J Thromb Thrombolysis (2011) 31:445–448

DOI 10.1007/s11239-010-0524-y

Tenecteplase in the treatment of acute pulmonary

thrombo-embolism
J. S. Bhuvaneswaran • Rajendra Kumar Premchand • S. S. Iyengar •
Rajeev Khare • C. B. Chabra • T. N. C. Padmanabhan • S. K. Sharma •

Alkesh Jain • S. A. Pandian • S. Rajdev • N. Modi • V. Kumar

Published online: 23 October 2010

Ó Springer Science+Business Media, LLC 2010

Abstract This is a retrospective study documenting the Eighteen patients had hypotension which recovered in all
use of tenecteplase in 41 cases of suspected or confirmed patients till the time of discharge (P \ 0.0001). There was
pulmonary embolism receiving in-hospital tenecteplase as a significant reduction in right ventricular systolic pressure
per weight-adjusted dosing in addition to standard heparin in all 18 patients who underwent 2-D echocardiography
and oral anticoagulant therapy. The presenting symptoms both before and after the tenecteplase therapy. Resolution
of dyspnoea, chest pain, hemoptysis and syncope were of pulmonary embolism on CT pulmonary angiography
found in 40 (97.56%), 19 (46.34%), 6 (14.63%) and 9 was documented in only two patients. No bleeding events
(21.95%) patients, respectively. There was one case of or any other adverse events were reported during this study.
mortality who was a 26 yrs old female of postpartum The present study suggests favourable efficacy of tenec-
pulmonary thrombo-embolism with severe hypotension, teplase in patients with suspected or confirmed acute pul-
cyanosis, bilateral crepitations in lungs and pulmonary monary embolism. Although no major adverse events were
hypertension. In the 40 survived patients, there was alle- noted, a large prospective study on the use of tenecteplase
viation of dyspnoea and hemoptysis in all patients. Sig- in pulmonary embolism is suggested.
nificant reduction in tachycardia (P \ 0.0001) and increase
in the oxygen saturation (SaO2) (P \ 0.0001) were seen at Keywords Tenecteplase
Pulmonary embolism

discharge as compared to at the time of presentation. Thrombolytic
Restrospective

J. S. Bhuvaneswaran (&) A. Jain

Department of Cardiology, PSG Hospitals, P.B. No. 1674, Gokuldas Hospital, Indore, India
Peelamedu, Coimbatore 641004, India
e-mail: drbhucbe@[Link] S. A. Pandian
Vadamalayan Hospital, Madurai, India
Rajendra Kumar Premchand
Krishna Institute of Medical Sciences Ltd, Hyderabad, India S. Rajdev
Greater Kailash Hospital, Indore, India
S. S. Iyengar
Department of Cardiology, St. John’s Medial College Hospital, N. Modi
Bangalore, India CHL Apollo Hospital, Indore, India

Rajeev Khare
S. K. Sharma V. Kumar

Vishesh Hospital, Indore, India Shri Vijaya Durga Cardiac Centre, Kurnool, India

C. B. Chabra
Choithram Hospital, Indore, India

T. N. C. Padmanabhan
Krishna Institute of Medical Sciences Ltd, Hyderabad, India

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446 J. S. Bhuvaneswaran et al.

