the majority of emboli arise from the heart in association with atrial fibrillation , myocardial infarction , or valvular heart disease [ 24 ] .
approximately two - thirds of non - cerebral emboli obstruct the lower extremities , involving aorto - ilio - femoral arteries in approximately two - thirds of the patients , with the most common site being the femoral artery .
presentation of ali varies from silent ischemia to acute extremity loss , depending on the presence and extent of atherosclerosis and collateral blood flow . in ali patients with certain comorbidities , loss of extremities and death
are not rare outcomes . without intervention , mortality , gangrene , and chronic ischemia rate in long - term follow - up
contemporary effective methods are mechanical thromboembolectomy , percutaneous thrombosuction ( pt ) , and catheter directed thrombolysis . despite use of these therapies ,
ali still carries a high risk for limb amputation ( 518% ) and death ( 814% ) [ 911 ] .
percutaneous removal of thrombi is a well - established treatment modality and is often used as the first - line therapy in ali patients .
pt and mechanical thrombectomy are effective methods for thrombus removal , but they can not be applied to all patients due to technical reasons [ 1214 ] .
regardless of the treatment method , the success rate is lower in below - knee arteries compared to upper segments .
pt method is easier than mechanical thromboembolectomy , with similar outcomes ; nevertheless , residual thrombus , distal microembolization , and dissection are disadvantages of both methods .
tirofiban is a strong antiaggregant that inhibits gpiib / iiia receptors and blocks 95% of platelet aggregation .
the reduction of thrombus load is a well - known effect of tirofiban in coronary interventions .
pt together with tirofiban decreases slow - flow / no - flow phenomenon in coronary interventions and improves coronary arterial circulation . despite being an established antiaggregant agent in patients with coronary thrombi , the efficacy and adverse effects of tirofiban in peripheral arterial diseases , especially in below - knee ali
the aims of this study were to evaluate the effects of early pt ( within the first 24 h ) and additional tirofiban usage on procedural success , long - term safety , and the need for amputation in knee and below - knee arterial ali .
data from consecutive ali patients with popliteal and infra - popliteal arterial thrombosis who underwent pt within the initial 24 h between january 2010 and september 2015 were analyzed retrospectively .
limbs were classified using the society for vascular surgery / international society for cardiovascular surgery ( svs / tscvs ) clinical categories of ali ( rutherford category ) .
the degree of baseline occlusion was determined by using the schema adapted from ansel et al . .
the patients with rutherford iia or iib , and patients with 91100% arterial occlusion on angiography were included in the study .
patients with a rutherford class i or iii , an inr higher than 1.5 , serum creatinine > 2.5 mg / dl , and with comorbidities requiring tirofiban use were excluded from the study .
minneapolis , mn ) using 7f ( popliteal ) and 6 - 5f ( infra - popliteal ) guiding catheters and a 0.014-inch wire in all 3 below - knee arteries until the thrombus completely disappears .
the procedure was accepted as successful when 70% revascularization of the arterial lumen ( thrombus removal ) and maintenance of distal arterial blood flow were achieved .
tirofiban was given as a 10 g / kg bolus followed by a 0.15 g / kg / min infusion for 12 h .
unfractionated heparin ( ufh ) was administered at a bolus dose of 50100 u / kg , with a target activated clotting time ( act ) of 250300 s. ufh infusion continued for 24 h. slow - flow was defined as a timi-2 flow grade ( i.e. , requiring 3 beats to opacify the vessel ) or a corrected timi frame count > 27 frames .
distal embolization was identified as disappearance or abrupt and unexpected occlusion of a distal vessel that had been visible in preprocedural cineangiograms .
sheath removal for the tirofiban - treated group was time - based ( 60 min after infusion discontinuation ) . the sheath was removed if act was below 180 s. major bleedings were accepted as intra- and retroperitoneal bleeding , intracranial bleeding , any overt procedure - related bleeding with a hemoglobin drop of 5 g / dl , and transfusion needing or invasive procedure needing bleedings .
minor bleedings were accepted as bleedings which did not need any transfusion or invasive procedure .
development of arterial occlusion or thrombus were checked in all patients by physical examination and doppler ultrasonography at the end of 6-month follow - up .
statistical analysis was performed using spss statistical software ( spss version 19 ; spss , inc . ,
to assess the significances of differences , the t test was used for means and chi - square for percentages .
statistical analysis was performed using spss statistical software ( spss version 19 ; spss , inc . ,
data are presented as mean  standard deviation or percentages . to assess the significances of differences ,
from these , 105 patients ( mean age 6716 years ; 53% men ) had 6-month follow - up .
the majority of patients ( 69% ) had infra - popliteal occlusion and below - knee atrial thrombus ( 67% ) presenting with a slightly higher frequency ( 54% ) of rutherford iib clinical status .
