Thrombolysis in Pulmonary Embolia at the Cardiology Department of Aristide le Dantec Cardiology Department

Introduction: Venous thromboembolic disease is the 3rd most common cardiovascular pathology. Acute pulmonary embolism constitutes its most serious presentation and a major cause of mortality, morbidity and hospitalization in Africa and Senegal. The objectives of this work were to study the epidemiological profile of pulmonary embolisms and to evaluate the practice of thrombolysis in patients in a cardiological setting. Methodology: A retrospective, descriptive study was carried out in the Cardiology department of the Aristide le Dantec Hospital (HALD) over the period from August 2011 to December 2019 in patients hospitalized in the cardiology department for pulmonary embolism confirmed by CT angiography and/or with thrombi on cardiac ultrasound and who had also benefited from thrombolysis. Results: Thirty-one patients with pulmonary embolism were thrombolyzed. There was a predominance of the female gender with an average age of 45.97 years. Risk factors were dominated by age (61.29%) followed by obesity (32.26%) and prolonged immobilization (22.5%). The functional signs were dominated by dyspnea (77.42%) followed by chest pain (51.62%) and cough (35.48%). The physical signs were dominated by right heart failure in 22.5% of cases, pulmonary condensation syndrome in 19.35%, and inflammatory large leg in 12.9% of cases. Echocardiography and chest CT angiography were the means of diagnosis. Nine of our patients presented with an intracardiac mass. Thrombotic treatment was administered in all patients. The average length of hospitalization was 12.32 days and in-hospital mortality was 32.26%. Conclusion: Pulmonary embolism does exist in our regions and is responsible for heavy mortality. Rapid and efficient support is essential. Prevention remains the corner-stone in the fight against this pathology.

Platelet-to-neutrophil ratio predicts hemorrhagic transformation and unfavorable outcomes in acute ischemic stroke with intravenous thrombolysis

BACKGROUND Acute ischemic stroke(AIS)retains a notable stance in global disease burden,with thrombolysis via recombinant tissue plasminogen activator(rtPA)serving as a viable management approach,albeit with variable outcomes and the potential for complications like hemorrhagic transformation(HT).The platelet-to-neutrophil ratio(P/NR)has been considered for its potential prognostic value in AIS,yet its capacity to predict outcomes following rtPA administration demands further exploration.AIM To elucidate the prognostic utility of P/NR in predicting HT and clinical outcomes following intravenous rtPA administration in AIS patients.METHODS Data from 418 AIS patients treated with intravenous rtPA at Thammasat University Hospital from January 2018 to June 2021 were retrospectively analyzed.The relationship between P/NR and clinical outcomes[early neurological deterioration(E-ND),HT,delayed ND(D-ND),and 3-mo outcomes]was scrutinized.RESULTS Notable variables,such as age,diabetes,and stroke history,exhibited statistical disparities when comparing patients with and without E-ND,HT,D-ND,and 3-mo outcomes.P/NR prognostication revealed an optimal cutoff of 43.4 with a 60.3%sensitivity and a 52.5%specificity for 90-d outcomes.P/NR prognostic accuracy was statistically significant for 90-d outcomes[area under the curve(AUC)=0.562],D-ND(AUC=0.584),and HT(AUC=0.607).CONCLUSION P/NR demonstrated an association with adverse 3-mo clinical outcomes,HT,and D-ND in AIS patients post-rtPA administration,indicating its potential as a predictive tool for complications and prognoses.This infers that a diminished P/NR may serve as a novel prognostic indicator,assisting clinicians in identifying AIS patients at elevated risk for unfavorable outcomes following rtPA therapy.

