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Block 7 Week 4 > Le Blanc: Pharm > Flashcards

Flashcards in Le Blanc: Pharm Deck (53):

Under normal physiological conditions, little or no intravascular coagulation occurs. This is primarily due to three effects - what are they?

dilution (of factors)
presence of plasma inhibitors
activated clotting factors are rapidly removed by the liver


When vascular damage occurs, several physiologic reactions participate to control blood loss. What are they?

platelet adhesion reaction
platelet activation
platelet aggregation
formation of a clot


Briefly describe platelet aggregation and formation of the platelet plug

damage to vessel endothelium exposes collagen - vWF comes in and binds - platelets bind to GPIb (platelet adhesion)- when platelets bind they undergo shape change and degranulate - degranulation releases enzymes like ADP and thromboxane A2 which draw in more platelets (aggregation) to create the platelet plug

**no activation of coag cascade yet, just formation of weak platelet plug


2 contents released by platelets that trigger powerful constrictions of blood vessels (transient reaction)

thromboxane A2
serotonin (5HT)


Coagulation occurs due to trauma originating from the extra-vascular space (formation of a macromolecular complex involving Thromboplastin or Tissue Factor, and Factor VII); the most important in vivo

Extrinsic pathway


Coagulation is triggered by trauma to the blood itself (from large glycoprotein complexes released by platelets)

Intrinsic pathway


What does plasmin do?

degrades a fibrin clot

**this produces D-dimer


What are the three categories of drugs used to treat coagulation disorders? Give an example of each

1. direct acting anticoagulants: calcium chelatlors like EDTA, heparin, factor IIa and 10a inhibitors)
2. indirect acting anticoagulants: Warfarin (coumadin)
3. antiplatelet agents: aspirin


What is a normal platelet count?

150,000 - 400,000


What does prothrombin time reflect?

reflects alterations in the EXTRINSIC pathway (~12 sec)


What is the INR measuring?

PT of the patient/PT reference

**normal is 1.0
2-3 is therapeutic INR


What does the activated PTT reflect?

reflects alterations in the INTRINSIC pathway (normal 24-34 secs)


Where is heparin derived from? Why is this important to consider?

from bovine lung and porcine intestinal mucosa; important to consider bc some people develop allergy


What does heparin bind to and form a complex with to inhibit blood coagulation? What does this essentially do?

alpha2-globulin (antithrombin III); antithrombin III is a natural anti-coagulant, and when bound by heparin it just accelerates the anti-coag effects by like 100x


At low doses, Heparin primarily neutralize Factor (blank). At high doses, it prevents the thrombin-induced activation of (blank), and activation Factors V and VIII

Xa; platelets


What is one concern with heparin use?

may cause moderate to severe thrombocytopenia **heparin-induced thrombocytopenia


How is heparin administered?

IV infusion

**not effective orally


Does heparin cross the placenta and pass into the maternal milk?



Contraindications with heparin use?

active bleeding
patients with low platelets or history of heparin-induced thrombocytopenia
patients with severe allergy
severe HTN
older patients, esp women


What to do if there is a heparin overdose?

simple withdrawal;
use Protamine Sulfate to bind heparin and neutralize its effects


What are 4 advantages of using low molecular weight heparin?

1. more predictable outcome, 2x longer half life
2. less frequent dosing requirements
3. increased bioavailability from the subcutaneous site of injection
4. less frequent bleeding


What would you use for any of these?

Blood transfusions
Atrial fibrillation
Disseminated intravascular coagulation (DIC)
Open heart surgery
Pulmonary embolism
Venous thromboembolism
Venous catheter occlusion



How do thrombin inhibitors work as anticoagulants? How are they administered?

they block the enzyme by binding to the catalytic site; given IV


When would you want to use thrombin inhibitors instead of heparin?

in patients that are susceptible to developing heparin induced thrombocytopenia and in coronary angioplasty or coronary bypass surgery


Another type of anticoagulatant is a factor 10a inhibitor. Name two.



This is the most common oral anticoagulant, only active in vivo after 12-24 hours

Warfarin (coumadin)


How does coumadin work?

it is a structural analog of Vitamin K, so it causes the same effects as Vitamin K depletion

**need Vitamin K for formation of clotting factors


What is Vit K used for in the synthesis of clotting factors?

it causes post-ribosomal carboxylation of specific glutamic acid residues; when carboxylated, these amino acid residues bind Ca++ making it less available for the Coag pathway


Warfarin inhibits blood clotting mechanisms by interfering with the hepatic synthesis of (blank)

vitamin K-dependent clotting factors

**VII, IX, X, prothrombin


Warfarin also down-regulates protein C. What effect does this have? What does protein C normally do?

