Heme - Coagulation Pathways

Front 1

What is primary hemostasis?

Back 1

Platelet plug formation at the site of vascular injury.

Front 2

What are the three components of primary hemostasis?

Back 2

1) Coag system activation (secondary hemostasis)
2) Platelet activation
3) Fibrinolytic system activation

Front 3

What's the difference between hemostasis and thrombosis?

Back 3

Hemostasis is considered an adaptive response.

Thrombosis is mal-adaptive.

Front 4

What is the basic function of the fibrinolytic system?

Back 4

To keep thrombus formation in check.

Front 5

What are the three elements of Virchow's Triad?

Back 5

1) Alterations in normal blood flow (stasis)
2) Damage to the vascular endothelium (injury)
3) Alterations to the constitution of blood (hypercoagulability)

Front 6

What initiates extrinsic pathway activation?

Back 6

The exposure of plasma factors to Tissue Factor from blood vessel adventitia.

Front 7

What is the central product of coagulation system activation?

Back 7

Thrombin

Front 8

What is the major action of Thrombin?

Back 8

To cleave Fibrinogen into Fibrin, which then polymerizes into a fibrin network, the scaffold of a clot. (Thrombin has other functions too, such as platelet activation.)

Front 9

What are the Vitamin K dependent factors?

Back 9

Factors II, VII, IX and X

Front 10

What are the two "tenase complexes"?

Back 10

Intrinsic: VIIIa + IXa

Extrinsic: Tissue Factor + VIIa

Front 11

What makes up the "prothrombinase complex"?

Back 11

Factors Xa + Va. This complex cleaves Factor II -> IIa

Front 12

What subset of coag factors are liver patients most likely to lack?

Back 12

Vitamin K-dependent factors:
II, VII, IX, X

Front 13

Where do the extrinsic and intrinsic pathways merge?

Back 13

With Factor X

Front 14

What class of enzymes are most coagulation cofactors?

Back 14

Serine proteases.

Front 15

What factors are activated by thrombin in a feedback amplification?

Back 15

Activated Thrombin (Factor IIa) will activate Factors V, VIII and XI

Front 16

What are three coagulation inhibitors which keep thrombus formation in check?

Back 16

1) Tissue Factor Pathway Inhibitor
2) Antithrombin III
3) Protein C

Front 17

What coagulation regulator is specific to the extrinsic pathway?

Back 17

Tissue Factor Pathway Inhibitor (TFPI)

Front 18

How does Anti-Thrombin work?

Back 18

Antithrombin (AT) irreversibly binds to the serine protease active site of coag factors (Factors IIa/Thrombin, IXa, Xa, XIa, XIIa)

Front 19

How does Heparin work?

Back 19

By activating Antithrombin (AT)

Front 20

What are the two major activators of the fibrinolytic cascade?

Back 20

1) Tissue Plasminogen Activator
2) Urokinase or uPA

Front 21

How is TPA inactivated?

Back 21

1) Inhibition by circulating Plasminogen Activator Inhibitor 1
2) Clearance of the enzyme by the liver

Front 22

What is the role of plasmin in coagulation?

Back 22

Plasmin degrades clots. Plasmin breaks down fibrin and fibrinogen.

Front 23

What is the major, absolute contraindication of Plasmin inhibitors?

Back 23

DIC

Front 24

What does the D-Dimer test measure?

Back 24

Specifically it measures a Plasmin-cleaved fragments of fibrin. The absence of D-Dimer fragments indicates an absence of active thrombosis.

Front 25

Which blood test measures the factors within the INTRINSIC and COMMON coagulation pathways?

Back 25

Activated Partial Thromboplastin Time

Front 26

Which blood test measures the factors within the EXTRINSIC and COMMON coagulation pathways?

Back 26

The Prothrombin Time

Front 27

What does the Thrombin Time (TT) blood test measure?

Back 27

The Thrombin Time assays only the final step in coagulation, the conversion of fibrinogen to fibrin.

Front 28

What cells produce platelets?

Back 28

Megakaryocytes, in the bone marrow.

Front 29

What bone marrow growth factor supports megakaryocytes?

Back 29

Thrombopoetin

Front 30

Organomegaly of what organ my cause thrombocytopenia?

Back 30

An enlarged spleen is likely to sequester high numbers of platelets.

Front 31

Asplenic patients are at risk for what coagulopathy?

Back 31

Hypercoagulopathy due to thrombocytosis.

Front 32

What is the circulating lifespan of a platelet?

Back 32

Platelets survive 9-10 days in the blood, although this may drop to minutes in certain pathologic conditions.

Front 33

What two major organelle systems make up platelet cell biology?

Back 33

1) Cannalicular system - for release of granules

2) Dense Tubular System - for Calcium release

Front 34

Give four examples of platelet adhesion factors produced by vascular endothelium

Back 34

1) vWF
2) laminin
3) fibronectin
4) thrombospondin

Front 35

What is one adhesion protein produced by platelets?

Back 35

Glycoprotein Ib is the main vWF adhesin.

Front 36

Name three platelet agonists:

Back 36

1) Collagen
2) ADP
3) thrombin
4) epinepherine
5) thromboxane A2
6) calcium

Front 37

What disorder is defined by the "pentad"?

Back 37

Thrombotic Thrombocytopenic Purpura
1) microangiopathic hemolytic anemia
2) thrombocytopenia
3) neurologic abnormalities
4) fever
5) renal dysfunction

Front 38

What are possible causes of Reactive Thrombocytosis?

Back 38

1) Iron deficiency
2) Inflammatory diseases

Front 39

What bone marrow signs correlate with Essential Thrombocytosis?

Back 39

ET is myoproliferative with many, possibly bizarre, megakaryocytes.

Front 40

How do platelets behave in Essential Thrombocytosis?

Back 40

ET platelets are large and possibly hyperreactive. Thrombosis may be an issue.

Front 41

1972 WEPT

Back 41

Factors 10, 9 & 2 - Vit. K dependent
Warfarin acts on the Extrinsic Pathway
PT (Prothrombin) time used to check it

Front 42

On which pathway does heparin act? Which test is used to check it?

Back 42

The Intrinsic Pathway.
PTT (Partial Thromboplastin Time) is used to check it.