Heme/Immuno Flashcards
When does fetal hemoglobin essentially disappear
6 months (<1% fetal is left)
2 conditions that are protective from malaria
G6PD and sickle cell
Heinz bodies seen in which 2 conditions
G6PD and alpha-thal
Methemoglobinemia:
- how is it inherited?
- when is cyanosis first seen, and when does it become symptomatic?
- treatment?
- Hgb M is auto doMinant, cytochrome B5 Reductase is auto Recessive
- cyanosis first seen at 10%, diminished oxygen transport at 30%
- Tx with methylene blue (response is diagnostic and therapeutic)
- contraindicated in G6PD (worsen hemolysis); Hb M will not respond
- think if cyanosis with low SaO2, normal PaO2 that doesn’t respond to oxygen
What is Kostmann syndrome?
Mutations in elastase gene
Arrest of neutrophils as promyelocytes –> severe congenital cyclic neutropenia
Also see epilepsy and cognitive delay
Tx: GCSF
What is Shwachman-Diamond syndrome?
- Bone marrow dysfunction (cytopenias, esp neutropenia), exocrine pancreatic insufficiency (steatorrhea), and skeletal dysplasia
- remember as shwachman anemia
- Presentation: steatorrhea, cytopenias (or at least neutropenia), FTT, maybe skeletal dysplasia
- Tx: panc enzymes
What is Fanconi anemia
- how is it inherited
- what body parts have defects
- what are the heme defects
- Dx
- Tx
- Defective double strand DNA repair
- abnormal or absent thumbs, no radii, café au lait spots, short stature, microcephaly, renal anomalies
- aplastic anemia and macrocytic anemia –> predisposition to cancers
- Dx: detection of increased chromosomal fragility in lymphocytes
Tx: may need androgens, BMT
What is Diamond Blackfan anemia?
- what are the physical defects?
- what are the heme defects?
- what are they at increased risk for?
- what is the treatment?
- Pure RBC aplasia
- Cellular defect in ribosome biosynthesis
- microcephaly, cleft palate, abnormal thumbs (triphalanygeal), cardiac defects, short stature and skeletal abnormalities
- Macrocytic anemia - see bone marrow with normal cellularity with absence of red cell precursors
- Increased risk of cancer
- Tx: steroids, BMT
NAIT has a high recurrence rate. What and when is the antenatal treatment of NAIT?
Treatment of NAIT in fetus?
Moms:
Tx - weekly IVIg and steroids
If prior infant with intracranial hemorrhage, start at ~13 weeks; if no ICH, start at ~23 weeks
Babies:
- Platelet transfusions (esp negative for HPA-1a or whatever antibody is present)
- IVIg
- prednisone
How and when do you treat thrombocytosis?
If greater than 1.5 million, give aspirin 5 mg/kg/day
What are symptoms of TAR?
Thrombocytopeni and Absent Radii
but normal thumbs! (Distinguishes from Fanconi and DBA)
also have CHD
Hemophilia A
- how is it inherited
- what’s deficient
- what’s prolonged
- how do you treat
- X-linked recessive
- Factor 8 is deficient
- prolonged PTT
- Tx with F8 (cryo if none available)
Hemophilia B
- how is it inherited
- what’s deficient
- what’s prolonged
- how do you treat
- X-linked recessive
- Factor 9 is deficient
- prolonged PTT
- Tx with F9
Hemophilia C
- how is it inherited
- what’s deficient
- what’s prolonged
- how do you treat
- what is it associated with
- AR (unlike other hemophilias which are XR)
- Factor 11 is deficient
- prolonged PTT
- Tx with FFP
- associated with Noonan’s (which is inherited AD. wtf.)
Factor 13 deficiency
- how is it inherited
- how does it present
- what’s prolonged
- how do you treat
- autosomal recessive
- prolonged bleeding from umbilical stump or after circumcision
- normal coags!!
- tx with F13 or cryo
*Factor 13 is fibrin stabilizing, so have weak clots
Vitamin K deficiency
- what’s prolonged
- which factors are dependent on vitamin K
- prolonged PT (only one!)
- 2, 7, 9, 10, protein C and S are dependent on Vitamin K
Purpura fulminans:
- associated with what infection?
- associated with what heme disorder?
- How is it treated?
- GBS
- protein C/S deficiency
- Tx: Protein C/S, FFP
Tetrad of RVT?
HTN, hematuria, palpable flank mass, and thrombocytopenia
MRI signs of:
- bilirubin encephalopathy
- kernicterus
- globus pallidus, hippocampus
- above plus basal ganglia and cerebellum (cerebral cortex is spared)
Absolute contraindication to phototherapy
If infant has Congenital Erythropoietic Porphyria, will get severe bullous lesions on skin, accelerated hemolysis, splenomegaly, pink to red urine that fluoresces orange under UV light
Goal of DVET?
Replace 85% of RBC and 50% of bilirubin
Most common heme malignancy?
Acute myeloid leukemia
Neonates with asplenia:
- are at risk for what two pathogens?
- have what two pathologies on smear?
- E. Coli and Klebsiella (CoKe)
- thrombocytosis and Howell Jolly bodies
Most common neutrophil dysfunction disorder?
