Acute Arterial Catheter Directed Thrombolysis: A Systematic

Review
Abstract:
Objectives: The objective of this article was to evaluate the efficacy and safety of CDT in the
first-line treatment of acute arterial thromboembolic occlusions, to look at the results of an
accelerated CDT protocol using higher rt-PA doses in patients with ALI, and to investigate the
safety and practical application of an intra-arterial thrombolytic agent infusion combined with
micro bubbles and ultrasound in peripheral arterial occlusions.

Methods: The PubMed database and EBSCO Information Services were utilized to choose the
articles. In our review, all pertinent articles related to both our topic and other articles were used.
Other articles that have nothing to do with this subject were not included. The group members
looked through a certain format in which the data had been extracted.

Conclusion: As a main therapy, CDT is safe and effective for revascularization of smaller vessel
acute arterial thromboembolism. Both UAT and CDT are safe and effective therapeutic methods
for patients with acute and subacute limb ischemia. Patients with acute peripheral artery
occlusions can be treated with contrast enhanced sonothrombolysis, which is both possible and
safe. There was no difference in periprocedural complications, hemorrhage, or outcomes
between PMT + CDT and CDT alone.

Keywords: Catheter-directed thrombolysis, Acute limb ischemia, Thromboembolism,

revascularization, Micro-bubbles, Ultrasound
Introduction:
Acute Limb Ischemia (ALI) can be caused by a thrombus occluding an artery in the arm or leg
[1]. The main cause of ALI in roughly 85% of patients is arterial thrombosis [2]. This is an
emergency scenario that, if not addressed properly, can end in amputation or death [1]. Acute
ischemia compromises limb viability because there is little time for new blood vessel formation
to compensate for the loss of perfusion. Additionally, systemic repercussions of ischemia have
been linked to increased morbidity and death in ALI patients. There are few endovascular
alternatives for mechanical revascularization of thromboembolic occlusions [3]. Endovascular
alternatives for mechanical revascularization of thromboembolic occlusions are limited. While
rheolytic thrombectomy and aspiration thrombectomy have shown promising outcomes, treating
smaller arteries with these procedures carries the risk of vascular spasm, dissection, vessel
rupture, or plaque breakup, as well as distal embolization [4-6]. Unlike these procedures, arterial
catheter-directed thrombolysis (CDT) can be used to dissolve thromboembolic plaques in smaller
(infrapopliteal) arteries without risk of artery rupture [7].

When the thromboembolic blockage is in the infrapopliteal arteries, CDT is thought to be better
to open surgical therapy. During balloon embolectomy, incomplete revascularization persists.
Moreover, it has been linked to significant morbidity and uncommon severe consequences [8,9].
CDT enables for more successful clot resolution due to enzymatic disintegration, particularly in
distant arterial beds that are generally resistant to surgical thrombectomy [7].

While CDT has been proved to be a good alternative to surgical therapy, it is still associated with
significant hemorrhagic consequences in up to 8.4% of cases [10]. Due to distal embolization of
the clot, limb ischemia may intensify during thrombolytic therapy. Moreover, CDT necessitates
frequent angiography, which carries the risk of nephrotoxicity. As a result, optimizing existing
thrombolytic therapy is required to reduce complications, reduce patient burden, and enhance
outcome. Numerous research have looked into the use of micro bubbles in conjunction with
ultrasonography in thrombolysis. Initially, these 1 to 10 mm gaseous bubbles were designed as
ultrasonic contrast agents to assist conventional ultrasound scanning [11]. The second generation
of ultrasonic contrast agents consists of a high molecular weight gas encased in a lipid shell,
which is utilized to increase stability and therefore allow the micro bubbles to pass through the
lungs and into the artery circulation [12]. The widely held belief is that low and intermediate
acoustic pressures induce micro bubble oscillations, which end in collapse under high acoustic
pressure. The destruction of these micro bubbles might result in the creation of free radicals,
which causes erosion and microscopic holes in the surface of the clot, weakening the fibrin
network and eventually increasing the clot's sensitivity to the fibrinolytic agent. It is worth noting
that the intravenous injected micro bubbles cause cavitation at the thrombus surface but do not
penetrate it [13].

