Journal of Clinical Medicine

Research

18 pages, 2165 KiB

Open AccessArticle

Vascular Occlusion in Kidney Biopsy Is Characteristic of Clinically Manifesting Thrombotic Microangiopathy

by Marja Kovala, Minna Seppälä, Kati Kaartinen, Seppo Meri, Eero Honkanen and Anne Räisänen-Sokolowski

J. Clin. Med. 2022, 11(11), 3124; https://doi.org/10.3390/jcm11113124 - 31 May 2022

Cited by 6 | Viewed by 2305

Abstract

Thrombotic microangiopathy (TMA) can sometimes manifest only histologically. Our aim was to retrospectively compare biopsy-proven adult TMA patients showing only histological (h-TMA) or both histological and clinical (c-TMA) TMA in 2006–2017. All native kidney biopsies with TMA were included. Biopsies were re-evaluated by [...] Read more.

Thrombotic microangiopathy (TMA) can sometimes manifest only histologically. Our aim was to retrospectively compare biopsy-proven adult TMA patients showing only histological (h-TMA) or both histological and clinical (c-TMA) TMA in 2006–2017. All native kidney biopsies with TMA were included. Biopsies were re-evaluated by light and electron microscopy, and immunofluorescence. Clinical characteristics, laboratory variables, and treatments were recorded from the electronic medical database. Patients were categorized into h-TMA and c-TMA and these groups were compared. In total, 30 biopsy-proven cases among 7943 kidney biopsies were identified and, of these, 15 had h-TMA and 15 c-TMA. Mean follow-up was 6.3 y, and 73.3% had secondary hemolytic uremic syndrome (HUS) and the rest were atypical HUS. Patient characteristics, treatments, and kidney, and patient survival in the groups were similar. Statistically significant differences were found in histological variables. Vascular myxoid swelling and vascular onion-skinning were almost exclusively detected in c-TMA and, thus, vascular occlusive changes indicate clinically apparent rather than merely histological TMA. In addition, regardless of clinical presentation, kidney and patient survival times were similar in the patient groups highlighting the importance of a kidney biopsy in the case of any kidney-related symptoms. Full article

(This article belongs to the Special Issue Advances in the Syndromes of Thrombotic Microangiopathy (TMA))

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Review

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11 pages, 1255 KiB

Open AccessReview

Severe Thrombotic Thrombocytopenic Purpura (TTP) with Organ Failure in Critically Ill Patients

by Sofiane Fodil and Lara Zafrani

J. Clin. Med. 2022, 11(4), 1103; https://doi.org/10.3390/jcm11041103 - 19 Feb 2022

Cited by 13 | Viewed by 10598

Abstract

Thrombotic thrombocytopenic purpura (TTP) is a multiorgan disorder. Organ dysfunction occurs as a consequence of widespread microvascular thrombosis, especially in the heart, brain and kidney, causing transient or partial occlusion of vessels, resulting in organ ischemia. Intensive care unit (ICU) admission varies between [...] Read more.

Thrombotic thrombocytopenic purpura (TTP) is a multiorgan disorder. Organ dysfunction occurs as a consequence of widespread microvascular thrombosis, especially in the heart, brain and kidney, causing transient or partial occlusion of vessels, resulting in organ ischemia. Intensive care unit (ICU) admission varies between 40% and 100% of patients with TTP, either because of severe organ failure or in order to initiate emergency plasma exchange (PEx). Severe neurologic manifestations and cardiac involvement have been associated with higher mortality. Acute kidney injury, although usually less severe than that in hemolytic and uremic syndrome, is common during TTP. Initial management in the ICU should always be considered in TTP patients. The current treatment of TTP in the acute phase is based on urgent PEx, combined with corticosteroid therapy, B-cell-targeted immunotherapy, rituximab and inhibition of the interaction between ultra-large Von Willebrand factor multimers and platelets, using caplacizumab, a monoclonal antibody. ICU management permits close monitoring and the rapid introduction of life-sustaining therapies. This review details the epidemiology of TTP in the ICU, organ failures of critically ill patients with TTP, and the initial management of TTP patients in the ICU. Full article

(This article belongs to the Special Issue Advances in the Syndromes of Thrombotic Microangiopathy (TMA))

