Hemostasis Modifier Drugs - Ch. 55 Flashcards
What is hemostasis?
Process that halts bleeding after injury to a blood vessel
1. Forms a platelet plug
2. Fibrin produced (clotting cascade, plasma proteins)
What are hemostasis modifier agents?
Anticoagulants
Antiplatelet drugs
Thrombolytic drugs
Hemostatic agents
What do anticoagulants do?
Inhibit the action or formation of clotting factors
Prevent clot formation
What do anti platelet drugs do?
Inhibit platelet aggregation
Prevent platelet plugs
What do thrombolytic drugs do?
Lyse existing/preformed clots
What do hemostatic agents do?
Promote blood coagulation
What is the final product of the clotting cascade?
Fibrin
What is the clotting/coagulation cascade divided into?
Intrinsic pathway
Extrinsic pathway
What is the other name for anticoagulants?
Blood thinners
How are anticoagulants used?
Prophylactically
What are anticoagulants used to prevent?
Clot formation (thrombus)
Emboli (dislodged clots)
What are anticoagulants not used for?
Do not use to lyse/break down existing clots
In what settings are anticoagulants used to prevent clot formation?
MI
Unstable angina
Atrial fibrillation
DVT e.g, major orthopaedic surgery
Indwelling devices (e.g, mechanical heart valves)
Pulmonary embolism
Examples of anticoagulants that all prevent clot formation?
Heparin and low molecular weight heparins (LMWH)
Warfarin -oral
Direct-Acting Oral Anticoagulants (DOACs)
-Direct factor X & Thrombin inhibitors
When is anticoagulant use contraindicated?
Known drug allergy
Acute bleeding process
Thrombocytopenia
What adverse effects are associated with anticoagulants?
Bleeding risk
-gums bleed
-nosebleeds
-unusual bruising
-anemia/low Hct
-tarry stools
What is the mechanism of action of Heparin?
Indirectly inhibits activity of multiple proteins on cascade
What proteins are inhibited by heparin?
-Thrombin (II)
-Factor Xa
-Intrinsic pathway factors
What is natural heparin?
Obtained from animal sources
how is heparin monitored because of its unpredictable dosage?
Activated partial thromboplastin times (aPTT)
What pathway does aPTT measure?
Intrinsic pathway
What do aPTTs need to be?
1.5 - 2.5 x greater than 40 sec (control)
How is Heparin administered?
Parenteral (IV or SC)
How long does it take for Heparin to be effective?
Seconds
What is the half life of Heparin?
Short half life
1-2 hours
What adverse effects are associated with Heparin?
Heparin-induced thrombocytopenia (HIT)
Hypersensitivity reactions
What is Heparin-induced thrombocytopenia (HIT)?
The body reacts to heparin in a way that causes platelets to clot instead of preventing them
-Increases blood clots
-1-5% population (>4 days of administration)
-stop heparin administration and use an alternative
What hypersensitive reactions does Heparin cause?
Urticaria (hives)
Fever
Chills
What is the antidote for heparin?
protamine sulfate
What does protamine sulphate do?
Reverses anticoagulant effects
Examples of low-molecular-weight heparins (LMWHs)?
Enoxaparin
Tinzaparin
Dalteparin
What do Low-molecular-weight heparins (LMWHs) have that heparins don’t?
More predictable anticoagulant response
low-molecular-weight heparins (LMWHs) do not require what?
Frequent lab monitoring
-Often given at home
How are low-molecular-weight heparins (LMWHs) administered?
SC q12h
What is the mechanism of action of low-molecular-weight heparins (LMWHs)?
Indirectly inhibits Factor X only
What antidote is used for low-molecular-weight heparins (LMWHs)?
Protamine sulfate
(same as heparin)
What are some other anticoagulant drugs?
Danaparoid
Fondaparinux
What is Danaparoid?
anticoagulant that is structurally distinct from heparin
Alternative to heparin
How is Danaparoid administered?
SC or IV
What is Fondaparinux?
