Could platelet mass index (PMI) be a new prognostic biomarker for COVID-19?

Aim: Although most patients with COVID-19 experience respiratory tract infections, severe reactions to the virus may cause coagulation abnormalities that mimic other systemic coagulopathies associated with severe infections, such as disseminated intravascular coagulation and thrombotic microangiopathy. Fluctuations in platelet markers, which are an indicator of the acute phase response for COVID-19, are of clinical importance. The aim of this study is to evaluate the relationship between disease severity and Platelet Mass Index (MPI) parameters in COVID-19 patients. Material(s) and Method(s): This retrospective observational study was conducted with patients who were diagnosed with COVID-19 in a tertiary hospital. The study was continued with the remaining 280 patients. All laboratory data were scanned retrospectively from patient files and hospital information system. Result(s): A very high positive correlation was found between PMI and PLT. The PMI value in women was significantly higher than in men. It was observed that PMI did not differ significantly in terms of mortality, intubation, CPAP and comorbidity. PMI vs. Pneumonia Ct Severity Score, biochemistry parameters (AST, CRP), hemogram parameters (WBC, HGB, HCT, MCV, LYM, MPV EO) and coagulation factors (aPTT and FIB) at various levels of positive/negative, weak and strong, and significant relationship was found. There was no significant relationship between hormone and D-dimer when compared with PMI. Discussion(s): Although platelet count alone does not provide information about the prognosis of the disease, PMI may guide the clinician as an indicator of lung damage in seriously ill patients.Copyright © 2022, Derman Medical Publishing. All rights reserved.

Complement-Mediated Thrombotic Microangiopathy Related to COVID-19 or SARS-CoV-2 Vaccination.

Introduction: Infectious diseases and vaccinations are trigger factors for thrombotic microangiopathy. Consequently, the COVID-19 pandemic could have an effect on disease manifestation or relapse in patients with atypical hemolytic syndrome/complement-mediated thrombotic microangiopathy (aHUS/cTMA). Methods: We employed the Vienna TMA cohort database to examine the incidence of COVID-19 related and of SARS-CoV-2 vaccination-related relapse of aHUS/cTMA among patients previously diagnosed with aHUS/cTMA during the first 2.5 years of the COVID-19 pandemic. We calculated incidence rates, including respective confidence intervals (CIs) and used Cox proportional hazard models for comparison of aHUS/cTMA episodes following infection or vaccination. Results: Among 27 patients with aHUS/cTMA, 13 infections triggered 3 (23%) TMA episodes, whereas 70 vaccinations triggered 1 TMA episode (1%; odds ratio 0.04; 95% CI 0.003-0.37, P = 0.01). In total, the incidence of TMA after COVID-19 or SARS-CoV-2 vaccination was 6 cases per 100 patient years (95% CI 0.017-0.164) (4.5/100 patient years for COVID-19 and 1.5/100 patient years for SARS-CoV-2 vaccination). The mean follow-up time was 2.31 ± 0.26 years (total amount: 22,118 days; 62.5 years) to either the end of the follow-up or TMA relapse (outcome). Between 2012 and 2022 we did not find a significant increase in the incidence of aHUS/cTMA. Conclusion: COVID-19 is associated with a higher risk for aHUS/cTMA recurrence when compared to SARS-CoV-2 vaccination. Overall, the incidence of aHUS/cTMA after COVID-19 infection or SARS-CoV-2 vaccination is low and comparable to that described in the literature.

Coagulopathy: A Vicious Indicator of COVID-19

COVID-19 is routinely associated with coagulopathy and complications associated with thrombosis. However, the difference between the coagulopathy, which is associated with COVID-19 and the coagulopathy, which is due to different causes, is that the "COVID-19 associated coagulopathy" shows raised levels of D-Dimer and that of fibrinogen. However, it shows quite some abnormalities in the levels of prothrombin time and also in the platelet count. "Venous thromboembolism" and arterial thrombosis is frequently seen in COVID-19 associated coagulopathy as opposed to "disseminated intravascular coagulopathy". Patients suffering from COVID-19 have many have multiple factors in common for thromboembolism which is associated with "Adult respiratory distress syndrome" from different etiologies like generalized inflammation and being unambulatory. "Cytokine storm" is the hallmark of COVID-19 associated coagulopathy which is distinguished by high levels of IL-6,1, tumour necrosis factor and other cytokines. The clinical features of COVID-19 associated coagulopathy overlap that of some syndromes like antiphos-pholipid syndrome and thrombotic microangiopathy. Studies have shown that patients diagnosed with disseminated intravascular coagulation have a poor prognosis compared to the one's that don't get diagnosed with DIC. The advancement of the condition from coagulopathy in the vasculature of the lungs to DIC in patients who have tested positive for COVID-19 shows that the patient's dysfunction associated with coagulation has evolved from local to generalized state. Investigating the coagulopathies will help in understanding the mechanism of COVID-19 associated coagulopathy.Copyright © International Journal of Research in Pharmaceutical Sciences.