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13 pages, 1511 KiB

Open AccessReview

Complement Blockade Is a Promising Therapeutic Approach in a Subset of Critically Ill Adult Patients with Complement-Mediated Hemolytic Uremic Syndromes

by Renaud Prével, Yahsou Delmas, Vivien Guillotin, Didier Gruson and Etienne Rivière

J. Clin. Med. 2022, 11(3), 790; https://doi.org/10.3390/jcm11030790 - 1 Feb 2022

Cited by 1 | Viewed by 3420

Abstract

Thrombotic microangiopathy (TMA) gathers consumptive thrombocytopenia, mechanical haemolytic anemia, and organ damage. Hemolytic uremic syndromes (HUS) are historically classified as primary or secondary to another disease once thrombotic thrombocytopenic purpura (TTP), Shiga-toxin HUS, and cobalamin C-related HUS have been ruled out. Complement genetics [...] Read more.

Thrombotic microangiopathy (TMA) gathers consumptive thrombocytopenia, mechanical haemolytic anemia, and organ damage. Hemolytic uremic syndromes (HUS) are historically classified as primary or secondary to another disease once thrombotic thrombocytopenic purpura (TTP), Shiga-toxin HUS, and cobalamin C-related HUS have been ruled out. Complement genetics studies reinforced the link between complement dysregulation and primary HUS, contributing to reclassifying some pregnancy- and/or post-partum-associated HUS and to revealing complement involvement in severe and/or refractory hypertensive emergencies. By contrast, no firm evidence allows a plausible association to be drawn between complement dysregulation and Shiga-toxin HUS or other secondary HUS. Nevertheless, rare complement gene variants are prevalent in healthy individuals, thus providing an indication that an investigation into complement dysregulation should be carefully balanced and that the results should be cautiously interpreted with the help of a trained geneticist. Several authors have suggested reclassifying HUS in two entities, regardless of they are complement-mediated or not, since the use of eculizumab, an anti-C5 antibody, dramatically lowers the proportion of patients who die or suffer from end-stage renal disease within the year following diagnosis. Safety and the ideal timing of eculizumab discontinuation is currently under investigation, and the long-term consequences of HUS should be closely monitored over time once patients exit emergency departments. Full article

(This article belongs to the Special Issue Advances in the Syndromes of Thrombotic Microangiopathy (TMA))

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19 pages, 1767 KiB

Open AccessReview

The Syndromes of Thrombotic Microangiopathy: A Critical Appraisal on Complement Dysregulation

by Sjoerd A. M. E. G. Timmermans and Pieter van Paassen

J. Clin. Med. 2021, 10(14), 3034; https://doi.org/10.3390/jcm10143034 - 8 Jul 2021

Cited by 25 | Viewed by 8862

Abstract

Thrombotic microangiopathy (TMA) is a rare and potentially life-threatening condition that can be caused by a heterogeneous group of diseases, often affecting the brain and kidneys. TMAs should be classified according to etiology to indicate targets for treatment. Complement dysregulation is an important [...] Read more.

Thrombotic microangiopathy (TMA) is a rare and potentially life-threatening condition that can be caused by a heterogeneous group of diseases, often affecting the brain and kidneys. TMAs should be classified according to etiology to indicate targets for treatment. Complement dysregulation is an important cause of TMA that defines cases not related to coexisting conditions, that is, primary atypical hemolytic uremic syndrome (HUS). Ever since the approval of therapeutic complement inhibition, the approach of TMA has focused on the recognition of primary atypical HUS. Recent advances, however, demonstrated the pivotal role of complement dysregulation in specific subtypes of patients considered to have secondary atypical HUS. This is particularly the case in patients presenting with coexisting hypertensive emergency, pregnancy, and kidney transplantation, shifting the paradigm of disease. In contrast, complement dysregulation is uncommon in patients with other coexisting conditions, such as bacterial infection, drug use, cancer, and autoimmunity, among other disorders. In this review, we performed a critical appraisal on complement dysregulation and the use of therapeutic complement inhibition in TMAs associated with coexisting conditions and outline a pragmatic approach to diagnosis and treatment. For future studies, we advocate the term complement-mediated TMA as opposed to the traditional atypical HUS-type classification. Full article

(This article belongs to the Special Issue Advances in the Syndromes of Thrombotic Microangiopathy (TMA))

