Quick search in Citations
This JournalAnywhereCitation
Advanced Search
Research Article
Originally Published 28 June 2013
Free Access

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

Mehmet Özkan, MD, Beytullah Çakal, MD, Süleyman Karakoyun, MD, Ozan Mustafa Gürsoy, MD, Cihan Çevik, MD, Macit Kalçık, MD, Ali Emrah Oğuz, MD, … Show All … , Sabahattin Gündüz, MD, Mehmet Ali Astarcioglu, MD, Ahmet Çağrı Aykan, MD, Zübeyde Bayram, MD, Murat Biteker, MD, Evren Kaynak, MD, Gökhan Kahveci, MD, Nilüfer Ekşi Duran, MD, and Mustafa Yıldız, MDAuthor Info & Affiliations
Circulation
Volume 128, Number 5
https://doi.org/10.1161/CIRCULATIONAHA.113.001145
Track CitationsAdd to favorites
PDF/EPUB

Abstract

Background—

Prosthetic valve thrombosis during pregnancy is life-threatening for mother and fetus, and the treatment of this complication is unclear. Cardiac surgery in pregnancy is associated with very high maternal and fetal mortality and morbidity. Thrombolytic therapy has rarely been used in these patients. The aim of this study is to evaluate the safety and efficacy of low-dose (25 mg), slow infusion (6 hours) of tissue-type plasminogen activator for the treatment of prosthetic valve thrombosis in pregnant women.

Methods and Results—

Between 2004 and 2012, tissue-type plasminogen activator was administered to 24 consecutive women in 25 pregnancies with 28 prosthetic valve thrombosis episodes (obstructive, n=15; nonobstructive, n=13). Mean age of the patients was 29±6 years. Thrombolytic therapy sessions were performed under transesophageal echocardiography guidance. The mean dose of tissue-type plasminogen activator used was 48.7±29.5 mg (range, 25–100mg). All episodes resulted in complete thrombus lysis after thrombolytic therapy. One patient had placental hemorrhage with preterm live birth at the 30th week, and 1 patient had minor bleeding.

Conclusions—

Low-dose, slow infusion of tissue-type plasminogen activator with repeated doses as needed is an effective therapy with an excellent thrombolytic success rate for the treatment of prosthetic valve thrombosis in pregnant women. This protocol also seems to be safer than cardiac surgery or any alternative medical strategies published to date. Thrombolytic therapy should be considered first-line therapy in pregnant patients with prosthetic valve thrombosis.

Introduction

Pregnancy is associated with increased risk of thrombosis among women with mechanical prosthetic heart valves.1 The largest literature review of women with a prosthetic heart valve who were on anticoagulation during pregnancy reported that thromboembolic complications occurred in 3.9% of women taking only warfarin, 9.2% of women who received unfractionated heparin in the first trimester followed by warfarin, and one fourth of women treated with unfractionated heparin throughout their pregnancy. Maternal death was observed in these groups in 2%, 4%, and 15%, respectively, and was usually related to prosthetic valve thrombosis (PVT).2 Similarly, 15% of pregnant women developed PVT while using low-molecular-weight heparin.3
Editorial see p 481
Clinical Perspective on p 540
PVT during pregnancy requires immediate therapy such as valve replacement, thrombolytic therapy (TT), or surgical thrombectomy. Recommendations of guidelines for this complication are similar to the management of PVT in nonpregnant patients.4,5 The guidelines suggest optimizing anticoagulation in noncritically ill patients with recent subtherapeutic anticoagulation. Surgery is recommended when anticoagulation fails, for critically ill patients with obstructive thrombosis, or for patients with large (≥10 mm) nonobstructive PVT complicated by embolism. Fibrinolysis is recommended for either critically ill patients when surgery is not immediately available or when PVT is right-sided. However, cardiac surgery in pregnancy is associated with very high maternal and fetal mortality (6% and 30%, respectively) and morbidity (24% and 9%, respectively).6 These patients are rarely considered for TT because of the concerns about bleeding and fetal harm and apprehension that thrombolytic agents are absolutely contraindicated in pregnancy. Recently, transesophageal echocardiography (TEE)—guided low-dose (25 mg), slow infusion (6 hours) of tissue-type plasminogen activator (tPA) was demonstrated to be a safe and effective strategy for the treatment of PVT in a large, prospective study.7 This trial involved 182 patients with 220 episodes of PVT. Low-dose, slow infusion of tPA protocol was associated with the highest (86%) thrombolytic success and lowest (10.5%) complication rates with no mortality, suggesting that guidelines for the treatment of PVT might need to be updated to reflect the utility of thrombolysis for all patients. In this study, we evaluated the safety and efficacy of this particular therapy in pregnant women With PVT.

Methods

Rationale of the Study Methods

Surgery Versus Thrombolytic Therapy

This study is the subgroup of Comparison of Different Transesophageal Echocardiography Guided Thrombolytic Regimens for Prosthetic Valve Thrombosis (TROIA) trial that was published earlier.7 The study is nonrandomized because of the relatively small number of patients with this highly specific clinical condition, the very high morbidity and mortality associated with surgery from the available data, and the lack of evidence supporting superiority of either therapy. Furthermore, TT and surgery were not considered alternative treatment options; instead, they were considered complementary from the beginning of the study. Hence, TT was the first treatment option for virtually all pregnant patients with PVT, and surgery was considered only in patients who had an absolute contraindication to TT, failed thrombolysis, or refused to receive TT. The same thrombolytic protocol used in TROIA (25-mg tPA infusion in 6 hours in each thrombolytic session) was used in this study. We conducted a prospective audit of pregnant women with PVT treated with TT at any stage during pregnancy.

Why Low-Dose, Slow-Infusion tPA?

tPA is a highly fibrin-specific drug and does not cause systemic thrombolytic effect. The placental passage of tPA is minimal and not sufficient to cause unwanted fibrinolytic effect in the fetus.8 It has short biological half-life and does not induce an antigenic reaction. We hypothesized that tPA could be an ideal agent for pregnant patients with PVT compared with streptokinase and urokinase. We also hypothesized that low-dose, slow infusion of tPA would lyse the clot gradually with reduced risk of thromboembolism and without compromising the success rates. Furthermore, we thought that bleeding risk could be reduced because tPA infusion would be stopped immediately with a slow infusion protocol.

TT Protocol and Dosing Regimen

Six-hour infusion of 25 mg tPA without a bolus (repeated once after 24 hours, up to 6 times if needed, for a maximum total dose of 150 mg) was used in all pregnant patients with PVT. We did not use intravenous heparin during tPA infusions to minimize bleeding risk. Heparin 70-IU/kg bolus and 16 IU/kg per hour (up to 1000 IU/h) infusion with a target activated partial thromboplastin time of 1.5 to 2.0 times the mean of the reference range was started immediately after the tPA infusion. If repeat thrombolytic infusion was needed, heparin was held again until activated partial thromboplastin time was <50 seconds, and then tPA infusion was started. If the TT was successful, we started anticoagulation with heparin and warfarin. Warfarin was used when its daily dose was ≤2.5 mg during the first trimester after obtaining informed consent from the patient. Otherwise, enoxaparin was used to achieve peak anti—factor Xa activity of 0.7 to 1.2 IU/mL. Study patients with rethrombosis and patients with multiple mechanical valves were started on aspirin 300 mg daily in addition to anticoagulation. Patients received warfarin in the second and third trimesters up to the end of 35th week of pregnancy (international normalized ratio=2.5–4). They were hospitalized after that, and intravenous heparin was started until cesarean section. All pregnant patients underwent transthoracic echocardiographic and TEE immediately if they had any signs or symptoms suggesting PVT and every 12 weeks after the TT until delivery.

