Hemostasis Flashcards
Hermansky Pudlak Syndrome
9mutations
1,4 form a complex. associated with pulmonary fibrosis and colitis
3,5,6 associated with ophtho
Emicizumab NEJM paper results
Population: Hemophilia A with high titer inhibitors
Dosing: 3mg/kg/week x 4 weeks, then 1.5mg/kg/week
Results:
- 87% decrease in bleeding events compared to no prophylaxis (2.9 vs 23.3 events/yr)
- 79% decrease in events compared to same patients when they were on bypassing agents
- 63% of emi group had no bleeds
- 5 cases of TMA and thrombosis when given with aPCC over 100U/kg/day
- no inhibitors found
Risk factors for Hemophilia A inhibitor development
- Severity of hemophilia
- Mutation type (null mutations)
- Intensity of exposure (RODIN study)
- Type of product - Sippet study suggesting early exposure to plasma derived is better than recombinant
- Family history - genetic variations in immunity
Factor VII deficiency
1:500,000 auto recessive.
FVII activity >0.2 rarely bleed, high risk if <0.1
Heterozygotes have activity 0.4-0.6 (INR usually normal when level >0.5)
Recommended replacement is rFVIIa 15-30ug/kg every 4-6 hours. Plasma half-life is estimated 2-3 hours.
**note dose lower than hemophilia
What is the mechanism of action of steroids in ITP?
Inhibits phagocytosis of antibody coated platelets
Inhibits antibody production
Suppress activation of t-cells
Name complications of hemophilia apart from bleeding
Development of inhibitors Synovitis Arthropathy Pseudotumors Infection from plasma derived products
What is the average lifespan of a platelet?
9-10 days
How are platelets distributed in the body?
1/3-in the spleen
2/3-in circulation
How long does it take for NAIT to resolve?
usually 2-4 weeks
Describe the pathophysiology of NAIT
When fetal platelets express platelet-specific antigens inherited from the father, are the target of maternal alloantibodies (mother doesn’t possess these platelet specific antigens)
What is the most common platelet specific antigen involved in NAIT?
HPA-1a accounts for ~75% cases
Another 10-20% are due to HPA-5b-these cases tend to be milder
neonates affected by NAIT have what rate of developing ICH?
10-20%
How is NAIT treated?
Random donor platelets usually are fine
If no response can use matched donor platelets or maternal platelets
IVIG 1g/kg/day for 1-3 days
Methylprednisone 1mg IV q8h with IVIG (says Lanzokowsky’s)
Head U/S
Follow-up until platelets recover
For neonatal autoimmune thrombocytopenia what pattern do you expect with the platelets?
Are near/normal at birth, then fall to a clinically significant nadir over the next 1-3 days, the platelet count will normalize over the next 3-12 weeks
What is the most common platelet antigen target in neonatal autoimmune thrombocytopenia?
GPIIB/IIIA or GPIb/IX
Which mothers are at risk of giving birth to a neonate with autoimmune thrombocytopenia?
Hx of previously affected infant Previously splenectomized for ITP Currently has thrombocytopenia Has SLE, hypothyroidism, preeclampsia, HELPP syndrome Maternal drug ingestion (thiazide)
What platelet characteristics are associated with Bernard-Soulier?
Moderate thrombocytopenia
Large platelets-usually the size of a red cell
What causes Bernard Soulier?
absence of the GPIb glycoprotein complex
this leads to inability of VWF binding, and significant bleeding (epistaxis)
What triad is associated with WAS?
eczema, microthrombocytopenia and immunodeficiency (T-cell function)
What mutation causes CAMT?
mutation in c-mpl (the thrombopoietin receptor)
What 4 drugs are most commonly associated with drug-induced thrombocytopenia?
heparin
quinine
penicillin
VPA
What causes HIT?
antibodies develop that are directed against complexes of heparin and platelet factor 4
What is pots-transfusion purpura
MIddle aged women with hx of pregnancy. Allo-antibody results in destruction of endogenous and transfused plt. Severe thrombocytopenia 7-10d post with bronchospasm and hemorrhage
MYH-9 features
renal failure
sensorineural hearing loss
cataracts
Abnormal radius with normal thumbs
TAR
- high TPO
- spontaneously recover at 12-24 m
Mutation: RBM8A
CAMT gene
c-MPL
Grey Platelet syndrome
AR
macrothrombocytopenia
absent alpha granule
assoc. with myelofibrosis
Hermansky-Pudlak
- AR
- absent dense granules - so no ATP secretion or second wave of aggregation with ADP and epi
- occulocutaneous albinism
What genetic defect causes Familial platelet syndrome with predisposition to AML? (FPS/AML)
RUNX1-a transcription factor
what are the 4 T’s of HIT?
thrombocytopenia
thrombosis
timing-usually 5-10 days after 1st heparin exposure, 3-5 days after subsequent
oTher-no other reason for thrombocytopenia
What is the pentad of TTP?
thromobcytopenia microangiopathic hemolytic anemia renal dysfunction neuro symptoms fever
What is the cause of both acquired and congenital TTP?
ADAMTS-13 deficiency mediated thrombotic microangiopathy
What is the treatment for congenital TTP?
because patients don’t have antibodies but instead very low levels of ADAMTS-13, plasma infusion is the treament
what is the treatment of acquired TTP?
start plasmapheresis right away! removes the antibodies
platelets don’t help, can worsen the coagulopathy
What test will diagnose acquired TTP?
ADAMTS13 assay which shows low ADAMTS13 activity (<10%) and also documents the presence of ADAMTS13 IgG autoantibodies
shouldn’t wait for results before starting plasmapheresis
What is the pathophys behind aHUS?
dysregulated alternative complement system
there’s an increase in formation of C5b-9 MAC attack complex
there’s also inhibition of the regulatory proteins
