Cardiovascular Revision Part 1.1

# Cardiovascular Revision Part 1.1 ## Oral Anticoagulants - 5 different oral anticoagulants are licensed in the UK: - Warfarin - Apixaban - Edoxaban - Rivaroxaban - Dabigatran ### Deep Vein Thrombosis (DVT) - A blood clot that develops within a deep vein in the body, usuall...

# Cardiovascular Revision Part 1.1 ## Oral Anticoagulants - 5 different oral anticoagulants are licensed in the UK: - Warfarin - Apixaban - Edoxaban - Rivaroxaban - Dabigatran ### Deep Vein Thrombosis (DVT) - A blood clot that develops within a deep vein in the body, usually in the leg. ### Pulmonary Embolism (PE) - A blood clot gets stuck in a capillary in the lung, blocking blood flow to part of the lung. ### Symptoms of DVT and PE - Pain and swelling in one (sometimes both) legs. - Tenderness. - Changes to skin colour and temperature. - Vein distension (enlargement, dilation, or ballooning effect). ### Predisposing Risk Factors for VTE - Age. - Obesity. - Family history. - Concomitant conditions. - Medication such as hormone replacement therapy (HRT), contraception with oestrogen. - Pregnancy. ## VTE Risk Assessment - Malignant disease. - Varicose veins (swollen and enlarged veins that usually occur on the legs and feet) with phlebitis (inflammation of a vein near the surface of the skin). - Critical care admission. - Significant co-morbidities. ## 3 Factors That Influence Thrombus Formation - Blood flow (e.g. Atrial fibrillation (AF)). - Surfaces in contact with blood (e.g. mechanical heart valves). - Clotting components (e.g. Factor V Leiden, Protein C and protein S deficiencies). - Factor V Leiden - Mutation of one of clotting factors in blood -> increase blood clot rate. ## VTE Prevention ### Mechanical VTE Treatment - Anti-embolic stockings. ### Pharmacological VTE Treatment - Parenteral: - Low molecular weight heparin (LMWH) - Fondaparinux. - Unfractionated heparin (use in severe renal impairment or renal failure). - Oral: - NOACS (e.g. Rivaroxaban). ## Duration of Prophylaxis VTE Treatment - Major cancer surgery in abdomen or pelvis: 28 days. - Knee/hip surgery: Extended duration. - General surgery: 5-7 days or until sufficient mobility. ## Treatment Of VTE - LMWH or Fondaparinux for 5 days or until INR = 2, or INR is more than 2 for at least a day. - Fondaparinux is a synthetic pentasaccharide that inhibits activated factor X. - Fondaparinux is delivered subcutaneously, and dose is dependent on patient's weight. - Begin oral anticoagulant alongside LMWH or Fondaparinux at the same time. - Warfarin takes a little while to kick into the system. ## Treatment Of VTE In Pregnancy - LMWH (preferred first choice of medication). - Does not cross placenta. - Lower risk of osteoporosis and heparin-induced thrombocytopenia (HIT). - LMWH eliminated rapidly during pregnancy, so dose adjustment may be needed frequently throughout the course. - Treatment should be STOPPED once patient goes into labour. - Seek specialist advice if needed to continue. ## Heparins - Heparins are injected (parenteral anticoagulant) and there are two main forms: - LMWH - Unfractionated heparin. ### Side Effects of Heparins - Haemorrhage. - If occurs, Heparin should be STOPPED immediately. - Protamine sulphate can be given to reverse the effects of Heparins. - Hyperkalaemia. - Inhibits aldosterone secretion. - High risk in patients with diabetes/kidney disease due to accumulation. - Monitor before treatment starts and then at 1 week marks following treatment. - Osteoporosis. - HIT #### LMWH - Platelet level drops sig ~ 35% reduction. - Monitor platelet count before treatment and then following 4/5 days as HIT only tend to occur in 4/5 - 10 days of treatment. - HIT can cause alopecia, rebound hyperlipidaemia (especially with Heparins). - Tinzaparin, Enoxaparin, Dalteparin. Take OD - Act by inhibiting factor Xa. - Longer duration of action. - Lower risk of osteoporosis and HIT. #### Unfractionated Heparin - Act by activating antithrombin. - Antithrombin is protein that acts as the body's own natural anticoagulant. - Part of coagulation