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Blood oozing: A cause of life-threatening bleeding without overt source after transcatheter aortic valve replacement
International Journal of Cardiology 224 (2016) 107–111
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Blood oozing: A cause of life-threatening bleeding without overt source after transcatheter aortic valve replacement Giuseppe Tarantini MD, PhD a,⁎,1, Marco Mojoli MD a,1, Alberto Barioli MD a,1, Michele Battistel MD b,1, Philippe Généreux MD c,d,e,1 a
Department of Cardiac, Thoracic and Vascular Sciences, University Hospital of Padua, Padua, Italy University Radiology, Department of Medicine, University Hospital of Padua, Padua, Italy New York-Presbyterian Hospital/Columbia University Medical Center, New York, NY, USA d Cardiovascular Research Foundation, 111 East 59th Street, 12th Floor, New York, NY, USA e Hopital du Sacre-Coeur de Montreal, Université de Montreal, Montreal, QC, Canada b c
a r t i c l e
i n f o
Article history: Received 28 May 2016 Received in revised form 29 August 2016 Accepted 8 September 2016 Available online 10 September 2016 Keywords: Interventional cardiology Transcatheter aortic valve replacement Non-access site bleeding
a b s t r a c t Background: Post-procedure non-access site-related bleedings have a significant impact on mortality in patients treated by transcatheter aortic valve replacement (TAVR). Notwithstanding, the source of these bleedings is frequently indeterminate, with potentially serious clinical implications related to lack of diagnosis and treatment. Methods: Out of 513 TAVR performed between June 2007 and January 2016 in the Interventional Cardiology Laboratory of the Department of Cardiac, Thoracic and Vascular Sciences, University Hospital of Padua, we identified few proven cases of concealed bleeding after TAVR due to blood oozing. Results: We report three cases of angiographically confirmed post-TAVR non-access bleedings related to spontaneous blood oozing, a life-threatening condition consisting of diffuse capillary hemorrhage developing from vessels not directly involved by the procedure. We hypothesize that spontaneous post-procedural blood oozing may account for a substantial proportion of non-overt, non-access site-related bleeding after TAVR. Conclusion: The possibility of post-TAVR blood oozing is largely neglected in the literature, and comprehensive categorization of non-access site bleedings in current standardized endpoints of TAVR studies is missing. Early assessment with arterial and venous contrast phase angio-MDCT scans in case of post-TAVR unexplained and persistent anemia may allow diagnosis and treatment of this subtle condition. © 2016 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Bleeding is a common adverse event after percutaneous cardiac procedures. [1–3] The direct access to vascular structures and the need for periprocedural anticoagulation are predisposing factors to bleeding in this setting. [4,5] In the early era of percutaneous cardiac interventions, the impact of bleeding on outcomes has been long overlooked, [6] while more recently a growing body of evidence has shown that periprocedural bleeding is associated with an increased risk of early
Abbreviations: angio-MDCT, multidetector computed tomography angiography; TAVR, transcatheter aortic valve replacement; UFH, unfractionated heparin; VARC, Valve Academic Research Consortium. ⁎ Corresponding author at: Department of Cardiac, Thoracic and Vascular Sciences, University of Padua Medical School, Via Giustiniani, 2, 35128 Padova, Italy. E-mail address: [email protected] (G. Tarantini). 1 All the authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
http://dx.doi.org/10.1016/j.ijcard.2016.09.009 0167-5273/© 2016 Elsevier Ireland Ltd. All rights reserved.
and late mortality. [7,8] In coronary percutaneous interventions, nonaccess site bleeding is as frequent as access site-related bleeding, and its impact on mortality seems stronger compared to access site bleeding. [8,9] Data regarding the prevalence and outcomes of non-access site bleeding after transcatheter aortic valve replacement (TAVR) are still scant. In a previous report, it was observed that 57% of patients treated by TAVR were transfused because of non-access site bleeding, and 14% of these cases ended up without any bleeding source identified. [10] Similarly, in other series of TAVR patients, up to 39% of periprocedural bleedings had an indeterminate origin. [11,12] These concealed bleedings might be related to spontaneous blood oozing, a condition frequently overlooked clinically and almost neglected in the literature. Oozing consists of a clinically silent and diffuse capillary hemorrhage developing from minute vessels that were not involved in any invasive maneuver during intervention. Blood oozing may be difficult to diagnose due to its usual origin from splanchnic vessels or parenchymal organs. This subtle complication is potentially life-threatening even though an early diagnosis and treatment might be therapeutic. We
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hypothesize that spontaneous post-procedural blood oozing may account for a substantial proportion of non-overt, non-access site-related bleeding after TAVR. 2. Materials and Methods Out of 513 TAVR performed between June 2007 and January 2016 in the Interventional Cardiology Laboratory of the Department of Cardiac, Thoracic and Vascular Sciences, University Hospital of Padua, we identified three proven cases of concealed bleeding due to blood oozing after intervention. Informed consent was obtained from each patient. The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the institution's human research committee.
