INTRODUCTION — Anticoagulation is required in patients with mechanical heart valves and in selected patients early after bioprosthetic valve implantation or after bioprosthetic valve thrombosis. (See 'Antithrombotic therapy for prosthetic valves' below.)
This topic will review management of overanticoagulation, bleeding, and invasive procedures in patients with prosthetic valves, focusing primarily on issues arising in patients with mechanical valves receiving an anticoagulant (typically, a vitamin K antagonist) to reduce the risk of prosthetic valve thrombosis and thromboembolism. (See 'Antithrombotic therapy for prosthetic valves' below.)
Indications for antithrombotic therapy for prosthetic valves and management of antithrombotic therapy in pregnant patients with prosthetic heart valves are discussed separately. (See "Antithrombotic therapy for mechanical heart valves" and "Antithrombotic therapy for surgical bioprosthetic valves and surgical valve repair" and "Transcatheter aortic valve implantation: Antithrombotic therapy" and "Management of antithrombotic therapy for a prosthetic heart valve during pregnancy".)
ANTITHROMBOTIC THERAPY FOR PROSTHETIC VALVES — Antithrombotic therapy to prevent valve thrombosis and thromboembolic events in patients with prosthetic heart valves differs among the various types of valves. This in turn affects bleeding risk.
Details are summarized briefly here and discussed in detail in the linked topic reviews:
●Mechanical valves – Patients with mechanical valves require anticoagulation. This generally involves early bridging with heparin after placement of the valve and long-term therapy with a vitamin K antagonist (VKA; eg, warfarin). The target international normalized ratio varies with valve position, valve type, and thromboembolic risk factors (table 1). (See "Antithrombotic therapy for mechanical heart valves".)
●Bioprosthetic valves – Patients with bioprosthetic valves are generally treated with long-term antiplatelet therapy, with only patients with low bleeding risk with surgical bioprosthetic valves completing a three- to six-month period of anticoagulation after valve implantation. Less commonly, patients with bioprosthetic valves are treated with anticoagulation to treat bioprosthetic valve thrombosis. (See "Bioprosthetic valve thrombosis, thromboembolism, and obstruction: Management", section on 'Long-term management after an event'.)
While long-term anticoagulation is not generally required for a bioprosthetic valve, many patients with bioprosthetic valves have concurrent indications for anticoagulation (eg, atrial fibrillation) and may be treated with a direct oral anticoagulant or VKA, depending upon the indication for anticoagulation and other clinical factors.
•Surgical bioprosthetic valves – The choice of antithrombotic therapy during the first three to six months after surgical bioprosthetic valve implantation depends upon the patient's bleeding risk. Patients with low bleeding risk are treated with anticoagulation (generally with early heparin bridging followed by VKA therapy); if the bleeding risk is elevated, patients are treated with aspirin 75 to 100 mg instead of anticoagulation. After the first three to six months, all patients are treated with aspirin 75 to 100 mg per day. Management of patients with concurrent indications for anticoagulation is discussed separately. (See "Antithrombotic therapy for surgical bioprosthetic valves and surgical valve repair", section on 'With a concurrent indication for anticoagulation'.)
•Transcatheter aortic valves – Patients receiving a transcatheter aortic valve who do not have a concurrent indication for dual antiplatelet therapy or anticoagulation are treated with single antiplatelet therapy (generally aspirin). Management of patients with concurrent indications for antithrombotic therapy is discussed separately. (See "Transcatheter aortic valve implantation: Antithrombotic therapy".)
General approaches to reducing bleeding risk in individuals receiving anticoagulants are presented separately. (See "Risks and prevention of bleeding with oral anticoagulants", section on 'Approaches to risk reduction'.)
MANAGEMENT OF OVERANTICOAGULATION WITHOUT BLEEDING — The risk of major bleeding with vitamin K antagonist (VKA; eg, warfarin) begins to rise steeply when the international normalized ratio (INR) increases to values ≥5 (figure 1), although some patients have bleeding at therapeutic or even subtherapeutic INR levels. However, rapid reversal of anticoagulation, leading to subtherapeutic INRs, increases the risk of mechanical valve thrombosis and thromboembolism. Given these concerns, we suggest an individualized approach based largely on expert opinion that is similar to the 2020 American Heart Association/American College of Cardiology and 2021 European Society of Cardiology valve guideline recommendations [1,2]:
●INR >5 and ≤10 – For patients who are not bleeding and have an INR >5 and ≤10, the VKA should be temporarily discontinued to permit a gradual reduction in INR. The INR should be monitored closely so that the VKA can be restarted when the INR reaches the therapeutic range.
