Hemostasis and Thrombosis Flashcards
define hemostasis
the arrest of blood loss from damaged blood vessles
hemostasis is caused by
- platelet adhesion and activation
- fibrin formation
define thrombosis
- pathological formation of a hemostatis plug within the vasculature in the absence of bleeding
- hemostasis in the wrong place
what makes up Virchow’s triad in thrombosis
- stasis
- vessel wall injury
- hypercoagulability
describe white thrombus
- arterial clot
- primarily platelets and some fibrin mesh
- associated with atherosclerosis
describe red thrombus
- venous clot
- mostly fibrin and small amount of platelets
- higher risk of embolus
what does antithrombin III do
prevents coagulation by lying factor Xa and thrombin
what does thrombin (factor IIa) do
causes platelet activation
describe the intrinsic pathway
- all components present in the blood
- starts when blood comes in contact with foreign object or damaged endothelium
- monitored by activated partial thromboplastin time (aPTT)
describe the extrinsic pathway
- some components come from outside blood: tissue factor
- starts when tissue damage releases tissue factor
- monitored by prothrombin time and INR
describe vitamin K and how it is obtained
- fat soluble vitamin with little stored in the body
- most vitamin K obtained from diet or produced by bacteria in the gut
vitamin K is a cofactor in the formation of which clotting factors:
- factor I
- factor 7
- factor 9
- factor 10
- protein C
- protein S
warfarin works by inhibiting the action of:
vitamin K
what is the platelet role in thrombus formation
- platelet adhesion: following vascular damage, VWF
- platelet activation: mediators are ADP, TXA2, collagen, thrombin -> shape change
- platelet aggregation: final common pathway, GP IIb/IIIa receptor
what is the key mediator in fibrinolysis
plasmin
what makes plasmin
tissue plasminogen activator and plasminogen
what does plasmin do
fibrin -> clot fragmentation
what are the types of anticoagulant medications
- vitamin K antagonist
- unfractionated heparin
- low molecular weight heparins
- direct thrombin inhibitors
- factor Xa inhibitors
what is an example of a vitamin K antagonist and its MOA
- warfarin
- acts only in vivo
- inhibits vitamin K epoxide reductase component 1
- this gene is polymorphic resulting in different affinities for warfarin
what are the pharmacokinetics of wafarin
- rapidly absorbed after oral administration
- highly bound to plasma proteins
- hepatically metabolized
- onset of action 5-7 days
- half life is about 40 hours
- requires new steady state of clotting factors to be achieved
- effects of dose change require 2-3 days to present
what are the effects of coagulation parameters from warfarin
- INR increases
- PT increases
warfarin exerts an ______ effect on aPTT
inconsistent
warfarin is monitored using ____ and the goal is ____
INR; 2-3
what are the adverse drug reactions for warfarin
- bleeding- can be life threatening
- GI bleeding most common
- rash
- skin necrosis
- taste disturbance
- purple toe syndrome
what are the drug-drug interactions with warfarin
- drugs that change hepatic metabolism of warfarin
- drugs that displace warfarin from protein binding sites
- drugs that change vitamin K levels
- drugs that increase the risk of bleeding
what are the effects of drugs that change hepatic metabolism of warfarin
- inhibition -> more effect of warfarin -> elevated INR
- induction -> less effect of warfarin -> decreased INR
what are the effects of drugs that displace warfarin from protein binding sites
- more free drug -> more effect of warfarin -> elevated INR
what are the effects of drugs that change vitamin K levels
- broad spectrum antibiotics reduce GI flora -> less vitamin K and more effect of warfarin -> elevated INR
- intake of vitamin K decreases effect of warfarin -> decreased INR
what is the use and main interactions with warfarin
- atrial fibrillation, DVT/PE tx and prevention
- interactions: acetominophen
- narrow therapeutic index medication
what are the dental implications for warfarin
- most procedures can be done without holding
- for dental procedure that may result in excessive bleeding consult prescribing physician to adjust dose or hold if possible
- consider local hemostasis measures to prevent excessive bleeding
- check INR level prior to performing dental surgical procedure
- AB use after dental procedure may increase the risk of bleeding
what is the MOA of heparin
- inhibits coagulation in vivo and in vitro
- activation of antithrombin III
- increases antithrombin III affinity for factor Xa and thrombin
what are the pharmacokinetics of heparin
- not absorbed from the GI tract
- administered IV or SQ
- fast onset: immediately after IV, 60 minutes after SQ
