Exam 3 Flashcards
abnormal clot in vitro, retraction and normal plt count
Glanzmann Thrombasthenia
What is clot retraction
volume of a formed clot is reduced through contraction of cytoskeleton of activated plts within the clot
Deficiency or abnormality of the plt membrane GP IIb/ IIIa complex
Glanzmann Thrombasthenia
Petechiae, purpura, menorrhagia, GI bleeding, hematuria
Glanzmann Thrombasthenia
What levels of GP in Glanzmann thrombasthenia
homo severely decreased to no GP IIb/ IIIa
hetero- 50-60% of normal GP IIb/ IIIa
Lab test in Glantzmann Thrombasthenia
plts normal
lack of aggregation in response to all plt activating agents
diminished plt activity
How is GT treated
normal plt transfusion
What type of platelet disorder is GT
platelet aggregation
platelet disorder where GP Ib/ IX/ V complex is missing from platelet surface
Bernard Soulier Giant platelet syndrome
If there is an inability to bind to VWF, then platelets have an inability to
adhere to exposed subendothelial cells, causes bleeding
In childhood: Ecchymoses, epistaxis, gingival bleeding
Bernard-Soulier Giant platelet syndrome
How is Bernard Soulier treated
cannot be correct by adding plasma
afibrinolytic therapy- treat the mucosal bleeding
What glycoprotein defect is most often the cause of BSS
GP Ib alpha
normal ADP, epi, collagen, arachadonic
no response to ristocetin
What lab results can be expected from BSS
What is the main disorder of plt aggregation
and plt adhesion?
aggregation- Glanzmann Thrombsthenia
adhesion- Bernard Soulier Giant plt
normal plt count
mucocutaneous hemorrhage, hematuria, epistaxis, easy bruising
platelet secretion
What are dense granules
storage site for serotonin, nucelotides, Ca and pyrophosphate
Deficiency associated with albinism
Dense granules
Plt aggregation test shows an aggregation pattern affected by ADP
What deficiency is this
Arachidonic acid …
epi and low dose ADP …..
Collagen …..
dense granules
Arachidonic acid … no response
epi and low dose ADP …..primary wave, no secondary
Collagen ….. decreased
dense granule deficiency that shows defective lysosomal function
Hermansky-Pudlak syndrome
Swiss cheese plts
Hermansky-Pudlak syndrome
Dense granule deficiency that causes giant lysosomal granules
Chediak Higashi syndrome
Dense granule deficiency that causes microthrombocytopenia
Wiskottp-Aldrich Syndrome WAS
Dense granule deficiency that is autosomal recessive and causes an absence of radial bones
Thrombocytopenia with absent Radii syndrome
TAR
What are alpha granules
storage site for proteins produced by the megakaryocyte or present in plasma and taken up by plts
Primary reason for platelets to have a granular appearance
alpha granules
absence of alpha granules
gray platelet syndrome
large plts with a gray appearance
gray plt syndrome
Which part of the platelet is affect in storage pool diseases
dense granules
Deficiency that leads to lifelong mild bleeding disorder,
platelets do not adhere to collagen
collagen receptor deficiencies
What are the 3 ADP receptors
P2X1 - Ca ion influx
P2Y1 Ca mobilization and shape change in response to ADP
P2Y12 macroscopic plt aggregation
No Phospholipid flip
Scott syndrome
no binding of vitamin K dependent factors
platelets always in activated state
Stormorken syndrome
What can case acquired defects of platelet function
drug ingestion
What drug
irreversible acetylates/ inactivates cyclooxygenase
aspirin
What is not affected by aspirin
endothelial cells- produce nitric oxide, a plt inhibitor, making them unaffected by aspirin
drugs that inhibit cyclooxygenase are ____
reversible
How do P2Y12 ADP receptor inhibitors work
plt activation and aggregation are induced by ADP and inhibited
Clopidogrel, prasugrel, ticlopidine, ticagrelor, cangrelor
P2Y12 ADP receptor inhibitors
How does clopidogrel (plavix) work
needs to be converted to an active drug by a liver enzyme
CYP2C19 gene
clopidogrel plavix
Platelet drug that interferes with fibrinogen, inhibits plt aggregation
GP IIb/ IIIa receptor inhibitor
Drug used with patients under percutaneous coronary intervention
GP IIb/ IIIa receptor inhibitors
Drug that inhibits thrombin by blocking binding site on PAR-1
PAR-1 antagonist
P2Y12 inhibitors when taken with aspirin inhibit plt function
platelet disorder that shows
PV, CML, ET, CMF
also decreased aggregation and secretion in response to epi, ADP and collagen
MPNs myeloproliferative neoplasms
plt disfunction that arises from coating of plt membrane by paraprotein
multiple myeloma and waldenstrom macroglobulinemia
causes plt activation and fragmentation in the extracorporeal circuit
CPB cardiopulmonary bypass surgery
associated with hemostatic abnormalities
alcoholic cirrhosis
liver disease
rare disorder where there is an absence or near absence of fibrinogen, causing abnormal platelet function
hereditary afrinogenemia
platelets aggregate at lower concentrations of aggregating agents than normal
hyperaggregable plts
sticky plt syndrome
hyperaggregable plts
Hereditary Vascular disorder where
thin walled blood vessels with a discontinuous endothelium
Hereditary Hemorrhagic Telangiectasia
Rendu Osler Weber Syndrome
giant cavernous hemangiomas (vascular tumors), present at ___
Hemangioma Thrombocytopenia
Kasabach Merrit Syndrome
present at birth
hyperextensible skin, hypermobile joints, defects in collagen production
Ehlers-Danlos Syndrome
allergy associated with foods, drugs, cold, insect bites, vaccinations
Henoch Schonlein purpura
allergic purpura
proteins coat the plt membrane- causes abnormalities in plt aggregation, adhesion and actibation
paraproteinemia
Deposition of abnormal quantities of amyloid protein in tissues
amyloidosis
fibrous protein consisting of rigid, aggregated fibrils
amyloid
dark flat blotches, leave ae spots, due to lack of collagen support
Senile pupura
when antibodies develop to vessel wall components and create complexes that change the wall permeability
Drug induced vascular purpuras
What is epistaxis
nose bleeds
small pinpoint hemorrhages, 1 mm diameter
Petechiae
3mm diameter, generally round
purpura
1cm or larger, irregular in shape
eccchymoses
Large plts- megathrombocytes
dohle like bodies in neutrophils
mostly asymptomatic
normal plt function
May-Hegglin Anomaly
What is the cause of most congenital types of plt disorders
impaired plt PRODUCTION due to chromosomal abnormalities or genetic defects
BM does not have enough megakaryocytes
What is the normal plt reference range
150-450
What is the range for thrombocytopenia
<100
What is the most common cause of clinically important bleeding?
