hemostatsis and thrombosis Flashcards
(100 cards)
1
Q
Hemostasis
caused by:
A
- “the arrest of blood loss from damaged blood vessels”
- Essential to life
- Caused by:
- Platelet adhesion and activation
- Fibrin formation
2
Q
Thrombosis
A
- “pathological formation of a ‘hemostatic plug’ within the vasculature in the absence of bleeding”
- Hemostasis in the wrong place
- Virchow’s triad
3
Q
Virchow’s triad
A
4
Q
White Thrombus
A
- Arterial clot
- Primarily platelets and some fibrin mesh
- Associated with atherosclerosis
5
Q
Red Thrombus
A
- Venous clot
- Mostly fibrin and small amount of platelets
- Higher risk of embolus
6
Q
Coagulation Cascade
A
7
Q
Antithrombin III
A
Prevents coagulation
by lysing
Factor Xa and Thrombin
8
Q
Thrombin (Factor IIa) also causes?
A
also causes platelet activation
9
Q
Intrinsic Pathway:
* All components present in?
* Starts when blood comes in contact with? or?
* Monitored by?
A
- 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)
10
Q
Extrinsic Pathway
A
- Some components come from outside blood
- Tissue factor
- Starts when tissue damage releases tissue factor
- Monitored by Prothrombin time (PT) and INR
11
Q
Vitamin K
A
- 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 several clotting factors
12
Q
vitamin K dependent factors
A
13
Q
Platelets Role in Thrombus Formation
A
14
Q
Platelet Activation and Aggregation diagramm
A
pathways
15
Q
Fibrinolysis
A
16
Q
Anticoagulant Medication classes
A
17
Q
Warfarin
Mechanism of Action**
A
- Acts only in vivo
- Inhibits vitamin K epoxide reductase component 1
(VKORC1) - The VKORC1 gene is polymorphic resulting in different affinities for warfarin
- Genetic testing is available for this polymorphism
18
Q
Warfarin Pharmacokinetics
* Rapidly absorbed after?
* Highly bound to?
* metab where? implication?
* Onset of action?
* Half-life?
* Requires what to be achieved?
* Vitamin K dependent clotting factors?
* Effects of dose change requires?
A
- Rapidly absorbed after oral administration
- Highly bound to plasma proteins (i.e. albumin)
- Hepatically metabolized (CYP 450 2C9 and 3A4)
- Polymorphism of CYP 450 2C9
- Onset of action 5-7 days
- Half-life is ~ 40 hours
- Requires new steady-state of clotting factors to be achieved
- Vitamin K dependent clotting factors: II, VII, IX, X, protein C, protein S
- Effects of dose change require 2-3 days to presen
19
Q
Warfarin Effect of coagulation parameters
A
20
Q
Warfarin
Adverse Drug Reactions
A
- Bleeding (can be life threatening), GI bleeding most common
- Rash
- Skin necrosis
- Taste disturbance
- “Purple toe” syndrome
21
Q
Drugs that change hepatic metabolism of warfarin
A
- Inhibition = more effect of warfarin = elevated INR
- Induction = less effect of warfarin = decreased INR
22
Q
Drugs that displace warfarin from protein binding sites
A
- More free drug = more effect of warfarin = elevated INR
23
Q
Drugs that change vitamin K levels effect on warfarin
A
- 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
24
Q
Drugs that increase risk of bleeding w warfarin
A
- ASA and NSAIDS inhibit platelet function = increased risk of bleeding
25
Warfarin moa
Inhibit vitamin K epoxide reductase
component 1 (VKORC1)
26
warfarin adrs
bleeding, taste disturbances, skin necrosis
27
warfarin therpeutic index
narrow
28
warfarin interactions
* Increased effect with?
* Decreased effects with?
* Increased effect with NSAIDs, antibiotics, acetaminophen?
* Decreased effects with barbiturates
29
Warfarin (Vitamin K Antagonist)
Dental Implications
* 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 a dental surgical
procedure
* Antibiotic use after dental procedure may increase risk of bleeding
30
Heparin
Mechanism of Action
* Inhibits coagulation in vivo and in vitro
* Activation of antithrombin III
* Increases antithrombin III affinity for Factor Xa and Thrombin
31
Heparin
Pharmacokinetics
* Not absorbed from?