3. Results Hereafter, we report a systematic description of the three cases of post-TAVR concealed blood oozing identified in our Institution, along with multidetector computed tomography angiography (angio-MDCT) findings and interventional treatment description. Bleedings were observed while the patients were still in the cardiology ward. 3.1. Case #1 An 80-year-old woman with severe aortic stenosis and a history of syncopal episodes was admitted for a TAVR procedure. At admission, her hemoglobin level was 12.6 g/dL, hematocrit 39.5%, and platelet count 246 × 109/L. Pre-procedural dual antiplatelet therapy (aspirin and clopidogrel) was given. At the time of procedure, intravenous unfractionated heparin (UFH) 5000 IU was administered. An uneventful transfemoral TAVR was successfully performed using a 26 mm Edwards SAPIEN 3 valve (Edwards Lifesciences, Irvine, California). In the 2 days
following the procedure, hemoglobin gradually decreased to 9.1 g/dL, hematocrit to 28.5%, and platelet count to 216 × 109/L. In the absence of any apparent source of bleeding, an angio-MDCT scan of the abdomen was performed, which revealed an 11 × 9 cm abdominal hematoma located in the hypogastric region and right iliac fossa. Minute hemorrhagic spots among the medial and lateral mass walls were detectable in the arterial contrast phase but appeared more evident in the venous contrast phase, raising the suspicion of microvascular bleeding (Fig. 1A and B). A selective angiography of the right iliac axis confirmed capillary bleeding originating from the inferior epigastric artery branches. The patient underwent percutaneous selective cannulation of this vessel from a left femoral artery approach by micro-embolization with particle injection (contour 150–200 μm) and delivery of three embolization coils (Tornado 3 × 20 mm, Cook Medical, Bloomington, Indiana) (Fig. 1C and D). The days following were uneventful, and the patient was discharged after 1 week with stable hemoglobin levels. 3.2. Case #2 An 84-year-old woman with severe aortic stenosis and symptoms of heart failure underwent transfemoral TAVR using a 26 mm CoreValve bioprosthesis (Medtronic, Minneapolis, Minnesota). At admission, hemoglobin was 11.4 g/dL, hematocrit 31.7%, and platelet count 213 × 109/L. At the time of the procedure, the patient had normal hemoglobin values and was on dual antiplatelet therapy with aspirin and clopidogrel. Intraprocedural anticoagulation therapy included UFH 5000 IU. In the 4 subsequent days, a hemoglobin drop of 3.6 g/dL was observed, while hematocrit dropped to 22.4%, and platelets were 142 × 109/L. The patient received a transfusion of 3 units of red blood cells and was asymptomatic up to day 10, when sudden right abdominal
Fig. 1. Angio-MDCT scan and angiography imaging in a case of abdominal hematoma arising from multifocal capillary bleeding. Minute hemorrhagic spots are detectable by arterial phase angio-MDCT scan (a) within a hematoma located in the hypogastric region and appear more evident in the venous contrast phase (arrows) (b), suggesting active bleeding originating from a capillary source (the so-called blood oozing). (c) Selective angiography of the right iliac axis confirming multifocal capillary bleeding deriving from inferior epigastric artery branches (arrows). (d) Right iliac artery angiography after micro-embolization with particle injection and delivery of three embolization coils, demonstrating resolution of blood oozing.
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Fig. 2. Angio-MDCT scan and angiography imaging in a case of right retroperitoneal hematoma related to blood oozing. Arterial (a) and venous (b) contrast phase angio-MDCT showing active retroperitoneal capillary bleeding within a large hematoma located in the right iliac fossa. A more pronounced hyperdensity in the venous contrast phase (arrows) compared to the arterial phase is a typical feature of active capillary bleeding when detected by angio-MDCT scan. (c) Active multifocal blood oozing originating from the deep circumflex iliac artery is confirmed by selective angiography of a right iliac artery branch (arrows). (d) Control angio-MDCT scan after coil delivery (arrow), showing no signs of active bleeding.