We do not routinely administer low-dose vitamin K in this setting [1]. A meta-analysis of three randomized trials of low-dose vitamin K therapy (compared with administration of Fresh Frozen Plasma, placebo, or no treatment) in patients with mechanical valves and supratherapeutic INR found uncertain benefit and uncertain harm [3]. Similar results were reported in a meta-analysis of six trials in individuals with INRs of 4.5 to 10 (not limited to patients with mechanical heart valves) [4].
●INR >10 – If the INR is >10 and there is no bleeding, the VKA should be temporarily discontinued and the INR monitored. If the patient is deemed to be at high risk of bleeding (table 2) (see "Risks and prevention of bleeding with oral anticoagulants", section on 'Risk factors for bleeding'), one or two doses of 1 to 2.5 mg of oral vitamin K may be administered, with close INR monitoring (eg, daily for at least two weeks [2]).
Low-dose (1 to 2.5 mg) vitamin K safely reduces the excessive degree of anticoagulation more rapidly than simply withholding the VKA, and, in contrast to higher doses of vitamin K, low-dose vitamin K does not make the patient temporarily resistant to further therapy with VKA. (See "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'INR >10 without bleeding'.)
Oral vitamin K replacement has been preferred to the intravenous route, as it will result in a more gradual decrease in the INR and lessen the chance of a subtherapeutic INR and risk of thromboembolism. However, low-dose intravenous vitamin K (1 to 2.5 mg) can be used to safely lower INRs >6 [5]. Since vitamin K is equally effective via oral and intravenous routes and there is a risk of anaphylaxis with the intravenous route, the oral route is generally preferred.
Additional information and supporting data for vitamin K are presented separately. (See "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'Vitamin K dose, route, formulation'.)
MANAGEMENT OF BLEEDING
Bleeding in patients with mechanical valves — In patients with a mechanical valve who are bleeding with a therapeutic or supratherapeutic international normalized ratio (INR), the risk of serious complications from major bleeding (eg, not amenable to local control, life threatening, causing hemodynamic instability) must be weighed against the risk of valve thrombosis.
●Identify and treat the cause – Bleeding in patients who are therapeutically anticoagulated or overanticoagulated often comes from an anatomic or pathologic cause (eg, gastrointestinal lesion, urinary infection) that should be identified and treated.
●Reverse anticoagulation as needed – Management decisions depend upon the severity of bleeding and the risk of worsening bleeding. (See "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'Treatment of bleeding'.)
•Life-threatening bleeding inaccessible to local control – If the risk from continued bleeding that is inaccessible to timely local control (particularly intracerebral hemorrhage) is considered greater than the risk of valve thrombosis, reversal of anticoagulation should be accomplished by the use of the combination of both:
-Vitamin K – The oral or intravenous vitamin K dose may vary from 2.5 to 10 mg. For life-threatening bleeding with no concern for restarting the vitamin K antagonist (VKA) within the next week, a 10 mg intravenous dose is used [1]. Reversal of VKA (eg, warfarin) with vitamin K takes several hours and is not sufficient to treat life-threatening bleeding; the main purpose is to maintain reversal of anticoagulation after a rapid, short-acting therapy such as prothrombin complex concentrate (PCC) wears off.
and
-PCC (or FFP) – Either a four-factor PCC or, if a PCC is not available, Fresh Frozen Plasma (FFP) is used to immediately reverse the effect of the VKA (eg, warfarin). Four-factor PCC (PCC containing significant levels of coagulation factors II, VII, IX, and X), when available, is preferred over three-factor PCC or FFP (table 3). Advantages of PCC over FFP include ability to administer more rapidly due to lower volume, and less risk of volume overload and other transfusion reactions. Additional information about PCC and supporting evidence are presented separately. (See "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'PCC products'.)
A four-factor PCC has been approved by the US Food and Drug Administration for urgent reversal of VKA in patients with acute major bleeding. Three-factor PCCs contain low concentrations of factor VII and thus may require coadministration of FFP to lower an elevated INR effectively. (See "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'Serious/life-threatening bleeding' and "Reversal of anticoagulation in intracranial hemorrhage", section on 'Warfarin'.)
The INR should be monitored frequently (eg, at 30 minutes and every four to six hours until INR normalization [2]), and doses of vitamin K may be repeated at 12-hour intervals if needed.
Repeated dosing of PCC has not been studied in this setting and may increase the risk of thrombosis. Thus, a second dose of PCC should be given only for life-threatening bleeding with persistent INR elevation. If intravenous vitamin K is given as advised, the INR should decline substantially within six to eight hours, and further PCC dosing is not generally required.
