Hematology Flashcards
Triad for renal vein thrombosis
Flank mass
Hematuria
Thrombocytopenia
Risk factors: Dehydration, hyperviscosity, asphyxia, hypercoagulable states, diabetes, indwelling catheters
Presentation: Hypotension then hypertension days/weeks later
Dx: US with Doppler
Most common intraerythrocytic pathogen transmitted by transfusion
Babesia!
Fetal Hgb is composed of which types of globin chains?
Alpha and gamma
How do globin chains develop in utero and once baby is born?
% fetal hemoglobin at birth
80%
Hematopoeisis at gestational ages
Conception-6 week: 2nd yolk sac
6-22 weeks: fetal liver
after 22 weeks: bone marrow
Characteristics of anemia of prematurity
Normocytic, monochromic, normal MCV, decreased retic
Neonatal leukemia
RARE
Increased risk: Fanconi’s, Diamond-Blackfan, T21
decreased platelets, anemia, increased WBC > 100, erythroid/lymphoid blasts
palpable cutaneous nodules
stem cells originate from where?
mesoderm
RBC indices and how they change over development:
RBC number
Hematocrit
MCV
Reticulocytes
Nucleated RBC
increases
increases
decreases
peaks at 26-27 wks, then declines
decreases
alpha globin genes on which chromosome
16
total of 4 genes
beta globin genes on which chromosome?
11
total of 2 genes
alpha thalassemia
severity based on the # of genes expressed
chinese subcontinent, malaysia, indochina, africa
absence of 1 gene: normal
absence of 2 genes (alpha thal trait): normal to inc Hgb Barts
- mild microcytosis, hypochromia
- erythrocytosis
- may be asymptomatic
absence of 3 genes (Hgb H): infant 20-30% Barts, child 4-20% Hgb H;
- moderately severe hemolytic anemia –> Hgb H is unstable
- Heinz bodies, +/- splenectomy
- susceptible to same drugs that cause hemolysis in G6PD
none (Alpha thal major): 80-90% Barts, no Hgb A or F
- FETAL HYDROPS SYNDROME
Hgb Barts
4 gamma chain hemoglobin present in alpha thalassemia
beta thalassemia
not usually detected in 1st month- beta not needed for fetal Hgb
blood smear- mild microcytic, hypochromic anemia, target cells
mediterranean, africa, china, pakistan, india, middle east
types of beta thalassemia
beta thal trait: mild increased A2/F
beta thal disease:
Beta zero: severe anemia in 1st yr, splenomegaly, poor growth, thalassemia bony changes, chronic transfusions
- increased Hgb F (>90%)
- increased Hb A2
- no change or decreased Hgb A
Beta+ : 20-40% A, 60-80% F
- moderate anemia, may not require transfusions
most common hemoglobinopathy in the world
Hemoglobin E
abnormal transcription message in the beta-globin chain –> dec production of beta chains –> chronic mild microcytic anemia
southeast asia
nucleotide substitution: GLU –> LYS
if inherited with beta-thal, more severe anemia
FS hemoglobin on newborn screen
differential: sick cell anemia, sickle-B thal, sick with hereditary persistence of fetal hgb
start PCN ppx
hematology referral
FSC on newborn screen
sickle C disease
start penicilin
hematology referral
FSA on newborn screen
sickle B+ thalassemia
start PCN ppx
hematology referral
Kleihauer Betke
done on maternal blood–> detects fetal blood
blood treated with citric acid buffer –> adult Hgb soluble –> Hgb F remains and stained with eosin –> appear red on slide
mothers/Hgb A appears as “ghosts”
KB equation
% Hgb F = (# feta cells/maternal cells) x 100
1% Hgb F = 50ml fetal blood
Rhogam
ml fetal blood/15
1 vial = 300mcg
Diamond Blackfan
congenital hypoplastic anemia
congenital erythroid asplasia- pure red cell asplasia
macrocytic anemia with reticulocytopenia in first year
leukocyte/plts normal