Most writers propose tiny doses of thrombolytic drug administered over a longer period of time
(even up to 48 hours) due to the risk of bleeding problems. This regimen, however, prohibits the
treatment of individuals with severe ischemia (Rutherford classes IIb and III) who require
immediate revascularization [14]. Large dosages of recombinant tissue plasminogen activator (rt-
PA) delivered over a short period of time, on the other hand, are not associated with an increased
incidence of substantial bleeding, as verified in patients with major and sub massive pulmonary
embolisms [15].

Therefore, the objective of this research was to assess the efficacy and safety of CDT in the first-
line treatment of acute arterial thromboembolic occlusions, to examine the results of an
accelerated CDT protocol using increased rt-PA doses in patients with ALI, and to investigate
the safety and practical application of an intra-arterial infusion of thrombolytic agent combined
with micro bubbles and ultrasound in peripheral arterial occlusions.

Methods:

Study design
A systematic review of the current evidence on Acute Arterial Catheter Directed Thrombolysis is
considered a robust way of identifying and synthesizing the peer reviewed articles for evidence
in this area to define a cohesive empirical research agenda that builds on prior knowledge. This
review will include qualitative evidence only to produce an interpretation. Further, a synthesis of
qualitative data aims to generate findings that are meaningful, relevant, and appropriate to
individuals, to inform a research agenda and ultimately to more effectively practices on Acute
Arterial Catheter Directed Thrombolysis. The review used methods of qualitative synthesis to
combine, integrate and interpret, where possible, the evidence from the included papers.

This article aims to assess the safety and efficacy of Acute Arterial Catheter Directed
Thrombolysis in treatment of arterial thromboembolic occlusions, and its protocol in ALI
patients. The article also investigates practical application of an intra-arterial infusion of
thrombolytic agent combined with micro bubbles and ultrasound in peripheral arterial
occlusions.

Study eligibility criteria

The review included qualitative peer-appraised studies. Qualitative data from mixed methods-
studies were screened for inclusion and included if the qualitative element is pertinent. All peer-
reviewed articles published in English, reporting Acute Arterial Catheter Directed Thrombolysis
over 10 past years were included.

The articles were selected based on the relevance to the project, English language and date
restrictions were considered. All other articles which do not have one of these topics as their
primary end, or repeated studies, and reviews studies were excluded. The reviewers excluded any
studies not available in English, conference abstracts, books or grey literature and editorial
comments. Studies reporting only qualitative data were excluded.
Search strategy
A systematic search strategy was developed in PubMed/MEDLINE database using a
combination of Medical Subject Headings (MeSH) and controlled vocabulary to identify peer-
reviewed articles on Acute Arterial Catheter Directed Thrombolysis. Search was limited to 10
years restriction.

Selection of study
The ENTREQ guidelines for reporting qualitative systematic reviews were used to demonstrate
the selection processes and results. All retrieved studies were initially imported into Endnote
library to assist in removing duplicates. After removing the duplicates, the Endnote library was
shared between two reviewers to independently screen the articles by title and abstract, guided
by the eligibility criteria. The studies which the two reviewers would have agreed on were
subjected to the full-text review. A third reviewer adjudicated any discrepancies between the two
reviewers. The two reviewers independently reviewed the full text of all eligible studies. In the
case where there are differences between the two reviewers, consensus was sought through
discussion on the differences with the third reviewer. Finally, the full texts of all relevant studies
found to meet the inclusion criteria were retained for the final framework synthesis.

Data extraction
Data was independently extracted by two reviewers from eligible studies onto a customized data
extraction form and populated with variables pertaining to the study population and phenomena
of interest. Double checking and verification of extracted articles was done by the third review
author. Study characteristics that were extracted included name of the first author and year of
publication, data collection period and region in which the study was conducted. Specific study
details including the study design, study population, sample size, sampling procedures and data
collection procedures were captured.

Data synthesis and analysis

No software was utilized to analyze the data. The reviewers sorted the data by theme and
presented the themes in the form of an analysis table (chart). The columns and rows of the table
reflected the studies, and related themes and enable us to compare findings of the studies across
different themes and subthemes.

Results:
Figure 1 shows the selection and identification of studies. The search of the mentioned database
returned a total of 79 studies that were included for title screening. 59 of them were included for
abstract screening, which lead to the exclusion of 20 articles. The remaining 39 publications full
texts were reviewed. The full-text revision led to the exclusion of 28 studies due to difference in
inclusion criteria, and 11 were enrolled for final data extraction (Table 1).

