Role Of Thrombolysis Research Articles

Novel Deep Sea Isoindole Alkaloid FGFC1 Exhibits Its Fibrinolytic Effects by Inhibiting Thrombin-Activatable Fibrinolysis Inhibitor

Background: The thrombin-activatable fibrinolysis inhibitor (TAFI) is an important regulator in the balance between blood clot formation (coagulation) and dissolution (fibrinolysis), which is mainly activated by thrombin bonded with thrombomodulin (TM). Methods: In this study, the investigation focused on the unique target TAFI of fungi fibrinolytic compound 1 (FGFC1), a novel fibrinolytic compound sourced from the deep sea. In this sense, the regulation of TAFI by FGFC1, in comparison to established TAFI inhibitors such as DS-1040 and PCTI in hPPP, was investigated, which was validated through the molecular docking of FGFC1 to TAFI. The inhibitory effect of FGFC1 on TAFI-mediating coagulation (ex vivo and in vitro) and its fibrinolytic effect (ex vivo) were investigated in hPPP and hCMEC/D3 cells, respectively, followed by SEM. Results: FGFC1 solutions ranging from 0.023 to 0.736 mM effectively inhibited TAFI activation. Notably, the 0.023 mM concentration demonstrated significant suppression, comparable to DS-1040 and PCTI. These inhibitory effects of FGFC1 (0.023–0.368 mM) were further validated through the enhancement in TAFI (TAFIa) activation by fibrins in the coagulum prior to proteolysis, resulting in the cleavage of TAFIa from 33 kDa to 28 kDa. Furthermore, these regulatory effects of FGFC1 on TAFI were demonstrated to have minimal association with TM-mediated control, as confirmed through a molecular docking analysis. FGFC1 (0.023–0.092 mM) was suggested to have obstructive effects on TAFI-mediated coagulation in the hPPP, which was demonstrated by the inhibition of clot aggregation, protein crystallization, and platelet anchoring, as observed through SEM. Simultaneously, FGFC1 (0.023 to 0.368 mM) significantly enhanced TAFI-mediated fibrinolysis, which was also supported by increased levels of t-PA, u-PA, and plasmin. Conclusions: From the above findings, FGFC1 is identified as a novel dual-target bioactive compound participating in blood formation/dissolution that demonstrates anti-coagulation and fibrinolytic effects by regulating TAFI activation, inhibiting TAFIa–fibrin combination, and initiating proteolysis. It also provided convincing evidence that TAFI plays a critical role in thrombolysis as a molecular link between coagulation and fibrinolysis. Furthermore, the application of FGFC1 was indicated as a potential therapeutic strategy in thromboembolic and hemorrhagic diseases.

The Role of Thrombolysis in the Complex Treatment of Complicated Popliteal Artery Aneurysms

RELEVANCE Thrombosis of a popliteal artery aneurysm is an intractable problem. For decades, the number of amputations in this disease has remained at the level of 20% and does not have a significant downward trend due to the fact that during thrombosis of an aneurysm, the infragenicular arteries, the only “outflow paths” for bypass surgery, are also thrombosed. Currently, in order to increase the capacity of the peripheral bloodstream, thrombolytic therapy has been proposed.AIM To evaluate the effectiveness of preoperative and intraoperative thrombolytic therapy in the surgical treatment of thrombosed popliteal aneurysms.MATERIAL AND METHODS In the period from 1997 to 2020, 94 patients with acute ischemia of the lower extremities caused by thrombosed popliteal aneurysms underwent 98 reconstructive surgeries at the N.V. Sklifosovsky Research Institute for Emergency Medicine. The age of the patients was 62.5±10.1 years. Group I (n=66/98 patients, 67.3%) consisted of patients after primary reconstructive surgery; Group II (n=32/98, 32.7%) consisted of patients who, in order to improve the patency of the infragenicular arteries, underwent thrombolytic therapy in addition to surgery (12 preoperative catheter-directed, 20 intraoperative). A retrospective analysis was carried out.RESULTS Limb preservation was achieved in 86.7% of patients. In Group I, early postoperative thrombosis occurred in 22.7% of cases (n=13/98), in Group II — in 6.3% (n=2/32), p<0.05; amputations were performed in Group I in 18.1% of patients (n=12/66), in Group II — in 3.1% of patients (n=1/32), p<0.04.