thrombocytopenia
severe neonatal thrombocytopenia that causes absence or extreme hypoplasia of radial bones
TAR syndrome
BM failure causes no megakaryocytes to be produced, TPO receptor is not functioning
can develop into luekemia, aplastic anemia, myelodysplasia
petechiae and bleeding
in infants at birth
Congenital Amegakaryocytic thrombocytopenia
thrombocytopenia due to incomplete megakaryocyte differentiation
normal plt functon and morphology
absent or mild bleeding
autosomal dominant thrombocytopeniaa
Disorders due to decreased plt production
X-linked thrombocytopenia
May-Hegglin Anomaly
TAR syndrome
Congenital Amegaakaryocytic Thrombocytopenia
Autosomal dominant thrombocytopenia
What can cause neonatal thrombocytopenia (platelet production issue)
TORCH syndrome infection - toxoplasmosis, rubella, CMV (most common), herpes
maternal ingestion of sulfonamides
Impaired plt production
Increased plt consumption or sequestration
What are 3 disorders that lead to decreased plt production
infections, chronic alcoholism, drug induced
Disorders that cause Immune platelet destruction
ITP
Immuno drug induced thrombocytopenia
neonatal immune mediated thrombocytopenia
posttransfusion Purpura
secondary thrombocytopenia, immune mediated
What is ITP
immune thrombocytopenia purpura
Distinguish ITP
acute
chronic
acute- kids, vaccines, infections
chronic- adults, mostly F
onset bruising, petechiae and epistaxis on normally healthy child, they had just received a vaccine
Acute ITP
What causes chronic ITP
IgG antibodies made against plts,
What is menorrhagia and what condition can it be seen in
very heavy period, chronic ITP
What lab test to expect with ITP
plt count low
plt morpho normla
BM hyperplasia
coag- abnormal if plts are non functioning
What type of Drug induced thrombocytopenia
immune complex induced, Drug induced autoabs,
hapten induced abs, drug dependet abs
abs interact with plts only in presence of drug
haptens act as a complete antigen
no drug presence needed
heparin induced
dependent- abs interact with plts only in presence of drug
hapten induced-haptens act as a complete antigen
drug induced- no drug presence needed
immune complex induced-heparin induced
What is neonatal alloimmune thrombocytopenia NAIT
IgG from mom crosses placenta and cause thrombocytopenia in fetus
What is neonatal autoimmune thrombocytopenia
passive transfer of maternal ITP autoantibodies
mostly patients that are multiparous, middle aged women, usually have history of a blood transfusion
1 week after transfusion shows purpura
PTP post transfusion purpura
What causes PTP
alloantibodies to antigens on plts in transfused product
thrombocytopenia due to loss of ADAMTS13
TTP
thromotic thrombocytopenic purpura
Mochcowitz syndrome
What does ADAMTS13 do
cuts VWF into small pieces allowing plts to be triggered
Who is more commonly affected by TTP
women 30-40
What lab tests to expect with TTP
intravascular hemolysis
BM- increased megakaryocytes
schistocytes
normal coag tests
How to treat TTP
infusion of plasma that are deficient of ADAMTS13
UL-VWF multimers removed
What is HUS
Hemolytic Uremic syndrome
thrombotic microangiopathies caused by bacteria
mostly Shigella in kids or E. coli O157
cause damage to colon- bloody diarrhea
What can cause adult HUS
immunosuppressive drugs or chemo, damaged kidneys, usually will need dialysis
What lab results to expect with HUS
hemolytic anemia
renal failure
thrombocytopenia
which is more severe HUS or TTP
in terms of thrombocytopenia
in terms of RBC anemia
TTP both
What is DIC
coag cascade activated and traps plts in fibrin clot
DIC and TTP
which is red and which is white clots
DIC-Red
TTP-White
What causes a big spleen syndrome
increased level of plts make spleen sequester more, there are too many plts produced because the plt count is low in blood vessels, BM is making more to compensate
What is the range for thrombocytosis
more than 450
What is reactive thrombocytosis
increased plt count due to inflammation trauma or underlying condition
What is postsplenectomy thrombocytosis
spleen is removed causes high plt count
What is Kawasaki disease
disorder caused by inflammation of the walls of small arteries in body
Who is most affected by Kawasaki disease
infants and young kids of Japanese descent
What lab tests to expect with exercise induced thrombocytosis
MPDs extreme values
What is the most common cause of thrombocytosis
Essential thrombocythemia ET
What lab results to expect in ET
way too many megakaryocytes in BM
super high plt count
abnormal plts, clumped agranular
Who is most affected by ET
middle aged/ older patients
Digital pain, gangrene, erythromelalgia, hemorrhagic episodes
ET