Clinical outcomes of Angio Jet pharmacomechanical thrombectomy versus catheter-directed thrombolysis for the treatment of filter-related caval thrombosis

BACKGROUND The inferior vena cava filter is utilized worldwide to intercept thrombi and to reduce the risk of fatal pulmonary embolism(PE).However,filter-related thrombosis is a complication of filter implantation.Endovascular methods such as AngioJet rheolytic thrombectomy(ART)and catheter-directed thrombolysis(CDT)can treat filter-related caval thrombosis,but the clinical outcomes of both treatment modalities have not been determined.AIM To compare the treatment outcomes of AngioJet rheolytic thrombectomy vs catheter-directed thrombolysis in patients with filter-related caval thrombosis.METHODS In this single-center retrospective study,65 patients(34 males and 31 females;mean age:59.0±13.43 years)with intrafilter and inferior vena cava thrombosis were enrolled between January 2021 and August 2022.These patients were assigned to either the AngioJet group(n=44)or the CDT group(n=21).Clinical data and imaging information were collected.Evaluation measures included thrombus clearance rate,periprocedural complications,urokinase dosage,incidence of PE,limb circumference difference,length of stay,and filter removal rate.RESULTS Technical success rates were 100%in the AngioJet and CDT groups.In the AngioJet group,grade II and grade III thrombus clearance was achieved in 26(59.09%)and 14(31.82%)patients,respectively.In the CDT group,grade II and grade III thrombus clearance was accomplished in 11(52.38%)patients and 8(38.10%)patients,respectively(P>0.05).The peridiameter difference of the thigh was significantly reduced in patients from both groups after treatment(P<0.05).The median dosage of urokinase was 0.08(0.02,0.25)million U in the AngioJet group and 1.50(1.17,1.83)million U in the CDT group(P<0.05).Minor bleeding was shown in 4(19.05%)patients in the CDT group,and when it was compared with that in the AngioJet group,the difference was statistically significant(P<0.05).No major bleeding occurred.Seven(15.91%)patients in the AngioJet group had hemoglobinuria and 1(4.76%)patient in the CDT group had bacteremia.There were 8(18.18%)patients with PE in the AngioJet group and 4(19.05%)patients in the CDT group before the intervention(P>0.05).Computed tomography angiopulmonography(CTA)showed that PE was resolved after the intervention.New PE occurred in 4(9.09%)patients in the AngioJet group and in 2(9.52%)patients in the CDT group after theintervention(P>0.05).These cases of PE were asymptomatic.The mean length of stay was longer in the CDT group(11.67±5.34 d)than in the AngioJet group(10.64±3.52 d)(P<0.05).The filter was successfully retrieved in the first phase in 10(47.62%)patients in the CDT group and in 15(34.09%)patients in the AngioJet group(P>0.05).Cumulative removal was accomplished in 17(80.95%)out of 21 patients in the CDT group and in 42(95.45%)out of 44 patients in the ART group(P>0.05).The median indwelling time for patients with successful retrieval was 16(13139)d in the CDT group and 59(12231)d in the ART group(P>0.05).CONCLUSION Compared with catheter-directed thrombolysis,AngioJet rheolytic thrombectomy can achieve similar thrombus clearance effects,improve the filter retrieval rate,reduce the urokinase dosage and lower the risk of bleeding events in patients with filter-related caval thrombosis.

Outcomes of catheter-directed thrombolysis versus systemic thrombolysis in the treatment of pulmonary embolism: a metaanalysis