A Case of Complete Resolution of Cauda Equina Syndrome Caused by Extensive Iliocaval Thrombosis: The Role of Thrombolysis and Venous Stents.

The cauda equina syndrome (CES) is a rare condition affecting less than 1 in 100,000 patients annually. Diagnosing CES is challenging because of its rare incidence, potentially subtle presentation, and various underlying etiologies. Vascular causes, such as inferior vena cava (IVC) thrombosis, are uncommon but should be considered, since timely recognition and treatment of deep vein thrombosis (DVT) as a cause of CES can avoid irreversible neurological damage. A 30-year-old male presented with partial CES caused by nerve root compression due to venous congestion from an extensive iliocaval DVT. He completely recovered after thrombolysis and stenting of the IVC. His iliocaval tract remained patent until the last date of follow-up at 1 year without signs of post-thrombotic syndrome. Broad molecular, infectious, and hematological laboratory tests did not reveal any underlying disease for the thrombotic event, particularly no hereditary or acquired thrombophilia. Timely recognition of venous thrombosis as a cause of CES is essential. This is the first case report of CES caused by an extensive iliocaval DVT successfully treated with thrombolysis and venous stenting with good resolution of DVT and CES. This case-report describes a patient with cauda equina syndrome resulting from an extensive iliocaval deep vein thrombosis due to an underlying stenosis of the inferior vena cava. Thrombolysis and venous stenting succesfully restored venous patency and thereby relieved symptoms and signs of cauda equina syndrome, in addition to (long-term) therapeutic dose anticoagulation. It is important to timely recognize deep vein thrombosis as a cause of cauda equina syndrome and to consider endovenous treatment in a specialized center.

Ultra-Low-Dose Systemic Tissue Plasminogen Activator in High-Risk Submassive Pulmonary Embolism

Risk stratification of pulmonary embolism (PE) is vital for clinical management. While low-risk and high-risk PE management are clearly defined in many societal guidelines, the management of moderate-risk, also called submassive, PE remains unsettled. There is a subgroup of patients with submassive PE that progress to the severe category despite receiving systemic anticoagulation. The role of thrombolysis in the management of submassive PE remains to be established. We share our experience with ultra-low-dose (25-mg) systemic tissue plasminogen activator in a series of 4 patients with high-risk submassive PE.

De Winter syndrome, a STEMI-equivalent ECG pattern leading to life-threatening arrhythmia: A case report from a non-cardiac catheterization laboratory hospital

de Winter syndrome is a rare but important electrocardiographic pattern to recognize in patients presenting with chest pain. Under-recognition and delayed revascularization in patients with de Winter syndrome may lead to poor clinical outcomes. Despite increasing evidence of its association with total occlusion of the left anterior descending artery, the role of thrombolysis in the absence of percutaneous coronary intervention is not specifically addressed in recent international guidelines. Herein, we report a case of a 50-year-old gentleman with no known medical illness who presented with excruciating chest pain associated with diaphoresis, nausea, and reduced effort tolerance. Clinical examination revealed a distressed patient with bibasal crepitations with no other significant findings. The first ECG was sinus bradycardia with poor R-wave progression. ECG repeated 6 h later revealed de Winter syndrome. Within minutes, the patient developed sustained pulse ventricular tachycardia requiring synchronized cardioversion. The patient was intubated for impending cardiorespiratory failure. We took the pharmacoinvasive approach. The patient received thrombolytic therapy as percutaneous coronary intervention (PCI) was not available and transferring to the nearest cardiac center was not possible within the therapeutic window. He was then subsequently transferred to the nearest cardiac center post thrombolysis for PCI. We report this case study to highlight the importance of recognizing this STEMI-equivalent ECG pattern in patients presenting with chest pain, and call for randomized control trials to evaluate the effectiveness of thrombolytic therapy as an alternative emergent reperfusion strategy in de Winter syndrome in non-cardiac centers.

Low-dose thrombolysis for submassive pulmonary embolism

The role of thrombolysis in submassive pulmonary embolism (PE) is controversial due to the high risk of hemorrhage. This study aimed to evaluate the role of half-dose tissue-type plasminogen activator...

