Flashcards in Zlotnik 5 Deck (19):
What is tertiary hemostasis? Primary? Secondary?
-primary: vascular constriction
-secondary: platelet aggregation
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
MADE IN LIVER mostly
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
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
What is the last step of the intrinsic and extrinsic pathways?
Factor X, then they go to common pathway (this is mediated by tenase)
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
More coagulation notes
-thrombin is CRUCIAL
-cleaves fibrinogen into monomers that can then make fibers
-forms the clot
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
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
What causes clot retraction?
-contraction of platelets
-integrins anchor platelets to fibrin threads
What can be used as anticoagulants?
-agents that decrease calcium
-coumadins (vitamin K antagonists)
-heparin and derivatives
-antithrombin-like agents (animals like leeches)
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)
-activated by heparin
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
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)
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
what leukocytes in atherosclerosis?
lots of monocytes
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
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