BRS Hematology Flashcards
when does fetal hemoglobin go away
by 6-9 months of age
describe hgb levels at birth and afterwards
high at birth and normally declines, reaches low between 2-3 months in term infant and between 1-2 months in a premie
-hgb reaches adult level after puberty
usually, retics make up ___% of RBCs
1%
MC blood disease during infancy and childhood
iron deficiency anemia mostly 2/2 inadequate intake
nutritional iron deficiency most common in these two age groups
- 9-24 months- inadequate intake, low iron stores
2. adolescent girls- poor diet, rapid growth, loss of iron in menstrual blood
spoon-shaped nails, diminished attention and ability to learn, pale
anemia
- early finding of iron deficiency anemia
- as serum iron decreases, you see these lab findings
- low serum ferritin- b/c iron stores disappear first
- iron binding capacity increases –> increased transferrin and decreased transferrin saturation
- may note increased free erythrocyte protoporphyrin
how to tx iron deficiency anemia
elemental iron; give with vitamin C to enhance absorption
dietary counseling
if anemia doesn’t improve, then you have to look for another cause
normally, most hemoglobin is hemoglobin ______, which is a tetramer containing _____ and ______
A1
2 alpha chains and 2 beta chains
what is wrong in alpha-thalassemia
what is wrong in beta-thalassemia
defective alpha-globin chain synthesis
defective beta-globin chain synthesis
how does thalassemia result in abnormal bones?
hemolysis –> increased bone marrow activity –> marrow space enlarges –> large bones in the face, skull, etc
alpha-thalassemia primarily occurs in this ethnic group
beta-thalassemia primarily occurs in this ethnic group
SE Asian
mediterranean
4 types of alpha-thalassemia
- silent carrier- 1 alpha gene deleted, no anemia, no sxs
- alpha thalassemia minor- 2 alpha genes deleted, mild anemia
- hgb H disease- 3 alpha genes deleted, pts have severe anemia at birth with elevated Hgb Bart’s (binds oxygen very strongly and does not release it to the tissue), anemia is lifelong and severe
- fetal hydrops- 4 alpha genes deleted, only Hgb Bart’s is formed which leads to in utero anemia, CHF, and death
2 types of beta-thalassemia
beta thalessemia major and minor
hemolytic anemia in infancy, marked HSM, bone marrow hyperplasia –> frontal bossing, maxillary hyperplasia with prominent cheekbones, skull deformities
beta-thalassemia major (Cooley’s anemia or homozygous beta-thalassemia)
-total absence of beta chains or deficient beta chain production
lab findings of beta-thalassemia major
- severe hypochromia and microcytosis, target cells and poikilocytes
- elevated unconjugated bili, serum iron, and LDH
- low or absent Hgb A and elevated Hgb F
how to tx beta thalassemia major
lifelong transfusions, splenectomy, +/- BMT
a potential complication of beta thalassemia major
how do you tx it
hemochromatosis
- increased iron absorption from intestine
- more iron in transfused RBCs
tx with deferoxamine (chelator)
this causes mild asymptomatic anemia with Hgb levels 2-3 g/dL below age-appropriate norms
-hypochromia and microcytosis with target cells and anisocytosis
beta thalassemia minor
how to tx beta thalassemia minor
no tx needed
*note, this is often mistaken for iron deficiency anemia… however, iron levels are actually normal or elevated
ring sideroblasts in the bone marrow 2/2 accumulation of iron in the mitochondria of RBC precursors
what is it and what might it be caused by?