pain occurred. An urgent abdominal angio-MDCT scan showed a right retroperitoneal hematoma with signs of active capillary bleeding clearly noticeable in the venous contrast phase within the right iliac fossa (Fig. 2A and B). A right iliac artery angiography was thus performed, demonstrating an active multifocal blood oozing originating from the deep circumflex iliac artery (Fig. 2C). Selective cannulation with a microcatheter was performed, followed by effective microembolization with placement of 3 Tornado embolization coils (Cook Medical, Bloomington, Indiana). Five days later, a follow-up angioMDCT scan showed no signs of active bleeding (Fig. 2D); hemoglobin values were stable, and the patient was discharged on day 21. 3.3. Case #3 An 84-year-old woman with severe aortic stenosis scheduled for an elective TAVR procedure was admitted because of acute pulmonary edema and atrial flutter. The patient underwent a successful transfemoral TAVR with a 29 mm CoreValve bioprosthesis. Dual antiplatelet therapy consisted of aspirin and clopidogrel (300 mg loading dose), and UFH 5000 IU was administered in the catheterization lab. At the time of the procedure, the hemoglobin level was 10.8 g/dL, hematocrit 34%, and platelet level 358 × 109/L. During the subsequent 6 days, hemoglobin dropped slowly to 8.4 g/dL, hematocrit to 26.9%, and platelets to 187 × 109/L. Ten days later, the patient developed acute right abdominal pain. An abdominal angio-MDCT scan was performed. A 9 × 8 × 7 cm hematoma involving the right kidney parenchyma, the posterior renal fascia, and the homolateral psoas muscle was observed. In the venous contrast phase, minute hyperdense areas were detectable in the kidney parenchyma (Fig. 3A and B). Right kidney arteriography showed multiple foci of capillary hemorrhage from the
ante- and retro-pyelic branches of the right renal artery. Microembolization of all three main branches was performed by sequential cannulation and delivery of 6 Tornado embolization coils and 4 Cirrus embolization coils (Balt Extrusion, Montmorency, France) (Fig. 3C and D). Even though procedural success was achieved, 11 days later, the patient developed sepsis complicated by multiorgan failure and shock, leading to death. 4. Discussion Newly acquired mild-to-moderate anemia is frequent after TAVR. In the absence of an obvious cause, it is often attributed to inherent procedural blood loss. By current Valve Academic Research Consortium 2 (VARC-2) definitions, the presence of bleeding without an overt source is not well characterized. [13] Indeed, the epidemiology and clinical impact of “non-overt” bleeding is largely lacking in TAVR trials and registries, potentially related to a lack of appropriate and aggressive investigation. In a series of 310 TAVR patients, Gurvitch et al. showed that 26.8% of them had a bleeding complication, and 7.7% underwent red blood cell transfusions due to non-overt bleeding. [1] Similarly, Genereux et al. reported a 30-day red blood cell transfusion rate of 25% in a cohort of 58 patients undergoing transfemoral TAVR. [10] Of them, 14% had no obvious source of bleeding. In another series of 250 TAVR patients, up to 39% of post-procedural bleeding had an indeterminate origin. [11]. In the present case series, we identified capillary oozing as one of the underlying causes for concealed bleeding that needs to be ruled out when unexplained and persistent new anemia is encountered after TAVR. The pathophysiology of such non-access site-related bleeding remains unclear. However, antithrombotic therapy has been addressed as
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Fig. 3. Angio-MDCT scan and angiography imaging of a hematoma related to capillary bleeding and involving the right kidney parenchyma, the posterior renal fascia and the homolateral psoas muscle. Arterial (a) and venous (b) contrast phase angio-MDCT, showing minute hyperdense areas (arrows) within the parenchyma of right kidney. (c) Right kidney arteriography showing multiple foci of capillary hemorrhage from the ante- and retro-pyelic branches of the right renal artery (arrows). (d) Right kidney angiography after micro-embolization with coil delivery, demonstrating effective treatment of bleeding.
the main factor involved in cases of spontaneous retroperitoneal hemorrhage (not necessarily linked to surgical or percutaneous procedures). [14] Non-access site bleeding complications have already been observed in percutaneous coronary intervention (PCI)-treated patients; in this setting, certain antithrombotic agents have proved to reduce bleeding complications compared to other drugs of the same category. [15] In the present case series, the antithrombotic regimen consisted of UFH 5000 IU during the procedure (activated clotting time was maintained between 250 and 300 s) and a standard DAPT therapy with acetylsalicylic acid and clopidogrel, with a 6-month DAPT indication. During hospitalization, patients received short-term prophylactic low molecular weight heparin (LMWH) for the prevention of venous thromboembolism. Although antithrombotic regimen post-TAVR is not standardized, it is likely that administration of LMWH especially in the presence of renal failure might be a contributing factor to non-access site bleeding. Furthermore, it appears interesting that microvascular injury occurred at the ipsilateral side after accessing the vasculature during TAVR; however, we cannot draw any conclusions from this association, since the hemorrhages originated from the capillary bed, which was not directly involved in the procedures. According to our experience, symptoms and signs of anemia or blood loss may occur after several days from index procedure; at that time, an early diagnostic workout with angio-MDCT scan, including arterial and venous phases, should be performed, since a subsequent endovascular percutaneous treatment might resolve the issue. We suppose that clinicians should pay more attention to slow hemoglobin decrease after interventional procedures, and extend in selected cases the in-hospital observation period. To this regard, the right timing for hospital discharge after TAVR is currently unclear. Ongoing trials, which are examining the feasibility and safety of early discharge after TAVR, will provide more evidence on this topic.
