Understanding Hemostasis, Coagulation, and Fibrinolysis

Hemostasis

• Defined as any process that halts bleeding.
• Coagulation is hemostasis resulting from the physiological clotting of blood.
• Complex interactions exist between substances that promote clot formation and those that inhibit coagulation or dissolve clots.
• A thrombus is the technical term for a blood clot.
• An embolus is a thrombus that travels through blood vessels.

Coagulation System

• Functions as a "cascade."
• Each activated factor acts as a catalyst, amplifying subsequent reactions.
• The end product is fibrin, the substance that directly forms the clot.
• Operates through intrinsic and extrinsic pathways.

Fibrinolytic System

• Initiates clot breakdown to balance the clotting process.
• Fibrinolysis is the process where formed thrombi are broken down to prevent excessive clot formation and vessel blockage.
• Fibrin binds to plasminogen, converting it to plasmin.
• Plasmin is an enzymatic protein that breaks down fibrin thrombi into fibrin degradation products.
• This process keeps the thrombus localized, preventing it from becoming an embolus.

Coagulation Modifier Drugs

• Anticoagulants are used to inhibit the action or formation of clotting factors and prevent clot formation.
• Antiplatelet drugs inhibit platelet aggregation and prevent platelet plugs.
• Hemorheological drugs alter platelet function, without preventing platelets from working.
• Thrombolytic drugs work to lyse existing clots.
• Antifibrinolytic drugs, or hemostatics, promote blood coagulation.

Anticoagulants

• Are also known as antithrombotic drugs.
• Have no direct impact on existing blood clots.
• Prevent intravascular thrombosis by reducing blood's ability to coagulate.
• They are used prophylactically to prevent thrombus and emboli formation.
• Heparins inhibit clotting factors IIa (thrombin), Xa, and IX.
• Factors XI and XII are also affected, but aren't important in this process.
• Unfractionated heparin is 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 for bleeding times, such as aPTT, is required for unfractioned heparin.
• Heparin for catheter flush (10-100 units/mL) doesn't need monitoring.
• LMWHs like enoxaparin have a smaller molecular structure.
• LMWHs have a more predictable anticoagulant response.
• LMWHs don't need freqent laboratory monitoring like unfractionated heparin.
• Warfarin (Coumadin) reduces vitamin K synthesis by bacteria in the GI tract.
• Warfarin inhibits vitamin K-dependent clotting factors II, VII, IX, and X, synthesized in the liver.
• The final effect of Warfarin is prevention of clot formation.
• Antithrombin medications inhibit thrombin (factor IIa).
• A 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 inhibit factor Xa, and include fondaparinux (Arixtra), rivaroxaban (Xarelto), and apixaban (Eliquis).
• Dabigatran functions as a direct thrombin inhibitor

Dabigatran Etexilate Mesylate

• Dabigatran etexilate mesylate (Pradaxa) is the first oral direct thrombin inhibitor for preventing strokes and thrombosis in nonvalvular atrial fibrillation patients.
• Functions as a prodrug, activated in the liver binding to free and clot-bound thrombin reversibly.
• It is excreted primarily through the kidneys, so the dose needs to be adjusted with kidney dysfunction.
• The standard dose is 150 mg twice daily, reduced to 75 mg twice daily if creatinine clearance is less than 30 mL per minute.
• Bleeding is its most common and serious adverse effect, and there is no antidote.
• Coagulation monitoring is not required when administrating Dabigatran etexilate mesylate.

Anticoagulants: Mechanism of Action

• Mechanisms vary depending on the specific drug.
• Act on various points in the clotting cascade.
• Prevent intravascular thrombosis by reducing blood coagulability.
• They do not break down existing clots.

Anticoagulants: Indications

• Used to prevent clot formation in situations where it is likely.
• These situations include myocardial infarction, unstable angina, atrial fibrillation and indwelling devices.
• Also used when blood flow is slowed or may pool, such as after major orthopedic surgery or during prolonged immobility.

Anticoagulants: Contraindications

• Include drug allergy and any active bleeding process or high risk of bleeding.
• Warfarin is strongly contraindicated during pregnancy.
• Other anticoagulants have lower pregnancy risk ratings.
• Low-molecular-weight heparins are contraindicated in patients with indwelling epidural catheters due to the risk of epidural hematoma.

