Cardiovascular Journal of Africa: Vol 31 No 6 (November/December 2020)

CARDIOVASCULAR JOURNAL OF AFRICA • Volume 31, No 6, November/December 2020

AFRICA

289

anticoagulant agents has been accepted as the standard of

care for the majority of the subjects with lower-extremity

DVT.

In addition, the use of elastic compression stockings is

recommended in order to support venous valve function and to

prevent PTS development.

Nevertheless, a considerable number

of patients with lower extremity DVT develop PTS and recurrent

DVT, despite anticoagulant therapy and the elastic compression

stockings.

Theoretically, anticoagulant agents prevent further thrombus

propagation but can neither remove the clot nor prevent the

sequelae of post-thrombotic alterations.

Given the insufficiency

of anticoagulant agents in preventing PTS, the consideration

of initial thrombolytic therapy in lower-extremity DVT has

attracted attention.

Rapid resolution of the thrombus with systemic thrombolysis

in DVT provided promising results concerning the prevention

of PTS through the preservation of venous valve function.

14-16

Thrombolytic agents may also prevent the organisation of an

occlusive thrombus, thus preventing the development of occlusive

disease and venous hypertension. The short-term complete

resolution rate of the thrombus with systemic thrombolytic

agents is 26 to 67%, and the long-term risk of developing

PTS ranges between zero and 80%.

However, major bleeding,

including intracranial haemorrhage and pulmonary embolism

are major drawbacks for systemic thrombolytic therapy in DVT.

Pooled analysis of systemic thrombolytic therapy in DVT

shows that nine to 13% of subjects receiving streptokinase

or TPA for DVT develop major bleeding.

17,18

Moreover, the

success of systemic thrombolysis in patients with organised

and old thrombus burden is unsatisfactory, most probably due

to the limited penetration of the thrombolytic agent into the

thrombus.

Although pulmonary embolism resulting from systemic

thrombolytic therapy is a theoretical concern, Schweitzer

. reported that 4.5% of their study group, which included

patients with leg or pelvic deep venous thrombosis, suffered a

pulmonary embolus during systemic thrombolytic therapy.

The

underlying mechanism associating systemic thrombolytic agents

and pulmonary embolism is not clear; however, complete removal

of a huge thrombus from the vessel wall with systemic application

of a thrombolytic agent may be the cause of such a scenario.

Regional thrombolytic therapy, which allows the delivery

of the thrombolytic agent directly into the venous thrombus,

has emerged in the last few decades as a potentially superior

approach in the management of DVT. With this technique,

physicians aspire to overcome the main limitations of systemic

thrombolysis, such as the unpredictability of thrombolytic

effects and the high risk for major bleeding. PMT relies on the

administration of low-dose thrombolytic agents directly into the

clot while optimising exposure of the lytic agent to the clot by

catheters with multiple side holes. The improved penetration of

the thrombolytic agent and additional mechanical fragmentation

of the thrombus by the administration of the lytic agent through

specialised catheters facilitates the complete resolution of the

thrombus. The efficacy of PMT in restoring venous patency and

reducing symptoms in the setting of acute DVT has been shown

in several studies.

9,21

Risk for the development of PTE is negatively correlated

with the amount of thrombus remaining at the end of CDT.

It has been shown that removal of

≥

90% of the thrombus

significantly reduces the risk for PTS.

A recent meta-analysis

including six trials has reported that compared to CDT, PMT

reduced thrombolysis time, length of hospital stay and thrombus

score. The meta-analysis also showed that PMT had similar

complication rates to CDT.

Findings of the recent ATTRACT

trial showed that 48% of the patients with lower-extremity DVT

who received CDT developed PTS within two years.

Although long-term follow-up data are lacking, our findings

demonstrate a higher efficacy of CDT compared to that of the

Venous Thrombolysis Registry. Restoration of forward venous

flow was achieved in 94% of our study population, despite the

enrollment of a considerable number of subjects with subacute

DVT. Supporting the findings of the Venous Thrombolysis

Registry, which reported complete lysis of the thrombus in 65%

of patients with acute (

10 days) DVT, the complete resolution

rate of the thrombus in acute DVT subjects of our study was

significantly higher than those with subacute DVT.

The increased success rate noted in complete resolution of

the thrombus in this study compared to previous studies might

be associated with technical advances and the use of second-

generation urokinase, as well as the exclusion of subjects with

recurrent DVT. In addition, the vein affected by DVT was patent

in all our subjects at mid-term follow up. Moreover, none of the

subjects in our study developed PTS, which is closely associated

with the forward flow at midterm follow up.

Although head-to-head comparisons of the risk of intracranial

bleeding in systemic thrombolysis, PMT and CDT are lacking, it

seems to be quite rare with CDT. A pooled analysis of 19 studies

revealed a zero to 1% rate of intracranial bleeding following

CDT, which is lower than the intracranial bleeding rate reported

with systemic thrombolysis.

The data regarding intracranial

bleeding in PMT are limited. None of the subjects enrolled in our

study suffered intracranial haemorrhage during the three months

of follow up. We consider that the low-dose administration of

urokinase with an accelerated regimen (15 to 20 minutes) in our

study was the main cause of the lower frequency of intracranial

bleeding, compared to previous studies.

With data from our study and previous studies on this topic,

we suggest that accelerated PMT with low-dose urokinase can be

used in both acute and subacute lower-extremity DVT with high

efficacy and safety. Accelerated PMT with low-dose urokinase

may completely prevent the development of PTS, at least until

midterm follow up.

This study has some limitations. First, it was a prospective

but single-arm study. Therefore, we could not provide data

comparing the safety and efficacy of other treatments with either

anticoagulant alone or with systemic thrombolysis. However,

there is sufficient evidence demonstrating the superiority of

PMT in terms of safety and efficacy compared to CDT, systemic

thrombolysis or anticoagulants. Second, the follow-up period of

the study for the outcomes was three months, which is relatively

short to reach a clear conclusion regarding the role of PMT on

the development of PTS. Further studies with longer follow

up are required to address the role of accelerated PMT with

low-dose urokinase in patients with lower-extremity DVT.

Conclusions

This study shows that PMT with an accelerated regimen of

low-dose urokinase provides excellent efficacy in the resolution