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Hemostasis and Thrombosis Flashcards

1
Q

What is the coagulation cascade (image)?

A
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2
Q

What is the difference bewteen intrinsic and extrinsic pathways?

A

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)

Extrinsic Pathway
* Some components come from outside blood
— Tissue factor
* Starts when tissue damage releases tissue factor
* Monitored by Prothrombin time (PT) and INR

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3
Q

What are the factors that increase the risk of thrombosis?

IMPORTANT

A

Virchow’s Triad
- stasis
- vessel wall injury
- hypercoagulability

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4
Q

What’s the difference between a white and red thrombosis?

A

White
* Arterial clot
* Primarily platelets and some fibrin mesh
* Associated with atherosclerosis

Red
* Venous clot
* Mostly fibrin and small amount of platelets
* Higher risk of embolus

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5
Q

What is the process of platele adhesion, activation, and aggregation (image)?

A
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6
Q

What are the key mediators of platelet adhesion, activation, and aggregation?

A
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7
Q

What is the process of fibrinolysis (image)?

A
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8
Q

What is the mechanism of action of vitamin K antagonist (warfarin)?

Warfarin (Coumadin)

A
  • Acts only in vivo
  • Inhibits vitamin K epoxide reductase component 1 (VKORC1)
  • The VKORC1 gene is polymorphic resulting in different affinities for warfarin
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9
Q

What is the mechanism of action of unfractionated heparin?

IMPORTANT

A
  • Inhibits coagulation in vivo and in vitro
  • Activation of antithrombin III
    — Increases antithrombin III affinity for Factor Xa and Thrombin
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10
Q

What is the mechanism of action of low molecular weight heparins (LMWH)?

Enoxaparin (Lovenox), Dalteparin (Fragmin), Tinzaparin (Innohep)

IMPORTANT

A
  • 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
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11
Q

What is the mechanism of action of direct thrombin inhibitors?

Argatroban, Bivalirudin (Angiomax), Dabigatran (Pradaxa)

A
  • Derived for the saliva of medicinal leeches
  • Binds to the fibrin-binding sites of thrombin preventing the conversion of fibrinogen to fibrin
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12
Q

What is the mechanism of action of factor Xa inhibitors?

IMPORTANT

A

Binds to factor Xa and prevent the conversion of prothrombin to thrombin

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13
Q

What is the route of administration of vitamin K antagonist (warfarin)?

A

oral administration

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14
Q

What is the route of administration of unfractionated heparin?

A

Administered intravenously (IV) or subcutaneously (SQ)

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15
Q

What is the route of administration of low molecular weight heparins (LMWH)?

Enoxaparin (Lovenox), Dalteparin (Fragmin), Tinzaparin (Innohep)

A

Administered subcutaneously (SQ)

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16
Q

What is the route of administration of direct thrombin inhibitors?

Argatroban, Bivalirudin (Angiomax), Dabigatran (Pradaxa)

A
  • Intravenous agents: Argatroban and Bivalirudin
  • Oral agent: Dabigatran (pro-drug)
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17
Q

What is the route of administration of factor Xa inhibitors?

A
  • Parenteral agent: Fondaparinux (SQ)
  • Oral agents: Apixaban, Edoxaban, Rivaroxaban
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18
Q

What are the effects on coagulation parameters of vitamin K antagonist (warfarin)?

A
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19
Q

What are the effects on coagulation parameters of unfractionated heparin?

A
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20
Q

What are the effects on coagulation parameters of low molecular weight heparins (LMWH)?

A

LMWH do NOT
require monitoring of coagulation parameters

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21
Q

What are the effects on coagulation parameters of direct thrombin inhibitors (i.e. dabigatran, bivalirudin)?

A
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22
Q

What are the effects on coagulation parameters of factor Xa inhibitors (i.e. apixaban, fondaparinux)?

A
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23
Q

What are the common adverse drug reactions of vitamin K antagonist (warfarin)?

IMPORTANT

A
  • Bleeding (can be life threatening)
  • Gastrointestinal bleeding most common
  • Rash
  • Skin necrosis
  • Taste disturbance
  • “Purple toe” syndrome
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24
Q

What are the common adverse drug reactions of unfractionated heparin?

