Hematology Flashcards
what is the most common transfusion related infection?
CMV
what proteins make up hemoglobin?
alpha
beta
delta
gamma
what proteins make up a fetus’s hemoglobin?
alpha
gamma
when does HgbA overtake HgbF?
HgA overtakes hemoglobin F by 3 months
by 6 months there is very little HbF
what is HbA
a2b2
what is HbA2
alpha 2 delta 2 (normally up to 3% of adult hgb)
what is HbH
Hb Bart
HbH: 4 beta
Hb Bart: 4 delta
are most mutations in alpha or beta??
beta!!
when do we see physiologic nadir of Hb in term babies?
8-10 weeks
after birth oxygen saturation increases and therefore causes decreased EPO, then EPO production is resumed with an increase in the retic count
when do we see physiologic nadir of Hb in preterm babies?
6-8 weeks
nadir is earlier and deeper (>70)
what is the definition of anemia
Hb 2 standard deviations below mean value for age, gender and race
how should you classify anemia?
decreased production
- microcytic
- macrocytic
- normocytic
increased destruction
- intrinsic- membrane, hemoglobin enzyme
- extrinsic- immune, non-immune
where is your blood made?
bone marrow
where is fetus’s blood made?
liver
where is embryo’s blood made?
yolk sac
what is normal hb for men? women? newborn?
men: 140-180
women: 120-160
newborn: up to 200/220
what are markers of RBC destruction?
icterus dark urine increased reticulocytes increased unconjugated bilirubin increased LDH hemoglobin (not rbc's) in urine urobilinogen decreased haptoglobin
Ddx of microcytic anemia
T- thalassemia A- anemia of chronic disease (usually normocytic but can be microcytic) I- iron deficiency L- lead S- sideroblastic
Ddx macrocytic anemia
megaloblastic:
folate
B12
marrow failure:
myelodysplasia, diamond-blackfan, falcon anemia, aplastic anemia
other: hypothyroidism, Down syndrome, chronic liver disease, drugs (AZT, alcohol)
Ddx of normocytic anemia
chronic disease chronic renal failure transient erythroblastopenia of childhood malignancy/marrow infiltration HIV HLH
Most common: TEC, malignancy or anemia of chronic disease
normocytic anemia with inadequate reticulocyte response should usually lead to consideration of a bone marrow exam
Ddx of intrinsic hemolytic disorders
membrane: hereditary spherocytosis, elliptocytosis
enzyme: G6PD deficiency, PK deficiency
hemoglobinopathy: HbSS, SC, S-B thal
Ddx of extrinsic hemolytic disorders
immune- autoimmune, iso-immune, drug-induced
non-immune- HUS, TTP, DIC, burns, Wilson, vit E deficiency
what are the 3 most important lab tests for evaluating anemia?
CBC: MCV, WBC, RBC, Plts
reticulocyte count
peripheral blood smear
what are some optional tests for iron deficiency anemia? (5)
serum iron transferrin/TIBC ferritin soluble transferrin receptor bone marrow biopsy
when do you see pencil cell on smear?
iron deficiency
when do you see basket cell on smear?
pathognomonic for G6PD deficiency
what is the most common cause of worldwide anemia?
iron deficiency anemia
10% of infants and adolescent girls are iron deficient of which one third are anemic
what are some complications of iron deficiency anemia
irritability poor concentration GI dysfunction reduced immunity pica poor school performance lead poisoning
what are 4 mechanisms causing iron deficiency anemia?
inadequate iron endowment at birth (prematurity)
insufficient iron in the diet
blood loss (menstruation)
malabsorption of iron (celiac disease, IBD, giardiasis)
why does excessive cows milk lead to iron deficiency anemia?
iron is absorbed at 50% efficiency from breast milk and 10% from cows milk
excessive cow’s milk interferes with balanced nutrition and causes GI blood loss
what is the treatment for iron deficiency anemia?
limit cows milk to 16-24 ounces/day
start 4-6mg/kg/day of elemental iron (Taking vit C helps with absorption)
check CBC and retics within 1-2 weeks of treatment
therapy should continue for at least 3-6 months to replenish iron stores
if hemoglobin is not increased within 2 weeks then consider non-compliance
which of the following is not a feature of iron deficiency pica koilonychia cheilosis scleral icterus psychomotor retardation
scleral icterus is NOT
koilonychia- groove in nails
cheilosis- cracking at corner of mouth
you are seeing a child with microcytic hypo chromic anemia. You believe it is iron deficiency. What other features of the CBC would be consistent with this?
