Clotting Flashcards
what happens during primary hemostasis?
activation of platelets
What happens when blood vessels are damaged?
They activate platelets and release
*ADP
*Epinephrine
*Collagen
*Thrombin
*Prostaglandins
*Thromboxane synthase
what is secondary hemostasis?
Formation of the fibrin clot
How is the fibrin clot activated
From the intrinsic or extrinsic pathway
How is the intrinsic pathway activated
activated as a result of blood trauma or vessel damage ( damage happens inside)
How is the extrinsic pathway activated
stimulated by traumatized tissue or vascular wall (damage happens outside)
Both intrinsic and extrinsic pathways result in activated
factor X.
Activated factor X converts inactive prothrombin to
active thrombin
Thrombin cleaves inactive fibrinogen to
fibrin
Fibrin monomers aggregate creating a cross-linked .
clot
what is the factor chain for the intrinsic pathway
12-> 12a-11-> 11a->9,->9a= 8a-> 10->10a
what is the factor chain for the extrinsic pathway
…
Clotting is limited to the injured site by
antithrombin III.
Antithrombin III binds to…
thrombin and inactivates it.
what is mechanism 2 of clot control?
The evolving fibrin clot traps surrounding thrombin in it. This thrombin is inactivated.
what is mechanism3 of clot control?
thrombomodulin/thrombin complex which activate protein c
what happens when protein c is activated?
Activated protein C complexes with protein S
what is plasminogen?
an inactive plasma compound
what happens when tPA is released from healing tissue
- The plasminogen is activated and becomes plasmin.
- The plasmin dissolves the clot and inactivates other factors in the clotting cascade
heparin’s MOA
Potentiates the action of antithrombin III
Increases the affinity of antithrombin III for thrombin by a factor of 1000
- Increased action of antithrombin III results in excess binding of thrombin. - No thrombin available to cleave fibrinogen
No new clots are formed. *Also inhibits some other clotting factors in the cascade
*Half-life 1 to 2 hours
what is heparin used for
DVT, PE prophylaxis.. helps the clot not get bigger
heparin monitoring is done how?
PTT (in patient), outpt ask about bleeding
LMWH
Dalteparin (Fragmin®) *Tinzaparin (Innohep®) *Enoxaparin (Lovenox®) *Fondaparinux (Arixtra®)
Heparin adverse effects
bleeding- (bruising, in urine, gums, vomit, stool)
peripheral neuropathy
priapism- erection sustained > 4 hrs
heparin induced thrombocytopenia
Heparin drug interactions
*Digoxin, tetracycline, antihistamines, IV nitroglycerin decrease effect of heparin *NSAID, ASA, dipyridamole, dextran and hydroxychloroquine will potentiate heparin.
what labs are checked for heparin
PTT
platelet
H/H
Thrombin inhibitors examples and what do they do?
*Argatroban (Novastan®), dabigatran (Pradaxa®)
Inhibits thrombin induced reactions *Fibrin formation, activation of factors V, VIII, XIII, and protein C, and platelet activation
Argatroban Indication and dosing?
Dosing –2 mcg/kg/min–Indication
*Prevention and treatment of thrombosis in heparin induced thrombocytopenia
Dabigatran (Pradaxa®) indicated for, dose?
oral
Indicated for stroke and embolic risk reduction in nonvalvular a-fib
150 mg BID with normal renal function
–75 mg BID Cr Clearance 15–30 mL/min
When converting from warfarin to dapigatran, overlap________ based on renal function
1–3 days
When converting from dabigatran to warfarin, time delay ______ based on renal function
12–24 hours
Bivalirudin (Angiomax®) is what?
A Thrombin inhibitor.
Bivalirudin (Angiomax®) indicated for?
Indicated for PCI or PCTA
Used concomitantly with aspirin
What is the reversal agent for Pradaxa?
Idarucizumab(Praxbind®)
what do factor Xa direct inhibitors do
Act directly upon thrombin without using antithrombin III as a mediator
what do factor Xa indirect inhibitors do
Acts through antithrombin III
Factor Xa Inhibitors are used for
–Prophylaxis of venous thrombosis
–Arterial thrombosis
–Thrombotic CVA
–Cancer-related thromboembolism
*Indirect Xa inhibitors meds
Fondaparinux (Arixtra®), idraparinux–Sulodexide (Vessel Due®), dermatan sulfate
Direct Xa inhibitors
–Apixaban (Eliquis®), otamixaban, rivaroxaban (Xarelto®)
Apixaban
*Indicated for nonvalvular a-fib and stroke risk reduction
*Prophylaxis of DVT/PE following hip or knee surgery
Rivaroxaban
Indicated for–Stroke and systemic embolism reduction in nonvalvular a-fib
–Treatment of DVT, PE, and risk reduction 6 months post dx–DVT prophylaxis for knee and hip surgical patients
Warfarin MOA
Inhibits the conversion of prothrombin to thrombin
Interferes with hepatic synthesis of vitamin k
Half life of 42 hrs
Dosing of warfarin
Begin @ 5-15 mg/day for 2-5 days
Warfarin adverse effects
Bleeding
Anorexia, nausea, vomiting, diarrhea, abd cramps
Adrenal insufficiency
Agranulocytosis
Hepatotoxicity
Warfarin drug interactions
Protein binding effect
Lab eval for Warfarin
PT/INR
H/H
Warfarin contraindications
Sever liver or kidney disease( no erythropoietin)
Uncontrolled bleeding
GI ulcers
Malignant hypertension
Pregnancy
Glycoprotein IIb/IIa inhibition effect what part of clotting
Primary clotting
Glycoprotein IIb/IIa examples
Abciximab, eptifibatide, tirofiban
Used in cath lab, unstable angina
Dipyridamole/ASA (Aggrenox) MOA
Inhibits ADP receptors that activate platelets in the first place
- twice as effective as ASA alone for TIA but higher cost
Clopidogrel (plavix) MOA
Blocks ADP receptor
75 mg once daily
After stents
CVA prophylaxis
Plaviz adverse effects
Chest pain, edema, hypertension
Headache dizziness
Rash pruritus purpura
Arthralgia and back pain
Neutropenia, agranulocytosis in <1% of patients
Plavix interactions
Substrate of cytochrome p450 2c19
Cyp2c19 inhibitors can decrease efficacy
PPI’s are inhibitor (except pantoprazole protonix, fluoxetine(Prozac), ketoconazole(nizoral)
Plavix lab eval
H/H
WBC diff
Platelets
LFT as indicated
Prasurgrel (Effients)
More effective then plavix but more bleeding risk
Less dependent on 2c19 for metabolism
Who should you not give effient to
Prior stroke or TIA
Over the age of 75
ASA MOA
Arachidonic acid is derived from membrane phospholipid
Cyclooxygenase acts on the acid and converts to PGH2
PGH2 acts in 2 ways
Promotes and inhibits clotting
ASA inhibits action of
Cyclooxygenase