More data from prospective studies are needed to further characterize these occult bleeding complications. Accordingly, we assume that this type of bleeding may warrant a separate category in future revisions of the VARC definitions, allowing a more precise appraisal of its epidemiology and clinical impact. Actually, one may argue that non-overt bleeding might be called as such only after a comprehensive diagnostic investigation was performed, ruling out all potential origins of bleeding intimately related to the TAVR procedure and non-access site bleeding such as gastroenterology or other etiology. A complete and thorough investigation might therefore reclassify such bleeding currently termed as “non-overt” into a well-defined category (access related vs. non-access related). 5. Study limitations This is a case-based, proof of concept study. We only report angiographically confirmed cases of blood oozing, thus the true rate of this complication might be higher. Further verification is needed by largerscale prospective studies. 6. Conclusion Among non-access site bleedings, the issue of post-TAVR blood oozing is often disregarded in the clinical setting and is totally unaddressed in the literature. At the present time, a comprehensive categorization of non-access site bleedings in current standardized endpoints of TAVR studies is missing, and more data are needed in order to reclassify such events into a well-defined category. Until then, awareness of these infrequent but possibly fatal clinical entities may be crucial for clinicians, and early assessment with arterial and venous contrast phase
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angio-MDCT scan in case of post-TAVR unexplained and persistent anemia may allow diagnosis and treatment of this subtle condition. Disclosure All the authors have no conflicts of interest to declare. Acknowledgements None. References [1] R. Gurvitch, S. Toggweiler, A.B. Willson, et al., Outcomes and complications of transcatheter aortic valve replacement using a balloon expandable valve according to the Valve Academic Research Consortium (VARC) guidelines, EuroIntervention 7 (2011) 41–48. [2] G. Ndrepepa, A. Kastrati, Bleeding complications in patients undergoing percutaneous coronary interventions: current status and perspective, Coron. Artery Dis. 25 (2014) 247–257. [3] P. Genereux, D.J. Cohen, M.R. Williams, et al., Bleeding complications after surgical aortic valve replacement compared with transcatheter aortic valve replacement: insights from the PARTNER I Trial (Placement of Aortic Transcatheter Valve), J. Am. Coll. Cardiol. 63 (2014) 1100–1109. [4] M. Moscucci, K.A. Fox, C.P. Cannon, et al., Predictors of major bleeding in acute coronary syndromes: the Global Registry of Acute Coronary Events (GRACE), Eur. Heart J. 24 (2003) 1815–1823. [5] J. Rodes-Cabau, H.L. Dauerman, M.G. Cohen, et al., Antithrombotic treatment in transcatheter aortic valve implantation: insights for cerebrovascular and bleeding events, J. Am. Coll. Cardiol. 62 (2013) 2349–2359.
