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Flashcards in Zlotnik 5 Deck (19):
1

What is tertiary hemostasis? Primary? Secondary?

Blood coagulation
-primary: vascular constriction
-secondary: platelet aggregation

2

What are the plasma factors in coagulation? What class?

Protease: II (prothrombin)
Protease cofactor: III (tissue factor), IV (calcium)
Other: I (fibrinogen), XIII (translgutaminase

proteases are zymogen and need activation
cofactors too

MADE IN LIVER mostly

3

Summarize coagulation notes

-coagulation factors are indicated by roman numerals
-generally serine proteases
-3 pathways: factor X, thrombin, and fibrin
-tissue pathway started by tissue injury (release of tissue factor; made of phospholipids and lipoproteins)
-intrinsic pathway starts from blood exposure to collagen of damaged blood vessel (contact activation)
-both act simultaneously, but extrinsic may be more important

4

What starts the contact activation pathway (intrinsic)?

HMWK bound to prekallikrein and facotr XII.
-HMWK attracted to negatively charged surfaces (damaged surface), so brings prekallikrein and factor XI to damaged site

5

What is the last step of the intrinsic and extrinsic pathways?

Factor X, then they go to common pathway (this is mediated by tenase)

6

What is thrombin? When does it become activated?

-thrombin (serine protease) is enzyme that cuts fibrinogen into monomers so that it can be used in the clot

7

More coagulation notes

-thrombin is CRUCIAL
-cleaves fibrinogen into monomers that can then make fibers
-forms the clot

8

What does vitamin K do? what factors use it?

Produces AA present in some of the factors
-co-factor that produces gamma-carboxyglutamate (gla), needed for vit K-dependent proteins (VKDP)

needed by factor IX (intrinsic), VII (extrinsic), prothrombin and factor X (common), protein C + S (anti coagulation factor)
-DEFICIENCY RESULTS IN PROLONGED COAGULATION AND BLEEDING

9

What do warfarin (coumadin) and dicoumarol (coumarin) do?

Inhibit epoxide reductase's activity, which is needed to 'recycle' vitamin K
-inhibits vitamin K production
-vitamin K is 'antidote'

THESE ARE ANTICOAGULANTS (used for chronic problems) effects last long time

10

What causes clot retraction?

-contraction of platelets
-integrins anchor platelets to fibrin threads

11

What can be used as anticoagulants?

-agents that decrease calcium
-coumadins (vitamin K antagonists)
-heparin and derivatives
-antithrombin-like agents (animals like leeches)

12

What is heparin sulfate? Antithrombin III?

-facilitates the interaction of antithrombin with thrombin
-inhibits thrombin action on fibrinogen and conversion of prothrombin to thrombin

antithrombin III is serpin (not commonly used)
-inactivates thrombin
-activated by heparin

13

What are some inherited coagulation disorders? Where are the genes for these located?

Chrismas disease (hemophilia B): deficiency of IX
hemophilia A: deficiency of cofactor VIII

-can administer cofactors made in lab
-both of these genes are in chromosome X (impacts males more severely)

X LINKED but can occur spontaneously

14

How to treat inherited coagulation deficiencies?

blood transfusions or give missing factor
problem: HIV, hep, iron overload
solution: administer recombinant factors (factors made in lab)

15

What is a thrombus? Embolus?

Thrombus: abnormal clot
Embolus: thrombus that is freed by blood flow (can go and plug arteries in brain, kidneys, elsewhere)
-thromboembolic conditions favored by atherosclerosis and slow blood flow

16

what leukocytes in atherosclerosis?

lots of monocytes

17

what is the desired level of cholesterol? drugs for treatment?

desired <200 mg/dL, more than 240 mg/dL is high risk
-treat with statins (lipitor, zocor)
-source is biosynthesis and diet
-zetia inhibits diet cholesterol uptake
-vytorin (zetia + zocor) = best reducer

18

How does fibrinolysis occur? what is tPA?

-Dissolving of clot by plasmin
-plasmin splits fibrin, the product then inhibits further thrombin activity
-plasminogen is activated to plasmin
-plaminogen is activated by tissue plasminogen activator (tPA); this is released by tissue

tPA is serine protease
-useful for pulmonary embolism, MI, stroke
-has risk of hemorrhage
-need to be given within 3hrs for better effect

19

alternatives to tPA?

urokinase and streptokinase