Platelet Disorders, ASPHO Flashcards
plt lifespan?
7-9 days
how do plts get removed from circ?
monocyte-macropahge system
sites of destruction/utilization of plts?
spleen, liver, endothelial cell junction
% of circ’ing plts in spleen?
25-35%
causes of low plts?
- shortened life span (immune or not)
- plt seq
- plt loss or dilution (massive transfusion)
- decrased production (marrow issue, folate def, b12 def)
DDX for low plts in newbron?
- impaired production (placental insuff, fetal hypox, fetal iugr, perinatal drugs)
- consumption/sequestration (nec, RDS, thrombosis, hemangiomas, splenic seq)
- infectoius (TORCH, sepsis)
- immune destruction
- genetic (BMF, trisomy 18/13/21, IEM)
Neonatal alloimmune thrombocytopenia: dx how?
- anti-plts alloAbs in teh mom
- document fetomat incompat
NAIT antigens involved in caucasians?
HPA1>, 5, 3
NAIT antigens in asian population?
HPA-4 and 5
NAIT managemetn?
- daily plt count
- HUS for ICH
- tx if plts <30k
- transfuse maternal plts
- if can’t get mat plts, give HPA1a neg plts
- or donor plts +/- IVIG and corticosteroids
moms with prior hx of NAIT..manage how?
future pregs more severe: maternal IVIG weekly +/- daily corticosteroids
maternal ITP __ occur while mom in remmission
CAN
tx for matenral ITP?
IVIG 1 g/kg for 1-2 dose
maternal ITP prog?
nadir aroudn 3-4 days of age…most infants show count recovery by 7 days
what’s more common: maternal ITP ro NAIT?
NAIT
describe antigens/abs in maternal ITP vs NAIT
maternal ITP: antigen present on mom AND baby’s plts…NAIT: HPA-1a antigen on baby’s plts while mom is HPA-1a neg
does ab affect plt functionin maternal itp? nait?
itp: no
nait: YES, via GP2b/3a
waht’s more severe- mat itp or nait?
nait! can get ICH, rarely fatal
maternal itp, nait tx?
itp: observation, IVIG for clinical bleeding
nait: maternal plts, HPA-1 neg plts, IVIG+ random donor…goal >30-50
peak age itp?
toddlers, adolescents
ITP: natural hx = rise in plts coutn within how long?
1-3 weeks
prog ITP?
80% resolve within 12 months
red flags in ITP for other dx?
-anemia
-abnormal MCV
-low ANC
hepatosplenoemgaly
-constitutional sx
ITP tx?
- observation (most)
- corticosteroids
- IVIG
- ANti-D= winrho
AE of winrho?
hemolysis…only works in pts who are Rh+ adn have spleen in tact
2nd line tx in ITP?
- splenectony
- ritux
- eltrombopag
risks of splenectomy? resposne rate?
- sepsis, thrombosis
- 60-80%
risks of ritux? resposne rate for ITP?
infusion rxn, serum sickness, CVID, 30%
risks fo TPO agonsists?
thrombocytosis, bone develop of marrow reticulin, thormbosis
non-immune low plts ddx, other than marrow issue?
- DIC
- TTp/hus
- cardiopulm bypass
- sepsis
- preeclampsia/HELPP
- catastrophic antiphospholipid antibides
- transplant related
TTP smear findings?
low plts
large pts
schistocytes
HUS pathophys?
endothelial activation
leuk activation
plt activation
HUS associatd iwth what trigger?
e. coli verotoxin O157:H7 and strep pneumonia
HUS features?
MAHA, renal failure
tx for HUS?
dialysis and other supportive care; no need for plasmapheresis
atypical HUS difference?
no prodrome illness..an have muts in or abs to factor H, I or membrane co-factor protein…can give eculizumab
ttp: pathophys
def or abs to ADAMTS13, which normally breaks down very large vWF multimers–> large vWF multimers–> microthrombi
pentad for ttp?
MAHA thrombocytopenia neuro findings renal manifestations fever ...must have no other identificable cause
dx features of ttp?
schistoytse, helmet cells elevated LDH elevated retics neg coombs normal PT, PTT, fibrinogen, etc renal manfisations not severe reduced ADAMTS13
ttp mort rate if no therpay?
80%! start plasmapheresis right away!
ttp tx?
daily plasma exchanrge until control of hemolytic anemia and normal plt count, then altenratve day and/or less frequently…start corticosteroids
relapse rate in ttp?
high, at 20-30%
congen ttp: maange how?
infusions of ffp q2-3 weeks to maintain ADAMTS13>5%
evan’s syndrome smear: see large plts adn? other lab findings? tx?
spherocytes…DAT+…corticosteroids
give 4 inherited d/os of plt function
glanzmann thrombashenia
bernard soulier
grey plt syndrome
hermansky-pudlak syndrome
alpha grandules contain what?
- VWF
- fibrinogen
- PF4=neutralizes heparin-like molecules
- Growth factors: PDGF, TGF-beta1
- coag factors (factor V)
- p-selectin= cell adhesion molec for plt aggreg
dense granules contain?
- ADP/ATP, activates and recruits plts
- serotonin, vasocontrictor
- calcium: needed for fibrinogen binding to GP 2b3a
which granules require EM to see?