Thrombotic thrombocytopenic purpura following ChAdOx1 nCov-19 vaccination: A case report.

Vaccine-associated thrombotic thrombocytopenic purpura (TTP) is a rare type of acquired TTP recently reported after COVID-19 vaccination. Merely four cases are ascribed to the ChAdOx1 nCoV-19 vaccine in the medical literature till the preparation of this study. In this case report, we describe a 43-year-old man who developed symptoms of TTP four days after receiving the second dose of the ChAdOx1 nCoV-19 vaccine. Peripheral blood smear demonstrated multiple schistocytes. Given a high plasmic score, he received plasma exchange, corticosteroids, and rituximab, and later, low ADAMTS 13 activity and high-titer ADAMTS inhibition antibody confirmed the diagnosis of COVID-19 vaccine-associated TTP. COVID-19 vaccine-associated TTP is an infrequent consequence of SARS-CoV-2 vaccination but with a substantial mortality rate which must be considered as one of the crucial differential diagnoses of post-COVID-19 vaccine thrombocytopenia besides vaccine-induced immune thrombotic thrombocytopenia and Immune thrombocytopenic purpura.

Immune and Hereditary Thrombotic Thrombocytopenic Purpura: Can ADAMTS13 Deficiency Alone Explain the Different Clinical Phenotypes?

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy caused by a hereditary or immune-mediated deficiency of the enzyme ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). TTPs are caused by the following pathophysiological mechanisms: (1) the presence of inhibitory autoantibodies against ADAMTS13; and (2) hereditary mutations of the ADAMTS13 gene, which is present on chromosome 9. In both syndromes, TTP results from a severe deficiency of ADAMTS13, which is responsible for the impaired proteolytic processing of high-molecular-weight von Willebrand factor (HMW-VWF) multimers, which avidly interact with platelets and subendothelial collagen and promote tissue and multiorgan ischemia. Although the acute presentation of the occurring symptoms in acquired and hereditary TTPs is similar (microangiopathic hemolytic anemia, thrombocytopenia, and variable ischemic end-organ injury), their intensity, incidence, and precipitating factors are different, although, in both forms, a severe ADAMTS13 deficiency characterizes their physiopathology. This review is aimed at exploring the possible factors responsible for the different clinical and pathological features occurring in hereditary and immune-mediated TTPs.

Mild forms of thrombotic microangiopathy in patients with advanced pancreatic cancer receiving gemcitabine and nab-paclitaxel.

INTRODUCTION: Thrombotic microangiopathy (TMA) is an uncommon complication that may occur in cancer patients usually as an expression of cancer-associated coagulopathy or due to drug-related toxicity. The clinical spectrum of TMA may vary from an incidental laboratory finding in cancer outpatients to potentially severe life-threatening clinical forms with organ involvement requiring prompt recognition and multidisciplinary evaluation. CASE REPORTS: We present the clinical characteristics and outcomes of four patients with advanced pancreatic cancer with acute non-immune intravascular haemolysis compatible with microangiopathic acute haemolytic anaemia associated with mild thrombocytopenia during long-term gemcitabine and nab-paclitaxel treatment. MANAGEMENT AND OUTCOMES: Abnormal blood parameters (all four cases) and renal involvement (one case) were reversed with a conservative approach and chemotherapy discontinuation. One patient required a short hospitalization while the other three were managed as outpatients. The rapid reversibility of the blood abnormalities supported gemcitabine dose-related toxicity as the most likely aetiologic mechanism and demonstrates the current challenges in daily long-term cancer survivor care. DISCUSSION: Clinicians must take into account TMA in the differential diagnosis of acute anaemia with or without thrombocytopenia and organ damage, since adequate recognition and early treatment discontinuation allow effective outpatient management and favourable patient outcomes.