sideroblastic anemia
-inherited or caused by toxins
iron deficiency anemia thalassemia sideroblastic anemia lead toxicity chronic disease
causes of microcytic, hypochromic anemia
B12 deficiency
thiamine deficiency
folate deficiency
causes of macrocytic anemia
macrocytic anemias have large RBCs and MCV > ______
95
causes of folic acid deficiency
- decreased folic acid intake (no fresh fruits and beggies, exclusive goat’s milk)
- decreased intestinal absorption of folic acid- small intestine dzs, anticonvulsants, OCPs
how to dx and tx folic acid deficiency
dx with low serum folic acid
tx with dietary folic acid and tx the underlying cause
describe normal vitamin B12 absorption
B12 combines with intrinsic factor and then is absorbed in terminal ileum
causes of B12 deficiency
- inadequate dietary intake (vegan diet)
- inability to secrete intrinsic factor (juvenile pernicious anemia)
- inability to absorb B12 (ex. Crohn’s disease)
anemia, smooth red tongue, neuro issues (ataxia, hyporefliexia, positive Babinski)
B12 deficiency
how to dx and tx B12 deficiency anemia
dx with low serum B12 level
tx with monthly IM B12 injections
splenomegaly by age 2-3 years, pallor, weakness, pigmentary gallstones, aplastic crises assoc with parvovirus B19 infection
what is it, what’s the demographic, how is it inherited, what protein is affected
hereditary spherocytosis
Northern Europeans
AD disorder
spectrin abnormality or deficiency
how to dx hereditary spherocytosis
spherocytes on blood smear
osmotic fragility studies
how to tx hereditary spherocytosis
transfusions
splenectomy is curative but should be delayed until > 5 years 2/2 risk of infection with encapsulated bacteria
mostly asymptomatic, elliptical RBCs on blood smear
what is it, how is it inherited, what protein is messed up, how do you tx it
hereditary elliptocytosis
AD
spectrin
tx: splenectomy for pts with chronci hemolysis; if no hemolysis, no tx is needed
AR disorder that results in decreased production of an enzyme, leading to ATP depletion and decreased RBC survival
what is it, what are the clinical features, what do you see on blood semar
pyruvate kinase deficiency- pallor, jaundice, splenomegaly
blood smear shows polychromatic RBCs
how to dx and tx pyruvate kinase deficiency
dx with decreased PK activity in RBCs
tx with transfusions and splenectomy for severe disease
acute hemolytic disease induced by infection or medications or chronic hemolytic disease
glucose-6-phosphate dehydrogenase deficiency (G6PD)
triggers for G6PD deficiency
infections
fava beans
drugs- sulfa, salicylates, antimalarials
hemolysis with abdominal pain, V/D, fever, and hemoglobinuria followed by jaundice, +/- HSM 24-48 hours after exposure to oxidant
G6PD deficiency
bite cells, hemighosts, Heinz bodies
hemoglobinuria
increased retic count
G6PD deficiency
how to dx and tx G6PD deficiency
dx- low G6PD in RBCs
tx- transfusions as needed; splenectomy not helpful
2 types of autoimmune hemolytic anemia
fulminant acute type
- infants and young children
- preceded by respiratory infection
- acute onset of apllor, jaundice, hemoglobinuria, splenomegaly
- complete recovery is expected
prolonged type
-protracted course, high mortality, underlying disease is often present
lab findings of autoimmune hemolytic anemia
anemia, spherocytes, reticulocytosis, direct Coombs test
how to tx autoimmune hemolytic anemia
transfusions for transient relief
steroids- esp good for acute form of AIHA
mother’s second baby has severe jaundice, anemia, HSN, hydrops fetalis, strongly positive Coombs
Rh hemolytic disease
-mom is Rh negative and produces Rh antibodies from the first pregnancy
in ABO hemolytic disease, a direct Coombs test is _______
it can occur during the first pregnancy
weakly positive
tx for Rh and ABO hemolytic disease
phototherapy if mild-moderate jaundice
