Brachial embolism from mechanical mitral valve thrombosis: Multimodality imaging-guided successful thrombolysis

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Brachial embolism from mechanical mitral valve thrombosis:

multimodality imaging-guided successful thrombolysis

Sinan Cers¸it

, Emrah Bayam

, Sabahattin Gu¨ndu¨z

, Ahmet Gu¨ner

and

Mehmet O

¨ zkan

We report the administration of low-dose (25 mg) prolonged infusion (25 h) of tissue-typed plasminogen activator (t-PA) in the treatment of brachial arterial thromboembolism (BAT) secondary to prosthetic valve thrombosis (PVT), under the guidance of multimodality imaging. BAT is a rare disorder with serious consequences. The case of BAT secondary to mitral PVT was successfully treated with low-dose prolonged infusion of t-PA under the guidance of multimodality imaging with upper extremity duplex Doppler ultrasonography, multislice computerized tomographic angiography, coventional angiography and advanced transesophageal echocardiography. This case has demonstrated that low-dose prolonged infusion of t-PA may be adequate in the treatment of

BAT.Blood Coagul Fibrinolysis 29:395–398 Copyright ß 2018

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Blood Coagulation and Fibrinolysis2018, 29:395–398

Keywords: brachial artery, computed tomography, prosthetic mitral valve, thromboembolism, thrombolytic therapy, two-dimensional and three-dimensional transesophageal echocardiography

a

Department of Cardiology, Kartal Kos¸uyolu Heart Training and Research Hospital, I˙stanbul andb

School of Health Sciences, University of Ardahan, Ardahan, Turkey

Correspondence to Sinan Cers¸it, MD, Atalar Mah. Seyrantepe Sok. No: 3 Kartal, I˙stanbul, Turkey

Tel: +90 5555202385; fax: +90 2164596321; e-mail: sinancersit@hotmail.com

Received17 October 2017 Revised 18 December 2017 Accepted2 January 2018

Introduction

Prosthetic valve thrombosis (PVT) is a potentially lethal complication of valve replacement surgery. Clinical pre-sentation of left-sided obstructive PVT includes dyspnea, decreased exercise capacity and/or thromboembolism. The nonobstructive PVT may be an incidental finding or may present with a thromboembolic event. Despite optimal Anticoagulation, the incidence of embolism from PVT is between 0.5 and1.7% [1–3]. Treatment modali-ties for PVT include intensified anticoagulation with or without addition of antiplatelets, thrombolytic therapy, or surgery [4,5].

Brachial artery thromboembolism (BAT) is a rare site of embolism, which requires surgical embolectomy in most cases with proximal involvement. Thrombolytic therapy is required for selected patients [2]. In this report, we present a case of nonobstructive mechanical mitral PVT compli-cated by BAT treated with prolonged infusion (25 h) of low-dose (25 mg) tissue-typed plasminogen activator (t-PA) under the guidance of multimodality imaging.

Case presentation

A 55-year-old woman who had undergone mechanical mitral valve replacement (St Jude Medical, No 25) 15 years ago presented with pain and paleness in her right forearm and hand lasting for six 6 h. She had a past history of two episodes of PVT associated with suboptimal anticoagulation, one of which accompanied by renal artery thromboembolism successfully treated with thrombolysis. Thereafter, the patient had been pre-scribed add-on aspirin with warfarin after previous

PVT episode. Physical examination showed weak pulses in her right brachial, ulnar and radial arteries. Electro-cardiogram revealed sinus rhythm. Biochemical analysis revealed otherwise normal findings with an international normalized ratio (INR) of 1.8. Although index INR was subtherapeutic on admission, the patient had been on strict anticoagulation with a target INR between 2.5 and 4 and recent adequate time in therapeutic range of 71%. Detailed analysis of hemostasis revealed elevated fibrin-ogen, homosistein and lupus anticoagulant. Genetic analysis also revealed heterozygous mutations of MTHFR (A1298C), beta-fibrinogen-455G>A, PAI-1 5G>4G (Table 1). Analysis of proteins C and S was not performed as the patient was on treatment with warfarin. Upper extremity duplex Doppler ultrasonog-raphy showed minimal flow, and focal and hyperecho-genic thrombus material in the distal portion of the right brachial artery. Right upper limb arterial angiography revealed a thrombus extending from brachial artery to ulnar artery (see Fig. 1 and Video, Supplemental Digital Content 5, http://links.lww.com/BCF/A45, which show occlusion of brachiocephalic artery). Transthoracic echo-cardiography (TTE) revealed normal valvular hemody-namics with a mean transmitral gradient of 5 mmHg and

a valve area of 2.2 cm2. However, real-time

two-dimen-sional and three-dimentwo-dimen-sional transesophageal echocar-diography (RT-2D TEE, 3D TEE) showed multiple highly mobile thrombi (the largest one measuring 11 mm

in length and 0.35 cm2in area) extending from a fixed

thrombus base of 0.5 cm2located on the lateral side of

prosthetic ring (see Figs 2 and 3, Supplemental Digital Content 2 – 3, http://links.lww.com/BCF/A44 and Video,

Case report 395

0957-5235 Copyright ß 2018 Wolters Kluwer Health, Inc. All rights reserved. DOI:10.1097/MBC.0000000000000696 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (www.bloodcoagulation.com).

