scholarly journals (More than) doubling down: Effective fibrinolysis at a reduced rt-PA dose for catheter-directed thrombolysis combined with histotripsy

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0261567
Author(s):  
Samuel A. Hendley ◽  
Aarushi Bhargava ◽  
Christy K. Holland ◽  
Geoffrey D. Wool ◽  
Osman Ahmed ◽  
...  

Deep vein thrombosis is a major source of morbidity and mortality worldwide. For acute proximal deep vein thrombosis, catheter-directed thrombolytic therapy is an accepted method for vessel recanalization. Thrombolytic therapy is not without risk, including the potential for hemorrhagic bleeding that increases with lytic dose. Histotripsy is a focused ultrasound therapy that generates bubble clouds spontaneously in tissue at depth. The mechanical activity of histotripsy increases the efficacy of thrombolytic therapy at doses consistent with current pharmacomechanical treatments for venous thrombosis. The objective of this study was to determine the influence of lytic dose on histotripsy-enhanced fibrinolysis. Human whole blood clots formed in vitro were exposed to histotripsy and a thrombolytic agent (recombinant tissue plasminogen activator, rt-PA) in a venous flow model perfused with plasma. Lytic was administered into the clot via an infusion catheter at concentrations ranging from 0 (control) to 4.54 μg/mL (a common clinical dose for catheter-directed thrombolysis). Following treatment, perfusate samples were assayed for markers of fibrinolysis, hemolysis, and intact red blood cells and platelets. Fibrinolysis was equivalent between the common clinical dose of rt-PA (4.54 μg/mL) and rt-PA at a reduction to one-twentieth of the common clinical dose (0.23 μg/mL) when combined with histotripsy. Minimal changes were observed in hemolysis for treatment arms with or without histotripsy, potentially due to clot damage from insertion of the infusion catheter. Likewise, histotripsy did not increase the concentration of red blood cells or platelets in the perfusate following treatment compared to rt-PA alone. At the highest lytic dose, a refined histotripsy exposure scheme was implemented to cover larger areas of the clot. The updated exposure scheme improved clot mass loss and fibrinolysis relative to administration of lytic alone. Overall, the data collected in this study indicate the rt-PA dose can be reduced by more than a factor of ten and still promote fibrinolysis when combined with histotripsy.

2017 ◽  
Vol 23 (8) ◽  
pp. 938-942
Author(s):  
Alenka Premuš Marušič ◽  
Igor Locatelli ◽  
Aleš Mrhar ◽  
Martin Caprnda ◽  
Ludovit Gaspar ◽  
...  

Deep vein thrombosis (DVT) and pulmonary embolisms (PEs) are common complications after surgical procedures. The influence of prescribed blood products on the occurrence of DVT and PE was evaluated in postsurgical patients in this retrospective case–control study. The records of 286 surgical patients were analyzed: DVT (n = 52), PE (n = 92), and a control group (n = 142). The amounts of prescribed blood, blood products, and vitamin K were reviewed, together with appropriate prescribing of low-molecular-weight heparins. The influence of prescribed blood products on the occurrence of DVT or PE was analyzed using multinomial logistic regression. We demonstrated a significant difference between the test and control groups ( P < .05) in relation to receiving packed red blood cells. Treatment with red blood cells was associated with an increased risk of PE but not DVT. Patients who developed PE after surgery were hospitalized for longer (median 10 days) than patients with DVT (median 6 days). There was no difference between the test and control groups concerning treatment with fresh frozen plasma. Inadequate thromboprophylaxis significantly increased the likelihood of DVT. There is a connection between receiving packed red blood cells and occurrence of postoperative PE in surgical patients. Thus, patients receiving red blood cells should be monitored more closely after surgery, as they are more likely to develop PE postoperatively.


1982 ◽  
Vol 7 (2) ◽  
Author(s):  
G. Jacolot ◽  
P. Legendre ◽  
L. Millour ◽  
J.F. Morin ◽  
P.P. Morin

Author(s):  
Ali Mohammad Haji Zeinali ◽  
Yaser Jenab ◽  
Hamid Ariannejad ◽  
Seyed Ebrahim Kassaian ◽  
Mohammad Alidoosti ◽  
...  

Iliofemoral deep vein thrombosis (IFDVT) is a potentially devastating condition comprising a quarter of all cases of lower extremity DVT. It can lead to serious consequences such as pulmonary embolism, limb malperfusion, and post-thrombotic syndrome (PTS), which is a chronic sequela of IFDVT. We herewith present 18 IFDVT cases managed with catheter-directed thrombolysis at our hospital. Nine of these patients underwent stenting of the involved iliac veins. The remaining 9, who did not receive stenting, had a residual stenosis of more than 50% in the common femoral or iliac veins following the procedure. Based on a final residual stenosis of less than 50% in the iliac veins, we had 9 successful (patients with stenting) and 9 unsuccessful procedures (patients without stenting). In subsequent follow-ups at a median follow-up of 39.5 months, using the Villalta score, while only 2 out of the 9 patients who underwent stenting suffered PTS, 4 patients among the other 9 patients comprising the non-stenting group developed PTS. Our results support the notion that stenting might have a role in decreasing the PTS risk in patients undergoing catheter-directed thrombolysis.  


1998 ◽  
Vol 79 (03) ◽  
pp. 517-519 ◽  
Author(s):  
Stephane Heymans ◽  
Raymond Verhaeghe ◽  
Luc Stockx ◽  
Désiré Collen

SummaryThe feasibility of catheter-directed thrombolysis with recombinant staphylokinase was evaluated in six selected patients with deep vein thrombosis. The patients underwent intrathrombus infusion of recombinant staphylokinase (2 mg bolus followed by a continuous infusion of 1 mg/h). Heparin was given via the catheter as a bolus (5000 U) and as a continuous infusion (1000 U/h). Complete lyis was obtained in five patients and partial lysis in one patient. Complications consisted of minor bleeding in four subjects. Symptomatic reocclusion occurred in one. Debulking of the thrombus mass by a high speed rotating impeller (n = 1) and stenting (n = 3) were used as additional interventions. An underlying anatomical abnormality was present in two patients. Long term follow up revealed normal patency in all patients and normal valve function in four patients. Symptomatic venous insufficiency with valve dysfunction was present in the two with a second thrombotic episode.Thus catheter-directed infusion of recombinant staphylokinase in patients with deep vein thrombosis appears feasible and may be associated with a high frequency of thrombolysis. Larger studies to define the clinical benefit of this treatment appear to be warranted.


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