Recombinant activated factor VII (rFVIIa) is not recommended for VKA reversal in individuals with mechanical heart valves because of lack of evidence of efficacy and concern for risk of thrombosis, especially in older individuals [6,7]. A study in healthy controls given VKA demonstrated correction of the INR and other coagulation tests with rFVIIa but no decrease in bleeding in a skin punch biopsy model [7].
●Other types of bleeding – For other types of bleeding, management is based upon the severity of bleeding, accessibility of control, and the estimated risk of worsening bleeding.
For minimal bleeding, VKA (eg, warfarin) is held. Decisions regarding whether to administer low-dose vitamin K and more aggressive reversal measures depend upon the risk of worsening bleeding. (See "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'Treatment of bleeding'.)
●Resumption of anticoagulation – The optimal time to resume anticoagulation (and to start heparin prior to VKA therapy) after a major bleeding episode is uncertain. Considerations include the site and cause of the bleeding and interventions performed to stop the bleeding or treat its cause. Decisions are individualized with close consultation between the cardiologist or cardiac surgeon and clinicians treating the bleeding episode. (See "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'Resumption of anticoagulation after bleeding'.)
Bleeding in patients with bioprosthetic valves — For most patients with a bioprosthetic valve who are receiving anticoagulation, the purpose of the anticoagulation is for a concurrent condition, such as atrial fibrillation, rather than to prevent valve thrombosis.
Consequently, the approach to management of bleeding in most anticoagulated patients with bioprosthetic valves is generally the same as the approach for other anticoagulated patients receiving a VKA or a direct oral anticoagulant. (See "Management of warfarin-associated bleeding or supratherapeutic INR" and "Management of bleeding in patients receiving direct oral anticoagulants".)
For patients receiving anticoagulation with VKA for a bioprosthetic valve (eg, for bioprosthetic valve thrombosis), the approach to bleeding is the same as described above for patients with mechanical valves. (See 'Bleeding in patients with mechanical valves' above.)
EMERGENCY PROCEDURES WITH SIGNIFICANT BLEEDING RISK — For a patient with a mechanical valve who is anticoagulated with a vitamin K antagonist (VKA) and requires emergency surgery or an invasive procedure that entails a significant bleeding risk, reversal of anticoagulation is often required. The decision to use a reversal agent depends upon the urgency of the surgery or procedure and the thrombotic and bleeding risks, with the understanding that both risks are increased in this setting. In patients with suspected acute coronary syndrome, the potential risk of promoting thrombogenicity is a consideration in determining whether to reverse anticoagulation prior to a procedure. (See "Periprocedural management of antithrombotic therapy in patients receiving long-term oral anticoagulation and undergoing percutaneous coronary intervention", section on 'Periprocedural bleeding'.)
If used, reversal of VKA can be accomplished by administering an intravenous four-factor prothrombin complex concentrate (PCC) [1] or Fresh Frozen Plasma (FFP) [1,2]. Given the results of the randomized trial discussed below, four-factor PCC is preferred in this setting [8]. In addition, low-dose (1 or 2 mg) oral vitamin K may be administered, which has a slower onset of effect but has a longer-lasting effect on VKA reversal than FFP or PCC.
Support for a four-factor PCC over FFP comes from an open-label, randomized multicenter trial involving 181 patients (16 percent with prosthetic heart valves or prosthetic joints) who were receiving a VKA, had an international normalized ratio (INR) >2, and needed rapid reversal of anticoagulation for an urgent surgical or invasive procedure; in this trial, a single dose of a four-factor PCC was shown to be superior to FFP in rapid INR reduction and hemostasis [8]. All patients received vitamin K, and the doses of PCC and FFP were based on INR and patient weight. Effective hemostasis was achieved in 90 percent in the PCC group versus only 75 percent of patients in the FFP group (difference 14.3 percent, 95% CI 2.8-25.8). The safety profile was similar for both treatments, with thromboembolism in 7 percent of PCC-treated patients versus 8 percent of FFP-treated patients. However, the applicability of this study to patients with prosthetic heart valves may be limited since most patients were receiving VKA therapy for other indications.
Additional evidence for PCC versus FFP for VKA reversal in the general population is presented separately. (See "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'Evidence for efficacy'.)
PLANNING FOR INVASIVE PROCEDURES
Use a standardized protocol and close communication — A standardized procedure for perioperative anticoagulant therapy may aid efficient evidence-based patient management [9,10].