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Supplemental Digital Content 6 – 7, http://links.lww. com/BCF/A46, http://links.lww.com/BCF/A47, which show nonobstructive thrombi of mechanical prosthetic mitral valve on 2D and 3D TEE, respectively). Pro-longed infusion (25 h) of low-dose (25 mg) t-PA was administered. Intravenous UFH was initiated immedi-ately after cessation of t-PA with a target activated partial thromboplastin time (aPTT) between 50 and 70 s. After thrombolytic therapy, symptoms of right forearm and brachial, ulnar and radial arteries became well palpable. Repeat TEE revealed disappearance of thrombus on

mechanical mitral valve. Multislice computerized

tomography angiography showed a residual thrombus without restriction of flow in the brachial artery (see

Fig. 4 which shows the residual thrombus in the brachial artery). Thereafter, the patient was anticoagulated with warfarin with a target INR between 3 and 4 with add-on 100 mg of aspirin. The patient was discharged uneventfully.

Discussion

Acute ischemia of an upper extremity occurs less fre-quently than vascular events of the leg and accounts for 15–32% of all cases [2]. Embolism, usually cardiac in origin, is the most common cause with atrial fibrillation being responsible in the majority of patients cases. The brachial artery is the most frequently occluded vessel in patients suffering from upper limb embolism [2]. Patients

396 Blood Coagulation and Fibrinolysis 2018, Vol 29 No 4

Table 1 Pretreatment hemostatic laboratory analysis of the patient

Test Result Normal range Platelet count (103/ml) 309 150–450 INR 1.8 Prothrombin time (s) 19.1 10–14 aPTT (s) 35 26–40 Fibrinogen (mg/dl) 495 200–400 Homosistein (mmol/l) 20.7 5.4–10 Lupus anticoagulant (s) 58 31.4–43.4 Mthfr (A1298C) Heterozygous mutation

Beta fibrinogen-455 g>a Heterozygous mutation PAI-1 (5g>4g) Heterozygous mutation

aPTT, activated partial thromboplastin time; INR, international normalized ratio.

Fig. 1

Figure that shows occlusion of brachiocephalic artery (arrows) in right upper extremity arterial angiography.

Fig. 2

Figure that shows mobile non-obstructive thrombus of mechanical prosthetic mitral valve (arrows) on two-dimensional transesophageal echocardiography. LA, left atrium; LV, left ventricule.

Fig. 3

Figure that shows mobile non-obstructive thrombus (arrows) of mechanical prosthetic mitral valve ring on three-dimensional transesophageal echocardiography. AV, aortic valve; LAA, left atrial appendage.

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generally present with acute pain, paresthesia, paralysis, pallor, perishing cold and pulselessness. Upper extremity duplex Doppler ultrasonography, catheter-based or com-puted tomography angiograph and magnetic resonance angiography are the imaging alternatives for acute BAT diagnosis. The standard treatment strategy for BAT is still controversial. The treatment approach for acute BAT is determined by the cause, comorbid status and degree of ischemia. In addition to thrombolytic therapy, percu-taneous thrombus aspiration with or without balloon angioplasty, and surgical embolectomy may also be per-formed in patients with acute BAT [6,7].

In patients with PVT, slow infusion of low-dose throm-bolytic therapy has been reported as a highly effective and well tolerated first-line therapy in the recent reports [4,8]. Although nonobstructive PVT does not develop hemodynamic compromise, it carries potential risk for thromboembolism. Although patients with isolated small nonobstructive PVT can initially be managed with an intensification of anticoagulation, thrombolysis or surgery may be required for large thrombi and/or those associated with embolism [9,10].

In the current case, there was a highly mobile and relatively large PVT, which was associated with BAT causing upper limb ischemia. Although isolated surgical brachial embolectomy was initially deemed an option for reperfusion, it would leave the patient at risk of re-embolism from PVT. A high-dose thrombolytic strategy might have caused severe bleeding. Moreover, very slow

(25 h) infusion of low-dose (25 mg) t-PA has been reported as equally well tolerated and efficacious strategy as surgery for left-sided PVT in the most recent guide-lines [1]. Hence thrombolysis was considered as a strategy with potentially targeting both the PVT and the BAT. The control of thrombolytic therapy success can be assessed by measuring circulating plasmin [11]. However, we do not routinely measure plasmin activity in patients with PVT undergoing thrombolytic therapy. Further-more, we believe that advanced imaging methods are more useful to assess the lytic success by direct visuali-zation of change in thrombus burden. Moreover, the potential hemorrhagic complications of thrombolytic therapy can be recognized by strict clinical and laboratory follow-up [12].

In conclusion, patients with acute BAT from PVT may be successfully treated with ultra-slow infusion of low-dose t-PA with full recovery of extremity flow along with successful lysis of valve thrombus. Those with absolute contraindications to thrombolytic therapy, still require surgical embolectomy for BAT and an additional treat-ment strategy for PVT.

Acknowledgements

All the authors contributed equally to this work. Conflicts of interest

There are no conflicts of interest.

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Brachial embolism from mechanical mitral valve thrombosisCers¸it et al. 397

Fig. 4

Figure that shows a remnant thrombus (arrow) without restriction of flow with the dose of 25 mg tissue-typed plasminogen activator in the brachial artery on multislice computerized tomographic angiography.

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