Between 2013 and 2023, many studies on acute arterial catheter directed thrombolysis were
done. Eleven studies which mentioned in this article, some of them are clinical trial and others
are observational studies and retrospective analysis.

CDT is considered superior to open surgical management when the thromboembolic occlusion is
in infrapopliteal arteries. Accelerating thrombolysis using microbubbles may benefit the patient
by reducing therapy time, risk of haemorrhagic consequences, and patient burden [21]. In all
cases, the application of microbubble contrast enhanced sonothrombolysis was beneficial. In 25
(83.33%) of the treated limbs, technical success was attained. Improvement clinical state (grade
3/2) was reached in 93.33% of the limbs studied in this study, which looks at the effectiveness
and safety of catheter-directed thrombolysis (CDT) as first-line therapy for popliteal and
infrapopliteal acute limb ischemia [16,17,18]. The use of Uni-Fuse and EKOS catheters as
thrombolytic therapy in the treatment of arterial occlusions resulting in acute limb ischemia
(ALI) is also safe and effective [19]. A retrospective analysis of 83 patients, some of whom had
CDT with PMT and others who had only CDT, demonstrated that patient characteristics, such as
occlusion length and location, Rutherford class, median duration of ischemia time, mean lysis
time, and outcomes, such as periprocedural complications, patency, reintervention, limb salvage,
and amputation-free survival, were comparable among treatment groups [20].

A study of 102 patients was conducted. The findings of a study comparing the safety and
efficacy of ultrasound-accelerated thrombolysis (UAT) with conventional catheter-directed
thrombolysis (CDT) in patients with acute and subacute limb ischemia revealed that the use of
UAT with CDT or CDT alone is equivalent. There were minor bleeding issues in both cases, and
hemorrhage was minimal [25].

CDT standards advocate treating patients with minimal doses of a thrombolytic drug, which
excludes individuals who require immediate revascularization. The effects of higher recombinant
tissue plasminogen activator (rt-PA) dosages on rapid thrombolysis were studied. In 90.2% of
patients, satisfactory lysis was obtained. All substantial underlying lesions (89.2%) were
repaired. Problems occurred in 22% of patients, with puncture site hematoma being the most
common. [22].

Additional studies were assigned to examine the influence of fibrinogen levels on bleeding
issues, as well as technical and clinical success. And the findings demonstrated that fibrinogen
levels less than 1.5 g/L during thrombolysis were not related with an increased risk of bleeding.
Only the higher dose and longer duration of thrombolysis were linked to an increased risk of
bleeding [24]. Yang, Shuofei, et al. [23] conducted a research with two groups, the first utilising
anticoagulants and the second undergoing postoperative CDT. The findings revealed that the
second group was linked with a better clinical outcome when compared to systemic
anticoagulation.

therefore, CDT in combination with or without endovascular methods is a successful reasonable

therapy choice for many ALI patients. In many patients, especially those with new thrombus or
emboli, immediate vascular patency can be accomplished with an acceptable complication rate.
It can also be used as an adjuvant therapy technique for persistent occlusion endovascular
treatments. Individual judgment should be used to choose one treatment technique over another
depending on limb viability, lesion characteristics, and bleeding risks.

.The included studies had different study designs

 Identification

Studies Identified from other Studies identified through

sources (n=0) database screening (n= 79)

Studies after duplicates removed (n=

59)
Screening

Studies excluded (n= 20) Studies screened (n= 59)

Eligibility

Full studies excluded

Full studies assessed for
(n= 28)
eligibility (n =39)

