inhibits erythropoesis
iron deficiency anemia (3) reasons
- nutritional deficiency of iron (common in infants, small children, and developing countries. PICA, eating non foodstuff)
- depletion of iron stores (chronic GIB, unable to absorb sufficient iron from diet)
- pregnancy (increased RBC mass required during gestation)
iron deficiency anemia effect on HGB
iron is required for HGB synthesis, iron deficiency impairs RBC maturation and diminishes red cell production (smaller and pale)
iron deficiency produces microcytic hypo chromic anemia)
treatment of iron deficiency
most important adverse effect of anemia is decreased O2 delivery
oral iron: if elective surgery can be postponed 2-4 months to allow correction of iron deficiency (continued for at least one year after source of blood loss has been corrected)
IV iron: urgent surgery within a few weeks. (not in OR, maybe seen or done in clinic)
RBC transfusion
hemolytic anemia
accelerated destruction (hemolysis) of RBC’s (removed too quickly or lysed too early)
often seen in immune DO’s
RBC lifespan <120 days
hemolytic anemia blood test findings:
increased immature erythrocytes (reticulocytes)
unconjugated hyperbiirubinemia/jaundice
increased lactate dehydrogenase (an enzyme released from lysed RBC’s)
decreased haptoglobin (plasma protein that binds free HGB)
sickle cell anemia as a type of hemolytic anemia
autosomal recessive DO used by single amino acid substitution of B globin that creates sickle HGB
most common familial hemolytic anemia
protective against malaria in heterozygotes (HbS)
in parts of africa, gene frequency approached 30%
8% of patients with AA descent are HbS carriers
most important variable that determines whether HbS containing red cells undergo sickling is:
concentration of other HGB’s
HGB A: normal HGB (2 alpha and 2 beta, the one that is transfused)
HGB F: fetal HGB. newborns with sickle cell anemia are asymptomatic until HbF falls at 5-6 months of age
consequences of sickling RBC’s (3)
- chronic hemolytic anemia
- ischemic tissue damage with episodic pain
- spleen auto infarction (increases risk of sepsis with encapsulated bacteria)
consequence of sickling RBC’s: chronic hemolytic anemia
repeat sickling damaged red cell membrane, eventually producing irreversible sickles cells that are removed from circulation (spleen gets enlarged)
consequence of sickling RBC’s: ischemic tissue damage with episodic pain
localized obstruction in microvasculature. acute chest syndrome, joints involved, risk for CVA or retinal damage
treatments for sickle cells
hydroxyurea, stem cell transplants
hydroxyurea
raises HbF levels, causes intermittent cytotoxic suppression of erythroid progenitors and cell stress signaling, which then affects erythropoiesis kinetics and physiology and leads to recruitment of erythroid progenitors with increased HbF levels.
anti inflammatory
first tested in sickle cell disease in 1084 and decreased rate of acute chest syndrome and blood transfusions by 50%
autoimmune anemia or autoimmune hemolytic anemia (AIHA)
antibodies (IgG and IgM) directed against a persons own RBC’s
RBC lifespan severely decreased
causes of AIHA autoimmune hemolytic anemia
idiopathic
leukemias
infectious (mononucleosis)
drug induced (PCN, quinidine)
treatment of autoimmune hemolytic anemia
immunosuppression and steroids
hemolytic disease of the newborn
incompatibility between mother and fetus, erythroblastosis fatalist
fetus inherits red cell antigenic determinants from father that are foreign to the mother
fetal red cells can enter maternal circulation during 3rd trimester and childbirth (fetomaternal bleed)
sensitizes mother to paternal red cell antigens and leads to production of IgG and anti D red cell antibodies (Rh factor) that cross the placenta and cause hemolysis of fetal red cells
fetus is RhD antigen positive and mother is RhD antigen negative
NEXT pregnancy is problematic and will attack fetus
Rh factor (rhesus)
protein found on surface of red blood cells. genetically inherited, “factor” refers to RhD antigen only (there are several Rh antigens)
RhD antigen is most immunogenic of all non ABO antigens
RhD status of individual
normally described with positive or negative suffix after ABO type (someone who is A positive has A antigen, and RhD antigen, whereas someone who is a negative lacks RhD antigen)
RhoD immune globulin
generally, first antigen incompatible pregnancy does not produce disease because the mother does not produce anti red cell IgG antibodies (the type that crosses the placenta) before delivery
when any incompatibility is detected, the mother often receives an injection at 28w gestation and at birth to avoid the development of antibodies towards the fetus.
