Deep Venous Thrombosis and Pulmonary Embolism Current Therapy

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Deep Venous Thrombosis and Pulmonary Embolism,contraindicated Guideline recommendations. SORT KEY RECOMMENDATIONS FOR PRACTICE for anticoagulation are divided into phases. initial phase first week after diagnosis long,Clinical recommendation rating References. term phase second week to three months,and extended phase beyond three months 9. Direct acting oral anticoagulants are an alternative A 4 19 20 In the initial phase of anticoagulation a. to vitamin K antagonist therapy warfarin,Coumadin for VTE. decision must be made between using the, Most patients with deep venous thrombosis and B 8 10 11.
vitamin K antagonist warfarin or a direct, selected patients with pulmonary embolism can acting oral anticoagulant If warfarin dabi. be safely treated as outpatients gatran Pradaxa or edoxaban Savaysa is. Inferior vena cava filters should be avoided in B 8 9 26 27 selected concomitant parenteral anticoagu. patients with VTE treated with anticoagulation lation is required for at least five days Guide. If there are no contraindications patients C 8 9 29. lines recommend low molecular weight over,diagnosed with acute VTE should receive. anticoagulation for a minimum of three months unfractionated heparin which is supported. by multiple therapeutic trials showing greater, VTE venous thromboembolism effectiveness and safety and lower mortality 12. A consistent good quality patient oriented evidence B inconsistent or limited However unfractionated heparin is preferred. quality patient oriented evidence C consensus disease oriented evidence usual in patients with severe renal insufficiency. practice expert opinion or case series For information about the SORT evidence. rating system go to http www aafp org afpsort high bleeding risk hemodynamic instability. or morbid obesity 7 9 Apixaban Eliquis and,rivaroxaban Xarelto do not require con. and not evidence based In a hemodynamically unsta comitant use of heparin at initiation The administration. ble patient with a high probability of VTE intravenous and dosing of anticoagulants are included in Table 1 13. thrombolytic therapy can be considered 9 Similarly if If a patient is admitted discharge should occur when. there is a delay in obtaining a definitive diagnostic test in the patient has clinically improved and is hemodynami. a hemodynamically unstable patient with a high prob cally stable The initial treatment phase first week can. ability of VTE parenteral anticoagulation should be be completed in the outpatient setting after thorough. considered until a diagnosis is confirmed patient education on anticoagulation therapy During. After diagnosis most patients with DVT can be treated the initial three months of anticoagulation patients. as an outpatient except in cases of limb ischemia sig should be evaluated periodically for adherence and com. nificant comorbidities e g end stage renal disease plications of treatment especially bleeding Frequency of. functional limitations high bleeding risk or nonadher physician visits is individualized based on patient knowl. ence concerns Anticoagulation is not recommended for edge and adherence and on which therapy is selected. isolated distal DVTs i e confined to calf veins unless If warfarin is used patients require careful education. the patient is symptomatic has risk factors for extension on food and drug interactions and the importance of. e g unprovoked DVT prior VTE or develops exten regular office visits to check international normalized. sion of DVT on serial imaging for two weeks 8 10 11 ratio until a steady state is achieved For selected patients. Evidence supports outpatient treatment of PE if the physician directed home based international normal. risk of nonadherence is low and the patient is clinically ized ratio monitoring provides a convenient alternative. stable has no contraindications to anticoagulation such to office visits 6. as recent bleeding severe renal or liver disease or platelet If a direct acting oral anticoagulant is selected no. count of less than 70 103 per mm3 70 109 per L and routine laboratory monitoring is required but dose. feels capable of managing the disease at home 8 10 Patients adjustments may be needed for certain agents Table 113. with PE who are hemodynamically unstable e g those Patients must be educated about adherence and what to. with hypotension or evidence of shock should be admit do in the event of bleeding. ted to an intensive care unit and systemic thrombolytic. therapy may be considered 9 Direct Acting Oral Anticoagulants. In 2012 rivaroxaban became the first direct acting oral. Anticoagulation Choices anticoagulant approved by the U S Food and Drug. Once VTE is diagnosed and the patient is stabilized Administration for treatment of DVT and PE Several. if needed anticoagulation should be initiated unless others followed These agents belong to two classes. 296 American Family Physician www aafp org afp Volume 95 Number 5 March 1 2017. Deep Venous Thrombosis and Pulmonary Embolism, Table 1 Anticoagulants for the Treatment of Pulmonary Embolism and Deep Venous Thrombosis.
