Lecture 29 - Anticoagulants + Hemostatic Flashcards
What are examples of hypercoaguable states?
Hypertrophic cardiomyopathy IMHA Cushing's disease Acute phase inflammation Protein-losing nephropathy
What are examples of a hypocoaguable state?
post-surgery
Genetic bleeding disorders
Liver failure
What are the three necessary components of a functional clotting system?
Production of clotting factors
Functional platelets
Break down of clots
What is the breaking down of blood clots called
Firbinolysis
What interacts with blotting factors to induce the coagulation cascade?
Platelets
What are the factors within the intrinsic pathway?
12 - 11 - 9 - 8
What are the factors within the extrinsic pathway?
Tissue factor - 7
Where are the extrinsic molecules located?
Wall of the blood vessel
What tests the extrinsic pathway?
PT
What tests the intrinstic pathway?
aPTT
What is part of the common pathway?
Factor 10
2 - 1
What is factor 2 known as?
Thrombin
What is factor I known as?
Fibrinogen
What does fibrinogen do?
Polymerizes into a clot
What are the factors that depend on Vitamin K?
2 - 7 - 9 - 10
How does vitamin K activate certain Factors in the coag pathway?
Reduced –> Oxidized state
with y-glutamyl carboxylase
What recycles y-glutamyl carboxylase back to reduced form?
Vitamin K epoxide reductase
What is warfarin used in, in an extra-label use manner?
Food animals + Horses
how is warfarin distributed throughout the body?
Via plasma protein
What are the differences that you see in 1/2 life of warfarin?
extremely long in cats
How is warfarin metabolized?
Hepatic
How is warfarin excreted?
Urine + Feces
Why is the use of warfarin complicated?
Very small theraputic index
What is seen with warfarin toxicity?
Fatal hemorrhade w/ anemia
Hematomas all over
Congenital malformation in dogs + cats
What are therapeutic complications seen with warfarin use?
Dogs tolerant within a month
Need frequent testing of PT
Drug interactions
When do you see warfarin toxicity?
Antirodenticides
Moldy sweet clover + Sweet vernal hay
What is the biggest problem when it comes to warfarin toxicity in AZ?
Sweet clover
Where does warfarin affect the coag pathway?
Vit. K epoxide reductase
Why does giving Vitamin K in Warfarin toxicity help the animal?
Concentration of Vitamin K now high enough it can bypass the reductase and use DL-diaphorase instead
When, besides warfarin toxicity, is Vitamin K used for treatment?
Chronic sulfonamide treatment of birds for coccidiosis
Congenital, vit. K dependent coagulopathy
Porcine hemorrhagic syndrome
Why wont Vitamin K adminstration help animals in chronic liver failure?
The enzyme used to bypass the system is no longer being made in high enough quantities to help
How should Vitamin K be given?
Dogs - with fatty meal PO
Food animals/Horses - IM/SC
Why is Vd of vitamin K low?
Bind to chylomicrons + concentrating in the liver
How long does it take for a therapeutic effect of Vitamin K to occur?
6 ot 12 hours
What adverse reactions are seen with vitamin K adminstration?
Anaphylaxis
What are the three types of blood products?
Fresh/Fresh frozen plasma
Whole blood
Packed RBC’s
Which of the blood products does not help with hemostasis?
Packed RBC’s
What is contained within whole blood?
Coagulation factors, platelets, + RBC’s
What is contained within FFP?
All Coagulation factors
What is the ranking of shelf life within the blood products?
FFP > WB ~ Fresh plasma
What is the risk, comparatively, of transfusion reactions wtih blood products?
FFP ~ FP
What are the two types of heparin?
Sulfate + LMW heparin
What is the structure of Heparin Sulfate?
Large glycosaminoglycan
What is the route of administration for heparin?
IV
What is the distribution of heparin?
Confined to the ciruclation
What is heparin metabolized by?
Liver + Reticuloendothelial cells
What is the length of therapeutic efficacy after a single dose in a dog?
