Hemostasis (Hemodynamics 2 ) Pathology

Front 1

What is hemostasis?

Back 1

Hemostasis is the arrest of bleeding, in a healthy vessel anti-clotting factors predominate, in an injured vessel pro-clotting factors predominate.

Front 2

What is the result of uncontrolled bleeding disorders?

Back 2

Hemorrhage, causing hypotension, and shock.

Front 3

What is the result of uncontrolled hypercoagulability disorders?

Back 3

Thrombus formation, which embolizes, and causes an infarct.

Front 4

What are the 3 components of hemostasis?

Back 4

Components of hemostasis: a) Vascular wall (endothelial cells and ECM) b) Platelets c) Coagulation cascade

Front 5

What are the 4 steps in hemostasis, including cause and response?

Back 5

4 steps: 1) Injury causes transient vasoconstriction. 2) Primary response creates the reversible platelet primary hemostatic plug. 3) Secondary response creates the permanent platelet and fibrin secondary hemostatic plug. 4) Counter regulation limits coagulation to the site of injury.

Front 6

Describe the 1st step of hemostasis.

Back 6

Injury leads to transient vasoconstriction mediated by neurogenic factors and endothelin from endothelial cells. ECM (specifically collagen) exposure leads to the rest.

Front 7

Describe the 2nd step of hemostasis

Back 7

Platelets adhere to ECM (collagen) and activate, secrete α and dense core granules, and aggregate in the primary plug.

Front 8

Describe the 3rd step of hemostasis

Back 8

Endothelial cells secreted tissue factor activates the coagulation cascade at the platelet surface. Thrombin cleaves fibrinogen to fibrin, which forms the permanent plug with platelets.

Front 9

Describe the 4th step of hemostasis

Back 9

Endothelial cells secrete tissue plasminogen activator (t-PA) to lyse fibrin, and thrombomodulin to block further coagulation, limiting the hemostatic response.

Front 10

What cells are responsible for hemostasis (in the broader definition)?

Back 10

Endothelial cells

Front 11

What is the anti-thrombotic action of endothelial cells?

Back 11

Antithrombotic: Thrombin binds to cells receptors, or thrombomodulin. The cell produces: ADPase, which degrades ADP (thrombosis mediator), and PGI 2 and NO which prevent thrombosis and cause vasodilation. Thrombomodulin causes Protein C to degrade Factor V and VIII from the cascade. Heparin-like molecules bind antithrombin III, which degrades thrombin, Factor IX-XII. // Summarized: cell: ADPase, PGI, NO. // Thrombomodulin: causes Protein C to degrade factor V and VIII. // Heparin-like molecules: antithrombin III: degrades thrombin, Factor IX and X.

Front 12

What is the Pro-thrombotic action of endothelial cells?

Back 12

Prothrombotic: von Willebrand factor (vWF) is secreted, aiding the binding of platelets to collagen. CK (TNF, IL-1, endotoxins) cause tissue factor (TF) release, which activates factors IX and X. tPA inhibitor (PAI) is released to block fibrinolysis. >> Summary: vWF: platelets bind collagen. /// CK: TF: IX and X /// PAI blocks tPA.

Front 13

What is contained in platelet α and dense core granules?

Back 13

Granules: 1) α granules: fibrinogen, fibronectin, cofactors V and VIII, platelet factor 4, PDGF, TGF α 2) dense core granules: serotonin, epinephrine, histamine, ADP, ATP, Ca2+.

Front 14

What endothelial factor aids platelet adherence? What is secreted?

Back 14

vWF. Receptor agonists, α and dense core granules, Ca2+ , ADP, phospholipids surface.

Front 15

What mediators are active in primary platelet plug formation?

Back 15

vWF, Ca2+ , ADP, thromboxane 2 (TXA2, aspirin inhibited) cause primary plug formation.

Front 16

How is the permanent plug formed? What is the effect of fibrin split products (FSP)

Back 16

Fibrinogen is activated by thrombin to fibrin and FSP. Platelets plus fibrin form the permanent plug. ADP causes the GpIIb-IIIa receptors on platelets to bind fibrinogen and coagulate. FSP and thrombin cause neutrophil and monocyte adhesion.

