Hematology Flashcards
What is hemoglobin A comprised of?
a tetramer consisting of one pair of alpha globin chains and one pair of beta globin chains
What is the defect in beta thalassemia?
impaired production of beta globin chains, leading to a relative excess of unstable alpha globin chains
What happens when you have excess alpha globin chains (as in beta thal)?
Excess alpha globin chains are unstable, incapable of forming soluble tetramers on their own, and precipitate within the cell, leading to a variety of clinical manifestations. The degree of alpha globin chain excess determines the severity of subsequent clinical manifestations, which are profound in patients homozygous for impaired beta globin synthesis
How do infants with beta thalassemia present at birth?
Infants with severe beta thalassemia major (BTM) are well at birth, because the production of beta globin is not essential during fetal life or the immediate perinatal period. The major non-alpha globin produced at the time of birth is gamma globin, such that the major hemoglobin in early postnatal life is fetal hemoglobin (Hb F, alpha2/gamma2).
When would an infant develop symptoms of beta thalassemia major?
During the second six months of life when gamma globin chain production decreases and should be replaced with the production of beta globin to form adult hemoglobin (Hb A, alpha2/beta2).
What is the classic xray finding in beta-thalassemia?
hair-on-end apperance of the skull
What is the Mentzer index?
MCV/RBC
if >13 iron deficiency is more likely
What is neonatal alloimmune thrombocytopenia (NAIT)?
fetal platelets contain an antigen inherited from the father that the mother lacks, most commonly human platelet antigen (HPA)-1a
What is the most likely cause for inability to reach therapeutic heparin level despite increasing doses?
Antithrombin III deficiency
1st line treatment for DVT?
Low molecular weight heparin
What does bone marrow aspirate show in transient erythroblastopenia of childhood?
Arrested erythroid precursors
What are predictors of poor outcome in sickle cell disease?
Dactylitis, Hb
What are the 3 main features of Wiskott-Aldrich?
(1) Severe eczema
(2) Thrombocytopenia
(3) Frequent infections
What would be the reason for increasing episodes of bleeding and hemarthrosis of the ankle despite meditation compliance?
Check FVIII and inhibitor levels
Types of Von Willebrand disease
Type 1 -Decrease in quantity
Type 2 - Abnormal quality
Type 3 - No VWF (most rare)
Medications used in VWD
DDAVP - increases release of VWF
*will not work in Type 2, Type 3
What is the antigen implicated in NAIT?
HPA-1A (used to be called PLA-1) *give PLA-1 negative platelets)
What is the pathophysiology/process in NAIT?
Caused by antibodies specific for platelet antigens inherited from the father but which are absent in the mother (analogous to Rh-)
What are the vitamin K-dependent factors?
10, 9, 7, 2
When does the classic form of hemorrhagic disease of the newborn present?
1 day - 2 weeks (not enough placental transfer from mom)
When does the early form of hemorrhagic disease of the newborn present?
< 24 hrs
When does the late form of hemorrhagic disease of the newborn present?
2 weeks - 12 weeks (exclusively in breastfed infants - not taking enough vitamin K)
Features of DIC
Elevated D-dimer, low platelets, low fibrinogen, elevated INR/PTT
Conditions associated with polycythemia
T21, recipient twin, LGA, maternal diabetes, Beckwith-Wiedemann, thyroid abnormalities, chromosomal abnormalities
Timing of physiologic hemoglobin nadir in preterm vs. term babies?
Term - 6 to 8 weeks
Preterm - 3 to 7 weeks
What do you see on the blood smear for a child with HUS?
Schistocytes (sign of intravascular hemolysis)
Signs of Diamond Blackfan anemia on physical exam
abnormal thumbs (long, bifid), absent radial pulse, craniofacial abnormalities
What is the objective of using leukoreduced white cells?
To prevent febrile transfusion reactions
What is Shwachman-Diamon syndrome?
Shwachman-Diamond syndrome (SDS, also known as Shwachman-Bodian-Diamond syndrome, Shwachman-Diamond-Oski syndrome, or Shwachman syndrome) is a rare inherited disorder associated with neutropenia that may progress to bone marrow failure, exocrine pancreatic insufficiency, and skeletal abnormalities that generally presents in infancy.
What is the appropriate empiric antibiotic regimen for ACS in HbSS?
Broad spectrum empiric coverage with a third generation cephalosporin (eg, cefotaxime or ceftriaxone) for bacterial coverage and a macrolide (eg, azithromycin or erythromycin) for coverage of atypical organisms (eg, mycoplasma and chlamydia) should be initiated immediately on admission.
Children with sickle cell are at risk of infection with which organisms?
Strep pneumo Haemophilus influenza Neisseria E coli Salmonella Klebsiella Group B strep
chronic ITP - length of time?
> 12 months
complications of IVIG
aseptic meningitis, hemolytic anemia, TRALI, thromboembolism…
How many genes are involved in alpha thalassemia?
4
how many genes are involved in beta-thalassemia?