Two-Hit Kidney Allograft Injury by SARS-CoV-2.

Coronavirus disease 2019 (COVID-19) has been associated with acute kidney injury in kidney transplant recipients by several mechanisms. The authors report a case of acute kidney allograft dysfunction in a 48-year-old patient who presented in the emergency room with anasarca and nephrotic syndrome close after mild COVID-19 and no other clinical condition. Histopathology of the allograft biopsy revealed two distinct and simultaneous kidney lesions, collapsing glomerulopathy and thrombotic microangiopathy. Renal function persistently deteriorated, and definitive dialysis was initiated. After excluding other plausible causes for the findings, this case strengthens the hypothesis that the kidney allograft is also a target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Cytokine Storm Syndromes in Pediatric Patients.

Cytokine storm syndromes (CSS) represent a diverse group of disorders characterized by severe overactivation of the immune system. In the majority of patients, CSS arise from a combination of host factors, including genetic risk and predisposing conditions, and acute triggers such as infections. CSS present differently in adults than in children, who are more likely to present with monogenic forms of these disorders. Individual CSS are rare, but in aggregate represent an important cause of severe illness in both children and adults. We present 3 rare, illustrative cases of CSS in pediatric patients that describe the spectrum of CSS.

Obesity and its impact on endotoxemia and systemic inflammation in acute SARS-CoV- 2 infection

Background: Given the coexistence of the COVID-19 pandemic and the worldwide epidemic of obesity, which in some Western countries affects up to 40% of the population, it is crucial today to understand the mechanisms involved in the worsening course of the new SARS-CoV- 2 coronavirus infection in obese patients. So-called "metabolic endotoxemia" associated with excess body weight and obesity may be one of the most important factors potentiating the effect of SARS-CoV- 2 virus influencing the prognosis of the disease. Method(s): 55 patients with SARS-CoV- 2 infection of moderate severity (patients with normal body mass index (BMI) -10;patients with BMI > 25 kg/m2 -19 and patients with BMI > 30 kg/m2 -26) and 20 controls were studied. Lipopolysaccharide binding protein (LBP), sCD14-ST and C-reactive protein (CRP) levels were measured by ELISA in plasma of patients taken on the day of admission to the hospital. Result(s): The plasma LBP (mug/ml) level was significantly greater in the group of patients with BMI > 30 kg/m2 (Me [Q1;Q3]) -52.5 [31.16;75.0], than in groups with BMI > 25 kg/m2 -48.3 [10.6;60] (p < 0.05), normal BMI -33.5 [8.3;54.8] (p < 0.01) and control group -18.6 [15.2;20.5] (p < 0.001). The plasma sCD14-ST (pg/ml) levels in the 2nd (2400.0 [1200.0;2900.0]) and 3rd (2100.0 [1290.0;1340.0]) group did not differ significantly (p > 0.05), but was significantly greater than in group with normal BMI -1310.0 [720.0;2325] (p < 0.05) and the control group -218.0 [80.0;292.0] (p < 0.01). The plasma CRP (mg/L) levels in the 1st (31.1 [9.3;51.0]) and 2nd (31.8 [15.7;57.3]) group did not differ significantly (p > 0.05), but was significantly less than in the group with BMI > 30 kg/m2 -40.5 [26.6;60.0] (p < 0.05) and the control group -0.5 [0.3;0.9] (p < 0.001). Conclusion(s): The phenomenon of "metabolic endotoxemia" in overweight and obese patients may contribute to the formation of high systemic inflammation in SARS-CoV- 2 virus-associated endothelial dysfunction and thrombotic microangiopathy.

Pitfalls of Thrombotic Microangiopathies in Children: Two Case Reports and Literature Review.

Thrombotic microangiopathy can present itself in the form of several clinical entities, representing a real challenge for diagnosis and treatment in pediatric practice. Our article aims to explore the evolution of two rare cases of pediatric thrombotic thrombocytopenic purpura (TTP) and atypical hemolytic uremic syndrome (aHUS) with extremely similar clinical pictures, which, coincidentally, presented at approximately the same time in our hospital. These cases and our literature review demonstrate the multiple facets of thrombotic microangiopathy, which can produce various determinations and salient manifestations even among the pediatric population. TTP and aHUS may represent genuine diagnostic pitfalls through the overlap of their clinical and biological findings, although they develop through fundamentally different mechanisms that require different therapeutic approaches. As a novelty, we underline that COVID-19 infection cannot be excluded as potential trigger for TTP and aHUS in our patients and we predict that other reports of such an association will follow, raising a complex question of COVID-19's implication in the occurrence and evolution of thrombotic microangiopathies. On this matter, we conducted literature research that resulted in 15 cases of COVID-19 pediatric infections associated with either TTP or aHUS. Taking into consideration the morbidity associated with TTP and aHUS, an elaborate differential diagnosis and prompt intervention are of the essence.

