Heme/Onc Flashcards
Most common malignancy in neonates (and it’s origin)
Neuroblastoma
Neural crest cells
Usually the primary identifiable location is liver
Findings of neuroblastoma and most common lab abnormalities
From catecholamines, but also depends on areas of metastasis
Catecholamine signs: hypertension, diarrhea, tachycardia
Usually in liver: hepatomegaly, jaundice, hypertension (second most common site is skin/SC)
Most common finding: urine HVA and VMA (homovanillic and vanillylmandelic acid)
Site of erythropoetin synthesis in preemie vs. term infants
Liver (and therefore insensitive to hypoxic stimulation) in preemies vs. kidney in term
Most sensitive lab marker for iron stores
Ferritin
Protein binding iron, regulated by intracellular Fe stores
Low ferritin indicates iron deficiency
Hepcidin’s role
Primary regulator of iron uptake (from placenta in-utero and from GI postnatally)
When high, blocks iron uptake
Which type of immunoglobulin crosses the placenta and causes hemolytic disease of the newborn?
IgG
Transplacental movement increases with gestation (greatest after 22 weeks)
In pregnancies with Rh incompatibility, _____ is actually protective
ABO incompatibility
Fetal cells more quickly destroyed after entering maternal circulation, reducing maternal immune system exposure to Rh antigen
When does OB give Rhogam to Rh-negative mothers
28 weeks–this is because most fetal-maternal hemorrhage happens at >28 weeks
Post-partum (if neonate was Rh +)
Any other exposures that could cause sensitization
Two mainstays of treatment for significant hemolytic disease of the newborn
- Intensive phototherapy (higher priority than IVIG)
- IVIG (1g/kg over 2h, can repeat 12-24h later)
Double-volume exchange transfusion: invasive and reserved for a) kernicterus or b) bilirubin at exchange level and recalcitrant to above treatments
How many alpha-globin genes does one have, and on what chromosome?
Four (two from each parent)
Chromosome 16
If you like the “alpha-four”, start with the “sweet (chromosome) 16”
What comprises Hemoglobin F and when does it “go away”
Two alpha- and two gamma-globin chains
Around 6 months
Higher oxygen affinity (its curve shifted to left) vs. normal Hb
What are the thalassemias?
Hemoglobinopathies with at least one mutation in the globin genes (of which everyone has two beta and four alpha genes)
How many alpha genes are mutated in alpha-thalassemia minor
AKA alpha-thalassemia trait 2 (of 4)–therefore have little/no anemia
What is Hemoglobin H?
Hb H is beta-chain tetramers
It’s the form of alpha-thalassemia where 3 of the 4 alpha genes (chromosome 16) are mutated
(Hb Barts AKA alpha thalassemia major is the worst)
Alpha thalassemia major’s synonym and cause
Hemoglobin Bart (gamma tetramer)
Loss of all 4 alpha-globin alleles
Causes hydrops/stillbirth, if survive need almost immediate bone marrow transplant
How many mL of O2 can 1g of hemoglobin carry?
1.34mL
Reason for this number in the O2 consumption and carrying capacity equations (always found multipled by [Hb])
What test can be performed to detect fetal-maternal hemorrhage
Kleihauer-Betke
Hb F stains red and adult Hb “ghosts out” from citrate-phosphate buffer
What is the difference between a direct and indirect Coombs (and which is normally done as the initial step in newborns)
Direct: detect antibodies already bound directly to patient’s RBCs
Indirect: detect antibodies in patient’s serum
On newborns you’re doing a direct test, in mothers for the screen you’re doing an indirect
D is the most antigenic of the Rh antigens–at what anti-D titer are you worried?
>1:32
Most fetal-maternal hemorrhage happens at >28 weeks which is the reason for the first Rhogam to be given then
What is the second-most antigenic of the Rh antigens
Rhc: 20-30% of Rhc+ infants [born to Rhc- mothers) will need phototherapy
While Rh antibodies require previous blood exposure to develop, A and B do not–why?
A and B are expressed on multiple tissue surfaces, so O individuals are “immediately” exposed and develop anti-A and anti-B by one year of age
Of the two sequelae (jaundice and anemia), anti-Kell antibodies cause which?