Components generally include:
●Advance planning – The plan for perioperative anticoagulant management should include whether and when anticoagulant interruption will occur and whether and when bridging heparin therapy will be administered during the period that the international normalized ratio (INR) level is subtherapeutic. The decision on whether to bridge is based upon the risk of thromboembolic complications (including valve thrombosis and thromboembolism) and the risk of bleeding, as discussed below. (See 'High thromboembolic risk / bridging' below.)
●Calendar – Patients and providers should be provided with a calendar or clearly presented timeline outlining the timing of anticoagulant changes and INR testing.
●Postoperative care and education – Appropriate education should be provided on postoperative hemostasis. If outpatient low molecular weight heparin is prescribed, it should be accompanied by education on heparin administration including injection technique, provided to the patient, family/caregivers, and other clinicians involved in the patient's care, so that all involved are aware of the plan for discontinuing heparin (if present) and resuming oral anticoagulation.
Avoid elective surgery soon after valve surgery — The risk of thromboembolism is highest in the first few months after mechanical or bioprosthetic valve replacement or valve repair. One method to reduce thromboembolic risk is to wait at least three to six months after surgical mechanical or bioprosthetic valve replacement and at least three months after surgical mitral valve repair for elective noncardiac surgery, when feasible. (See "Antithrombotic therapy for surgical bioprosthetic valves and surgical valve repair", section on 'Approach for surgical bioprosthetic valves' and "Antithrombotic therapy for mechanical heart valves", section on 'Early heparin bridging'.)
Assessing bleeding and thrombotic risks — Decisions regarding anticoagulation management in a patient anticoagulated for a prosthetic valve who requires surgery or other invasive procedure are based upon assessment of the risk of bleeding and the risk of thromboembolic complications.
The discussion here applies primarily to patients with mechanical valves, since anticoagulation for a bioprosthetic valve is indicated only in patients with low bleeding risk during the first three to six months after implantation and in patients with bioprosthetic valve thrombosis, with management considerations similar to those for mechanical valves. (See "Antithrombotic therapy for surgical bioprosthetic valves and surgical valve repair" and "Bioprosthetic valve thrombosis, thromboembolism, and obstruction: Management".)
The approach to patients with bioprosthetic valves who are anticoagulated for concurrent conditions (such as atrial fibrillation) is the same as the general approach described separately. (See "Perioperative management of patients receiving anticoagulants", section on 'General approach' and 'Risk of bleeding' below and 'Risk of thromboembolism' below.)
The assessment of bleeding and thromboembolic risks is used to decide whether to interrupt anticoagulation and whether to administer bridging heparin while long-term anticoagulation is interrupted (algorithm 1). (See 'Risk of bleeding' below and 'Risk of thromboembolism' below.)
●Minimal bleeding risk – Vitamin K antagonist (VKA) therapy is generally continued for procedures in which bleeding is unlikely or easily controlled.
●Greater than minimal bleeding risk – The VKA is generally interrupted if the bleeding risk for the procedure is more than minimal.
•Low or moderate thromboembolic risk – Among patients with interrupted VKA therapy with low or moderate thromboembolic risk, bridging heparin is not used.
•High thromboembolic risk – Among patients with interrupted VKA therapy, those with high thromboembolic risk are treated with bridging heparin therapy.
Since limited evidence is available, the recommendations presented here are based largely on expert opinion and are similar to recommendations in the 2020 American College of Cardiology/American Heart Association valve guidelines [1], the 2021 European Society of Cardiology valve guidelines [2], and the 2022 American College of Chest Physicians guideline for perioperative management of antithrombotic therapy [9].
Risk of bleeding — This includes assessment of procedural (table 4A-B) and patient risk factors for bleeding. (See "Perioperative management of patients receiving anticoagulants", section on 'Estimating procedural bleeding risk'.)
Risk of thromboembolism — This includes assessment of procedural and patient risk factors for thromboembolic complications (including the type, location, and number of mechanical heart valves) (table 5) [9]. (See "Perioperative management of patients receiving anticoagulants", section on 'Estimating thromboembolic risk'.)
●Low risk – The presence of a bileaflet aortic mechanical valve with no other thromboembolic risk factors is classified as low risk.
●Moderate risk – The presence of a bileaflet mechanical aortic valve with one or more major risk factors for stroke (atrial fibrillation, prior stroke or transient ischemic attack, hypertension, diabetes, heart failure, or age >75 years) is classified as moderate risk.
●High risk – The following are among the clinical settings associated with high risk:
•Mechanical aortic valve plus an additional thromboembolic risk factor (eg, prior thromboembolism [within the previous three months or perioperative]).
•Older generation mechanical aortic valve (tilting-disc or caged ball).