Bone marrow = absence of erythroid precursors
increased serum erythropoietin
increased RBC adenosine deaminase levels
increased RBC Hgb F and I antigen
features:
- low birthweight
- short stature
- abnormal facies
- TRIPHALANGEAL THUMBS
- cardiac/renal systems
increased risk for aplastic anemia, myelodysplastic syndrome, acute leukemia
Fanconi anemia
constitutional aplastic anemia
AR
chromosomal instability with breaks –> test chromosomes with mitomycin C
TRIPHALANGEAL THUMBS
hyperpigmentation
microcephaly
mental deficiency
strabismus
malformed ears
renal anomalies
marrow hypoplasia–> pancytopenia
macrocytosis, incr Hgb F, i antigen
at risk for malignancy: AML, lymphoma
I:i antigen system
based on a gene on chromosome 6
I = cell membrane on RBCs in adults
i = cell membrane on RBCs in fetuses and newborns until 13 - 20 months then switches to I antigen
hereditary spherocytosis
AD, Northern European, North America
issue with RBC cell membrane: absent spectrin, ankyrin –> sphere shape of RBC instead of disk –> increased hemolysis –> splenic sequestration
classic triad: jaundice, anemia, splenomegaly
Neonate: jaundice with signs of hemolysis without Coombs +
positive osmotic fragility test, low MCV, high MCHC
microcytic anemia
thalassemia
iron deficiency
lead poisoning
macrocytic anemia
methylmalonic aciduria
folate/vitamin B 12 def
acquired aplastic anemia
Diamond-Blackfan anemia
Fanconi anemia
Hypothyroidism
Down Syndrome
Mentzer index = MCV/#RBC
greater than 13.5 = iron deficiency
less than 11.5 = thalassemia major
anemia of prematurity
normocytic, normochromic
decreased retic count
physiologic drop caused by low EPO output in response to anemia
physiologic hgb nadir
term = 10-12 at 8-10 wks
preterm:
7-8 if < 1.2 kg –> 5-6 wks
9 if > 1.2 kg –> 5-6 wks
erythropoietin source
Predominant = fetal liver
3rd trimester = kidneys
hepatic > renal at birth
pharmacokinetics of EPO in neonates
plasma EPO levels drop rapidly post exogenous administration
increased volume of distribution
increased metabolism or clearance
EPO increased by iron supplementation
direct coombs
performed on INFANT’s blood
antibodies noted DIRECTLY on infant’s RBCs
indirect coombs
performed on MOTHER’s blood
detects ANTIBODIES in SERUM
ABO incompatibility
mothers who are A/B –> produce IgM which DO NOT cross placenta
mother’s who are O –> produce IgG which CROSSES placenta –> isoimmune hemolytic anemia
alloimmune = isoimmune
immune response to non-self antigens
G6PD
most frequently inherited enzyme defect –> XR, M>F
anemia, reticulocytosis, hyperbilirubinemia
decreased NADPH levels
exacerbation with exposure to oxidant stress
pyruvate kinase deficiency
2nd MC inherited RBC enzyme defect
AR
Northern European ancestry, AMISH
labs: anemia, hyperbilirubinemia
normocytic, normochromic, abnormal RBC shapes, reticulocytosis
blood volume term vs preterm
term = 80ml/kg
preterm = 100ml/kg
methemoglobinemia
Hgb oxidized to ferric state (Fe3+)
decreased blood oxygen capacity and transport –> normal PaO2 but dec oxygen saturation
blood = brown when exposed to oxygen
TX: METHYLENE BLUE = incr activity of NADPH-MET Hgb reductase –> urine blue/green
neonatal alloimmune thrombocytopenia
NAIT
production and placental transfer of MATERNAL alloantibodies against PATERNALLY inherited antigens on fetal platelets
MC = HPA 1a
first infant can be severely affected
INFANT plts low AT BIRTH, decline over first several days then increase over next 4 weeks, positive for HPA (as well as father)
MATERNAL plts normal, negative for HPA
intrauterine intracranial bleeding, death