2
what are the possible mutations in alpha-thal trait?
aa/– (cis), a-/a- (trans)
what is the gene deletion in Hb-H? (alpha-thalassemia)
a-/–
what is Hemoglobin Barts Disease?
complete absence of alpha-thalassemia gene (–/–)
fatal
what is the gene deletion in beta-thal trait?
B/-
what is beta-thal major?
-/- (homozygous), cannot make HbA (makes HbF, aa/gg)
CD19 - what type of cell
B-cell
CD3 - what type of cell
T-cell
CD33 - what type of cell
myeloid
MPO - what type of cell
myeloid
what % of childhood cancer is acute leukemia
25%
favourable cytogenetics in acute leukemia
ETV-RUNX1 (TEL-AML), trisomy 4 and 10
translocation in Ph chromosome positive acute leukemia
t(9;22)
translocation in APML
PML-RARa, t(15;17)
which steroid is worse for causing osteonecrosis?
dex is worse than pred
side effects of cisplatin
N/V, hypomagnesemia, hypokalemia, tubular dysfunction, hearing loss
what is Li Fraumeni?
mutation in p53 - results in sarcomas, breast ca, medulloblastoma, adrenocortical ca
What is Gorlin syndrome?
mutation in PTCH gene, causes basal cell ca, medulloblastoma
What is DICER-1 syndrome?
mutation in DICER-1, causes pleuropulmonary blastoma, thyroid ca, ovarian ca, renal tumours
what tumours do patients with NF1 get?
neurofibromas, nerve sheath tumours, optic nerve glioma
B-symptoms
- drenching sweats (w/i last month)
- weight loss > 10% (x 6 months)
- unexplained fever > 38C (within last month)
what cell is characteristic of hodgkin’s lymphoma?
reed-sternberg
Hemoglobin A - subunits
A2 B2
Hemoglobin A2 - subunits
A2 delta 2
Hemoglobin F - subunits
A2 gamma 2
alpha globin genes on what chromosome?
chr 16
beta, delta, gamma globin chains - on what chromosome?
chr 11
How many normal hemoglobin types are there?
SIX! 3 embryonic fetal hemoglobin HbA HbA2
Neonate and adult RBC lifespan
Neonate: 60-90 days
Adult: 120 days
Effect of anemia on 2,3-DPG in RBCs and O2 saturation curve
anemia increases 2,3-DPG in RBCS
results in RIGHT SHIFT of O2 saturation curve (oxygen more likely to be distributed to tissues and less likely to saturate hemoglobin)
PE features of DBA
short stature hypertelorism snub nose triphalangeal thumbs absent radial pulse
How can you distinguish DBA from TEC?
DBA - elevated RBC ADA activity, may have dysmorphic features, macrocytosis
How do you treat DBA
Steroids after 6-12 mos of age
If unresponsive to steroids, then pRBCs + chelation
Can also do matched sib allogeneic transplant < 10 yrs - good outcomes but controversial
20% spontaneously remit in their first decade of life!
What causes mortality in DBA?
Treatment (infections relating to steroid tx, iron overload)
Aplastic anemia, malignancy
What age group of kids gets TEC?
6mo - 5 yrs
usually 1-3yrs
TEC - other cell lines?
20% have neutropenia
Can have thrombocytosis
When do kids recover from TEC?
1-2 mos
Who gets aplastic crises with parvovirus?
children with hemolytic anemia conditions (HbSS, spherocytosis)
fetuses (congenital parvo), preterm infants
immunocompromised
(anyone with shortened RBC lifespan)
What lab test differentiates anemia of chronic disease and iron deficiency anemia?
total iron binding capacity (serum transferrin) is normal/low in anemia of chronic disease and increased in iron deficiency
Name three factors contributing to the physiologic anemia of infancy
- Increased O2 at birth
- Change in hemoglobin from fetal to adult (less affinity for oxygen, shift in O2 saturation curve to right)
- decreased EPO production
When does the physiologic nadir in HgB occur in the newborn?
8-12 weeks
Why does the physiologic nadir occur earlier in pre-term infants? (3 reasons)
- shorter RBC lifespan
- less EPO upregulation (made by kidney in term infants, liver macrophages in preterm infants)
- frequent blood sampling
What are the other cell lines like in a megaloblastic anemia?
usually there is thrombocytopenia and leukopenia! (characterized by ineffective myelopoeisis)
Where is Vit B12 absorbed?
ileum
Where is folate absorbed?
jejunum
ddx folate deficiency
increased requirements (hemolysis, pregnancy, growth)
decreased intake (malnutrition, powdered milk, goat’s milk)
malabsorption (jejunum - IBD, diarrhea, certain AEDs)
abnormal folate metabolism
What test do you order to investigate folate deficiency?