Synthetic anticoagulant
How is Fondaparinux administered?
SC or IV
Subcutaneous LMWH doses should be injected only in what area?
Abdomen only
-Rotate sites around abdomen
What is an oral anticoagulant?
Warfarin (Coumadin)
What is warfarin?
Modified coumarin
What is the mechanism of action of Warfarin?
Vitamin K “antagonist”
-Reduces ‘ready for action” clotting factors in plasma so clotting time is extended
What is Vitamin K used for?
Production of several clotting factors (VII, IX, X, prothrombin) in liver cells
What do Warfarin effects depend on?
Clotting factors turnover (proteins degradation)
How long may Warfarin’s max effect take?
3-5 days
-effects start within 24 hours
Patients may be started on 5 days on a combination of what anticoagulants?
LMWHs + warfarin
-then LMWH is withdrawn
How is warfarin monitored?
Clotting lab test
-Prothrombin time (PT)
INR (international normalization reference ratio)
What pathway does PT/INR measure?
Extrinsic
For the drug to be therapeutic, PT needs to be within what range?
1.3-1.5 times the normal (control) level
What is the normal target INR range?
2 to 3 x control
Some need to be 2.5 to 3.5 (normal is 0.8 to 1.2) eg mechanical heart valves
If excessive PT/INR during Warfarin, use of what can begin?
Vit K
How can Vitamin K be administered if excessive PT/INR?
IV (slow infusion) 4-8h effect
PO effect within 24 hours
When is Warfarin use contraindicated?
Pregnancy
-Risk for fatal bleeding, teratogenicity and spontaneous abortion
-Use LMWH instead
What should someone do is they are taking Warfarin?
Maintain intake of vitamin K
-Tomatoes, dark leafy green veggies)
Wear medical alert bracelet
Consult physician before taking other drugs because warfarin has many drug-drug interactions
Warfarin administration may be started while the client is still on what drug?
Heparins
-until prothrombin times/INR indicate adequate anticoagulation
How long does it take for the full therapeutic effect of warfarin ?
several days
What are the advantages of Direct-Acting Oral Anticoagulants (DOACs) over Warfarin?
Rapid onset and offset
Fixed doses
No blood test
Few drug-drug interactions
no dietary concerns
Lower risk of bleeds
Example of Direct-Acting Oral Anticoagulants (DOACs)??
dabigatran
rivaroxaban
apixaban
betrixaban
edoxaban
What is the mechanism of action of Dabigatran?
Directly inhibits thrombin
How is dabigatran administered?
PO
Adverse effects associated with dabigatran?
GI disturbances
-Nausea, vomiting, abdominal pain, bloating
What is the mechanism of action of rivaroxaban
apixaban, betrixaban and edoxaban?
Directly inhibit Factor Xa
How is rivaroxaban, apixaban, betrixaban and edoxaban adminsitered (Factor X inhibitor DOACs)?
PO
What is the antidote for dabigatran?
Idarucizumab (antibody)
What is the antidote for Factor X inhibitor DOACs?
andexanet alfa (modified factor X)
All DOACs use required what?
Annual renal function test
- if below min function, changed to Vit K antagonist
All anticoagulants increase the risk for what?
Bleeding
-Mild to life-threatening
What are signs of abnormal bleeding?
bleeding of gums while brushing teeth
unexplained nosebleeds
bruising
heavier menstrual bleeding
bloody or tarry stools, vomiting blood
bloody urine or sputum
abdominal pain
What are some anti platelet agents?
Acetylsalicyclic acid (Aspirin) - 81 mg EC
Pentoxifylline
Clopidogrel (plavix), prasurgel, ticlopidine
ticagrelor
GPIIb/IIIa antagonists
What is the mechanism of action of Aspirin?
Inhibits COX enzyme pathway in platelets (irreversible)
What is the mechanism of action of clopidogrel?
Irreversible ADP receptor blocker
-effects last the entire life-time of the platelet
What is the mechanism of action of ticagrelor?