* Administered?
* onset?
* Half-life?
* Not absorbed from the gastrointestinal (GI) tract
* Administered intravenously (IV) or subcutaneously (SQ)
* Fast onset: immediate after IV, 60 minutes after SQ
* Half-life is ~ 40-90 minutes
32
heparin effects on coagulation parameters:
33
Heparin
Adverse Drug Reactions
* Bleeding (can be life threatening), Protamine can reverse effects (binds heparin)
* Thrombosis
* Heparin associated thrombocytopenia (HAT)
* Heparin induced thrombocytopenia (HIT)
* Osteoporosis- with long-term treatment, mechanism unclear
* Aldosterone inhibition= hyperkalemia
* Hypersensitivity reaction
34
Heparin moa
* MOA: Activation of antithrombin III leading to
inhibition of thrombin and factor Xa
35
heparin adrs
bleeding, thrombosis, osteoporosis, hyperkalemia, hypersensitivity
36
heparin interactions/dental
* Drug-Drug interactions: none of significance to dentistry
* Dental implications: none beyond bleeding
37
Low Molecular Weight Heparin (LMWH)
Mechanism of Action
* 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
38
Low Molecular Weight Heparin (LMWH)
Pharmacokinetics
* Not absorbed from?
* Administered how?
* onset/response?
* Cleared by?
* Half-life?
* Not absorbed from the GI tract
* Administered subcutaneously (SQ)
* Fast onset and predictable response
* Cleared by the kidneys
* Half-life is 4.5-7 hours
39
Low Molecular Weight Heparin (LMWH effects on coag perameters
LMWH do NOT require monitoring of coagulation parameters
40
enoxaparin moa
Activation of antithrombin III leading to
inhibition factor Xa but NOT thrombin
41
enoxaparin adrs
bleeding, thrombosis, osteoporosis, hyperkalemia,
hypersensitivity
* Lower incidence of HIT than unfractionated heparin
42
enoxaparin interactions
Increased risk of bleeding with NSAIDs and Aspirin
43
Low Molecular Weight Heparin (LMWH)
Example: enoxaparin- Dental Implications
* Determine why patient is taking medication
* Delay procedure until treatment complete
* Do not discontinue therapy
* Consider local hemostasis measures to prevent
excessive bleeding
44
Direct Thrombin Inhibitors Mechanism of Action
* Derived for the saliva of medicinal leeches
* Binds to the fibrin-binding sites of thrombin preventing the conversion of fibrinogen to fibrin
45
Direct Thrombin Inhibitors
* Intravenous agents:
* Oral agent:
* Intravenous agents: Argatroban and Bivalirudin
* Oral agent: Dabigatran (pro-drug)
46
Direct Thrombin Inhibitors effect on coag perameters
Dabigatran does not require monitoring of coagulation tests
* Argatroban and bivalirudin may be monitored by aPTT depending in indication
47
Argatroban and INR
Argatroban has a
drug-lab interaction
resulting in a falsely
elevated INR
48
Dabigatran moa
Binds to thrombin preventing conversion of fibrinogen to fibrin
49
Dabigatran adrs
bleeding (reversal agent available- idarucizumab), Reversal costs ~$5,000
dyspepsia/gastritis- due to formulation
50
Dabigatran interactions
ncreased risk of bleeding with NSAIDs and Aspirin
51
Dabigatran dental
* High risk of bleeding
* High risk of thrombosis if stopped (short half-life)
52
Factor Xa inhibitors
Mechanism of Action
* Binds to factor Xa and prevent
the conversion of prothrombin
to thrombin
53
Factor Xa Inhibitors
* Parenteral agent:
* Oral agents:
* Parenteral agent: Fondaparinux (SQ)
* Oral agents: Apixaban, Edoxaban, Rivaroxaban
54
factor Xa inhibitors effect on coag perameters
55
factor Xa inhibitors monitoring
* Factor Xa inhibitors have an inconsistent effect on coagulation tests
* Factor Xa inhibitors do NOT require routine monitoring- do require renal dosing
56
Apixaban moa
Binds to factor Xa and prevents conversion of prothrombin to
thrombin
57
apixaban adrs
bleeding (reversal agent available- andexanet alfa)
Reversal costs between $25,000-$30,000
58
Apixaban interactions
Increased risk of bleeding with NSAIDs and Aspirin
59
apixaban dental
* High risk of bleeding
* High risk of thrombosis if stopped (short half-life)
60
NOACs
Non-Vitamin K Oral Anticoagulants
* Overarching term referring to:
* Apixaban
* Dabigatran
* Edoxaban
* Rivaroxaban
* * Also called DOACs= Direct-acting Oral Anticoagulants
61
Generally NOACs are recommended in?