Studied included in the qualitative Included

analysis (n= 11)
Table 1: Authors name, sample size, age and gender.
Author, No. of Main age Gender
Publishing patients
Year
Doelare, 20 median age 68.0 16 men
Sabrina A N et patients years
al. (2021) [16]
Lian, 28 Patients between 19 men /9 women
Wei Shuai et patients the ages of 18
al.  (2020) [17] and 80 years
Lukasiewicz, 121 ---- ----
Aleksander et patients
al. (2020) [18]
Chait, Jesse, et 91 Median age 71 ----
al. (2019) [19] patients
Gandhi, Sagar S 83 ---- ----
et al. (2018) patients
[20]
Ebben, Harm P 20 From 18 to 85 ----
et al. (2017) patients years
[21]
Lukasiewicz, 41 range 44–78 40 male /1 female
Aleksander et patient
al. (2016) [22]
Yang, Shuofei 32 mean age of 20 male
et al. (2016) patients 44.9 ± 10.6 years
[23]
Lee K, Istl A, 49 mean age of 52.0 ----
Dubois L, et al. patients ± 18.4 years
(2015) [24]
Schernthaner, 102 ---- ----
Melanie B et patient
al. (2014) [25]
de Donato, 322 Group TE: 72.5 Group TE: 71
Gianmarco et patients ± 10.3 male /41 female
al. (2014) [26] Group Group HP: 73.3 Group HP: 121
TE: 112 ± 11.6 male/89 female
Group
HP: 210
Table 1: Author, year of publication, type of research, methodology and
outcome:
Author, Type of Method
Publishing research
Year
Doel Clinical trial During the first hour of normal intra-
are, Sabrina arterial thrombolytic treatment, 20
A N et al. patients with acute lower limb ischemia
(2021) [16] underwent CDT coupled with an
intravenous infusion of micro-bubbles and
locally administered ultrasonography.
The primary objective was safety, which
was defined as the incidence of major
adverse events (hemorrhagic
complications and/or amputation) and
mortality within a year. Angiographic and
clinical success, thrombolysis duration,
further therapies, conversion, and quality
of life were all secondary objectives.
Lian Single-center 2012 - 2017, 28 patients (30 limbs)
, Wei Shuai prospective received CDT for the treatment of
et al.  (2020) observational popliteal and infrapopliteal acute limb
[17] study ischemia of thromboembolic etiology.
Limbs were divided into three runoff
score categories by the Society for
Vascular Surgery: less than 5 is good, 5
to 10, compromised, and >10, terrible.
Kaplan-Meier survival analysis was used
to examine the key end points of primary
patency and limb salvage.
The procedure's safety was assessed using
the Society of Interventional Radiology's
categorization system for periprocedural
problems.
Lukasiewicz, retrospective 121 individuals with various kinds of
Aleksander et analysis lower limb ischemia were treated with
al. (2020) intra-arterial, catheter-directed
[18] thrombolysis.
The basic therapy procedure, used in 92%
of patients, was a 3.5-hour catheter-
directed infusion of 40 mg of alteplase.
Pre- and intra-procedural parameters
(indications, demographic information,
comorbidities, the dose of alteplase used,
underlying lesions operations) and
postoperative outcomes (lysis grade,
mortality, complications, reinterventions,
and limb loss after 1-month monitoring)
were examined.
Chait, Jesse, A retrospective  patients satisfied the criteria for
et al. (2019) analysis inclusion. Uni-Fuse and EKOS catheters
Outcome
The use of micro-bubble contrast enhanced
sonothrombolysis was effective in all cases.
After 23.1 hours, a duplex examination
revealed flow distal to the blockage, with a
median thrombolysis duration of 47.5 hours.
The short-term ABI and pain ratings improved
dramatically; however, no alterations in the
microcirculation were identified before or after
thrombolysis. Within one year, both overall
death and amputation rates were 2%. The
patency rate after one year was 55%.
83.33% of the treated limbs, technical success
was attained.
93.33% of the limbs, clinical status was
improved.
Primary patency and limb salvage rates for the
total group were 76.67% and 90% at 6 months,
and 60.0% and 76.67% at 12 months.
The excellent runoff group's patency rate at 6
months and 12 months was 91.67%, the
compromised runoff group's patency rate was
80%, and the bad runoff group's patency rate
was 25%.
At 12 months, the major amputation rate and
death rate were 16.67% and 7.14%,
respectively.
At 6 months, the reintervention rate was
3.57%, and at 12 months, it was 21.42%.
76.1% of patients had successful thrombolysis.
The success rate for acute, subacute, and
thrombotic consequences of vascular
operations was comparable.
Procedures to address underlying lesions were
done on around 67.8% of patients.
The overall complication rate was 28.1%,
while only 5% of patients experienced serious
hemorrhage.
During the one-month follow-up, there was no
death, a 1.7% re-intervention rate, and a 10.7%
amputation rate.
There was no significant difference between
the Uni-Fuse and EKOS cohorts in mean
[19] were utilized in 69 and 22 patients,
respectively, who had ALI with
thrombosis in both native arteries and
bypass grafts.
The duration of thrombolysis, the amount
of thrombolytic drug used, and the rate of
technical success were all reported.
Gandhi, Sagar A retrospective 83 ALI patients who had CDT with or
S et al. (2018) analysis without pharmaco-mechanical
[20] thrombectomy (PMT). Group 1 consisted
of 54 patients who had PMT + CDT,
whereas Group 2 consisted of 29
individuals who underwent CDT alone.
Lesions were classified further according
on their anatomic location: iliac disease (n
= 14), femoropopliteal disease (n = 53),
tibial disease (n = 2), and multilayer
disease (n = 14). Patient and limb
characteristics, treatment duration,
complications, clinical results, adjunctive
therapies, and follow-up were all
collected.
Ebben, Harm Clinical trial 20 individuals with acute peripheral artery
P et al. (2017) occlusions qualified for thrombolytic
[21] therapy. Urokinase will be employed in
low-dose catheter-directed thrombolysis.
During the first hour after thrombolysis,
the explored therapy will consist of an
intravenous infusion of 4 Luminity phials
of micro-bubbles with the application of
local ultrasonography at the site of
blockage. The incidence of problems and
technical feasibility are the primary end
goals.
Lukasiewicz, prospective A total of 41 individuals with acute ALI
Aleksander observational were treated with accelerated CDT.
et al. (2016) study The therapy included a 30-minute
[22] infusion of 10 mg rt-PA, followed by a 3-
hour course of a continuous intra-arterial
10 mg/hour rt-PA infusion.
Concurrently, 500 IU/hour of intravenous
unfractionated heparin was delivered.
Yang, A single-center Thirty-two individuals were studied, with
Shuofei et al. retrospective 17 in group I receiving postoperative
(2016) [23] study systemic anticoagulation and 15 in group
II receiving postoperative CDT.
The study analyzed demographics,
etiology, imaging characteristics, clinical
outcomes, and complications.
Moreover, univariate analysis was used
to uncover confounding factors of 30-day
mortality.
infusion length, amount of tissue plasminogen
activator, or technical success rate. Also, there
was no difference between the groups in terms
of catastrophic limb loss or compartment
syndrome. When treated with either catheter
method, the total complication rate was 14% in
both groups, with a 30-day death rate of 4%.
There were no significant variations in patient
characteristics, occlusion length and location,
Rutherford class, median duration of ischemia
time, or mean lysis time between therapy
groups.
Outcomes, such as periprocedural
complications, patency, reintervention, limb
salvage, and amputation-free survival, were
also similar among treatment groups.
Due to mechanical effects generated by
oscillation, contrast-enhanced ultrasonography
employing micro-bubbles might speed
breakdown of thrombi by thrombolytic drugs;
this could allow for lower thrombolytic doses
and quicker thrombolysis, minimizing the risk
of hemorrhagic consequences. The safety and
practical usefulness of this therapy will be
examined in this investigation.
37 of 41 patients (90.2%) had satisfactory lysis.
All substantial underlying lesions (89.2%) were
repaired.
Problems occurred in 22% individuals, 9.8%
of them with puncture site hematoma.
At the 1- and 6-month follow-ups, the
reintervention rate was 2.6% and 15.4%,
respectively. At the 1- and 6-month follow-ups,
the major amputation rate was 10.3% and
12.8%, respectively.
Group II had a much better percentage of
complete thrombus clearance than group I. In
group II, fewer patients required a second-look
laparotomy and repeat bowel resection. In
group II, the incidence of short-bowel
syndrome and 30-day mortality were reduced.
Group II likewise had a higher one-year
survival rate. Massive abdominal bleeding
requiring blood transfusion and surgical
intervention occurred in 11.8% of group I and