Protein C promotes the degradation of factors 5a and 8a, rendering them inactive. If this is downregulated, you will have increased 5a and 8a and this explains the pro-coagulant activity of warfarin seen in early stages of therapy


So early on in warfarin treatment, what will you observe in regards to coagulation?

first, increased coagulant activity due to increased levels of factor 5a and 8a


What are two measures used to monitor the anticoagulant effects of warfarin?

prothrombin time


What are 3 things you could do if you overdose a patient on warfarin?

1. withdraw the drug
2. give vit K supplements
3. tranfuse with whole blood or plasma if major bleeding noted


When should warfarin NOT be used?

when you need to avoid active bleeding
Vit K deficiency
pregnant women!!!
severe hepatic/renal disease


Does warfarin pass the placental barrier?

YES; don't use in pregnant women!

**may lead to abortion and birth defects


Why are newborns more sensitive to oral anticoagulants than adults?

they have lower vitamin K levels (things like warfarin will decrease vit K) and also they have lower rates of metabolism


What is one drug that is known to increase the response to warfarin?

aspirin **any drug that decreases platelet aggregation


What is desmopressin? What is it used for?

synthetic analogue of ADH; stimulates factor 8; used for hemophilia A or in pts with factor 8 antibodies

**think of this: hemophilia a-ate (8 - factor 8)


How does aspirin inhibit platelet aggregation?

aspirin inhibits platelet release of ADP which prevents aggregation; it also acetylates COX, which prevents the formation of thromboxane A2; thromboxane A2 causes platelet aggregation and is a potent vasoconstrictor


Aspirin inhibits the release of (blank) by platelets and their aggregation by acetylating the enzymes (cyclo-oxygenases or COX) of the platelet that synthesize the precursors of (blank), a labile inducer of platelet aggregation and a potent vasoconstrictor

ADP; thromboxane A2


Is the effect of aspirin reversible?

no; it causes a covalent modification due to acetylation of the enzymes (COX)


How do the antiplatelet drugs Ticlopidine and Clopidogrel bisulfate work? When are they used?

they inhibit ADP-mediated platelet aggregation; prevent aggregation by impairing the GPIIb/IIIa receptor; they are used as an alternative to aspirin for recurrent stroke patients


How does abciximab work? When is it used?

it is a chimeric monoclonal antibody that blocks the glycoprotein IIb/IIIa receptor - prevents platelet aggregation;
used in acute coronary syndromes and percutaneous coronary intervention


The Fibrinolytic System dissolves intravascular clots as a result of the action of (blank), an enzyme that digests Fibrin

Plasminogen, an inactive precursor, is converted to (blank) by cleavage of a single peptide bond. (blank) is a relatively non-specific protease, which digests fibrin clots and other plasma proteins, including several coagulation factors

plasmin; plasmin


Therapy with thrombolytic drugs tends to dissolve both pathological thrombi and also fibrin deposits at sites of vascular injury. What can these drugs cause as a result?



What should patients with the following conditions receive?

extensive pulmonary emboli
severe iliofemoral thrombophlebitis
acute coronary occlusion

thrombolytic therapy to break up clots


This is released from endothelial cells in response to various signals, including stasis produced by vascular occlusion

tissue plasminogen activator (t-PA)


What does t-PA bind to? Its binding causing the conversion of what to what?

t-PA binds to FIBRIN and converts plasminogen (also binds to fibrin) to plasmin


What does fibrin bind to in the plasma to inhibit its action?

an alpha2-antiplasmin


t-PA is a serine protease. It is a poor Plasminogen activator in the absence of (blank). t-PA binds to (blank) and activates bound Plasminogen several hundred-fold more rapidly than it activates Plasminogen in the circulation.

fibrin; fibrin


a protein produced by β-hemolytic streptococci. It has no intrinsic enzymatic activity, but forms a stable non-covalent 1:1 complex with Plasminogen. This produces a conformational change that exposes the active site on Plasminogen that cleaves a peptide bond on free Plasminogen molecules to form free Plasmin



When should you NOT use thrombolytic therapy?

surgery w/i 10 days
serious GI bleeding w/i 3 months
history of HTN
active bleeding or hemorrhagic disorder


prevents the binding of Plasminogen and Plasmin to Fibrin. It is a potent inhibitor for Fibrinolysis and can reverse states that are associated with excessive Fibrinolysis

aminocaproic acid