Clinical outcomes of submassive pulmonary embolism thrombolysis\u2014an Indian experience

BackgroundAcute pulmonary thromboembolism is the most dangerous presentation of venous thromboembolic disease. The role of thrombolysis in massive pulmonary embolism has been studied extensively, but the same is not there for submassive pulmonary embolism. This study is aimed at evaluating the effects of thrombolysis in acute submassive pulmonary embolism. This was a prospective, case-control, observational study. Patients presenting with acute submassive pulmonary embolism were divided into thrombolysis group and control group depending on whether they received thrombolysis plus anticoagulation or anticoagulation only, respectively.ResultsA total of 86 patients were included in the study. Forty-two patients were in the thrombolysis group, and 44 patients were in the control group. The mean ± SD age in the control and thrombolysis groups was 63.3 ± 14.7 and 56.4 ± 13.8 years, respectively. The two groups were well matched in sex distribution and associated comorbidities like COPD, active surgery, major trauma, and immobilization. On echocardiography, dilated RA/RV in pre-treatment vs. post-treatment was seen in 20 (45.5%) vs. 20 (45.5%) in the control group and 26 (61.9%) vs. 11 (26.2%) in the thrombolysis group. Similarly, RV systolic dysfunction in pre-treatment vs. post-treatment was seen in 24 (54.5%) vs. 21 (47.7%) in the control group and 22 (52.4%) vs. 8 (19.0%) in the thrombolysis group. Pulmonary artery pressure in pre-treatment vs. post-treatment was 64.4 ± 15.0 vs. 45.9 ± 9.9 mmHg in the control group and 68.3 ± 17.4 vs. 31.4 ± 6.9 mmHg in the thrombolysis group. In control vs. thrombolysis group, there were 5 vs. 1 death, 6 vs. 1 hemodynamic decompensation, and 6 vs. 1 patient needing mechanical ventilation.ConclusionThrombolysis in submassive pulmonary embolism is associated with better right ventricular functions, lower pulmonary artery pressures, and comparable mortality rates.

P5715Trends in indications and outcome in thrombolytic therapy: a retrospective single center study

Abstract Background Thrombolytic therapy is used as a lifesaving treatment for a broad range of acute thrombotic events. The role of thrombolysis for its various indications has rapidly evolved. Purpose To provide a contemporary overview of current indications and outcome of thrombolytic therapy in clinical practice. Methods This retrospective single-center study analyzed indications, complications and short-term mortality of systemic thrombolytic therapy between 2010 and 2016 in a university hospital, totaling 763 cases. Major bleedings were defined using criteria published by the International Society on Thrombosis and Haemostasis (ISTH). Results Thrombolytic drugs were mostly used for ischemic strokes (66.6%) and peripheral arterial disease (16.9%). Acute coronary syndrome only represented a minority of cases (in this PCI-center). Overall seven- and thirty-day-mortality were 7.3% and 12.0%, respectively. Major bleeding occurred in 8.3% of patients and was fatal in 0.9% of all patients. Both major bleeding and mortality differed by the indication for thrombolysis. Thrombolytic therapy for pulmonary embolism and peripheral arterial disease were associated with the highest rates of major bleeding, 28.6% and 23.3% respectively. Short-term mortality was highest in patients receiving thrombolysis for pulmonary embolism. Predictors for major bleeding included use of antiplatelet and anticoagulation drugs prior to thrombolysis. Major bleedings, age and concomitant anticoagulation were associated with lower survival rates. Indications in absolute numbers – 2010 – – 2011 – – 2012 – – 2013 – – 2014 – – 2015 – – 2016 – Ischemic Stroke 56 63 66 57 96 88 82 Peripheral Arterial Disease 21 23 21 28 14 16 6 Pulmonary Embolism 4 9 10 10 5 8 8 Deep Vein Thrombosis 2 1 2 0 2 3 3 Acute Coronary Syndrome 0 1 0 1 0 0 0 Mechanical Heart Valve Thrombosis 1 3 3 1 2 7 1 Other 5 8 3 10 2 5 6 TOTAL 89 108 105 107 121 127 106 Mortality and major bleeding in % Conclusion The use of thrombolytic therapy has evolved, with stroke now being the most frequent indication. Mortality and bleeding rates are significant and vary considerably per indication. Major bleedings, age and maintenance anticoagulant therapy were risk factors associated with lower survival rates, but the underlying disease and patient population seem to play a major role in survival as well.