Reversible ADP receptor blocker
What are anti platelet drugs used for?
Antithrombotic effects
-Reduce risk of MI
-Reduce risk of stroke
The combination of anti platelet drugs, Aspirin + clopidogrel produces what effects?
Additive anti platelet activity but increased bleeding potential
Where are the receptors for GPIIb/IIIa antagonists?
On platelets
What activates GPIIb/IIIa receptors?
TXA2, ADP and 5-HT
What are Glycoproteins IIb/IIIa used for?
Required for fibrinogen cross-linking = platelet aggregation
What do GPIIb/IIIa antagonists do?
Prevent fibrinogen cross linking
-no platelet aggregation
Example of GPIIb/IIIa antagonists?
Abciximab
Tirofiban
How does Abciximab bind to GPIIb/IIIa receptors on platelets?
Irreversibly binds
-Is an antibody
How does Tirofiban bind to GPIIb/IIIa receptors on platelets?
Reversibly binds
Clients taking anti platelet drugs should be taught the same things as those taking what kind of drugs?
Anticoagulation drugs
What is a group of thrombolytic agents?
Recombinant tissue plasminogen activator (tPA)
Examples of tPA drugs?
Alteplase
Tenecteplase
reteplase
How is Alteplase administered?
Slow infusion
Describe the half life of alteplase?
short
How is tenectephase administered?
Single bolus
Describe the half life of tenectephase?
Long
How is Reteplase administered?
2x bolus
Describe the half life of Reteplase?
long
What is the mechanism of action of thrombolytic agents?
Activate fibrinolytic system to break down clot in blood vessel
What enzyme do thrombolytic agents activate to cause fibrinolysis?
Plasminogen which converts to Plasmin
-Plasmin digests fibrin, dissolves clot
When thrombolytic agents lyse existing clots, what happens?
Blood flow is re-established
e.g, Heart muscle via coronary arteries (MI)
broin (stroke)
What are thrombolytic agents used for?
Acute MI
Arterial thrombolysis
DVT
Occlusion of shunts or catheters
Pulmonary embolus
When os thrombolytic agent use contraindicated?
Allergy
Concurrent use of other anticoagulation
What adverse effects are associated wit thrombolytic agents?
Bleeding
Nausea, vommiting
Hypotension
Anaphylactoid reactions
Dysrhythmias
What kind of bleeding is associated with thrombolytic agents?
(adverse effects)
Internal
Intracranial
Superficial
What do antifibrinolytic agents do?
Some prevent the lysis of fibrin in an existing clot so clot remains
-
What do antifibrinolytic agents promote?
Promote clot formation and/or clot maintenance
-improve clotting factor survival
Examples of Antifibrinolytic agents?
Aminocaproic acid
tranexamic acid (TXA)
Desmopressin
What is the mechanism of action of aminocaproic acid, tranexamic acid (TXA)?
Inhibits fibrinolysis by blocking plasminogen activation
What is aminocaproic acid and tranexamic acid (TXA) used for?
Trauma (bleeding)
Antidote to thromolytic agents e.g, alteplase
What is desmopressin?
Synthetic pituitary hormone similar to Vasopressin (ADH)
What is desmopressin used for?
Diabetes insipidus
Mild hemophilla A (VIII deficiency)
What does desmopressin do to plasma concentration of factor VIII?
Increases plasma concentration of factor VIII by von Willibrand factor release from endothelial cells
What are antifibrinolytic agents used to prevent and treat?
Excessive bleeding
-Hyperfibronolysis
-Surgical complications
-Excessive oozing from surgical sites e.g, chest tubes
-reduces total blood loss and duration of bleeding in post op period
When is antifibrinolytic drug use contraindicated?
Allergy
Never used in DIC (disseminated intravascular coagulation)
-very rare but critical
-uncontrolled clotting
What adverse effects are associated with antifibrinolytic agents?
Uncommon and mild
Rare reports of thrombotic events
