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Anticoagulants Grugs
- 3. Coagulation • Platelets and clotting factors are responsible for initiating coagulation. When an injury occurs, platelets (thrombocytes) immediately migrate to the damaged area. Because platelets stick to each other (aggregation) and to the vessel walls (adhesion), they form a plug around the injured tissue. Plasma clotting factors reach the platelet plug and interact with each other to form a stable blood clot. Hemostasis is the balance between clot formation and clot breakdown that occurs throughout the day. 1-3
- 4. Coagulation • Intrinsic Pathway: – Damage to vessels – Physical/chemical activation within the blood (blood components within the vessels) • Extrinsic Pathway – Damage outside of vessels – Tissue factor released by damaged cells activation outside the blood (blood escaped from vessels) 1-4
- 5. 1-5
- 6. Coagulation • Coagulation happens in a four-stage process: –Stage 1 –Stage 2 –Stage 3 –Stage 4 27-6
- 7. Stage 1 • A substance known as thromboplastin is produced. • The intrinsic system requires many clotting factors and platelets to stimulate production of thromboplastin. • The extrinsic system requires factor VII and tissue extract, a substance that is released from injured cells. Regardless of the pathway involved, once thromboplastin is produced, clotting proceeds automatically. 1-7
- 8. Stage 2 & 3 • Stage 2. Thromboplastin converts prothrombins to thrombin. • Stage 3. Thrombin converts fibrinogen to fibrin and activates several clotting factors (V, VIII, XIII, and protein C). – Fibrin is the primary element of a blood clot, and these activated factors build a fibrin mesh that holds the platelets (developing clot) together. – Require calcium ions in order to function efficiently. Vitamin K is required for the synthesis of many of the factors in the coagulation pathway. – Usually, the clot is dissolved once its function has ended. 1-8
- 9. Stage 4 • Stage 4: Plasmin is formed from the conversion of plasminogen by tissue plasminogen activator (tPA). Plasmin is an enzyme that acts upon the fibrin elements to produce a more soluble product. 1-9
- 10. Drug Class Prototype Action Effect Anticoagulant Parenteral Heparin Inactivation of clotting factors Prevent DVT Oral Warfarin Decrease synthesis of clotting factors Prevent DVT
- 11. Anticoagulants Heparin Structure Mucopolysaccharide Metabolism Partially in the liver by heparinase to uroheparin, which has only slight antithrombin activity. 20-50 % is excreted unchanged. {The heparin polysaccharide chain is degraded in the gastric acid} administered IV or SC. Heparin should not be given IM }danger of hematoma formation{.
- 12. Unfractionated heparin (UFH) Mol weight: 3000-30000 Mechanism of action: •Primarily: interaction with antithrombin III: alters the molecular configuration of antithrombin III, making it 1,000 to 4,000 times more potent as an inhibitor of thrombin formation: limits conversion of fibrinogen to fibrin: prolongs aPTT •Also inhibits the effects of factor Xa on the coagulation cascade & limits platelet aggregation. Half-life: IV: 1 hr SC: 3 hrs.
