Ch 20: Normal Hemostasis

Question 1

3 general things needed for normal hemostatic balance

Answer 1

Platelets, endothelial cells, coag factors

Question 2

Normal platelet level

Answer 2

150 to 350 x 10^9/uL

Question 3

Steps in platelet formation

Answer 3

1) TPO produced by liver binds to c-Mpl (a type 1 hematopoietic cytokine receptor) on megakaryocyte in BM
2) megakaryocyte proliferates, divides, and forms proplatelets
3) megakaryocyte fragmentation releases one to four thousand platelets

Question 4

Platelet morphology and function

Answer 4

1) small discoid cells, 2-3 um in diameter, live for 10 days
2) dense granules have ATP, Ca++, histamine, 5HT, Epi, and ADP (a potent aggregator)
3) alpha granules express adhesive P-selection, and contain PDGF, TGF-a, vWF, fibronectin, thrombospondin, PF4, neutrophil-activating peptide 2

Question 5

Stimulus for platelet activation

Answer 5

Endothelial damage leads to contact between platelets and ECM (esp. collagen 1)

Question 6

Steps in Platelet activation (plug formation)

Answer 6

1) platelets adhere to ECM via platelet glycoproteins (Gp Ia/IIa and Gp IV) attaching to collagen and Gp Ib/IX attaching to vWF [initial signal]
2) shape changes from discoid to spherical to stellate
3) secretion of dense and alpha granules releases adp, Epi, Ca++, vWF, and PDGF [positive feedback]
4) thromboxane A2 is made by COX1 [+ feed]
5) membrane changes expose p-selectin and pro coag anionic phospholipids like phosphatidylserine
6) platelet aggregation occurs by fibrinogen receptor-Gp IIb/IIIa cross linking

Question 7

Role of P-selectin and PDGF

Answer 7

Binds and localizes leukocytes (respectively) to it nitrate healing at the site of the platelet plug

Question 8

Factor Xa/Va complex

Answer 8

Cleaves factor II (prothrombin) to IIa (thrombin)

Question 9

TF/VIIa complex

Answer 9

1 of 2 “Xase” complexes (activates factor x). Also activates a small amount of IX. (TF= tissue factor! encountered with endothelial damage)

Question 10

IXa/VIIIa complex

Answer 10

1 of 2 “Xase” complexes (activates factor X), with ongoing activation of Factor IX by XIa

Question 11

What are the three procoagulant complexes?

Answer 11

Factor Xa/Va complex, TF/VIIa complex, and IXa/VIIIa complex.

All three must be localized to a phospholipid surface (PL), and so sometimes this designation is added.

Question 12

Alpha-thrombin-thrombomodulin

Answer 12

Anticoagulant complex that activates protein C

Aka Protein C-ase complex
Located in endothelial cell mem

Question 13

Protein C

Answer 13

With cofactor Protein S, Inactivates key cofactors VIIIa and Va, limiting new Xa and IIa

Question 14

Anti thrombin III

Answer 14

Inhibits thrombin activity, and cleaves IXa, Xa, XIa, and XIIa. Accentuated by heparin

Question 15

Basics of Fibrinolysis

Answer 15

Endothelial cells near the thrombus release tissue plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA), which cleave plasminogen to plasmin. Process is regulated by plasminogen activator inhibitor-I (PAI-I) and thrombin-activatable fibrinolysis inhibitor (TAFI).