Case Anecdotes, Comments and Opinions
Disclosure statement The authors have no conflicts of interest to disclose.
References 1. Noris M, Caprioli J, Bresin E, et al. Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype. Clin J Am Soc Nephrol 2010;5:1844-59.
Device thrombosis in continuous-flow left ventricular assist devices: A new manifestation of Kounis syndrome? Nicholas G. Kounis, MD, PhD,a George D. Soufras, MD, PhD,b and Periklis Davlouros, MD, PhDc From the aDepartment of Medical Sciences, Patras Highest Institute of Education and Technology; the bDepartment of Cardiology, “Saint Andrews” General Hospital; and the C Department of Cardiology, University of Patras Medical School, Patras, Achaia, Greece
In the very important article published recently in the Journal of Heart and Lung Transplantation, Uriel et al1 reported that 19 of 177 patients (11%) with HeartMate II (Thoratec, Pleasanton, CA) assist device implantation were found to have device thrombosis of various etiologies. Five had mechanically induced thromboses, 1 had a hypercoagulable disorder with prior arterial embolism, and the remaining 13 patients had non-mechanical device thrombosis. They concluded that device thrombosis is a multifactorial phenomenon, its precise prevalence and etiology still remains uncertain, and that differentiation of mechanical and non-mechanical causes is an essential step for individual diagnosis and treatment plans. A similar study that was conducted in 3 institutions found that pump thrombosis related to the use of the HeartMate II pump was 12.3% during 24 months of support and was associated with substantial morbidity and death.2 In that study, histologic examination of thrombotic material deposited near the inflow bearing showed infiltration by lymphocytes, plasma cells, and eosinophils, thus possibly pointing to hypersensitivity-related inflammation. Examinations at pump replacement, urgent transplantation, or at autopsy revealed thrombotic material in blood-contacting surfaces of the HeartMate II, including the inflow cannula and outflow conduit. The high rate of thrombosis makes the search for causality of thrombosis mandatory to predict and prevent this morbid complication. An important question that arises is whether the titanium parts of this device can induce hypersensitivity inflammation and, consequently, thrombosis. Metal anions eluted from titanium, nickel, cobalt, chromium, palladium, and gold are common allergic sensitizers. Allergy to nickel is the most frequent cause of allergic contact
665 2. Galli FC, Damon LE, Tomlanovich SJ, et al. Cyclosporine-induced hemolytic uremic syndrome in a heart transplant recipient. J Heart Lung Transplant 1993;12:440-4. 3. Myers JN, Shabshab SF, Burton NA, et al. Successful use of cyclosporine in a lung transplant recipient with tacrolimus-associated hemolytic uremic syndrome. J Heart Lung Transplant 1999;18:1024-6. 4. Noris M, Remuzzi G. Atypical hemolytic-uremic syndrome. N Engl J Med 2009;361:1676-87.
dermatitis. That patients are sensitized to multiple metal anions is common. Concurrent sensitization, cross-reactivity, or both, seem to be possible. Sensitization to one metal anion has been shown to increase the possibility of being sensitized to additional metals. Metals seem to “join forces” to sensitize individuals. Titanium metal ions from the HeartMate II and salts from metal corrosion could be eluted at any time through the action of blood, saline, proteins, and mechanical stress. They can act as haptens and become full allergens after reaction with proteins that can be present in the host’s antigen-presenting cells. Although titanium is considered an excellent biocompatible metal with good corrosion behavior, hypersensitivity reactions to titanium have been already reported.3 Titanium alloy can induce hypersensitivity and immune dysfunctions that render titanium no longer biologically inert. Elution of titanium ions is influenced by environmental pH and by crevice corrosion and can result in further implant corrosion and titanium allergy. The specific antigenicity of titanium ions released by biocorrosion can induce Kounis hypersensitivityassociated acute thrombotic syndrome by activating platelets via Fc receptors FcγRΙ, FcγRII, FcεRI, and FcεRII. Therefore, careful history of hypersensitivity reactions, monitoring of inflammatory mediators, and lymphocyte transformation studies must be done to detect metal allergy, especially for titanium, because such specific T lymphocytes demonstrate strong sensitivity to titanium ions released by biocorrosion. Further systematic studies in this regard are warranted to elucidate the exact cause of thrombosis and to prevent and treat this complication.
Disclosure statement None of the authors has a financial relationship with a commercial entity that has an interest in the subject of the presented manuscript or other conflicts of interest to disclose.
References 1. Uriel N, Han J, Morrison KA, et al. Device thrombosis in HeartMate II continuous-flow left ventricular assist devices: a multifactorial phenomenon. J Heart Lung Transplant 2014;33:51-9. 2. Starling RC, Moazami N, Silvestry SC, et al. Unexpected abrupt increase in left ventricular assist device thrombosis. N Engl J Med 2014;370:33-40. 3. Muller K, Valentine-Thon E. Hypersensitivity to titanium: clinical and laboratory evidence. Neuro Endocrinol Lett 2006;27:31-5.
