Prosthetic Valve Thrombosis

Prosthetic valve thrombosis is thrombus on a mechanical or bioprosthetic valve that restricts leaflet motion (obstructive thrombosis) or lies on the valve without obstruction.

It is more frequent with mechanical valves, especially in the mitral and tricuspid position, with an obstructive rate of about 0.3 to 1.3% for each patient year. Subclinical leaflet thrombosis is detected in a notable minority of bioprosthetic valves on CT.

Risk factors are subtherapeutic INR (the most important), interruption of anticoagulation for procedures, pregnancy, atrial fibrillation, low ejection fraction, a hypercoagulable state, older valve designs, mitral or tricuspid position, non-adherence, use of a direct oral anticoagulant in a mechanical valve, and infection.

Tricuspid prostheses thrombose more often than left sided valves.

Pathophysiology. Flow disturbance across the valve, exposure of tissue factor and platelet activation promote thrombus at the hinges and leaflets. Thrombus immobilises leaflets (a stuck leaflet), causing obstruction, regurgitation, or both, and it can embolise.

Fibrous pannus can coexist and behaves differently, as it does not respond to anticoagulation or lysis.

• Obstructive thrombosis, left sided: dyspnoea, orthopnoea, acute pulmonary oedema, cardiogenic shock, low cardiac output, a muffled or absent mechanical click, and a new murmur (diastolic rumble in the mitral position, systolic ejection murmur in the aortic position). Onset may be abrupt or over days to weeks.
• Right sided: peripheral oedema, ascites, hepatomegaly, fatigue.
• Embolism: stroke, transient ischaemic attack, peripheral or visceral embolism. This may be the presenting event.
• Non-obstructive thrombus: often found on imaging after an embolic event or unexplained rise in INR variability.

Red flags.

• Acute pulmonary oedema or shock
• Absent or muffled valve closure click
• INR under target with new symptoms
• Embolic stroke or limb ischaemia
• Thrombus area of 0.8 cm2 or more, or length of 10 mm or more
• Pregnancy with a mechanical valve
• Fever (infective endocarditis)
• Interruption of anticoagulation, or a direct oral anticoagulant in a mechanical valve

• Transthoracic echocardiography. Compare with the baseline postoperative study. Aortic prosthesis: peak velocity over 3 m/s (4 m/s or more is significant), mean gradient over 20 mm Hg (35 mm Hg or more is significant), Doppler velocity index under 0.30 (under 0.25 is significant), acceleration time over 100 ms. Mitral prosthesis: peak E velocity over 1.9 m/s, mean gradient over 5 mm Hg, pressure half time over 130 ms, velocity time integral ratio over 2.5.
• Transoesophageal echocardiography. Thrombus size (area and length), leaflet motion, valve regurgitation and left atrial appendage thrombus. A thrombus area of 0.8 cm2 or more, or length of 10 mm or more, is large.
• Cine fluoroscopy. Leaflet opening angles (normal tilting disc 60 to 70 degrees, bileaflet 80 to 90 degrees).
• ECG-gated CT. Separates thrombus (usually under 90 Hounsfield units) from pannus (usually over 145 Hounsfield units).
• Laboratory. INR, platelet count (heparin induced thrombocytopenia), haemoglobin, LDH, haptoglobin, CRP, troponin, and blood cultures.
• Timing of symptoms and INR history help separate recent thrombus (days to weeks) from chronic obstruction (pannus).

Differential diagnosis.

• Pannus ingrowth
• Patient prosthesis mismatch
• Infective endocarditis with vegetation
• Structural degeneration of a bioprosthesis
• Paravalvular leak
• Tissue or suture entrapment of a leaflet
• High flow states (anaemia, pregnancy, sepsis)
• Left atrial or ventricular thrombus or myxoma
• Dynamic left ventricular outflow obstruction
• Other causes of pulmonary oedema

Left sided obstructive thrombosis, critically ill (NYHA class III to IV) or large thrombus. Emergency valve surgery (thrombectomy or replacement) is first choice when available and operative risk is acceptable. Operative mortality is high in critically ill patients, in the order of 10 to 20%. Thrombolysis is used when surgery is unavailable, immediately unsafe or declined.

