Platelet Disorders, ASPHO Flashcards
1
Q
plt lifespan?
A
7-9 days
2
Q
how do plts get removed from circ?
A
monocyte-macropahge system
3
Q
sites of destruction/utilization of plts?
A
spleen, liver, endothelial cell junction
4
Q
% of circ’ing plts in spleen?
A
25-35%
5
Q
causes of low plts?
A
- shortened life span (immune or not)
- plt seq
- plt loss or dilution (massive transfusion)
- decrased production (marrow issue, folate def, b12 def)
6
Q
DDX for low plts in newbron?
A
- 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)
7
Q
Neonatal alloimmune thrombocytopenia: dx how?
A
- anti-plts alloAbs in teh mom
- document fetomat incompat
8
Q
NAIT antigens involved in caucasians?
A
HPA1>, 5, 3
9
Q
NAIT antigens in asian population?
A
HPA-4 and 5
10
Q
NAIT managemetn?
A
- 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
11
Q
moms with prior hx of NAIT..manage how?
A
future pregs more severe: maternal IVIG weekly +/- daily corticosteroids
12
Q
maternal ITP __ occur while mom in remmission
A
CAN
13
Q
tx for matenral ITP?
A
IVIG 1 g/kg for 1-2 dose
14
Q
maternal ITP prog?
A
nadir aroudn 3-4 days of age…most infants show count recovery by 7 days
15
Q
what’s more common: maternal ITP ro NAIT?
A
NAIT
16
Q
describe antigens/abs in maternal ITP vs NAIT
A
maternal ITP: antigen present on mom AND baby’s plts…NAIT: HPA-1a antigen on baby’s plts while mom is HPA-1a neg
17
Q
does ab affect plt functionin maternal itp? nait?
A
itp: no
nait: YES, via GP2b/3a
18
Q
waht’s more severe- mat itp or nait?
A
nait! can get ICH, rarely fatal
19
Q
maternal itp, nait tx?
A
itp: observation, IVIG for clinical bleeding
nait: maternal plts, HPA-1 neg plts, IVIG+ random donor…goal >30-50
20
Q
peak age itp?
A
toddlers, adolescents
21
Q
ITP: natural hx = rise in plts coutn within how long?
A
1-3 weeks
22
Q
prog ITP?
A
80% resolve within 12 months
23
Q
red flags in ITP for other dx?
A
-anemia
-abnormal MCV
-low ANC
hepatosplenoemgaly
-constitutional sx
24
Q
ITP tx?
A
- observation (most)
- corticosteroids
- IVIG
- ANti-D= winrho
25
AE of winrho?
hemolysis...only works in pts who are Rh+ adn have spleen in tact
26
2nd line tx in ITP?
- splenectony
- ritux
- eltrombopag
27
risks of splenectomy? resposne rate?
- sepsis, thrombosis
| - 60-80%
28
risks of ritux? resposne rate for ITP?
infusion rxn, serum sickness, CVID, 30%
29
risks fo TPO agonsists?
thrombocytosis, bone develop of marrow reticulin, thormbosis
30
non-immune low plts ddx, other than marrow issue?
- DIC
- TTp/hus
- cardiopulm bypass
- sepsis
- preeclampsia/HELPP
- catastrophic antiphospholipid antibides
- transplant related
31
TTP smear findings?
low plts
large pts
schistocytes
32
HUS pathophys?
endothelial activation
leuk activation
plt activation
33
HUS associatd iwth what trigger?
e. coli verotoxin O157:H7 and strep pneumonia
34
HUS features?
MAHA, renal failure
35
tx for HUS?
dialysis and other supportive care; no need for plasmapheresis
36
atypical HUS difference?
no prodrome illness..an have muts in or abs to factor H, I or membrane co-factor protein...can give eculizumab
37
ttp: pathophys
def or abs to ADAMTS13, which normally breaks down very large vWF multimers--> large vWF multimers--> microthrombi
38
pentad for ttp?
```
MAHA
thrombocytopenia
neuro findings
renal manifestations
fever
...must have no other identificable cause
```
39
dx features of ttp?
```
schistoytse, helmet cells
elevated LDH
elevated retics
neg coombs
normal PT, PTT, fibrinogen, etc
renal manfisations not severe
reduced ADAMTS13
```
40
ttp mort rate if no therpay?
80%! start plasmapheresis right away!
41
ttp tx?
daily plasma exchanrge until control of hemolytic anemia and normal plt count, then altenratve day and/or less frequently...start corticosteroids
42
relapse rate in ttp?
high, at 20-30%
43
congen ttp: maange how?
infusions of ffp q2-3 weeks to maintain ADAMTS13>5%
44
evan's syndrome smear: see large plts adn? other lab findings? tx?
spherocytes...DAT+...corticosteroids
45
give 4 inherited d/os of plt function
glanzmann thrombashenia
bernard soulier
grey plt syndrome
hermansky-pudlak syndrome
46
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
47
dense granules contain?
- ADP/ATP, activates and recruits plts
- serotonin, vasocontrictor
- calcium: needed for fibrinogen binding to GP 2b3a
48
which granules require EM to see?
