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      Hydroxychloroquine, TTP, COVID-19, and SLE Translated title: Hidroksiklorokin, TTP, COVID-19 ve SLE

      letter
      1 , * , 2
      Turkish Journal of Hematology
      Galenos Publishing
      Hydroxychloroquine, TTP, COVID-19, SLE

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          Abstract

          To the Editor, The recent report entitled “Hydroxychloroquine-associated thrombotic thrombocytopenic purpura” (TTP) was very interesting [1]. Arıkan et al. [1] concluded that the patient represented a possible case of hydroxychloroquine-induced TTP and called for awareness of this possible adverse effect of hydroxychloroquine (HQ) in alternative therapy for coronavirus disease-19 (COVID-19). In fact, TTP might be the result of many disorders. In the present case, it can be confirmed that the patient had TTP, but the etiology is not clear. There is a lack of explanation of the patient’s presenting symptom. The exact disease of the patient at the first presentation is a question to be discussed. First, hydroxychloroquine-related TTP is extremely rare and the dosage should be high. In this patient, the dosage might not have been high. Also, there are many criteria of the Naranjo scale that might not have been completely fulfilled, such as proven drug existence in the blood, history of previous reaction, reappearance after re-administration, worsening after increasing dose, improvement after discontinuation, and exclusion of other possible objective evidence. Second, whether this was COVID-19 or not has to be discussed. It is clear that there was a negative polymerase chain reaction (PCR) result. It is possible that this patient might have had a clinical presentation resembling a COVID-19 case such that the physician in charge decided to use H alternative therapy without waiting for the PCR test for COVID-19. Regarding negative PCR results, there is a chance of a false negative. In a recent publication, Arevalo-Rodriguez et al. [2] stressed “the need for repeated testing in patients with suspicion of SARS-CoV-2 infection given that up to 54% of COVID-19 patients may have an initial false-negative reverse transcription polymerase chain reaction.” To decrease the false negative rate, it was suggested to consider the evidence of abnormal blood aspartate aminotransferase and lactate dehydrogenase level [3], which were also observed in the present case. Additionally, TTP might also be induced by COVID-19 [4]. Third, if we believe that this was not a COVID-19 case, it should be further considered what illness the patient had. Another possibility that might be easily forgotten is systemic lupus erythematosus (SLE). The patient had many clinical features, such as hematological findings, that might be seen in SLE. Nevertheless, there was a lack of complete laboratory work-up for SLE; therefore, that diagnosis was not possible. In SLE, TTP might be the clinical presentation [5]. The use of steroids as well as plasmapheresis can also help treat patients with SLE-related TTP.

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          Most cited references7

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          False-negative results of initial RT-PCR assays for COVID-19: A systematic review

          Background A false-negative case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is defined as a person with suspected infection and an initial negative result by reverse transcription-polymerase chain reaction (RT-PCR) test, with a positive result on a subsequent test. False-negative cases have important implications for isolation and risk of transmission of infected people and for the management of coronavirus disease 2019 (COVID-19). We aimed to review and critically appraise evidence about the rate of RT-PCR false-negatives at initial testing for COVID-19. Methods We searched MEDLINE, EMBASE, LILACS, as well as COVID-19 repositories, including the EPPI-Centre living systematic map of evidence about COVID-19 and the Coronavirus Open Access Project living evidence database. Two authors independently screened and selected studies according to the eligibility criteria and collected data from the included studies. The risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. We calculated the proportion of false-negative test results using a multilevel mixed-effect logistic regression model. The certainty of the evidence about false-negative cases was rated using the GRADE approach for tests and strategies. All information in this article is current up to July 17, 2020. Results We included 34 studies enrolling 12,057 COVID-19 confirmed cases. All studies were affected by several risks of bias and applicability concerns. The pooled estimate of false-negative proportion was highly affected by unexplained heterogeneity (tau-squared = 1.39; 90% prediction interval from 0.02 to 0.54). The certainty of the evidence was judged as very low due to the risk of bias, indirectness, and inconsistency issues. Conclusions There is substantial and largely unexplained heterogeneity in the proportion of false-negative RT-PCR results. The collected evidence has several limitations, including risk of bias issues, high heterogeneity, and concerns about its applicability. Nonetheless, our findings reinforce the need for repeated testing in patients with suspicion of SARS-Cov-2 infection given that up to 54% of COVID-19 patients may have an initial false-negative RT-PCR (very low certainty of evidence). Systematic review registration Protocol available on the OSF website: https://tinyurl.com/vvbgqya.
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            COVID-19 presenting as thrombotic thrombocytopenic purpura (TTP)