bleeding diathesis /petechiae at birth
20% mortality
management: platelet antigen testing in parents, HUS, random donor plts, consider IVIG
autoimmune
body can’t tell the difference between self and foreign
neonatal autoimmune thrombocytopenia
ITP
MATERNAL antiplatelet antibodies caused to autoimmune disease
MOTHERS plts count LOW
INFANTs plts count LOW –> mildler than NAIT, lower risk of IVH
maternal plt count is not a good indicator of neonatal platelet count/severity
management: platelet tx, IVIG, steroids
minor blood group antigens that can cause hemolytic disease
Kell = K and k
Duffy = Fya
Kidd = Jka, Jkb
common Rh antigens that cuase hemolytic disease
D, c, C, e, E
Thrombocytopenia with absent radii syndrome
TAR
AR
M:F = 1:2
severe thrombocytopenia with absent/reduced megakaryocytes –> blockage of early differentiation
leukemoid reactions, eosinophilia
bilateral absent radii and ulnar abnormalities
thumbs/digits formed - contast to Fanconi
30-35% = cardiac disease: TOF, ASD
facial capillary hemangioma
25% mortality, MC IVH
Management: platelet transfusiosn unti spontaneous resolution
oxygen dissociation curve
amegakaryocyte thrombocytopenia
BM absent or scarce megakaryocytes
M:F = 2:3
SEVERE ISOLATED thrombocytopenia
50% = aplastic anemia, risk of leukemia
HIGH MORTALITY
clotting factor development
maternal clotting factors DO NOT cross placenta = endogenous production for infant
clotting proteins synthesized during 1st trimester
levels comparable to adult ~ 6 months
clotting cascade
PT = extrinsic pathway
(< 28 wks 14.5-20.9 sec)
(28-34 wks 13.9-20.6 sec)
~10-13 sec
inherited factor VII def
liver disease
DIC
vit K def
coumadin/warfarin
inherited/acquired factor V, X, II if also prolonged PTT
PTT = intrinsic pathway
(< 28 wks 27-64 sec)
(28-34 wks 30-57 sec)
hemophilia A (VIII)
hemophilia B (IX)
VWf (if also prolonged bleeding time)
heparin
lupus anticoagulant
inherited/acquired factor V, X, II defect (if also prolonged PT)
vitamin K dependent factors
II, VII, IX, X
protein C & S
hemophilia A
factor VIII deficiency
XR, 70% of hemophilia
increased bleeding after blood draws, circ, hemarthrosis, IVH
prolonged PTT
give factor VIII
correlation between level of deficiency and sx
hemophilia B
factor IX deficiency
Christmas disease
XR, 30% hemophilia
given factor IX
correlation between level of deficiency and sx
hemophilia C
factor XI deficiency
AR, Ashkenazi jews
Noonan syndrome
increased risk of GU bleeding
give FFP
NO correlation b/w level of deficiency and sx
factor XIII def
bleeding with normal coag studies
give cryo or factor XIII
vonWillebrand disease
AD/R
component of factor VIII functioning as a ligand b/w plt and vessel
mucous membrane bleeding
abnormal bleeding time
+/- prolonged PTT, PT/plts NORMAL
Dx: ristocetin factor
Give CRYO, factor VIII with vWF, DDAVP
hemorrhagic disease of the newborn
early - first 24 hours, maternal drugs
classic - 2-7 days, inadequate vit K
late - 2 wks to 6 mo, inadequate intake of hepatobiliary disease
PROLONGED PT, NORMAL PTT
GIVE IM VIT K- oral doesnt prevent this
histiocytosis
infant < 2 yrs old
fever, pancytopenia, multiorgan infiltration
familial hemophagocytic lymphohistiocytosis
fHLH
AR
abnormally hyper-activated T-cells and macrophages
fever, pancytopenia, HSM, adenopathy
FATAL
Dx: find hemophagocytosis in samples of bone marrow, spleen, lymph nodes
decreased NK cells, neutropenia
virus-associated hemophagocytic lymphohistiocytosis
fever
pancytopenia
HSM
viruses: CMV, EBV, HSV, adenovirus
MC solid tumor in the neonatal period
teratoma