OBJECTIVE To evaluate the safety and efficacy of catheter-directed thrombolysis(CDT)versus systemic thrombolysis(ST)in the treatment of pulmonary embolism(PE).METHODS The Cochrane Library,PubMed,and Embase databases were searched to collect the literature on the comparison of the results of CDT and ST in the treatment of PE from the beginning of their records to May 2020,and meta-analysis was performed by STATA software(version 15.1).Using standardized data-collection forms,the authors screened the studies and independently extracted data,and assessed the quality of the studies using the Newcastle-Ottawa Scale for cohort studies.Cohort studies that examined the following results were included in the current study:in-hospital mortality,all-cause bleeding rate,gastrointestinal bleeding rate,intracranial hemorrhage rate,the incidence of shock,and hospital length of stay.RESULTS A total of eight articles,with 13,242 participants,involving 3962 participants in the CDT group and 9280 participants in the ST group were included.CDT compared with ST in the treatment of PE can significantly affect in-hospital mortality rate[odds ratio(OR)=0.41,95%CI:0.30–0.56,P<0.05],all-cause bleeding rate(OR=1.20,95%CI:1.04–1.39,P=0.012),gastrointestinal bleeding rate(OR=1.43,95%CI:1.13–1.81,P=0.003),the incidence of shock(OR=0.46,95%CI:0.37–0.57,P<0.05),and hospital length of stay[standard mean difference(SMD)=0.16,95%CI:0.07–0.25,P<0.05].However,there was no significant effect on intracranial hemorrhage rate in patients with PE(OR=0.70,95%CI:0.47–1.03,P=0.070).CONCLUSIONS CDT is a viable alternative to ST in the treatment of PE,as it can significantly reduce in-hospital mortality rate,all-cause bleeding rate,gastrointestinal bleeding rate,and incidence of shock.However,CDT may prolong hospital length of stay to a certain extent.Further research is needed to evaluate the safety and efficacy of CDT and ST in the treatment of acute PE and other clinical outcomes.

Successful treatment of veno-arterial extracorporeal membrane oxygenation complicated with left ventricular thrombus by intravenous thrombolysis:A case report

BACKGROUND Left ventricular thrombus is a rare condition,for which appropriate treatments are not extensively studied.Although it can be treated by thrombectomy,such surgery can be difficult and risky,and not every patient can tolerate the surgery.CASE SUMMARY We report a case of a middle-aged man receiving veno-arterial extracorporeal membrane oxygenation(VA-ECMO)for acute myocardial infarction who developed left ventricular thrombus despite systemic anticoagulation.After systemic thrombolysis with urokinase,the left ventricular thrombus disappeared,ECMO was successfully withdrawn 9 days later,and the patient recovered and was discharged from hospital.CONCLUSION Systemic thrombolysis is a treatment option for left ventricular thrombus in addition to anticoagulation and thrombectomy.

The Effect of the Early Application of Tirofiban on Acute Ischemic Stroke (AIS) after Intravenous Thrombolysis with Urokinase

Objective:Discussion and analysis of the effect of the early application of Tirofiban on acute ischemic stroke(AIS)after intravenous thrombolysis with urokinase.Method:The subjects of this study are 40 patients with AIS admitted at the Yibin Fourth People’s Hospital,of which were computer-randomized into a control group(20 cases,with regular urokinase intravenous thrombolysis therapy)and a research group(20 cases,combined with early Tirofiban treatment)from January 2018 to December 2022.The intervention outcomes between these two groups were compared and analyzed.Result:The blood platelet-related parameters before treatment had no statistical difference between the two groups(P>0.05),but the research group was higher than that of the control group after treatment(P<0.05).The Barthel index before treatment in both groups had no statistical difference(P>0.05),but the research group was higher than that of the control group after treatment(P<0.05).Conclusion:Early Tirofiban treatment for patients with AIS after intravenous thrombolysis with urokinase could effectively regulate the blood platelet-related parameters,hence improving treatment benefits and living capacity for patients,with definite clinical benefits.

A randomized trail comparing primary percutaneous coronary intervention with a strategy of short-acting thrombolysis and immediate planned primary percutaneous coronary intervention in acute myocardial infarction