Renal Thrombotic Microangiopathy: A Review.

Thrombotic microangiopathy (TMA), a pathological lesion observed in a wide spectrum of diseases, is triggered by endothelial injury and/or dysfunction. Although TMA lesions are often accompanied by clinical features of microangiopathic hemolytic anemia, thrombocytopenia, and ischemic end-organ injury, renal-limited forms of TMA are not infrequently encountered in clinical practice. The presence of renal-limited manifestations can be diagnostically challenging, often delaying the initiation of targeted therapy. Prompt investigation and empirical treatment of TMA is warranted to reduce associated morbidity and mortality. Major advances have been made with respect to the pathophysiology of primary TMA entities, with the subsequent development of novel diagnostic tools and lifesaving therapies for diseases like thrombotic thrombocytopenic purpura and complement-mediated TMA. This article will review the clinical presentation and pathologic hallmarks of TMA involving the kidney, and the disease-specific mechanisms that contribute to the endothelial injury that characterizes TMA lesions. Diagnostic approach and both empirical and disease-specific treatment strategies will be discussed, along with the potential role for emerging targeted disease-specific therapies.

Secondary thrombotic microangiopathy or secondary HUS: drugs or malignant hypertension to blame? Case report and review of the literature

Currently, thrombotic microangiopathy (TMA) is a common finding in the histological examination of kidney biopsy specimens, while verification of the nosological diagnosis is difficult due to the many etiological factors and the variety of clinical phenotypes. Today, along with primary TMAs, which include thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), a large group of secondary TMAs associated with a variety of diseases and conditions, considered secondary HUS, is attracting more and more attention. The article presents a clinical case of the development of thrombotic microangiopathy in a 48-year-old man with a history of intravenous drug user who suffered from severe arterial hypertension for a long time. A feature of the disease was clinically – the almost complete absence of hematological manifestations with a progressive nature of nephropathy with an outcome in end-stage kidney disease, morphologically – mainly chronic changes in small extraglomerular vessels (arteries and arterioles), which led to severe ischemic damage to the glomeruli. Considering the predominantly chronic nature of the morphological manifestations of TMA, the absence of signs of acute TMA, and hematological syndrome, the patient did not undergo plasma therapy. In connection with the development of end-stage kidney disease, hemodialysis was initiated. The presented observation illustrates the complex genesis of secondary TMA in a patient with a history of drug addiction and severe arterial hypertension approaching malignant downstream. The presence in the anamnesis of such complement-activating conditions as intravenous drug use, severe arterial hypertension, as well as vaccination against a new coronavirus infection preceding the clinical manifestation, allowed us to interpret this condition as secondary HUS, which, however, does not exclude the presence of protein gene mutations, regulators of the alternative pathway of complement activation, which could act as a predisposing factor, which requires a genetic study of the complement system, since the information obtained will determine the tactics of management in case of kidney transplantation. In addition, this clinical observation demonstrates the importance of a thorough history taking in such patients, the analysis of which will help to identify complement-activating conditions and thereby accelerate the verification of the diagnosis. © 2022 Authors. All rights reserved.