Generally NOACs are recommended in guidelines over
warfarin for prevention of stroke and systemic embolism AF and DVT/PE treatment due to ease of use
62
Antiplatelet Medications types
Epoprostenol- this medication is addressed in the vascular section
63
Aspirin
Mechanism of Action
* Inhibits?
* Prevents?
* Low dose?
* length of effect?
* Inhibits cyclo-oxygenase 1 (COX 1)
* Prevents formation of prostaglandin which is subsequently converted to thromboxane A2
* Low dose ASA (81mg) inhibits > 95% of platelet TXA2 formation
* Platelets can not make new COX-1, ASA effects last for life of platelet 7- 10 days
64
Aspirin Adverse Reactions
More Common:
Less common:
More Common:
* Bleeding- gastrointestinal
* Gastrointestinal distress
* Rash
Less common
* Angioedema
* Tinnitus
* Respiratory distress
65
Aspirin moa
Inhibition of COX-1 preventing the formation of TXA2
66
aspirin adrs
bleeding, rash, GI distress, angioedema, tinnitus, respiratory distress
67
aspirin interactions
* Increased risk of bleeding with NSAIDs and other anticoagulants
* May lower the effectiveness of anti-hypertensive agents
68
Aspirin
Dental Implications
* Determine why ASA is being taken- most procedures can be done without holding ASA
* Increased risk of bleeding
* Consider local hemostasis measures to prevent excessive bleeding
69
P2Y12 inhibitors
Mechanism of Action
70
Clopidogrel pharmacokenetics
*CYP 2C19 polymorphisms effect the efficacy of clopidogrel
71
prasugrel pharmacokenetics
72
Ticagrelor pharmacokenetics
73
Cangrelor pharmacokenetics
74
P2Y12 inhibitors
Adverse Drug Reactions
* Bleeding, Less occurrence than aspirin when used as monotherapy and Increased occurrence when combined with aspirin (DAPT)
* Skin rash (~ 10%)
* Thrombocytopenia (rare)
75
* ADRs unique to ticagrelor:
* Dyspnea- due to off-target adenosine effects
* Elevated serum creatinine- unknown mechanism usually clinically insignifican
76
P2Y12 inhibitors Drug-Drug interactions
* Mainly due to?
* Prodrugs?
* Proton Pump Inhibitor?
* Ticagrelor?
* All P2Y12 inhibitors interact with?
* Mainly due to CYP 450 inhibition: Ticagrelor 3A4, Clopidogrel & Prasugrel 2C19
* Prodrugs (Clopidogrel & Prasugrel) require activation by CYP 450 therefore have less activity resulting in increased risk of thrombotic event
* Proton Pump Inhibitor resulting in a significant drug-drug interaction
* Ticagrelor active upon administered therefore inhibition results in increased levels and activity leading to increased risk of bleeding
* All P2Y12 inhibitors interact with other medications that increase risk of bleeding (i.e. anticoagulants, NSAIDs, etc..