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[6] G. Ndrepepa, P.B. Berger, J. Mehilli, et al., Periprocedural bleeding and 1-year outcome after percutaneous coronary interventions: appropriateness of including bleeding as a component of a quadruple end point, J. Am. Coll. Cardiol. 51 (2008) 690–697. [7] C.S. Kwok, S.V. Rao, P.K. Myint, et al., Major bleeding after percutaneous coronary intervention and risk of subsequent mortality: a systematic review and meta-analysis, Open Heart 1 (2014), e000021. [8] G. Ndrepepa, F.J. Neumann, G. Richardt, et al., Prognostic value of access and nonaccess sites bleeding after percutaneous coronary intervention, Circ. Cardiovasc. Interv. 6 (2013) 354–361. [9] C.S. Kwok, M.A. Khan, S.V. Rao, et al., Access and non-access site bleeding after percutaneous coronary intervention and risk of subsequent mortality and major adverse cardiovascular events: systematic review and meta-analysis, Circ. Cardiovasc. Interv. 8 (2015), e001645. [10] P. Genereux, S. Kodali, M.B. Leon, et al., Clinical outcomes using a new crossover balloon occlusion technique for percutaneous closure after transfemoral aortic valve implantation, J. Am. Coll. Cardiol. Intv. 4 (2011) 861–867. [11] G. Tarantini, V. Gasparetto, M. Napodano, et al., Transcatheter aortic valve implantation and bleeding: focus on Valve Academic Research Consortium-2 classification, Int. J. Cardiol. 168 (2013) 5001–5003. [12] G. Tarantini, M. Mojoli, P. Purita, et al., Unravelling the (arte)fact of increased pacemaker rate with the Edwards SAPIEN 3 valve, EuroIntervention 11 (2015) 343–350. [13] A.P. Kappetein, S.J. Head, P. Genereux, et al. Valve Academic Research Consortium (VARC)-2. Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document (VARC-2), Eur. J. Cardiothorac. Surg. 42 (2012) S45–S60. [14] S. Pieri, P. Agresti, G.L. Buquicchio, I. Di Giampietro, M. Trinci, V. Miele, Endovascular management of the rectus muscle hematoma, Radiol. Med. 120 (2015) 951–958. [15] U. Zeymer, S.V. Rao, G. Montalescot, Anticoagulation in coronary intervention, Eur. Heart J. (2016) (Epub ahead of print).
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Blood oozing: A cause of life-threatening bleeding without overt source after transcatheter aortic valve replacement Giuseppe Tarantini MD, PhD a,⁎,1, Marco Mojoli MD a,1, Alberto Barioli MD a,1, Michele Battistel MD b,1, Philippe Généreux MD c,d,e,1 a
Department of Cardiac, Thoracic and Vascular Sciences, University Hospital of Padua, Padua, Italy University Radiology, Department of Medicine, University Hospital of Padua, Padua, Italy New York-Presbyterian Hospital/Columbia University Medical Center, New York, NY, USA d Cardiovascular Research Foundation, 111 East 59th Street, 12th Floor, New York, NY, USA e Hopital du Sacre-Coeur de Montreal, Université de Montreal, Montreal, QC, Canada b c
a r t i c l e
i n f o
Article history: Received 28 May 2016 Received in revised form 29 August 2016 Accepted 8 September 2016 Available online 10 September 2016 Keywords: Interventional cardiology Transcatheter aortic valve replacement Non-access site bleeding
a b s t r a c t Background: Post-procedure non-access site-related bleedings have a significant impact on mortality in patients treated by transcatheter aortic valve replacement (TAVR). Notwithstanding, the source of these bleedings is frequently indeterminate, with potentially serious clinical implications related to lack of diagnosis and treatment. Methods: Out of 513 TAVR performed between June 2007 and January 2016 in the Interventional Cardiology Laboratory of the Department of Cardiac, Thoracic and Vascular Sciences, University Hospital of Padua, we identified few proven cases of concealed bleeding after TAVR due to blood oozing. Results: We report three cases of angiographically confirmed post-TAVR non-access bleedings related to spontaneous blood oozing, a life-threatening condition consisting of diffuse capillary hemorrhage developing from vessels not directly involved by the procedure. We hypothesize that spontaneous post-procedural blood oozing may account for a substantial proportion of non-overt, non-access site-related bleeding after TAVR. Conclusion: The possibility of post-TAVR blood oozing is largely neglected in the literature, and comprehensive categorization of non-access site bleedings in current standardized endpoints of TAVR studies is missing. Early assessment with arterial and venous contrast phase angio-MDCT scans in case of post-TAVR unexplained and persistent anemia may allow diagnosis and treatment of this subtle condition. © 2016 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Bleeding is a common adverse event after percutaneous cardiac procedures. [1–3] The direct access to vascular structures and the need for periprocedural anticoagulation are predisposing factors to bleeding in this setting. [4,5] In the early era of percutaneous cardiac interventions, the impact of bleeding on outcomes has been long overlooked, [6] while more recently a growing body of evidence has shown that periprocedural bleeding is associated with an increased risk of early
Abbreviations: angio-MDCT, multidetector computed tomography angiography; TAVR, transcatheter aortic valve replacement; UFH, unfractionated heparin; VARC, Valve Academic Research Consortium. ⁎ Corresponding author at: Department of Cardiac, Thoracic and Vascular Sciences, University of Padua Medical School, Via Giustiniani, 2, 35128 Padova, Italy. E-mail address: [email protected] (G. Tarantini). 1 All the authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
http://dx.doi.org/10.1016/j.ijcard.2016.09.009 0167-5273/© 2016 Elsevier Ireland Ltd. All rights reserved.