Right sided obstructive thrombosis. Thrombolysis is first line.

Thrombolysis regimens (with a contraindications check):

• Alteplase 25 mg intravenously as an infusion over 6 hours without a bolus, repeated at 24-hour intervals if thrombus persists (up to 3 infusions). Start unfractionated heparin when the infusion ends.
• Alternative: alteplase 10 mg bolus, then 90 mg over 90 minutes (maximum total 100 mg), followed by an unfractionated heparin infusion at 18 units/kg/h, adjusted to anti-Xa 0.3 to 0.7 IU/mL.
• Streptokinase 1,500,000 units over 60 minutes where alteplase is unavailable. Avoid if streptokinase was given in the previous 12 months or after a recent streptococcal infection.
• Contraindications: active internal bleeding, previous intracranial haemorrhage, ischaemic stroke within 6 months, intracranial neoplasm, major surgery or trauma within 3 weeks, uncontrolled hypertension, bleeding disorder. Pregnancy is a relative contraindication.
• Success is about 70 to 85%, with embolism or stroke in about 5 to 10% and major bleeding in about 5%.

Small thrombus in a stable patient (area under 0.8 cm2 or length under 10 mm, no obstruction or mild obstruction):

• Unfractionated heparin infusion at 18 units/kg/h, adjusted to anti-Xa 0.3 to 0.7 IU/mL or an aPTT ratio of 1.5 to 2.5, no fixed maximum. Omit the bolus when thrombolysis is planned or bleeding risk is raised. Check platelets on days 5 to 14 for heparin induced thrombocytopenia.
• Repeat transoesophageal echocardiography at 1 to 2 weeks. Move to surgery or thrombolysis if thrombus fails to resolve, grows or embolises.

Warfarin after treatment.

• Warfarin 5 mg orally once daily at the start (2 to 3 mg in older adults, liver impairment or interacting drugs), adjusted to the INR target, no fixed maximum. INR every 2 to 3 days at the start, weekly until stable, then every 4 to 12 weeks. Overlap with heparin until the INR is in range on 2 readings 24 hours apart.
• INR target: mechanical aortic bileaflet valve without risk factors, 2.5 (2.0 to 3.0). Mitral or tricuspid mechanical valve, or any mechanical valve with risk factors (atrial fibrillation, previous thromboembolism, ejection fraction under 35%, hypercoagulable state, older generation valve), 3.0 (2.5 to 3.5).
• Add aspirin 75 to 100 mg orally once daily after embolism or thrombosis despite an adequate INR. Direct oral anticoagulants are contraindicated with mechanical valves.
• Address the cause: adherence, interacting drugs, dietary change, interrupted therapy.

Bioprosthetic valve thrombosis. Warfarin to an INR of 2.5 (2.0 to 3.0) for at least 3 months and repeat imaging. If haemodynamics are compromised, emergency valve surgery is first choice, with alteplase 25 mg intravenously over 6 hours without a bolus when surgery is unavailable.

Pannus. Does not respond to anticoagulation or lysis. Surgery for significant obstruction.

Special groups.

• Pregnancy: manage in a specialist centre. Use enoxaparin 1 mg/kg subcutaneously every 12 hours with peak anti-Xa 0.8 to 1.2 IU/mL 4 to 6 hours after the dose, or unfractionated heparin, and avoid direct oral anticoagulants. Warfarin is teratogenic in weeks 6 to 12, and its use at other times is decided by the specialist team. Thrombolysis is used for life threatening obstruction when surgery is not immediately available.
• Renal impairment: avoid enoxaparin or monitor anti-Xa closely.

Monitoring. Haemodynamics, neurological state and bleeding during lysis, with aPTT or anti-Xa every 6 hours on heparin, and fibrinogen and haemoglobin daily. Repeat echocardiography within 24 hours of lysis and daily until the gradients normalise. INR every 4 to 12 weeks once stable. Echocardiography at 1 month and after any new symptoms.

Referral and escalation. Refer immediately to a cardiac surgical centre with a heart team. Emergency for shock, pulmonary oedema or embolism.