RBC folate (more reflective of chronic deficiency)
Lab values reflecting vit B12 deficiency
elevated homocyteine and methylmalonic acid (elevated urine MMA)
elevated LDH (as a marker of ineffective erythropoiesis)
thrombocytopenia, leukopenia
PE findings of vit B12 deficiency (not anemia-related)
glossitis neurologic abnormalities (paresthesias, weakness, seizures)
most common nutritional deficiency worldwide?
iron deficiency anemia
non-hematologic side effects of iron deficiency
impaired cognition
impaired motor development
poor concentration
irritability
What is pica?
the desire to ingest non-nutritive substances
DDX of microcytic anemia that does not respond to iron supplementation
- incorrect dose of iron
- not taking iron
- malabsorption
- ACD
- concurrent folate/B12 deficiency
- bleeding
- thalassemias
When would you give IV iron?
malabsorption
poor compliance
How much bovine milk should a child > 1 yr drink per day in order to prevent iron-deficiency anemia?
16-24 ounces per day
Serum haptoglobin in hemolysis?
decreased
binds to free hemoglobin, cleared more rapidly when conjugated
what pathogen can cause an aplastic crisis in a patient with hemolytic anemia, and how long does the aplastic crisis last?
parvovirus b19
typically lasts 10-14 days
Why do RBC membrane abnormalities cause hemolysis?
Abnormal shape = less deformable = hemolyze in spleen
HS is caused by mutations in what genes?
spectrin
ankyrin
band 3
HS - PE and other findings
extra-medullary expansion
splenomegaly
pigmented gallstones
DDX spherocytes
HS AIHA Hemolytic disease of the newborn Coombs + hemolysis clostridial sepsis Thermal injury
What should a patient with chronic hemolysis take?
Folic acid 1mg per day
What is Paroxysmal nocturnal hemoglobinuria?
RBCs are sensitive to complement, causes them to break down! results in intravascular hemolysis, hemoglobinuria
What are two life-threatening things that patients with paroxysmal nocturnal hemoglobinuria at risk for?
thrombosis
aplastic crisis
On what chromosome are the genes encoding alpha-globin?
chr 16
On what chromosome are the genes encoding beta-globin?
chr 11
Normal adult hemoglobin patterns
HbA > 95%
HbA2 < 3.5%
HbF < 2.5%
HbSS - why is there an increased risk of bacterial infection? (two reasons)
- functional asplenia
2. deficient in alternative complement pathway serum opsonins against pneumococcus
Criteria associated with increased risk of bacteremia in HbSS with fever
- unwell appearing
- hypotensive
- fever > 40
- WBC > 30
- Plts < 100
- hx of pneumococcal sepsis
- severe pain
- dehydrated
- Hgb < 50
- infiltrates on CXR
Bugs causing osteomyelitis in HbSS
Salmonella
Staph aureus
Clinical signs of splenic sequestration
Increase in spleen size
Hypovolemia
Drop in Hgb > 20 from patient’s baseline
Treatment of splenic sequestration
Supportive care, IV fluids
consider small RBC transfusion (don’t want to over-transfuse, when blood returns to circulation can be hyper viscous and have stroke!)
Risk of recurrence highest within 6 mos post episode
Splenectomy - only way to prevent
Stimuli for pain crises in HbSS
physical stress infection dehydration hypoxia acidosis cold prolonged swimming
Treatment of HbSS priapism lasting > 4 hrs
supportive therapy - sitz baths, pain medication
aspiration of blood from corpora cavernosa, irrigate with dilute epinephrine (urology consultation!)
Management of stroke in HbSS
Urgent peds neuro consult
O2
Transfuse to Hb > 100
Consider exchange transfusion (to HbS < 30%)
HbSS - CNS risks
Stroke
PRES
CSVT
Reduction of stroke in HbSS
Transcranial doppler assessments - if abnormal, life-long transfusion therapy is initiated to keep HbS < 30%
(results in 85% reduction in rate of stroke!)
How do you assess for iron overload in patients w/ HbSS on transfusion therapy?
MRI heart + liver
alternative: Ferriscan
How do you treat ACS in HbSS?
- oxygen
- ceftriaxone + macrolide
- incentive spirometry
- pain management
- avoid fluid overload
- physio
- consider t/f +/- exchange
What two genotypes can cause Sickle Cell Anemia?
HbSS
HbS/b-thal 0
What complications of sickle cell disease do patients with HbSC have more frequently?
Retinopathy
Splenic sequestration
Renal medullary carcinoma
What complications are associated with HbSA (sickle trait)
Renal medullary cancer Hematuria Splenic infarction Exertional rhabdomyolysis Exercise-related sudden death Protection from falciparum malaria Hyphema Thrombosis Recurrent spontaneous abortions
HbAC phenotype
Asymptomatic
HbSC phenotype
Less severe version of HbSS
HbCC phenotype
Mild anemia, splenomegaly, pigmented gallstones
NO SICKLING
HbC causes hemolysis through disruption of RBC membrane
What is Methemoglobin?
Hemoglobin that contains ferric iron (Fe 3+)
instead of ferrous iron, Fe 2+
What can increase the methemoglobin percentage?
Nitrate exposures
G6PD
Medications (benzocaine, chloroquine, dapsone)
How do you treat methemoglobinemia?
Methylene blue infusion
can’t use in G6PD!