            We present the case of a 39-year-old man with epigastric pain, nausea and vomiting. The patient scored 4 in the Visual Triage Checklist of acute respiratory symptoms; a COVID-19 swab was taken. Prompt review of the peripheral blood smear showed evidence of microangiopathic haemolytic anaemia and thrombocytopenia. Because the patient had a picture of thrombotic thrombocytopenic purpura, plasma exchange and corticosteroids were started immediately. After 3 days, he developed severe ischaemic stroke and his swabs came back positive for COVID-19 by reverse transcription PCR. Therefore, triple therapy was started (lopinavir/ritonavir, ribavirin and interferon beta-1b). White blood cell count reached 50×109/L (normal range, 4.5–11×109/L), mainly neutrophils. All the workup for autoimmune diseases was negative. The patient showed delayed improvement in lactate dehydrogenase, haemoglobin and platelet count until we increased the volume of plasma exchange and subsided the inflammatory response of COVID-19. After that, the patient showed an excellent recovery.
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              Cardiac implications of thrombotic thrombocytopenic purpura

              Thrombotic thrombocytopenic purpura (TTP) is a multisystem disorder that essentially can affect any organ in the human body. The hallmark of the pathogenesis in TTP is the large von Willebrand factor multimers on platelet-mediated micro-thrombi formation, leading to microvascular thrombosis. Autopsy studies showed that cardiac arrest and myocardial infarction are the most common immediate causes of death in these patients. Clinical manifestations of cardiac involvement in TTP vary dramatically, from asymptomatic elevation of cardiac biomarkers, to heart failure, MI and sudden cardiac death. There is limited knowledge about optimal cardiac evaluation and management in patients with TTP. The absence of typical cardiac symptoms, combined with complicated multi-organ involvement in TTP, may contribute to the under-utilization of cardiac evaluation and treatment. Prompt diagnosis and timely initiation of effective therapy could be critically important in selected cases. Based on our experience and this review of the literature, we developed several recommendations for focused cardiac evaluation for patients with acute TTP: (1) patients with suspected or confirmed TTP should be screened for the potential presence of cardiac involvement with detailed history and physical, electrocardiogram and cardiac enzymes; (2) clinical deterioration of TTP patients warrants immediate cardiac reevaluation; (3) TTP patients with clinical evidence of cardiac involvement should be monitored for telemetry, cardiac biomarkers and evaluated with transthoracic echocardiography. These patients require urgent targeted TTP treatment as well as cardiac-specific treatment. Aspirin therapy is indicated for all TTP patients. Since epicardial coronary artery involvement is rare, cardiac catheterization is usually not required, given the high risk for hemorrhage and kidney injury; (4) we recommend evidence-based medical therapy for ischemic symptoms and heart failure. TTP patients with evidence of cardiac involvement would also benefit from routine cardiology follow up during remission.
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                Author and article information

                Journal
                Turk J Haematol
                Turk J Haematol
                TJH
                Turkish Journal of Hematology
                Galenos Publishing
                1300-7777
                1308-5263
                March 2021
                25 February 2021
                : 38
                : 1
                : 99-100
                Affiliations
                [1 ]Private Academic Consultant, Bangkok, Thailand
                [2 ]Adjunct Professor, Joseph Ayobabalola University, Ikeji-Arakeji, Nigeria
                Author notes
                * Address for Correspondence: Private Academic Consultant, Bangkok, Thailand E-mail: pathumsook@ 123456gmail.com
                Author information
                https://orcid.org/0000-0002-8859-5322
                Article
                45802
                10.4274/tjh.galenos.2021.2020.0770
                7927449
                33401889
                6c034095-fdd2-49cd-940d-9a730e7c6e2d
                © Copyright 2021 by Turkish Society of Hematology / Turkish Journal of Hematology, Published by Galenos Publishing House.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 25 December 2020
                : 5 January 2021
                Categories
                Letters to the Editor

                hydroxychloroquine,ttp,covid-19,sle
                hydroxychloroquine, ttp, covid-19, sle

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