Inclusion and Exclusion Criteria

All pregnant patients with obstructive PVT, nonobstructive PVT with recent systemic thromboembolism and thrombus diameter of >5 mm, and asymptomatic mobile nonobstructive PVT with a thrombus diameter of at least 10 mm were included in this study. Patients with an absolute contraindication to TT, asymptomatic nonobstructive PVT patients without a history of recent thromboembolism and with thrombus diameter <10 mm,7 and patients with imminent abortion or placenta previa were excluded. Patients with prosthetic valve obstruction who had no thrombus/mass/pannus in the TEE study and normal prosthetic valve leaflet motion were considered a patient-prosthesis mismatch and were excluded from the study.
Twenty-four consecutive pregnant patients with 28 episodes of PVT between December 2004 to March 2012 were included in this study. A PVT episode refers the entire treatment period of a patient who is admitted to the hospital with a PVT and includes all tPA infusions per thrombolytic regimen regardless of whether each infusion is successful. If the same patient was readmitted at a different time with rethrombosis of the prosthetic heart valve during pregnancy, the readmission was considered a separate PVT episode.
Clinical characteristics, including New York Heart Association functional class, demographics, and medications, were recorded into a database. All pregnant patients with mechanical heart valves routinely underwent 2-dimensional TEE (GE Medical Systems, Milwaukee, WI) between 2004 and 2008 and Philips IE33 2-dimensional TEE and real-time 3-dimensional TEE (Philips Medical Systems, Andover, MA) between 2008 and 2012 when they presented with thromboembolism or worsening New York Heart Association functional class or if transthoracic echocardiographic demonstrated prosthetic valve dysfunction, thrombus, or any echodensity suspicious for thrombus. Thrombus was recognized as a homogeneous, mobile, or fixed mass with as echodensity similar to the myocardium located at the valve occluder or valve struts and was visualized in all patients with PVT by echocardiography. All patients also underwent transthoracic echocardiographic and TEE examination within an hour after the thrombolytic sessions. Fetal assessment was performed by an obstetrician after admission and after every TT episode. Finally, fetal ultrasounds were obtained after TT and every 4 weeks until delivery. Fetal outcome was classified as termination of pregnancy before 20 weeks’ gestation, miscarriage (spontaneous fetal loss at <20 weeks’ gestation), stillbirth (fetal death at >20 weeks’ gestation), baby death (neonatal or infant death), or live birth. Preterm birth was delivery before 37 weeks’ gestation and included both spontaneous and iatrogenic preterm births.
All the risks, benefits, and alternatives of TT were explained to the patients in detail. Each patient gave written informed consent, and the study was approved by the local ethics committee.

Criteria for Thrombolytic Success

In patients with obstructive PVT, in the absence of fatal or nonfatal major complications, Doppler documentation of the resolution of increased gradient and decreased valve area, a reduction by ≥75% in major diameter or area of the thrombus, and clinical improvement in symptoms were considered the major criteria for TT success. Complete success was defined as all 3 criteria being met, and partial success was defined as <3 criteria being met. In patients with nonobstructive PVT, in the absence of fatal or nonfatal major complications, complete success was defined as ≥75% reduction in thrombus area or length. Partial success was defined as 50% to 75% reduction in thrombus area or length. For the interpretation of results in patients with PVT, partial and complete success rates were combined.

Definition of Complications

Major fatal complication was defined as all-cause in-hospital mortality. Nonfatal major complications included ischemic stroke; intracranial hemorrhage; systemic thromboembolism; bleeding, including placental hemorrhage requiring transfusion or surgery; and tPA-related preterm delivery. Nonfatal minor complications were defined as bleeding without the need for transfusion and transient ischemic attack.

Statistical Analysis

Statistical analysis was performed with SPSS 19.0. All analyses were based on episodes. The variables were investigated with the use of analytical methods (Kolmogorov-Smirnov/Shapiro-Wilk test) to determine whether they are approximately normally distributed. Descriptive statistics were reported as mean, standard deviation, median, and minimum and maximum values for continuous variables and as frequencies with percentages for the categorical variables. The paired t test was used to compare pre-TT and post-TT prosthetic valve area and peak and mean gradients. The significance level was set at P=0.05.

Results

Over an 8-year period, 24 women received tPA during 25 pregnancies with 28 episodes of PVT. Their mean age was 29±6 years (range, 19–42 years). The demographic and clinical characteristics are reported in Table 1. The mean gestational age on admission was 19±11 weeks (range, 6–36 weeks). The most common symptom was dyspnea (n=18, 64%). Three patients were asymptomatic. Only 1 episode presented with transient ischemic attack. Patients had atrial fibrillation in 14% of PVT episodes (n=4). Two patients (7%) were using low-dose aspirin (100 mg) on admission. None of the patients had hypertension or diabetes mellitus. There was no medication use other than warfarin, aspirin, and prenatal vitamins. Twenty-three women had only mechanical mitral valves, and 1 patient had a mechanical mitral and a normally functioning aortic valve. All PVT episodes involved mitral prosthesis only. Poor compliance with warfarin or subtherapeutic anti—factor Xa or international normalized ratio level was detected in 26 of 28 episodes (93%) on admission. Fifteen episodes occurred on warfarin therapy (international normalized ratio levels on admission were <2 in all except 1 of them), and 10 episodes occurred in patients who were on enoxaparin. Three patients had rethrombosis during the same pregnancy; 1 woman had PVT in her second pregnancy. Fourteen episodes (50%) occurred in during the first trimester, 4 (14%) in the second trimester, and 10 (36%) in the third trimester. Three patients declined TT and wished to proceed with surgery. One of these patients (28 weeks’ pregnant) and the fetus died during surgery.
Table 1. Demographic and Clinical Characteristics of the Pregnant Patients With Prosthetic Valve Thrombosis
     NYHAClass     Maternal
No.Age, yProsthetic ValveThrombus TypeElapsed Time Since Valve Surgery, moI–IIIII–IVClinicalPresentationAnticoagulation at Prosthetic Valve Thrombosis Diagnosis—DoseTissue-Type Plasminogen Activator DoseGestational WeekFetal StatusFinalResultsComplication
122MitralNOT67+ PalpitationWarfarin—2.5 mg5011ASNone
231MitralOT124 +DyspneaWarfarin—5 mg5020HSNone
338MitralOT11 +DyspneaWarfarin—5 mg2534HSNone
438MitralOT74 +DyspneaWarfarin—7.5 mg2518HSNone
535MitralNOT56+ PalpitationN/A1006ASNone
626MitralNOT36+ DyspneaWarfarin—10 mg5025HSNone
7†19MitralNOT27+ PalpitationLMWH—4000 IU1006ASNone
8† (Re)21MitralNOT58+ AsymptomaticWarfarin—7.5 mg2511HSNone
922Mitral aortic: N/FNOT13+ Transient ischemic attackWarfarin—2.5ASA–100 mg5011HSNone
10‡25MitralOT18 +DyspneaLMWH–6000 IU7514HSNone
11‡ (Re)25MitralNOT21+ DyspneaWarfarin–5 mg5035HSNone
12§25MitralOT26+ DyspneaLMWH–6000 IU1006HSNone
13§ (Re)25MitralNOT32+ PalpitationN/A2512HSNone
1442MitralOT47 +DyspneaWarfarin–7.5 mg7530HS#PH
1538MitralOT56 +DyspneaWarfarin–5 mg1009HSNone
1621MitralNOT77 +PalpitationLMWH– 6000 IU*2535HSNone
1723MitralOT37 +DyspneaWarfarin–5 mg10033HSNone
1825MitralOT27 +DyspneaWarfarin–5 mgASA–100 mg2532HSNone
1934MitralOT76 +DyspneaWarfarin–7.5 mg7510HSNone
2035MitralNOT15+ PalpitationLMWH–4000 IU259HSNone
2133MitralNOT45+ AsymptomaticLMWH–6000 IU2511ASNone
2236MitralNOT17+ DyspneaWarfarin–2.5 mg2536HSNone
2327MitralOT16 +DyspneaWarfarin–10 mg509ASNone
2428MitralOT23 +DyspneaLMWH–6000 IU2536HSNone
2535MitralOT60+ DyspneaN/A258HSNone
26‖30MitralOT28 +DyspneaLMWH–6000 IU2522HSNone
27‖ (Re)30MitralOT38 +DyspneaLMWH–4000 IU2532HSNone
2828MitralNOT28+ AsymptomaticLMWH–6000 IU259HSEpistaxis
A indicates abortion; ASA, acetyl salicylic acid; H, healthy; LMWH, low-molecular-weight heparin; N/A, not available; N/F, normally functioning; NOT, nonobstructive thrombus; NYHA, New York Heart Association; OT, obstructive thrombus; PH, placental hemorrhage; Re, rethrombosis; and S, success.
*
Additional aspirin use.
†,‡,§,‖
The same sign represents the same patient.
Baby had complete hearing loss.
#
This patient developed placental hemorrhage and preterm delivery.

