© JAPI • DECEMBER 2012 • VOL.

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Case Report

Use of Tenecteplase for Left-Sided Prosthetic Valve

Thrombosis
Vinod Sharma1, Ruchi Singh2, Rekha Mishra3, AP Arora3, LC Gupta3, OP Yadava4

Abstract
Introduction: Prosthetic valve thrombosis (PVT) following cardiac valve replacement in rheumatic heart disease
patients is a common cause for referral to tertiary care centre. Although surgery has been described as the
traditional choice of therapy, thrombolytic therapy has reported high success rates in published literature.
Case report: This is a case report of ten patients with left-sided PVT receiving tenecteplase. The mean dose of
tenecteplase used was 1.01 mg/kg given as IV bolus injection along with enoxaparin, heparin and acenocoumarol.
The diagnosis and response was assessed based on trans-thoracic echocardiography. The reduction in peak
transvalvular gradient was in the range of 46% - 81% and in mean transvalvular gradient was in the range of 50%
- 84%. There was normalization of valve motion in all patients. There was no incidence of mortality, intracerebral
hemorrhage, systemic bleeding or embolism.
Conclusion: To our knowledge, this is the largest published evidence so far showing efficacy and safety of
tenecteplase for PVT.

Introduction All patients had mechanical valves of disc type. The clinical

W ith high prevalence of rheumatic heart disease, there are
large numbers of patients in India undergoing cardiac
valve replacement. Prosthetic valve thrombosis (PVT) is a serious
complication of mechanical prosthetic valves, as it may lead
to life threatening peripheral thromboembolism. The risk of
embolism is greater with the valve in mitral position as compared
to aortic position. Inadequate thromboprophylaxis due to
interruption in oral anticoagulant therapy or recent episodes of
atrial fibrillation are important causes of PVT.1,2
Although surgery has been described as the traditional method
of choice for PVT, thrombolytics have been used successfully in
the past for the resolution of PVT. Thrombolytic therapy has
shown high success rates with low rate of complications and
mortality especially in patients with low clot burden (<0.08 cm2)
and no history of stroke. Further, use of thrombolytics does not
preclude the option of surgery in the event of failure.3
characteristics of patients are depicted in Table 1.
Majority of them were cases of mitral valve thrombosis
except one who had developed aortic valve thrombosis. All
patients were on oral anti-coagulants for thromboprophylaxis
and had a history of interrupted usage or inadequate therapy
in the recent past. The INR at presentation ranged between 2
to 3. There was no history of recent atrial fibrillation in any
patient. The main presenting complaints were sudden onset
breathlessness with or without chest pain and inability to hear
the metallic heart sound. All the patients had NYHA functional
class II/III except for patient no. 3 who had NYHA functional
class IV. Three patients had systemic hypotension and two of
them were in acute pulmonary oedema. The diagnosis of PVT
was made using TTE which showed obstruction to the valve and
restricted valve motion. Mean and peak trans-valvular gradients
(TVG) were measured.

Tenecteplase is a new generation thrombolytic with higher
fibrin specificity, greater resistance to plasminogen activator
inhibitor – I (PAI–I) and longer half life, thus can be given as
a convenient single intravenous bolus injection.4 This is a case
report of ten patients with PVT who received tenecteplase in
our hospital.
Case Report
All patients were diagnosed to have PVT based on clinical
suspicion followed by transthoracic 2D- echocardiography (TTE).
All except two were cases of rheumatic heart disease and had
undergone prosthetic valve replacement 1-12 years back. One
patient had a valvular heart disease of non-rheumatic in origin
and for one patient the previous records were not available.
1
Consultant Cardiologist, 2Jr. Consultant Physician, 3Consultant
Cardiologist (Non Invasive Lab), 3Consultant cardiologist, 3Consultant
cardiologist, 4Chief Consultant Cardiac Surgeon and CEO, National
Heart Institute, New Delhi.
Received: 01.10.2011; Accepted: 04.02.2012
Tenecteplase approximately in the dose of 1 mg/kg was
administered as IV bolus injections except for case no. 9 where
a lower dose was used (Table 1). None of the patients had
contraindications for thrombolytic therapy. Enoxaparin 60 mg
12 hourly SC or IV for 5 days was given to all patients. The dose
of warfarin and acenocoumarol was adjusted according to INR.
TTE was repeated following thrombolysis to assess the valve
motion and TVG.
Symptoms recovered in all the patients within 4-6 hours of
thrombolysis without any history of complication or recurrence.
The post-thrombolysis TTE revealed normal sharp motion of
valve leaflets and reduction in mean as well as peak transvalvular
gradient. The reduction in peak transvalvular gradient was in
the range of 46% - 81% and in mean transvalvular gradient was
in the range of 50% - 84%. At least 50% reduction in the mean
transvalvular gradient was achieved in all patients and in peak
transvalvular gradient in 9 out of 10 patients. The findings on
TTE before and after thrombolysis are depicted in Table 2.
There was no incidence of mortality, intracranial or non-
intracranial bleeding or peripheral embolism in any patient. All
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Table 1: Clinical characteristics of patients with prosthetic valve thrombosis

