Coagulation Modifier Drugs

• Coagulation Modifier Drugs alter the body's ability to form blood clots
• Hemostasis is any process that stops bleeding
• Coagulation is hemostasis from blood's physiological clotting
• Thrombus is technical term for a blood clot
• Embolus is a thrombus that moves

Coagulation System

• It occurs from a cascade of reactions
• Each activated factor acts as a catalyst to amplify the next reaction
• The result is fibrin, a clot-forming substance
• Involves both intrinsic and extrinsic pathways

Fibrinolytic System

• It initiates the breakdown of clots, balancing the clotting process
• Fibrinolysis is the mechanism that lyses formed thrombi, preventing excessive clot formation and blockage
• Fibrin binds to plasminogen; converting it to plasmin
• Plasmin is an enzyme that breaks down the fibrin thrombus into degradation products
• Plasmin keeps the thrombus localized, preventing embolus formation

Coagulation Modifier Drugs

• Anticoagulants inhibit clotting factor action or formation, thus preventing clot formation
• Antiplatelet drugs inhibits platelet aggregation, preventing plugs
• Hemorheological drugs alter platelet function without fully stopping platelet work
• Thrombolytic drugs lyse existing clots
• Antifibrinolytic or hemostatic drugs promote blood coagulation

Anticoagulants

• It is also known as antithrombotic drugs
• These drugs have no direct effect on already formed clots
• Anticoagulants prevent intravascular thrombosis by reducing blood coagulability
• Used to prevent clot formation or thrombus and embolus formation
• Heparins are a type of anticoagulant
• It inhibits factors IIa (thrombin), Xa, and IX
• Factors XI and XII are also impacted
• Unfractionated heparin is commonly referred to as "heparin"
• Low-molecular-weight heparins include enoxaparin (Lovenox), dalteparin (Fragmin), nadroparin calcium (Fraxiparine), and tinzaparin sodium (Innohep).
• Unfractionated heparin is derived from animal sources
• Frequent lab monitoring is important with aPTT with unfractionated heparin
• No monitoring is needed with heparin for catheter flush at 10-100 units/MmL
• LMWHs like enoxaparin are synthetic with a smaller molecular structure
• It has a predictable anticoagulant response, with no lab testing

Warfarin

• Warfarin (Coumadin) inhibits vitamin K synthesis
• It inhibits vitamin K-dependent clotting factors II, VII, IX, and X, made normally in liver
• The final preventative effect, is the prevention of clot formation
• Action begins 24-72 hr, with a peak in 4 hours
• The elimination half-life is 0.5-3 days, and the duration of action is 2-5 days

Antithrombin Medications

• They inhibit thrombin and factor IIa
• Natural antithrombin medication is human antithrombin III (Thrombate)
• Synthetic antithrombin medications include lepirudin (Refludan), argatroban (Argatroban), bivalirudin (Angiomax), and dabigatran (Pradaxa)
• Direct acting Xa inhibitors include fondaparinux (Arixtra), rivaroxaban (Xarelto), and apixaban (Eliquis)
• Direct thrombin inhibitor is dabigatran
• Dabigatran etexilate mesylate (Pradaxa) is the first oral direct thrombin inhibitor
• It is approved to prevent strokes and thrombosis in nonvalvular conditions
• It is activated by the liver and binds to free and clot-bound thrombin
• Excreted by the kidneys, the dose depends on kidney function
• The standard dose is 150 mg BID, and must be reduced to 75 mg BID with renal impairment (less than 30 mL creatine clearance)
• Bleeding is its most serious adverse event
• Coagulation monitoring not required
• The onset of action is 2-3 hours PO, reaching peak in 2 hours
• Elimination is 12-17 hours, with 12 hours duration of action
• Anticoagulants act at different areas of the clotting cascade
• It does not lyse existing clots

Anticoagulant Indications

• Used to prevent clot formation, for settings:
• Myocardial infarction
• Unstable angina
• Artial fibrillation
• Indwelling devices like mech heart valves
• Conditions that slow blood flow like major orthopedic surgery and prolonged immobility

Anticoagulant Contraindications & Adverse Effects

• Drug allergies
• Any acute bleeding
• Warfarin is contraindicated in pregnancy, and other anticoagulants have lower categories
• LMWH is also contraindicated in patients with an indwelling epidural catheter, due to the risk of an epidural hematoma
• Bleeding has increased risk with increased dosages, and maybe systemic
• Cause Heparin-induced thrombocytopenia, nausea, abdominal cramps
• Warfarin may cause bleeding, lethargy, “purple toes” syndrome
• Heparin-Induced Thrombocytopenia has type I and type II
• Type I = platelets are reduced, and therapy is continued
• Type II = platelets acutely fall, treatment must be discontinued
• Clinical signs of Type II is thrombosis, that can be fatal
• Treat by administrating thrombin inhibitors bivalirudin and argatroban
• There is higher risk with bovine vs porcine heparins
• Occurs in 5-15% of patients
• Toxic effects of heparin require stopping the dug immediately
• Give IV protamine sulphate with 1 mg per 100 units heparin. 1 mg of protamine is for each low-molecular-weight heparin given
• For Warfarin toxicity, wait 36-42 hours so the liver can resynthesize clotting factors
• Vitamin K1 can hasten the return to normal coagulation
• 10 mg of high dose vitamin K given intravenously reverses anticoagulation within 6 hours
• It can cause resistance for up to 7 days if given
• Severe bleeding treated with transfusions
• Risk of anaphylaxis is diminished by diluting it and giving it over 30 minutes when admistering Warfarin
• Injectable form is often given orally
• Anticoagulant drug interactions occur with enzyme inhibition, displacement of drugs, decreased vitamin K and changes in platelet count

