Hemostasis and Coagulation

Hemostasis

• It is the general term for any process that stops bleeding.
• Coagulation is a part of hemostasis, specifically referring to blood clotting.
• Clot formation involves a complex interaction of substances that either promote or inhibit coagulation, or dissolve existing clots.
• A thrombus is the technical term for a blood clot.
• An embolus is a thrombus that moves through blood vessels.

Coagulation System

• The coagulation system operates as a "cascade."
• Each activated factor acts as a catalyst, amplifying the subsequent reaction.
• Fibrin, a clot-forming substance, is the end result.
• The coagulation system involves the intrinsic and extrinsic pathways.

Fibrinolytic System

• The system is responsible for breaking down clots and balancing the clotting process.
• Fibrinolysis: mechanism to lyse thrombi, preventing excessive clot formation and vessel blockage.
• Fibrin binds to plasminogen, converting it to plasmin.
• Plasmin: enzymatic protein which breaks down fibrin thrombus into degradation products, preventing embolus formation.

Coagulation Modifier Drugs

• Anticoagulants: inhibit the action or formation of clotting factors, therefore preventing clot formation.
• Antiplatelet drugs: inhibit platelet aggregation and prevent platelet plugs.
• Hemorheological drugs: alter platelet function without stopping platelets from working.
• Thrombolytic drugs: lyse/break down existing clots.
• Antifibrinolytic or hemostatic drugs: promote blood coagulation.

Anticoagulants

• They are also known as antithrombotic drugs.
• They do not directly affect already formed blood clots.
• Anticoagulants prevent intravascular thrombosis by decreasing blood's ability to coagulate.
• They are used prophylactically to prevent clot formation (thrombus) and emboli (dislodged clots).

Heparins

• Action: inhibit clotting factors IIa (thrombin), Xa, and IX.
• Factors XI and XII are also inactivated but are less critical.
• Unfractionated heparin is simply "heparin."
• Low-molecular-weight heparins include enoxaparin (Lovenox), dalteparin (Fragmin), nadroparin calcium (Fraxiparine), and tinzaparin sodium (Innohep).
• Unfractionated heparin is derived from animal sources and needs monitoring for bleeding times, like aPTT.
• Heparin for catheter flush (10-100 units/mL) does not require monitoring.
• LMWHs (enoxaparin) have a smaller molecular structure, a more predictable anticoagulant response, and typically do not need frequent aPTT monitoring.

Warfarin (Coumadin)

• It inhibits vitamin K synthesis by bacteria in the gastrointestinal tract.
• Action: inhibit vitamin K-dependent clotting factors II, VII, IX, and X, normally made in the liver.
• The final effects is the prevention of clot formation.

Antithrombin Medications

• Action: inhibit thrombin (factor IIa).
• Human antithrombin III (Thrombate) is a natural form.
• Synthetic forms include lepirudin (Refludan), argatroban (Argatroban), bivalirudin (Angiomax), and dabigatran (Pradaxa).

Direct Acting Xa Inhibitors

• Action: inhibit factor Xa.
• Examples: fondaparinux (Arixtra), rivaroxaban (Xarelto), and apixaban (Eliquis).
• Dabigatran is a direct thrombin inhibitor.

Dabigatran Etexilate Mesylate (Pradaxa)

• It is the first oral direct thrombin inhibitor approved to prevent strokes and thrombosis in nonvalvular atrial fibrillation patients.
• It is a prodrug that activates in the liver, specifically and reversibly binding to free and clot-bound thrombin.
• It is excreted via the kidneys, therefore the dose relies on kidney function.
• The normal dose is 150 mg twice daily, lowered to 75 mg twice daily if creatinine clearance is below 30 mL/minute.
• There is no antidote, and the most significant adverse effect is bleeding.
• Coagulation monitoring isn't needed.

Anticoagulants: Mechanism of Action

• Mechanisms vary by drug.
• Target different points in the clotting cascade.
• Prevent intravascular thrombosis by reducing blood coagulability.
• Anticoagulants do not break down existing clots.

Anticoagulants: Indications

• Used to prevent clot formation risk, such as in myocardial infarction, unstable angina, atrial fibrillation, indwelling devices (mechanical heart valves), and conditions with slowed blood flow (major orthopedic surgery, prolonged immobility).

Anticoagulants: Contraindications

• Include drug allergy, any acute bleeding process or high risk and pregnancy (especially Warfarin).
• Low-molecular-weight heparins are contraindicated in patients with an indwelling epidural catheter because of the risk of epidural hematoma.