exchange transfusion for severe jaundice
**prevent kernicterus
severe HTN, HUS, artificial heart valves, giant hemangioma, DIC can all cause ______
lab findings of this condition
how to tx
MAHA
anemia (burr cells, target cells, irregularly shaped RBCs), thrombocytopenia
supportive care; tx the underlying cause
sickle cell disease is caused by a single AA substitution of _____ for _______ on the number 6 position of the ______ chain of Hgb
valine for glutamic acid
beta-globin chain
pathophys of sickle cell disease
Hgb stacks when exposed to low O2 or acidosis –> distorted RBC shape –> hemolysis and occlusion of small vessels
persons with SS trait have these types of Hgb
clinical features of SS trait
Hgb A (50-60%) Hgb S (35-45%) Hgb F (small amount) -pts usually asymptomatic unless exposed to severe hypoxemia
how to dx sickle cell disease
electrophoresis shows Hgb S and Hgb F in the newborn
SS disease does not present until _____ of age 2/2 protective effects of Hgb F
6 months
most common crisis in SS disease
how to manage it
vaso-occlusive crisis/painful bone crisis
-pain control, IVF, +/- partial exchange transfusion
what is acute abdominal crisis in SS disease
how to tx it
abdominal pain and distention 2/2 sickling within mesenteric artery
tx with pain control, IVF, +/- partial exchange transfusion
dysarthrai, hemiplegia in SS disease patient
what is it and how to tx
stroke
tx with urgent exchange transfusion and start chronic transfusion program to prevent recurrence
always consider _____ in any pt presenting with priapism
SS disease
acute chest syndrome in SS disease
define it and tx it
new pulmonary infiltrate associated with respiratory sxs
-hydration, pain management, abx, O2, incentive spirometry, partial exchange transfusion
sequestration crisis in SS disease
what is it and how to tx
rapid accumulation of blood in spleen or less commonly the liver
tx with transfusion of RBCs +/- splenectomy
aplastic crisis in SS disease
what is it and how to tx
temporary cessation of RBC production often caused by parvovirus B19 or other infectious agent
-tx with transfusion of RBCs
hyperhemolytic crisis in SS disease
what is it and how to tx
- rapid hemolysis –> fatigue, pallor, tachycardia, jaundice
- tx with transfusion of RBCs
which SS disease crises can you do an RBC transfusion and not exchange transfusion
sequestration crisis
aplastic crisis
hyperhemolytic crisis
_____ is the leading cause of death from SS disease
what are the 4 main causes of this
infection 2/2 decreased splenic function
-HIB, strep pneumo, salmonella, Neisseria meningitidis
osteomyelitis in SS disease may mimic painful bone crisis and is usually caused by this organism
salmonella from GI tract
less likely is staph aureus
preventative care for SS disease (3 drugs and 2 other interventions)
- hydroxyurea- increases Hgb F –> decrease incidence of vasoocclusive crises
- daily PCN ppx against strep pneumo infection
- folic acid supplementation
- routine vaccines + prevnar/pneumovax and menactra
- serial transcranial doppler US or MRA to look for pts at risk for stroke
sickle cell-hemoglobin C disease is less severe/more severe than SS disease
less severe
symptomatic anemia within first year of life
rapid onset
often with physical findings: craniofacial, renal, cardiac anomalies; short stature; triphalangeal thumbs
decreased Hgb and retics
what is it and how to tx?
congenital hypoplastic anemia (Diamond-Blackfan anemia)
-tx with RBC transfusion, steroids, and BMT if no response to steroids
slow onset of symptomatic anemia > 1 year of age
decreased Hgb and retics
what is it and how to tx?
transient erythroblastopenia of childhood (TEC)
-no treatment needed… spontaneous recovery
asymptomatic anemia after URI ad slapped cheek
can present as aplastic crisis in kids with SS disease
decreased Hgb and retics
what is it and how to tx?
