Blood Clot

Question 1

Platelet products

Answer 1

Alpha granules, Dense granules, and Thromboxane A2

From megakaryocytes

Question 2

Platelet Alpha granules

Answer 2

vWF promotes platelet adhesion to collagen. Synth in vesicular cells and megakaryocytes, self polymer.
Free floating vWF binds to factor 8 and stabilizes it

Question 3

Platelet Dense Granules

Answer 3

ADP = platelet activator
Serotonin = vasoconstrictor

Question 4

Platelet Thromboxane

Answer 4

TXA2 is a potent platelet activator

Inhibited by aspirin

Question 5

Overview of blood coag

Answer 5

1. Vasoconstriction: seals vasulature so no excess bleed
2. Platelet Activating factor: forms platelet plug (adhesion, aggregation, secretion)
3. Form fibrin meshwork (soft to hard clot)
4. Fibrinolysis: removes clots

Question 6

Platelet activation: Adhesion

Answer 6

Vascular damage leads to exposed collagen which activates platelets. Free vWF binds collagen and GP1b on platelet binds vWF.

Question 7

Platelet activation: Secretion

Answer 7

Secretes: ADP, Serotonin, vWF, TXA2, Fibrinogen. These along with epi, thrombin, and PAF turn on other platelets

Question 8

Platelet Activation: Aggregation

Answer 8

Brings together activated platelets. Released fibrinogen sticks everything together by binding GP2b/GP3a on platelet membrane

Question 9

Intrinsic Pathway

Answer 9

Factor 12 exposed to collagen activates it to 12a.
12a activates factor 11 which activates 9 on phosphatidyl serine flipped to outer leaflet
8a and 9a together activate 10
5a and 10a together activate 2 (prothrombin to thrombin)

Question 10

Extrinsic Pathway

Answer 10

Trauma induces factor 7a, 7a activates 9 (same as intrinsic)
Factor 7a with TF will activates 10 (Ca makes connection btwn carboxylated Glu in Gla domain and neg charged surface of platelet coming from phosphatidyl serine)
Factor 5a and 10a together activates 2 (prothrombin to thrombin)

Question 11

Both pathways

Answer 11

Factor 2a/thrombin activates 1 (fribrinogen to fibrin = soft clot). Thrombin removes negative charges on fibrinogen so binding can occur).
Factor 13 is activated by thrombin which is a transglutamidase which forms cross linked hard clot

Question 12

All pathways drawn

Answer 12

on paper

Question 13

Facts about clotting

Answer 13

Most clot factors are made in liver in zymogen form, activated forms are serine proteases (serine proteases cut at carboxy terminal side of Arg in zymogens)

Calcium is required for most steps

Carboxylation is vit K dependent and is needed for carboxy of prothrombin, protein C, protein S, factors 7 9 10 in order for them to stick on membrane

Question 14

Thrombin information

Answer 14

Is self limiting. Binds to thrombomodulin on endo cell surface. Activates APC which binds protein S to inhibit factors 5a and 8a

Question 15

Natural Anti-Coag

Answer 15

Antithrombin is a serpin (serine protease inhib), inactivates Ser proteins (10a and thrombin) and is activated by heparin

Question 16

Fibrinolysis

Answer 16

Plasminogen floats around and activated by tPA and uPA to plasmin which degrades fibrin clots

Question 17

Glanzmans Thromboasthemia

Answer 17

Def in GP2b/GP3a leading to aggregation problems and severe bleeding

Question 18

Von Willebrands Disease

Answer 18

mut in vWF leading to defect in platelet aggregation, pt bleeds out

Question 19

Von Willebrands Disease Table Drawn

Answer 19

On paper

Question 20

Factor 5 Leiden

Answer 20

Factor 5a resistant to APC due to missense mutation leading to continuous clotting

Question 21

Hemophilia

Answer 21

X-linked
A = Factor 8 and flip inversion
B= Factor 9 and is Christmas disease
Tx= infuse missing factor

Question 22

Plavix

Answer 22

Antithrombatic

Interferes with GP2b/GP3a/fribrinogen leading to aggregation misfx

Question 23

Coumarin/Warfarin

Answer 23

Inhibits Vitamin K leading to inhib of carboxylation of clot factors therefore inhibiting clotting

Question 24

Thrombatic Therapy

Answer 24

Plasminogen activating, breaks clots for MI’s and stroke
tPA=activase
uPA = abbokinase
Streptokianse = steptase