5 to 6 hours
What happens with IM or deep admin of heparin?
Hematomas
What can cause thrombocytopenia with heparin administration?
Nonspecific binding of heparin to platelets
What happens as an adverse reaction in horses due to heparin admin?
RBC agglutination
What is the reversal agent for heparin?
Prothamine sulfate
What are the adverse effects of prothamine?
Pulmonary hypertension + Hypersensitivity rxn + Vascular hypotension + Bradycardia
What are the four steps to clot activation?
Injury + Initiation + Extension + Stabilization
At what step in clot activation does thrombin come in?
Extension
What is released by endothelial cells when injury occurs?
PGI + NO
CD39 on surface
With aspirin administration what do you have to keep in mind when giving it to a wind range of animals?
Only works in monogastrics
What is the distribution of acetylsalicylic acid within the body?
Plasma protein binding
What is acetylsalicylic acid converted to once in the body?
Salicylate
What time of metabolism does acetylsalicylic acid go through?
Modified by 2nd pass mechanisms
What occurs in cats given acetylsalicylic acid ?
Prolonged half life due them lacking the glucoronylation pathway
How is acetylsalicylic acid eliminated?
Renal
Acetylsalicylic acid 1/2 life: Dogs
8 hours
Acetylsalicylic acid 1/2 life: Cats
38 hours
Acetylsalicylic acid 1/2 life: Horses
30 min
What happens with Acetylsalicylic acid overdose?
Metabolic acidosis
Depression + Vomiting + Hyperventilation + Hyperthermia
What adverse reaction can be seen in horses with colic when given Acetylsalicylic acid ?
Nephrotoxicity
Even more so when horse is on aminoglycoside AB’s
What drugs does Acetylsalicylic acid interaction?
Furosemide + Spironolactone
Increase clearance of corticosteroids
Increase or decrease secretion if urine pH is changed
What is Clopidogrel being found to be great to treat?
Cardiogenic embolism in cats - survival rate DOUBLEd
Where does Clopidogrel work in the pathway?
Blocks receptor for platelet activation = no plug formation NO ADP, can't bind to R on platelet anymore
What does Clopidogrel require to work?
Low pH
What are the characteristics of the metabolism of Clopidogrel?
Inactive until 1st pass metabolism
Clopidogrel 1/2: Cats
3 days
Clopidogrel 1/2 life: dogs
3 hours
Clopidogrel 1/2 life: horses
What drug interactions are seen with Clopidogrel?
Proton pump inhibitors
– and –
Histamine inhibitors
What are the two types of topicals used for the coag pathway?
Type 1: Activate patients platelets
Type 2: Fibrinogen + Activating agent = Quick clot/gel formation
Describe: Collasate
Type I collagen foam
Activates platelets by binding to collagen receptor
What protein is responsible for fibrinolysis?
Plasmin
What activates plasmin?
Tissue plasminogen activators
What are the indications for using TPa?
Pulmonary thormboembolism
– and –
Arterila thromboembolism
What does the drug E-aminocaproic acid affect?
stops tPA from activating plasminogen
How is E-aminocaproic acid used in horses?
Guttural pouch bleeding
How is E-aminocaproic acid used in dogs?
Post-sx bleeding in sighthounds
How is E-aminocaproic acid admin?
IV
What are the hemostatic drug groups?
Topical
Systemic
Anti-fibrinolytic
Drugs within: Topical
Collasate
Drugs within: Hemostatic Systemic
Vitamin K
– and –
Blood + Blood components
Drugs within: Anti-fibrinolytic
E-aminocaproic acid
What are the anticoagulant drug groups?
Fibrinolytics
Antiplatelet drugs
Systemic
Drugs within: Fibrinolytics
tPA
Drugs within: Anti-platelet
Clopidogrel
– and–
Asprin
Drugs within: Anti-coagulant Systemic
Heparin
– and –
Warfarin
