Ch 20: Normal Hemostasis Flashcards Preview

Pathology Unit 2 > Ch 20: Normal Hemostasis > Flashcards

Flashcards in Ch 20: Normal Hemostasis Deck (15):
1

3 general things needed for normal hemostatic balance

Platelets, endothelial cells, coag factors

2

Normal platelet level

150 to 350 x 10^9/uL

3

Steps in platelet formation

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

4

Platelet morphology and function

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

5

Stimulus for platelet activation

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

6

Steps in Platelet activation (plug formation)

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

7

Role of P-selectin and PDGF

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

8

Factor Xa/Va complex

Cleaves factor II (prothrombin) to IIa (thrombin)

9

TF/VIIa complex

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

10

IXa/VIIIa complex

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

11

What are the three procoagulant complexes?

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.

12

Alpha-thrombin-thrombomodulin

Anticoagulant complex that activates protein C

Aka Protein C-ase complex
Located in endothelial cell mem

13

Protein C

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

14

Anti thrombin III

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

15

Basics of Fibrinolysis

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).