A
  • 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
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25
What are the common adverse drug reactions of low molecular weight heparins (LMWH)?
- bleeding, thrombosis, osteoporosis, hyperkalemia, hypersensitivity * Lower incidence of HIT than unfractionated heparin
26
What are the common adverse drug reactions of direct thrombin inhibitors (i.e. dabigatran, bivalirudin)?
- bleeding (reversal agent available- idarucizumab), - dyspepsia/gastritis (25%-35%)- due to formulation
27
What are the common adverse drug reactions of Factor Xa inhibitors (i.e. apixaban, fondaparinux)?
bleeding (reversal agent available- andexanet alfa)
28
What are the common drug-drug interactions of vitamin K antagonist (warfarin)?
* Drugs that change hepatic metabolism of warfarin --- Inhibition → more effect of warfarin → elevated INR --- Induction → less effect of warfarin → decreased INR * Drugs that displace warfarin from protein binding sites --- More free drug → more effect of warfarin → elevated INR * 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 * Drugs that increase risk of bleeding --- ASA and NSAIDS inhibit platelet function → increased risk of bleeding
29
What are the common drug-drug interactions of unfractionated heparin?
none of significance to dentistry
30
What are the common drug-drug interactions of low molecular weight heparins (LMWH)?
Increased risk of bleeding with NSAIDs and Aspirin
31
What are the common drug-drug interactions of direct thrombin inhibitors (dabigatran, bivalirudin)?
Increased risk of bleeding with NSAIDs and Aspirin
32
What are the common drug-drug interactions of factor Xa inhibitors (apixaban, fondaparinux)
Increased risk of bleeding with NSAIDs and Aspirin
33
What are the dental implications of vitamin K antagonist (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 a dental surgical procedure * Antibiotic use after dental procedure may increase risk of bleeding
34
What are the dental implications of unfractionated heparin?
none beyond bleeding
35
What are the dental implications of low molecular weight heparins (LMWH)?
* Determine why patient is taking medication * Delay procedure until treatment complete * Do not discontinue therapy * Consider local hemostasis measures to prevent excessive bleeding
36
What are the dental implications of direct thrombin inhibitors?
* High risk of bleeding * High risk of thrombosis if stopped (short half-life)
37
What are the dental implications of factor Xa inhibitors?
* High risk of bleeding * High risk of thrombosis if stopped (short half-life)
38
What is the mechanism of action of aspirin? | IMPORTANT
* 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
39
What is the mechanism of action of P2Y12 inhibitors (clopidogrel)?
Inhibition of ADP binding to the P2Y12 receptor
39
What is the mechanism of action of glycoprotein IIb/IIIa inhibitors (eptifibatide)?
* Bind to GP IIa/IIIb receptor preventing platelet aggregation * Only available intravenously * Eptifibatide and tirofiban --- small molecules
40
What is the mechanism of action of PAR-1 antagonist (vorapaxar)?
* 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
41
What is the route of administration of P2Y12 inhibitors (i.e. clopidogrel)?
Oral or Intravenous
42
What is the route of administration of Glycoprotein IIb/IIIa inhibitors (i.e. eptifibatide)?
only intravenously
43
What is the common adverse drug reactions of aspirin?
More Common: * Bleeding- gastrointestinal * Gastrointestinal distress * Rash Less common * Angioedema * Tinnitus * Respiratory distress
44
What is the common adverse drug reactions of P2Y12 inhibitors (clopidogrel)?
* Bleeding --- Less occurrence than aspirin when used as monotherapy --- Increased occurrence when combined with aspirin (DAPT) * Skin rash (~ 10%) * Thrombocytopenia (rare) * ADRs unique to ticagrelor: --- Dyspnea- due to off-target adenosine effects --- Elevated serum creatinine- unknown mechanism usually clinically insignificant
45
What is the common adverse drug reactions of Glycoprotein IIb/IIIa inhibitors (i.e. eptifibatide)?
bleeding (highest of all antiplatelet agents), thrombocytopenia
46
What is the common adverse drug reactions of PAR-1 antagonist (vorapaxar)?
bleeding (~25%)
47
What is the common drug-drug interactions of aspirin?
* Increased risk of bleeding with NSAIDs and other anticoagulants * May lower the effectiveness of anti-hypertensive agents
48
What is the common drug-drug interactions of P2Y12 inhibitors (clopidogrel)?
* Mainly due to CYP 450 inhibition * Prodrugs (Clopidogrel & Prasugrel) require activation by CYP 450 therefore have less activity resulting in increased risk of thrombotic event * 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..)
49
What is the common drug-drug interactions of glycoprotein IIb/IIIa inhibitors (eptifibatide)?
* none of significance to dentistry * other drugs that increase bleeding
50
What is the common drug-drug interactions of PAR-1 antagonist (vorapaxar)?
* Other drugs that increase bleeding (i.e. aspirin, NSAIDs, anticoagulants)
51
What is the dental implications of aspirin?
* Determine why ASA is being taken --- Most procedures can be done without holding aspirin * Increased risk of bleeding --- Consider local hemostasis measures to prevent excessive bleeding
52
What is the dental implications of P2Y12 inhibitors (clopidogrel)?
* 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 --- shortness of breath/dyspnea
53
What is the dental implications of glycoprotein IIb/IIIa inhibitors (eptifibatide)?
none
54
What is the dental implications of PAR-1 antagonist (vorapaxar)?
* High bleeding risk medication
55
What is the mechanism of action of fibrinolytic plasminogen activators (**alterplase**, tenecteplase) | IMPORTANT
- Binds to tissue bound fibrin and plasminogen **converting plasminogen to plasmin** (fibrin specific) - Recombinant form of tissue plasminogen activator (TPA)
56
What is the mechanism of action of antifibrinolytic (aminocaproic acid, tranexamic acid)?
- Competitive inhibition of plasmin activation by binding to plasminogen - At higher concentrations non-competitive inhibition of plasmin
57
What is are the common adverse drug reactions of fibrinolytic plasminogen activators (alterplase, tenecteplase)?
bleeding from virtually any site
58
What are the common adverse drug reactions of antifibrinolytic (aminocaproic acid, tranexamic acid)?
IV- hypotension and giddiness; PO- headache, abdominal pain, and nasal/sinus symptoms
59
What is are the common drug-drug interactions of fibrinolytic plasminogen activators (alterplase, tenecteplase)?
* None of significance to dentistry * Other drugs that increase bleeding (i.e. heparin, aspirin, and clopidogrel)
60
What are the common drug-drug interactions of antifibrinolytic (aminocaproic acid, tranexamic acid)?
* Reduces the effectiveness of anticoagulants * Increased risk of thrombosis
61
What is are the dental implications of fibrinolytic plasminogen activators (alterplase, tenecteplase)?
none
62
What are the dental implications of antifibrinolytic (aminocaproic acid, tranexamic acid)?
* 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

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