•Any mechanical mitral, tricuspid, or pulmonic valve.
PROCEDURES WITH MINIMAL BLEEDING RISK
Skin, dental, and eye procedures — For patients with mechanical valves who are undergoing minor surgical or other invasive procedures in which bleeding is unlikely or can be easily controlled (eg, minor dermatologic procedure, dental cleaning, simple treatment of dental caries, or eye surgery for cataract removal or glaucoma), vitamin K antagonist (VKA) anticoagulation can generally be continued with a therapeutic international normalized ratio (INR). Similar recommendations are included in the American College of Cardiology/American Heart Association, European Society of Cardiology, and American College of Chest Physicians guidelines [1,2,9].
In preparation for procedures during which VKA will be continued, it is important to confirm that the INR does not exceed the therapeutic range prior to the procedure (exact timing of testing is individualized). (See "Perioperative management of patients receiving anticoagulants" and "Management of anticoagulants in patients undergoing endoscopic procedures".)
For a minor dental procedure (eg, tooth extraction or endodontal [root canal] procedure), we suggest continuing the VKA with coadministration of an oral antifibrinolytic agent (eg, tranexamic acid 4.8 percent administered off label as an oral rinse of 5 mL [swish for one minute and spit] taken 5 to 10 minutes before the procedure and three to four times daily for one to two days after the procedure). (See "Perioperative management of patients receiving anticoagulants".)
Pacemaker or ICD surgery — VKA therapy is generally continued in patients undergoing pacemaker or implantable cardioverter-defibrillator (ICD) surgery. In patients at moderate to high risk of thromboembolism undergoing nonemergency surgery for pacemaker and ICD surgery, the BRUISE CONTROL trial, which randomly assigned these patients to heparin bridging or continued VKA, found that device pocket hematomas were significantly more common in the heparin-bridging group [11]. The study included many patients with mechanical heart valves, and in those patients, an INR of up to 3.5 was allowed. This study supports continued VKA therapy rather than bridging anticoagulation in patients undergoing cardiac implantable electronic device insertion. (See "Perioperative management of patients receiving anticoagulants", section on 'Settings in which continuing the anticoagulant may be preferable'.)
Cardiac catheterization — The acceptable level of anticoagulation in patients with prosthetic heart valves undergoing cardiac catheterization depends on the specific procedure being performed. Many patients with a mechanical valve undergoing cardiac catheterization do not require bridging anticoagulation with heparin, since no or only minor modification of VKA dosing is required for low- to moderate-risk procedures. (See 'Procedures with more than minimal risk of bleeding' below.)
The management of anticoagulation in patients undergoing percutaneous coronary intervention (PCI) is discussed separately. Similar considerations apply to patients undergoing diagnostic coronary angiography for suspected coronary artery disease. (See "Periprocedural management of antithrombotic therapy in patients receiving long-term oral anticoagulation and undergoing percutaneous coronary intervention".)
The following comments address coronary angiography and two other clinical settings: cardiac catheterization performed to evaluate conditions other than coronary syndromes (eg, valvular heart disease or chronic heart failure) and procedures that pose high risks of bleeding such as transseptal or left ventricular puncture.
Preprocedural management — In each patient, we assess the risk of periprocedural bleeding if the anticoagulant is continued and the risk of thrombosis if anticoagulant is withheld. When time allows, we suggest the following approach to preprocedural management of anticoagulation:
●Low- to moderate-risk procedures – For procedures with low to moderate risk of bleeding (table 4A-B) (eg, right heart catheterization and/or coronary angiography), we measure the INR at least two days in advance of the procedure. We make adjustments to the VKA dose to allow the INR to be at the lower end of the target range (eg, 2.5; or just below 2 when risk of bleeding is higher) the morning of the procedure.
•Upper extremity access – For procedures with a low bleeding risk, such as coronary angiography from a radial artery approach and/or right heart catheterization from a forearm or antecubital vein, no modification of VKA dosing may be needed. Arterial and venous access via an upper extremity site may allow for reduced risk of major access-related bleeding in patients with an INR of 1.5 to 3.
•Femoral access – For procedures anticipated to involve placement of a large sheath in the femoral artery, we allow the INR to fall below 2 at the time of the procedure.
●High-risk procedures – For higher-risk procedures such as transseptal or left ventricular puncture (table 4A-B) in patients with an INR maintained between 2.5 to 3.5, we suggest holding the VKA at least four to six days to allow the INR to fall to the normal (not anticoagulated) range [12]. As noted above, individual responses to discontinuation of anticoagulation vary widely, so careful monitoring is required, including INR testing on the day before and the day of the procedure. If the INR is 1.5 to 1.9 on the day before the procedure, administration of a low dose of oral vitamin K (eg, 1 to 2.5 mg) on the day before the procedure is likely to reduce the INR to 1.4 or less on the day of the procedure [10].