- half life is about 40-90 minutes
what is heparins effect on coagulation paramaters
aPTT increases
heparin is monitored using ____ and the goal is _____
aPTT; 1.5-2.5 times control
what are the adverse drug reactions for heparin
- bleeding
- thrombosis: heparin associated thrombocytopenia (HAT) and heparin induced thrombocytopenia (HIT)
- osteoporosis with long term treatment
- aldosterone inhibition -> hyperkalemia
- hypersensitivity reaction
what can reverse the bleeding effects of heparin and how
protamine - binds heparin
what is the use, drug interactions and dental implications of heparin
- use: many including ACS, DVT/PE, atrial fibrillation
- drug interactions: none significant to dentistry
- dental implications: none besides bleeding
what is the MOA of low molecular weight heparin
- inhibits coagulation in vivo and in vitro
- smaller portion of the heparin molecule
- not large enough to interact with thrombin
- activation of antithrombin III
- increases. antithrombin III affinity for factor Xa but not thrombin
what are the pharmacokinetics of low molecular weight heparin
- not absorbed from the GI tract
- administered SQ
= fast onset and predictable response - cleared by the kidneys
- half life is 4.5-7 hoursw
what is LMWH effect on coagulation parameters
LMWH do not require monitoring of coagulation parameters
what is the use, ADRs and drug interactions of LMWH
- use: many including ACS, DVT/PE, atrial fib
- ADRs: bleeding, thrombosis, osteoporosis, hyperkalemia, hypersensitivity
- lower incidence of HIT than unfractionated heparin
- drug interactions: increased risk of bleeding with NSAIDs and aspirin
what are the dental implications of LMWH
- determine why pt is taking medication
= delay proceudre until tx complete - do not discontinue therapy
- consider local hemostasis to prevent excessive bleeding
what is the MOA for direct thrombin inhibitors
- derived for the saliva of medicinal leeches
- binds to the fibrin binding sites of thrombin preventing the conversion of fibrinogen to fibrin
what are the pharmacokinetics of direct thrombin inhibitors
- IV agents: argatroban and bivalirudin
- oral agent: dabigatran
what are the direct thrombin inhibitors effect on coagulation parameters
- argatroban has a drug-lab interaction resulting in falsely elevated INR
- dabigatran does not require monitoring of coagulation tests
- argatroban and bivalirudin may be monitored by aPTT depending on indication
what is the brand name, use, ADRs, drug inreactions, dental implications of direct thrombin inhibitors
- pradaxa
- use: atrial fibrillation, DVT/PE treatment and prevention
- ADRs: bleeding, dyspepsia/gastrisis (25-35%)
- drug interactions: incresed risk of bleeding with NSAIDs and aspirin
- dental implications: high risk of bleeding, high risk of thrombosis if stopped- short half life
what drug reverses direct thrombin inhibitors for bleeding issues and what is the downside of it
- idarucizumab
- reversal costs $5,000
what is the MOA of factor Xa inhibitors
- binds to factor Xa and prevents the conversion of prothrombin to thrombin
what are the pharmacokinetics of factor Xa inhibitors
- parenteral agent: fondaparinux (SQ)
- oral agents: apixaban, edoxaban, rivaroxaban
what are the factor Xa inhibitor effects on coagulation parameters
- factor Xa inhibitors have an inconsistent effect on coagulation tests
- factor Xa inhibitors do not require monitoring, do require renal dosing
what is the brand name, use, ADRs, drug interactions and dental implications of factor Xa inhibitors
- eliquis
- use: atrial fibrillation and DVT/PE treatment and prevention
- ADRs: bleeding
- drug interactions: increases risk of bleeding with NSAIDs and aspirin
- dental implications: high risk of bleeding, high risk of thrombosis if stopped - short half life
what is the reversal agent for factor Xa inhibitors and what is the downside of it
- andexanet alfa
- $25,000-$30,000
non vitamin K oral anticoagulants is an overarching term referring to:
- apixaban
- dabigatran
- edoxaban
- rivaroxaban
NOACs are recommended over warfarin for:
prevention of stroke and systemic embolism AF and DVT/PE treatment due to ease of use
what is another name for NOACs
direct acting oral anticoagulants
what is the coagulation cascade of the intrinsic pathway
- factor 12 -> factor 11 -> factor 10 -> factor Xa
what is the extrinsic pathway coagualtion cascade
factor 7 + tissue factor -> factor 7a -> factor Xa
what are the antiplatelet medications
- COX inhibitor
- P2Y12 inhibitors
- glycoprotein IIb/IIa inhibitors
- PAR-1 antagonist
what is the MOA of aspirin
- inhibits cyclo oxygenase 1
- prevents formation of prostaglandin which is converted to thromboxane A2
