Thrombolytic Therapy for the Treatment of Prosthetic Heart Valve Thrombosis in Pregnancy With Low-Dose, Slow Infusion of Tissue-Type Plasminogen Activator

Background: Thrombolysis is an effective treatment strategy for prosthetic valve thrombosis (PVT). Recombinant tissue-type plasminogen activator (rt-PA) is widely used as a thrombolytic agent. Infusion of rt-PA may trigger the production of anti–tissue plasminogen activator (tPA) antibodies (ATAs). We aimed to evaluate the possible relationship between ATA levels and PVT formation, and the role of baseline ATA levels on outcomes of thrombolytic therapy in patients with PVT. Methods: This prospective, single-center cohort study included 28 patients with PVT undergoing thrombolysis and 31 controls with normal prostheses. Plasma samples were collected from patients with PVT at baseline and at 15th, 30th, 90th, and 180th days after thrombolysis and from controls at baseline only. The ATA levels were assessed in human plasma by an enzyme-linked immunosorbent assay. Results: Baseline ATA-immunoglobulin (Ig) G and IgM were significantly higher in patients with PVT than in controls. The levels of IgM and IgG peaked at 15th and 30th days after rt-PA infusion, respectively. Subtherapeutic international normalized ratio and baseline ATA-IgM were independent predictors of PVT. Thrombolysis failed in 6 patients (21%) in whom baseline IgM levels were significantly higher than successfully lysed patients. Rethrombosis occurred in 9 patients (32%) in whom baseline IgG levels were significantly higher than those without rethrombosis. There was a moderate positive correlation between baseline and 15th-day IgM levels and the dose of rt-PA needed for successful lysis. Conclusion: The ATA levels tended to be higher in patients with PVT at the time of initial diagnosis compared to controls without PVT. In addition, such patients with PVT and high ATA levels may be at high risk for failed thrombolysis or rethrombosis.

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Comparative Effects of Staphylokinase and Alteplase in Rabbit Bleeding Time Models

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650372 ◽

1996 ◽

Vol 75 (05) ◽

pp. 816-819 ◽

Cited By ~ 4

Author(s):

Steven Vanderschueren ◽

Désiré Collen

Keyword(s):

Thrombolytic Therapy ◽

Low Dose ◽

Bleeding Time ◽

Tissue Type ◽

High Dose ◽

Time Model ◽

Spontaneous Bleeding ◽

Tissue Type Plasminogen Activator ◽

Type Plasminogen Activator ◽

Combined Administration

Summary Background: The pathogenesis of bleeding associated with thrombolytic therapy remains largely unknown, although spontaneous bleeding appears to correlate with bleeding time prolongation. Here, the comparative effects on cuticle bleeding times (CBT) and ear puncture bleeding times (EBT) of recombinant staphylokinase (Sak) and alteplase (recombinant tissue-type plasminogen activator, rt-PA) at equivalent doses, alone and in combination with aspirin and heparin, were studied in rabbits. Methods and Results: Groups of 4 to 9 rabbits were allocated to one of the 8 following intravenous infusions: saline; aspirin 15 mg/kg and heparin - 100 IU/kg bolus and 10 IU/kg infusion over one hour; 1.5 mg/kg rt-PA; 1.5 mg/kg rt-PA plus aspirin and heparin; 4.5 mg/kg rt-PA; 0.5 mg/kg Sak; 0.5 mg/kg Sak plus aspirin and heparin and 1.5 mg/kg Sak. Bleeding times were determined 30 and 15 min before and 5,15,30 and 60 min after the administration over one min of saline, rt-PA or Sak, by simultaneously severing a nail cuticle (CBT) and by puncturing the ear (EBT). Bleeding times were unaffected by saline and by both doses of Sak in monotherapy. Heparin-aspirin and low dose rt-PA significantly lengthened EBT but not CBT. Both CBT and EBT were significantly prolonged (to a mean of >4 times pretreatment at 5 min) after high-dose rt-PA and after the combined administration of heparin and aspirin with either Sak or rt-PA. rt-PA provoked significantly longer bleeding than Sak in the CBT (p = 0.001; mean estimated difference = 23 min), but not in the EBT. rt-PA but not Sak degraded plasma fibrinogen dose-dependently. CBT correlated inversely with fibrinogen (r = −0.66, p = 0.001) but EBT did not. Conclusions: At equivalent doses Sak displays a significantly higher fibrin specificity and prolongs bleeding time less than rt-PA, particularly in the nail cuticle bleeding time model in which larger vessels are injured that require fibrinogen for hemostasis.

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Low-dose intravenous tissue-type plasminogen activator for prosthetic valve thrombosis is better than standard dose streptokinase

Revista Portuguesa de Cardiologia (English Edition) ◽

10.1016/j.repce.2015.08.013 ◽

2015 ◽

Vol 34 (9) ◽

pp. 569

Author(s):

Murat Biteker ◽

Özcan Başaran ◽

Nesrin Filiz Başaran ◽

Funda Sungur Biteker

Keyword(s):

Plasminogen Activator ◽

Prosthetic Valve ◽

Low Dose ◽

Standard Dose ◽

Tissue Type ◽

Tissue Type Plasminogen Activator ◽

Prosthetic Valve Thrombosis ◽

Type Plasminogen Activator ◽

Valve Thrombosis ◽

Better Than

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P6487Sequential combination of different thrombolytic therapy regimens in the management of patients with prosthetic valve thrombosis and stuck valves

European Heart Journal ◽

10.1093/eurheartj/ehz746.1077 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

M Kalcik ◽

A Guner ◽

E Bayam ◽

S Kalkan ◽

M Yesin ◽

...