- 13. Dosing options. Preoperative: 5,000U 2 hours before surgery. {The single preoperative dose seems to be as effective as multiple preoperative doses}. Postoperative: 8 to 12 hrs after surgery & every 8 to 12 hrs until the patient is fully ambulatory. Antidote: Protamine sulphate Monitor: aPTT Use in pregnancy: {does not cross the placenta} safe
- 15. Half-life: 4 hrs, by any route: longer dosing interval. Bioavailability More consistent than that of UFH: dosing is based on lean body mass & Less thrombocytopenia. Use in pregnancy: Does not cross the placenta: safe. Dosing options. Prophylaxis: Once a day Therapy: Twice-daily. Enoxaparin is an LMWH Moderate risk: 20 mg/d High risk: 40 mg/d. •Advantage Decreased need for monitoring
- 17. Oral anticoagulants Warfarin Structure: small, lipid-soluble molecules, Structurally related to vitamin K, isolated from clover leaves Mechanism: • Inhibits production of active clotting factors • blocks the Vitamin K-dependent glutamate carboxylation of precursor clotting factors e.g. FII, VII, IX , X Metabolism: • Absorption: rapid • Binds to albumin • Clearance is slow: 36 hrs • Delayed onset: 8-12 hr {T1/2 of clotting factors in plasma}
- 18. WarfarinHeparin OralParentral onlyAbsorption 7.6-13.9 LPlasma vol (0.07 L/kg)Vol of distribution HepaticHepatic metabolism & uptake by reticulo endothelial system Also by thrombin & other clotting factors Metabolism/Clearance 36-42 hr50-90 minElimination t1/2 99.4% bound to albuminBound to antithrombin III & other serine proteases Protein binding 1.5 mg/L0.2-0.4 U/mlPlasma concentration (therapeutic) Bleeding Skin necrosis Drug interactions Bleeding Thrmbocytopenia Osteoporosis Side effects •Mild: hold 1-2 doses, observe, restart at lower dose •Severe: Vit K or fresh frozen plasma •Mild: Slow or stop infusion •Severe: Protamine 1 mg/100 u of estimated heparin remaining in body Treatment of bleeding
- 19. Contraindications • Pregnancy • Risk of hemorrhage > clinical benefits –Active hemorrhage (e.g., GI bleed) –Uncontrolled alcohol/drug abuse –Unsupervised dementia/psychosis
- 20. Effective Patient Education • Teach basic concepts of safe, effective anticoagulation • Discuss importance of regular INR monitoring • Counsel on use of other medications, alcohol • Develop creative strategies for improving compliance –Evening, same time –Dosettes, blisterpacks
- 21. Warfarin Tablets • 1mg – pink • 2mg – lavendar • 2.5mg – green • 3mg – tan • 4mg – blue • 5mg – peach • 6mg – teal • 7.5mg – yellow • 10mg - white
- 22. Warfarin Management • Serious bleeding, – Hold Warfarin – Give Vitamin K1 10mg slow IV plus fresh plasma or prothrombin complex concentrate, depending on urgency – Repeat Vitamin K1 every 12 hours as needed • Life-threatening bleeding, – Hold warfarin – Give prothrombin complex concentrate (or recombinant factor VIIa as an alternative) supplemented with vitamin K1 10mg slow IV; repeat as needed
- 23. Clexane (enoxaparin) • Clexane injection contains the active ingredient enoxaparin, which is a type of medicine called a low molecular weight heparin. It is used to stop blood clots forming within the blood vessels. • Blood clots normally only form to stop bleeding that has occurred as a result of injury to the tissues. The clotting process is complicated and begins when blood cells called platelets clump together and produce chemicals that activate the clotting process. The final part of this process involves a substance called thrombin being activated to produce a protein called fibrin. Fibrin binds the platelets together, forming a blood clot. This is the body’s natural way of repairing itself.
- 24. • Sometimes, however, a blood clot can form abnormally within the blood vessels. This is known as a thrombus. It can be dangerous because the clot may detach and travel in the bloodstream, where it becomes known as an embolus. The embolus may eventually get lodged in a blood vessel, thereby blocking the blood supply to a vital organ such as the heart, brain or lungs. This is known as a thromboembolism.
- 25. • Enoxaparin is used to prevent and treat these types of abnormal blood clots. It works by inactivating thrombin in the clotting process described above. This stops the formation of fibrin, the essential component of blood clots. The medicine is administered by injection under the skin (subcutaneous injection). • Enoxaparin can also be used to prevent blood clotting when it is filtered through a kidney dialysis machine.
- 26. What is it used for? • Treatment of blood clots in the veins of the leg (deep vein thrombosis). • Treatment of blood clots that travel to the lungs (pulmonary embolism). • Preventing these types of blood clots (thromboembolic disorders), particularly following general surgery or surgery on the bones (orthopaedic surgery), or in people bedridden due to illness. • Treating blood clots in the coronary arteries in unstable angina and heart attack (myocardial infarction). • Preventing blood from clotting when it is filtered through an 'artificial kidney' (haemodialysis) machine as part of the management of kidney failure. •
- 27. • Warning! • During treatment with this medicine you should have regular blood tests to monitor the numbers of blood cells called platelets in your blood. • Your doctor may also want to monitor the level of potassium in your blood while you are having this medicine, particularly if treatment lasts for longer than 7 days.