Echocardiographic Results

In obstructive PVT episodes (n=15, 54%), the mean valve area was 1.2±0.2 cm2; the average peak and mean gradients were 25.6±5.3 and; 17.8±4.4 mm Hg, respectively. After the thrombolytic protocol, mean valve area, peak and mean gradients improved significantly (mean valve area, 2.3±0.3 cm2; peak gradient 12.2±2.9 mm Hg; mean gradient, 5.3±1.4 mm Hg; P<0.01 for each). In nonobstructive PVT episodes (n=13, 46%), the mean valve area was 2.4±0.2 cm2, and the average peak and mean gradients were 11.1±1.7 and 4.7±1.09 mm Hg, respectively. After the thrombolytic protocol, mean valve area and peak and mean gradients remained similar (mean valve area, 2.5±0.2 cm2 [P=0.96]; peak gradient, 10.8±3.4 mm Hg [P=0.78]; mean gradient, 4.2±1.3 mm Hg [P=0.24]). The thrombus area could be measured in all (100%) of the episodes (obstructive PVT group: n=15; mean, 1.7±1.2 cm2; range, 0.8–6 cm2; nonobstructive PVT group: n=13; mean, 0.9±0.4 cm2; range, 0.4–1.8 cm2; P=0.022). There was no remaining thrombus after TT on TEE. Figure 1 demonstrates Doppler tracing (Figure 1A), 2-dimensional TEE (Figure 1B), and 3-dimensional TEE (Figure 1C) images (see also Movies I and II in the online-only Data Supplement) of one of the study patients with obstructive thrombus.
Figure 1. A study patient with obstructive prosthetic valve thrombosis. Doppler image demonstrates increased transprosthetic gradient and decreased valve area (A). The 2-dimensional transesophageal echocardiographic (TEE) image of the bileaflet mechanical valve with obstructive thrombus (Thr) measuring 0.95×2 cm with an area of 1.8 cm2 (arrows) and the immobile medial leaflet (B). Real-time 3-dimensional TEE view also demonstrates the thrombus and the immobile medial leaflet (arrows; C). Ant indicates anterior; LA, left atrium; LAA, left atrial appendage; and LV, left ventricle.
Figure 2. Tissue-type plasminogen activator doses required for complete thrombolysis in both obstructive and nonobstructive prosthetic valve thrombosis in pregnant patients. THR indicates thrombus.

Maternal and Fetal Outcomes

There were 20 live births, including 1 delivery that occurred on the 30th week of pregnancy in a 42-year-old woman as a result of placental hemorrhage after 3 TT sessions (total, 75 mg tPA). This woman had received 7.5 mg/d warfarin throughout the entire pregnancy. Both mother and fetus were healthy after the preterm delivery. However, this baby was found to have complete hearing loss (patient 14). Overall, there were 5 miscarriages (20%; 2 in the first trimester, 3 in the second trimester). Miscarriages occurred 1 to 5 weeks after TT. None of the pregnant patients developed systemic thromboembolism after TT.

TT Outcomes

The average dose of TT per PVT episode used was 48.7±29.5 mg (median, 27.5 mg; range, 25–100 mg). All episodes resulted in complete thrombolytic success. The initial rate of success after the first dose of tPA thrombosis was 47% (7 of 15) in the obstructive PVT group and 61% (8 of 13) in the nonobstructive PVT group. The average dose to obtain complete thrombus lysis was similar between the obstructive and nonobstructive PVT groups (54.3±30.8 mg in the obstructive PVT group versus 42.3±27.7 mg in the nonobstructive PVT group; P=0.23; Figure 2).

