Plasma Proteins, Coagulation, and Fibrinolysis

Question 1

What are the contents of blood plasma?

Answer 1

water, nutrients, metabolites, hormones, electrolytes, and proteins

Question 2

What is osmotic pressure?

Answer 2

Plasma proteins provide osmotic pressure to maintain fluid balance between the tissues and the blood. It helps to draw the fluid back out of the tissues.

Question 3

Function of plasma proteins?

Answer 3

Provide transport for many molecules,
aid in immune defense,
and in association with the platelets they maintain the integrity of circulatory system.

Question 4

Basics of blood coagulation cascade:

Answer 4

Extrinsic Pathway (VII, tissue factor) and Intrinsic Pathway (XI, IX, VIII) converge on factor X which converts prothrombin to thrombin.
Thrombin activates platelets and converts fibrinogen to fibin to form a soft clot.
Factor XIII cross-links the fibrin to form a hard clot.

Question 5

Initiation phase of blood coagulation cascade:

Answer 5

TF is exposed and binds to VII.
Small amounts of IX and X activated.
X (and cofactor V) convert prothrombin to thrombin. (This only occurs at the TF-bearing cell)

Question 6

Amplification phase of blood coagulation cascade:

Answer 6

Thrombin feeds-back on the intrinsic and extrinsic pathways, up regulating everything.
Thrombin activates platelets, which change shape and secrete 3 types of granules.
Platelets are further activated (ADP), vasoconstriction (serotonin), more clotting factor V, heparin antagonist, vWF, fibrinogen, AND modulators.

Question 7

Propagation phase of blood coagulation cascade:

Answer 7

Occurs on the surface of large numbers of platelets at the site of injury.
Factor X is activated at many sites on platelets, generates a burst of thrombin large enough to clot fibrin and form a hemostatic plug.
Factor XIII cross-links the fibrin monomers allowing hard clots to form.

Question 8

How does the fibrinogen - fibrin deal work?

Answer 8

Fibrinogen can’t polymerize unless thrombin cleaves the terminal portions.
Once free, fibrin monomers can aggregate and form a soft clot.
XIII cross-links the fibrin monomers allowing hard clots to form.

Question 9

Where is gamma-carboxyglutamate found and what does it do?

Answer 9

This is found on factors II, VII, IX, and X.
It binds factors to calcium ion/phospholipid head groups on the plasma membrane.
This anchors the complexes to the cell surface.

Question 10

What is needed to form gamma-carboxyglutamate?

Answer 10

Vitamin K is needed to form it.

Question 11

Warfarin (Coumadin)

Answer 11

It is a slow and long-acting anticoagulant.

Analog of Vitamin K that blocks gamma-carboxylation reaction

Question 12

Regulation of clotting

Answer 12

Proteins S and C regulate clotting and are activated by thrombin.
Serpins are serine protease inhibitors, serpins antithrombin III (ATIII) modulates thrombin activity.
Plasmin can dissolve fibrin clots.

Question 13

Factor V Leiden

Answer 13

(Genetic) Factor V cannot be inactivated by protein C, leading to hypercoagulation and DVT.

Question 14

Hemophilia B

Answer 14

(Genetic) Lack of factor IX

Question 15

Hemophilia A

Answer 15

(Genetic) Lack of factor VIII

Question 16

alpha1-antiproteinase deficiency

Answer 16

(Genetic) leads to elastase destruction of lung tissue, progressing to emphysema and COPD

Question 17

Kwashiorkor

Answer 17

(Environmental) protein deficiency due to diet leads to reduction in circulating blood proteins = edema, swollen belly.

Question 18

Thrombocytopenic Purpura (TTP)

Answer 18

(Environment and Genetics) Formation of microscopic thrombi, leads to hemolysis and organ failure.
May be caused by autoimmune destruction of platelets.

Question 19

vWF deficiency

Answer 19

(Environment and Genetics) Without this factor clotting will not occur. Common presentation in mucous membranes,

Question 20

Bernard-Soulier Syndrome

Answer 20

(Genetic) Lack of Gplb, the receptor for vWF. Leads to lack of function of vWF and bleeding disorder.