overall , atrial fibrillation ( n 64 , 61% ) and hypertension ( n 60 , 57% ) were the most important comorbidities .
clinical features of the tirofiban - treated and -untreated patients were similar to each other , except for a higher frequency of diabetes ( 52% vs. 40% ; p=0.05 ) and structural heart disease ( 5% vs. 21% p=0.001 ) in the tirofiban - treated group .
slow flow entity was significantly higher in patients with diabetes mellitus ( 67% ) and in smokers ( 57% ) .
post - procedural slow flow rate ( 17% vs. 30% ; p<0.01 ) and distal embolization ( 6% vs. 16% ; p=0.01 ) were significantly lower in patients receiving tirofiban .
rate of major ( 8% vs. 5% ) and minor ( 29% vs. 9% ) bleeds were higher in the tirofiban group , but the only statistically significant difference was minor bleeding rate . during 6-month follow - up , post - procedural hemodialysis requirement , need for amputation , recurrent emboli , significant vessel lesions , and mortality were recorded in all patients .
the amputation rate was 9% and the rate of new occlusion was 19% . in both groups , hemodialysis requirement and recurrent emboli rates
also , development of significant occlusion in the thrombus region was similar between those receiving and not receiving tirofiban ( table 2 ) .
from these , 105 patients ( mean age 6716 years ; 53% men ) had 6-month follow - up .
the majority of patients ( 69% ) had infra - popliteal occlusion and below - knee atrial thrombus ( 67% ) presenting with a slightly higher frequency ( 54% ) of rutherford iib clinical status .
overall , atrial fibrillation ( n 64 , 61% ) and hypertension ( n 60 , 57% ) were the most important comorbidities .
clinical features of the tirofiban - treated and -untreated patients were similar to each other , except for a higher frequency of diabetes ( 52% vs. 40% ; p=0.05 ) and structural heart disease ( 5% vs. 21% p=0.001 ) in the tirofiban - treated group .
slow flow entity was significantly higher in patients with diabetes mellitus ( 67% ) and in smokers ( 57% ) .
post - procedural slow flow rate ( 17% vs. 30% ; p<0.01 ) and distal embolization ( 6% vs. 16% ; p=0.01 ) were significantly lower in patients receiving tirofiban .
rate of major ( 8% vs. 5% ) and minor ( 29% vs. 9% ) bleeds were higher in the tirofiban group , but the only statistically significant difference was minor bleeding rate .
during 6-month follow - up , post - procedural hemodialysis requirement , need for amputation , recurrent emboli , significant vessel lesions , and mortality were recorded in all patients .
in both groups , hemodialysis requirement and recurrent emboli rates were the same ( table 2 ) .
also , development of significant occlusion in the thrombus region was similar between those receiving and not receiving tirofiban ( table 2 ) .
early pt intervention in ali even without tirofiban use is an easy and effective approach .
major bleeding rate has not increased but the minor bleeding rate was high . in all groups of patients , additional procedures increased the success rate to 91.5% .
however , with exclusion , none of the patients were in rutherford iii stage in the first 24 h. there is not any criterion standard invasive or medical treatment approach in ali . though knee and below - knee region thromboses rate are 50% of all cases , their response rate to treatment is lower than in upper segments .
below - knee arterial thromboses occurred in 67% of our cases ; they were complicated lesions for successful bypass or thrombectomy .
even if the operation is successful , the surgical mortality rate can reach to 20% , especially in old and comorbid patients .
its use in knee and below - knee arterial thromboses is rare and not easy .
the rates of major and minor bleeding using the thrombolytic approach are 617% and up to 17% , respectively [ 2730 ] .
the low success rate in thrombolytic treatment is due to slow revascularization effect , inability to prevent myocardial infarction , organization of thrombus with different ages , and resistance to thrombolytic therapy .
mechanical thrombectomy is another effective approach to below - knee arterial thromboses , with a success rate of 90% .
other possible complications are residual occlusion , distal embolization , dissection , or lesions which need balloon or stent . acute renal insufficiency due to hemoglobinuria caused by extreme muscle damage during or after mechanical thromboembolectomy may occur .
administration of pt in the coronary system or in acute myocardial infarction effectively reduces thrombus load and prevents no - reflow / slow flow . in myocardial infarction , aspiration of the thrombus and cleaning of atherosclerosis material before stent implantation has improved blood flow in arterioles and capillaries .
there are studies that show pt administration in ali is effective . however , distal microembolization and dissection are disadvantages of pt use . in our study ,
the most important disadvantage was dissection via catheter , which significantly interrupts the flow ( 8% ) .
this could be related to our catheter selection according to the vessel diameter for pt .