Objective This study was to evaluate the efficacy and safety of a short acting reduced dose fibrinolytic regimen to promote early infarct related artery (IRA) patency for acyute myocardial infarction (AMI) patients referred for percutaneous coronary intervention (PCI).Methods Following aspirin and heparin, 166 patients were randomized to a 50 mg bolus of recombinant tissue type plasminogen activator(rt PA) or to a same volume sodium chloride injection followed by immediate primary PCI. The end points included patency rates on catheterization laboratory (cath lab) arrival, revascularization results when PCI was performed, complication rates, left ventricular function and restored patency rate following PCI. Results Patency on cath lab arrival was 64% with rt PA (34% TIMI 3,30% TIMI 2), while 31% of placebo (13% TIMI 3, 18% TIMI 2). There was no difference in the restored TIMI 3 rates of IRA between the two groups (85% vs 87%). No difference were observed in stroke or major bleeding. Left ventricular function was similar in both groups (52±9% vs 50±8%), but left ventricular ejection fraction fraction (LVEF) was higher with patent IRA (TIMI 3) on cath lab arrival than that of others (56±12% vs 48±10%).Conclusions Strategy thrombolytic regimens were compatible with subsequent PCI lead to more frequenc early recanalization (before cath lab arrival), which facilitates greater left ventricular function preservation with no augmentation of adverse events.

Intracoronary arterial retrograde thrombolysis with percutaneous coronary intervention: a novel use of thrombolytic to treat acute ST-segment elevation myocardial infarction

Background Clearance of coronary arterial thrombosis is necessary in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing urgent percutaneous coronary intervention (PCI). There is currently no highly-recommended method of thrombus removal during interventional procedures. We describe a new method for opening culprit vessels to treat STEMI: intracoronary arterial retrograde thrombolysis (ICART) with PCI. Methods & Results Eight patients underwent ICART. The guidewire was advanced to the distal coronary artery through the occlusion lesion. Then, we inserted a microcatheter into the distal end of the occluded coronary artery over the guidewire. Urokinase (5–10 wu) mixed with contrast agents was slowly injected into the occluded section of the coronary artery through the microcatheter. The intracoronary thrombus gradually dissolved in 3–17 min, and the effect of thrombolysis was visible in real time. Stents were then implanted according to the characteristics of the recanalized culprit lesion to achieve full revascularization. One patient experienced premature ventricular contraction during vascular revascularization, and no malignant arrhythmias were seen in any patient. No reflow or slow flow was not observed post PCI. Thrombolysis in myocardial infarction flow grade and myocardial blush grade post-primary PCI was 3 in all eight patients. No patients experienced bleeding or stroke. Conclusions ICART was accurate and effective for treating intracoronary thrombi in patients with STEMI in this preliminary study. ICART was an effective, feasible, and simple approach to the management of STEMI, and no intraprocedural complications occurred in any of the patients. ICART may be a breakthrough in the treatment of acute STEMI.

Acute extensive portal and mesenteric venous thrombosis after splenectomy:Treated by interventional thrombolysis with transjugular approach

AIM:To present a series of cases with symptomatic acute extensive portal vein(PV)and superior mesenteric vein(SMV)thrombosis after splenectomy treated by transjugular intrahepatic approach catheter-directed thrombolysis. METHODS:A total of 6 patients with acute extensive PV-SMV thrombosis after splenectomy were treated by transjugular approach catheter-directed thrombolysis. The mean age of the patients was 41.2 years.After access to the portal system via the transjugular approach,pigtail catheter fragmentation of clots, local urokinase injection,and manual aspiration thrombectomy were used for the initial treatment of PV-SMV thrombosis,followed by continuous thrombolytic therapy via an indwelling infusion catheter in the SMV,which was performed for three to six days. Adequate anticoagulation was given during treatment, throughout hospitalization,and after discharge. RESULTS:Technical success was achieved in all 6 patients.Clinical improvement was seen in these patients within 12-24 h of the procedure.No complications were observed.The 6 patients were discharged 6-14 d(8±2.5 d)after admission.The mean duration of follow-up after hospital discharge was 40±16.5 mo.Ultrasound and contrast-enhanced computed tomography confirmed patency of the PV and SMV,and no recurrent episodes of PV-SMV thrombosis developed during the follow-up period. CONCLUSION:Catheter-directed thrombolysis via transjugular intrahepatic access is a safe and effective therapy for the management of patients with symptomatic acute extensive PV-SMV thrombosis.

Initial transcatheter thrombolysis for acute superior mesenteric venous thrombosis

AIM: To determine the optimal initial treatment modality for acute superior mesenteric vein thrombosis (ASMVT) in patients with circumscribed peritonitis.