Discussion

This single-center, prospective study including a relatively large number of pregnant patients with PVT demonstrated that low-dose, slow infusion of tPA was associated with successful thrombus lysis in all episodes. Our findings also indicated that the incidence of maternal and fetal adverse events with this protocol was lower than with surgery or medical therapy on the basis of the available published data. Therefore, low-dose, slow infusion of tPA with repeated doses as needed under TEE guidance seems to be effective and relatively safe for both mother and fetus, and we suggest that it should be used as first-line therapy for PVTs in pregnant women.
Currently, there are no evidence-based guidelines for pregnancies complicated by PVT. We performed a comprehensive literature review on articles discussing TT in pregnant patients with PVT (Table 2) and compared the TT outcome results of our study with the published articles9–34 (Table 3). Overall, TT has been administered in 32 pregnancies (38 episodes) complicated by PVT. These reports yielded average thrombolytic success, maternal mortality, major complication, and minor complication rates of 76%, 10%, 14%, and 32%, respectively. Fetal/neonatal mortality was 28%. Similarly, Leonhardt et al35 reported a literature review on TT with tPA (reteplase or alteplase) used in 21 pregnant patients for the treatment of non-PVT causes such as stroke (n=10), pulmonary embolism (n=7), deep venous thrombosis (n=3), and myocardial infarction (n=1). The report did not include case reports after delivery and use of other thrombolytic drugs. Thrombolytic success, maternal mortality, and morbidity were 71%, 5%, and 24%, respectively. Fetal/neonatal mortality was 24%. In our study, the TEE-guided, low-dose, slow-infusion tPA protocol was associated with 100% thrombolytic success with no maternal mortality. Fetal mortality was 20%. In general, TT for the treatment of PVT in nonpregnant patients is successful in ≈85% of patients.36–43 On the other hand, our protocol demonstrated a complete success rate among all pregnant patients with PVT. This could be explained by the fresh and rapid development of clot in this specific patient population compared with nonpregnant patients with gradually developed and organized thrombus. These findings suggest that low-dose, slow infusion of tPA can dramatically improve maternal or fetal outcomes in pregnant patients with PVT and that this effect may be more pronounced as a result of the nature of the thrombus in pregnant patients compared with nonpregnant patients.
Table 2. Published Case Reports on Thrombolytic Therapy of Prosthetic Valve Thrombosis During Pregnancy
        Maternal Status 
AuthorsPatients, nYearAge, yGestational WeekThrombolytic AgentDoseValve PositionComplicationsResultsFetal Status
Moisson et al911979259 moStreptokinase750 000 U/12 hMitral (SE)Uterine hemorrhageSuccessHealthy
Witchitz et al1011980268 moStreptokinase500 000 bolus+1 200 000 U/12 hMitral (SE)Uterine hemorrhageSuccessHealthy
Jimenez et al11119883614Urokinase2000 U·kg−1·h−1, 24 hAortic (SJM)NoneSuccessHealthy
 Same patient  36Urokinase2000 U·kg−1·h−1 3 times+4000 U·kg−1·h−1Aortic (SJM)NoneSuccessHealthy
Tissot et al12119913214Urokinase2000 U·kg−1·h−1Mitral (SJM)Uterine hemorrhageSuccessHealthy
 Same patient  28Streptokinase250 000 U+500 000 U/1 hAortic (SJM)NoneSuccessHealthy
Souto et al131199135First trimesterStreptokinase1 500 000 U/1 hMitral (BS) DeathSpontaneous abortus
Ramamurthy et al14119942828Streptokinase250 000 bolus+2 400 000/24 hMitral (BS)Uterine hemorrhageSuccessHealthy
Azzano et al15119953817tPA50 mg/2 hTricuspid (SJM)Uterine hemorrhageSuccessHealthy
Di Roio et al16Same patient  17+4 dtPA0.1 mg·kg−1·h−1, 8 hTricuspid (SJM)Uterine hemorrhage*FailureMedical abortus
Rinaldi et al17119992815tPA50 mgAortic (SJM)NoneSuccessHealthy
Fleyfel et al18119973228tPA50 mgMitral (SJM)Placental hematomaSuccessHealthy
Sánchez et al19120012714tPAN/AMitral (CM)ThromboembolismFailureHealthy
Anbarasan et al2012001288Streptokinase250 000 bolus+1 400 000 U/14 hMitral (SJM)NoneSuccessHealthy
Nanas et al21120014325tPA100 mgMitral (SJM)NoneSuccessHealthy
Abbadi22120013713Streptokinase250 000 bolus+7 200 000 U/72 hMitral (SJM)ThromboembolismFailureHealthy
Behrendt et al23120023317tPA50 mg/2 hAortic (SJM)AEMIFailureIUFD
Nassar et al24120032026Streptokinase +tPA6 650 000 U+100 mgMitral (CM)NonePartial successHealthy
Sahnoun-Trabelsi et al25120043714Urokinase2000 U·kg−1·12 h−1Aortic (SJM)NoneSuccessHealthy
 Same patient20043832Urokinase4500 U·kg−1·24 h−1+2000 U·kg−1·h−1Aortic (SJM)NoneSuccessHealthy
 220043114Urokinase4500 U·kg−1·24 h−1Mitral (SJM)NoneSuccessHealthy
 Same patient20043128Streptokinase500 000 bolus+ 1 500 000 UAortic (SJM)MetrorrhagiaSuccessSpontaneous abortus
 320041735Urokinase+streptokinase2000 U·kg−1·12 h−1, 500 000 bolus+1 500 000 UMitral (BS)HematomaSuccessSpontaneous abortus
 420043412tPA0.75 m·kg−1·2 h−1Mitral (SJM) DeathSpontaneous abortus
 52004208tPA0.75 mg·kg−1· 2 h−1Mitral (SJM) DeathSpontaneous abortus
Varadarajan et al261200628Early second trimestertPA50 mgMitral (SJM)NoneSuccessHealthy
Sandset et al.2712007 6tPA+UFHN/AN/A Success…
 Same patient   tPAN/AN/A Success…
 Same patient   tPAN/AN/A SuccessMedical abortus
Choi et al28120073614tPA100 mg/2 hSAVP (SJM)ThromboembolismSuccessHealthy
Wei et al29120083713tPA100 mg+100 mgPulmonary (MAP)HematomaFailureHealthy
Maegdefessel et al30120082726Tenecteplase7000 UAortic (SJM)NoneSuccessHealthy
Slaoui et al3112010 32Tenecteplase60 mgMitralNoneSuccessHealthy
Kaya et al32120104417tPA100 mg/3 hMitral (SJM)EpistaxisSuccessHealthy
Ozer et al33120102434tPA50 mg/6 h+25 mg/4 h+25 mg/4 hMitral (SJM)NoneSuccessHealthy
 22010218tPA50 mg/4 h+25 mg/4 hMitral (SJM)TIASuccessHealthy
 320102028tPA50 mg/4 h+25 mg/4 hMitral (SJM)EpistaxisSuccessHealthy
Srinivas et al34120122510Streptokinase250 000 U+2 400 000 U/24 hMitral (SJM)NoneSuccessHealthy
AEMI indicates acute embolic myocardial infarction; BS, Bjork-Shiley; CM, Carbomedics; IUFD, intrauterine fetal death; MAP, Medtronic Advantage prosthesis; N/A, not available; SAVP, systemic atrioventricular position; SE, Starr-Edwards; SJM, St. Jude Medical; tPA, tissue-type plasminogen activator; and UFH, unfractionated heparin.
*
Uterine hemorrhage requiring surgery.
Table 3. Comparison of Our Study With the Published Articles With Regard to Maternal and Fetal Success, Major and Minor Complications, and Mortality
 Current Study,n (%)Literature (1979–2012),n (%)
Patients2431
Pregnancies2532
Thrombolytic therapy episodes2838
Fetal anomalies0 (0)0 (0)
Fetal status  
  Healthy20 (80)24 (75)
  Miscarriage5 (20)5 (16)
  Medical abortion0 (0)2 (6)
  Intrauterine fetal death0 (0)1 (3)
Maternal status  
  Major complications  
  Hysterectomy*0 (0)1 (3)
  Thromboembolism0 (0)3 (8)
  Acute embolic myocardial infarction0 (0)1 (3)
  Placental hemorrhage1 (4)0 (0)
  Total1 (4)5 (14)
Minor complications  
  Epistaxis1 (4)2 (5)
  Hematoma0 (0)2 (5)
  Uterine hemorrhage**0 (0)5 (16)
  Placental hemorrhage†0 (0)1 (3)
  Metrorrhagia†0 (0)1 (3)
  Transient ischemic attack0 (0)1 (3)
  Total1 (4)12 (32)
Fetal death5 (20)8 (25)
Maternal death0 (0)3 (10)
Thrombolytic therapy success28 (100)30 (76)
Maternal success27 (96)30 (76)
*
Secondary to uterine hemorrhage.
†
Accepted as major complication if blood transfusion, surgery, or preterm delivery was necessary.
Administration of TT is considered a relative contraindication during pregnancy.4,5 Therefore, clinicians hesitate to use TT during pregnancy because of the anticipated maternal and fetal risk of hemorrhagic and thromboembolic complications. The risks of TT during pregnancy have never been evaluated with randomized trials. The best level of evidence comes from case reports or case series. Although TT in these reports was performed with a different drug, a different protocol, and various indications, the overall complication rates of TT in these patients are not worse than the complication rates in the large randomized TT trials on stroke, myocardial infarction, and pulmonary embolism.44–47 PVT during pregnancy is uncommon but requires urgent therapy. Among 172 pregnancies with thrombotic disorders, there were only 4 cases of PVT, and the most commonly used regimen in these patients was streptokinase, which was initiated for mostly deep venous thrombosis or pulmonary embolism. Only 5 of these 172 pregnant women received tPA for the treatment of acute thrombosis.47 There was no maternal death resulting from any TT in that report. However, surgery is traditionally considered a first-line therapy in patients with PVT. Cardiac surgery exposes mother and child to a greater risk than TT does.6 It is associated with very high maternal and fetal mortality (6% and 30%, respectively) and morbidity (24% and 9%, respectively), suggesting that the risk might exceed the risk of administration of TT.
A specific concern with TT in pregnancy is increased risk of spontaneous abortion. The incidence of this complication with different anticoagulant regimens is up to 37.5% in patients with a prosthetic heart valve.2,3 McLintock etal3 reported a spontaneous abortion rate of 26% with only oral anticoagulation, 23% with heparin in the first trimester followed by oral anticoagulation, and 9% with low-molecular-weight heparin in the first trimester followed by oral anticoagulation during pregnancy. Approximately one quarter of pregnant patients on oral or intravenous anticoagulation develop miscarriage. The incidence of spontaneous miscarriage in Turkish pregnant women who were not on oral anticoagulants was reported as 20%.48 In our study, spontaneous miscarriages occurred in 5 episodes (20%). Although the total number of miscarriages was too low to make a definite conclusion, it was similar to the expected rate among this specific patient population, suggesting that our protocol did not increase the baseline miscarriage rate. This observation seemed robust, especially in patients who received fewer TT sessions and small doses of oral anticoagulation. One woman who was on warfarin 7.5 mg/d developed placental hemorrhage after TT. She had received 3 sessions of heparin after 3 doses of tPA, which could have caused the development of placental hemorrhage. Her baby had total hearing loss, which could also be secondary to the high-dose warfarin rather than the tPA. Nevertheless, our findings indicate that this TT protocol is associated with a successful thrombus lysis in pregnant PVT patients without increasing the complication rates for mother and fetus.

Study Limitations

Our study is a single-center, nonrandomized, observational study. However, it has remarkable size for this specific study population. All pregnant patients with PVT were treated similarly in our hospital. All patients had thrombosed mitral mechanical valves. Therefore, the applicability of our findings to other mechanical and bioprosthetic valves may be questionable. Finally, this study is not a head-to-head comparison of TT and surgery for the treatment of PVT in pregnant patients. However, among 3 patients who underwent surgery in our patient population, 1 patient (and fetus) died, which may reflect the high mortality of this strategy.

Conclusions

Low-dose, slow infusion of tPA with repeat doses as needed is an effective therapy with very high thrombolytic success rate for the treatment of PVT in pregnant women. This protocol also seems to be safer than cardiac surgery or alternative medical strategies published to date. TT should be considered first-line therapy in pregnant patients with PVT.

Acknowledgments

We thank the physicians who participated at the study: Cihangir Kaymaz, Nihal Özdemir, Ali Metin Esen, Yusuf Karavelioğlu, Ruken Bengi Bakal, Emre Ertürk, Tayyar Gökdeniz, and Hasan Kaya. We also thank Dr Ubeydullah Deligönül, Jefferson City Medical Group, Jefferson City, MO, for his critical revision of the manuscript.