Drug Dosage Half life Renal dosing,Direct factor Xa inhibitors. Apixaban 10 mg orally twice daily for 7 days followed by 12 hours 27 renal clearance. Eliquis 5 mg orally twice daily 2 5 mg orally twice daily if at least 1 criterion is. met serum creatinine 1 5 mg per dL 133 mol,per L or more age 80 years or older weight. 60 kg 132 lb 4 oz or less, Edoxaban Adults 60 kg 60 mg orally 10 to 14 50 renal clearance. Savaysa Adults 60 kg 30 mg orally once daily following hours CrCl 15 to 50 mL per minute per 1 73 m2 0 25 to. 5 to 10 days of initial therapy with a parenteral 0 83 mL per second per m2 30 mg orally once. anticoagulant per day,CrCl 15 mL per minute per 1 73 m2 avoid use. CrCl 95 mL per minute per 1 73 m2 1 59 mL,per second per m2 avoid use.
Rivaroxaban 15 mg orally with food twice daily for 21 days 5 to 9 66 renal clearance. Xarelto then 20 mg orally once daily hours CrCl 15 to 80 mL per minute per 1 73 m2 0 25 to. 1 34 mL per second per m2 avoid use in,patients receiving a combined P glycoprotein and. moderate cytochrome P450 3A4 inhibitor unless, the potential benefit justifies the potential risk. CrCl 30 mL per minute per 1 73 m2 0 50 per,second per m2 avoid use. Direct thrombin inhibitors, Dabigatran 150 mg orally twice daily following 5 to 10 days of 12 to 17 80 renal clearance. Pradaxa initial therapy with a parenteral anticoagulant hours CrCl 30 mL per minute per 1 73 m2 dosing. recommendations are not provided by the,manufacturer.
CrCl 50 mL per minute per 1 73 m2 avoid use,in patients taking a P glycoprotein inhibitor. Indirect factor Xa inhibitors, Fondaparinux Concomitant treatment with warfarin should be 17 to 21 100 renal clearance. Arixtra initiated as soon as possible hours CrCl 30 to 50 per minute per 1 73 m2 use with. Adults 50 kg 110 lb 4 oz 5 mg subcutaneously caution and consider reducing dosage by 50. once daily CrCl 30 per minute per 1 73 m2 avoid use. Adults 50 to 100 kg 110 lb 4 oz to 220 lb 7 oz,7 5 mg subcutaneously once daily. Adults 100 kg 10 mg subcutaneously once daily,Low molecular weight heparin. Dalteparin 100 units per kg subcutaneously every 12 hours 3 to 5 Primarily renally eliminated. Fragmin or 200 units per kg subcutaneously once daily hours CrCl 30 per minute per 1 73 m2 monitor anti. Enoxaparin 1 mg per kg subcutaneously every 12 hours or 4 5 to 7 Primarily eliminated renally. Lovenox 1 5 mg per kg subcutaneously every 24 hours hours CrCl 30 per minute per 1 73 m2 reduce dosage. to 1 mg per kg once daily, CrCl creatinine clearance INR international normalized ratio.
direct thrombin inhibitors dabigatran and direct factor pharmacokinetics Other benefits compared with warfa. Xa inhibitors apixaban edoxaban and rivaroxaban 14 17 rin include fewer dietary restrictions fewer drug interac. There are logistic benefits of direct acting anticoagu tions and relatively fixed dosing Rivaroxaban should be. lants compared with warfarin primarily that no regu taken with food and it interacts with cytochrome P450. lar monitoring is required because of their predictable 3A4 and P glycoprotein inhibitors Dabigatran may be. March 1 2017 Volume 95 Number 5 www aafp org afp American Family Physician 297. Deep Venous Thrombosis and Pulmonary Embolism, Table 1 Anticoagulants for the Treatment of Pulmonary Embolism and Deep Venous Thrombosis. Drug Dosage Half life Renal dosing,Fibrinolytics, Alteplase 100 mg intravenous infusion over 2 hours 30 to 45 Approximately 80 renal clearance. Activase minutes No dosage adjustments are needed, Unfractionated 80 units per kg intravenous bolus then 1 to 5 Primarily cleared and metabolized by the. heparin maintenance infusion of 18 units per kg per hours reticuloendothelial system. hour of intravenous continuous infusion further Adjust dosage based on activated partial. adjustment per nomogram thromboplastin time,8 000 to 10 000 units subcutaneously every. 8 hours or 15 000 to 20 000 units,subcutaneously every 12 hours.