DENSE
steps that plts undergo?
adhesion-> activation-> aggregation–> propogration of coagulation
what happens during plt adhesion?
plts bind to subendothelial vWF/collagen via the plt GPIb-IX-V adn GPVI
what happens during plt activation?
plt shape change exposes the GPIIb/IIIa receptors
what happens during plt aggreagtion?
cross-linking of plt activated GP2b/3a by fibrinogen or vWF
what happens during plt propogation of coagulation?
activated plts provide an anionic aminophospholipid (PL) rich surface for the assemby of procoagulant enzyme complexes
macrothrombocytoepnia seen in what 2 disorders?
bernard-soulier
gray plt syndrome
normal plt count seen in what 2 plt disorders?
glanzmann
hermansky-pudlak
describe pfa-100
exposure of blood to a membrane coated with collagen and adenosine diphosphate or collagen adn epi–> foramtion fo plt plug closes aperture
in aspirin use, what resul will you see in pfa-100?
prolonged col/epi results, normal col/adp result
4 agonsits in plt aggreg
col arachidonic acid epi ADP ristocetin
plt aggreg measures?
light transmission thru plt-rich plasma or whole blood
limitations of plt aggreg?
not reliable when pl count <100
not clear how to intrepret mild defects
arachidonic acid agonist checks what in plt aggreg?
gets converted to thromboxane a2 by cyclooxygenase
genes in glanzmann
ITGA2B, ITGB3
Bernard-soulier: inheritance?
AR
BSS: abnormal or absent surface receptor for VWF: waht is it?
GP Ib/IX…CD42
gnes in BSS?
GP1BA, GP1BB, GP9
dx BSS how?
plt aggreg
flow
macothrombocytoepnia
tx for GT, BSS
supportive
plt transfusion (risk abs)
rF7a
sct
alpha granule: disorder where they’re absent?
gray plt syndrome
2 disordres wehre there’s an absence in dense granules?
hermansky-pudlak syndrome
chediak-higashi syndrome
grey plt syndrome inheritance?
AR, AD
gene in grey plts?
NBEAL2
confirm grey plts how after seeing on light micrsocopy?
EM
grey plts associated with waht 2 things?
myelofibrosis, splenomegaly
tx for grey plts?
transfusion
desmopressin
splenectomy
HPS: 2 clinical features?
mild bleeding
occulocuaneous albinism
nystagmus
HPS: inherit?genes?
AR…HPS1, HPS3, HPS5, etc
HPS tx?
plt transfusions
see waht on aggregatometry for HPS?
absent ATP secretion adn secondary wave of aggregation with ADP and epi…line will go back upwards again for ADP
plt count in HPS?
normal
Wiskott-Aldrich syndrome: inheritance? gene?
x-linked; WASP
WASP gene encodes what?
surface glycoprotein CD43, an actin-binding signaling protein
features of WAS
- low plts
- small plts
- defects in T cell adn B-cells
x-linked thrombocytopenia gene?
also WASP…microthrombocytoepnia but no eczema or immunodef
traid in WAS
low plts
eczema
frequent infections
dx WAS how? 2
gene testing
flow for WASP protein
complications of WAS?
hemorrahge
infection
autoimmune disordrs
malig like ALL, lymphoma
tx of WAS (3)
supportive for eczema, infection
splenectomy
SCT
MYH9-related disorders: inheritance?
AD
MYH9 dx?
leukocyte inclusions= dohle bodies
gene testing
features of MYH9 related disordres? 3
renal failure
SNHL
cataracts
MYH9 management
supportive
TAR = thrombocytopnia absent radii syndrome…thumbs are?
normal
heme issue in TAR?
absent megakaryocytes with elevated TPO levels
TAR tx?
plt transfusions…most have increase in plt count by 12-24 months though…self-correction!
cleft palate, heart defect, learning issue, low plts…think?
velocardiofacial syndrome
congential heart disease, dev delay, faical dysmorph, short stature, low plts…think?
jacobson syndrome/paris-trousseau
size of plts in MYH9?
large
MYH9 gene?
MYH9
other than absent radii and low plts, 2 other features of TAR?
cow milk intolerance
cardiac issues
renal issues
organ dysfunction–> plt dysfunction? 1 reason?
renal; decreased thromboxane A2 formation
ASA leads to irreversible inhibition of what? last for how long?
cyclooxygenase 1; 7 days
NSAID effect on plts: reversible or irrev? of what specifically?
reversible; cyclooxygenase 1
how does cyanotic heart disease and ECMO affect plts?
plt activation
other than NSAIDs adn ASA, other drugs–> plt dysfunction?
valporic acid
psychotropic drugs
semi synthetic penicillin derviatives
what does plt aggreg look like on ASA?
ADP goes down a bit then BACK UP, everythign else is really dampened
mange acquire plt dysfucntion how?
remove offending agent tx underlying disease lcoal pressures, pressure TXA desmopressin conjguated estrogens plt tranfusions rbcs if anemic
mut in essential thrombocytosis?
JAK>CALR, MPL
causes of reactive thrombocytosis
inflamm iron def marrow recovery asplenia young infants (esp prem)
reactive thrombocytosis def’n
> 450k (usually caps at 1 million)
for seconary thrombocytosis, do they get clots?
no
ET: clinical featuers?
splenomegaly
bleeding-acquired vWD
-thrombosis
-numbness and tingling, fatigue, headache, vision changes
ET plt count?
> 450k
ET lab test?
high levels of thrombopoeitin
management of ET?
ASA
HU
anagrelide