Cause significantly worse anemia than jaundice, unclear why
Why do gram-negative/polymicrobic infections result in anemia
T-cell mediated hemolysis from ubiquitous activation
Three categories of hemoglobin pathologies that’re predominantly in Mediterranean or African patients
Alpha mutations: alpha-thalessemia spectrum
Beta globin mutations: Sickle cell disease
Enzyme deficiency: G6PD
One type of hemoglobin pathology that’s more common in Caucasians
Hereditary spherocytosis (and elliptosis)
Compared to the three in African/Mediterraneans, THIS is autosomal dominant
What two hemoglobin diseases result in Heinz bodies
G6PD (most classic)
Alpha-thalassemias
Heinz bodies are clumps of denatured hemoglobin
What test (other than genetics) is diagnostic of Hereditary Spherocytosis
Osmotic fragility test
HS caused most often by Spectrin mutation
G6PD facts
- X-linked recessive
- See Heinz bodies on specific [supravital] stain
- RBC G6PD activity: can be falsely elevated in times of hemolytic crisis
What makes methemoglobinemia patients cyanotic
MetHb is oxidized form of Hb, can’t bind O2
Cyanosis evident at level >10%, treat with methylene blue if >20%
What is the cause of Fanconi anemia
Defective DNA repair so increased chromosomal fragility
Absent thumbs AND radii, pancytopenia, renal anomalies (but NOT Fanconi syndrome)
(Remember TAR has just absent radii and just thrombocytopenia)
Of the bone marrow failure syndromes that can present in neonates, which two can cause pancytopenia
Fanconi Anemia (and less commonly Schwachman-Diamond)
Diamond-Blackfan Anemia, Kostmann’s and TAR affect only one lineage
Equation for partial-volume exchange transfusion
Volume exchanged= ([Pt Hct - desired Hct] x blood volume) / Pt Hct
(Used for polycythemia, exchange patient blood for normal saline)
Two most common causes of Neonatal Alloimmune Thrombocytopenia
HPA-1a and HPA-5b
(NAIT is most common cause of severe thrombocytopenia [<50])
Group of IEMs that’re associated with thrombocytopenia
Organic acidemias
(Propionic, methylmalonic acidemia)
Neonates are relatively deficient in which coagulation factors
Everything but factor VIII; but also deficient in anticoagulants so balance is relatively maintained
Facts for Hemophilias
A: factor VIII, B: factor IX
Both X-linked recessive
Rarely present in neonatal period, if they do it’s oozing and ICH
Hemophilia C: factor XI–associated with Noonan’s
Cause of Hemorrhagic Disease of the Newborn and part of clotting cascade it impacts
Vitamin K deficiency
Extrinsic pathway (II, VII, IX, and X)–see prolonged PT
Usually presents at 2-7 days with oozing, bloody stools, can see intracranial hemoorrhage (ICH)
Most common artery affected in neonatal stroke
Left MCA (believed to be way left carotid gets preferential flow from placenta)
(Any stroke tends to present–if symptomatic–with apnea, seizures and/or feeding difficulties)
Most common site of venous thrombosis
Renal vein: see thrombocytopenia, flank mass, hematuria, and hypertension
(Risk factors: asphyxia, maternal diabetes)
What is the blood volume of a neonate
80-100mL/kg
What coagulation deficiencies might present as purpura fulminans
Protein C or S deficiency
(Always consider infection–GBS and N. meningitidis)
The level of methemoglobinemia that warrants treatment (and the treatment)
MetHb >40%
Methylene bue
What is a hereditary cause of a hemolytic anemia with structurally normal RBCs
Pyruvate Kinase Deficiency (PKD)
Variable presentation at birth, usually normochromic anemia with high reticulocyte count and “echinocytes” on smear (can be bad enough to cause extramedullary hematopoeisis and hydrops)
Gold standard test is pyruvate kinase enzyme activity
What is the most common laboratory abnormality in hemorrhagic disease of the newborn (AKA vitamin K deficiency bleeding), and what’s the most specific
Most common: prolonged PT (usually with a less but still prolonged PTT)
Most specific: high undercarboxylated factor II
What vitamin K is needed for is carboxylation (ie functionality) of coagulation factors
Oral vitamin K prophylaxis is not good at preventing which of the three timings of vitamin-K deficient bleeding (VKDB)?
Late bleeding, ie >7 days
Which of the clotting times is abnormal in Hemophilia (A and B)
aPTT
