liveonearth (liveonearth) wrote,

Coagulation, Vitamin K and Clotting Factors

What is the most common hereditary clotting problem?
--Von Willebrand's Dz (factor is absent or abnormal, many varieties)

What do you call an inactive enzyme precursor in the clotting cascade?
--a zymogen

What do you call a coagulation deficiency from to a deficiency of Factor VIII due to an X-linked recessive gene?

--hemophilia A

Which pathway is Factor VIII a part of?
--the INTRINSIC pathway

How long does the intrinsic pathway normally take to form a clot?
--1-6 seconds

Who gets this kind of hemophilia?
--1/2 of the sons of mothers who carry the recessive gene

Which factor is deficient in hemophilia B?
--factor IX

What is the factor that allows platelets to adhere to endothelial basement membranes to begin a clot?
--Von Willebrand's factor (VWF) = large, multimeric circulating proteins which link platelet glycoproteins (Ib/IX/V) to collagen fibrils-->activating the platelets

Where does von Willebrand's factor come from?
--endothelial cells (also make plasminogen activator and possibly factor V)

What syndrome is a lack of platelet glycoproteins receptors for VWF? (also decreases clotting)
--Bernard-Soulier syndrome

Where do platelets come from?
--megakaryocytes in the bone marrow

What do platelets release from their granules once they are activated?
--ADP, serotonin, platelet-activating factor (PAF), vWF, platelet factor 4, and thromboxane A2 (TXA2)

How do those chemicals cause increased clotting?
-->activate a Gq-linked protein receptor cascade-->increased calcium concentration in PLT cytosol-->activates protein kinase C-->activates phospholipase A2 (PLA2)-->modifies integrin membrane glycoprotein IIb/IIIa increasing its affinity for fibrinogen-->activated platelets change shape from spherical to stellate-->fibrinogen cross-links with glycoprotein IIb/IIIa aggregates more platelets

Why does clotting speed increase exponentially once started?
--autoactivation: many of the factors increase activation of themselves or other supporting factors in the cascade

What common drug irreversibly inhibits thromboxane A2 (vasoconstrictor) via the COX pathway?

What did Wiggins teach us activates protein C?
--excess thrombin

And what activates prothrombin-->thrombin?

Calcium ions are required for promotion/acceleration of all clotting reactions EXCEPT?
--the first two steps of the intrinsic pathway

Which clotting factors are dependent on Vitamin K?
--synthesis of factors II (prothrombin), VII, IX, X
--also protein C and protein S which form the PCa/PS complex which inhibits factors V and VIII
--factor VII and protein C are MOST SENSITIVE to vit K levels
--if K deficient PT is always prolonged, PTT mb prolonged
--if factors II, VII, IX, X, PC and PS are all deficient-->diagnostic for low K

Where are clotting factors II, VII, IX, X, XI, XII, plasminogen and prothrombin made?
--in the liver
--note: plasminogen also made in kidney
--factor V may be made in liver or by endothelial cells, not sure
What causes vitamin K deficiency?
--malabsorption dt biliary tract dz

Why do you need bile to absorb vitamin K?
--it's fat soluble and won't be digested or absorbed w/o bile salts

What cofactor besides calcium and vitamin K is needed for many clotting reactions?
--platelet phospholipid

What is the most common cause of abnormal bleeding?
--thrombocytopenia, usu PLT below 70,000

What are some of the causes of thrombocytopenia?
--decreased PLT production dt BM damage
--congenital abn ie: Fanconi's aplastic anemia
--nutritional deficiency esp: B12 and folate
--DIC or purpura-->increased destruction of PLTs

What common hemorrhagic syndrome occurs following the uncontrolled activation of clotting factors and fibrinolytic enzymes throughout small blood vessels?
--disseminated intravascular coagulation (DIC)
--involves clotting throughout CV system
--fibrin deposited everywhere
--PLT's and clotting factors consumed
--anticoagulation systems are overwhelmed and worsen process as fibrin degradation products (incl D-dimers) inhibit fibrin polymerization and block PLT fx-->lethal tissue necrosis and bleeding

What triggers DIC?
--acute usudt massive tissue damage such as large severe burns, sepsis, or complication of pregnancy
--chronic dt certain cancers, retained dead fetuses, aneurysms or hemangiomas, insidious onset

What are the new names for the intrinsic and extrinsic coagulation pathways?
--contact activation pathway and tissue factor pathway respectively

What drug acts very quickly to antagonize thrombin in the intrinsic/&common pathway?