Clinical Perspective

Prosthetic heart valve thrombosis (PVT) is an uncommon but very serious complication of heart valve replacement procedures. Normal pregnancy is accompanied by changes in hemostasis that produce a hypercoagulable state. Most clotting factors usually increase in pregnancy, together with a decrease in several anticoagulants and fibrinolytic activity. Because of these alterations, pregnancy in women with mechanical heart valves carries a high rate of PVT and thromboembolic complications, a double jeopardy to mother and fetus. This single-center, prospective, nonrandomized, observational study included 24 consecutive pregnant women (25 pregnancies with 28 PVT episodes over an 8-year period) with left-sided PVT (all mitral; n=27). Patients with obstructive and nonobstructive PVT with recent systemic thromboembolic and thrombus diameter of >5 mm and patients with asymptomatic mobile nonobstructive PVT with thrombus diameter of at least 10 mm were included in this study. A specific thrombolytic protocol (25 mg tissue-type plasminogen activator infusion in 6 hours for each thrombolytic session, repeated once after 24 hours up to 6 times with a maximum total dose of 150 mg). We found a 100% thrombolytic success rate without any maternal mortality. Despite the limitations of this study, our protocol seems to be an effective therapy with an excellent success rate for the treatment of PVT in pregnant women. This protocol also seems to be safer than cardiac surgery or alternative medical strategies published to date. We suggest that low-dose, slow-infusion tissue-type plasminogen activator should be considered first-line therapy in pregnant patients with PVT.

Supplemental Material

File (001145_supplemental_material.pdf)
File (movie_1.avi)
File (movie_2.avi)