Disclosure statement The authors have no conflicts of interest to disclose.
References 1. Noris M, Caprioli J, Bresin E, et al. Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype. Clin J Am Soc Nephrol 2010;5:1844-59.
Device thrombosis in continuous-flow left ventricular assist devices: A new manifestation of Kounis syndrome? Nicholas G. Kounis, MD, PhD,a George D. Soufras, MD, PhD,b and Periklis Davlouros, MD, PhDc From the aDepartment of Medical Sciences, Patras Highest Institute of Education and Technology; the bDepartment of Cardiology, “Saint Andrews” General Hospital; and the C Department of Cardiology, University of Patras Medical School, Patras, Achaia, Greece
In the very important article published recently in the Journal of Heart and Lung Transplantation, Uriel et al1 reported that 19 of 177 patients (11%) with HeartMate II (Thoratec, Pleasanton, CA) assist device implantation were found to have device thrombosis of various etiologies. Five had mechanically induced thromboses, 1 had a hypercoagulable disorder with prior arterial embolism, and the remaining 13 patients had non-mechanical device thrombosis. They concluded that device thrombosis is a multifactorial phenomenon, its precise prevalence and etiology still remains uncertain, and that differentiation of mechanical and non-mechanical causes is an essential step for individual diagnosis and treatment plans. A similar study that was conducted in 3 institutions found that pump thrombosis related to the use of the HeartMate II pump was 12.3% during 24 months of support and was associated with substantial morbidity and death.2 In that study, histologic examination of thrombotic material deposited near the inflow bearing showed infiltration by lymphocytes, plasma cells, and eosinophils, thus possibly pointing to hypersensitivity-related inflammation. Examinations at pump replacement, urgent transplantation, or at autopsy revealed thrombotic material in blood-contacting surfaces of the HeartMate II, including the inflow cannula and outflow conduit. The high rate of thrombosis makes the search for causality of thrombosis mandatory to predict and prevent this morbid complication. An important question that arises is whether the titanium parts of this device can induce hypersensitivity inflammation and, consequently, thrombosis. Metal anions eluted from titanium, nickel, cobalt, chromium, palladium, and gold are common allergic sensitizers. Allergy to nickel is the most frequent cause of allergic contact
665 2. Galli FC, Damon LE, Tomlanovich SJ, et al. Cyclosporine-induced hemolytic uremic syndrome in a heart transplant recipient. J Heart Lung Transplant 1993;12:440-4. 3. Myers JN, Shabshab SF, Burton NA, et al. Successful use of cyclosporine in a lung transplant recipient with tacrolimus-associated hemolytic uremic syndrome. J Heart Lung Transplant 1999;18:1024-6. 4. Noris M, Remuzzi G. Atypical hemolytic-uremic syndrome. N Engl J Med 2009;361:1676-87.
dermatitis. That patients are sensitized to multiple metal anions is common. Concurrent sensitization, cross-reactivity, or both, seem to be possible. Sensitization to one metal anion has been shown to increase the possibility of being sensitized to additional metals. Metals seem to “join forces” to sensitize individuals. Titanium metal ions from the HeartMate II and salts from metal corrosion could be eluted at any time through the action of blood, saline, proteins, and mechanical stress. They can act as haptens and become full allergens after reaction with proteins that can be present in the host’s antigen-presenting cells. Although titanium is considered an excellent biocompatible metal with good corrosion behavior, hypersensitivity reactions to titanium have been already reported.3 Titanium alloy can induce hypersensitivity and immune dysfunctions that render titanium no longer biologically inert. Elution of titanium ions is influenced by environmental pH and by crevice corrosion and can result in further implant corrosion and titanium allergy. The specific antigenicity of titanium ions released by biocorrosion can induce Kounis hypersensitivityassociated acute thrombotic syndrome by activating platelets via Fc receptors FcγRΙ, FcγRII, FcεRI, and FcεRII. Therefore, careful history of hypersensitivity reactions, monitoring of inflammatory mediators, and lymphocyte transformation studies must be done to detect metal allergy, especially for titanium, because such specific T lymphocytes demonstrate strong sensitivity to titanium ions released by biocorrosion. Further systematic studies in this regard are warranted to elucidate the exact cause of thrombosis and to prevent and treat this complication.
Disclosure statement None of the authors has a financial relationship with a commercial entity that has an interest in the subject of the presented manuscript or other conflicts of interest to disclose.
References 1. Uriel N, Han J, Morrison KA, et al. Device thrombosis in HeartMate II continuous-flow left ventricular assist devices: a multifactorial phenomenon. J Heart Lung Transplant 2014;33:51-9. 2. Starling RC, Moazami N, Silvestry SC, et al. Unexpected abrupt increase in left ventricular assist device thrombosis. N Engl J Med 2014;370:33-40. 3. Muller K, Valentine-Thon E. Hypersensitivity to titanium: clinical and laboratory evidence. Neuro Endocrinol Lett 2006;27:31-5.