The role of bridging anticoagulation with heparin prior to a procedure in selected patients with risk factors for thrombosis is discussed below. (See 'High thromboembolic risk / bridging' below.)
Intraprocedural management — Intraprocedural anticoagulant management involves continued weighing of the risks and benefits of anticoagulation, including the following considerations:
●Preference for radial arterial and/or forearm/antecubital venous access over femoral access for anticoagulated patients.
●Management of intraprocedural unfractionated heparin based upon INR at the time of the procedure.
●Minimizing use of vitamin K and prothrombin complex concentrate (PCC; or Fresh Frozen Plasma if four-factor PCC is unavailable). (See 'Emergency procedures with significant bleeding risk' above.)
VKA can generally be restarted as soon as the procedure is completed.
PROCEDURES WITH MORE THAN MINIMAL RISK OF BLEEDING — For surgical or invasive procedures as anticipated to be associated with more than a minimal risk of bleeding (ie, with low, moderate, or high bleeding risk), interruption of anticoagulation (vitamin K antagonist [VKA]) is generally advised. The decision on whether or not to bridge is based upon patient and procedural risk factors for thromboembolism (table 5).
Low or moderate thromboembolic risk — For patients with low to moderate thromboembolic risk (eg, a current generation mechanical bileaflet aortic valve and no other risk factors for thrombosis) (see 'Risk of thromboembolism' above) who are undergoing an invasive procedure requiring interruption of anticoagulation, the VKA can generally be temporarily interrupted without bridging while the international normalized ratio (INR) is subtherapeutic [1,9].
●The VKA is stopped approximately three to four days prior to the procedure (aiming for an INR <1.5 at the time of a major surgical procedure) [1]. However, effects of discontinuation of anticoagulation on the INR vary widely, and careful monitoring is required, including INR testing on the day before and the day of the procedure.
●The INR is checked on the day prior to the procedure. If the INR is 1.5 to 1.9 on the day before the procedure, administration of a low dose of oral vitamin K (eg, 1 to 2.5 mg) on the day before the procedure is likely to reduce the INR to ≤1.4 on the day of the procedure [10].
In contrast, high-dose vitamin K should not be routinely administered before invasive procedures since this will significantly delay and reduce the anticoagulant effects of VKA after the procedure.
●The VKA is restarted as soon after the procedure as prudent, typically 12 to 24 hours after the procedure. It will take a few days for the INR to reach a therapeutic level. As noted above, bridging with heparin is not generally required for patients with low or moderate thromboembolic risk.
High thromboembolic risk / bridging — For patients with one or more conditions associated with high thromboembolic risk (eg, a mechanical mitral valve) (see 'Risk of thromboembolism' above) who are undergoing invasive procedures requiring interruption of anticoagulation, bridging heparin is administered if the risk associated with potential thrombotic complications is deemed to exceed the risk of bleeding.
Choice of heparin for bridging — When bridging is required, either subcutaneous low molecular weight heparin (LMWH) or intravenous unfractionated heparin (UFH) is used (table 6). Subcutaneous LMWH is more convenient and may result in a more predictable degree of anticoagulation. When used as a "bridging" therapy in patients with mechanical valve prostheses, LMWH may be more cost-effective than UFH [13,14].
A potential concern is that, if severe bleeding occurs, the effect of LMWH cannot be reversed as easily as that of UFH [15]. (See "Heparin and LMW heparin: Dosing and adverse effects".)
How to bridge
●Stop VKA – The VKA is stopped two to four days prior to the procedure (aiming for an INR <1.5 on the day of a major surgical procedure). The VKA is restarted as soon as bleeding risk allows, typically 12 to 24 hours after the procedure.
●Start heparin – Heparin bridging is started when the INR falls below the therapeutic range (typically, approximately 48 hours prior to the procedure).
•LMWH – Subcutaneous LMWH is administered using therapeutic level, weight-adjusted dosing, twice daily (eg, enoxaparin 100 international units/kg [equivalent to 1 mg/kg] every 12 hours). In patients receiving LMWH heparin for bridging, routine measurement of anti-factor Xa levels is not required [9]. The last dose of LMWH is administered 24 hours before the procedure.
or
•UFH – Intravenous UFH (eg, initial 18 units/kg/hour) is started without a bolus and is adjusted to achieve an activated partial thromboplastin time that is 1.5 to 2 times control. Intravenous UFH is stopped four to six hours before the procedure.