Vitamin K antagonists, Warfarin Initially 5 mg orally or intravenously once daily 21 to 89 Up to 92 of the orally administered dose is. Coumadin consider lower dose in geriatric malnourished hours recovered in the urine primarily as metabolites. debilitated patients or patients with congestive No adjustment continue to dose based on INR. heart failure liver failure or high bleeding risk,Clinical practice guidelines recommend 10 mg. orally once daily for the first 2 days for patients. healthy enough to be treated as outpatients,Warfarin should be started on the same day as. heparin low molecular weight heparin or,fondaparinux and continued for 5 days and. until the INR is 2 for at least 24 hours, CrCl creatinine clearance INR international normalized ratio.
Information from reference 13, affected by P glycoprotein inducers or inhibitors Dose idarucizumab Praxbind a monoclonal antibody that. adjustment may be required for these medications 4 binds dabigatran in the serum 21 In instances of major. The drawbacks of direct acting anticoagulants are bleeding there are case series and expert recommenda. cost 349 to 430 per month U S average wholesale tions to guide interventions For patients experiencing a. price 18 and uncertainties regarding management of devastating bleed such as intracranial hemorrhage treat. major bleeding or emergent surgery Direct acting anti ment includes stopping the direct acting anticoagulant. coagulants have shorter half lives than warfarin and initiating supportive therapy and administering acti. missed doses or premature discontinuation increases the vated charcoal antifibrinolytic agents and prothrombin. risk of thrombotic events Also because elimination of complex concentrate 22 Hemodialysis should be consid. direct acting anticoagulants is more dependent on renal ered for severe cases in patients taking dabigatran but it is. function than with warfarin dose adjustment may be not effective for patients taking factor Xa inhibitors. required for patients with chronic kidney disease 19 20 The The ACCP recommends the use of direct acting anti. initial studies of direct acting anticoagulants excluded coagulants over warfarin for VTE treatment in patients. several important patient populations such as pregnant without cancer weak recommendation based on moder. women patients with an active cancer diagnosis and ate quality evidence per the ACCP grading system 8 For. patients who are morbidly obese thus there are no data patients with recurrent VTE who are already taking an. to guide therapy in these groups 19 20 oral anticoagulant low molecular weight heparin is rec. Only dabigatran has a commercially available reversal ommended over other oral anticoagulants For patients. agent although other reversal agents are in development with recurrent VTE while taking a low molecular weight. In 2015 the U S Food and Drug Administration approved heparin the dose should be increased by 25 to 33. 298 American Family Physician www aafp org afp Volume 95 Number 5 March 1 2017. Deep Venous Thrombosis and Pulmonary Embolism, weak recommendations based on moderate to poor Treatment Duration. quality evidence per the ACCP grading system 8 The risk of VTE recurrence is greatest in the first year. For patients transitioning from one anticoagulant to after the event and remains elevated indefinitely com. another specific recommendations for conversion are pared with the general population Lifetime recurrence. available in eTable A and from the U S Food and Drug rates for DVT ranges from 21 to 30 depending on. Administration s approved drugs section http www the population 10 28 Risk of VTE is increased by patient. access data fda gov scripts cder daf factors such as active cancer and thrombophilia. Long term anticoagulation reduces the risk of recur. Thrombolysis rent VTE but results in more bleeding events Consid. Because of the high risk of bleeding thrombolysis is ering this trade off it is critical that the duration of. restricted to specific circumstances Expert consensus anticoagulation therapy be individualized based on the. guidelines support thrombolytic therapy in patients with patient s risk of recurrence vs risk of bleeding Risk fac. persistent hypotension or shock secondary to acute PE 9 tors for bleeding are summarized in Table 2 9 If there. Also when patients with acute PE who are on anticoagu are no contraindications current guidelines recom. deep venous thrombosis should be treated with anticoagulation but asymptomatic patients may be monitored with serial imaging for two weeks and treated only if there is extension Am Fam

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