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10 pages, 1038 KiB

Open AccessCase Report

A Life-Threating Postpartum Atypical Hemolytic-Uremic Syndrome with Multiorgan Involvement

by Laura Sarno, Paolo Conca, Alfredo Capuano, Giovanni Tarantino, Domenico Russo and Maurizio Guida

J. Clin. Med. 2022, 11(23), 6957; https://doi.org/10.3390/jcm11236957 - 25 Nov 2022

Cited by 2 | Viewed by 1605

Abstract

Atypical Hemolytic Uremic Syndrome is a very rare condition that can be triggered in predisposed patients. It can remain undiagnosed and can result in a life-threatening event or permanent renal failure. We report a case of a 36-year-old pregnant woman who developed atypical [...] Read more.

Atypical Hemolytic Uremic Syndrome is a very rare condition that can be triggered in predisposed patients. It can remain undiagnosed and can result in a life-threatening event or permanent renal failure. We report a case of a 36-year-old pregnant woman who developed atypical hemolytic uremic syndrome postpartum. She underwent an emergency caesarean section due to abruptio placenta, and she developed biochemical alterations suggestive of a thrombotic microangiopathy. Due to worsening of renal function after plasma exchange therapy, we decided to start therapy with eculizumab. Therapy was carried out with a weekly dose of 900 mg IV for five weeks. An improvement of clinical and biochemical parameters was rapidly observed, and her renal function completely recovered. The therapy was continued for six months, with a dose of 1200 mg of eculizumab every two weeks. One year after discontinuation of the therapy, her blood pressure and renal function were still normal. Our case confirms that it is important to promptly identify a pregnancy-related thrombotic microangiopathy and that early therapy can be life-saving for the patient and can preserve renal function, avoiding dialysis. Full article

(This article belongs to the Special Issue Advances in the Syndromes of Thrombotic Microangiopathy (TMA))

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10 pages, 1246 KiB

Open AccessCase Report

A Limited Course of Eculizumab in a Child with the Atypical Hemolytic Uremic Syndrome and Pre-B Acute Lymphoblastic Leukemia on Maintenance Therapy: Case Report and Literature Review

by Daniel Turudic, Danko Milosevic, Katarina Bilic, Zoltán Prohászka and Ernest Bilic

J. Clin. Med. 2022, 11(10), 2779; https://doi.org/10.3390/jcm11102779 - 14 May 2022

Cited by 5 | Viewed by 2507

Abstract

Acute lymphoblastic leukemia (ALL) is considered a possible risk for the occurrence of thrombotic microangiopathies. We present a girl with pre-B ALL successfully treated according to the BFM ALL IC-2009 protocol on maintenance therapy followed by aHUS occurrence. This is the seventh case [...] Read more.

Acute lymphoblastic leukemia (ALL) is considered a possible risk for the occurrence of thrombotic microangiopathies. We present a girl with pre-B ALL successfully treated according to the BFM ALL IC-2009 protocol on maintenance therapy followed by aHUS occurrence. This is the seventh case of HUS/aHUS on ALL maintenance therapy and the first with clearly documented eculizumab use in the early stage of aHUS/secondary TMA. Standard and additional parameters were used in aHUS monitoring alongside the reticulocyte production index adjusted for age (RPI/A) and the aspartate aminotransferase-to-platelet ratio index (APRI) as markers of hemolysis and rapid response following treatment. RPI/A and APRI are markers of bone marrow response to anemia serving as red blood cell vs. platelet recovery markers. Together they mark the exact recovery point of thrombotic microangiopathy and serve as a prognostic marker of eculizumab treatment success. During the 8-month treatment and 6-month follow-up, no recurrence of hemolysis, ALL relapse, or renal damage were observed. A systematic review of the literature revealed 14/312 articles; five children had aHUS before the onset of ALL, and two children had both diseases concurrently. At least 3/7 patients are attributed to aHUS, of whom 2/7 have renal damage. Potential undiagnosed/unpublished cases may be assumed. Full article

(This article belongs to the Special Issue Advances in the Syndromes of Thrombotic Microangiopathy (TMA))

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7 pages, 7581 KiB

Open AccessCase Report

Postsurgical Thrombotic Microangiopathy and Deregulated Complement

by Thijs T. W. van Herpt, Sjoerd A. M. E. G. Timmermans, Walther N. K. A. van Mook, Bas C. T. van Bussel, Iwan C. C. van der Horst, Jos G. Maessen, Ehsan Natour, Pieter van Paassen and Samuel Heuts

J. Clin. Med. 2022, 11(9), 2501; https://doi.org/10.3390/jcm11092501 - 29 Apr 2022

Cited by 3 | Viewed by 2133

Abstract

Postsurgical thrombotic microangiopathy (TMA) is a complication associated with significant morbidity and mortality. Still, the pathophysiological underlying mechanism of postsurgical TMA, a diagnosis often overlooked in postoperative patients with acute kidney injury and thrombocytopenia, is largely unknown. Here, we report the case of [...] Read more.