●Postoperative heparin – Use of postoperative heparin bridging while awaiting the VKA to become therapeutic is individualized based upon the risk of bleeding and risk of thrombosis. If used, intravenous UFH or subcutaneous LMWH should be restarted as soon as possible after the procedure, considering both the risk for bleeding and the adequacy of surgical hemostasis.
•Following a relatively minor surgical or other invasive procedure when adequate hemostasis has been achieved, resumption of therapeutic dose UFH or LMWH is suggested after approximately 24 hours.
•Following major surgery or a high bleeding risk surgery or procedure, we resume therapeutic dose UFH or LMWH at least 48 to 72 hours after the procedure and when hemostasis is secure, or we completely avoid LMWH or UFH after the procedure. We do not administer therapeutic dose UFH or LMWH earlier than 48 to 72 hours after a procedure with a substantial bleeding risk. The timing of UFH or LMWH resumption depends on the anticipated bleeding risk and adequacy of postprocedural hemostasis for each patient.
●Postoperative resumption of VKA – VKA therapy is superior to heparin for preventing valve thrombotic complications. Thus, the VKA should be reinstituted as soon as possible after the procedure, as determined in consultation with the surgeon or interventionalist. A typical time of reinitiation is 12 to 24 hours after the procedure and when there is adequate hemostasis. Intravenous UFH or subcutaneous LMWH should be discontinued once the INR has been in the therapeutic range for two consecutive days.
Evidence on perioperative management — Much of the available data on perioperative management of patients with prosthetic valves are from small, uncontrolled case series that often include patients with older-generation prosthetic valves. In these reports, thromboembolic risk was variable, depending upon the type and location of the valve prosthesis and upon a number of patient-specific clinical factors.
●Most patients tolerate short-term interruption of anticoagulation without valve thrombosis or thromboembolism. This was illustrated by the PERIOP2 trial, which enrolled VKA (warfarin)-treated patients undergoing elective procedures; 20.7 percent (304 of 1471) patients had a mechanical valve [16]. All patients received preoperative bridging with dalteparin and were randomly assigned to receive either placebo or dalteparin postoperatively until the INR was ≥2.0. Among patients with a mechanical valve, there were similar rates of major thromboembolism (0 versus 0.7 percent) and major bleeding (2.0 versus 0.7 percent) in the groups without and with postoperative bridging.
●In an earlier meta-analysis of 34 studies and one randomized trial with a total of 12,278 patients (24 percent with a mechanical valve), the risk of thromboembolic events was similar in bridged and nonbridged groups (odds ratio [OR] 0.80, 95% CI 0.42-1.54), but bridging was associated with an increased risk of major bleeding (OR 3.60, 95% CI1.52-8.50) [17].
●Limited data are available on outcomes of bridging therapy in individuals with mechanical valves. In observational studies of patients with mechanical valves receiving perioperative heparin bridging, the pooled incidence of acute thromboembolic complications was 0.9 percent (95% CI 0.2-1.5) and of major bleeding was 2.8 percent (0.8-4.8) [9].
Although the risk of thromboembolic complications during short-term interruption of anticoagulation appears to be low in most patients with mechanical valves, it should be recognized that most cases of valve thrombosis (70 percent in one series) occur during periods of inadequate anticoagulation [18]. (See "Diagnosis of mechanical prosthetic valve thrombosis or obstruction".)
Additional information and supporting evidence for bridging and not bridging in the general population are presented separately. (See "Perioperative management of patients receiving anticoagulants", section on 'Bridging anticoagulation'.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cardiac valve disease".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Prosthetic valves (The Basics)")
●Beyond the Basics topic (see "Patient education: Warfarin (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Anticoagulation – Long-term anticoagulation with a vitamin K antagonist (VKA) is required in patients with mechanical heart valves. Anticoagulation with a VKA for a bioprosthetic valve is indicated only in selected patients early after valve implantation or for valve thrombosis. (See "Antithrombotic therapy for mechanical heart valves" and "Antithrombotic therapy for surgical bioprosthetic valves and surgical valve repair" and "Transcatheter aortic valve implantation: Antithrombotic therapy".)
Some patients with bioprosthetic valves require long-term anticoagulation for concurrent conditions, most often atrial fibrillation. Anticoagulation recommendations then are based on the concurrent condition, not the presence of a bioprosthetic valve. (See "Atrial fibrillation in adults: Selection of candidates for anticoagulation" and "Atrial fibrillation in adults: Use of oral anticoagulants".)