parvovirus B19 associated pure RBC aplasia
- tx with RBC transfusion for SS disease pts in aplastic crisis
- otherwise, no tx needed
-pancytopenia
-ecchymosis and petechiae around age 7
-short stature, absence of hypoplasia of the thumb and radius
-skin hyper pigmentation
-renal abnormalities
what is it
Congenital aplastic anemia (Fanconi anemia)
AR inheritance
how to tx fanconi anemia
RBC and platelet transfusions PRN
BMT from HLA-compatible person if possible
immunosuppressives like steroids may help
causes of acquired aplastic anemia
drugs- sulfonamides, anticonvulsants, chloramphenicol infections- HIV, EBV, CMV chemicals radiation idiopathic
how to tx acquired aplastic anemia
stop the causative agent
transfusions PRN
BMT
immunosuppressive therapy
define polycythemia
increase in RBCs relative to total blood volume
Hct > 60%
what is polycythemia vera
malignancy involving the RBC that causes polycythemia
causes of secondary polycythemia
appropriate and inappropriate
- appropriate: chronic hypoxemia (cyanotic congenital heart disease, pulmonary disease, residence at high altitudes)
- inappropriate: benign of malignant tumors, excess hormone production, kidney abnormalities
ruddy facial complexion with normal size liver and spleen
sign of polycythemia
EPO level in secondary polycythemia
high
when do you most commonly see relative polycythemia
dehydration
complications of polycythemia (2)
thrombosis- vasoocclusive crisis, stroke, MI
bleeding
factor VIII and IX deficiency PTT PT bleeding time plt count petechiae hemarthroses
prolonged normal normal normal no yes
von Willebrand's PTT PT bleeding time plt count petechiae hemarthroses
prolonged normal prolonged normal no rare
thrombocytopenia PTT PT bleeding time plt count petechiae hemarthroses
normal normal prolonged low yes no
platelet function defect PTT PT bleeding time plt count petechiae hemarthroses
normal normal prolonged normal yes no
vitamin K deficiency PTT PT bleeding time plt count petechiae hemarthroses
prolonged prolonged normal normal yes yes
DIC and liver disease PTT PT bleeding time plt count petechiae hemarthroses
prolonged prolonged prolonged low yes sometimes
_______ = defect in factor VIII procoagulant activity. Plt function is normal
Hemophilia A
________ = factor VIII procoagulant activity is variable but pot function is defective b/c of a decrease of defect in von Willebrand’s factor (needed for pot adhesion to blood vessel walls)
von Willebrand’s disease
inheritance of hemophilia
X linked
hemarthroses and deep soft tissue bleeding are hallmarks of _____
risk of serious and life threatening hemorrhage is lifelong
hemophilia A and B
3 categories of hemophilia severity
severe- spontaneous bleeding, < 1% activity
moderate- bleeding only w/ trauma (1-5%)
mild- bleeding only after surgery or major trauma (> 5%)
how to manage hemophilia A
factor VIII
DDAVP can be useful in mild hemophilia
inheritance of von Willebrand’s disease
AD
3 types of von Willebrand’s disease
type I (classic)- mild quantitative deficiencies of vWF and factor VIII protein... this is the most common form type II- qualitative abnormality in vWF type III- absence of vWF; most severe form
common sxs of von Willebrand’s disease
epistaxis, menorrhagia, bruising, bleeding, mucocutaneous bleeding
how to dx von Willebrand’s disease
quantitative assay for vWF antigen and activity (ristocetin cofactor assay)
how to tx von Willebrand’s disease
DDAVP for mild to moderate bleeding and for ppx
cryoprecipitate for serious bleeding or type III disease
vitamin K dependent factors
II, VII, IX, X, protein C and S
causes of vitamin K deficiency
inadequate intake is unusual
- mediations- cephalosporins, riframpin, isoniazid, warfarin
- decreased absorption- pancreatic insufficiency, prolonged diarrhea, biliary obstruction
- hemorrhagic dz of the newborn- within 24 hrs - 3 months
serious bleeding in new born
-cutaneous bleeding, hematemesis, bleeding from circumcision site or umbilical cord
how do you prevent this?
hemorrhagic dz of newborn
give IM vitamin K after birth
how to tx vitamin K deficiency bleeding
vitamin K
if severe disease, give FFP as needed
prolonged PT and PTT, increased fibrin degradation products, thrombocytopenia
this could be 2 things
how do you tx it?