Systematic Review: The Role of Thrombolysis in Intermediate-Risk Pulmonary Embolism.

This systemic review provides practicing emergency physicians updated information about the role of thrombolysis in the treatment of intermediate-risk pulmonary embolism. A PubMed literature search from January 1, 2005 to December 31, 2018 was conducted and limited to human clinical trials written in English with relevant keywords. High-quality studies were identified and then underwent a structured review. Recommendations are made based on the literature review. Sixty-three articles met criteria for rigorous review, of which 13 were appropriate for citation in this review. Of these 13, there were 6 prospective studies and 7 retrospective studies. Thrombolysis, either catheter-directed or systemic, is a treatment option in the management of patients with intermediate-risk pulmonary embolism and a high likelihood of clinical deterioration. Each method of thrombolysis carries risks and benefits. Based on the available evidence, transfer to a facility for the purpose of catheter-directed thrombolysis is not recommended.

In silico Analysis of Several Signal Peptides for the Excretory Production of Reteplase in Escherichia coli

Background: Solubility of recombinant therapeutic enzymes is one of the major purpose their production in bacterial host The factors such as metabolic system, a cellular stress response of the bacterial host and formation of inclusion bodies cause undesirable expression results. One method to overcome this problem is secretion of recombinant protein into the extracellular growth medium by selection of proper signal peptides. Reteplase (Retavase) is a serine protease simulating endogenous tissue plasminogen activator (t-PA), fibrin-specific plasminogen activator, playing role in thrombolysis and fibrinolysis (clot lysis) by converting plasminogen to plasmin. Objective: The aim of this study was to evaluate several signal peptides in order to selection the proper one which suitable for excretory production of the reteplase. Method: The presence and cleavage site location in signal peptides was predicted by SignalP 4.1. The prediction of secretory pathway of signal peptides was performed using high accurate database. Several critical features of the signal peptide were evaluated applying various online web-servers such as ProtParam and Solpro with high sensitivity and specificity. Finally, the selected signal peptides were compared and the one which was appropriate candidate for high yields production of secretory reteplase in the E. coli host was defined. Results: Among total 30 signal peptides, 6 of them, CHIS_BACSU, MPT53_MYCTU, PET_ECOLX, PIC_ECOL6, PIC_ECLOX, TSH_ECOLX were omitted. CPLR_DESHA, AGAR_ALTAT, CDGT_BACS2, PAG_BACAN could be considered as proper candidate for efficient extracellular production of reteplase in E. coli. Conclusion: Theoretical analysis and evaluation of signal peptides by using computational tools can be acceptably carried out, but these results must be established via practical effort. Keywords: E. coli host, bioinformatics, secretion, physicochemical properties, solubility, signal peptides.

Abstract 187: Reversible Aptamer Inhibition of Von Willebrand Factor is a Potent Thrombolytic and Ameliorates Stroke Burden Following Vascular Injury Compared to Recombinant Tissue Plasminogen Activator