and late mortality. [7,8] In coronary percutaneous interventions, nonaccess site bleeding is as frequent as access site-related bleeding, and its impact on mortality seems stronger compared to access site bleeding. [8,9] Data regarding the prevalence and outcomes of non-access site bleeding after transcatheter aortic valve replacement (TAVR) are still scant. In a previous report, it was observed that 57% of patients treated by TAVR were transfused because of non-access site bleeding, and 14% of these cases ended up without any bleeding source identified. [10] Similarly, in other series of TAVR patients, up to 39% of periprocedural bleedings had an indeterminate origin. [11,12] These concealed bleedings might be related to spontaneous blood oozing, a condition frequently overlooked clinically and almost neglected in the literature. Oozing consists of a clinically silent and diffuse capillary hemorrhage developing from minute vessels that were not involved in any invasive maneuver during intervention. Blood oozing may be difficult to diagnose due to its usual origin from splanchnic vessels or parenchymal organs. This subtle complication is potentially life-threatening even though an early diagnosis and treatment might be therapeutic. We
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hypothesize that spontaneous post-procedural blood oozing may account for a substantial proportion of non-overt, non-access site-related bleeding after TAVR. 2. Materials and Methods Out of 513 TAVR performed between June 2007 and January 2016 in the Interventional Cardiology Laboratory of the Department of Cardiac, Thoracic and Vascular Sciences, University Hospital of Padua, we identified three proven cases of concealed bleeding due to blood oozing after intervention. Informed consent was obtained from each patient. The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the institution's human research committee.
3. Results Hereafter, we report a systematic description of the three cases of post-TAVR concealed blood oozing identified in our Institution, along with multidetector computed tomography angiography (angio-MDCT) findings and interventional treatment description. Bleedings were observed while the patients were still in the cardiology ward. 3.1. Case #1 An 80-year-old woman with severe aortic stenosis and a history of syncopal episodes was admitted for a TAVR procedure. At admission, her hemoglobin level was 12.6 g/dL, hematocrit 39.5%, and platelet count 246 × 109/L. Pre-procedural dual antiplatelet therapy (aspirin and clopidogrel) was given. At the time of procedure, intravenous unfractionated heparin (UFH) 5000 IU was administered. An uneventful transfemoral TAVR was successfully performed using a 26 mm Edwards SAPIEN 3 valve (Edwards Lifesciences, Irvine, California). In the 2 days
following the procedure, hemoglobin gradually decreased to 9.1 g/dL, hematocrit to 28.5%, and platelet count to 216 × 109/L. In the absence of any apparent source of bleeding, an angio-MDCT scan of the abdomen was performed, which revealed an 11 × 9 cm abdominal hematoma located in the hypogastric region and right iliac fossa. Minute hemorrhagic spots among the medial and lateral mass walls were detectable in the arterial contrast phase but appeared more evident in the venous contrast phase, raising the suspicion of microvascular bleeding (Fig. 1A and B). A selective angiography of the right iliac axis confirmed capillary bleeding originating from the inferior epigastric artery branches. The patient underwent percutaneous selective cannulation of this vessel from a left femoral artery approach by micro-embolization with particle injection (contour 150–200 μm) and delivery of three embolization coils (Tornado 3 × 20 mm, Cook Medical, Bloomington, Indiana) (Fig. 1C and D). The days following were uneventful, and the patient was discharged after 1 week with stable hemoglobin levels. 3.2. Case #2 An 84-year-old woman with severe aortic stenosis and symptoms of heart failure underwent transfemoral TAVR using a 26 mm CoreValve bioprosthesis (Medtronic, Minneapolis, Minnesota). At admission, hemoglobin was 11.4 g/dL, hematocrit 31.7%, and platelet count 213 × 109/L. At the time of the procedure, the patient had normal hemoglobin values and was on dual antiplatelet therapy with aspirin and clopidogrel. Intraprocedural anticoagulation therapy included UFH 5000 IU. In the 4 subsequent days, a hemoglobin drop of 3.6 g/dL was observed, while hematocrit dropped to 22.4%, and platelets were 142 × 109/L. The patient received a transfusion of 3 units of red blood cells and was asymptomatic up to day 10, when sudden right abdominal
Fig. 1. Angio-MDCT scan and angiography imaging in a case of abdominal hematoma arising from multifocal capillary bleeding. Minute hemorrhagic spots are detectable by arterial phase angio-MDCT scan (a) within a hematoma located in the hypogastric region and appear more evident in the venous contrast phase (arrows) (b), suggesting active bleeding originating from a capillary source (the so-called blood oozing). (c) Selective angiography of the right iliac axis confirming multifocal capillary bleeding deriving from inferior epigastric artery branches (arrows). (d) Right iliac artery angiography after micro-embolization with particle injection and delivery of three embolization coils, demonstrating resolution of blood oozing.