DIC- fibrinogen, FFP, plts as needed
severe liver dz- vitamin K, FFP, plts as needed
what shape RBCs do you see on smear of DIC
fragmented and helmet shaped RBCs
palpable purpura on LE and buttocks, renal insufficiency, arthritis, abdominal pain
-normal plt count
Henoch-Schonlein purpua (IgA mediated vasculitis)
locally dilated and tortuous veins and capillaries of the skin and mucous membranes
-AD disorder
hereditary hemorrhagic telangiectasia
impaired collagen synthesis –> weakened blood vessels
due to a vitamin deficiency
vitamin C
scurvy
steroids can cause blood vessel weakness and bleeding (T/F)
T
X linked disorder: thrombocytopenia with unusually small plts, eczema, defects in T and B cell immunity
Wiskott-Aldrich syndrome
AR disorder: thrombocytopenia, limb abnormalities like absence of radius (however, compared to falcon anemia, the thumb is present here)
thrombocytopenia-absent radius syndrome (TAR)
cutaneous bleeding or mucous membrane bleeding 1-4 weeks after a viral infection
-thrombocytopenia, few large “sticky” plts
immune thrombocytopenia purpura (ITP)
how to tx ITP
supportive care
- plts < 20,000 or active bleeding warrant IVIG or steroids
- generally do not transfuse plts b/c it will be rapidly destroyed anyways
- can try anti-D immunoglobulin as second line
prognosis and tx of ITP
70-80% resolve spontaneously within months
-if it continues, splenectomy is often curative but due to infection risk, we hesitate to do that in young kids
mother has ITP –> antibodies against her own plts cross the placenta –> antibodies destroy fetus’s plts
-mom has thrombocytopenia
passive autoimmune thrombocytopenia
mother makes antibodies against fetus’s plts –> antibodies cross placenta and destroy fetus’s plts
-mom has normal pot count
isoimmune thrombocytopenia
enlarging hemangioma, MAHA, thrombocytopenia, consumptive coagulopathy
Kasabach-Merritt syndrome
AR disorder: diminished ability of plts to aggregate 2/2 deficient adhesive glycoprotein IIb/IIIa on the plt cell membrane
Glanzmann’s thrombasthenia
AR disorder: decreased plt adhesion as a result of absence of plt membrane glycoproteins
bernard-soulier syndrome
causes of acquired qualitative plt disorders
drugs- aspirin, depakote
uremia and severe liver disease
purpura fulminans- nonthrombocytopenic purpura (fever, shock, rapidly spreading skin bleeding and intravascualr thrombosis )
presentation of homozygous protein C deficiency
how do protein C heterozygotes present
later with DVT or CNS thrombosis
how to tx protein C deficiency
heparin, FFP, warfarin, protein C
define neutropenia levels (3)
mild- ANC 1000-1500
moderate- ANC 500-1000, infection of mucous membranes and skin
severe- ANC <500, severe infections esp with staph aureus and gram negative bacteria
_______ are the most common cause of neutropenia during childhood
infections
- HIV, EBV, EMV, Hep A and B, influenza, parvovirus
- typhus, RMSF
- protozoans
increased incidence of mild infections
noncyclic neutropenia
otherwise healthy with normal appearance and growth
chronic benign neutropenia of childhood (CBN)
what does the bone marrow look like in chronic benign neutropenia of childhood
immature neutrophil precursors
prognosis of chronic benign neutropenia of childhood
resolves spontaneously in months to years
AR disorder where ANC is usually < 300
severe congenital agranulocytosis (Kostmann syndrome)
how to dx cyclic neutropenia
how long are the cycles
dx with serial neutrophils counts during a 2-3 months period
cycles are usually 21 days
AR disorder: oculocutaneous albinism, large blue-gray granules in cytoplasm of neutrophils, *neutropenia, blond or brown hair with silver streaks
chediak-higashi syndrome
AR disorder: short stature, immunodeficiency, fine hair, *neutropenia
cartilage-hair hypoplasia syndrome
exocrine pancreatic insufficiency with malabsorption, short stature 2/2 metaphyseal chondrodysplasia, *neutropenia
schwachman-diamond syndrome
isoimmune neutropenia
mother makes antibodies to baby’s neutrophils –> causes neutropenia in baby that resolves by 8 weeks of life
autoimmune neutropenia can happen 2/2 infection, drugs, SLE, JRA, etc (T/F)
T
in iron deficiency anemia, the free erythrocyte protoporphyrin is elevated/decreased
elevated
pts with SS trait may have these sxs
inability to concentrate urine, hematuria
beta thalassemia puts you at increased risk for hemochromatosis (T/F)
T
goat’s milk only leads to ____ deficiency
folic acid
spoon shaped nails seen in ____ deficiency
iron
smooth red tongue seen in _____ deficiency
B12