Lee K, Istl A, Retrospective Depending on their fibrinogen level
Dubois L, et study throughout therapy, 49 patients 16 of
al. (2015) them were placed in the low-fibrinogen
[24] group ,26 in the high-fibrinogen group
and 7 patients had any bleeding
complications . Demographics, bleeding
problems, and technical and clinical
success were compared between groups to
see if low fibrinogen levels during
catheter-directed thrombolysis are related
with an increased risk of bleeding.
Schernthane Comparative In 102 patients with acute and subacute
r, Melanie B study limb ischemia, researchers compared the
et al. (2014) safety and effectiveness of ultrasound-
[25] accelerated thrombolysis (UAT) with
traditional catheter-directed thrombolysis
(CDT).
Medical records of all patients who had
thrombolysis.
Coprimary (ankle-brachial index rise,
degree of lysis) and secondary outcomes
(technical success, distal embolization,
bleeding complications, requirement for
further procedures) were evaluated. UAT
was conducted on 75 individuals, whereas
CDT was performed on 27.
de Donato, Comparative 322 patients with ALI were hospitalized
Gianmarco study to compare the results of surgical arterial
et al. (2014) thrombo-embolectomy (TE) and hybrid
[26] procedure (HP). 112 patients were treated
urgently with a Fogarty balloon catheter
and 210 patients were treated with
endovascular completion. The Kaplan-
Meier technique was used to compute in-
hospital complications, 30-day mortality,
primary and secondary patency,
reintervention rate, limb salvage, and
overall survival rates, which were then
compared using the log-rank test.
20.0% of group II. In this research, age, serum
D-dimer level, SBS, and postoperative CDT
were all significant risk factors for 30-day
death.
Participants in the low-fibrinogen group were
substantially younger and had a larger
proportion of venous occlusive events than
those in the high-fibrinogen group.
Gender, afflicted extremities, prothrombotic
risk factors, contraindications to thrombolysis,
baseline fibrinogen, international normalized
ratio, partial thromboplastin time, and platelets
were similar between groups.
The low-fibrinogen group received a higher
total dosage of tissue plasminogen activator
and received it for a longer period of time.
The incidence of severe and mild bleeding did
not differ substantially between the low- and
high-fibrinogen groups.
Complete lysis was obtained in 72.0% of
patients (UAT) and 63.0% of patients (CDT);
hemodynamic success was achieved in 91.8%
of patients (UAT) and 92.3% of patients
(CDT). Overall, 6.9% (UAT) and 3.9% (CDT)
of patients experienced significant or mild
bleeding problems. The total rate of major and
mild hemorrhage was lower: 6.7% (UAT)
versus 22.2% (CDT). At 8.0 months, overall
target vessel patency was 73.5%; target vessel
patency for UAT was 75.9% against 64.3% for
CDT.
Following surgical TE, the HP group consisted
of 90 cases of angioplasty (PTA) stenting, 24
cases of catheter-directed intra-arterial
thrombolysis + PTA stenting, 67 cases of
thrombus fragmentation and aspiration by large
guiding catheter + PTA stenting, 9 cases of
vacuum-based accelerated thromboaspiration
by mechanical devices, and 12 cases of primary
covered stenting. Estimated main patency for
HP and TE patients was 90.4% vs. 70.4% at 2-
year and 87.1% vs. 66.3% at 5-year follow-up,
respectively. The HP group had the highest rate
of limb salvage (95%). At 1 year, the estimated
independence from reintervention for HP
patients was 94.4% versus 82.1% for TE
patients, and at 5 years, it was 89% vs. 73.7%,
respectively.
Discussion:
We have seen remarkable improvement in the treatment of ALI during the last 20 years.
Endovascular procedures have gained popularity. CDT has been demonstrated to be an effective
therapy for restoring arterial patency and alleviating symptoms of Acute Limb Ischemia. Yet,
even after successful revascularization, Acute Limb Ischemia is still associated with a high
likelihood of systemic complications and mortality, according to a recently issued European
Society of Cardiology/European Society for Vascular Surgery guideline on peripheral artery
disease [27].

