platelet function and pt approach

Question 1

Platelets stem from

Answer 1

megakaryocytes

Question 2

Newly formed platelets are larger in size and termed _____

Answer 2

megathrombocytes

Question 3

Plt maturation time is ____ days and circulating life span of ____ days

Answer 3

4-5; 9-10

Question 4

What do platelets have and do NOT have?

Answer 4

Have mitochondria and 3 functional granules (alpha, dense, lysosomal)
Canalicular system
cytoplasmic framework
DO NOT have nucleus

Question 5

Dense Granules contains:

Answer 5

ATP, ADP, Serotonin, calcium

Question 6

Alpha granules contain:

Answer 6

procaogulant proteins (fibrinogen, F5, vWF), plt specific factors (for activation) and growth factor

Question 7

Lysosomal granules contain

Answer 7

acid hydrolases

Question 8

Internal membrane tunnels in platelets are called ____ where granules can be secreted

Answer 8

canalicular system

Question 9

What interactions occur during platelet adhesion

Answer 9

GP1b - vWF
GPIIb/IIIa (aIIbb3) - vWF (and fibrinogen)
GPVI - collagen
b1 integrin - ligands in subendothelium (collagen, laminin, fibronectin)

Question 10

What stick to vWF during adhesion?

Answer 10

GP1B

GPIIb/IIIa

Question 11

What sticks to collagen during adhesion?

Answer 11

GPVI

b1 integrin

Question 12

what are soluble agents?

Answer 12

thrombin, thromboxane A2, epinephrine, ADP

Question 13

Effects of soluble agents?

Answer 13

Increase GPIIb-IIIa to vWF

Question 14

Soluble agents –> G protein coupled platelet membrane receptor leads to?

Answer 14

Intracellular signaling, ca mobilization

Question 15

Calcium mobilization leads to ____?

Answer 15

activation of phospholipase A2

Question 16

Phospholipase A2 does what?

Answer 16

releases arachidonic acid from phospholipids

Question 17

COX 1 convert AA –>?

Answer 17

Thromboxane A2 (TXA2)

Question 18

TxA2 with other agonist will ____?

Answer 18

further amplify platelet activation

Question 19

Platelet activation = membrane will?

Answer 19

Switch phospholipid phosphatidylserine to outer membrane

Question 20

Phospholipid phosphatidylserine is important to ?

Answer 20

interact with clotting factor –> generate thrombin

Question 21

GPIIb IIIa from low to high affinity requires:

Answer 21

soluble agonists, subendothelial matrix, talin (membrane protein) to G protein

Question 22

High affinity GPIIb IIIa can bind

Answer 22

vWF AND Fibrinogen

Question 23

Fibrinogen and platelet interaction

Answer 23

fibrinogen acts as a bridge to lace/connect platelets together –> aggregate

Question 24

Thrombin effect on clot

Answer 24

Fibrinogen to fibrin –> stablize clot

Factor XIII –> stablizes clot

Question 25

vWD tests to run

Answer 25

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

Question 26

Bernard Soulier SYndrome is autosomal ____ disorder; Expression of ____ on platelet surface is reduced

Answer 26

recessive; GP1b

Question 27

Bernard soulier syndrome - platelet aggregation studies only show abnormal _____?

Answer 27

platelet aggregation with ristocetin

Question 28

Gray platelet syndrome:

Answer 28

deficiency in alpha granules

Question 29

gray platelet syndrome can be acquired _______ or rare defect in signal transduction pathway within plt

Answer 29

platelet pass across abnormal vascular surface (cardiopulmonary bypass apparatus)

Question 30

Afibrogenemia is _______ and leads to ________ hemostatis defect

Answer 30

Lack of fibrinogen (for GPIIbIIIa - for aggregation); primary (platelet plug) AND secondary (fibrin crosslinking)

Question 31

vWD presents with

Answer 31

mucosal/skin bleeding

Question 32

afibrogenemia presents with

Answer 32

mucosal and cutaneous bleeding + deep muscle hematomas

Question 33

Glanzmann thrombasthenia is a _____ bleeding disorder caused by _______

Answer 33

AR | Absent/defective GPIIbIIIa

Question 34

Glanzmann thrombasthenia - platelets can ____ but cannot ____

Answer 34

adhere | (no) aggregate

Question 35

Glanzmann thrombasthenia presents with

Answer 35

petechiae and easy brusing

Question 36

ITP = aka?

Answer 36

Immune thormbocytopenic purpura

Question 37

Etiology of ITP

Answer 37

antibody to platelet antigen --> remove by macrophage/RES | Acute (viral) or Chronic

Question 38

Acute ITP typically in ____ (pt population), presents with _____, likely caused by _____

Answer 38

children/young adults petechiae/nosebleeds viral infection - self resolving 2-6 weeks (can give steroids)

Question 39

Chronic ITP typically in ____ (pt population), caused by __________, typical treatments are ______

Answer 39

adults concurrent autoimmune disorder, lymphoa, HIV, (?) corticosteroids, IVIG, splenectomy

Question 40

ITP and steroid - how does it work

Answer 40

steroids dampen B cell proliferation = decrease antibody = less autoimmune (7-9 day lag)

Question 41

ITP and IVIS - how does it work?

Answer 41

IVIG - block FcR - prevents binding to antibody coated platelets (1-2 day lag)

Question 42

Splenectomy and ITP, why?

Answer 42

Remove site of autoanitbody induced platelet removal - 60-70% lasting responses

Question 43

Alloimmune thrombocytopenia is when _________________, typically caused by ______

Answer 43

pt develop Ab to platelet antigen not present on self plts | transfusion, neonates, drug induced, heparin induced

Question 44

TTP =?

Answer 44

thrombotic thrombocytopenic purpua

Question 45

TTP characterized by ___?

Answer 45

fever, renal insufficiency, microangiopathic hemolytic anemia, mental status changes, thrombocytopenia

Question 46

TTP occurs because

Answer 46

damage to endothelial tissue + Large vWF; antibody to ADAMTS13; large vWF = plt adhesion/aggre - plt plugs in small arterioles

Question 47

ADAMTS13

Answer 47

metalloprotease - digest vWF to smaller multimers

Question 48

TTP treatment

Answer 48

plasmapheresis - remove vWF multimer | Replace missing ADAMTS13

Question 49

HUS = ?

Answer 49

hemolytic uremic syndrome

Question 50

HUS associated/presents with

Answer 50

renal failure (children), similar to TTP

Question 51

HUS caused by

Answer 51

(bacterial toxin) damage to endothelial lining - microthrombi - self limiting

Question 52

Thrombocytopenia lab will show abnormal:

Answer 52

platelet count

Question 53

Platelet dysfunction lab will show abnormal:

Answer 53

bleeding time

Question 54

hemophilia lab will show abnormal:

Answer 54

APTT

Question 55

Factor 7 deficiency lab will show abnormal:

Answer 55

PT/INR

Question 56

Dysfibrinogenemia lab will show abnormal:

Answer 56

TCT - thrombin clotting time - fibrinogen defects/ fibrin split products, heparin effects

Question 57

Hypofibrinogenemia lab will show abnormal:

Answer 57

FIbrinogen

Question 58

PFA-100 or Bleeding time evalutes

Answer 58

primary hemostasis

Question 59

APTT screens ______ pathway, PT/INR screens ____

Answer 59

intrinsic, extrinsic