DENSE
49
steps that plts undergo?
adhesion-> activation-> aggregation--> propogration of coagulation
50
what happens during plt adhesion?
plts bind to subendothelial vWF/collagen via the plt GPIb-IX-V adn GPVI
51
what happens during plt activation?
plt shape change exposes the GPIIb/IIIa receptors
52
what happens during plt aggreagtion?
cross-linking of plt activated GP2b/3a by fibrinogen or vWF
53
what happens during plt propogation of coagulation?
activated plts provide an anionic aminophospholipid (PL) rich surface for the assemby of procoagulant enzyme complexes
54
macrothrombocytoepnia seen in what 2 disorders?
bernard-soulier
| gray plt syndrome
55
normal plt count seen in what 2 plt disorders?
glanzmann
| hermansky-pudlak
56
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
57
in aspirin use, what resul will you see in pfa-100?
prolonged col/epi results, normal col/adp result
58
4 agonsits in plt aggreg
```
col
arachidonic acid
epi
ADP
ristocetin
```
59
plt aggreg measures?
light transmission thru plt-rich plasma or whole blood
60
limitations of plt aggreg?
not reliable when pl count <100
| not clear how to intrepret mild defects
61
arachidonic acid agonist checks what in plt aggreg?
gets converted to thromboxane a2 by cyclooxygenase
62
genes in glanzmann
ITGA2B, ITGB3
63
Bernard-soulier: inheritance?
AR
64
BSS: abnormal or absent surface receptor for VWF: waht is it?
GP Ib/IX...CD42
65
gnes in BSS?
GP1BA, GP1BB, GP9
66
dx BSS how?
plt aggreg
flow
macothrombocytoepnia
67
tx for GT, BSS
supportive
plt transfusion (risk abs)
rF7a
sct
68
alpha granule: disorder where they're absent?
gray plt syndrome
69
2 disordres wehre there's an absence in dense granules?
hermansky-pudlak syndrome
| chediak-higashi syndrome
70
grey plt syndrome inheritance?
AR, AD
71
gene in grey plts?
NBEAL2
72
confirm grey plts how after seeing on light micrsocopy?
EM
73
grey plts associated with waht 2 things?
myelofibrosis, splenomegaly
74
tx for grey plts?
transfusion
desmopressin
splenectomy
75
HPS: 2 clinical features?
mild bleeding
occulocuaneous albinism
nystagmus
76
HPS: inherit?genes?
AR...HPS1, HPS3, HPS5, etc
77
HPS tx?
plt transfusions
78
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
79
plt count in HPS?
normal
80
Wiskott-Aldrich syndrome: inheritance? gene?
x-linked; WASP
81
WASP gene encodes what?
surface glycoprotein CD43, an actin-binding signaling protein
82
features of WAS
- low plts
- small plts
- defects in T cell adn B-cells
83
x-linked thrombocytopenia gene?
also WASP...microthrombocytoepnia but no eczema or immunodef
84
traid in WAS
low plts
eczema
frequent infections
85
dx WAS how? 2
gene testing
| flow for WASP protein
86
complications of WAS?
hemorrahge
infection
autoimmune disordrs
malig like ALL, lymphoma
87
tx of WAS (3)
supportive for eczema, infection
splenectomy
SCT
88
MYH9-related disorders: inheritance?
AD
89
MYH9 dx?
leukocyte inclusions= dohle bodies
| gene testing
90
features of MYH9 related disordres? 3
renal failure
SNHL
cataracts
91
MYH9 management
supportive
92
TAR = thrombocytopnia absent radii syndrome...thumbs are?
normal
93
heme issue in TAR?
absent megakaryocytes with elevated TPO levels
94
TAR tx?
plt transfusions...most have increase in plt count by 12-24 months though...self-correction!
95
cleft palate, heart defect, learning issue, low plts...think?
velocardiofacial syndrome
96
congential heart disease, dev delay, faical dysmorph, short stature, low plts...think?
jacobson syndrome/paris-trousseau
97
size of plts in MYH9?
large
98
MYH9 gene?
MYH9
99
other than absent radii and low plts, 2 other features of TAR?
cow milk intolerance
cardiac issues
renal issues
100
organ dysfunction--> plt dysfunction? 1 reason?
renal; decreased thromboxane A2 formation
101
ASA leads to irreversible inhibition of what? last for how long?
cyclooxygenase 1; 7 days
102
NSAID effect on plts: reversible or irrev? of what specifically?
reversible; cyclooxygenase 1
103
how does cyanotic heart disease and ECMO affect plts?
plt activation
104
other than NSAIDs adn ASA, other drugs--> plt dysfunction?
valporic acid
psychotropic drugs
semi synthetic penicillin derviatives
105
what does plt aggreg look like on ASA?
ADP goes down a bit then BACK UP, everythign else is really dampened
106
mange acquire plt dysfucntion how?
```
remove offending agent
tx underlying disease
lcoal pressures, pressure
TXA
desmopressin
conjguated estrogens
plt tranfusions
rbcs if anemic
```
107
mut in essential thrombocytosis?
JAK>CALR, MPL
108
causes of reactive thrombocytosis
```
inflamm
iron def
marrow recovery
asplenia
young infants (esp prem)
```
109
reactive thrombocytosis def'n
>450k (usually caps at 1 million)
110
for seconary thrombocytosis, do they get clots?
no
111
ET: clinical featuers?
splenomegaly
bleeding-acquired vWD
-thrombosis
-numbness and tingling, fatigue, headache, vision changes
112
ET plt count?
>450k
113
ET lab test?
high levels of thrombopoeitin
114
management of ET?
ASA
HU
anagrelide
