W14, Ch 55 Anticoagulants, Anti-Platelet Drugs and Thrombolytics

What is hemostasis?

Physiologic process by which bleeding is stopped

What is stage 1 (of 2) in hemostasis?

Platelet plug is formed by platelet aggregation

What is stage 2 (of 2) in hemostasis?

Coagulation where fibrin is produced to finish clot

What are 2 pathways in coagulation cascade that both lead to common pathway?

Intrinsic coagulation pathway, extrinsic coagulation pathway

What clotting factor do both intrinsic and extrinsic coagulation pathways lead to and start common pathway?

Factor X, which starts common pathway in coagulation cascade and accelerates thrombin formation, which ultimately leads to formation of fibrin being accelerated too

What are 3 major classifications of drugs that work on clotting (dissolving or preventing formation of clots)?

Anticoagulants, antiplatelet drugs, thrombolytic drugs

What are drugs classified as anticoagulants?

Heparin, warfarin, lovenox, dabigatran etexilate (Pradaxa)

What are drugs classified as antiplatelet drugs?

Aspirin, clopidogrel

What are drugs classified as thrombolytic drugs?

Altepase (TPA), streptokinase

What is main mechanism of action of anticoagulants?

To disrupt coagulation cascade, thereby suppressing production of fibrin (inhibit synthesis and activity of clotting factors)

What is mechanism of action of antiplatelet drugs?

To inhibit platelet aggregation

What is mechanism of action of thrombolytic drugs?

To promote lysis (breaking down) of fibrin, causing dissolution of thrombus

True/False: Since Alteplase (tPA) is typically given in acute, life-threatening situations where rapid clot dissolution is needed, it is used if patient has had stroke or has an occluded PICC line

True

What is thrombosis?

Formation of a blood clot (thrombus) inside blood vessel, which blocks or slows blood flow and can cause serious issues like heart attacks, strokes, or pulmonary embolisms

What are 2 types of thrombosis?

Arterial thrombosis, venous thrombosis

How does arterial thrombosis form?

Begins with adhesions of platelets to arterial wall which occludes artery and causes localized tissue injury (right at site and tissue can die because oxygen isn’t getting to it)

How does venous thrombosis form?

Slow flow initiates clotting cascade, fibrin is produced, and ultimately forms a clot by enmeshing RBCs and platelets

True/False: Two main types of thrombosis are arterial thrombosis, a clot in an artery (like causing heart attacks/strokes), and venous thrombosis, a clot in a vein (like Deep Vein Thrombosis or DVT, which can lead to pulmonary embolism)

True

Why are clots removed?

To restore blood flow, heal body, and prevent tissue damage or life-threatening complications

How are clots removed physiologically?

Plasminogen is activated and turned into plasmin, which digests fibrin and breaks down clot

What classification of drugs are arterial thrombi best prevented with?

Antiplatelet drugs like aspirin, clopidogrel (Plavix)

What classification of drugs are venous thrombi best prevented with?

Anticoagulants like warfarin (Coumadin), heparin, dabigatran, lovenox

True/False: Arterial thrombi are best prevented with anticoagulants like warfarin (Coumadin), heparin, dabigatran, lovenox

False; VENOUS thrombi are best prevented with anticoagulants like warfarin (Coumadin), heparin, dabigatran, lovenox

What is goal of anticoagulants?

To reduce formation of fibrin

Are anticoagulants used as prevention treatment or as treatment once clot is already formed?

Both; they are used as prevention or treatment of pre-existing clots (like DVT and PE)

What are two, specific mechanisms of action of anticoagulants?

Inhibit synthesis of clotting factors, inhibit activity of clotting factors

When anticoagulants inhibit synthesis of clotting factors (mechanism of action), how long does it take for these anticoagulants to work?

It takes days to peak and days to replace inhibited factor, so this mechanism of action is slow to start and slow to stop

When anticoagulants inhibit activity of clotting factors (mechanism of action), how long does it take for these anticoagulants to work?

These anticoagulants have quick action and short duration, so they are fast in and fast out of body

What do anticoagulants do in body to perform mechanism of action that inhibits synthesis of clotting factors?

Anticoagulants stop liver from making clotting factors

What do anticoagulants do in body to perform mechanism of action that inhibits activity of clotting factors?

Block active clotting factors

True/False: All drugs classified as anticoagulants inhibit synthesis of clotting factors

False; only some drugs, like warfarin, that are classified as anticoagulants inhibit synthesis of clotting factors, and the other drugs that are classified as anticoagulants perform other mechanism of action (inhibit activity of clotting factors)

What is drug classified as an anticoagulant that performs specific mechanism of action that inhibits synthesis of clotting factors?

Warfarin (PO)

What are drugs classified as anticoagulants that perform specific mechanism of action that inhibits activity of clotting factors?