Spectrum of Indication Kidney Biopsies in Community Acquired Aki

Introduction: Community acquired acute kidney injury (CA-AKI) in low income settings is different from that in the high income settings. Infections, poisoning, toxic envenomations and pregnancy related AKI are common. Kidney biopsy is seldom performed in these patients unless atypical clinical course or features are present. We have established a prospective cohort of patients with CA-AKI at the Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh in India. We present the spectrum of kidney biopsies in patients who underwent kidney biopsy in this cohort. Method(s): The study is a single centre, prospective, observational cohort study of patients with CA-AKI at PGIMER. Patients aged >12 years and with a diagnosis of CA-AKI are eligible for enrolment. Patients with underlying CKD, urinary tract obstruction, COVID 19, malignancy or heart failure are excluded. Clinical and laboratory data are recorded at baseline. Follow up visits are scheduled at 1 and 4 months after hospital discharge. Kidney biopsies are done only in those patients who have atypical clinical course or features (e.g. persistent kidney dysfunction despite other clinical improvement, strong clinical suspicion of dominant glomerular involvement or interstitial nephritis etc.). We present the spectrum of histopathological diagnoses that were recorded in such patients till date. Result(s): Till now, 646 patients have been included in the cohort. The leading causes of CA-AKI are sepsis (52%), obstetric complications (14%), envenomation (8%), nephrotoxic drugs (6%) and poisons (3%) (figure 1). 18.4% patients had died after CA-AKI. At >=3 months after CA-AKI, 16.3% patients had not recovered completely with persistent eGFR <60 ml/min/1.73m2. 44 patients had undergone kidney biopsy in this cohort. Incomplete recovery, and clinical or diagnostic dilemmas were indications for doing kidney biopsy. The leading clinical diagnoses in this subgroup were sepsis (23%), nephrotoxic drugs (23%), envenomation (9%), obstetric causes (6.8%) and others (25%). Acute interstitial nephritis, acute tubular necrosis and acute cortical necrosis were most common histologic diagnoses (table 1). Combinations of various histologic features were not uncommon. Pigment casts were recorded in 13 patients. 4 patients had acute cortical necrosis, 2 being after post-partum AKI and one each due to acute gastroenteritis and unknown animal bite. Glomerular involvement were recorded in 8 patients (table 1). Thrombotic microangiopathy was present in 4 patients. In this subgroup of patients who underwent kidney biopsy, 3 (7%) had died and 8 (18%) had eGFR <60 ml/min/1.73m2 at >=3 months. Figure 1: Causes of CA-AKI in patients [Formula presented] Table 1: Histologic diagnoses in kidney biopsies in CA-AKI cohort. [Formula presented] Conclusion(s): Acute interstitial nephritis and acute tubular necrosis, alone or in combination with other findings, were the most common histologic diagnoses in indication kidney biopsies in CA-AKI. Adverse outcomes (mortality or progression to CKD) are common after CA-AKI. No conflict of interestCopyright © 2023

Diagnosis and treatment strategies for solid organ transplant recipients with SARS-CoV-2 infection

Due to long-term use of immunosuppressive agents, solid organ transplant recipients (SOTR) belong to high-risk populations of multiple pathogenic infection, including SARS-CoV-2. In addition, SOTR are constantly complicated by chronic diseases, such as hypertension and diabetes mellitus, etc. After infected with SARS-CoV-2, the critically ill rate and fatality of SOTR are higher than those of the general population, which captivates widespread attention from experts in the field of organ transplantation. Omicrone variant is currently the significant pandemic strain worldwide, rapidly spreading to more than 100 countries worldwide and causing broad concern. According to the latest international guidelines on the diagnosis and treatment of SARS-CoV-2 infection and relevant expert consensus in China combined with current domestic situation of SARS-CoV-2 pandemic and China's "diagnosis and treatment regimen for SARS-CoV-2 infection (Trial Version 10)”, the epidemiology, clinical manifestations and prognosis, diagnosis, clinical classification and treatment of SARS-CoV-2 infection were briefly reviewed. (English) [ABSTRACT FROM AUTHOR] 实体器官移植受者 (SOTR) 由于长期服用免疫抑制药, 属于各种病原体感染的高危人群, 包括新 型冠状病毒 (新冠病毒) . 另外, SOTR 往往伴有高血压、糖尿病等慢性基础疾病, 感染新冠病毒后重型率和病 死率高于普通人群, 因此得到移植领域专家的高度重视. 奥密克戎株目前为全球范围内的主要流行毒株, 快速扩 散至全球 100 多个国家, 引起广泛关注. 根据最新的国际关于新冠病毒感染诊治指南和我国相关专家共识, 结合 目前新冠病毒感染疫情形势及我国《新型冠状病毒感染诊疗方案 (试行第十版) 》, 本文从新冠病毒感染的流行 病学、临床表现和预后、诊断和临床分型以及治疗方面进行简单述评. (Chinese) [ABSTRACT FROM AUTHOR] Copyright of Organ Transplantation / Qi Guan Yi Zhi is the property of Organ Transplantation Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Diagnosis and treatment strategies for solid organ transplant recipients with SARS-CoV-2 infection.