Anticoagulants: Adverse Effects

• Bleeding risk increases with higher dosages and can be localized or systemic.
• May also cause heparin-induced thrombocytopenia, nausea, vomiting, abdominal cramps, or thrombocytopenia.
• Warfarin can cause bleeding, lethargy, muscle pain, skin necrosis, or "purple toes" syndrome.

Heparin-Induced Thrombocytopenia

• Type I is a gradual reduction in platelets where heparin can usually be continued.
• Type II is an acute fall in platelet numbers by more than 50% from baseline; heparin should be stopped.
• Clinical manifestations may include fatal thrombosis.
• Treatment includes thrombin inhibitors like bivalirudin and argatroban.
• It is more common with bovine-derived heparin compared to porcine.
• Incidence ranges from 5-15% of patients.

Treatment: Toxic Effects of Heparin

• Aimed at reversing the cause.
• Symptoms include hematuria, melena (bloody stool), petechiae, ecchymoses, and bleeding mucous membranes.
• Stop drug immediately.
• Intravenous (IV) protamine sulphate: 1 mg reverses 100 units of heparin (1 mg of protamine for each milligram of low-molecular-weight heparin given).

Treatment: Toxic Effects of Warfarin

• Stop the Warfarin.
• It may take 36-42 hours to resynthesize clotting factors and reverse effects.
• Vitamin K₁ (phytonadione) speeds up the return to normal coagulation.
• High doses (10 mg) of IV vitamin K will reverse anticoagulation within 6 hours.

Treatment: Toxic Effects of Warfarin - Cautions

• Vitamin K causes Warfarin resistance for up to 7 days following.
• Severe bleeding requires human plasma or clotting factor transfusions.
• IV vitamin K may cause anaphylaxis, which can be reduced by diluting the dose, followed by administration over 30 minutes.
• Injectable form is commonly delivered orally.

Drug Interactions: Anticoagulants

• Interactions are profound and complicated.
• The interactions can involve enzyme inhibition of metabolism, displacement of the drug from inactive protein-binding sites, decreased vitamin K absorption/synthesis via the bacterial flora of the large intestine, or changes in the platelet count or activity.

Heparin Sodium

• Natural anticoagulant from the lungs/intestinal mucosa of pigs.
• Dosage: 10 to 10,000 units/mL.
• DVT prophylaxis: 5,000 units subcutaneously two or three times a day, which doesn't require monitoring.
• Weight-based protocol.
• For therapeutic use, continuous IV infusion and aPTT monitoring (usually every 6 hours until therapeutic effects are seen) are necessary.

Heparin Flushes

• Heparin Leo is administered via a small vial of aqueous heparin IV flush solution.
• Due to the risk of heparin-induced thrombocytopenia, many institutions use 0.9% normal saline as a flush for heparin-lock IV ports.
• Heparin flushes (100 units/mL) remain in use for central catheters.

Warfarin Sodium (Coumadin)

• It is the most commonly prescribed oral anticoagulant.
• Monitoring the prothrombin time (PT)/international normalized ratio (INR) is important.
• A normal INR is around 0.8 to 1.2 without Warfarin; the therapeutic INR with Warfarin varies from 2 to 3.5, relative to use (e.g., atrial fibrillation, thromboprevention, prosthetic heart valve).
• It has dietary considerations, genetic variations (CYP2CP and VKORC1), age-related factors, maintenance dose determination via INR and natural health product cautions.

Antiplatelet Drugs

• Prevent platelet adhesion and include aspirin, clopidogrel bisulfate (Plavix), prasugrel (Effient), treprostinil (Remodulin), abciximab (ReoPro), eptifibatide (Integrilin), tirofiban (Aggrastat), anagrelide hydrochloride (Agrylin), and dipyridamole (Aggrenox, Persantine).

Antiplatelet Drugs: Indications and Adverse Effects

• Antithrombotic effects.
• Adverse effects can be serious, with a risk of bleeding, therefore they vary by drug.

Aspirin

• Aspirin can be found in numerous combinations including prescription and nonprescription drugs.
• One contraindication is its use in children/adolescents with flu-like symptoms, due to the risk of Reye's syndrome, which is a rare, often fatal condition that affects the liver and the central nervous system (CNS).

Clopidogrel Bisulphate Plavix

• The most widely used antiplatelet drug.