- 28. Use with caution in • People over 80 years of age. • People who are underweight or overweight. • Decreased kidney function. • Chronic kidney failure. • Decreased liver function. • People who have previously developed a reduced platelet count in the blood due to treatment with heparin or low molecular weight heparin (heparin-associated thrombocytopenia). • People with problems stopping bleeding. • History of peptic ulcer. • Recent stroke caused by a blood clot in the brain (ischaemic stroke). • Severe uncontrolled high blood pressure (hypertension). • Diabetes. • Diabetes affecting the eyes (diabetic retinopathy). • People who have recently had eye surgery. • People who have recently had surgery on the brain or spinal cord (neurosurgery). • People having spinal or epidural anaesthesia. • High level of potassium in the blood (hyperkalaemia). • Increase in the acidity of the blood (metabolic acidosis). •
- 29. Not to be used in • Allergy to heparin or other low molecular weight heparins. • Bacterial infection of the heart valves and the lining surrounding the heart (bacterial endocarditis). • Active major bleeding. • Conditions with a high risk of uncontrolled bleeding, for example the blood clotting disorder haemophilia, or the conditions listed below. • Active peptic ulcer. • Recent stroke caused by bleeding in the brain (haemorrhagic stroke). • Reduced platelet count in the blood (thrombocytopenia). • This medicine is not recommended for use in children.
- 30. Side effects • Bleeding. • Pain and irritation at the injection site. • Blood clots which form a solid swelling at the injection site (haematoma). • Decrease in the number of platelets in the blood (thrombocytopenia). • Major bleeding (haemorrhage), for example in the abdomen or inside the skull. • Alteration in results of liver function tests. • High blood potassium level (hyperkalaemia). • Death of skin cells (necrosis) at the site of injection. • Blood clots in the spinal cord (intraspinal haematoma) in people also having spinal or epidural anaesthesia. • Osteoporosis (a reduction in bone density leading to bones which may fracture easily) has occurred after long-term treatment with a similar medicine called heparin. It is possible that this could happen with Clexane.
- 31. ANTICOAGULATION DRUGS: WHAT NURSES NEED TO KNOW • The goal of activity is to provide nurses and nurse practitioners with knowledge and skills to manage patients on anticoagulant drugs. After reading this article, you will be able to: • Identify common indications for use of anticoagulants • Describe monitoring requirements • Consider important safety implications to help prevent complications • Discuss patient/family educational needs related to anticoagulants
- 32. • Monitoring and Safety Implications Heparin requires close monitoring because of its narrow therapeutic index, increased risk for bleeding, and potential for heparin-induced thrombocytopenia (HIT). Monitoring includes thorough head-to-toe patient assessments for potential side effects, and laboratory monitoring. • Bleeding is the most common side effect, and may present in a variety of ways: epistaxis, gum bleeding, hemoptysis, hematuria, melena or hemorrhage. Undiagnosed and uncontrolled bleeding may lead to cardiovascular collapse or cardiac tamponade. In the event of major bleeding, heparin should be stopped, and, if necessary, protamine sulfate may be administered.
- 33. • Patient Education • Patients on anticoagulant therapy must be educated about their increased risk for bleeding, monitoring for bleeding, managing bleeding if it occurs, and drug- specific information. • Monitoring and Safety Implications Warfarin has a narrow therapeutic index, so monitoring includes assessment for potential side effects, laboratory tests for dose titration, and vigilance for potential drug and food interactions. • Bleeding is the most common side effect, most frequently in the GI tract. Warfarin may cause skin necrosis, or cholesterol embolus syndrome. Specific patient variables may impact drug metabolism. For example, active hepatic disease, certain drugs, and old age are likely to enhance the response to warfarin.
- 34. Conclusion Anticoagulation drugs can be life-saving. Nurses must carefully assess, closely monitor, and comprehensively educate the patient receiving anticoagulation drugs to ensure the full benefit of anticoagulation therapy and to minimize potential harm.