References

1.
Elkayam U, Singh H, Irani A, Akhter MW. Anticoagulation in pregnant women with prosthetic heart valves. J Cardiovasc Pharmacol Ther. 2004;9107-115.
Crossref
PubMed
Google Scholar
2.
Chan WS, Anand S, Ginsberg JS. Anticoagulation of pregnant women with mechanical heart valves: a systematic review of the literature. Arch Intern Med. 2000;160191-196.
Crossref
PubMed
Google Scholar
3.
McLintock C, McCowan LM, North RA. Maternal complications and pregnancy outcome in women with mechanical prosthetic heart valves treated with enoxaparin. BJOG. 2009;1161585-1592.
Crossref
PubMed
Google Scholar
4.
Vahanian A, Alfieri O, Andreotti F, Antunes MJ, Barón-Esquivias G, Baumgartner H, Borger MA, Carrel TP, De Bonis M, Evangelista A, Falk V, Iung B, Lancellotti P, Pierard L, Price S, Schäfers HJ, Schuler G, Stepinska J, Swedberg K, Takkenberg J, Von Oppell UO, Windecker S, Zamorano JL, Zembala M. Guidelines on the management of valvular heart disease (version 2012): the Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology and the European Association for Cardio-Thoracic Surgery. Eur Heart J. 2012;332451-2496.
Crossref
PubMed
Google Scholar
5.
Bonow RO, Carabello BA, Chatterjee K, de Leon AC, Faxon DP, Freed MD, Gaasch WH, Lytle BW, Nishimura RA, O’Gara PT, O’Rourke RA, Otto CM, Shah PM, Shanewise JS. 2008 Focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2008;52e1-e142.
Crossref
PubMed
Google Scholar
6.
Weiss BM, von Segesser LK, Alon E, Seifert B, Turina MI. Outcome of cardiovascular surgery and pregnancy: a systematic review of the period 1984-1996. Am J Obstet Gynecol. 1998;179(pt 1):1643-1653.
Crossref
PubMed
Google Scholar
7.
Ozkan M, Gunduz S, Biteker M, Astarcioglu MA, Cevik C, Kaynak E, Yildiz M, Oğuz E, Aykan AÇ, Ertürk E, Karavelioğlu Y, Gökdeniz T, Kaya H, Gürsoy OM, Çakal B, Karakoyun S, Duran N, Özdemir N. Comparison of different TRansesophageal echocardiography guided thrOmbolytic regimens for prosthetIc vAlve thrombosis: TROIA Trial. JACC Imaging. 2013;6206-216.
Crossref
Google Scholar
8.
Leeander I, Nilsson M, Astedt B. Depression of plasminogen activator activity during pregnancy by the placental inhibitor PAI 2. Fibrinolysis. 1988;2165-167.
Crossref
Google Scholar
9.
Moisson P, Cornier E, Rozensztajn L, Catinat J. Thrombosis of a mitral valve prosthesis in a pregnant woman: treatment with streptokinase [in French]. Coeur Med Interne. 1979;18425-432.
PubMed
Google Scholar
10.
Witchitz S, Veyrat C, Moisson P, Scheinman N, Rozenstajn L. Fibrinolytic treatment of thrombus on prosthetic heart valves. Br Heart J. 1980;44545-554.
Crossref
PubMed
Google Scholar
11.
Jimenez M, Vergnes C, Brottier L, Dequeker JL, Billes MA, Lorient Roudaut MF, Choussat A, Boisseau MR. Recurrent thrombosis of an aortic valve prosthesis in a pregnant woman: treatment with urokinase [in French]. J Mal Vasc. 1988;1346-49.
PubMed
Google Scholar
12.
Tissot H, Vergnes C, Rougier P, Bricaud H, Dallay D. Fibrinolytic treatment with urokinase and streptokinase for recurrent thrombosis in two valve prostheses for the aortic and mitral valves during pregnancy [in French]. J Gynecol Obstet Biol Reprod (Paris). 1991;201093-1096.
PubMed
Google Scholar
13.
Souto JC, Zuazu-Jausoro I, Mateo J, Borrás X, Fontcuberta J. Short-term treatment of thrombosis of heart valve prostheses with high doses of streptokinase: presentation of 5 cases [in Spanish]. Med Clin (Barc). 1991;96261-264.
PubMed
Google Scholar
14.
Ramamurthy S, Talwar KK, Saxena A, Juneja R, Takkar D. Prosthetic mitral valve thrombosis in pregnancy successfully treated with streptokinase. Am Heart J. 1994;127446-448.
Crossref
PubMed
Google Scholar
15.
Azzano O, French P, Robin J, Quinson P, de La Bourdonnaye T, Champsaur G, Mellier G, Normand J, Bozio A. Thrombolytic therapy with rtPA for thrombosis of tricuspid valve prosthesis during pregnancy [in French]. Arch Mal Coeur Vaiss. 1995;88267-270.
PubMed
Google Scholar
16.
Di Roio C, Perrot D, Védrinne JM, Méllier G, Robin J, Motin J. Thrombolytic therapy with rtPA of recurrent thrombosis in tricuspid valve prosthesis during pregnancy [in French]. Ann Fr Anesth Reanim. 1996;15666-668.
PubMed
Google Scholar
17.
Rinaldi JP, Yassine M, Aboujaoudé F, Belhakem H, Alsagheer S, Ben Ahmed F, Lemarié P, Boursier M, Khalifé K. Successful thrombolysis on an aortic valve prosthesis by plasminogen tissue activator during pregnancy [in French]. Arch Mal Coeur Vaiss. 1999;92427-430.
PubMed
Google Scholar
18.
Fleyfel M, Bourzoufi K, Huin G, Subtil D, Puech F. Recombinant tissue type plasminogen activator treatment of thrombosed mitral valve prosthesis during pregnancy. Can J Anaesth. 1997;44735-738.
Crossref
PubMed
Google Scholar
19.
Sánchez A, Cortadellas J, Figueras J, González T, Soler Soler J. Fibrinolytic treatment for patients with prosthesis thrombosis and high surgical risk [in Spanish]. Rev Esp Cardiol. 2001;541452-1455.
PubMed
Google Scholar
20.
Anbarasan C, Kumar VS, Latchumanadhas K, Mullasari AS. Successful thrombolysis of prosthetic mitral valve thrombosis in early pregnancy. J Heart Valve Dis. 2001;10393-395.
PubMed
Google Scholar
21.
Nanas JN, Kontoyannis SA, Mitsibounas DN, Stamatelopoulos SF. Thrombolytic treatment for thrombosis of a mitral valve prosthesis during pregnancy. Intensive Care Med. 2001;271668-1669.
Crossref
PubMed
Google Scholar
22.
Abbadi H. Successful thrombolysis of mitral valve prosthesis by streptokinase during pregnancy. East Mediterr Health J. 2001;7283-286.
Crossref
PubMed
Google Scholar
23.
Behrendt P, Schwartzkopff B, Perings S, Gerhardt A, Zotz RB, Strauer BE. Successful thrombolysis of St. Jude medical aortic prosthesis with tissue-type plasminogen activator in a pregnant woman: a case report. Cardiol Rev. 2002;10349-353.
Crossref
PubMed
Google Scholar
24.
Nassar AH, Abdallah ME, Moukarbel GV, Usta IM, Gharzuddine WS. Sequential use of thrombolytic agents for thrombosed mitral valve prosthesis during pregnancy. J Perinat Med. 2003;31257-260.
Crossref
PubMed
Google Scholar
25.
Sahnoun-Trabelsi I, Jimenez M, Choussat A, Roudaut R. Prosthetic valve thrombosis in pregnancy: a single-center study of 12 cases [in French]. Arch Mal Coeur Vaiss. 2004;97305-310.
PubMed
Google Scholar
26.
Varadarajan P, Isaeff D, Pai RG. Prosthetic valve thrombosis presenting as an acute embolic myocardial infarction in a pregnant patient: issues on anticoagulation regimens and thrombolytic therapy. Echocardiography. 2006;23774-779.
Crossref
PubMed
Google Scholar
27.
Sandset PM, Arnesen H, Jakobsen AF, Wergeland H. Anticoagulant treatment in a hypercoagulable woman with mechanical prosthetic mitral valve: failure of high dose low molecular weight heparin (LMWH) treatment. Second International Symposium. on Women’s Health Issues in Thrombosis and Hemostasis. 2007;119(suppl 1):S97-S118.
Google Scholar
28.
Choi C, Midwall S, Chaille P, Conti CR. Treatment of mechanical valve thrombosis during pregnancy. Clin Cardiol. 2007;30271-276.
Crossref
PubMed
Google Scholar
29.
Wei A, Alison J, Goldstein J, Tippett C, Coughlan PB. Prosthetic pulmonary valve thrombosis in pregnancy successfully treated with thrombolysis. Intern Med J. 2008;38142-143.
Crossref
PubMed
Google Scholar
30.
Maegdefessel L, Issa H, Scheler C, Thäle V, Schlitt A, Hartelt U, Grabitz R, Buerke M. 27-Year old pregnant woman with syncope and dyspnea after aortic alloplastic heart valve replacement 15 years ago [in German]. Internist (Berl). 2008;49868-872.
Crossref
PubMed
Google Scholar
31.
Slaoui M, Cherradi R, Ounzar M, Massou S, Srairi JE. Thrombosis valvular prosthesis of Starr treated successfully by tenecteplase during pregnancy [in French]. Ann Fr Anesth Reanim. 2010;29500-501.
Crossref
PubMed
Google Scholar
32.
Kaya EB, Kocabaş U, Aksoy H, Aytemir K, Tokgözoğlu L. Successful fibrinolytic treatment in a pregnant woman with acute mitral prosthetic valve thrombosis. Clin Cardiol. 2010;33E101-E103.
Crossref
PubMed
Google Scholar
33.
Ozer O, Davutoglu V, Soydinc HE, Cebesoy FB, Sari I, Akcay M. Fibrinolytic therapy of prosthetic mitral valve thrombosis during pregnancy: three case reports and review of the literature. Clin Appl Thromb Hemost. 2010;16406-413.
Crossref
PubMed
Google Scholar
34.
Srinivas BC, Moorthy N, Kuldeep A, Jeevan H, Chandrasekaran D, Manjunath CN. Thrombolytic therapy in prosthetic valve thrombosis during early pregnancy. Indian Heart J. 2012;6474-76.
Crossref
PubMed
Google Scholar
35.
Leonhardt G, Gaul C, Nietsch HH, Buerke M, Schleussner E. Thrombolytic therapy in pregnancy. J Thromb Thrombolysis. 2006;21271-276.
Crossref
PubMed
Google Scholar
36.
Ozkan M, Kaymaz C, Kirma C, Sönmez K, Ozdemir N, Balkanay M, Yakut C, Deligönül U. Intravenous thrombolytic treatment of mechanical prosthetic valve thrombosis: a study using serial transesophageal echocardiography. J Am Coll Cardiol. 2000;351881-1889.
Crossref
PubMed
Google Scholar
37.
Alpert JS. The thrombosed prosthetic valve: current recommendations based on evidence from the literature. J Am Coll Cardiol. 2003;41659-660.
Crossref
PubMed
Google Scholar
38.
Ozkan M, Biteker M, Duran NE, Yildiz M. Images in cardiovascular medicine: huge prosthetic mitral valve thrombosis in a pregnant woman. Circulation. 2009;120e151-e152.
Crossref
PubMed
Google Scholar
39.
Tong AT, Roudaut R, Ozkan M, Sagie A, Shahid MS, Pontes Júnior SC, Carreras F, Girard SE, Arnaout S, Stainback RF, Thadhani R, Zoghbi WA; Prosthetic Valve Thrombolysis—Role of Transesophageal Echocardiography (PRO-TEE) Registry Investigators. Transesophageal echocardiography improves risk assessment of thrombolysis of prosthetic valve thrombosis: results of the international PRO-TEE registry. J Am Coll Cardiol. 2004;4377-84.
Crossref
PubMed
Google Scholar
40.
Cáceres-Lóriga FM, Pérez-López H, Morlans-Hernández K, Facundo-Sánchez H, Santos-Gracia J, Valiente-Mustelier J, Rodiles-Aldana F, Marrero-Mirayaga MA, Betancourt BY, López-Saura P. Thrombolysis as first choice therapy in prosthetic heart valve thrombosis: a study of 68 patients. J Thromb Thrombolysis. 2006;21185-190.
Crossref
PubMed
Google Scholar
41.
Karthikeyan G, Math RS, Mathew N, Shankar B, Kalaivani M, Singh S, Bahl VK, Hirsh J, Eikelboom JW. Accelerated infusion of streptokinase for the treatment of left-sided prosthetic valve thrombosis: a randomized controlled trial. Circulation. 2009;1201108-1114.
Crossref
PubMed
Google Scholar
42.
Roudaut R, Lafitte S, Roudaut MF, Courtault C, Perron JM, Jaïs C, Pillois X, Coste P, DeMaria A. Fibrinolysis of mechanical prosthetic valve thrombosis: a single-center study of 127 cases. J Am Coll Cardiol. 2003;41653-658.
Crossref
PubMed
Google Scholar
43.
Keuleers S, Herijgers P, Herregods MC, Budts W, Dubois C, Meuris B, Verhamme P, Flameng W, Van de Werf F, Adriaenssens T. Comparison of thrombolysis versus surgery as a first line therapy for prosthetic heart valve thrombosis. Am J Cardiol. 2011;107275-279.
Crossref
PubMed
Google Scholar
44.
Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P, Bengel F, Brady AJ, Ferreira D, Janssens U, Klepetko W, Mayer E, Remy-Jardin M, Bassand JP; ESC Committee for Practice Guidelines (CPG). Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J. 2008;292276-2315.
Crossref
PubMed
Google Scholar
45.
Hacke W, Kaste M, Fieschi C, von Kummer R, Davalos A, Meier D, Larrue V, Bluhmki E, Davis S, Donnan G, Schneider D, Diez-Tejedor E, Trouillas P. Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II): Second European-Australasian Acute Stroke Study Investigators. Lancet. 1998;3521245-1251.
Crossref
PubMed
Google Scholar
46.
Menon V, Harrington RA, Hochman JS, Cannon CP, Goodman SD, Wilcox RG, Schünemann HJ, Ohman EM. Thrombolysis and adjunctive therapy in acute myocardial infarction: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126(suppl):549S-575S.
Crossref
PubMed
Google Scholar
47.
Ahearn GS, Hadjiliadis D, Govert JA, Tapson VF. Massive pulmonary embolism during pregnancy successfully treated with recombinant tissue plasminogen activator: a case report and review of treatment options. Arch Intern Med. 2002;1621221-1227.
Crossref
PubMed
Google Scholar
48.
Sezer K, Kamel N, Unlu C, Celik HK. Impact of first trimester and postpartum period thyroid autoantibodies on abortus incidence in Turkish pregnant women. Gynecol Endocrinol. 2009;25387-391.
Crossref
PubMed
Google Scholar

eLetters(0)

eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.

Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.

Sign In to Submit a Response to This Article

Information & Authors

Information

Published In

Go to Circulation
Circulation
Volume 128 • Number 5 • 30 July 2013
Pages: 532 - 540
PubMed: 23812180

Copyright

© 2013 American Heart Association, Inc.

Versions

You are viewing the most recent version of this article.

History

Received: 21 January 2013
Accepted: 4 June 2013
Published online: 28 June 2013
Published in print: 30 July 2013

Permissions

Request permissions for this article.