Postsurgical thrombotic microangiopathy (TMA) is a complication associated with significant morbidity and mortality. Still, the pathophysiological underlying mechanism of postsurgical TMA, a diagnosis often overlooked in postoperative patients with acute kidney injury and thrombocytopenia, is largely unknown. Here, we report the case of a 56-year-old male that developed anuric acute kidney injury, Coombs-negative hemolysis, and thrombocytopenia after surgical aortic arch replacement. Massive ex vivo complement activation on the endothelium, a rare complement gene variant in C2, at-risk haplotype MCPggaac, and excellent response to therapeutic complement inhibition, points to the pivotal role of complement in the pathophysiology of disease. Moreover, the importance of a multidisciplinary team approach in (postsurgical) thrombocytopenia is emphasized. Full article

(This article belongs to the Special Issue Advances in the Syndromes of Thrombotic Microangiopathy (TMA))

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9 pages, 1231 KiB

Open AccessBrief Report

Urine Protein/Creatinine Ratio in Thrombotic Microangiopathies: A Simple Test to Facilitate Thrombotic Thrombocytopenic Purpura and Hemolytic and Uremic Syndrome Diagnosis

by Laure Burguet, Benjamin Taton, Mathilde Prezelin-Reydit, Sébastien Rubin, Walter Picard, Didier Gruson, Anne Ryman, Cécile Contin-Bordes, Paul Coppo, Christian Combe and Yahsou Delmas

J. Clin. Med. 2022, 11(3), 648; https://doi.org/10.3390/jcm11030648 - 27 Jan 2022

Cited by 6 | Viewed by 2468

Abstract

Background: Early diagnosis of thrombotic thrombocytopenic purpura (TTP) versus hemolytic and uremic syndrome (HUS) is critical for the prompt initiation of specific therapies. Objective: To evaluate the diagnostic performance of the proteinuria/creatininuria ratio (PU/CU) for TTP versus HUS. Patients/Methods: In a retrospective study, [...] Read more.

Background: Early diagnosis of thrombotic thrombocytopenic purpura (TTP) versus hemolytic and uremic syndrome (HUS) is critical for the prompt initiation of specific therapies. Objective: To evaluate the diagnostic performance of the proteinuria/creatininuria ratio (PU/CU) for TTP versus HUS. Patients/Methods: In a retrospective study, in association with the “French Score” (FS) (platelets < 30 G/L and serum creatinine level < 200 µmol/L), we assessed PU/CU for the diagnosis of TTP in patients above the age of 15 with thrombotic microangiopathy (TMA). Patients with a history of kidney disease or with on-going cancer, allograft or pregnancy were excluded from the analysis. Results: Between February 2011 and April 2019, we identified 124 TMA. Fifty-six TMA patients for whom PU/CU were available, including 35 TTP and 21 HUS cases, were considered. Using receiver–operating characteristic curves (ROC), those with a threshold of 1.5 g/g for the PU/CU had a 77% sensitivity (95% CI (63, 94)) and a 90% specificity (95% CI (71, 100)) for TTP diagnosis compared with those having an 80% sensitivity (95% CI (66, 92)) and a 90% specificity (95% CI (76, 100) with a FS of 2. In comparison, a composite score, defined as a FS of 2 or a PU/CU ≤ 1.5 g/g, improved sensitivity to 99.6% (95% CI (93, 100)) for TTP diagnosis and enabled us to reclassify seven false-negative TTP patients. Conclusions: The addition of urinary PU/CU upon admission of patients with TMA is a fast and readily available test that can aid in the differential diagnosis of TTP versus HUS alongside traditional scoring. Full article

(This article belongs to the Special Issue Advances in the Syndromes of Thrombotic Microangiopathy (TMA))

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