Introduction 162.05 ± 11 cm. The presenting symptoms of dyspnoea,

chest pain, hemoptysis and syncope were found in 40
Pulmonary embolism (PE) is a life-threatening condition (97.56%), 19 (46.34%), 6 (14.63%) and 9 (21.95%)
associated with significant morbidity and mortality. In patients respectively. Thirty-one (75.6%) patients had one
massive pulmonary embolism and consequent right ven- or more risk factors for pulmonary embolism that included
tricular failure, where restoration of pulmonary arterial history of deep venous thrombosis or pulmonary embolism
flow is urgently required, prompt therapeutic intervention in past, hospitalization or surgery or trauma in the pre-
is imperative. Anticoagulation with unfractionated and low ceding 4 weeks, diabetes mellitus, hypertension, smoking
molecular weight heparin has shown to improve outcome and air travel. Eleven (26.83%) patients had an associated
in pulmonary embolism [1]. Thrombolytic therapy has a hypercoagulable state including hyperhomocysteinemia,
potential to produce faster thrombolysis, improve hemo- systemic lupus erythematosus, polycythemia vera, protein
dynamic instability and eliminate the venous thrombi [2]. C deficiency and postpartum state. Twelve patients
Despite the approval of streptokinase, urokinase and alte- (29.27%) had abnormalities in chest X-ray which included
plase for thromolysis in PE, the efficacy of these thromo- consolidation, decreased bronchovascular marking, hazi-
lytics remain unclear due to the high mortality associated ness in the lung fields, signs of pulmonary hypertension
with this condition and lack of large randomized controlled and Hampton’s hump. Fifteen patients (36.58%) had an
trials [3, 4]. evidence of deep venous thrombosis.
Tenecteplase is a third generation thrombolytic with According to Well’s score for pretest probability of
longer plasma half-life, better fibrin specificity, and higher pulmonary embolism, 12 patients had high probability
resistance to inhibition by plasminogen-activator than (Well’s score [6), 28 patients had moderate probability
alteplase [5]. We present the efficacy and safety data of (Well’s score between 2 and 6) and 1 patient had low
weight-adjusted tenecteplase in 41 patients of acute pul- probability (Well’s score \2). The diagnosis of pulmonary
monary embolism. embolism could be confirmed only in 22 (53.66%) patients
using CT pulmonary angiography. In others, pulmonary
embolism was the most likely diagnosis based on Well’s
Patients and methods score, abnormal X-ray findings and evidence of right
ventricular wall stress on 2D-echocardiography. The signs
Tenecteplase is approved for the thrombolysis of myocar- of right heart failure documented were raised jugular
dial infarction by USFDA in 2000 and by the Drug Con- venous pressure (46.34%), hepatomegaly (9.76%) and
troller General of India in 2007. There are few case reports pleural effusion (4.88%). The ECG findings included
and case studies reporting the use of tenecteplase in the S1Q3T3 pattern (68.29%), right bundle branch block
treatment of acute pulmonary embolism [6, 7]. (26.83%), and ST-T changes (26.83%).
The present study is a retrospective study documenting The baseline echocardiography findings included evi-
the use of tenecteplase in 41 cases of suspected and con- dence of thrombus in right atrium (4%), dilated right
firmed pulmonary embolism. All the patients had received ventricle (85.37%), tricuspid regurgitation (60.98%) and
in-hospital weight-adjusted dosage of tenecteplase (Elaxim) evidence of pulmonary artery thrombus (7.32%). Accord-
as prescribed by the manufacturer in addition to standard ing to the ESC 2008 guidelines, numbers of patients with
heparin and oral anticoagulant therapy [8]. Data obtained high, intermediate and low risk of mortality due to pul-
from case records included findings of detailed medical monary embolism were 8 (19.5%), 20 (48.78%) and 13
history, clinical examination and investigations performed. (31.7%)respectively [10].
The outcomes could be assessed in form of improvement Of 41 patients that received weight-adjusted tenectep-
in symptoms of dyspnoea and hemoptysis as well as lase injection, 40 patients survived. There was one case of
improvement in heart rate, blood pressure, oxygen satura- mortality who was a 26 yrs old female of postpartum
tion, electrocardiogram and echocardiography. Well’s cri- pulmonary thromboembolism with severe hypotension,
teria were used for assessment for pretest probability of cyanosis, bilateral crepitations in lungs and pulmonary
pulmonary embolism [9]. hypertension. The outcomes of tenecteplase therapy in
survived patients are depicted in Table 1.
In the 40 survived patients, there was alleviation of
Results dyspnoea and hemoptysis in all patients. Significant
reduction in tachycardia (P \ 0.0001) and increase in the
The 41 cases included 29 males and 12 females with oxygen saturation (SaO2) (P \ 0.0001) was seen at the
mean (±SD) age of 44.85 (±14.84) years, mean (±SD) time of discharge as compared to at the time of presenta-
weight of 73.65 ± 17.34 kg and mean (±SD) height of tion. Of 40 patients, 18 had hypotension (systolic blood

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Tenecteplase in the treatment of acute pulmonary thrombo-embolism 447