Body weight
Sr. No Age (yrs) /Sex Prosthesis and type Valve age (yrs) Previous history H/o PVT Present complaints Dose of tnk-tPA
(kg)
RHD, severe Fever, cough,
Mitral, disc, MR and TR; expectoration and
1 30/M 76 2 N 80 mg IV bolus
mechanical hypertension and shortness of breath
AF; moderate PAH since 2-3 days
Sudden onset
RHD, AF with
Mitral and aortic, breathlessness with
2 50/F 74 12 fast ventricular N 80 mg IV bolus
disc, mechanical palpitations since 2
response
hours
Mitral valve
obstruction with Sudden onset
Mitral, disc, left ventricular breathlessness,
3 35/M 92 1 N 100 mg IV bolus
mechanical failure and lower mild fever and
respiratory tract hemoptysis
infection
Mild breathlessness,
Mitral, disc, 2 dose of 50 mg
4 35/M 88 6 RHD with MR Y chest pain and
mechanical IV one hour apart
epigastric pain
Sudden onset
Mitral, disc RHD with MS,
5 39/M 52 <1 N breathlessness since 50 mg IV bolus
mechanical moderate PAH
6 hours
Chest pain, anxiety
Mitral, disc, RHD with MS and
6 37/M 54 3 N and breathlessness 50 mg IV bolus
mechanical mild MR
for 6 hours
Sudden onset
Mitral, aortic, disc, RHD with MS
7 49/M 90 <1 N breathlessness since 100 mg IV bolus
mechanical and AS
half an hour
Shortness of breath,
Mitral, disc, uneasiness, patient
8 40/M 43 4 RHD with MS N 40 mg IV bolus
mechanical unable to hear the
‘click’
Breathing difficulty,
Aortic, disc,
9 50/M 55 18 NA N patient unable to 35 mg IV bolus
mechanical
hear the ‘click’
RHD with severe
Mitral, disc, Breathlessness with
10 38/F 50 1 MS, moderate N 60 mg IV bolus
mechanical minimal exertion
PAH
RHD- rheumatic heart disease, MS – mitral stenosis, MR – mitral regurgitation, AS – aortic stenosis, AR – aortic regurgitation, PAH – pulmonary artery
hypertension, AF – atrial fibrillation, NA – not available , PVT – prosthetic valve thrombosis