- increased RDW
- thrombocytosis
- MCV/RBC >13 (<13 is suggestive of thal trait)
- pencil cells
what is seen if a patient has 3 alpha genes (1 alpha gene missing)
silent carrier state
slightly reduced hemoglobin and MCV
Hb electrophoresis pattern is the same as normal
what is seen if a patient has 2 alpha genes missing
anemia (100)
microcytosis
not picked up on Hb electrophoresis
what are the differences between iron deficiency anemia and alpha thal trait?
in alpha thal, iron studies are normal
in alpha thal, RDW is normal. in IDA RDW is high.
in alpha thal, RBC is increased, usually around 5 and the MCV is very low
in IDA the platelets are often increased
Hb electrophoresis is normal in both
what is the Mentzer’s index?
MCV/RBC is >13 in IDA
<13 in thal trait
what is seen if a patient has 3 alpha genes missing
Hb H disease moderate anemia (70-100) hypochromia microcytosis target cells heinz bodies splenomegaly jaundice HbBart may be present
what does Bo mean?
absent production (more severe thalassemia)
what does B+ mean?
reduced production
what does B thalassemia minor mean?
one defective gene
either BBo or BB+
how do you diagnose B thalassemia minor? what is seen on hemoglobin electrophoresis? is treatment required?
based on Hb electrophoresis pattern
increased HbA2 and HbF
they do not need any treatment at all other than genetic counselling
there is no increased incidence of complications
what is B thalassemia major?
either BoB+ or BoBo
severe anemia
abnormal growth
iron overload and the need for transfusion
on electrophoresis: HbF (95%)
No HbA for BoBo
what is the most common complication seen with B thalassemia major?
iron overload
mostly in the liver then the heart and endocrine glands
what is the treatment for thalassemia major?
regular transfusions and iron chelation
iron chelation: parenteral desferoxamine or oral deferasirox
bone marrow transplant can be curative
what is the most likely diagnosis with the following HbA- none HbA2- 2% HbF- 75% HbS- 25%
sickle cell trait
sickle cell disease
beta thalassemia
alpha thalassemia
sickle cell disease
Ddx of normocytic anemia
anemia of chronic disease
malignant infiltration
diamond-blackfan anemia
transient erythroblastopenia of childhood
what is transient erythroblastopenia of childhood
normocytic anemia
usually appears in otherwise health children age 1-3
often after a viral trigger (not necessarily Parvo)
onset is gradual, anemia can be severe
recovery is spontaneous within 1-2 months
the main ddx is diamond-blackfan anemia
key is that it is transient!!
HbF normal whereas HbF increased with diamond blackfan
what causes an aplastic crisis
parvovirus B19
what test can help confirm the diagnosis of hereditary spherocytosis
osmotic fragility (although nonspecific)
what is the treatment for hereditary spherocytosis
splenectomy- corrects the anemia and normalizes the RBC survival even though the spherocytes persist
what is the most common presentation of spherocytosis in a newborn?
jaundice
what is the most common complication of hereditary spherocytosis?
gall stones
how is G6PD inherited
X chromosome enzyme
what are some oxidants that can trigger G6PD
sulfa drugs nitrofurantoin dapsone anti-malarial fava beans infection rasburicase
what is the treatment for G6PD
supportive
avoidance of triggers
what are the 3 types of autoimmune hemolytic anemia
warm (IgG)
cold (IgM)
biphasic
what is the treatment for warm autoimmune hemolytic anemia?
supportive care
transfusions
steroids
What is given to moms to prevent hemolytic disease of the newborn
rhogam is given at 28 weeks if Rh-
also at delivery or if any invasive procedures
the severity of Rh incompatibility at the time of birth is best predicted by what?
cord hemoglobin
what is the triad for HUS
microwngiopathic hemolytic anemia
thrombocytopenia
renal impairment
caused by Ecoli O157:H7 toxin
what is primary hemostasis
platelet plug
what is secondary hemostasis
coagulation cascade
what factors are involved in the intrinsic pathway
12, 11, 9 and 8
**primarily 8 and 9
what factors are involved in the extrinsic pathway
factor 7
what factors are involved in the common pathway
factor 10
factor 2
fibrin (factor 13)
= clot
what does plasmin do?
degrades your fibrin clot
what can activate plasminogen to plasmin
tPA
urokinase
what are vit k dependent factors
2, 7, 9, 10
pn c and s
what factors do protein c and s work on
5 and 8
what does heparin do to antithrombin
binds to antithrombin and forces it to come into close proximity with thrombin
what factors is affected by LMWH? UFH?
LMWH: factor 10
UFH: factor 10 and thrombin
differences between UFH and LMWH
UFH fast onset and offset not affected by renal function can be given IV cheap monitor with PTT
LMWH more predictable can be given at home less frequent monitoring monitor with anti-Xa
why do you need bridging when you start warfarin?
because protein c and s have shorter half life so they go down first and you are at increased risk of clotting for the first couple of days
therefore always need bridging with heparin
what test should you do if you have an abnormal INR or PTT
mixing study
what test should you do if you have a normal platelet count but primary hemostasis problem suspected?