even with the thrombolytic approach , catheter - related trauma is 1.4% . in our cases ,
although ali can be treated up to 14 days after injury , early intervention reduces tissue damage and improves success .
interventions within 24 h has good outcomes . in our study , we have seen the same outcomes .
good outcomes and high success rate are due to intervention within 24 h. in the early stages , the thrombus is softer and more mobile .
later , the thrombus gets more organized and does not respond to thrombus aspiration and other medical procedures .
outcomes are also good in long - term follow - up ( amputation 9% , survival rate 99% ) . in our study , no patient with clinical stage of rutherford iii was included within 24 h. this shows that early intervention prevented irreversible damage .
we observed no acute renal insufficiency case in our study , due to early intervention that reduces tissue damage and reopens the vessels .
it has the same early revascularization benefits in myocardial infarction and cerebrovascular events , and in our study we had the same results .
distal embolization is another factor affecting amputation and success rates of the procedure . in our study ,
amputation could be needed despite successful revascularization . in our study , the amputation rate was 11% , and in the tirofiban group it was lower ( 6% ) .
aha and esc have recommended tirofiban use in patients with massive thrombus , no - flow , slow flow , and thrombolytic complications for st segment elevation myocardial infarction .
tirofiban is effective in peripheral arterial disease with massive thrombus load , and using ali with tpa has been shown to be effective and safe . decreased distal microembolization , platelet aggregation , and vascular thrombus formation potentially decreased abrupt ppi closure
have increased the efficacy of thrombolytic therapy and improved long - term revascularization rates , with a potential decreased need for secondary re - interventions , especially in the diabetic ali population .
pt in ali has not been evaluated yet . in our study , tirofiban was effective and useful on slow flow and distal embolization .
the importance of slow flow in ali is not known well , but slow flow is associated with distal embolization .
diabetes mellitus and smoking , which are risk factors for slow flow , are also risk factor for slow flow entity in ali [ 4749 ] . despite the different amputation rates , it is lower in the tirofiban group ( 11% vs. 6% ) .
the amputation rate was not significant in our study , probably due to patient number ; however , significant outcomes could be reached in studies with more patients .
amputation can be secondary to distal embolization , so a lower amputation rate can be due to lower slow flow and distal emboli rate .
as mentioned before , tirofiban is useful when applied to peripheric vascular disease for slow flow and distal microemboli .
so during or post - surgical intervention , when slow flow or distal embolization is seen , tirofiban infusion can improve long - term success of the intervention .
however , the adverse effect of bleeding on mortality and morbidity ( 8% ) was lower than with other methods like thrombolytic approach .
major bleeding and minor bleeding rates were 613% and 517% , respectively . in ali when patients other diseases are taken in account , tirofiban has a negative effect on them but not on the procedure - related morbidity .
our study has some limitations : it was a non - randomized retrospective study , and the number of patients in the study group was small because of inclusion of patients presenting within 24 h of symptom onset and the localization of the thrombus .
pt approach only within 24 h of symptoms of ali in knee and below - knee arteries is impressively effective , with satisfactory results .
tirofiban could be used effectively in patients with slow flow entity and distal embolization , without increasing further risk .
 backgroundacute limb ischemia ( ali ) is a clinical entity with a high rate of morbidity and mortality . despite advances and variety of its management 
 , there is still no criterion standard treatment . 
 the goal of this study was to evaluate the effect of tirofiban use on the early and 6-month prognosis of patients with knee and below - knee arterial thrombosis who were treated with percutaneous thrombosuction ( pt ) within 24 h.material/methodsdata of consecutive ali patients who were diagnosed with popliteal and infra - popliteal arterial thrombosis and underwent pt procedure within 24 h between january 2010 and september 2015 were evaluated retrospectively . 
 patients were separated into 2 groups according to tirofiban usage.resultsa total of 105 patients ( mean age 6716 ; 53% men ) were included in the study . 
 atrial fibrillation ( n 64 , 61% ) and hypertension ( n 60 , 57% ) were the most frequent comorbidities in patients with thromboembolic events . a significantly higher rate of distal embolization ( 6% vs. 16% ; p=0.01 ) and slow - flow ( 17% vs. 30% ; p<0.01 ) developed in patients who were not treated with tirofiban after the pt procedure . although major and minor bleeding were more frequent in the tirofiban group , only the rate minor bleeding was statistically significant ( 29% vs. 9% , p=0.001 ) . 
 reverse embolic event ratio was similar in both groups . 
 although there was a higher rate of amputation in patients not treated with tirofiban , the difference was not significant.conclusionsadding tirofiban to pt reduces angiographic thromboembolic complications . 
 usage of tirofiban in patients prone to thromboembolic events may be useful for improving success of the pt procedure , with a reasonable bleeding ratio . 