Table 1 Outcome of therapy with tenecteplase in acute pulmonary Due to this fact, the current guidelines recommended the
embolism use of thrombolytics only in high risk patients with massive
Parameter Pretreatment At discharge pulmonary embolism associated with circulatory collapse
[10, 12] considering that mortality of PE in patients with-
Number of patients 41 40
out shock treated with heparin and oral anticoagulants is in
Dyspnoea 41/41 0/40@ the range of 2% [13]. In spite of the regulatory approval for
Hemoptysis 5/41 0/41NS thrombolytic therapy in the treatment of pulmonary
Heart rate (min) [Mean ± SD] 123.34 ± 22.10 82.94 ± 7.73* embolism, it probably remains underutilized in clinical
SaO2 (%) [Mean ± SD] 87.64 ± 12.12 97.7 ± 2.5* practice due to fears of hemorrhagic complications [14]
RSVP (mmHg) [Mean ± SD] 58.90 ± 10.57 27.27 ± 13.89* and complicated regimes of thrombolytics. This risk can be
Patients with RVH 4 (9.76%) 1 (2.44%)NS reduced by use of more selective thrombolytics with better
Patients with RBBB 7 (17.07%) 0# safety profile.
@
P \ 0.0001 using Fisher exact test Tenecteplase is an alteplase molecule with three point
* P \ 0.0001 using unpaired t test substitution that increases its half life, increases the resis-
#
P = 0.0117 using Fisher exact test tance to plasminogen activator inhibitor-I (PAI-1) by 200
NS not significant folds and decreases the clearance by eightfolds. These
properties offer great therapeutic convenience in throm-
bolysis allowing a single weight-adjusted bolus dose of
pressure \120 mmHg and diastolic blood pressure tenecteplase as against the older thrombolytics. It also has
\80 mmHg) which recovered in all patients till the time greater fibrin specificity which has been reflected in
of discharge (P \ 0.0001). There was 100% resolution of reduced bleeding rates in ASSENT 2 trial [5, 15].
right bundle branch block and reduction in the number of There are few case reports and case series documenting
patients with right ventricular hypertrophy as documented the use of tenecteplase in cases of acute pulmonary
on echocardiography. There was a significant reduction in embolism [6] including a case report from Pathak et al. [7].
right ventricular systolic pressure in all 18 patients who Recently, Becattini et al., demonstrated the efficacy of
underwent 2-D echocardiography both before and after the tenecteplase in 58 hemodynamically stable patients of
tenecteplase therapy. However, the resolution of pulmon- pulmonary embolism with right ventricular dysfunction
ary embolism on CT pulmonary angiography was docu- [16]. There are no published large randomized controlled
mented in only two patients. trials on tenecteplase use in pulmonary embolism till date.
There were no major bleeding events defined as bleed- The data of 41 patients from this retrospective study
ing that required hospitalization or transfusion, was intra- depicts the favourable efficacy of tenecteplase in pulmon-
cranial or into a body cavity, or was fatal during the study. ary embolism with hemodynamic improvement and
No other adverse events were reported during this study. At reduction in right ventricular systolic pressure. All patients
the first follow up visit after one month of tenecteplase in this study except two had massive or submassive pul-
therapy, all patients were clinically stable and there was no monary embolism. However, only 9 patients had severe
additional mortality. hemodynamic compromise with diastolic blood pressure
of B60 mmHg at the time of presentation. This is not in
consensus with the previous recommendations for the use
Discussion of thrombolytics in only hemodynamically compromised
patients of pulmonary embolism [12], but confirms the
The use of thrombolytics for the treatment of pulmonary results of recently published study in 58 hemodynamically
embolism has remained controversial over several decades stable patients [16].
since the USFDA approval of streptokinase for acute This study suffered from a limitation that CT pulmonary
pulmonary embolism in 1977 [4]. The clinical trials angiography could not be done in all patients due to
demonstrated early resolution of pulmonary embolism unavailability of this facility in some centres. Although CT
with streptokinase and urokinase. However, the overall angiography is desirable, in resource-limited settings a high
improvement on lung scan was similar to the conventional clinical suspicion of pulmonary embolism warrants a
heparin treated groups. Both streptokinase as well as uro- therapeutic trial of tenecteplase as the benefits can be quite
kinase showed greater mortality possibly due to the serious significant.
bleeding complications associated [4]. On the similar lines, The present study has not found any incidence of doc-
even alteplase was associated increased bleeding risk and umented major hemorrhagic adverse event. But there was a
2.2% incidence of fatal hemorrhage including intracranial one case of fatal pulmonary embolism in which the cause
hemorrhage [11]. of death could not be assessed. The data for post-fibrinolyic

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CT pulmonary angiography is also not available for all 7. Pathak L, Patil S, Parikh AP, Seth SA (2010) Tenecteplase in
patients. acute pulmonary embolism. Indian Heart J 62:342–343
8. Prescribing Information: Elaxim. Gennova Biopharmaceuticals
Ltd, India. Downloaded from [Link]
pdf on 31 Aug 2010
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M, Turpie AG, Bormanis J, Weitz J, Chamberlain M, Bowie D,
Barnes D, Hirsh J (2000) Derivation of a simple clinical model to
The present study suggests favourable efficacy of tenec- categorize patients probability of pulmonary embolism: increas-
teplase in patients with suspected or confirmed acute pul- ing the models utility with the SimpliRED D-dimer. Thromb
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noted, a large prospective study on the use of tenecteplase 10. Guidelines on the diagnosis, management of acute pulmonary
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11. Konstantinides S, Geibel A, Heusel G, Heinrich F, Kasper W
(2002) Heparin plus alteplase compared with heparin alone in
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