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Fig. 2. Angio-MDCT scan and angiography imaging in a case of right retroperitoneal hematoma related to blood oozing. Arterial (a) and venous (b) contrast phase angio-MDCT showing active retroperitoneal capillary bleeding within a large hematoma located in the right iliac fossa. A more pronounced hyperdensity in the venous contrast phase (arrows) compared to the arterial phase is a typical feature of active capillary bleeding when detected by angio-MDCT scan. (c) Active multifocal blood oozing originating from the deep circumflex iliac artery is confirmed by selective angiography of a right iliac artery branch (arrows). (d) Control angio-MDCT scan after coil delivery (arrow), showing no signs of active bleeding.
pain occurred. An urgent abdominal angio-MDCT scan showed a right retroperitoneal hematoma with signs of active capillary bleeding clearly noticeable in the venous contrast phase within the right iliac fossa (Fig. 2A and B). A right iliac artery angiography was thus performed, demonstrating an active multifocal blood oozing originating from the deep circumflex iliac artery (Fig. 2C). Selective cannulation with a microcatheter was performed, followed by effective microembolization with placement of 3 Tornado embolization coils (Cook Medical, Bloomington, Indiana). Five days later, a follow-up angioMDCT scan showed no signs of active bleeding (Fig. 2D); hemoglobin values were stable, and the patient was discharged on day 21. 3.3. Case #3 An 84-year-old woman with severe aortic stenosis scheduled for an elective TAVR procedure was admitted because of acute pulmonary edema and atrial flutter. The patient underwent a successful transfemoral TAVR with a 29 mm CoreValve bioprosthesis. Dual antiplatelet therapy consisted of aspirin and clopidogrel (300 mg loading dose), and UFH 5000 IU was administered in the catheterization lab. At the time of the procedure, the hemoglobin level was 10.8 g/dL, hematocrit 34%, and platelet level 358 × 109/L. During the subsequent 6 days, hemoglobin dropped slowly to 8.4 g/dL, hematocrit to 26.9%, and platelets to 187 × 109/L. Ten days later, the patient developed acute right abdominal pain. An abdominal angio-MDCT scan was performed. A 9 × 8 × 7 cm hematoma involving the right kidney parenchyma, the posterior renal fascia, and the homolateral psoas muscle was observed. In the venous contrast phase, minute hyperdense areas were detectable in the kidney parenchyma (Fig. 3A and B). Right kidney arteriography showed multiple foci of capillary hemorrhage from the
ante- and retro-pyelic branches of the right renal artery. Microembolization of all three main branches was performed by sequential cannulation and delivery of 6 Tornado embolization coils and 4 Cirrus embolization coils (Balt Extrusion, Montmorency, France) (Fig. 3C and D). Even though procedural success was achieved, 11 days later, the patient developed sepsis complicated by multiorgan failure and shock, leading to death. 4. Discussion Newly acquired mild-to-moderate anemia is frequent after TAVR. In the absence of an obvious cause, it is often attributed to inherent procedural blood loss. By current Valve Academic Research Consortium 2 (VARC-2) definitions, the presence of bleeding without an overt source is not well characterized. [13] Indeed, the epidemiology and clinical impact of “non-overt” bleeding is largely lacking in TAVR trials and registries, potentially related to a lack of appropriate and aggressive investigation. In a series of 310 TAVR patients, Gurvitch et al. showed that 26.8% of them had a bleeding complication, and 7.7% underwent red blood cell transfusions due to non-overt bleeding. [1] Similarly, Genereux et al. reported a 30-day red blood cell transfusion rate of 25% in a cohort of 58 patients undergoing transfemoral TAVR. [10] Of them, 14% had no obvious source of bleeding. In another series of 250 TAVR patients, up to 39% of post-procedural bleeding had an indeterminate origin. [11]. In the present case series, we identified capillary oozing as one of the underlying causes for concealed bleeding that needs to be ruled out when unexplained and persistent new anemia is encountered after TAVR. The pathophysiology of such non-access site-related bleeding remains unclear. However, antithrombotic therapy has been addressed as
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Fig. 3. Angio-MDCT scan and angiography imaging of a hematoma related to capillary bleeding and involving the right kidney parenchyma, the posterior renal fascia and the homolateral psoas muscle. Arterial (a) and venous (b) contrast phase angio-MDCT, showing minute hyperdense areas (arrows) within the parenchyma of right kidney. (c) Right kidney arteriography showing multiple foci of capillary hemorrhage from the ante- and retro-pyelic branches of the right renal artery (arrows). (d) Right kidney angiography after micro-embolization with coil delivery, demonstrating effective treatment of bleeding.