Anticoagulants: Adverse Effects

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

Heparin-Induced Thrombocytopenia

• Type I is a gradual reduction in platelets, where heparin therapy can generally continue.
• Type II involves an acute drop in platelets (more than 50% reduction from baseline), where heparin therapy must be stopped.
• Clinical manifestations include thrombosis, which can be fatal.
• Treatment involves thrombin inhibitors such as bivalirudin and argatroban.
• Incidence ranges from 5 to 15% in patients.
• It is more common with bovine than porcine heparins.

Treatment: Toxic Effects of Heparin

• Treatment aims to reverse the underlying cause.
• Symptoms include hematuria, melena (blood in stool), petechiae, ecchymoses, and gum or mucous membrane bleeding.
• Stop the drug immediately upon toxicity.
• Administer intravenous (IV) protamine sulphate.
• 1 mg protamine reverses effects of 100 units of heparin, and 1 mg protamine should be administered for each milligram of low-molecular-weight heparin given.

Treatment: Toxic Effects of Warfarin

• Discontinue the warfarin.
• The liver may take 36 to 42 hours to resynthesize enough clotting factors to reverse effects.
• Administer Vitamin K1 (phytonadione) to hasten return to normal coagulation.
• High doses (10 mg) of intravenous vitamin K can reverse anticoagulation within 6 hours.
• Caution with Vitamin K: Warfarin resistance may last up to 7 days following administration.
• Treat severe bleeding with transfusions of human plasma or clotting factor concentrates.
• Intravenous Vitamin K carries a risk of anaphylaxis, lowered by diluting and administering it over 30 minutes.
• Giving the injectable form orally is common.

Drug Interactions: Anticoagulants

• Interactions are often complex and significant.
• Enzyme inhibition of metabolism, displacement of drug from inactive protein binding sites may cause issues.
• Decreased vitamin K absorption/synthesis in the large intestine , and platelet count or activity, can interfere with anticoagulants.

Heparin Sodium

• Is a natural anticoagulant derived from the lungs or intestinal mucosa of pigs.
• Dosages range from 10 to 10,000 units/mL.
• For DVT prophylaxis, administer 5,000 units subcutaneously two or three times a day, without monitoring when used for prophylaxis.
• Weight-based protocols are common.
• Continuous IV infusion is required when heparin is used therapeutically .
• Measure activated partial thromboplastin time (aPTT) at least every 6 hours until therapeutic effects are seen.

Heparin Flushes

• Heparin Leo comes with a small vial of aqueous heparin IV flush solution
• Risk of heparin-induced thrombocytopenia led most institutions to switch to 0.9% normal saline to flush heparin-lock IV ports.
• Heparin flushes in concentration 100 units/mL are still standard for central catheters.

Warfarin Sodium (Coumadin)

• Warfarin is the most commonly prescribed oral anticoagulant.
• Therapy needs careful monitoring of prothrombin time (PT) and international normalized ratio (INR).
• A normal INR (without warfarin) is 0.8 to 1.2.
• A therapeutic INR on warfarin is 2 to 3.5, based on the condition (atrial fibrillation, thromboprevention, prosthetic heart valve).
• Dietary considerations and variations in certain genes (CYP2CP and VKORC1) are important for this therapy.
• Age, dose maintenance, the INR and the use of other natural health products are also to be considered.

Antiplatelet Drugs

• Prevent platelet adhesion to surfaces and other platelets.
• Examples are 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

• Produces antithrombotic effects.
• Adverse effects can be serious due to the risk of bleeding.
• Effects vary according to the specific drug.

Aspirin

• Available in combination with many prescription / nonprescription drugs and product names.
• Unique contraindication: Avoid in children/adolescents with flu-like issues because it is connected with Reye's syndrome, which is a rare, acute and sometimes fatal condition that impacts the liver and central nervous system (CNS).

Clopidogrel Bisulphate Plavix

• Plavix is among the most prescribed.

Thrombolytic Drugs

• Designed to break down, or lyse, preformed clots, especially in the coronary arteries.
• Older drugs include streptokinase and urokinase.
• Current drugs are alteplase (Activase) and tenecteplase (TNKase).