cascade that blocks blood clotting mechanism that blocks clotting protein called thrombin. - Shorter duration of action. - Preferred if patient has a high risk of bleeding or renal impairment. - Measure patient's response to Heparin w activated partial thromboplastin time (APTT). #### Increased Risk of Bleeding with Heparins - **In Heparins**, there is an increased risk of bleeding if the patient has: - Thrombocytopenia. - Liver failure. - Concurrent anticoagulants. - Inherited disorders (e.g. haemophilia, Von Willebrand). #### Protamine Sulphate - **Protamine sulphate** can be given to (partially) reverse effects of Heparins. - Binds to Heparins to form stable ionic pair which does not have the anticoagulation activity. ## Warfarin - Warfarin is a vitamin K antagonist, oral anticoagulant and a high risk drug. - Takes 48-72 hours to work. - If immediate anticoagulation is needed Warfarin is given with Heparin to give cover until Warfarin action kicks in. ### Duration of Warfarin Treatment - 6 weeks for isolated calf DVT. - 3 months for VTE provoked by: - Surgery. - Combined oral contraception. - Pregnancy. - Leg plaster. - 3 months plus for VTE unprovoked caused by AF. ### Important to Avoid Warfarin in Pregnancy - Warfarin is teratogenic. - Avoid in pregnancy, especially in the 1st and 3rd trimesters. - Risk of congenital malformations and haemorrhaging. ### Patient Counselling - Yellow treatment book/Anticoagulant alert card - Used to record current INR levels and to tell healthcare professionals what the patient's current dose is. - Take Warfarin at the same time each day. - Notify anticoagulation clinic changes to medication, lifestyle or diet. - Brown tablets = 1mg - Blue tablets = 3mg - Pink tablets = 5mg. - Warfarin dose expressed in milligrams and not number of tablets. - Stopped 5 days before elective surgery. - Patients are advised to stop taking Warfarin and to seek medical attention when there are signs of bleeding (e.g. nose bleed/blood in urine). ### MHRA/CHM – Calciphylaxis - Calciphylaxis – Accumulation of calcium in smaller blood vessels of skin/fat tissues, blood clots. - This can cause skin cells to die due to lack of blood flow. - Patient will report symptoms of painful skin rash. - **Consider STOPPING Warfarin if calciphylaxis is diagnosed.** - Patients at a higher risk of calciphylaxis are patients with kidney failure, on dialysis, or who have had a kidney transplant. ### Warfarin Interactions - Vitamin K antagonist and antivirals - Cause changes in INR. Affects efficacy of warfarin. - OTC oral miconazole gel (Daktarin) and Warfarin - increase in INR and increase in bleeding risk. #### Warfarin Dosing - **If rapid anticoagulation is needed:** - Give 5mg once daily for 2 days. Can be 10 mg OD. - Check INR on day 3. - **Maintenance dose** depends on patient. Some patients' doses can stay the same for 7 days. #### Target INR - Should be within 0.5 units of the patient's INR target (within range). - 2.5 = VTE, AF, MI, cardioversion. - 3 - 3.5 = Mechanical prosthetic heart valves. - 3.5 = Recurrent VTE whilst on anticoagulants, where the anticoagulant control is within target. #### Monitoring While On Warfarin - **Monitor INR:** On alternate days initially, then every 1-2 weeks until stable, then every 3 months. - **Monitor liver function:** Caution in mild to moderate impairment. Monitor before and during treatment. - **Avoid** in severe impairment. - **Monitor renal function:** Caution in mild to moderate impairment. - In severe impairment – Monitor INR more frequently. - **Monitor FBC**, BP, **Thyroid function**: - Warfarin metabolism can be affected by the thyroid function of patients. - Patients on thyroid medications or with hypo/hyperthyroidism should be monitored closely. - These three are key indications for bleeding. #### What To Do When Bleeding On Warfarin - **Major bleeding:** Stop Warfarin. Give IV Phytomenadione (Vitamin K), dried prothrombin complex or fresh frozen plasma. - **Minor bleeding – INR 5.0 or more:** Stop Warfarin. Give SLOW IV Phytomenadione. - **No bleeding but