Heparin, dabigatran, apixaban, rivaroxaban

True/False: Since anticoagulants have two mechanisms of action, some drugs can perform both mechanisms of action (inhibition of synthesis and inhibition of activity of clotting factors) while some drugs can only perform one of the mechanisms of action

False; although anticoagulants have two mechanisms of action, drugs classified as anticoagulants can only perform one of these mechanisms of action, NOT BOTH

What are 2 types of heparin?

Unfractionated heparin, low molecular weight (LMW) heparin

How are two types of heparin, unfractionated (UFH) and low molecular weight (LMWH), differentiated?

Distinguished by their size and how they affect blood clotting, with UFH being larger, requiring monitoring, and LMWH being smaller, more predictable, and often used for outpatient care

What are both types of heparin, unfractionated (UFH) and low molecular weight (LMWH), classified as?

Anticoagulant

What is classification of unfractionated heparin?

Anticoagulant

What route is unfractionated heparin given?

Parenteral, IV, subQ; just not IM because patient could bleed into muscle

Why can unfractionated heparin not be given into muscle (as route)?

Unfractionated heparin (UFH) should not be given intramuscularly (IM) because it can cause serious bleeding into the muscle

Is unfractionated heparin rapid-acting or slow-acting?

Rapid-acting as it has quick onset and short duration

What is mechanism of action of unfractionated heparin?

Binds to antithrombin, enhances its activity and together they inactivate thrombin (factor IIa) and factor Xa, and prevents conversion of fibrinogen to fibrin

What factors in coagulation cascade does unfractionated heparin inactivate?

Thrombin (factor IIa), factor Xa

When a factor in coagulation cascade is labeled as its number followed by “a”, like factor IIa (thrombin) for example, what does “a” mean?

In the coagulation cascade, when you see a factor labeled with an “a” (like factor IIa, Xa, IXa), the “a” stands for “activated”

When unfractionated heparin inactivates factor Xa, what is inhibited? (don’t forget unfractionated heparin also inactivates factor IIa, thrombin)

Common pathway in coagulation cascade is inhibited (so fibrinogen is never converted into fibrin to form final mesh in clot)

True/False: Each anticoagulant inhibits a different factor in coagulation process

True; different anticoagulants target different factors in coagulation cascade

What is antidote to unfractionated heparin?

Protamine sulfate

How does protamine sulfate function as antidote to unfractionated heparin?

Binds to heparin for 2 hours, and 1 mg of protamine sulfate will inactivate 100u heparin

What is therapeutic use of unfractionated heparin?

To prevent the formation and growth of harmful blood clots in medical conditions like in pregnancy, pulmonary embolism (PE), deep vein thrombosis (DVT), open heart surgery, low-dose therapy post-op, in patients with evolving stroke

How is dosage of unfractionated heparin determined?

Based off of patient’s weight

Since dose of unfractionated heparin is determined by weight, what should nurse do before giving this drug?

Take patient’s weight

What should nurse monitor when patient is taking unfractionated heparin?

aPTT level (activated partial thromboplastin time), and platelet count

True/False: Low molecular weight heparin is bigger in size than unfractionated heparin

False; low molecular weight heparin is smaller than unfractionated heparin

How often are labs taken when patient is taking unfractionated heparin?

Every 4 to 6 hours to see if adjustment is needed

Why is platelet count monitored when patient is taking unfractionated heparin?

Unfractionated heparin can cause low platelet count (thrombocytopenia)

Why is aPTT level monitored when patient is taking unfractionated heparin?

aPTT values guide safe and effective heparin therapy by showing how “thin” the blood is relative to normal clotting time, and shows if adjustment in dose of heparin need to be made (increase vs. decrease drip to get therapeutic level)

What is baseline clotting time for someone who is not on anticoagulation therapy (like unfractionated heparin), the normal aPTT?

25 to 40 seconds

What is clotting time for someone who is taking unfractionated heparin, the therapeutic aPTT?

60 to 80 seconds, which is 1.5 to 2.5 times normal value

What are side effects of unfractionated heparin?

Hemorrhage, heparin-induced thrombocytopenia (HIT), hypersensitivity reactions

What are signs and symptoms of hemorrhage (side effect of unfractionated heparin)?

Drop in BP, increase HR, bruising, discolored (dark) stools, discolored (bloody) urine, headache, faintness, low back pain, weakness (due to blood loss)

What is most common side effect of unfractionated heparin?

Hemorrhage

What should nurse warn/educate patient about when taking unfractionated heparin?

Patient is at risk for bleeding!!

True/False: When patient is taking unfractionated heparin, biggest side effect risk is constipation

False; patient is at risk for bleeding and most common side effect is hemorrhage

What are contraindications to taking unfractionated heparin?

Those with thrombocytopenia, uncontrollable bleeding, or use during and immediately after surgery of eye, brain, or spinal cord as using it can cause severe bleeding and damage

What is classification of low molecular weight (LMW) heparin?

Anticoagulant

What are brand names of low molecular weight heparin?