Keywords

  1. echocardiography, transesophageal
  2. heart valves
  3. mechanical thrombolysis
  4. pregnancy
  5. thrombosis

Subjects

  1. Echocardiography
  2. Thrombosis
  3. Valvular Heart Disease

Authors

Affiliations

Mehmet Özkan, MD
From the Kosuyolu Kartal Heart Training and Research Hospital, Department of Cardiology, İstanbul, Turkey (M.Ö, B.Ç, S.K., O.M.G., M.K., A.E.O., S.G., M.A.A., A.Ç.A., Z.B., M.B., G.K., N.E.D., M.Y.); Texas Heart Institute at St. Luke’s Episcopal Hospital, Baylor College of Medicine, Division of Adult Cardiology, Houston (C.Ç.); and University of Texas Health Science Center, Division of Adult Cardiology, Houston (E.K.).
View all articles by this author
Beytullah Çakal, MD
From the Kosuyolu Kartal Heart Training and Research Hospital, Department of Cardiology, İstanbul, Turkey (M.Ö, B.Ç, S.K., O.M.G., M.K., A.E.O., S.G., M.A.A., A.Ç.A., Z.B., M.B., G.K., N.E.D., M.Y.); Texas Heart Institute at St. Luke’s Episcopal Hospital, Baylor College of Medicine, Division of Adult Cardiology, Houston (C.Ç.); and University of Texas Health Science Center, Division of Adult Cardiology, Houston (E.K.).
View all articles by this author
Süleyman Karakoyun, MD
From the Kosuyolu Kartal Heart Training and Research Hospital, Department of Cardiology, İstanbul, Turkey (M.Ö, B.Ç, S.K., O.M.G., M.K., A.E.O., S.G., M.A.A., A.Ç.A., Z.B., M.B., G.K., N.E.D., M.Y.); Texas Heart Institute at St. Luke’s Episcopal Hospital, Baylor College of Medicine, Division of Adult Cardiology, Houston (C.Ç.); and University of Texas Health Science Center, Division of Adult Cardiology, Houston (E.K.).
View all articles by this author
Ozan Mustafa Gürsoy, MD
From the Kosuyolu Kartal Heart Training and Research Hospital, Department of Cardiology, İstanbul, Turkey (M.Ö, B.Ç, S.K., O.M.G., M.K., A.E.O., S.G., M.A.A., A.Ç.A., Z.B., M.B., G.K., N.E.D., M.Y.); Texas Heart Institute at St. Luke’s Episcopal Hospital, Baylor College of Medicine, Division of Adult Cardiology, Houston (C.Ç.); and University of Texas Health Science Center, Division of Adult Cardiology, Houston (E.K.).
View all articles by this author
Cihan Çevik, MD
From the Kosuyolu Kartal Heart Training and Research Hospital, Department of Cardiology, İstanbul, Turkey (M.Ö, B.Ç, S.K., O.M.G., M.K., A.E.O., S.G., M.A.A., A.Ç.A., Z.B., M.B., G.K., N.E.D., M.Y.); Texas Heart Institute at St. Luke’s Episcopal Hospital, Baylor College of Medicine, Division of Adult Cardiology, Houston (C.Ç.); and University of Texas Health Science Center, Division of Adult Cardiology, Houston (E.K.).
View all articles by this author
Macit Kalçık, MD
From the Kosuyolu Kartal Heart Training and Research Hospital, Department of Cardiology, İstanbul, Turkey (M.Ö, B.Ç, S.K., O.M.G., M.K., A.E.O., S.G., M.A.A., A.Ç.A., Z.B., M.B., G.K., N.E.D., M.Y.); Texas Heart Institute at St. Luke’s Episcopal Hospital, Baylor College of Medicine, Division of Adult Cardiology, Houston (C.Ç.); and University of Texas Health Science Center, Division of Adult Cardiology, Houston (E.K.).
View all articles by this author
Ali Emrah Oğuz, MD
From the Kosuyolu Kartal Heart Training and Research Hospital, Department of Cardiology, İstanbul, Turkey (M.Ö, B.Ç, S.K., O.M.G., M.K., A.E.O., S.G., M.A.A., A.Ç.A., Z.B., M.B., G.K., N.E.D., M.Y.); Texas Heart Institute at St. Luke’s Episcopal Hospital, Baylor College of Medicine, Division of Adult Cardiology, Houston (C.Ç.); and University of Texas Health Science Center, Division of Adult Cardiology, Houston (E.K.).
View all articles by this author
Sabahattin Gündüz, MD
From the Kosuyolu Kartal Heart Training and Research Hospital, Department of Cardiology, İstanbul, Turkey (M.Ö, B.Ç, S.K., O.M.G., M.K., A.E.O., S.G., M.A.A., A.Ç.A., Z.B., M.B., G.K., N.E.D., M.Y.); Texas Heart Institute at St. Luke’s Episcopal Hospital, Baylor College of Medicine, Division of Adult Cardiology, Houston (C.Ç.); and University of Texas Health Science Center, Division of Adult Cardiology, Houston (E.K.).
View all articles by this author
Mehmet Ali Astarcioglu, MD
From the Kosuyolu Kartal Heart Training and Research Hospital, Department of Cardiology, İstanbul, Turkey (M.Ö, B.Ç, S.K., O.M.G., M.K., A.E.O., S.G., M.A.A., A.Ç.A., Z.B., M.B., G.K., N.E.D., M.Y.); Texas Heart Institute at St. Luke’s Episcopal Hospital, Baylor College of Medicine, Division of Adult Cardiology, Houston (C.Ç.); and University of Texas Health Science Center, Division of Adult Cardiology, Houston (E.K.).
View all articles by this author
Ahmet Çağrı Aykan, MD
From the Kosuyolu Kartal Heart Training and Research Hospital, Department of Cardiology, İstanbul, Turkey (M.Ö, B.Ç, S.K., O.M.G., M.K., A.E.O., S.G., M.A.A., A.Ç.A., Z.B., M.B., G.K., N.E.D., M.Y.); Texas Heart Institute at St. Luke’s Episcopal Hospital, Baylor College of Medicine, Division of Adult Cardiology, Houston (C.Ç.); and University of Texas Health Science Center, Division of Adult Cardiology, Houston (E.K.).
View all articles by this author
Zübeyde Bayram, MD
From the Kosuyolu Kartal Heart Training and Research Hospital, Department of Cardiology, İstanbul, Turkey (M.Ö, B.Ç, S.K., O.M.G., M.K., A.E.O., S.G., M.A.A., A.Ç.A., Z.B., M.B., G.K., N.E.D., M.Y.); Texas Heart Institute at St. Luke’s Episcopal Hospital, Baylor College of Medicine, Division of Adult Cardiology, Houston (C.Ç.); and University of Texas Health Science Center, Division of Adult Cardiology, Houston (E.K.).
View all articles by this author
Murat Biteker, MD
From the Kosuyolu Kartal Heart Training and Research Hospital, Department of Cardiology, İstanbul, Turkey (M.Ö, B.Ç, S.K., O.M.G., M.K., A.E.O., S.G., M.A.A., A.Ç.A., Z.B., M.B., G.K., N.E.D., M.Y.); Texas Heart Institute at St. Luke’s Episcopal Hospital, Baylor College of Medicine, Division of Adult Cardiology, Houston (C.Ç.); and University of Texas Health Science Center, Division of Adult Cardiology, Houston (E.K.).
View all articles by this author
Evren Kaynak, MD
From the Kosuyolu Kartal Heart Training and Research Hospital, Department of Cardiology, İstanbul, Turkey (M.Ö, B.Ç, S.K., O.M.G., M.K., A.E.O., S.G., M.A.A., A.Ç.A., Z.B., M.B., G.K., N.E.D., M.Y.); Texas Heart Institute at St. Luke’s Episcopal Hospital, Baylor College of Medicine, Division of Adult Cardiology, Houston (C.Ç.); and University of Texas Health Science Center, Division of Adult Cardiology, Houston (E.K.).
View all articles by this author
Gökhan Kahveci, MD
From the Kosuyolu Kartal Heart Training and Research Hospital, Department of Cardiology, İstanbul, Turkey (M.Ö, B.Ç, S.K., O.M.G., M.K., A.E.O., S.G., M.A.A., A.Ç.A., Z.B., M.B., G.K., N.E.D., M.Y.); Texas Heart Institute at St. Luke’s Episcopal Hospital, Baylor College of Medicine, Division of Adult Cardiology, Houston (C.Ç.); and University of Texas Health Science Center, Division of Adult Cardiology, Houston (E.K.).
View all articles by this author
Nilüfer Ekşi Duran, MD
From the Kosuyolu Kartal Heart Training and Research Hospital, Department of Cardiology, İstanbul, Turkey (M.Ö, B.Ç, S.K., O.M.G., M.K., A.E.O., S.G., M.A.A., A.Ç.A., Z.B., M.B., G.K., N.E.D., M.Y.); Texas Heart Institute at St. Luke’s Episcopal Hospital, Baylor College of Medicine, Division of Adult Cardiology, Houston (C.Ç.); and University of Texas Health Science Center, Division of Adult Cardiology, Houston (E.K.).
View all articles by this author
Mustafa Yıldız, MD
From the Kosuyolu Kartal Heart Training and Research Hospital, Department of Cardiology, İstanbul, Turkey (M.Ö, B.Ç, S.K., O.M.G., M.K., A.E.O., S.G., M.A.A., A.Ç.A., Z.B., M.B., G.K., N.E.D., M.Y.); Texas Heart Institute at St. Luke’s Episcopal Hospital, Baylor College of Medicine, Division of Adult Cardiology, Houston (C.Ç.); and University of Texas Health Science Center, Division of Adult Cardiology, Houston (E.K.).
View all articles by this author