PFA-100 to assess platelet function
Ddx for normal INR with elevated PTT
factor 8 factor 9 factor 11 vWD heparin
Ddx for elevated INR with normal PTT
factor 7
early vit k deficiency
warfarin
early liver disease
Ddx for elevated INR and PTT
liver disease
late vit k deficiency
DIC
does factor 13 affect INR or PTT
NO!!
therefore if bleeding disorder is strongly suspected in the face of normal coags a facto 13 level should be measured
delayed bleeding, umbilical stump separation
what factor affects PTT but is not a bleeding disorder
factor 12
what is the dose for oral vitamin k and when should it be given?
2mg PO
repeated at 2-4 weeks and 6-8 weeks
what is the most common inherited bleeding disorder
vonwillebrands disease
what does ristocetin test?
vWF function
what is the biggest side effect from DDAVP? how does it work?
hyponatremia
therefore hold free water
DDAVP appears to act by causing the release of vWF from the endothelial cells
what is the treatment for vWD
DDAVP (for type 1 and 2 vWD) factor VIII-vWF concentrate OCP and treatment for anemia if needed for menorrhagia supportive care: avoid NSAIDs, helmet TXA is useful for mucocutaneous bleeds
what is type 3 vWD
absence of vWF
what is type 1 vWD
quantitative deficiency of normal vWF
what is type 2 vWD
qualitative problems with vWF (abnormal function)
what is hemophilia A
factor 8 deficiency
what is hemophilia B
factor 9 deficiency
how is hemophilia inherited
x-linked
women are carriers but can have the disease with turner,s lyonizaition or homozygosity
how is hemophilia classified into mild, moderate and severe
severe <1% factor activity level
moderate: 1-5%
mild: 5-30%
what is the most common chronic sequelae of hemophilia
arthritis
what is the treatment for hemophilia
prophylactic factor after delivery can be considered
don’t forget to give vitamin K- lots of pressure on site
acute treatment- factor should be given
DDAVP can be used for mild/moderate hemophilia A but must have a DDAVP challenge first
list 4 clinical presentations of hemophilia in the neonatal period
IVH circumcision bleeding IM hematoma after IM vit k large caput or smbgaleal hemorrage excessive bleeding with phlebotomy
name one indication for transfusion of FFP
reversal of warfarin
when would you transfuse cryoprecipitate
for low fibrinogen (<0.8-1.0)
for bleeding with vWD or hemophilia ONLY if factor or DDAVP is unavailable
what does leukoreduction do?
reduced febrile non-hemolytic reactions
reduces Allo-immunization
reduces viral transmission
what does irradiation do
reduced GVHD for immunosuppressed recipients
what is the most common fatal reaction associated with transfusion
TRALI and sepsis
what is the most common acute reaction
allergy
then fever
what is the most common pathogenic infection associated with transfusions
parvovirus
what should you do if there is a transfusion reaction
stop the transfusion
keep IV
send blood and samples to lab
provide supportive care
what is the treatment for massive hemorrhage
1 unit of plts and 1 unit of FFP for every 4 units of pRBCs
what are some complications following splenectomy
infection- pneumococcal/h influenza, meningococcal
thrombo-embolic complications
pulmonary hypertension
List 3 long term effects of cyclophosphamide
pulmonary fibrosis
bladder cancer
Reproductive effects: Gonadal dysfunction, delayed or arrested puberty, premature menopause, germ cell dysfunction or failure, infertility
List 4 indications for blood transfusion in sickle cell disease
Acute chest syndrome
Abnormal transcranial dopplers, or acute stroke
Acute splenic sequestration (but only give ½ volume BECAUSE of autotransfusion)
Aplastic crisis
Prior to surgery (for Hb around 100)
Exchange transfusion is reserved for stroke, severe ACS, and pre-op some major surgeries.
Generally, transfusion NOT indicated for vasoocclusive
crisis.
Black kid from Kenya very sick with chest symptoms. Hgb is 48- what is underlying dx and 4 things to do (ie. symptoms of acute chest)
- Pain management
- supplemental O2
- antibiotics (ceftriaxone and azithromycin)
- transfusion
Young kid with behaviour change, microcytic, hypochromic anemia with basophilic stippling. Physician has already done iron studies, which were normal. What would you test?
lead levels (basophilic stippling)
Newborn with non-hemorrhagic stroke – 4 inheritable etiologies for clot
- factor V Leiden
- Pn C deficiency
- Protein S deficiency
- Antithrombin deficiency
- Prothrombin mutation
A full term newborn develops petechiae and bruising. The baby is otherwise well appearing. On bloodwork his platelets are 12, WBCs are 18 and his Hgb is 140. He is given a platelet transfusion and a repeat platelet count is 16. The mother’s CBC shows platelets of 80. What is the best treatment: PLA-1 negative platelets IVIG Washed maternal platelets Steroids
IVIG
due to maternal ITP
Give 4 mechanisms of anemia in a child with chronic renal disease.