Transhepatic catheter-directed thrombolysis for portal vein thrombosis after partial splenic embolization in combination with balloon-occluded retrograde transvenous obliteration of splenorenal shunt

A 66-year-old woman underwent partial splenic embolization （PSE） for hypersplenisrn with idiopathic portal hypertension （IPH）. One week later, contrast-enhanced CT revealed extensive portal vein thrombosis （PVT） and dilated portosystemic shunts. The PVT was not dissolved by the intravenous administration of urokinase. The right portal vein was canulated via the percutaneous transhepatic route under ultrasonic guidance and a 4 Fr. straight catheter was advanced into the portal vein through the thrombus. Transhepatic catheter-directed thrombolysis was performed to dissolve the PVT and a splenorenal shunt was concurrently occluded to increase portal blood flow, using balloon-occluded retrograde transvenous obliteration （BRTO） technique. Subsequent contrast-enhanced CT showed good patency of the portal vein and thrombosed splenorenal shunt. Transhepatic catheter-directed thrombolysis combined with BRTO is feasible and effective for PVT with portosystemic shunts.

Do statins reduce the mortality rate in stroke patients treated with systemic thrombolysis in a 5-year single-center study?

The present study investigated the association between pre-treatment with a cholesterol-lowering drug(statin) or new setting hereon and the effect on the mortality rate in patients with acute ischemic stroke who received intravenous systemic thrombolysis. During a 5-year period(starting in October 2008), 542 consecutive stroke patients who received intravenous systemic thrombolysis with recombinant tissue plasminogen activator(rt-PA) at the Department of Neurology, University Hospital Schleswig-Holstein, Campus Lübeck, Germany, were included. Patients were characterized according to statins. The primary endpoint was mortality;it was assessed twice: in hospital and 3 months after discharge. The secondary outcome was the rate of symptomatic intracerebral hemorrhage. Of the 542 stroke patients examined(mean age 72 ± 13 years;51% women, mean National Institutes of Health Stroke Scale(NIHSS) score 11), 138 patients(25.5%) had been pretreated with statin, while in 190 patients(35.1%) statin therapy was initiated during their stay in hospital, whereas 193(35.6%) never received statins. Patients pre-treated with statin were older and more frequently had previous illnesses(arterial hypertension, diabetes mellitus and previous cerebral infarctions), but were comparably similarly affected by the stroke(NIHSS 11 vs. 11;P = 0.76) compared to patients who were not on statin treatment at the time of cerebral infarction. Patients pretreated with statin did not differ in 3-month mortality from those newly treated to a statin(7.6% vs. 8%;P = 0.9). Interestingly, the group of patients pretreated with statin showed a lower rate of in hospital mortality(6.6% vs. 17.0;P = 0.005) and 3-month mortality(10.7% vs. 23.7%;P = 0.005) than the group of patients who had no statin treatment at all. The same effect was seen for patients newly adjusted to a statin during the hospital stay compared to patients who did not receive statins(3-month mortality: 7.1% vs. 23.7%;P < 0.001). With a good functional outcome(mRS ≤ 2), 60% of patients were discharged, the majority(69.6%;P < 0.001) of whom received a statin at discharge. The rate of symptomatic intracerebral hemorrhages in the course of cranial computed tomography was independent of whether the patients were pretreated with a statin or not(8.8% vs. 8.7%, P = 0.96). Pre-treatment with statin as well as new adjustment could reveal positive effect on prognosis of intravenous thrombolyzed stroke patients. Further investigations are required. The study was approved by the Ethic Committee of the University of Lübeck(approval No. 4-147).

Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 expression in early focal cerebral infarction following urokinase thrombolysis in rats

Activity of matrix metalloproteinase-9 increases following cerebral ischemia/reperfusion, and is associated with cerebral microvascular permeability, blood-brain barrier destruction, inflammatory cell infiltration and brain edema. Matrix metalloproteinase-9 also likely participates in thrombolysis. A rat model of middle cerebral artery infarction was established by injecting autologous blood clots into the internal carotid artery. At 3 hours following model induction, urokinase was injected into the caudal vein. Decreased neurological severity score, reduced infarct volume, and increased expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 were observed in the cerebral cortex 24 hours after urokinase thrombolysis. These results suggest that urokinase can suppress damage in the acute-early stage of cerebral infarction.

Synthesis and evaluation of cationic polymeric micelles as carriers of lumbrokinase for targeted thrombolysis

To achieve targeted thrombolysis, a targeted delivery system of lumbrokinase(LK) was constructed using RGDfk-conjugated hybrid micelles. Based on the specific affinity of RGDfk to glycoprotein complex of GP Ⅱ b/Ⅲ a expressed on the surface of membrane of activated platelet, LK loaded targeted micelles(LKTM) can be delivered to thrombus. The hybrid micelles were composed of polycaprolactone-block-poly(2-(dimethylamino) ethyl methacrylate)(PCL-PDMAEMA), methoxy polyethylene glycol-block-polycaprolactone(mPEG-PCL)and RGDfk conjugated polycaprolactone-block-polyethylene glycol(PCL-PEG-RGDfk). PCLPDMAEMA was synthesized via ring open polymerization(ROP) and atom transfer radical polymerization(ATRP). PCL-PEG-RGDfk was synthesized via ROP and carbodiimide chemistry. The prepared LKTM was characterized by dynamic light scattering(DLS) and transmission electron microscope(TEM). Colloidal stability assay showed the prepared LKTM was stable. Biocompatibility assay was performed to determine the safe concentration range of polymer. The assay of fluorescent distribution in vivo demonstrated that LKTM can be efficiently delivered to thrombi in vivo. Thrombolysis in vivo indicated the thrombolytic potency of LKTM was optimal in all groups. Notably, the laboratory mice treated with LKTM exhibited a significantly shorter tail bleeding time compared to those treated with LK or LK-loaded micelles without RGDfk, which suggested that the targeted delivery of LK using RGDfk-conjugated hybrid micelles effectively reduced the bleeding risk.

Mechanical breakdown and thrombolysis in subacute massive pulmonary embolism: A prospective trial

AIM: To assess role of combined modality of mechanical fragmentation and intralesional thrombolysis in patients with massive pulmonary embolism presenting subacutely. METHODS: Eight of 70 patients presenting in tertiary care centre of North India with massive pulmonary embolism within 4 years had subacute presentation (symptom onset more than 2 wk). These patients were subjected to pulmonary angiography with intention to treat basis via mechanical breakdown and intra lesional thrombolysis. Mechanical breakdown of embolus was accomplished with 5-F multipurpose catheter to reestablish flow, followed by intralesional infusion of urokinase (4400 IU/kg over 10 min followed by 4400 IU/kg per hour over 24 h). RESULTS: Eight patients, mean age 47.77±12.20 years presented with subacute pulmonary embolism (mean duration of symptoms 2.4 wk). At presentation, mean heart rate, shock index, miller score and mean pulmonary pressures were 101.5±15.2/min, 0.995±0.156, 23.87±3.76 and 37.62±6.67 mmHg which reduced to 91.5±12.2/min (P=0.0325), 0.789±0.139 (P=0.0019), 5.87±1.73 (P=0.0000004) and 27.75±8.66 mmHg (P=0.0003) post procedurally. Mean BP improved from 80.00±3.09 mmHg to 90.58±9.13 mmHg (P=0.0100) post procedurally. Minor complications in the form of local hematoma-minor hematoma in 1 (12.5%), and pseudoaneurysm (due to femoral artery puncture) in 1 (12.5 %) patient were seen. At 30 d and 6 mo follow up survival rate was 100% and all the patients were asymptomatic and in New York Heart Association class 1. CONCLUSION: Combined modality of mechanical fragmentation and intralesional thrombolysis appears to be a promising alternative to high risk surgical procedures in patients with subacute massive pulmonary embolism.

