Hemostasis and Thrombosis Flashcards
Anti-platelet (aggregates) vs. Anti-coagulants
Anti-aggregates –> stop platelet activity, act on the primary stage of hemostasis
Anti-coagulants –> stop coagulation cascade, act on the secondary stage of hemostasis
Stages of Hemostasis
- Primary (2-5min): bleeding time, platelet count increases, anti-platelet drugs
- Secondary (8-15min): clotting time, APTT, PT, fibrinogen
- Tertiary (90-240min): fibrinolysis
Hemostasis steps
- Injury
- Vessel wall + platelets
- Activation of plasma coagulation factors
- Formation of stable fibrin clot
- Dissolution of fibrin clot
Pulmonary embolism treatment
Massive thrombus –> fibrinolytic drugs is necessary to restore normal circulation
Smaller thrombus –> anti-coagulants are necessary
Arterial vs. Venous thrombus
Arterial –> more platelets, less fibrin –> white thrombus made of thrombocytes
-use anti-aggregates
Venous –> more fibrin, less platelets –> red thrombus
First choice for Acute MI
Anti-aggregates
Anti-platelet drugs
-classes and names
- Cyclooxygenase inhibitors (COX1) – Aspirin
- ADP receptors inhibitors – Clopidogrel, Prasugrel, Ticagrelor
- Glycoprotein IIB/IIa receptor antagonists – Abciximab
ASPIRIN
- mechanism of action
- adverse effects
- COX-1 inhibitor
- IRREVERSIBLY blocks platelet
- rapidly hydrolyzed
- anti-platelet effect lasts 8-10 days
-ulcers, hepatotoxicity, asthma, rashes, renal toxicity, GI bleeding
How does thromboxane affects platelets?
Arachidonic acid (inside platelets) –> thromboxane by the action of COX
-Stimulate activation of new platelets and promote their activation
DIPYRIDAMOLE (4)
-mechanism of action
- “double effect”
- vasodilator - adenosine is inhibited
- inhibits adenosine and decreases phosphodiesterase activity = increase cAMP and cGMP
- increased cAMP levels –> decrease calcium levels –> inhibit platelet activation
ADP RECEPTOR INHIBITORS
- names
- mechanism of action
- unwanted effect
-Clopidogrel, Prasugrel, Ticagrelor
- IRREVERSIBLY block ADP receptor on platelets
- duration 7-10 days
- Clopidogrel requires activation via cytochrome P450 enzyme isoform CYP2C19
-risk of bleeding
Why is Clopidogrel usually the drug of choice?
- cheaper
- main problem: resistance
Glycoprotein IIB/IIa receptor antagonists
- name
- mechanism of action
- side effect
-Abciximab
- inhibits the final common pathway for platelet aggregation - prevents fibrinogen from binding to platelet, disrupting the cross-link
- monoclonal Ab directed against the IIb/IIIa complex
- given for a short period of time
- irreversible inhibition
- intravenous
- use in high risk patients
-bleeding
Anti-platelet drugs indications (5)
- Acute coronary syndrome
- High risk of MI
- Coronary artery bypass grafting, angioplasty or stenting
- Cerebral ischemi atack
- Arterial fibrillation
Anti-coagulants
-classes and names
- Indirect thrombin inhibitors – Heparin, Low-molecular weight Heparin (Nadroparin)
- Direct thrombin inhibitors – Dabigatran
- Oral direct Xa inhibitors – Apixaban, Rivaroxaban
- Warfarin
HEPARIN (unfractionated heparin)
- mechanism of action
- pharmacokinetics
- unwanted effects
- bind to anti-thrombin III and accelerates the inactivation of factor Xa and thrombin
- heparin molecule need to be long enough to binf both anti-thrombin and thrombin
- intravenous (immediate action) or subcutaneous
- hepatic clearance
-bleeding, osteoporosis, thrombosis, heparin-induced thrombocytopenia (HIT)
Low-molecular weight Heparin
- name
- mechanism of action
- pharmacokinetics
- Nadroparin
- more selectively increases degradation of factor Xa, less effect on thrombin
- intravenous or subcutaneous
- renal clearance
- no need to do blood tests because response is predictable