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Flashcards in Platelets Deck (60):
1

artery vs vein clots

artery: predominetly composed of platelets, pale red in color, inhibited by aspirin, likely to occur in setting of turbulence

vein: composed of clotting factors,erythrocytes, and platelets

2

artery vs vein clots

artery: predominetly composed of platelets, pale red in color, inhibited by aspirin, likely to occur in setting of turbulence

vein: composed of clotting factors,erythrocytes, and platelets

3

shape of resting vs activated platelets

resting: smooth, round
activated: irregular, sticky (if on surface, look like over easy egg)

4

what are platelets lacking?

nuclei (what they have is what they get. very little protein production)

5

factors secreted by artery endothelial that inhibits platelets activation

NO & PGI2 (Prostaglandin I2). make platelets more resistant to activation by increasing cAMP levels

6

von Willebrand factor (VWF)

molecular glue with binding sites for platelet surface and collagen. works to adhere platelets to site of vessel damage. necessary for adhesion at the flow rates seen in arteries

7

role of collagen in vessel damage

platelets stick to collagen fibrils and become activated.

8

role of tissue factor in vessel damage

activates platelets indirectly via thrombin production

9

what factors are secreted by activated platelets that recruit more platelets to the clot?

ADP & TxA2

10

relationship of platelets to the clotting cascade

support the ten-ase and prothrombinase complexes since the negatively charged lipids on their outer membrane act as the rxn surface

11

what is the main integrin responsible for cohesion in platelets?

alpha 2b beta 3

12

what is the main integrin responsible for cohesion in platelets?

alpha 2b beta 3

13

platelet activation GPCR agonist ligands

TxA2, locally generated thrombin, ADP released from platelet granules

14

what are platelets lacking?

nuclei (what they have is what they get. very little protein production)

15

factors secreted by artery endothelial that inhibits platelets activation

NO & PGI2 (Prostaglandin I2). make platelets more resistant to activation by increasing cAMP levels

16

von Willebrand factor (VWF)

molecular glue with binding sites for platelet surface and collagen. works to adhere platelets to site of vessel damage. necessary for adhesion at the flow rates seen in arteries

17

role of collagen in vessel damage

platelets stick to collagen fibrils and become activated.

18

role of tissue factor in vessel damage

activates platelets indirectly via thrombin production

19

what factors are secreted by activated platelets that recruit more platelets to the clot?

ADP & TxA2

20

relationship of platelets to the clotting cascade

support the ten-ase and prothrombinase complexes since the negatively charged lipids on their outer membrane act as the rxn surface

21

how do platelets aggregate?

upon activation, platelets activate surface integrins via GPCR signals. Once activated, these proteins display fibrinogen receptors, which cross link platelets

22

what is the main integrin responsible for cohesion in platelets?

alpha 2b beta 3

23

GPCR signals after platelet activation

agonists of platelet activation bind to the GPCR on the platelet, which then signal downstream causing a rise in intracellular Ca levels. This triggers activation of the integrin via the binding of talin protein to integrin

24

platelet activation GPCR agonist ligands

TxA2, locally generated thrombin, ADP released from locally damaged cells

25

TxA2

pro platelet activation ligand generated by platelets. one of the most potent activators of platelets.

26

Production pathway of TxA2

phosphatidylcholine (PC) --> arachidonate --> PGG2 (via COX-1) --> PGH2 --> TxA2

27

COX-1

enzyme that converts arachidonate to PGG2. inhibited by aspirin

28

aspirin mechanism

irreversibly inhibits Cox1 so that platelets are not activated via TxA2 and clotting is inhibited.

29

progenitor of platelets

megakaryocytic from common myeloid progenitor

30

how do megakaryocytics produce platelets?

spit out long psuedopods called pro-platelets, which produce platelets at tips. process isn't entirely understood, but needs to have made everything the platelet will need in its life.

31

final cytokine in megakaryocyte generation?