vast majority of Rh disease is preventable in modern antenatal care by injections of IgG and anti D antibodies (RhoD immune globulin aka rhoGAM)
glucose 6 phosphate dehydrogenase (G6PD) deficiency
X linked genetic disease, involved in the pentose phosphate pathway which is important in RBC metabolism
half life of erythrocytes approx 60 days
hemolysis occurs due to inability of G6PD deficient RBC’s to protect itself from oxidative damage
G6PD and oxidative damage can be precipitated by (4)
infection
DKA
medictions
fava beans
G6PD deficiency peripheral smears
“bite” cells, red cells with severely damaged membranes that have portions “bitten off” by macrophages removing patches of membrane with associated HGB precipitates known as heinz bodies, leading to intravascular hemolysis
G6PD and response to oxidative stress
hemolysis is often transient, even with persistent infection or drug exposure, because lysis of older cells leaves younger cells with higher levels of G6PD that are resistant to oxidant stress
G6PD and anesthetic risks (includes 4 drugs and 4 other)
avoid risk of hemolysis by not exposing patient to oxidative drugs including metoclopramide PCN sulfa methylene blue
hypothermia
acidosis
hyperglycemia
infection
treatment of G6PD deficiency
no cure
avoid triggers
treat hemolytic episodes with hydration or blood transfusions
polycythemia overview
sustained hypoxia results in compensatory increase in RBC mass and Hct
increases blood viscosity (this slows blood flow and decreases oxygen delivery)
significant when HCT >55-60% (threatens vital organ perfusion, at risk for venous/arterial thromboses)
relative polycythemia
concentrated r/t FVD (dehydration, diuretic OD, vomiting)
physiologic polycythemia
occurs in natives who live at altitudes of 14,000-17,000 feet
atmospheric oxygen is low
RBC count rises to approximately 30% compared to non extreme altitude
first reported in 1980 when french doctor noted that number of RBC’s increased in high altitude environment
polycythemia vera (PCV)
stem cell (or myeloproliferative) DO in which HCT may be as high as 60-70% instead of the normal 40-45%
Mutation of the JAK2 gene which doesnt stop production of RBC when there are already too many present
produces excess erythrocytes and number of platelets and leukocytes may also be increased
most sx appear in 6th or 7th decade
PCV: tyrosine kinase JAK2 gene
signaling molecule in pathways downstream of EPO receptor and other growth factor receptors)
PCV sx
cyanosis HA dizziness GI sx hematemesis melena
effects of PCV:
total blood volume also increases
hepatic, coronary, or cerebral thrombosis is common presenting sign
30% of patients with PV will die from thrombotic complications
30% of patients with PV will succumb to cancer (leukemia)
viscous and engorged vessels (can increase from normal 3x viscosity of water to 10x that of water)
blood passes sluggishly through skin capillaries and a greater amount becomes deoxygenated resulting in bluish/ruddy skin appearance
marrow fibrosis (marrow is replaced by fibroblasts and collagen) is seen in 10% of patients
PCV treatment
without tx, death from vascular complications occurs within months minimize thrombosis risk phlebotomy; helps extend survival by 10y myelosuppressive drugs (hydroxyurea) ruxolitinib (JAK2 inhibitor)
anesthesia and PCV
at risk for thrombosis, reduce HCT prior to surgery (phlebotomy and hydration)
hydration (NPO status versus IVF, admit the night before)
continue hydroxyurea (cytoreductive agent)