Front 17

Of the coagulation factors, which is most associated with bleeding disorders (number and name)? Which is the Liden factor, associated with deep vein thrombosis?

Back 17

VIII, Antihemophilic factor. V, proaccerin.

Front 18

What are the general players in the coagulation cascade?

Back 18

zymogens, proteases, cofactors, Ca2+ , phospholipid surface.

Front 19

Describe the Intrinsic pathway in the coagulation cascade.

Back 19

Intrinsic: XII (Hageman factor) is activated by kallikrein, XII activates XI, which (plus VIII cofactors and Ca2+) activates X. 2)

Front 20

Describe the Extrinsic pathway in the coagulation cascage.

Back 20

Extrinsic: VIII (plus TF and Ca2+) activates X.

Front 21

Describe the Common pathway in the coagulation cascade.

Back 21

Common: X (plus phospholipid, Ca2+, and cofactor V) activates II (prothrombin) to thrombin (IIa), which activates fibrinogen (I) to fibrin (Ia), and XIII aids cross linking.

Front 22

What is the inhibitory activity of antithrombin III?

Back 22

Antithrombin III : binds heparin like molecules on endothelial cells: blocks Thrombin, IX, X, XI, and XII (IX-XII).

Front 23

What is the inhibitory activity of Thrombomodulin?

Back 23

Thrombomodulin on endothelial cell surface: binds thrombin: activates protein C, inactivates V and VIII.

Front 24

What is the inhibitory activity of tPA? What blocks tPA?

Back 24

tPA: activates plasminogen to plasmin, which lyses fibrin clots to FSP. Plasminogen activator inhibitor (PAI) blocks tPA.

Front 25

What is the effect of FSP?

Back 25

FSP are chemotactic for inflammatory cells, such as neutrophils and monocytes.

Front 26

What is the Virchow triad, for thrombus in a vessel without gross injury?

Back 26

Virchow triad: 1) Endothelial injury 2) Blood flow disturbance (stasis or turbulence). Clotting factors concentrate, platelets reach the endothelial wall because laminar flow is disturbed. 3) Hypercoagulability

Front 27

What are some causes of abnormal blood flow?

Back 27

Arterial bifurcations, aneurysms, occlusions (atherosclerotic plaque/stenosis), MI, hyperviscosity (sickle cell, etc.).

Front 28

What are 4 primary (genetic) causes of hypercoagulatibility?

Back 28

Primary hypercoagulatibility: a) Factor V (Liden) mutation, causing Protein C resistance. B) Prothrombin mutation c) Antithrombin III deficiency d) Protein C or S deficiency

Front 29

5 secondary (acquired) causes?

Back 29

Secondary hypercoagulatibility: a)Bed rest/immobilization. B) Oral contraceptives c) Tumor products d) Age: causes decreasd PGI2. e) High molecular weight heparin: causes HIT: heparin antibodies form, bind heparin-like proteins on platelets, which are activated, clotting ensues.

Front 30

What is a characteristic shared by all thrombi in high flow areas?

Back 30

Zahn lines, of alternating fibrin and platelets/RBCs.

Front 31

Describe a cardiac thrombus?

Back 31

Intracardiac thrombus, often is mural.

Front 32

Describe an arterial thrombus? How does it propagate?

Back 32

Arterial thrombus elongates retrograde. Causes occlusion and infarct.

Front 33

Describe a venous thrombus?

Back 33

Venous thrombi frequently appear in lower extremities (DVT), can embolize, elongate in direction of flow, towards the heart. Less fibrin strands, more RBCs, causing a gel like thrombus.

Front 34

When a venous thrombus embolizes to the pulmonary trunk branches and lodges on a bifurcation, what is the resulting often fatal condition?

Back 34

Saddle Thrombus.

Front 35

What are the 4 fates of thrombi?

Back 35

Thrombus fates: a) Propagation b) Resolution: fibrinolysis c) Embolization: boom! d) Organization: become connective tissue

Front 36

What is the presentation and end result of disseminated intravascular coagulation (DIC)?

Back 36

Secondary to a diseases state, systemic microscopic thrombi exhaust coagulation products, and activate fibrinolysis, leading to a bleeding disorder state. Diffuse petechiae throughout the body.