Thrombolytic Drugs: Mechanism of Action

• These medications activate the fibrinolytic system to rapidly break down clots in blood vessels.
• They activate plasminogen, converting it to plasmin, which then lyses the thrombus.
• Plasmin is a proteolytic enzyme.
• Thrombolytics mimic the body’s natural clot destruction process.

Thrombolytic Drugs: Indications

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

Thrombolytic Drugs: Adverse Effects

• Bleeding can be internal, intracranial, or superficial.
• Other effects include nausea, vomiting, hypotension, hypersensitivity, anaphylactoid reactions, and cardiac dysrhythmias, which can be dangerous.

Antifibrinolytic Drugs

• Prevent the lysis of fibrin.
• Promote clot formation to stop or reduce bleeding.
• Are used for the prevention and treatment of excessive bleeding.
• Also used as a treatment for hemophilia A or type I von Willebrand’s disease with desmopressin.
• Aprotinin (Artiss, Trasylol), tranexamic acid (Cyklokapron), and desmopressin acetate (DDAVP) are all antifibrinolytic drugs.

Antifibrinolytic Drugs: Adverse Effects

• Reactions are uncommon and generally mild.
• Rare reports of thrombotic events.
• Other effects include dysrhythmia, orthostatic hypotension, bradycardia, headache, dizziness, fatigue, hallucinations, convulsions, nausea, vomiting, abdominal cramps, and diarrhea.

Nursing Implications

• Prior to administering any coagulation modifier drug, nursing assessments should include:
  • Patient history: including medication and allergy history.
  • Reviewing any contraindications.
  • Recording baseline vital signs and relevant laboratory values.
  • Checking for potential drug interactions.
  • Documenting any history of abnormal bleeding conditions.

Heparin: Nursing Implications

• Intravenous heparin dosages must be double-checked with another nurse.
• Subcutaneous doses must be given subcutaneously, not intramuscularly.
• Administer subcutaneous doses in areas of deep subcutaneous fat, rotating sites
• Do not inject subcutaneous doses within 5 cm of the umbilicus, abdominal incisions, open wounds, scars, drainage tubes, stomas, or areas of bruising/oozing.
• Should not aspirate or massage site of subcutaneous heparin injections, as it can cause hematoma formation.
• IV heparin doses can be given by bolus or IV infusions.
• Anticoagulant effects are immediate.
• Daily monitoring aPTT is required.
• Protamine sulphate is the antidote for excessive anticoagulation.

Low-Molecular-Weight Heparins: Nursing Implications

• Give the agent subcutaneously in the abdomen.
• Injection sites should be rotated with each dose.
• Consider protamine sulphate as an antidote to excessive anticoagulation.

Warfarin (Coumadin): Nursing Implications

• Warfarin therapy may be started while the patient is still on heparin until PT/INR levels indicate adequate anticoagulation.
• Full therapeutic effect takes several days.
• Regular PT/INR monitoring and follow-up appointments are necessary.
• Vitamin K is the antidote.
• Many herbal products have potential interactions and increased bleeding.

Warfarin (Coumadin): Nursing Implications - Herbal Products

• Avoid natural products such as: capsicum pepper, garlic, ginger, ginkgo, St. John’s wort, Feverfew because they can lead to severe interactions with Warfarin.

Anticoagulants: Patient Education

• The education should include the importance of regular laboratory testing, signs of abnormal bleeding, and measures to prevent bruising, bleeding, and tissue injury.
• Wearing a medical alert bracelet
• Avoiding foods high in vitamin K (tomatoes, dark leafy green vegetables)
• Consulting the physician before taking other drugs or over-the-counter products, including herbals, are key considerations and education for the patient.

Antiplatelet Drugs: Nursing Implications

• Nursing implications are the same as for anticoagulants.
• Check for any drug–drug interactions, adverse reactions to report, and monitoring for abnormal bleeding.

Thrombolytic Drugs: Nursing Implications

• Strict adherence to the manufacturer’s guidelines for preparation and administration is critical.
• Monitor IV sites for bleeding, redness, and pain.
• Keep track of bleeding from gums, mucous membranes, nose, and injection sites.
• Watch for signs of internal bleeding; changes in blood pressure, increased pulse or restlessness.