Introduction: While recombinant tissue plasminogen activator (rTPA) is the mainstay of ischemic stroke treatment, few patients are eligible for treatment, and recanalization is only seen in 25-50%. Von Willebrand Factor (VWF) inhibition may play a role in thrombolysis. Hypothesis: VWF inhibition with an RNA aptamer lyses arterial thrombus and decreases ischemic injury. Furthermore, aptamer reversal with an antidote oligonucleotide ameliorates intracranial hemorrhage (ICH). Methods: Adult wild-type (C57BL/6J) mice were anesthetized, and the right carotid artery was exposed. Baseline carotid flow was obtained using a Doppler flow probe, and thrombotic occlusion was induced with a ferric chloride patch. After clot stabilization, mice were administered vehicle (platelet binding buffer, n=11), no infusion (n=8), rTPA (n=5) or VWF aptamer (n=5). Carotid flow was monitored for an additional 100 minutes. In a second cohort of mice, a 6-0 nylon suture was advanced within the carotid artery to generate vascular injury and ICH. Mice were given vehicle (n=16), rTPA (n=11), VWF aptamer (n=9) or aptamer/antidote (n=8). An MRI was obtained after 90 minutes to assess stroke and ICH volumes. Results: VWF aptamer successfully restored carotid blood flow 45 minutes following carotid occlusion (Figure 1) compared to controls (p<0.01*) and rTPA (p<0.05 + ). Stroke volume was significantly decreased in mice treated with VWF aptamer (23.03 ± 6.81 mm 3 ) and aptamer/antidote (12.48 ± 5.68 mm 3 ) compared to vehicle (45.25 ± 4.14 mm 3 , p<0.01). ICH volumes in mice treated with rTPA (2.64 ± 0.84 mm 3 ) were trending higher than vehicle (1.51 ± 0.17 mm 3 ), VWF aptamer (1.92 ± 0.22 mm 3 ) or aptamer/antidote (1.31 ± 0.35 mm 3 ). Conclusions: Aptamer inhibition of VWF is a potent thrombolytic agent with greater efficacy compared to rTPA. VWF inhibition appears safe with a trend toward lower ICH volumes in animals treated with aptamer and aptamer/antidote compared to rTPA.

Abstract WP69: Reversible Aptamer Inhibition of Von Willebrand Factor is a Potent Thrombolytic and Ameliorates Stroke Burden Following Vascular Injury Compared to Recombinant Tissue Plasminogen Activator

Introduction: While recombinant tissue plasminogen activator (rTPA) is the mainstay of ischemic stroke treatment, few patients are eligible for treatment, and recanalization is only seen in 25-50%. Von Willebrand Factor (VWF) inhibition may play a role in thrombolysis. Hypothesis: VWF inhibition with an RNA aptamer lyses arterial thrombus and decreases ischemic injury. Furthermore, aptamer reversal with an antidote oligonucleotide ameliorates intracranial hemorrhage (ICH). Methods: Adult wild-type (C57BL/6J) mice were anesthetized, and the right carotid artery was exposed. Baseline carotid flow was obtained using a Doppler flow probe, and thrombotic occlusion was induced with a ferric chloride patch. After clot stabilization, mice were administered vehicle (platelet binding buffer, n=11), no infusion (n=8), rTPA (n=5) or VWF aptamer (n=5). Carotid flow was monitored for an additional 100 minutes. In a second cohort of mice, a 6-0 nylon suture was advanced within the carotid artery to generate vascular injury and ICH. Mice were given vehicle (n=16), rTPA (n=11), VWF aptamer (n=9) or aptamer/antidote (n=8). An MRI was obtained after 90 minutes to assess stroke and ICH volumes. Results: VWF aptamer successfully restored carotid blood flow 45 minutes following carotid occlusion (Figure 1) compared to controls (p<0.01*) and rTPA (p<0.05 + ). Stroke volume was significantly decreased in mice treated with VWF aptamer (23.03 ± 6.81 mm 3 ) and aptamer/antidote (12.48 ± 5.68 mm 3 ) compared to vehicle (45.25 ± 4.14 mm 3 , p<0.01). ICH volumes in mice treated with rTPA (2.64 ± 0.84 mm 3 ) were trending higher than vehicle (1.51 ± 0.17 mm 3 ), VWF aptamer (1.92 ± 0.22 mm 3 ) or aptamer/antidote (1.31 ± 0.35 mm 3 ). Conclusions: Aptamer inhibition of VWF is a potent thrombolytic agent with greater efficacy compared to rTPA. VWF inhibition appears safe with a trend toward lower ICH volumes in animals treated with aptamer and aptamer/antidote compared to rTPA.