Agitation thrombolysis combined with catheter-directed thrombolysis for the treatment of non-cirrhotic acute portal vein thrombosis

AIM To evaluate the safety and efficacy of agitation thrombolysis(AT) combined with catheter-directed thrombolysis(CDT) for the treatment of non-cirrhotic acute portal vein thrombosis(PVT). METHODS Nine patients with non-cirrhotic acute PVT who underwent AT combined with CDT were analyzed retrospectively. Portography was carried out via the transjugular intrahepatic portosystemic(commonly known as TIP) or percutaneous transhepatic(commonly known as PT) route, followed by AT combined with CDT. Complications of the procedure, and the changes in clinical symptoms, hemodynamics of the portal vein and liver function were recorded. Follow-up was scheduled at1, 3 and 6 mo after treatment, and every 6 mo thereafter, or when the patients developed clinical symptoms related to PVT. Color Doppler ultrasound and contrast-enhanced computed tomography/magnetic resonance imaging were performed during the follow-up period to determine the condition of the portal vein.RESULTS AT combined with CDT was successfully performed. The portal vein was reached via the TIP route in 6 patients, and via the PT route in 3 patients. All clinical symptoms were relieved or disappeared, with the exception of 1 patient who died of intestinal necrosis 9 d after treatment. Significant differences in the changes in portal vein hemodynamics were observed, including the maximum lumen occupancy of PVT, portal vein pressure and flow velocity between pre-and posttreatment(P < 0.05). During the follow-up period, recurrence was observed in 1 patient at 19 mo after the procedure, and the portal vein was patent in the remaining patients.CONCLUSION AT combined with CDT is a safe and effective method for the treatment of non-cirrhotic acute PVT.

Recombinant Tissue Plasminogen Activator-conjugated Nanoparticles Effectively Targets Thrombolysis in a Rat Model of Middle Cerebral Artery Occlusion

The efficacy and safety of recombinant tissue plasminogen activator （rtPA） need to be improved due to its low bioavailability and requirement of large dose administration. The purpose of this study was to develop a fibrin-targeted nanoparticle （NP） drug delivery system for thrombosis combination therapy. We conjugated rtPA to poly（ethylene glycol）- poly（ε-caprolactone） （PEG-PCL） nanoparticles （rtPA-NP） and investigated its physicochemical characteristics such as particle size, zeta potential, enzyme activity of conjugated rtPA and its storage stability at 4℃. The thrombolytic activity of rtPA-NP was evaluated in vitro and in vivo as well as the half-life of rtPA-NP, the properties to fibrin targeting and its influences on systemic hemostasis in vivo. The results showed that rtPA-NP equivalent to 10% of a typical dose of rtPA could dissolve fibrin clots and were demonstrated to have a neuroprotective effect after focal cerebral ischemia as evidenced by decreased infarct volume and improved neurological deficit （P〈0.001）. RtPA-NP did not influence the in vivo hemostasis or coagulation system. The half-life of conjugated rtPA was shown to be approximately 18 times longer than that of free rtPA. These experiments suggested that rtPA-conjugated PEG-PCL nanoparticles might be a promising fibrin-targeted delivery system for a combination treatment of thrombosis.

Thrombolysis during extended cardiopulmonary resuscitation for autoimmune-related pulmonary embolism

BACKGROUND: Massive pulmonary embolism(MPE) and acute myocardial infarction are the two most common causes of cardiac arrest(CA). At present, lethal hemorrhage makes thrombolytic therapy underused during cardiopulmonary resuscitation, despite the potential benefits for these underlying conditions. Hypercoagulability of the blood in autoimmune disorders(such as autoimmune hemolytic anemia) carries a risk of MPE. It is critical to find out the etiology of CA for timely thrombolytic intervention.METHODS: A 23-year-old woman with a 10-year medical history of autoimmune hemolytic anemia suffered from CA in our emergency intensive care unit. ECG and echocardiogram indicated the possibility of MPE, so f ibrinolytic therapy(alteplase) was successful during prolonged resuscitation.RESULTS: Neurological recovery of the patient was generally good, and no fatal bleeding developed. MPE was documented by CT pulmonary angiography.CONCLUSIONS: A medical history of autoimmune disease poses a risk of PE, and the causes of CA(such as this) should be investigated etiologically. A therapy with alteplase may be used early during cardiopulmonary resuscitation once there is presumptive evidence of PE. Clinical trials are needed in this setting to study patients with hypercoagulable states.

