platelet function and pt approach Flashcards
Platelets stem from
megakaryocytes
Newly formed platelets are larger in size and termed _____
megathrombocytes
Plt maturation time is ____ days and circulating life span of ____ days
4-5; 9-10
What do platelets have and do NOT have?
Have mitochondria and 3 functional granules (alpha, dense, lysosomal)
Canalicular system
cytoplasmic framework
DO NOT have nucleus
Dense Granules contains:
ATP, ADP, Serotonin, calcium
Alpha granules contain:
procaogulant proteins (fibrinogen, F5, vWF), plt specific factors (for activation) and growth factor
Lysosomal granules contain
acid hydrolases
Internal membrane tunnels in platelets are called ____ where granules can be secreted
canalicular system
What interactions occur during platelet adhesion
GP1b - vWF
GPIIb/IIIa (aIIbb3) - vWF (and fibrinogen)
GPVI - collagen
b1 integrin - ligands in subendothelium (collagen, laminin, fibronectin)
What stick to vWF during adhesion?
GP1B
GPIIb/IIIa
What sticks to collagen during adhesion?
GPVI
b1 integrin
what are soluble agents?
thrombin, thromboxane A2, epinephrine, ADP
Effects of soluble agents?
Increase GPIIb-IIIa to vWF
Soluble agents –> G protein coupled platelet membrane receptor leads to?
Intracellular signaling, ca mobilization
Calcium mobilization leads to ____?
activation of phospholipase A2
Phospholipase A2 does what?
releases arachidonic acid from phospholipids
COX 1 convert AA –>?
Thromboxane A2 (TXA2)
TxA2 with other agonist will ____?
further amplify platelet activation
Platelet activation = membrane will?
Switch phospholipid phosphatidylserine to outer membrane
Phospholipid phosphatidylserine is important to ?
interact with clotting factor –> generate thrombin
GPIIb IIIa from low to high affinity requires:
soluble agonists, subendothelial matrix, talin (membrane protein) to G protein
High affinity GPIIb IIIa can bind
vWF AND Fibrinogen
Fibrinogen and platelet interaction
fibrinogen acts as a bridge to lace/connect platelets together –> aggregate
Thrombin effect on clot
Fibrinogen to fibrin –> stablize clot
Factor XIII –> stablizes clot
vWD tests to run
prolonged BT (abnormal plt-endothelial interactions)
PFA-100 (platelet function analyzer - should be normal)
Factor 8 level
vW Ab –> determine # of vWF
Ristocetin cofactor activity - vWF activity
vWF multimer assay - qualitative defect
Bernard Soulier SYndrome is autosomal ____ disorder; Expression of ____ on platelet surface is reduced
recessive; GP1b
Bernard soulier syndrome - platelet aggregation studies only show abnormal _____?
platelet aggregation with ristocetin
Gray platelet syndrome:
deficiency in alpha granules
gray platelet syndrome can be acquired _______ or rare defect in signal transduction pathway within plt
platelet pass across abnormal vascular surface (cardiopulmonary bypass apparatus)
Afibrogenemia is _______ and leads to ________ hemostatis defect
Lack of fibrinogen (for GPIIbIIIa - for aggregation); primary (platelet plug) AND secondary (fibrin crosslinking)
vWD presents with
mucosal/skin bleeding
afibrogenemia presents with
mucosal and cutaneous bleeding + deep muscle hematomas
Glanzmann thrombasthenia is a _____ bleeding disorder caused by _______
AR
Absent/defective GPIIbIIIa
Glanzmann thrombasthenia - platelets can ____ but cannot ____
adhere
(no) aggregate
Glanzmann thrombasthenia presents with
petechiae and easy brusing
ITP = aka?
Immune thormbocytopenic purpura
Etiology of ITP
antibody to platelet antigen –> remove by macrophage/RES
Acute (viral) or Chronic
Acute ITP typically in ____ (pt population), presents with _____, likely caused by _____
children/young adults
petechiae/nosebleeds
viral infection - self resolving 2-6 weeks (can give steroids)
Chronic ITP typically in ____ (pt population), caused by __________, typical treatments are ______
adults
concurrent autoimmune disorder, lymphoa, HIV, (?)
corticosteroids, IVIG, splenectomy
ITP and steroid - how does it work
steroids dampen B cell proliferation = decrease antibody = less autoimmune (7-9 day lag)
ITP and IVIS - how does it work?
IVIG - block FcR - prevents binding to antibody coated platelets (1-2 day lag)
Splenectomy and ITP, why?
Remove site of autoanitbody induced platelet removal - 60-70% lasting responses
Alloimmune thrombocytopenia is when _________________, typically caused by ______
pt develop Ab to platelet antigen not present on self plts
transfusion, neonates, drug induced, heparin induced
TTP =?
thrombotic thrombocytopenic purpua
TTP characterized by ___?
fever, renal insufficiency, microangiopathic hemolytic anemia, mental status changes, thrombocytopenia
TTP occurs because
damage to endothelial tissue + Large vWF; antibody to ADAMTS13; large vWF = plt adhesion/aggre - plt plugs in small arterioles
ADAMTS13
metalloprotease - digest vWF to smaller multimers
TTP treatment
plasmapheresis - remove vWF multimer
Replace missing ADAMTS13
HUS = ?
hemolytic uremic syndrome
HUS associated/presents with
renal failure (children), similar to TTP
HUS caused by
(bacterial toxin) damage to endothelial lining - microthrombi - self limiting
Thrombocytopenia lab will show abnormal:
platelet count
Platelet dysfunction lab will show abnormal:
bleeding time
hemophilia lab will show abnormal:
APTT
Factor 7 deficiency lab will show abnormal:
PT/INR
Dysfibrinogenemia lab will show abnormal:
TCT - thrombin clotting time - fibrinogen defects/ fibrin split products, heparin effects
Hypofibrinogenemia lab will show abnormal:
FIbrinogen
PFA-100 or Bleeding time evalutes
primary hemostasis
APTT screens ______ pathway, PT/INR screens ____
intrinsic, extrinsic