Neonatal renal vein thrombosis: Role of anticoagulation and thrombolysis—An institutional review

ABSTRACTNeonatal renal vein thrombosis (NRVT) is a rare thromboembolic complication in the neonatal period, and sequelae from renal dysfunction can cause significant morbidity. The authors retrospectively reviewed 10 patients with NRVT treated at their institution. The majority of the cohort were male (n = 9), preterm (n = 6), and had unilateral NRVT (n = 6). Six patients received thrombolysis and/or anticoagulation, and 4 patients received supportive care only. Two of the 6 patients treated with anticoagulation who had bilateral NRVT and anuria received thrombolysis with low-dose tissue plasminogen activator. Thrombolysis was not associated with any major adverse events, and both patients had marked improvement of renal function. Eight patients subsequently developed renal atrophy (3 received anticoagulation, 2 received thrombolysis with anticoagulation, and 3 received supportive care). Anticoagulation/thrombolysis did not appear to prevent renal atrophy. The role of thrombolysis needs to be further studied and considered in the setting of bilateral NRVT and acute renal failure.

Compression in acute stroke: nursing considerations

British Journal of Neuroscience NursingVol. 11, No. Sup2 CommentCompression in acute stroke: nursing considerationsEmma GeeEmma GeeSearch for more papers by this authorEmma GeePublished Online:27 Apr 2015https://doi.org/10.12968/bjnn.2015.11.Sup2.20AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View article References CLOTS trial collaboration (2009) Effectiveness of thigh-length graduated compression stockings to reduce the risk of deep vein thrombosis after stroke (CLOTS Trial 1): a multicentre, randomised controlled trial. Lancet 373(9679): 1958–65 Crossref, Google ScholarCLOTS trials collaboration (2010) Thigh-length versus below-knee stockings for DVT prophylaxis after stroke: a randomised trial. Ann Intern Med 153(9): 553–62 Crossref, Google ScholarCLOTS (Clots in Legs Or sTockings after Stroke) Trials Collaboration et al. (2013) Effectiveness of intermittent pneumatic compression in reduction of risk of deep vein thrombosis in patients who have had a stroke (CLOTS3): a multicentre randomised controlled trial. Lancet 382(9891): 516–24 Crossref, Google ScholarCLOTS (Clots in Legs Or sTockings after Stroke) Trials Collaboration (2014) Effect of intermittent pneumatic compression on disability, living circumstances, quality of life, and hospital costs after stroke: secondary analyses from CLOTS 3, a randomised trial. Lancet Neurol 13(12): 1186–92 Crossref, Google ScholarKearon C (2003) Natural History of Venous Thromboembolism. Circulation 107(23): 122–30 Google ScholarKelly J, Rudd A, Lewis RR, Coshall C et al. (2004) Venous Thromboembolism after acute ischaemic stroke; a prospective study using magnetic resonance direct thrombus imaging. Stroke 35: 2320–25 Crossref, Google ScholarKohro S, Yamakage M, Sato K et al. (2005) Intermittent pneumatic foot compression can activate blood fibrinolysis without changes in blood coagulability and platelet activation. Acta Anaesthesiologica Scandinavica 49: 660–4 Crossref, Google ScholarLankeit M, Konstantinides S (2011) Mortality risk assessment and the role of thrombolysis in pulmonary embolism. Critical Care Clinics 27(4): 953–67 Crossref, Google ScholarNational Institute for Health and Care Excellence (2010) NICE clinical guidance 92. Venous thromboembolism: reducing the risk: Reducing the risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism) in patients admitted to hospital. https://www.nice.org.uk/guidance/cg92 (accessed 26 March 2015) Google ScholarNational Institute for Health and Care Excellence (2015) Addendum to NICE clinical guidance CG92. Reducing the risk of venous thromboembolism in patients admitted to hospital (Chapter 24-stroke patients). Draft for consultation. http://tinyurl.com/pdyk9xz (accessed 26 March 2015) Google ScholarStevens S, Woller S (2013) Intermittent pneumatic compression in patients with stroke. Lancet 382(9891): 484–6 Crossref, Google Scholar FiguresReferencesRelatedDetails 1 April 2015Volume 11Issue Sup2ISSN (print): 1747-0307ISSN (online): 2052-2800 Metrics History Published online 27 April 2015 Published in print 1 April 2015 Information© MA Healthcare LimitedPDF download

Role of thrombolysis in reperfusion therapy for management of AMI: Indian scenario

