Coagulation/Platelets Flashcards
primary hemostasis consists of
platelet adherence, activation, and aggregation
what do platelets initially adhere to?
exposed sub endothelium via vWF
what does activation of platelets entail
shape change and release of granule contents
what is secondary hemostasis
activation of coagulation, generation of thrombin
what initiates coagulation
tissue factor
IIa function
thrombin (IIa)- removes 4 fibronopeptides, allows conversion of fibrinogen to fibrin
thrombomodulin function
enhances activation of PC by IIa
release of tPA causes
plasminogen conversion to plasmin
what does plasmin do
breaks up fibrin chains
what is elevated in DIC
plasma D-dimers
2 main deficiencies of hemophilia
factor VIII or IX (VIII is more common)
why is hemophilia more common in males?
because it is X-linked
treatment of hemophilia
IV injection of factor VIII or IX
clinical phenotype of severe hemophilia
spontaneous soft tissue and joint bleeds
clinical phenotype of moderate hemophilia
only after minor injury or surgery
1-5% coagulation factor level
clinical phenotype of mild hemophilia
post-op and post-trauma bleeding
5-40% coagulation factor level
population that is at high risk for factor XI deficiency
Ashkenazi Jews
when is prothrombin time prolonged
II, V, VII, X, or fibrinogen are reduced
what does NOT affect PT
VIII, IX, XI, XII, PK, or HMWK levels
when is PTT prolonged
if any factor (except VII) is low
what factor does NOT affect either PT or PTT
XIII
sources of acquired bleeding disorders
liver dysfunction
vitamin K deficiency
disseminated intravascular coagulation (DIC)
what factors need vitamin K to function
II, VII, IX, X, protein C and protein S
function of vitamin K
changes conformation of proteins so that they bind phospholipid membranes
what are 3 coagulation inhibitors
protein C
protein S
antithrombin
what is the most common cause of hereditary thrombophilia
Factor V Leiden
what does Lupus Anticoagulants do to the PTT
prolongs it
in the case of thrombosis and/or recurrent pregnancy loss, check for
lupus anticoagulants, autoimmune disease
action of heparin
enhance binding of AT and Thrombin
purpose of INR
standardize the reporting of test results for patients taking coumadin
dabigatran
direct thrombin inhibitor
rivaroxaban, apixaban
direct Xa inhibitor
purpura fulmina is associated with
group A beta hemolytic streptococcus
clinical conditions associated with DIC
bacterial sepsis burns extensive trauma placental abruption hypoxia
cause of DIC
exposure of patient’s blood to tissue factor
ASA action
anti platelet drug
inhibits prostaglandin synthesis
Dipyridamole action
elevates cAMP by inhibition of phosphodiesterase
clopidogrel, prasugrel, ticagrelor action
interferes with ADP binding
abciximab action
inhibition of GP IIb/IIIa
2 pathways essential for platelet activation
phosphoinositide hydrolysis pathway
eicosanoid pathway
dense granule contents
ADP, ATP, serotonin- amplify platelet activation
lysosomal granule contents
proteases and glycosidases
how is platelet bleeding different than coagulation factor abnormality bleeding?
platelet factor: bruises, petechiae, everywhere.
coagulation factor- hemorrhage into joints, soft tissues
cause of ATP
bound anti-platelet antibodies (IgG)- increased platelet destruction
platelet size correlates with
megakaryocyte number
platelet diameter correlates inversely with
platelet survival
vWF function
carrier for FVIII and adhesive link between platelets and injured blood vessel wall
vWD cause
defective binding of platelets to injured vessel walls, then to each other.
prolonged bleeding time
where is vWF stored
alpha granules of platelets and in the Weibel-Palade body organelle in endothelial cells
most common vWD
type 1- scattered mutations, autosomal dominant
mutants with inhibition of secretion
thrombotic thrombocytopenic purpura
acute onset of platelet consumption
risk factors of TTP
HIV, SLE, pregnancy, drugs, e. coli
features of TTP
thrombocytopenia hemolytic anemia- microangiopathic, reticulocytes increased LDH neurological symptoms renal impairment fever NO DIC
etiology of TTP
increased vWF multimers- lead to platelet clumping under shearing conditions
ADAMTS-13 absence is associated with
Thrombotic thrombocytopenic purpura