the patients were followed up in the outpatient department and
had uneventful recovery.
Discussion
The estimated incidence of prosthetic valve thrombosis is
0.03% - 4.3% per year and is reported to occur in 0.5% - 8% of
the left-sided prosthetic valves and in up to 20% of tricuspid
prostheses. Similar to previous reports, the most important
cause of thrombosis in our cases was interrupted use of oral
anticoagulants.5-7
Use of thrombolytics for left-sided prosthetic valve thrombosis
in literature has shown promising results. Streptokinase has
been reported with clinical resolution rate in the range of
64-92% in various publications.8-10 A review by Koller et al.
reported a clinical success rate of 72% with thrombolytics and
mortality of 9.9%.11 A large meta-analysis including 515 cases
has reported an initial success rate of 84%, a mortality of 5%,
bleeding complications in 3% and systemic embolism in 9%
patients receiving thrombolytic therapy for PVT.12 There is
a large evidence for the use of streptokinase as compared to
urokinase and alteplase and there are no comparative studies so
far showing benefits of one thrombolytic over the other.
In the recent years, tenecteplase has been introduced for the
reperfusion of ST-elevation myocardial infarction and has shown
equivalent efficacy as well as lower risk of systemic bleeding as
compared to alteplase.13 There are few case reports published
showing the successful use of tenecteplase resolution of mitral
and aortic prosthetic valve thrombosis.14-16 To our knowledge,
this is the largest published evidence so far for PVT cases treated
with tenecteplase.
The decision to thrombolyse patients with tenecteplase was
taken, as there are no clear benefits of surgery over thrombolysis
in randomized clinical trials and as majority patients were
hemodynamically stable. This gave a window period to assess
the efficacy with thrombolysis and decide for surgery in case
of failure. There are no clear guidelines on the dosage of
tenecteplase in PVT. The previous case reports have utilized the
doses of 30 mg (0.5 mg/kg as IV infusion) and 40 mg as IV bolus
dose. The average dose in our cases was 1.01 mg/kg [0.63-1.2 mg/
kg]. There was successful recovery of symptoms in all patients
without any adverse outcomes. As the baseline transvalvular
gradients were not available for all patients, we assessed the
response in terms of reduction in TVG following thrombolysis.
Based on the previous evidence, 50% or more reduction in mean
transvalvular gradient with normalization of valve motion can
be taken as a criterion for complete restoration of valve function
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Table 2 : Outcomes of patients with prosthetic valve thrombosis following thrombolysis on 2D echocardiography
Before thrombolysis After thrombolysis
Sr.
Peak TVG Mean TVG Peak TVG Mean TVG Findings
No Findings
(mmHg) (mmHg) (mmHg) (mmHg)
Sharp motion of MVP, LA clot
Obstructed MVP, large LA clot (6.8 x 4
1. 32 20 cm), LVEF = 35-40%, PASP = 70 mmHg
17 5 reduced to 4.8 x 2 cm, LVEF =
40%
Restricted MVP motion, normal AVP,
2. 30 19 14 6 Sharp motion of MVP
PASP = 65 mmHg
Partially obstructed MVP with one
3. 34 24 leaflet motion normal 14 7 Sharp motion of MVP
PASP = 75 mmHg
4. 22 16 Obstructed MVP, LVEF = 40% 7 3 Sharp motion of MVP
5. 27 19 Restricted MVP motion 5 3 Sharp motion of MVP
Partially obstructed MVP, one leaflet
6. 27 12 8 6 Sharp motion of MVP
stuck, PASP = 54 mmHg
7. 32 18 Obstructed MVP, PASP = 70 mmHg 10 5 Sharp motion of MVP
Restricted motion of MVP, AVP
8. 24 19 8 4 Sharp motion of MVP
motion normal, PASP = 50 mmHg
Restricted motion of AVP, distal half Sharp motion of AVP, distal half
9. 48 24 of IVS and apex akinetic, inferior wall 24 11 of IVS and apex akinetic, inferior
moving well , LVEF = 45% wall moving well , LVEF = 45%
Obstruction in the mitral valve Partially obstructed mitral valve
10 30 17 8 4
prosthesis prosthesis
MVP – mitral valve prosthesis, AVP = aortic valve prosthesis, LVEF – left ventricular ejection fraction,, PASP – pulmonary artery systolic pressure, LA- left
atrium, TVG – transvalvular (transprosthetic) gradient, IVS – interventricular spectrum

based on which the success rate in our cases can be assessed
as 100%.2,10 TTE was used for diagnosis and assessment in our
patients which is the most feasible tool available at bedside.
Trans-esophageal echocardiography or fluoroscopy was not
performed due to lack of routine availability.
The doses of tenecteplase as high as 100 mg intravenous bolus
have not reported any hemorrhagic complication in our patients.
This is probably due to higher fibrin specificity associated with
tenecteplase.
Conclusion
This collection of cases provides an evidence for efficacy
for the use of tenecteplase in the treatment of left sided PVT.
However, a randomized controlled clinical study using larger
patient population is needed to assess the efficacy in comparison
with other thrombolytics or surgery and also to decide the
optimal dose of tenecteplase in this regard.
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