the main factor involved in cases of spontaneous retroperitoneal hemorrhage (not necessarily linked to surgical or percutaneous procedures). [14] Non-access site bleeding complications have already been observed in percutaneous coronary intervention (PCI)-treated patients; in this setting, certain antithrombotic agents have proved to reduce bleeding complications compared to other drugs of the same category. [15] In the present case series, the antithrombotic regimen consisted of UFH 5000 IU during the procedure (activated clotting time was maintained between 250 and 300 s) and a standard DAPT therapy with acetylsalicylic acid and clopidogrel, with a 6-month DAPT indication. During hospitalization, patients received short-term prophylactic low molecular weight heparin (LMWH) for the prevention of venous thromboembolism. Although antithrombotic regimen post-TAVR is not standardized, it is likely that administration of LMWH especially in the presence of renal failure might be a contributing factor to non-access site bleeding. Furthermore, it appears interesting that microvascular injury occurred at the ipsilateral side after accessing the vasculature during TAVR; however, we cannot draw any conclusions from this association, since the hemorrhages originated from the capillary bed, which was not directly involved in the procedures. According to our experience, symptoms and signs of anemia or blood loss may occur after several days from index procedure; at that time, an early diagnostic workout with angio-MDCT scan, including arterial and venous phases, should be performed, since a subsequent endovascular percutaneous treatment might resolve the issue. We suppose that clinicians should pay more attention to slow hemoglobin decrease after interventional procedures, and extend in selected cases the in-hospital observation period. To this regard, the right timing for hospital discharge after TAVR is currently unclear. Ongoing trials, which are examining the feasibility and safety of early discharge after TAVR, will provide more evidence on this topic.
More data from prospective studies are needed to further characterize these occult bleeding complications. Accordingly, we assume that this type of bleeding may warrant a separate category in future revisions of the VARC definitions, allowing a more precise appraisal of its epidemiology and clinical impact. Actually, one may argue that non-overt bleeding might be called as such only after a comprehensive diagnostic investigation was performed, ruling out all potential origins of bleeding intimately related to the TAVR procedure and non-access site bleeding such as gastroenterology or other etiology. A complete and thorough investigation might therefore reclassify such bleeding currently termed as “non-overt” into a well-defined category (access related vs. non-access related). 5. Study limitations This is a case-based, proof of concept study. We only report angiographically confirmed cases of blood oozing, thus the true rate of this complication might be higher. Further verification is needed by largerscale prospective studies. 6. Conclusion Among non-access site bleedings, the issue of post-TAVR blood oozing is often disregarded in the clinical setting and is totally unaddressed in the literature. At the present time, a comprehensive categorization of non-access site bleedings in current standardized endpoints of TAVR studies is missing, and more data are needed in order to reclassify such events into a well-defined category. Until then, awareness of these infrequent but possibly fatal clinical entities may be crucial for clinicians, and early assessment with arterial and venous contrast phase
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angio-MDCT scan in case of post-TAVR unexplained and persistent anemia may allow diagnosis and treatment of this subtle condition. Disclosure All the authors have no conflicts of interest to declare. Acknowledgements None. References [1] R. Gurvitch, S. Toggweiler, A.B. Willson, et al., Outcomes and complications of transcatheter aortic valve replacement using a balloon expandable valve according to the Valve Academic Research Consortium (VARC) guidelines, EuroIntervention 7 (2011) 41–48. [2] G. Ndrepepa, A. Kastrati, Bleeding complications in patients undergoing percutaneous coronary interventions: current status and perspective, Coron. Artery Dis. 25 (2014) 247–257. [3] P. Genereux, D.J. Cohen, M.R. Williams, et al., Bleeding complications after surgical aortic valve replacement compared with transcatheter aortic valve replacement: insights from the PARTNER I Trial (Placement of Aortic Transcatheter Valve), J. Am. Coll. Cardiol. 63 (2014) 1100–1109. [4] M. Moscucci, K.A. Fox, C.P. Cannon, et al., Predictors of major bleeding in acute coronary syndromes: the Global Registry of Acute Coronary Events (GRACE), Eur. Heart J. 24 (2003) 1815–1823. [5] J. Rodes-Cabau, H.L. Dauerman, M.G. Cohen, et al., Antithrombotic treatment in transcatheter aortic valve implantation: insights for cerebrovascular and bleeding events, J. Am. Coll. Cardiol. 62 (2013) 2349–2359.
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