Heparin

• Obtained from the lungs or intestinal mucosa of pigs
• 10 to 10,000 units/mL
• 5,000 units subQ for DVT prophylaxis two or three times a day
• When used for prophylaxis, no need for monitoring
• Used therapeutically in a weight-based protocol
• Monitor therapeutic effects with aPTT every 6 hours

Heparin Flushes

• Heparin Leo in a small vial of aqueous IV flush solution
• Due to Heparin induced thrombocyptenia, most institutions have moved to using 0.9% normal saline
• Heparin flushes at 100 units/mL are still used for central catheters

Warfarin Sodium

• Warfarin is the most commonly prescribed oral anticoagulant
• Requires careful monitoring of the prothrombin time(PT)/international normalized ratio (INR)
• A normal INR without the treatment medication is 0.8 to 1.2
• A therapeutic INR with drug ranges from 2 to 3.5
• It varies with the indication of use, for the drug such as atrial fibrillation

Antiplatelet Drugs

• Drugs prevent platelet adhesion, including:
• aspirin
• clopidogrel bisulfate (Plavix)
• prasugrel (Effient)
• treprostinil (Remodulin)
• abciximab (ReoPro)
• eptifibatide (Integrilin)
• tirofiban (Aggrastat)
• anagrelide hydrochloride (Agrylin)
• dipyridamole(Aggrenox, Persantine)
• Antiplatelet drugs are used for anti-thrombotic effects
• They can cause serious adverse effects, as they pose a risk for bleeding
• Vary according to the medication
• Aspirin is often combined in many prescriptions
• Aspirin use is contraindicated among children, with conditions that appear as flu-like symptoms, because it can increase risk for Reye's. a rare, acute and fatal condition
• Aspirin 15-30 min to onset PO, with a 0.25-2 hr peak. Half life 2-3 hr for 4-6 hr

Clopidogrel Bisulphate

• Clopidogrel bisulphate Plavix, is the most widely used
• Action can begin is 1-2 hours PO, with a peak 1 hour
• A half-life of 8 hr can last 7-10 day

Thrombolytic Drugs

• Breaks down of preformed clots in the coronary arteries
• Older drugs such as streptokinase and urokinase
• Current drugs alteplase (Activase) and tenecteplase (TNKase)
• Activate the fibrinolytic system, that breaks down quickly in the blood vessel
• It activates plasminogen, and converts it to the plasmin
• Plasmin is a proteolytic enzyme
• Mimics the body's process of clot destruction
• It is indicated in myocardial infarction, arterial thrombolysis, DVT
• And for occlusion of shunts, pulmonary embolism, and acute ischemic stroke
• Bleeding is an adverse effect, wether it is internal, intracranial or superficial
• Other adverse effects include nausea, vomiting, hypotension, hypersensitivity or cardiac dysrhythmias

Antifibrinolytic Drugs

• These types of drugs prevent the lysis of fibrin
• Promoting clot formation
• Used for excessive bleeding and hyperfibrinolysis complications
• Treatment of hemophilia A or type I von Willebrand's disease with desmopressin
• It also contains aprotinin (Artiss, Trasylol)
• tranexamic acid (Cyklokapron)
• desmopressin acetate (DDAVP) as antifibrolytics
• Effects are uncommon and mild
• Rare reports of thrombotic events
• Other effects involve Dysrhythmia, orthostatic hypotension, bradycardia, headache, dizziness. fatigue, hallucinations, convulsions, nausea, vomiting, abdominal cramps, diarrhea

Nursing Implications

• Assess patient history, medication history, allergies, allergies, and contraindications
• Review baseline vital signs, laboratory values and potential drug interactions
• History of abnormal bleeding conditions
• The nurse ensures appropriate and safe administration
• Intravenous doses often require a double check with another nurse
• Subcutaneous doses should be giving subQ, not intramuscularly
• Subcutaneous doses require areas of deep layer of subcutaneous fat, and rotating sites
• No insertion wihtin 5 cm of umbilicus or open wounds
• Do not aspirate or massage site
• Cause hematoma
• Intravenous doses may be given in bolus or IV infusion
• Monitor lab values daily, and observe aPTT
• Protamine sulphate is administered in excessive coagulation
• Administer SubQ in the abdomen
• Rotate injection sites
• Protamine sulphate is given for excessive anticoagulation
• Warfarin may be administer while on heparin, with PT/INR monitoring
• Takes days, ensure adequate follow
• Antidote is Vitamin K
• Many herbal products have potential interactions, increasing bleeding
• Capsicum pepper
• Garlic
• Ginger
• Ginkgo
• St. John's wort
• Feverfew
• Education is required for lab testing, signs of bleeding
• Measure to prevent bruising/bleeding
• And with appropriate patient education
• Concerns and teaching tips same as for anticoagulants
• Referrals on drug-drug interactions & monitoring
• Adverse reactions to report for side effects
• Thromboltyics require manufactures guidlines
• Watch iV sites for bleeding and pain
• Watch for bleeding from nose and gums
• Internal bleeding signs are low bp, restlessness and pulse