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Clinical Case Report

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Dramatic thrombolysis after rapid injection of
tissue plasminogen activator
A case report
Jin-Sung Park, MD, Jaechun Hwang, MD

∗

Abstract

Rationale: The regimen of the recombinant tissue plasminogen activator (rt-PA) is identical in every case where it is indicated in the
treatment of cerebral infarction. We report a case of efficient recanalization of large arterial occlusion after rapid injection of rt-PA.
Patient Concerns: A 78-year-old man was admitted with right-sided hemiplegia and global aphasia that occurred an hour ago.
Diagnosis: His brain computed tomography (CT) revealed no hemorrhage, suggesting cerebral infarction.
Interventions: Ten percent of a total rt-PA dose was injected over 1 minute promptly. The remainder of rt-PA was designed to be
infused for 60 minutes. Unexpectedly, during the study of CT angiography, administration of rt-PA was completed within 5 minutes.
CT angiography showed occlusion from carotid bifurcation to the middle cerebral artery.
Outcomes: After 2 hours of rt-PA administration, the patient began to regain strength in his right arm and leg. By the next day, he

had only mild dysarthria and aphasia. Follow-up CT angiography revealed recanalized internal cervical artery and severe residual
stenosis with a plaque. He was discharged without any neurologic symptoms.
Conclusions: The infusion protocol of rt-PA administration is established in 1995 and has not changed. Successful recanalization
of long segmental large vessel occlusion with only intravenous rt-PA is relatively low. In our case, a high concentration of rt-PA may
have influenced the successful dissemination of large thrombus in the whole internal cervical artery. Our case is of significance as it
raises the question of unanswered efficacy of diverse injection protocol according to thrombus size and bleeding risk.
Abbreviations: CT = computed tomography, ICS = internal carotid artery, NIHSS = National Institutes of Health Stroke Scale, rtPA = recombinant tissue plasminogen activator.
Keywords: intravenous rt-PA, ischemic stroke, rapid recanalization, thrombolysis

tion of large arterial occlusion without hemorrhagic complication
after rapid injection of rt-PA over 7 minutes.

1. Introduction
Currently, recombinant tissue plasminogen activator (rt-PA)
remains the only approved thrombolytic medication in acute
ischemic stroke.[1] The standard regimen of rt-PA is that total
dose of 0.9 mg/kg of body weight, 10% of which was given as a
bolus followed by constant infusion of the remaining 90% over
60 minutes. However, it is known that the rate of recanalization is
low when the rt-PA is infused by this administration method,
especially in occlusion of a large vessel such as an internal carotid
artery (ICA).[2] We report our experience of efficient recanaliza-

2. Case report
A 78-year-old man was admitted to our emergency department
with right-sided hemiplegia and global aphasia that occurred an
hour ago. His National Institutes of Health Stroke Scale (NIHSS)
score of 21. Computed tomography (CT) of the brain performed
20 minutes after arrival revealed no hemorrhage or hypodense
lesion. Ten percent of a total rt-PA dose was injected over 1
minute promptly after CT check. The remainder of rt-PA was
designed to be infused for 60 minutes. Unexpectedly, during the
study of CT angiography, administration of rt-PA was completed
within 5 minutes with a significant disparity of the standard rt-PA
protocol. Initial CT angiography showed nonvisualization of the
ICA from carotid bifurcation to the middle cerebral artery
(Fig. 1A). Because of the technical difficulties and bleeding risk,
we concluded not to proceed with endovascular thrombectomy
considering the long segmental thrombus of ICA. Two hours
later, the patient began to regain strength in his right arm and leg
(NIHSS 8). By the next day, he had only mild dysarthria and
aphasia (NIHSS 2). Follow-up CT angiography revealed
recanalized ICA and plaques on left proximal ICA with severe
residual stenosis (Fig. 1B). It is thought that long segmental
occlusion occurred from the proximal carotid artery to the
middle cerebral artery due to the rupture of the carotid plaque.
Magnetic resonance imaging scan showed multiple small

Editor: N/A.
The authors have no funding and conflicts of interest to disclose.
Department of Neurology, School of Medicine, Kyungpook National University,
Kyungpook National University Chilgok Hospital, Daegu, South Korea.
∗

Correspondence to: Jaechun Hwang, Department of Neurology, Kyungpook
National University Chilgok Hospital, 807, Hoguk-ro, Buk-gu, Daegu, South
Korea (e-mail: ghkdwocns@gmail.com).