Various endovascular approaches have been investigated in order to improve the effects of CDT.
The first randomized experiment comparing endoluminal ultrasound accelerated thrombolysis to
traditional catheter guided thrombolysis found a decrease in therapy time and fibrinolytic drugs
given [28]. Nevertheless, ultrasound-assisted thrombolysis did not appear to be better to standard
treatment in terms of significant bleeding problems. The use of ultrasound with intravenous
micro-bubbles, which has already shown a therapeutic impact in animal trials with massive
peripheral artery occlusions, might be a potential accelerator of existing thrombolytic treatment.
There were less bleeding problems noted. Nonetheless, because of the limited sample size, it
should be read with care. In a study [16] , the overall one-year amputation and mortality rates
were both 2%, which was much lower than the 25% mortality rate and 13% amputation rate
reported by Koraen et al [29]. It has been suggested that the degree of ischemia may impact
thrombolysis success as well as mortality and morbidity rates. Korn et al. discovered that the
group presenting with acute onset claudication had a relief of ischemia rate of 43% after two
years and a combined 30 day mortality and morbidity rate of 18%. As a result, recommendations
advocating cautious treatment in patients with viable limbs were developed [30]. Historically,
fibrinogen depletion measures during thrombolysis were used to forecast bleeding problems or to
guide fibrinolytic procedures. Current research, however, has established no link between low
fibrinogen levels and hemorrhagic consequences [27].