Notes

Continuing medical education (CME) credit is available for this article. Go to http://cme.ahajournals.org to take the quiz.
The online-only Data Supplement is available with this article at http://circ.ahajournals.org/lookup/suppl/doi:10.1161/CIRCULATIONAHA.113.001145/-/DC1.
Correspondence to Mehmet Özkan, MD, Department of Cardiology, Koşuyolu Kartal Heart Training and Research Hospital, Denizer Caddesi, Cevizli Kavşaği, No. 2, 34846, İstanbul, Turkey. E-mail [email protected]

Disclosures

None.

Metrics & Citations

Metrics

Citations

Download Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Select your manager software from the list below and click Download.

    • Adela Serban,
    • Dana Gavan,
    • Diana Pepine,
    • Alexandra Dadarlat,
    • Raluca Tomoaia,
    • Stefan Mot,
    • Alexandru Achim,
    Mechanical valve thrombosis: Current management and differences between guidelines, Trends in Cardiovascular Medicine, 34, 6, (351-359), (2024).https://doi.org/10.1016/j.tcm.2023.07.004
    Crossref
    • Mechthild Westhoff-Bleck,
    • Johann Bauersachs,
    • Philipp Beerbaum,
    • Constantin von Kaisenberg,
    Erwachsene mit angeborenen Herzfehlern (EMAH), Die Geburtshilfe, (635-665), (2024).https://doi.org/10.1007/978-3-662-63506-3_66
    Crossref
    • Pouya Ebrahimi,
    • Babak Sattartabar,
    • Homa Taheri,
    • Parnian Soltani,
    • Pegah Bahiraie,
    • Seyedeh Maryam Mousavinezhad,
    • Mehrdad Gooshvar,
    • Polydoros N. Kampaktsis,
    • Reza Arsanjani,
    • Mohammad Sahebjam,
    • Kaveh Hosseini,
    • Robert J Siegel,
    Mechanical prosthetic valve thrombosis: A literature review of treatment strategies, Current Problems in Cardiology, 49, 7, (102628), (2024).https://doi.org/10.1016/j.cpcardiol.2024.102628
    Crossref
    • Mehmet Özkan,
    • Ahmet Güner,
    • Sabahattin Gündüz,
    • Gazi Yıldız,
    • Ayşe İnci Yıldırım,
    • Macit Kalçık,
    • Mahmut Yesin,
    • Emrah Bayam,
    • Semih Kalkan,
    • Mustafa Ozan Gürsoy,
    • Alev Kılıçgedik,
    • Zübeyde Bayram,
    • Münevver Sarı,
    • Mehmet Aytürk,
    • Süleyman Karakoyun,
    • Mehmet Ali Astarcıoğlu,
    • Elif Cansu Gündoğdu,
    • Asuman Biçer,
    • Emre Gürcü,
    • Tuncer Koçak,
    • Recep Demirbağ,
    Combination anticoagulation strategy in pregnancy with mechanical valves: The KYBELE study, American Heart Journal, 273, (21-34), (2024).https://doi.org/10.1016/j.ahj.2024.03.015
    Crossref
    • N.E. Guzmán-Delgado,
    • C.E. Velázquez-Sotelo,
    • M.J. Fernández-Gómez,
    • L.G. González-Barrera,
    • A. Muñiz-García,
    • V.M. Sánchez-Sotelo,
    • P. Carranza-Rosales,
    • A. Hernández-Juárez,
    • J. Morán-Martínez,
    • V. Martínez-Gaytan,
    Eventos adversos cardiovasculares, obstétricos y perinatales en el embarazo y puerperio en pacientes cardiópatas, Revista Clínica Española, 224, 6, (337-345), (2024).https://doi.org/10.1016/j.rce.2024.04.004
    Crossref
    • Semih Kalkan,
    • Mustafa Ozan Gürsoy,
    • Ahmet Güner,
    • Macit Kalçık,
    • Emrah Bayam,
    • Sabahattin Gündüz,
    • Mehmet Özkan,
    Management of prosthetic valve thrombosis with unfractionated heparin, International Journal of Cardiology, 404, (131968), (2024).https://doi.org/10.1016/j.ijcard.2024.131968
    Crossref
    • Niveditha Devasenapathy,
    • Velayoudam Devagourou,
    • Milind P. Hote,
    • Palleti Rajashekar,
    • Bharathraj Kidambi,
    • Aayush Singal,
    • Mohsin Raj Mantoo,
    • Manoj Soni,
    • Gaurav Purohit,
    • Sandeep Singh,
    • Ganesan Karthikeyan,
    Surgery compared to fibrinolytic therapy for symptomatic left-sided prosthetic heart valve thrombosis (SAFE-PVT): Rationale and design of a randomized controlled trial, Indian Heart Journal, 76, 3, (192-196), (2024).https://doi.org/10.1016/j.ihj.2024.06.013
    Crossref
    • N.E. Guzmán-Delgado,
    • C.E. Velázquez-Sotelo,
    • M.J. Fernández-Gómez,
    • L.G. González-Barrera,
    • A. Muñiz-García,
    • V.M. Sánchez-Sotelo,
    • P. Carranza-Rosales,
    • A. Hernández-Juárez,
    • J. Morán-Martínez,
    • V. Martínez-Gaytan,
    Adverse cardiovascular, obstetric and perinatal events during pregnancy and puerperium in patients with heart disease, Revista Clínica Española (English Edition), (2024).https://doi.org/10.1016/j.rceng.2024.04.016
    Crossref
    • Rebecca Haraf,
    • Tamara Atkinson,
    • Dai-Trang Elizabeth Le,
    • Bhaskar Arora,
    Mechanical Tricuspid Valve Thrombosis Successfully Treated With Tissue Plasminogen Activator, JACC: Case Reports, 29, 3, (102180), (2024).https://doi.org/10.1016/j.jaccas.2023.102180
    Crossref
    • Ramakrishna Gorantla,
    • Aiham Albaeni,
    • Muhammad W Choudhry,
    • Vincent Conti,
    • Scott Lick,
    • Wissam I Khalife,
    • Khaled Chatila,
    A low-dose thrombolytic infusion protocol for safe and successful treatment of left ventricular assist device thrombosis: a case series, European Heart Journal - Case Reports, 8, 1, (2024).https://doi.org/10.1093/ehjcr/ytae001
    Crossref
  11. See more

View Options

View options

PDF and All Supplements

Download PDF and All Supplements

PDF/EPUB

View PDF/EPUB
Login options

Check if you have access through your login credentials or your institution to get full access on this article.

Personal login Institutional Login
Save for later Item saved, go to cart
Purchase Options

Purchase this article to access the full text.

Purchase access to this article for 24 hours

Thrombolytic Therapy for the Treatment of Prosthetic Heart Valve Thrombosis in Pregnancy With Low-Dose, Slow Infusion of Tissue-Type Plasminogen Activator
Circulation
  • Vol. 128
  • No. 5

Purchase access to this journal for 24 hours

Circulation
  • Vol. 128
  • No. 5
Restore your content access

Enter your email address to restore your content access:

Note: This functionality works only for purchases done as a guest. If you already have an account, log in to access the content to which you are entitled.

Figures

Tables

Media

Share

Share

Share article link

Share

View full text|Download PDF

Comment Response