Myeloperoxidase deficiency
- recurrent candida infections (or asymptomatic - other parts of immune system compensate)
- Nitroblue Tetrazolium test turns blue
Complements!
- what are the classical and alternative pathways?
- what is the most common complement deficiency?
- they converge where?
- where are they produced?
- Classical requires Ag-Ab reaction, but alternative can be Ab independent
- Most common deficiency is C2 (leads to pneumococcal infections and collagen vascular diseases)
- They converge at C3 (the alternate pathway just starts at C3)
- They are produced in the liver, except C7 which is secreted by neutrophils
Hyper IgM
- what is it
- what is low
- what are symptoms
- primary antibody defect: absence of CD40L on T cells prevents class switching of antibodies, so you end up with a lot of IgM that can’t do anything
- Low IgG and IgA, as well as neutropenia (may need GCSF)
- perirectal abcesses, rubella
X-linked agammaglobulinemia
- what is low and what is normal
- what are symptoms
- BTK mutation causes failure of B cell maturation
- undetectable IgG, M, and A but normal T cells
- see infections after 6 months of age when mother’s supply runs out
- unlike transient hypogammaglobulinemia - only IgG is low
Hemophagocytic LymphoHistiocytosis
- what is it
- labs?
- hyper-activated T cells and macrophages
- similar to hemochromatosis (high LFT’s, ferritin, anemia, thrombocytopenia, low fibrinogen) but with fever, high triglycerides, neutropenia and low NK cells, lytic lesions
2 tumors a/w BWS?
Wilms and hepatoblastoma
Three primary antibody deficiency examples?
Hyper-IgM
X-linked agammaglobulinemia
CVID
Combined immune deficiency examples?
Omenn, Zap-70, Wiskott Aldrich
- MCC of neonatal (28 WGA to 28 days of life) stroke?
- Which side?
- MC problem in childhood?
- Thromboembolism d/t inherited coagulation disorder
- More commonly on left
- motor deficits (although seizure is a common presenting symptoms, only 10% go on to have epilepsy)
What are the three embryonic hemoglobins? When does embryonic hemoglobin last until?
Gower 1: Z2E2
Gower 2: A2E2
Portland: Z2Y2
Lasts until 8 weeks
What are the two fetal hemoglobins? When do the chains begin to switch?
F: A2Y2 (75%)
A: A2B2 (25%)
at 30 weeks, Y starts decreasing and B starts increasing, but A2Y2 is still predominant at birth (70-90%)
What are the two main adult hemoglobins?
A: A2B2
A2: A2D2
How much unsaturated hemoglobin do you need to be cyanotic
3 g/dL
eg:
hgb 15 –> cyanotic at 80%
hgb 10 –> cyanotic at 70%
Most common cause of primary neutropenia
Elastase mutation = severe congenital cyclic neutropenia aka Kostmann
What does a granulocyte agglutination test look for?
immune-mediated neutropenias
Neuroblastoma, which is the MC malignancy and second MC tumor (secondary to teratoma)
- derived from?
- MC primary site?
- symptoms?
- dx?
- prognosis?
- diseases associated with?
- derived from primitive sympathetic ganglia/neural crest cells
- most commonly in adrenal glands
- symptoms: bluish nodules on skin, Horner’s, orbital ecchymoses, HTN
- Dx: tumor biopsy is gold standard; will also see elevated urine catecholamines (HVA/VMA)
- better prognosis if diagnosed <1 year (called stage 4-S or M-S); less favorable if N-myc amplification
- associated with central hypoventilation, Hirschprung’s, and NF1
Microcytic anemia at birth?
alpha thal (probably HbH)
Transient hypogammaglobulinemia of infancy
- what is it
- what is low (B cells, T cells, IgG)
- can you give vaccines
- exaggerated physiologic nadir > 6 months
- B and T cells are normal, but IgG is >2 SD’s below
- vaccines are okay
Which Ig begins production in utero?
IgM
What adult production of IgG, IgM and IgA by 1 year? When do they reach adult levels?
IgM - 75%
IgG - 60% (adult levels at 4 years)
IgA - 20% (closer to adult levels at 4 years)
Which Ig levels are higher at birth than adult? When does it nadir, and then reach adult levels again?
IgG due to maternal transfer by endocytosis
Nadir at 6-8 months, then adult levels by 4 years
B cells!
- high or low at birth?
- when does it peak and then reach adult levels?
- absolute number are significantly higher at birth
- peaks at 3-4 months, then decreases to adult levels at 5-6 years
G6PD variant (African-Americans with reduced G6PD activity) is associated with jaundice and ____?
methemoglobinemia
what are howell jolly bodies and what are they specific for?
small, round nuclear remnants seen in patients with asplenia
what are heinz bodies?
denatured hemoglobin
MCC malignancy in neonates
neuroblastoma
Most common antigen of hemolytic disease (HDN)
little c
enzyme that unconjugates bilirubin; present in EBM and thought to breastmilk jaundice
(present in GI and increases enterohepatic circulation because increases unconjugated bilirubin)
beta-glucuronidase
What has target cells at birth?
alpha thal
mechanism of FVL - how does it present?
protein C cleaves and inactivates FV
In FVL it can’t, so FV causes thrombosis
stroke, RVT
pyruvate kinase deficiency is a problem of what?
ATP production