Cardiovascular disorders are the major cause of morbidity & mortality globally as well in India. In 2008, out of the 57 million deaths globally; around 63% (i.e., nearly 30 million deaths) were due to non-communicable diseases.1 Cardiovascular diseases accounts for nearly half of the deaths due to non-communicable diseases worldwide, thus becoming the leading cause of death due to non-communicable diseases. Approximately, 80% of these deaths have been reported to occur in low and middle-income countries.1 Moreover, out of nine million premature deaths due to non-communicable diseases (viz. age < 60 years); around eight million occurred in low and middle-income countries. With 6.8% and 5.0% of disability-adjusted life-years (DALYs) lost, CAD is the second largest causes of disease burden in population aged 15 years and older globally.1 1.1. Trends of cardiovascular diseases in India Cardiovascular diseases have assumed epidemic proportions in India as well. The Global Burden of Diseases (GBD) study reported the estimated mortality from coronary heart disease (CHD) in India to be 1.6 million in the year 2000 which is estimated to increase to ∼64 million by the year 2015.2 The projected rise in disease burden due to CVD is expected to make it the prime contributor of total mortality and morbidity.2 Reports on CAD in Indians have shown that Asian Indians are at 3–4 times higher risk of CAD than white Americans, 6 times higher than Chinese, and 20 times higher than Japanese.3 Various independent epidemiological studies conducted in North India suggest that the prevalence of CAD has increased from 1% in 1960 to 10.5% in 1998 in the urban population.3 A higher prevalence of CAD, ranging from 11.0% to 14.2%, has been reported from South India.3 Taking into account the size of the Indian population, these prevalence rates indicate that a large number of deaths can be attributed to CAD.3

Thrombolysis for Ischemic Stroke Associated With Infective Endocarditis

Cerebral ischemic events are highly prevalent and associated with high rates of death and disability in patients with infective endocarditis (IE). However, the role of thrombolysis in these patients remains unclear. We sought to determine the rates and outcomes of acute ischemic stroke patients with IE treated with intravenous thrombolysis (IVT). We determined the rates of post-thrombolytic intracerebral hemorrhage and favorable outcome among acute ischemic stroke patients with IE treated with IVT. Patients were identified using Nationwide Inpatient Sample data from 2002 to 2010. We compared the rates of various outcomes with ischemic stroke patients without IE treated with IVT. There were 222 patients (mean age 59±18 years; 46% women) who were treated with IVT for acute ischemic stroke associated with IE and 134,048 patients (mean age 69±15 years; 49% women) who were treated for stroke without IE. The rate of post-thrombolytic intracerebral hemorrhage was significantly higher in patients with IE compared with those without IE (20% versus 6.5%; P=0.006). There was a significantly lower rate of favorable outcome in the IE group (10% versus 37%; P=0.01). High rates of post-thrombolytic intracerebral hemorrhage and low rates of favorable outcome mandate caution in using IVT in acute ischemic stroke patients with IE.

Educational Exhibit Abstract No. 407 - Symptomatic pulmonary embolus during lower extremity deep venous thrombolysis: the role of IVC filters

Learning Objectives 1. Determine the prevalence of trapped thrombus in IVC filters during lower extremity deep venous thrombolysis 2. Determine the prevalence of symptomatic pulmonary embolus (PE) requiring evaluation with pulmonary angiography 3. Discuss the role of IVC filters in preventing symptomatic PE Background IVC filters are known to trap thrombus during lower extremity thrombolysis, but also are known to serve as a nidus for thrombosis. The role of IVC filters in preventing clinically important PE in thrombolysis patients remains uncertain. Clinical Findings/Procedure Details Between January 2003 and December 2011, 64 patients underwent 76 lower extremity thrombolysis procedures at a single institution. Venograms were retrospectively evaluated for presence or placement of an IVC filter and for trapped thrombus in the filter at any time during the lysis. Pulmonary angiography within one year was also reviewed. A filter was in place for 53 procedures (70%). Trapped thrombus could be evaluated in 43 cases; of these, thrombus measuring an average of 9 mm (range 4 - 16 mm) was present in 16 cases (37%). CT or conventional pulmonary angiography was performed following only 11 procedures (14%), all in patients with a filter in place (Fisher exact p = 0.018). Four were positive for PE (36%, 5% of procedures). Conclusion and/or Teaching Points Trapped thrombus was seen in a relatively high proportion of IVC filters, but symptoms requiring evaluation for PE were an unusual event and clinically apparent PE a rare event. Filters did not protect against either evaluation for PE or presence of PE, and therefore their role in thrombolysis remains unclear.