Copyright © 2019 the Author(s). Published by Wolters Kluwer Health, Inc.
This is an open access article distributed under the Creative Commons
Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
How to cite this article: Park JS, Hwang J. Dramatic thrombolysis after rapid
injection of tissue plasminogen activator. Medicine 2019;98:38(e17331).
Received: 20 April 2019 / Received in final form: 1 August 2019 / Accepted: 2
September 2019
http://dx.doi.org/10.1097/MD.0000000000017331

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Park and Hwang Medicine (2019) 98:38

Medicine

Figure 1. Computed tomography angiography before (A) and after (B) intravenous tissue plasminogen activator. Long segmental occlusion of the internal carotid
artery (arrow) is recanalized after intravenous thrombolysis.

considering the short half-life of rt-PA, the primary purpose of
intravenous thrombolysis is early recanalization. However, most
previous studies have not shown that rt-PA administration is
beneficial for early recanalization of large vessel occlusion
compared to placebo. Successful revascularization was the most
critical factor affecting clinical improvement after ischemic stroke
in the previous study.[6] Further effort to achieve early
recanalization and an excellent clinical outcome is crucial in
thrombolytic therapy.
Second, the rate of successful recanalization depends on the
amount of thrombus. Long segmental thrombus located in a large
vessel would be less likely dissolved compared to a small
thrombus. In previous studies and clinical field, recanalization of
large vessels has been observed up to 30% after only rt-PA
administration.[2] Because the ICA occlusion is more resistant to
intravenous rt-PA than the MCA, only 4% of ICA occlusion is
completely recanalized.[7,8] The recanalization rate of whole ICA
thrombus will be even lower than simple intracranial ICA. The
presence of abundant blood clot in the whole ICA might prevent
the delivery of an adequate dose of rt-PA to the thrombus.
Nevertheless, the current protocol does not differentiate rt-PA
administration between cerebral infarction due to small vessel
disease and large artery occlusion. In our case, the high
concentration of t-PA may have influenced the successful
dissemination of large thrombus in the whole ICA.

diffusion-restricted lesions in the left basal ganglia and cerebral
cortex. After 2 weeks, the patient underwent carotid endarterectomy for residual stenosis and was discharged without any
neurological sequelae.
Informed consent was obtained from the patient for publication and accompanying images.

3. Discussion
In this case, the rt-PA was administered in a different protocol
than the conventional method, resulting in the effective
dissolution of the large thrombus without hemorrhagic complication. The conventional infusion protocol of rt-PA administration is established based upon NINDS trial in 1995 and has not
changed in both clinical and research field.[1,3,4] However, the
dosing regimen used in this study was identical to the previous
pilot study and did not consider the various administration
methods. Although the study demonstrated the long-term clinical
benefit of rt-PA compared to placebo, data related to early
neurological improvement, which was the primary endpoint, did
not reach statistical difference.[1] Additional studies were
conducted to extend the therapeutic time window or expand
the eligible indication of rt-PA with identical protocol.[3,5]
There may be some limitations in applying the one identical
thrombolytic protocol to all acute cerebral infarction. First,
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Park and Hwang Medicine (2019) 98:38

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Author contributions

In consideration of the administration of thrombolytic agents,
another vital aspect is the risk of intracranial hemorrhage. In
acute ischemic stroke, the size of cerebral infarction and the time
from symptom onset are the main factors related to the risk of
intracerebral hemorrhage.[9,10] In a patient with large infarct
core, low-dose rt-PA may be administered to reduce the risk of
bleeding. The Enhanced Control of Hypertension and Thrombolysis Stroke Study was showed fewer symptomatic intracerebral hemorrhages with low-dose alteplase compared to fulldose.[11] The longer the duration of thrombolytics administration from the onset of symptoms, the higher the risk of
bleeding.[12] In the ECASS III trial, intravenous rt-PA administration between 3 and 4.5 hours after the onset of symptoms
significantly improved clinical outcome despite increased
intracranial hemorrhage.
Conversely, patients with short time to onset of symptoms may
have small infarct core and a lower risk of hemorrhage. In this
case, increasing the dose or the administration rate as needed may
not increase the bleeding risk to the effect. Despite these findings,
there has been no study on the diversity of infusion protocol
according to the risk of bleeding, and the guidelines only mention
one method of administration.
Currently, endovascular thrombectomy is the most effective
and essential treatment for a patient with large vessel occlusion.
However, mechanical endovascular procedures require the
facilities, equipment, and professional staff. Therefore, intravenous thrombolytic therapy is still an important treatment in many
situations. Further studies are needed to increase the recanalization rate and early neurological recovery through intravenous rtPA treatment. It is essential to make patient-tailored treatment
decisions, such as recent studies of an endovascular thrombectomy or wake-up stroke that show effective results with different
patient selections.[5]
This case is not an intended study, and there is a limit to
generalization. However, our case is of significance as it raises the
question of unanswered efficacy of various injection protocol
according to thrombus size and bleeding risk and further
discussion and well-designed studies are warranted.

Conceptualization: Jaechun Hwang.
Investigation: Jaechun Hwang.
Validation: Jin-Sung Park.
Writing – original draft: Jin-Sung Park.
Writing – review & editing: Jaechun Hwang.

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