INR more than 8.0:** Stop Warfarin. Give IV preparation Phytomenadione orally. - **No bleeding but INR between 5.0 – 8.0:** Withhold Warfarin for 1 or 2 days. Reduce maintenance doses. ## Novel Oral Anticoagulants (NOACs) - NOACs inhibit specific clotting factors. - **Dabigatran**: Direct thrombin inhibitor. - **Apixaban**, **Edoxaban** and **Rivaroxaban**: Direct factor Xa inhibitor. ### Indication for NOACs - **Rivaroxaban:** - Prophylaxis VTE hip and knee. - Treatment and prevention of recurrent DVT/PE. - **Dabigatran:** Elective knee and hip. - **Apixaban:** - Elective hip and knee. - Treatment DVT/PE - Treatment and prevention of recurrent DVT/PE ### Patient Counselling for NOACs - NOACs come with patient alert card. ### Advantages of NOACs - Easy fix dosage - don't need to adjust dose. - Lower or less bleeding risk. - Predictable effect without the need for regular monitoring - Fewer food and drug interactions. ### Bleeding Risk With NOACs - Concomitant use of NSAIDs. - Other anticoagulants. - Antiplatelets. - Strong CYP3A4 inhibitors (e.g. Clarithromycin, Erythromycin, Diltiazem, Itraconazole). - SSRI and SNRI. ### Renal Function and NOACs - With use of NOACs, doses needs to be changed with deterioration of renal function. ## Apixaban and Renal Function - No dose adjustment is necessary in people with mild or moderate renal impairment. - **Reduce dose if:** - CrCl = 15-29ml/min (probably half dose) OR - Cr > 133micromol/L PLUS Age 80 years old and older OR Weight < 61kg. - **Avoid** if CrCl < 15ml/min. ## Rivaroxaban and Renal Function - 60% of Rivaroxaban is excreted by the kidneys, so avoid in renal impairment (lead to increased bleeding risk). - Take with or after food for improved absorption. - **Use with caution if CrCl is 15-29 ml/min**. - **Reduce dose if CrCl is 15-49ml/min**. - **Avoid** if CrCl < 15ml/min. ## Dabigatran and Renal Function - 80% of Dabigatran is excreted in the kidneys, so avoid in renal impairment (lead to increased bleeding risk). - No dose adjustment is necessary in mild renal impairment. CrCL = 50-80 ml/min. - **Reduce dose if:** - CrCl = 30-50 ml/min OR - Age 80 years or older OR - High bleeding risk OR. - Also on Verapamil or Amiodarone - **Avoid** if CrCl < 30 ml/min. ## Ischaemic Stroke - Ischaemic stroke - Blood clot obstructs blood supply in the brain. Sudden onset. Can last longer than 24 hours. - Transient ischaemic attack (mini stroke) - Temporary neurological dysfunction. Sudden onset. Lasts <24 hrs. - Haemorrhagic stroke: Weak vessel in brain burst. Blood rush out of brain. Can be caused by hypertension. ### Indicator/Symptoms Of Ischaemic Stroke - Face dropping. - Arm weakness. - Speech difficulty. - Time to call 999. ## Antiplatelets - Antiplatelets are used in ischaemic stroke to decrease platelet aggregation and inhibit thrombus formation. - Antiplatelets are not routinely prescribed for the primary prevention of cardiovascular disease. ### Important Considerations - **Consider** PPI/H2 antagonist to prevent dyspepsia. - Impaired renal and hepatic function = increased risk of gastrointestinal bleeds. ## Intracerebral Haemorrhagic Stroke - **Avoid Aspirin, Statin, and Anticoagulants** - Increases risk of bleeding. - Treat hypertension and take care to avoid hypoperfusion (poor circulation of blood from the heart and lungs to the body's organs). ### Long Term Management For Intracerebral Haemorrhagic Stroke - **Clopidogrel** 75mg daily. - **Aspirin & MR Dipyridamole** (If Clopidogrel CI). - Take tablets 30-60 mins before food. - MR Dipyridamole caps have a 6-week expiry once opened and kept in the original container. - Can give MR Dipyridamole alone if Aspirin CI. - In AF related stroke, consider anticoagulant. - Normally 14 days after having stroke and starting antiplatelet treatment as you dont want to affect neurological effect of stroke. ### Other Management For Intracerebral Haemorrhagic Stroke - Lower cholesterol (add Statin irrespective of serum cholesterol). - Treat hypertension. Not with BB unless indicated for another condition. - Give lifestyle advice.