Many investigations on the therapeutic use of contrast agents in patients with ischemic stroke
and myocardial infarction have been conducted [31]. A comprehensive analysis of
sonothrombolysis found that it improves short- and long-term clinical outcomes in individuals
with ischemic stroke while potentially lowering bleeding risk. Yet, dosage escalation studies
reveal that safety (in terms of bleeding and micro-emboli) should be explored further before
enrolling patients in phase III trials. Minimal and disparate research investigated the therapeutic
use of sonothrombolysis in individuals with myocardial infarction [32]. Although pilot studies
confirm safety and feasibility, a recent clinical experiment found that using therapeutic
ultrasound with extended pulse durations resulted in unanticipated coronary vasoconstriction
[33].
The first attempt to enhance the surgical technique  for treating acute artery blockage was
documented by Parsons et al in 1996 [34]. Suggesting the use of intraoperative fluoroscopy and
the performance of fluoroscopically assisted thromboembolectomy (TE), the authors provided
the first case of scombination of surgical and endovascular method for treatment of ALI. This
novel approach reduced arterial damage and blood loss during clot removal by allowing the
catheter to travel through twisted or damaged arteries. It might also help with the correct
detection, localization, and treatment of major concurrent arterial lesions. Since then, regular
angiography after TE has been advised [35,36], however adherence to this guideline remains
restricted in clinical practice [37]. CDT has been used successfully as an alternative to surgical
embolectomy for ALI, but its effectiveness is dependent on the ability to pass a guide through
and implant a multisided catheter into the occlusion [38]. In addition, surgical TE is still
effective and time-efficient method of removing a big clot from the femoropopliteal artery
section [39].

The relevance of CDT for thromboembolism involving smaller vessels stands out, and A study
[17] has validated it by attaining improved technical and longer patency rates with no significant
consequences. Treatment of thromboembolic occlusion in smaller arteries is difficult and can
result in significant morbidity and death if not handled effectively [4]. When large-bore catheters
are used to perform these endovascular operations in tiny arteries, the risks of spasm, dissection,
vessel rupture, and plaque disruption rise. Additionally, despite the provision of distal protection,
the majority of these operations are plagued by angiographically visible distal thromboembolic
consequences. Also, in terms of safety, the study indicated that CDT may be conducted rather
safely in terms of problems. Nevertheless, the precise status of the CDT technique for popliteal
and infrapopliteal thrombo-occlusive lesions has not been established [40,41].

CDT is now the most well-documented, minimally invasive approach for treating ALI. The
primary benefit of the accelerated thrombolysis procedure was that we were able to treat patients
in a time frame equivalent to surgery while achieving great outcomes.

Conclusion:
In conclusion, In the treatment of popliteal and infrapopliteal artery thromboembolic lesions,
CDT produces outstanding therapeutic outcomes with a tolerable complication rate. According to
the protocol used, thrombolysis gave outstanding therapeutic results in a timeframe equivalent to
surgery and with an acceptable complication rate. The usefulness of high dosage CDT should be
carefully evaluated in light of new endovascular thrombectomy methods for the treatment of
ALI. This first-in-human research, on the other hand, reveals encouraging safety and technical
feasibility findings for contrast enhanced ultrasonography in patients with significant peripheral
artery occlusions treated with CDT. As a result, accelerating thrombolysis with micro-bubbles
may eventually benefit the patient by reducing therapy time, risk of hemorrhagic consequences,
and patient burden. Because of the high occurrence of underlying lesions that might induce acute
artery occlusion, an intraoperative imaging investigation is recommended. A combination of
surgical and endovascular alternatives, based on angiographic findings following TE, may
overcome the limits of the standard method in patients with ALI. When used to particular
therapeutic circumstances, HPs may offer instruments with the ability to minimize morbidity
previously associated with acute artery occlusion and enhance early and midterm clinical
outcomes.
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