What drug slows the extrinsic pathway?
--warfarin/coumarin, use PT lab to monitor

How does coumadin work?
--inhibits vit K utilization by competing with it as a cofactor
--slow acting, onset of action is 2-7 days, the half life of the factors
--usu pts use heparin therapy until coumadin takes effect

Which lab do you use to monitor conversion of X to Xa?
--PT, still

Which pathway is faster?
--the extrinsic one

Which pathway are you testing with the PT lab?

At what factor do the intrinsic and extrinsic pathways merge to form the common one?
--factor Xa (activated)

How long does the intrinsic pathway take to form a clot after trauma to a vessel or blood?
--15 seconds to a minute

What lab test do you use to measure intrinsic pathway function?
--the PTT
--measure heparin therapy

What does plasmin do?
--attacks fibrin at 50 sites to break down tight clots

Where does antithrombin III come from?
--basophils and platelets

How do basophils know to release it?
--I have no idea

What does antithrombin III do?
--inhibits factors IIa, IX, Xa, XI, XII (three in the intrinsic pathway, two in the common)

What drug increases the action of antithrombin III by 1000 times?

Note to self:
--intrinsic, heparin, PTT, slow
--extrinsic, tissue factor, warfarin, PT, fast

What's another name for tissue factor?
--factor III

What may trigger idiopathic thrombocytopenic purpura?
--a viral URI in a child

What is the most common hereditary hypercoagulability disorder amongst Eurasians?
--Factor V Leiden
--present in 3-8% of caucasians
--risk of venous thrombosis, OB complications
--increased risk for women on birth control pills (35X)!!!

What is the principle clot eliminator of the body?

What causes the hypercoagulability in Factor V Leiden?
--the Leiden variant of factor V cannot be inactivated by activated protein C

What is a FDP?
--fibrin degradation product (after plasmin breaks fibrin clot to fragments)

Diagnostic testing for venous thromboembolisms & pulmonary embolisms relies on finding what?

What two actions does thrombin take to activate clotting?
--activates factor XIII and converts fibrinogen to fibrin monomers

What two actions does plasmin take to break down clots?
--breaks fibrinogen to FDPs and fibrin clots to D-dimers

What affects PT, prothrombin time?
--extrinsic and common coag pathways
--first effect: vactor VII, later II, IX, and X
--time INCREASED by hepatocellular liver disease, obstructive biliary disease (low vit K), and coumadin

How does coumadin increase PT?
--inhibition of vit K dependent factor depletion

What's INR?
--international normalized ratio = patient protime / normal protime
--a calculation to eliminate variation in PT measurements between labs
--used for monitoring effect of coumadin therapy

What factors can interfere with PT?
--alcohol increases time dt liver damage
--diarrhea prolongs dt vit K malabsorption
--high fat/leafy veg diet may shorten due to high vit K intake

Which factor is activated by the PTT test (partial thromboplastin time)?
--factor XII
--monitor heparin therapy

What can cause increased PTT times?
--congenital (hemophilia, A/classical is factor VIII, B and VWDz act on factor IX)
--liver cirrhosis
--vit K deficiency
--heparin or coumadin therapy

What can decrease PTT times?
--early DIC
--extensive cancer

What screening test for platelet function abnormalities is likely to be on ND boards but barely used anymore?
--bleeding time
--PLT count under 50,000 prolongs BT

What other outdated test was mentioned in lecture and will likely be on boards?
--venous clotting time, 4-10 minutes, heparin monitoring
Tags: birth control, blood, clotting, genetics, vit b, vit k, vitamins

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