Decreased erythropoietin production (major cause)
- Iron deficiency
- Anemia of chronic disease
- Increased blood loss (dialysis, hematuria, blood tests)
- secondary hyperparathyroidism - can suppress RBC production
You are treating a 7-year-old girl with ALL for a
central line line-associated thrombus. Despite
regular increases in her heparin dose you can’t
achieve a therapeutic level. What is a possible
cause?
1. Antithrombin III deficiency
The way heparin works is by binding to thrombin and antithrombin and bringing them together
Antithrombin then antis-the thrombin
2. Protein C deficiency
3. Factor V Leiden
4. Factor VIII deficiency
Antithrombin III deficiency
3 year old new Canadian with sickle cell disease comes to you for the first time. List 5 things that are important to do for this child right now.
Immunizations - encapsulated organisms
Penicillin prophylaxis
CBC + smear
Hgb electrophoresis
Educate for pain crisis/risk of infection (management of fever and spleen palp)
Transcranial doppler starting at 2yoa - if high flow may need blood transfusions to keep HbS <30% (decreases stroke risk)
what is the main risk from partial exchange transfusion for polycythemia
NEC
What is seen on peripheral smear for HUS
Schistocytes
10 year old girl with Sickle Cell Disease and a history of stroke. Which treatment is most recommended given her history of stroke?
Hydroxyurea
Transfusion with PRBCs
Folic acid
transfusion with pRBCs
what are 3 management strategies for tumor lysis syndrome
- IVF
- Rasburicase/ allopurinol
- Monitor electrolytes q4-6h
A 7 year old girl comes to see you with
decreased energy and pallor for the past week.
She had a viral illness 1-2 weeks ago. You notice
that her sclerae are “a bit yellow”. Her CBC show
a Hb 70, WBC 8.6, Platelets 245, 24% retics.
1. What type of anemia is this?
2. What test would you do to confirm?
3. What treatment could you offer?
hemolytic anemia (autoimmune)
DAT
Steroids
when do you see Howell-Jolly bodies on smear
asplenia
what are two causes of osteomyelitis in sickle cell disease
salmonella and staph aureus
what is the treatment for stroke in SCD? How can you prevent a second stroke?
exchange transfusion
After a stroke, chronic transfusion to maintain Hb S below 30% can prevent a second stroke by 80%.
when should transcranial dopplers be performed on patients with sickle cell disease
starting at age 2, annually
if abnormal then indefinite transfusion
what are some risk factors for stroke in sickle cell patients
- rate of and recent episode of acute chest crisis
- low baseline hemoglobin
- previous TIA
- high blood pressure
- SS genotype
what is required for a diagnosis of acute chest crisis
fever and new infiltrate
hypoxia is not necessary for the diagnosis
what is the treatment for an acute chest crisis
Tx: Antibiotics (including cephalosporin and macrolide), oxygen, hydration, incentive
spirometry, bronchodilators.
Simple transfusion for hypoxia needing oxygen or a Hct<18%.
Exchange transfusion for progressive multilobe infarcts and hypoxia.
Recurrent ACS should have referral to respirology for PFTs.
how does hydroxyurea work
Hydroxyurea: raises fetal Hb levels
Question. A 14 yo girl with sickle cell disease presents
with a red, swollen, painful hand. (No vitals
mentioned).
What are three things you would do for management?
After leaving the hospital, what is one medication that can
be taken for prevention of these episodes?
- Admit
- Pain management
- IVF
- antibiotics
- imaging
- physio
- hydroxyurea
what are 3 inherited bone marrow failure syndrome
- dyskeratosis congenita
- fanconi anemia
- shwachman-diamond
List 5 causes of neonatal thrombocytopenia
- TAR
- sepsis
- TORCH
- Maternal ITP
- NAIT
- NEC
- RDS
what is a treatment option for a baby with low platelets secondary to maternal ITP
IVIG
what is the treatment for a baby with NAIT
PLA-1 negative platelets
Question. What would you advise a child with hemophilia regarding immunization? A. Delay Immunization B. Give factor VIII before immunization C. Apply pressure for 10 minutes after immunization D. Have factor VIII readily available in office to use if bleed occurs
Apply pressure for 10 minutes after immunization
What is the probable diagnosis of a 6-year-old child with pancytopenia, short
stature, abnormal thumbs, and areas of hyperpigmentation?
Fanconi anemia
Diagnosed with chromosomal breakage analysis