Lovenox, Fragmin

Is low molecular weight heparin bigger or smaller than unfractionated heparin?

Smaller than unfractionated heparin

What are characteristics of low molecular weight heparin?

Has longer half life than unfractionated heparin, is not protein bound

Does low molecular weight heparin need to be monitored at home?

Just needs little monitoring for home use

True/False: Typically, low molecular weight heparin needs little monitoring for home use, but antifactor Xa levels may be monitored in special populations

True; antifactor Xa levels may be monitored due to renal impairment, obesity, pregnancy, pediatrics

In what special populations would antifactor Xa possibly be monitored when taking low molecular weight heparin?

Those experiencing renal impairment, obesity, pregnancy, pediatrics

Typically, low molecular weight heparin needs little monitoring for home use, but what is the exception?

Antifactor Xa levels may be monitored if patient has renal impairment, obesity, pregnancy, pediatrics

What are advantages to using low molecular weight heparin instead of unfractionated heparin?

Uses fixed dose schedule, there’s no lab testing, it may be used at home, and there is less thrombocytopenia

What drug is first line therapy for DVT?

Low molecular weight heparin

True/False: Low molecular heparin is first line therapy for DVT

True

What is therapeutic use of low molecular heparin?

To prevent DVT after hip or knee replacement, to treat established DVT, to prevent ischemia with unstable angina or after MI

What route is low molecular heparin administered?

SubQ injection, given once or twice daily

How is dosage of low molecular heparin determined?

By patient’s body weight

What is antidote for overdose of low molecular heparin?

Protamine sulfate

True/False: Unfractionated heparin and low molecular weight heparin have same antidote: protamine sulfate

True

What should nurse do when administering low molecular heparin?

Document which side (R/L) medication is injected because nurse wants to alternate sides

What are adverse effects of low molecular heparin?

Bleeding, thrombocytopenia, neuro injury

What is cost of low molecular heparin in comparison to unfractionated heparin?

Overall cost of low molecular heparin is less because there is no need to monitor aPTT (without labs, low molecular heparin is higher in cost than unfractionated heparin, but labs will always be needed if taking unfractionated heparin so cost of LMW heparin will still be less)

What is brand name of warfarin?

Coumadin

What is classification of warfarin?

Anticoagulant

What route is warfarin given?

Oral

Is onset of warfarin immediate or delayed?

Delayed onset as it takes 8 to 12 hours for warfarin to start working in body, and several days to reach peak effects

How long does it take warfarin to start working in the body?

It takes 8 to 12 hours for warfarin to start working in body, and several days to reach peak effects (due to delayed onset)

What is antidote for warfarin?

Vitamin K

Why is vitamin K antidote to warfarin?

Giving vitamin K bypasses warfarin’s inhibition, as warfarin is antagonist of vitamin K

When nurse is giving vitamin K as antidote to warfarin, what should nurse keep in mind?

Reversal with vitamin K is not immediate (takes several hours), because new clotting factors must be synthesized

What is mechanism of action of warfarin?

Blocks biosynthesis of clotting factors VII, IX, X, and prothrombin (II) by inhibiting vitamin K (these clotting factors need vitamin K to be synthesized in liver, so by inhibiting vitamin K, all these factors are blocked)

What factors in coagulation cascade does warfarin block?

Blocks biosynthesis of clotting factors VII, IX, X, and prothrombin (II) by inhibiting vitamin K (these clotting factors need vitamin K to be synthesized in liver, so by inhibiting vitamin K, all these factors are blocked)

True/False: Warfarin is useful in emergencies, and is often considered most useful drug for emergencies

False; warfarin is NOT useful in emergencies

What is prophylaxis?

Action taken to prevent disease, especially by specified means or against specified disease

What is therapeutic use of warfarin?

Long-term prophylaxis, prevents thrombus formation

Since therapeutic effect of warfarin is prevention of thrombus formation (as well as long-term prophylaxis), what are all types of thrombi that warfarin prevents?

Warfarin prevents venous thrombosis and associated pulmonary embolism, prevents thromboembolism (in patients with prosthetic heart valves), prevents thrombosis for patients with arterial fibrillation

True/False: Therapeutic effects of warfarin include long-term prophylaxis, prevention of venous thrombosis and associated pulmonary embolism, prevention of thromboembolism (in patients with prosthetic heart valves), prevention of thrombosis for patients with arterial fibrillation, and used in medical emergencies

False; therapeutic effects of warfarin include long-term prophylaxis, prevention of venous thrombosis and associated pulmonary embolism, prevention of thromboembolism (in patients with prosthetic heart valves), prevention of thrombosis for patients with arterial fibrillation (but are NOT used in medical emergencies)

How are patients monitored when beginning to take warfarin?

Patients are monitored using international normalized ratio (INR) daily for first 5 days, then less frequent checks like every few days or weekly, and finally every 2 to 4 weeks or sometimes longer INR checks continue

What INR is considered therapeutic for most patients taking warfarin?

2 to 3