TPO

32

Thrombopoieton (TPO)

prinicple cytokine regulating the platelet count

33

where is TPO produced

constitutively in liver & somewhat in kidney

34

TPO receptor

MPL, expressed on megakaryocytic and on platelets

35

what happens when the platelet count falls?

free TPO levels increase (amount that makes it to bone marrow increases), stimulating increased megakaryocytopoiesis.

36

what is a normal platelet count?

150-400,000

37

how long do platelets last?

10 days

38

thrombocytopenia

low platelet count

39

functions of platelet

contribute to homeostasis, regulate platelet production (TxA2), promote activation of factors 2/10 (lipophospholipids)

40

pathophysiology of ITP

antibodies that recognize epitopes on surface of platelets (integrin, etc), reticuloendothelial system then phagocytoses antibody bound platelets

41

petechiae

pin head size hemorrhages which reflect the absence of platelets

42

typical symptoms of bleeding due to platelet defect (inability to form platelet plugs)

petechiae/ecchymoses, epistaxis/menorrhagia, skin and mucus membrane bleeding, immediate bleeding

43

typical symptoms of bleeding due to coagulation defects (inability to form thrombin and fibrin)

deep spreading hematomas, hemarthroses, retroperitoneal bleeding, delayed bleeding when an inadequate fibrin clot breaks down prematurely (platelet clot occurs, but it is not great and is broken down quickly by plasmin)

44

why does application of pressure stop bleeding?

creates local stasis so that coagulation factors can accumulate and work faster

45

mechanism of death from coronary artery occlusion

atherosclerotic plaques bulge into vessel and restrict flow. eventually plaque ruptures into vessel, exposing blood to tissue factor, collagen, oxidized lipids. causes rapid pile up of platelets in already constricted area

46

causes of thrombocytopenia

failure of production, reduced survival/increased destruction, increase pooling in spleen

47

causes of decreased platelet production

decreased megakaryocytes and/or ineffective production

48

thrombocythemia

neoplastic thrombocytosis. clonal disorder or malignancy driving platelet production. JAK gain of function mutation. >>1million

49

clinical features of ITP (Immune thrombocytopenic purport)

autoimmune disorder, more common in women, chronic in adult, acute in kids, petechiae and ecchymoses at low platelet counts.

50

physical and lab findings of ITP

low platelet counts, rest of CBC is normal, spleen size is usually normal, fatal bleeding is rare (platelets that are present are normal, there are just fewer of them)

51

pathophysiology of ITP

antibodies that recognize epitopes on surface of platelets (integrin, etc), reticuloendothelial system then phagocytoses antibody bound platelets

52

ITP treatments

inhibit phagoctye mediated clearance of Ab coated platelets (steroids, splenectomy, IVIG), decrease antibody production (steroids, rituximab), impair T/B cell interactions (steroids, immunosuppresants), enhance platelet production (TPO mimetics)

53

how do steroids inhibit phagocytosis of platelets?

they down regulate Fc receptors on surface of megakaryocytes

54

rituximab

drug that binds to CD20 (on B cells) and reduces the B cell population.

55

drug induced thrombocytopenia

drug sticks to glycoprotein on platelet surface, Ab recognizes drug.glycoprotein complex, Ab covered platelets destroyed by RES (quinine is example drug). worse upon second exposure

56

causes of increased sequestration of platelets

typically 1/3 of all platelets reside in spleen, so when spleen enlarges, so does this %.

57

glanzmann's thrombasthenia

alpha2 beta3 deficiency that leads to defect in platelet aggregation

58

thrombocytosis

elevated platelet count (>450k), normal platelets, no problems with bone marrow. commonly acquired after splenectomy, iron deficiency, inflammatory states, etc. sometimes inherited as TPO/MPL mutations

59

thrombocythemia

neoplastic thrombocytosis. clonal disorder or malignancy driving platelet production. JAK gain of function mutation. >>1million

60

functions of TPO

stimulate megakaryocyte maturation & promote platelet release (bound to platelets via MPL when platelet levels are normal)