Intravenous and oral administrations of DD2 [7-Amino-2-(sulfanylmethyl)heptanoic acid] produce thrombolysis through inhibition of plasma TAFIa in rats with tissue factor-induced microthrombosis

Thrombin-activatable fibrinolysis inhibitor (TAFI) is a plasma zymogen that is activated by thrombin in plasma. In fibrinolytic processes, carboxy-terminal lysine (Lys) residues in partially degraded fibrin are important sites for plasminogen binding and activation, and an active form of TAFI (TAFIa) inhibits fibrinolysis by eliminating these residues proteolytically. We synthesized DD2 [7-Amino-2-(sulfanylmethyl)heptanoic acid], a Lys analogue containing sulfur, as an inhibitor of TAFIa and investigated its pharmacological profile and pathophysiological role in thrombolysis via in vitro and in vivo studies. DD2 specifically inhibited plasma TAFIa activity with an apparent IC50 (50% inhibitory concentration) value of 3.4×10-8M under the present experimental condition and enhanced tissue plasminogen activator-mediated clot lysis in a concentration-dependent manner. In order to study tissue factor (TF)-induced microthrombosis in an animal model, rats were given intravenous injection (2.5mg/kg and higher) or oral administration (10mg/kg and higher) of DD2. This attenuated TF-induced glomerular fibrin deposition and increased the plasma levels of fibrin degradation products and D-dimer in a dose-dependent manner. A DD2 dose approximately 4X higher than the dose used in intravenous injections was required to achieve an equivalent thrombolytic effect to that seen following oral administration. Moreover, the oral absorption efficiency of DD2 into the vasculature was 29.8%. These results indicate that both intravenous and oral administration of DD2 enhanced endogenous fibrinolysis and reduced thrombi in a TF-induced microthrombosis model.

Thrombolytic effects of Douchi Fibrinolytic enzyme from Bacillus subtilis LD-8547 in vitro and in vivo

BackgroundToday, thrombosis is one of the most widely occurring diseases in modern life. Drugs with thrombolytic functions are the most effective methods in the treatment of thrombosis. Among them, Douchi fibrinolytic enzyme (DFE) is a promising agent. DFE was isolated from Douchi, a typical and popular soybean-fermented food in China, and it can dissolve fibrin directly and efficiently. A strain, Bacillus subtilis LD-8547 produced DFE with high fibrinolytic activity has been isolated in our lab previously.ResultsIn the study, thrombolytic effect of DFE from Bacillus subtilis LD-8547 was studied in vitro and in vivo systematically. The results showed that DFE played a significant role in thrombolysis and anticoagulation in vitro. And the thrombolytic effects correlated with DFE in a dose-dependent manner. In vivo, the acute toxicity assay showed that DFE had no obvious acute toxicity to mice. Test of carrageenan-induced thrombosis in mice indicated that the DFE significantly prevented tail thrombosis, and arterial thrombosis model test indicated that Douchi fibrinolytic enzyme DFE had thrombolytic effect on carotid thrombosis of rabbits in vivo. Other results in vivo indicated that DFE could increase bleeding and clotting time obviously.ConclusionsThe DFE isolated from Bacillus subtilis LD-8547 has obvious thrombolytic effects in vitro and in vivo. This function demonstrates that this enzyme can be a useful tool for preventing and treating clinical thrombus.

Severe refractory hypoxaemia in submassive pulmonary embolism: a surrogate marker of severe right ventricular dysfunction and indication for thrombolysis

The role of thrombolysis in pulmonary thromboembolism is controversial. We describe a case of life-threatening acute pulmonary embolism where thrombolysis was successfully administered because of extreme refractory hypoxaemia. We suggest that profound refractory hypoxaemia in this clinical setting was due to the combination of severe right ventricular dysfunction and shunting from pulmonary infarction. The shunt was not likely to have resolved in the short term, but right ventricular function and hypoxaemia improved with clot lysis. Similar clinical presentations should prompt active consideration of thrombolysis.