Thrombolytic Drugs

• Drugs that break down/lyse preformed clots in the coronary arteries.
• Older drugs include streptokinase and urokinase.
• Current drugs include alteplase (Activase) and tenecteplase (TNKase).

Thrombolytic Drugs: Mechanism of Action

• Activate the fibrinolytic system to break down clots in blood vessels quickly.
• Activate plasminogen and convert it to plasmin to lyse the thrombus.
• Plasmin is a proteolytic enzyme.
• Mimics the body’s own process of clot destruction.

Thrombolytic Drugs: Indications

• Acute myocardial infarction, arterial thrombolysis, DVT, occlusion of shunts or catheters, pulmonary embolism and acute ischemic stroke.

Thrombolytic Drugs: Adverse Effects

• Include bleeding such as internal, intracranial, and superficial bleeding.
• Other effects are nausea, vomiting, hypotension, hypersensitivity, and anaphylactoid reactions, and cardiac dysrhythmias.

Antifibrinolytic Drugs

• Prevent the lysis of fibrin.
• Result in the promotion of clot formation.
• Used for prevention and treatment of excessive bleeding from hyperfibrinolysis or surgical complications.
• Treatment of hemophilia A or type I von Willebrand’s disease with desmopressin.

Antifibrinolytic Drugs Examples

• Aprotinin (Artiss, Trasylol), tranexamic acid (Cyklokapron) and desmopressin acetate (DDAVP).

Antifibrinolytic Drugs: Adverse Effects

• Uncommon and mild; rare reports of thrombotic events.
• Other effects are dysrhythmia, orthostatic hypotension, bradycardia, headache, dizziness, fatigue, hallucinations, convulsions, nausea, vomiting, abdominal cramps, and diarrhea.

Nursing Implications

• Assessments include patient history, medication history, allergies, contraindications, baseline vital signs, laboratory values, potential drug interactions, and history of abnormal bleeding conditions.

Heparin: Nursing Implications

• Intravenous doses require a double-check with another nurse.
• Subcutaneous doses are administered subcutaneously instead of intramuscularly.
• Subcutaneous doses are given in areas of deep subcutaneous fat and sites are rotated.

Heparin: Nursing Implications (2 of 3)

• Subcutaneous doses should not be injected within 5 cm of the umbilicus, abdominal incisions, open wounds, scars, drainage tubes, stomas, or bruise/ooze areas.
• Do not aspirate during subcutaneous injections or massage the injection site so as to avoid hematoma formation.

Heparin: Nursing Implications (3 of 3)

• IV doses can be given as bolus or infusions.
• Anticoagulant effects take place immediately.
• Daily monitoring of aPTT monitors coagulation.
• Protamine sulphate is an antidote in case of excessive anticoagulation.

Low-Molecular-Weight Heparins: Nursing Implications

• Given subcutaneously in the abdomen, and sites should be rotated.
• Protamine sulphate is an antidote for excessive anticoagulation.

Warfarin (Coumadin): Nursing Implications (1 of 2)

• Can be started while still on Heparin, until PT/INR levels show adequate anticoagulation.
• It takes several days for a full therapeutic effect.
• Regularly monitor PT/INR and keep up with follow-up appointments.
• Vitamin K is the antidote.

Warfarin (Coumadin): Nursing Implications

• Many herbal products can have potential interactions, which may create increased bleeding.
• Examples include capsicum pepper, garlic, ginger, ginkgo, St. John’s wort and feverfew.

Anticoagulants: Patient Education

• Education includes emphasizing regular lab testing, the signs of abnormal bleeding, and measures to take to prevent bruising, bleeding, and tissue injury.
• Include wearing a medical alert bracelet and avoiding Vitamin K-rich foods like tomatoes and dark leafy greens.
• The physician should be consulted before taking other drugs/over-the-counter products, this includes herbals.

Antiplatelet Drugs: Nursing Implications

• Concerns and teaching tips are like those for anticoagulants.
• Be aware of drug-drug interactions.
• Monitor/report adverse reactions and monitor for abnormal bleeding.

Thrombolytic Drugs: Nursing Implications

• Follow preparation and administration guidelines by the manufacturer.
• Monitor IV sites for bleeding, redness, and pain.
• Monitor gums, mucous membranes, nose, and injection sites for bleeding.
• Watch for signs of internal bleeding, such as decreased blood pressure, restlessness, or increased pulse.