77
ticagrelor moa
Inhibition of ADP binding to the P2Y12 receptor
78
ticagrelor adrs
bleeding, rash, dyspnea, elevated serum creatinine
79
ticagrelor interactions
* Increased risk of bleeding with NSAIDs, aspirin, and other anticoagulants
* CYP 3A4 inhibitors (i.e. macrolide antibiotics and azoles) may increase effect
80
P2Y12 inhibitors
Example: ticagrelor- Dental Implications
* Plan for increased bleeding
* Consider local hemostasis measures to prevent
excessive bleeding
* Do not stop/hold without consulting prescribing
physician
* Do not alter aspirin dose prescribed
* Ticagrelor specific- potential shortness of breath
81
Glycoprotein IIb/IIIa inhibitors
Mechanism of Action
* Bind to GP IIa/IIIb receptor preventing platelet aggregation
* Only available intravenously
* Eptifibatide and tirofiban: small molecules
82
Eptifibatide moa
Bind to GP IIa/IIIb receptor preventing platelet aggregation
83
Eptifibatide adrs
bleeding (highest of all antiplatelet agents), thrombocytopenia
84
Eptifibatide interactions/ dental
* none of significance to dentistry
* other drugs that increase bleeding
* Dental Implications: none
85
PAR-1 antagonist (Vorapaxar)
Mechanism of Action
* 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
86
Vorapaxar moa
Antagonist of the protease activated receptor-1 inhibiting thrombin receptor agonist peptide (TRAP)- induced platelet aggregation
87
Vorapaxar adr
bleeding (~25%
88
Vorapaxar interactions/dental
* Drug-Drug interactions: Other drugs that increase bleeding (i.e. aspirin, NSAIDs, anticoagulants)
* Dental Implications: High bleeding risk medication
89
hold or nor hold these meds in dentistry?
“There is general agreement that in most cases, treatment regimens with older anticoagulants (e.g., warfarin) and antiplatelet agents (e.g., clopidogrel,
ticlopidine, prasugrel, ticagrelor, and/or aspirin) should NOT be altered before dental procedures. The risks of stopping or reducing these medication regimens
(i.e., thromboembolism, stroke, MI) far outweigh the consequences of prolonged bleeding, which can be controlled with local measures.”
“On the basis of limited evidence, general consensus appears to be that in most patients who are receiving the newer target-specific oral anticoagulants (i.e.,
dabigatran, rivaroxaban, apixaban, or edoxaban) and undergoing dental interventions (in conjunction with usual local measures to control bleeding), NO
CHANGE to the anticoagulant regimen is required.”
90
In patients with comorbid medical conditions that can increase the risk of prolonged bleeding after dental treatment or who are receiving other therapy that can increase bleeding risk, dental practitioners may wish to?
In patients with comorbid medical conditions that can increase the risk of prolonged bleeding after dental treatment or who are receiving other therapy that can increase bleeding risk, dental practitioners may wish to consult the patient’s physician to determine whether care can safely be delivered in a primary care office. Any suggested modification to the medication regimen
prior to dental surgery should be done in consultation and on advice of the patient’s physician
91
Fibrinolytic and Antifibrinolytic medication types
92
Plasminogen activators
Mechanism of Action
Binds to tissue bound fibrin and plasminogen
converting plasminogen to plasmin (fibrin specific)
Recombinant form of tissue plasminogen activator (TPA)
93
Tenecteplase moa
Binds to tissue bound fibrin and plasminogen converting plasminogen to plasmin
94
Tenecteplase adrs
bleeding from virtually any site
95
Tenecteplase interactions/dental
* Drug-Drug interactions:
* None of significance to dentistry
* Other drugs that increase bleeding (i.e. heparin, aspirin, and clopidogrel)
* Dental Implications: none
96
Hemostatic Agents
Mechanism of Action
Competitive inhibition of plasminogen activation by binding to plasminogen
At higher concentrations non-competitive inhibition of plasmin
97
Tranexamic acid moa
Competitive inhibition of plasminogen activation by binding to plasminogen; at higher concentrations non-competitive inhibition of plasmin
98
Tranexamic acid adrs
IV- hypotension and giddiness;
PO- headache, abdominal pain, and nasal/sinus symptoms
99
Tranexamic acid interactions
* Reduces the effectiveness of anticoagulants
* Increased risk of thrombosis
100
Tranexamic acid- Dental Implications
* Used as an antifibrinolytic mouthwash following
dental surgery to prevent hemorrhage in patients taking oral anticoagulants.
* Topical administration should have limited systemic effects. If systemic administration considered consult with physician prescribing anticoagulant
