Le Blanc: Pharm Flashcards
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 fibrinolysis
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
- direct acting anticoagulants: calcium chelatlors like EDTA, heparin, factor IIa and 10a inhibitors)
- indirect acting anticoagulants: Warfarin (coumadin)
- 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?
No!
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?
- more predictable outcome, 2x longer half life
- less frequent dosing requirements
- increased bioavailability from the subcutaneous site of injection
- 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
heparin
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