- low dose ASA (81mg) inhibits more than 95% of platelet TXA2 formation
- platelets can not make new COX-1 ASA effects last for life of platelet 7-10 days
what are the more common and less common adverse reactions from aspirin
- more common: bleeding (GI), GI distress, rash
- less common: angioedema, tinnitus, respiratory distress
what is the use, and drug interactions of aspirin
- use: many including secondary prevention of coronary disease, arthritis, anti-inflammatory
- drug interactions: increased risk of bleeding with NSAIDS and other anticoagulants. may lower the effectiveness of anti hypertensive agents
what are the dental implictions of aspirin
- determine why it is being taken
- most procedures can be done without holding aspirin
- increased risk of bleeding
- consider local hemostatis mesure to prevent excessive bleeding
what is the MOA of P2Y12 inhibitors
inhibition of ADP binding to the P2Y12 receptor
what is the metabolism of P2Y12 inhibitors
- clopidogrel: CYP 2C19
- prasugrel: CYP 2C19
what are the ADRs of P2Y12 inhibitors
- bleeding: less occurence than aspirin when used as a monotherapy, increased ocurrence when used with aspriin
- skin rash (10%)
- thrombocytopenia (rare)
- ADRs unique to tricagrelor: dyspnea and elevated serum creatinine
what are the drug interactions of P2Y12 inhibtors
- mainly due to CYP 450 inhibition
- prodrugs require activation by CYP 450 therefore have less activity resulting in increased risk of thrombotic event
- tricagrelor active upon administered therefore inhibition results in increased levels and activity leading to increased risk of bleeding
- all P2Y12 inhibitors interact with other medciations that increase risk of bleeding
what is the use of P2Y12 inhibitors
treatment of acute coronary syndrome
what are the dental implications of P2Y12 inhibitos
- plan for increased bleeding
- do not stop without consulting prescribing physician
- do not alter aspirin prescribed dose
- ticagrelor specific
what is the mechanism of action of glycoprotein IIb/IIIa inhibitors
- bind to GP IIa/IIIa receptor preventing platelet aggregation
- only available IV
- eptifibatide and tirofiban
what is the example, use, ADRs, drug interactions and dental implications of glycoprotein IIb/IIIa inhibitors
- eptifibatide
- use: treatment of acute coronary syndrome
- ADRs: bleeding (highest of all antiplatelet agents), thrombocytopenia
- drug interactions: none significant to dentistry
- dental implications: none
what is the MOA of PAR-1 antagonist
- antagonist of the protease activated receptor 1 inhibiting thrombin receptor agonist peptide (TRAP) induced platelet aggregation
- does NOT effect the conversion of fibrinogen to fibrin by thrombin
what is the brand name, use, ADRs, drug interactions and dental implications of PAR-1 antagonist
- brand name: Zontivity
- use: secondary prevention of coronary artery disease
- ADRs; bleeding (25%)
- drug interactions: other drugs that increase bleeding
- dental implications: high bleeding risk
should warfarin or antiplatelet medications be alterred before dental procedures
no
in patients with comorbid medical conditions that can increase the risk of prolonged bleeding after dental treatment:
consult with patients physician
what are the fibrinolytic and antifibrinolytic medications
- fibrinolytic therapy: plasminogen activators
- antifribinolytic therapy: hemostatic agents
what is the MOA of plasminogen activators
- binds to tissue bound fibrin and plasminogen converting plasminogen to plasmin
- recombinant form of tissue plasminogen activator (TPA)
what is the example, use, ADRs, drug interactions and dental implications of plasminogen activators
- tenecteplase
- use: STEMI, stroke
- ADRs; bleeding from any site
- drug interactions: none significant to dentisry
- other drugs that increase bleeding
- dental implications: none
what is the MOA of hemostatic agents
- competitve inhibition of plasmin activation by binding to plasminogen
- at higher concentrations non competitive inhibition of plasmin
what is the example, use, ADRs, drug interactions of hemostatic agents
- tranexamic acid
- use: prohylaxis of bleeding in patients at high risk of bleeding during dental procedures of surgery
- ADRs: IV- hypotension and giddiness; PO- headache, abdominal pain and nasal/sinus symptoms
- drug interactions: reduced the effectiveness of anticoagulants, increased risk of thrombosis
what are the dental implications of hemostatic agents
- used as an antifibrinolytic mouthwash following dental surgery to prevent hemorrhage in patients taking oral anticoagulants
- topical administration should have limited systemic effects. if sysemic adminsitration considered consult with physician prescribing anticoagulant