Keyword(s):

Adverse Events ◽

Thrombolytic Therapy ◽

Prosthetic Valve ◽

Low Dose ◽

Tissue Type ◽

Prosthetic Heart Valves ◽

Prosthetic Valve Thrombosis ◽

Valve Thrombosis ◽

Slow Infusion ◽

Sequential Combination

Abstract Introduction Prosthetic valve thrombosis (PVT) is serious complication among patients with prosthetic heart valves. Recently, thrombolytic therapy (TT) regimens with low-dose, slow and ultra-slow infusions of tissue type plasminogen activator (tPA) has been widely used as a first-line treatment for PVT. PVT with stuck valves is a special entity which deserves particular management. In our study, we aimed to investigate the effectiveness and safety of sequential combination of different TT regimens in the management of patients with PVT and stuck valves. Methods The study included 52 patients with PVT and stuck valves [female: 34 (65.4%), mean age: 47.5±12.4] who underwent TT with sequential combination of slow (25mg/6 hours) and ultra-slow (25mg/25 hours) infusion of low dose t-PA regimens which was mainly based on the New York Heart Association functional class of the patients according to a previously established algoritm. All patients were evaluated by cinefluoroscopy, transthoracic and transesophageal echocardiography (Figure 1). Results The median number of TT sessions with slow and ultra-slow infusion of tPA were 1 (0–2.75) and 3 (1.25–5) respectively. Total tPA dose was 120 (96–175) mg and TT was successful in 46 (88.4%) patients. There were 3 major complications (cerebrovascular accident: 1, intracranial bleeding: 1, gastrointestinal bleeding requiring transfusion: 1) and 6 minor complications. The in-hospital mortality rate was 1.9%. Increased thrombus area was found to be the only independent predictor of both failed TT and adverse events. Thrombus area above 1.45 cm2 predicted failed TT with a sensitivity of 83% and a specificity of 70% (AUC: 0.871; 95% CI: 0.752–0.991; p=0.003) and predicted adverse events with a sensitivity of 77% and a specificity of 73% (AUC: 0.854; 95% CI: 0.747–0.961; p=0.001). There was a moderate positive correletion between thrombus area and total tPA dose used (r=479; p<0.001). Figure 1 Conclusion This study demostrated that TT with sequential combination of slow and ultra-slow infusion of low dose t-PA regimens may be useful for the treatment of patients with PVT and stuck valves with acceptable success and complications rates.

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Reply to the Letter to the Editor entitled “Low-dose intravenous tissue-type plasminogen activator for prosthetic valve thrombosis is better than standard dose streptokinase”

Revista Portuguesa de Cardiologia (English Edition) ◽

10.1016/j.repce.2015.07.017 ◽

2015 ◽

Vol 34 (9) ◽

pp. 571

Author(s):

Gonçalo Cardoso

Keyword(s):

Plasminogen Activator ◽

Prosthetic Valve ◽

Low Dose ◽

Standard Dose ◽

Tissue Type ◽

Tissue Type Plasminogen Activator ◽

Prosthetic Valve Thrombosis ◽

Type Plasminogen Activator ◽

Valve Thrombosis ◽

Better Than

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Safety of low-dose prolonged infusion of tissue plasminogen activator therapy in patients with thromboembolic events in the intensive care unit

Kardiologiia ◽

10.18087/cardio.2020.7.n1091 ◽

2020 ◽

Vol 60 (7) ◽

pp. 86-90

Author(s):

Mehmet Emin Kalkan ◽

Mustafa Yildiz ◽

Hulya Yilmaz Ak ◽

Hicaz Zencirkiran Agus ◽

Yasemin Ozsahin ◽

...

Keyword(s):

Intensive Care Unit ◽

Acute Coronary Syndrome ◽

Low Dose ◽

Prosthetic Heart Valve ◽

Thromboembolic Events ◽

Coronary Syndrome ◽

Artery Embolism ◽

Valve Thrombosis ◽

Slow Infusion ◽

Heart Valve Thrombosis

Objective Thromboembolic events such as acute coronary syndrome related prosthetic heart valve thrombosis, pulmonary artery embolism and renal artery embolism are a rare condition but a major cause of morbidity and mortality. In this study we discussed low-dose thrombolytic therapy, in patients with thromboembolic events in the intensive care unit.Methods The study was performed on 12 consecutive patients [8 female; 50.3±16.0 (35–95) years] with acute thromboembolism including acute coronary syndrome related prosthetic heart valve thrombosis, acute pulmonary embolism and acute renal embolism who were treated with low-dose (25 mg) and slow infusion (6 hours) of t-PA. We evaluated mainly in-hospital safety and also effectiveness.Total treatment episodes was 1.66±0.88 (1-4) times.Results All thromboembolic events have been successfully treated with low-dose (25 mg) and slow infusion (6 hours) of t-PA. The success criteria were clinically improvement and radiologically lysis. None of the patients had ischemic stroke, intracranial hemorrhage, embolism (peripheral and recurrence of coronary artery embolism), bleeding requiring transfusion. The most frequent in-hospital complication was a gum bleeding without need for transfusion (two patients).Conclusions In our case series low-dose (25 mg) and slow infusion (6 hours) of t-PA have been performed successfully for thromboembolic events including acute coronary syndrome related prosthetic heart valve thrombosis, pulmonary embolism and renal embolism in patients with in the intensive care unit. Safety is promising and if efficacy will be proved; this method may be a valuable alternative to standard fibrinolytic regimen.

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