EFFECTS OF THROMBOLYSIS WITH ULTRASOUND ON THE STRUCTURE OF ERYTHROCYTE AND ITS SAFETY THRESHOLD

The study was to investigate thrombolysis in vitro with ultrasound, and to discuss effects of thrombolysis with ultrasound on the structure of erythrocyte and its safety threshold under different ultrasound intensity and exposure time. The structure of erythrocyte in thrombus was evaluated under light microscope. The relationship between the structure of erythrocyte in thrombus and ultrasound intensity and exposure time was obtained. The results showed that ultrasound eliminated the thrombus. According to the change of the structure of erythrocyte in thrombus and ultrasound intensity and exposure time, the effects of thrombolysis with ultrasound could be divided into three kinds of areas: the A, B, C area. The area A was the safe area, the area B was the relatively safe area, and the area C was the irreversible damage area. The study suggested that ultrasound intensity and exposure time had significant impact on the structure of erythrocyte. Stronger ultrasound intensity or longer exposure time could cause erythrocytes irreversible damage. It could accelerate thrombolysis and shorten the exposure time that the ultrasound intensity was little bit increased. The study of effects of thrombolysis with ultrasound on the structure of erythrocyte and its safety threshold were important for practical applications.

Intra-arterial thrombolysis for early hepatic artery thrombosis after liver transplantation

BACKGROUND Early hepatic artery thrombosis(E-HAT)is a serious complication after liver transplantation(LT),which often results in graft failure and can lead to patient deaths.Treatments such as re-transplantation and re-anastomosis are conventional therapeutic methods which are restricted by the shortage of donors and the patient’s postoperative intolerance to re-laparotomy.Due to the advances in interventional techniques and thrombolytics,endovascular treatments are increasingly being selected by more and more centers.This study reviews and reports our single-center experience with intra-arterial thrombolysis as the first choice therapy for E-HAT after deceased donor LT.AIM To evaluate the feasibility and reasonability of intra-arterial thrombolysis for EHAT after deceased donor LT.METHODS A total of 147 patients who underwent deceased donor LT were retrospectively reviewed in our hospital between September 2011 and December 2016.Four patients were diagnosed with E-HAT.All of these patients underwent intraarterial thrombolysis with alteplase as the first choice therapy after LT.The method of arterial anastomosis and details of the diagnosis and treatment of EHAT were collated.The long-term prognosis of E-HAT patients was also recorded.The median follow-up period was 26 mo(range:23 to 30 mo).RESULTS The incidence of E-HAT was 2.7%(4/147).E-HAT was considered when Doppler ultrasonography showed no blood flow signals and a definite diagnosis was confirmed by immediate hepatic arterial angiography when complete occlusion of the hepatic artery was observed.The patients were given temporary thrombolytics(mainly alteplase)via a 5-Fr catheter which was placed in the proximal part of the thrombosed hepatic artery followed by continuous alteplase using an infusion pump.Alteplase dose was adjusted according to activated clotting time.The recanalization rate of intra-arterial thrombolysis in our study was 100%(4/4)and no thrombolysis-related mortality was observed.During the follow-up period,patient survival rate was 75%(3/4),and biliary complications were present in 50%of patients(2/4).CONCLUSION Intra-arterial thrombolysis can be considered first-line treatment for E-HAT after deceased donor LT.Early diagnosis of E-HAT is important and follow-up is necessary even if recanalization is successful.