2nd is neuroblastoma
retinoblastoma
most frequent eye tumor
AD in 40%
unilateral (70%), bilateral (30%)
sxs: leukocoria, strabismus, decreased vision, secondary glaucoma
2nd malignancies: osteosarcoma, pinealoblastoma
components of FFP
ALL clotting factors
fibronectin
gamma-globulins
albumin
plasma proteins
components of cryo
VIII
vWF
fibrinogen
XIII
fibronectin
bilirubin pathway
phototherapy dose dependent on…
spectrum of light: blue wavelength 460-490
irradiance of light source: standard = 10, high intensity = > 30
maximize exposure of skin to light
distance of infant to light: optimal is 10-15 cm
exchange transfusion
double volume:
- fresh IRRADIATED whole blood or reconstituted with FFP
- HCT = 50-55%
- 5-20ml aliquots
- replaced 87% of blood volume
- removes bilirubin and any free antibody
- monitor: HR, BP, pH, K, glucose, Ca, Mg
morbidities: hypocalcemia, thrombocytopenia, NEC, air embolus, thrombosis, infection, GVH
abnormal activity of glucuronyl transferase (UGTP1A1)
absent = crigler-najjar
reduced = gilbert’s
direct vs indirect bilirubin
IVIG MOA
binds to Fc receptor on reticuloendothelial cells so that destruction of RBCs cannot occur
DOES NOT GET RID OF BILIRUBIN ALREADY IN THE SYSTEM –> PREVENTS CONTINUED ACCUMULATION
Gilberts syndrome
impairment in conjugation process (dec UGT)
intermittent increases in INDIRECT/UNCONJUGATED bilirubin
kasabach-meritt
thrombocytopenia
blood volume exchange
[(pts hct - desired hct) / pts hct] x infant’s blood volume
transient myeloproliferative disease
transient leukemia
5-10% T21
diagnosed in neonatal period
asymptomatic but may present with HSM, effusions, bleeding/petechiae
HALLMARK = leukocytosis with neutrophilia, thrombocytopenia, blasts on blood smear
self-limited- 60-70% resolve spontaneously by 2 months
20% of T21 develop myeloid leukemia
areas of yellow deposition/bilirubin due to kernicterus
basal ganglia
cranial nerve nuclei
hippocampus
how does 2,3 DPG change oxygen affinity
2,3 DPG is an organic phosphate normally found in the human erythrocyte
it REDUCES oxygen affinity by stabilizing deoxyhemoglobin
Cooley anemia
severe beta-thalassemia
Why do babies get anemia of prematurity?
low EPO production
insufficient placental transfer of iron- occurs mostly in 3rd trimester
short survival of fetal/neonatal RBCs
phlebotomy losses
Hepcidin
regulates maternal-fetal iron metabolism
Mother: decreases iron absorption and placental transfer
Fetus: downregulate placental iron delivery once its needs are met
Levels decrease throughout pregnancy to allow for more iron absorption
enzyme responsible for enterohepatic bilirubin circulation
beta-glucuronidase
deconjugates bilirubin –> reabsorbed by intestine
enzyme breaks down biliverdin to unconjugated bilirubin in RES of spleen, liver, bone marrow
biliverdin reductase
irradiation
prevents GVH disease
WATCH for hyperkalemia
complications of hemangiomas
- hypothyroidism: increased type 3 iodothyronine deiodinase which inactivates thyroid hormones
- high output heart failure: if involves liver
Think Kasabach-Meritt
leukocyte reduced
prevents CMV
DCC decreases?
need for transfusion
risk for IVH and NEC
bilirubin/albumin ratio can tell you what?
marker for amount of unbound bilirubin
exchange:
> 6.8 - preterm with risk factors
> 8 - term with risk factors
PTT measures all factors in pathway except for?
factor VII
serum ferritin is a gauge for what?
total body iron stores
what cell line can be elevated in BPD?
Eosinophils
exchange transfusion volume
blood volume = wt x est blood volume/kg (80 or 100)
