Syndromes: blood disorders

Question 1

Severity of alpha thalassemia

Answer 1

a-/–: silent carrier
a-/a- or aa/–: trait, mild anemia
a-/–: intermedia/Hb H: variable, Hgb 7-10, hemolytic crises w/stressors
–/–: Hb Barts (4 gamma chains), hydros fetalis

Question 2

Alpha thal + developmental delay

Answer 2

ATR-16 syndorme (somatic large deletions on Chr 16) or ATRX variants (transcription factor regulates HgbA)

Question 3

Severity of beta thalassemia

Answer 3

b+ = some function remaining.
b0/b or b+/b: trait, low MCV
b+/b+ or b0/b+: intermedia, variable anemia. Develop complications later in life w/iron overload due to ineffective erythropoiesis (cirrhosis, cardiomyopathy, diabetes).
b0/b0: major, transfusion dependent anemia, growth failure, osteoporosis due to marrow expansion, HSM due to extramedullary hematopoiesis, iron overload.

Question 4

Treatment of beta thal major

Answer 4

Luspatersept - recombinant fusion protein that binds TGF-B ligands to reduce SMAD2/3 signaling, decreased ineffective erythropoiesis

Question 5

High HbF into adulthood

Answer 5

Hereditary persistence of fetal hemoglobin: 50-100kb deletion of delta and beta globin genes

Question 6

Better or worse than normal sickle cell (HbSS)?
HbS/B0

Answer 6

Similar

Question 7

Better or worse than normal sickle cell (HbSS)?
HbS/B+

Answer 7

Milder

Question 8

Better or worse than normal sickle cell (HbSS)?
HbSC

Answer 8

Milder

Question 9

Thrombocytopenia, abnormal platelet function (bleeding out of proportion to #), autoinflammation, and up to 50% lifetime risk of leukemia, small megakaryocytes & abnormal platelet shapes

Answer 9

Familial platelet disorder with propensity to develop myeloid malignancy: AD, RUNX1 (TF) haploinsufficiency

Question 10

Thrombocytopenia, cardiac defects, DD/ID, dysmorphic digits and facies

Answer 10

Jacobsen Syndrome/Paris-Trousseau syndrome: 11q23 deletion syndrome w/FLI-1 and ETS-1 haploinsufficiency

Question 11

Macrothrombocytopenia, Dohle bodies in WBCs, +/- deafness, cataracts, nephritis

Answer 11

MYH9-related disorders (myosin)

Question 12

Thrombocytopenia w/tiny platelets, severe eczema, immunodeficiency w/poor mitogen response, decreased IgM, elevated IgE

Answer 12

Wiskott-Aldrich syndrome, XL WASP

Question 13

Thrombocytopenia, very large platelets, easy bruising; risk of immune response w/transfusion

Answer 13

Bernard-Soulier syndrome: AR deficiency of GPIb/V/IX complex (glycoprotein binding to vWF)

Question 14

Absence of alpha granules, large gray platelets; development of myelofibrosis w/age, inflammatory

Answer 14

Gray Platelet syndrome: variants in NBEAL2 (packaging alpha granules), GFI1b, and GATA1

Question 15

Deficient dense granules synthesis/release, horizontal nystagmus, oculocutaneous albinism

Answer 15

Hermansky-Pudlak Disease: genes HPS1-10

Question 16

Primary mucocutaneous bleeding indicates problem with…

Answer 16

Platelet function or vWF

Question 17

Deep tissue/joint bleeding indicates problem with…

Answer 17

Coagulation factors

Question 18

Delayed bleeding indicates problem with…

Answer 18

Factor XIII, PAI-1/a2 antiplasmin

Question 19

X-linked coagulopathies

Answer 19

Hemophilia A/Factor VIII deficiency, Hemophilia B/Factor IX deficiency

Question 20

Diagnosis of vWD & 3 types

Answer 20

vWF panel w/antigen (amount), vWF activity (risto cofactor), factor VII activity
Type 1/AD: <30% Ag & Activity or <50% with abnormal bleeding
Type 2/AD or AR: functional defects in vWF function
Type 3/AR: total absence of vWF

Question 21

aPTT tests…

Answer 21

Intrinsic and common pathways

Question 22

PT tests…

Answer 22

Extrinsic and common pathway (factor VII)