Hemostasis occurs in 2 stages.  What are they?

1.  Physiologic process by which bleeding is stopped.

1.  Formation of platelet plug.

2.  Followed by coagulation.(production of fibrin)

What is platelet aggregation dependent on?

Activation of platelet gllycoprotein (GP) IIb/IIIa receptors (which binds fibrinogen to form corss links between platelets).

Fibrin is produced in two ways.

What are they?

1.  Contact activation pathway (aka instrinsic pathway)

2.  Tissue Factor pathway (aka extrinsic pathway).

Converge at clotting factor Xa, which catalyzes formation of thrombin, which in turn catalyzes formation of fibrin.

Four factors in the coagulation pathways require an activated form of Vitamin K for their synthesis.

True or False

True

What is a thrombus?

Blood clot formed within a blood vessel or the atria of the heart.

What is the difference between how an arterial thrombi begins and how a venous thrombi begins?

Artterial thrombi begin with platelet plug reinforced with fibrin.

Venous thrombi begin with formation of fibrin, then enmeshes RBC's and platelets

Heparin is a large polymer (molecular wt 3000-30,000) that carries many negative charges.

True or False

True

How does heparin suppress coagulation?

Helping antithrombin inactivate thrombin and factor Xa.

Why is heparain administered IV or Sq?

Because it's so large and negative charges, would never be able to coss membranes, so can't be administered po.

How long does it take for anticoagulant effects to take place with IV heparin?

Within minutes.

What is the major adverse effect of heparin?

Bleeding

How do you treat heparin-induced bleeding?

Protamine Sulfate - binds heparin and stops it from working.

What is heparin induced thrombocytopenia?

Potentially fatal condition caused by development of antibodies against heparin-platelet protein complexes.

When is heparin contraindicated?

Thrombocytopenia

Uncontrollable bleeding

all pt's with high liklihood of bleeding.

How is heparin therapy monitored?

PTT

Partial Thromboplastin Time

INR

What is a target PTT?

60-80 seconds (1.5-2x normal value of 40 seconds)

What is the oldest oral anticoagulant?

Warfarin

How does warfarin work?

By preventing the activation of Vitamin K, thereby blocks biosynthesis of vitamin K dependent clotting factors.

disrupts coagulation cascade and thereby suppresses production of fibrin

 Anticoagulant responses to warfarin develop slowly and persist for several days after being discontinued.

True or False

True

How do you treat pt's with A-Fib?

Warfarin therapy to prevent:

VTE

Stroke

Systemic Embolism

How do you monitor warfarin therapy?

Pt (Prothrombin Time)

Results expressed as INR - International Normalized Ratio

INR of 2-3 is target for most patients.

What is the major complication of warfarin?

Bleeding

What are the 2 genetic codes for variant genes indicating sensitivity to warfarin?

VKORC1 and CYP2C9

Use a reduced dosage.

What is the antidote for warfarin?

Vitamin K

Is warfarin safe during pregnancy?

Absolutely not.

Can cause feltal malformation, CNS defects, and optic atrophy

Warfarin is subject to a large number of clinically significant drug interactions.  Why?

Drugs can increase anticoagulant effects by displacing warfarin from plasma albumin and by inhibiting hepatic enzymes that degrade it.

Drugs can decrease anticoagulant effects by inducing hepatic drug-metabolizing enzymes, increasing synthesis of clotting factors, and inhibiting warfarin absorption.

What is Dabigatrain?

Oral anticoagulant that works by direct inhibition of thrombin and is an alternative to warfarin in A-Fib patients.

What are the 3 drug groups used in coaguation disorders?

1.  anticoags

2.  thrombolytics

3.  antiplatelets

What are the 5 advantages of Dabigastran?

1. Rapid onset

2.  Fixed dosage

3.  no need for labs

4.  few drug/food interactions

5. lower risk of hemorrhagic stroke and other major bleeds.

What are the 3 disadvantages of Dabigatrin?

1.  No antidote

2.  Limited clinical experience

3.  More GI disturbance.

What is Rivaroxaban?

Oral anticoagulant that works by

direct inhibition of factor Xa.

How is Rivaroxaban like dabigatran?

1.  Safer

2.  Easier to use

ASA and other antiplatelet drugs suppress thrombus formation in arteries.

True or False

True

How does ASA work as an anticoagulant?

Inhibits platelet aggregation by causing irreversible inhibition of cyclooxygensase; inhibition persists for the life of the platelet (7-10 days)

ASA is given for multiple purposes as an anticoagulant.  What are they?

Prevent MI

Acute management of MI

Reduction of cardiac events in patients wtih angina, ischemic stroke, or TIA's

When used to suppress platelet aggregation, what dose is ASA given in?

Low doses - 81-325mg

Plavix suppresses platelet aggregation how?

By causing irreversible blockade of P2Y12 ADP receptors on the platelet surface.

Plaxix is a prodrug that requires what enzyme to convert to its active form?

Hepatic CYP2C19 - pt's with this deficiency may have unreliable response to Plavix.

What is the major adverse effect of Plavix?

Bleeding

What is the greatest concern with thrombolytic drugs?

Intracranial Hemorrhage

Thrombolytic Therapy is most effective when started early - how soon for acute MI?

within 4-6 hours of symptom onset and preferably sooner.

Thrombolytics work by converting plasminogen to what?

plasmin, an enzyme that degrades the fibrin matrix of thrombi.

What are the 3 groups of drugs used in coagulation disorders?

Anticoagulants

Thombolytics

Antiplatelets

What 3 groups of drugs facilitate clotting?

Replacement Factors

Vitamin K

Antiplasmin drugs

What is the most common side effect of unfractionated heparin?

Alopecia

Name 3 LMWH's

1.  Lovenox

2.  Fragmin

3.  Innohep

What is the typical fixed dose of LMWH?

30-40mg and can use at home

What are the advantages of LMWH over UFH?

more predictable anticoag response

better bioavailability

dose independent coverage

longer half life - once or twice daily

relatively safe

easier to give - sq vs iv at home

less costly

What is the name of the drug group for warfarin?

Vitamin K Antagonist

What are the uses for warfarin?

1.  Reduce incidence of thromboembolism - prostetic heart valve and a-fib

2.  long-term prophylaxis & treatment - various thromboses or pulmonary emboli

What are the drugs that decrease effects of warfarin?

1.  Phenobarbital

2.  Tegretol

3. Rifampin

4. Vitamin K

What drugs increase effects of warfarin?

amlodarone

ASA/clopidogrel

Tagamet

Clofibrate

Sulfa's

Macrolid antibxs

What herbs effect warfarin and how?

1.  co q10 - decrease

2.  ginkgo, garlic, ginger - increase

What is the protocol for managing high INR?

Stop dose for 1-2 days and resume with a smaller dose.

OR

Vitamin K with caution

How do you dose warfarin?

Loading dose no longer needed

Start with expected maintenance dose of 4-5mg/daily

Use INR guide for changes

What population is at highest risk for hemorrage due to low Vitamin K levels?

Infamts

What is the first new oral anticoag Direct Thrombin Inhibitor?

Dabigatran / Pradaxa

What is a better qualitative marker for pradaxa monitoring?

PTT - Ecarin Clotting Time (ECT)

What are 2 Xa Inhibitors?

1.  Arixtra

2. Xarelto

What is the antidose for Xarelto?

None

What is oneo f the most powerful antiplatelet drugs?

  ASA - very powerful drug!