●Balancing risks of overanticoagulation and anticoagulation reversal – The risk of major bleeding with VKAs begins to rise steeply with international normalized ratios (INRs) ≥5.
However, rapid reversal of anticoagulation with subtherapeutic INR increases risks of valve thrombosis and thromboembolism. (See 'Management of overanticoagulation without bleeding' above and "Bioprosthetic valve thrombosis, thromboembolism, and obstruction: Clinical manifestations and diagnosis" and "Diagnosis of mechanical prosthetic valve thrombosis or obstruction".)
●Management of overanticoagulation without bleeding (see 'Management of overanticoagulation without bleeding' above):
•INR 5 to 10 – The VKA should be temporarily held to permit a gradual reduction in INR. The INR is monitored closely and VKA restarted when the INR reaches the therapeutic range. Vitamin K is generally not necessary.
•INR >10 – The VKA should be discontinued. For patients with increased bleeding risk, we suggest one or two doses of oral vitamin K (1 to 2.5 mg per dose) (Grade 2C). Close INR monitoring is required (eg, daily for ≥2 weeks). The VKA is restarted when the INR reaches the therapeutic range.
•Address the cause – Reasons for overanticoagulation should be sought and corrected (or counseling provided) when possible. (See "Biology of warfarin and modulators of INR control", section on 'Risk factors for supratherapeutic INR'.)
●Management of bleeding
•Address cause of bleeding – Bleeding in patients who are therapeutically anticoagulated or overanticoagulated often comes from an anatomic or pathologic cause (gastrointestinal lesion, urinary infection) that should be identified and treated. (See 'Management of bleeding' above.)
•Address anticoagulation - The risk from bleeding must be weighed against the risk of valve thrombosis if VKA is reversed.
-Intracerebral hemorrhage (ICH) – Patients with ICH require reversal. The VKA should be reversed with oral or intravenous vitamin K (2.5 to 5 mg) and either a four-factor prothrombin complex concentrate (PCC), or, if PCC is not available, Fresh Frozen Plasma (FFP). If only a three-factor PCC is available, supplementation with FFP may be needed. (See "Reversal of anticoagulation in intracranial hemorrhage" and "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'Serious/life-threatening bleeding' and "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'PCC products'.)
-Other bleeding – Management is based upon the severity of bleeding, accessibility of control, and estimated risk of worsening. (See "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'Treatment of bleeding'.)
For life-threatening bleeding inaccessible to local control, management is as described above for ICH.
For minimal bleeding, warfarin is held. Decisions regarding use of low-dose vitamin K and more aggressive reversal measures depend on the risk of worsening.
●Emergency procedures – Emergency high bleeding risk procedures typically require anticoagulant reversal, although risks and benefits should be weighed. Rapid reversal is achieved using a four-factor PCC or FFP, plus low-dose vitamin K. (See 'Emergency procedures with significant bleeding risk' above.)
●Elective procedures
•General approach – Advance planning and close communication with patients and providers is needed regarding the timing of anticoagulant changes and follow-up testing. (See 'Use a standardized protocol and close communication' above.)
•Delay after recent valve placement – The risk of thromboembolism is highest in the first few months after mechanical or bioprosthetic valve replacement or valve repair. Waiting at least three months after valve surgery for elective noncardiac surgery, when feasible, may reduce thromboembolism risk. (See 'Avoid elective surgery soon after valve surgery' above.)
•Assessing bleeding and thrombotic risks – Decisions regarding anticoagulant discontinuation and heparin bridging in the patient with a mechanical valve (or anticoagulated to prevent bioprosthetic valve thrombosis) are based on the risks of bleeding and thromboembolism. The tables summarize patient and procedural bleeding risks (table 4A-B) and thromboembolic risks (table 5). (See 'Risk of bleeding' above and 'Risk of thromboembolism' above.)
•Procedures with minimal bleeding risk – For minor procedures in which bleeding is unlikely or easily controlled (eg, minor dermatologic, dental, ophthalmologic), the VKA can generally be continued with a therapeutic INR. (See 'Procedures with minimal bleeding risk' above.)
•Procedures with more than minimal bleeding risk – VKA interruption is generally advised. The figure illustrates an approach to heparin bridging, which is based on patient and procedural risk factors for thromboembolism (algorithm 1). (See 'Low or moderate thromboembolic risk' above and 'High thromboembolic risk / bridging' above.)
Details of bridging are discussed separately. (See "Perioperative management of patients receiving anticoagulants", section on 'General approach'.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges William Gaasch, MD (deceased), who contributed to an earlier version of this topic review.