Due to long-term use of immunosuppressive agents, solid organ transplant recipients (SOTR) belong to high-risk populations of multiple pathogenic infection, including SARS-CoV-2. In addition, SOTR are constantly complicated by chronic diseases, such as hypertension and diabetes mellitus, etc. After infected with SARS-CoV-2, the critically ill rate and fatality of SOTR are higher than those of the general population, which captivates widespread attention from experts in the field of organ transplantation. Omicrone variant is currently the significant pandemic strain worldwide, rapidly spreading to more than 100 countries worldwide and causing broad concern. According to the latest international guidelines on the diagnosis and treatment of SARS-CoV-2 infection and relevant expert consensus in China combined with current domestic situation of SARS-CoV-2 pandemic and China's "diagnosis and treatment regimen for SARS-CoV-2 infection (Trial Version 10)”, the epidemiology, clinical manifestations and prognosis, diagnosis, clinical classification and treatment of SARS-CoV-2 infection were briefly reviewed. (English) [ABSTRACT FROM AUTHOR] 实体器官移植受者 (SOTR) 由于长期服用免疫抑制药, 属于各种病原体感染的高危人群, 包括新 型冠状病毒 (新冠病毒) . 另外, SOTR 往往伴有高血压、糖尿病等慢性基础疾病, 感染新冠病毒后重型率和病 死率高于普通人群, 因此得到移植领域专家的高度重视. 奥密克戎株目前为全球范围内的主要流行毒株, 快速扩 散至全球 100 多个国家, 引起广泛关注. 根据最新的国际关于新冠病毒感染诊治指南和我国相关专家共识, 结合 目前新冠病毒感染疫情形势及我国《新型冠状病毒感染诊疗方案 (试行第十版) 》, 本文从新冠病毒感染的流行 病学、临床表现和预后、诊断和临床分型以及治疗方面进行简单述评. (Chinese) [ABSTRACT FROM AUTHOR] Copyright of Organ Transplantation / Qi Guan Yi Zhi is the property of Organ Transplantation Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

RENAL FLARE IN ADOLESCENTS WITH LUPUS NEPHRITIS RECEIVED COVID-19 mRNA VACCINE

Introduction: Patients with systemic lupus erythematosus (SLE) are at increased risk of the Coronavirus disease 2019 (COVID-19), whereas vaccines against the COVID-19 increase type I interferon and may trigger SLE flares. Lupus nephritis (LN) is common in adolescents with SLE and usually more severe than in adults. The incidence and severity of renal flare among these patients following COVID-19 mRNA vaccination are limited. Method(s): Adolescents, aged 12-18 years, with SLE and ever biopsy-proven lupus nephritis who had renal remission were prospectively studied following the COVID-19 (BNT162b2) mRNA vaccination. Renal remission was defined as having stable renal function and normal urinalysis at recruitment. SLE disease activity index 2000 (SLEDAI-2K) scores during the last 3 months prior to the vaccination were reviewed, and compared to SLEDAI-2K scores at 1, and 3 months after two-dose primary series. Renal flare included new onset significant proteinuria, abnormal urine sediment, and/or significant increased serum creatinine. Result(s): 35 adolescents (female 88.6%), with mean age of 15.4 +/-1.6 years, were included. Median (IQR) duration of SLE was 41.4 (18.9, 70.4) months. LN included class II (2, 5.7%) class III (2, 5.7%), class IV (12, 34.3%) class V (7, 20.0%), and class III/IV + V (10, 28.6%). Median daily dose of prednisolone prior to vaccination was 5 (2.5, 5) mg. SLEDAI-2K scores at pre-vaccination, 1-, and 3-months post vaccination were not significantly different [2 (0.25,4), 2 (0, 4) and 2 (0, 4);p=0.06). Three (8.6%) patients had renal flare within 3 months post vaccination. One had mild microscopic hematuria and mild proteinuria but improved after increased prednisolone to 0.5 mg/kg/day. Two patients had severe renal flare with biopsy proven LN class IV (1 with class V and 1 with thrombotic microangiopathy). Moreover, one patient developed COVID-19 at 2 months post vaccination without renal flare. Conclusion(s): Within 3 months post COVID-19 mRNA vaccine in adolescents with remission of LN, incidence of renal flare was 8.6%. Renal flare could be severe and required increasing immunomodulatory treatment. Larger population and longer follow-up are needed. No conflict of interestCopyright © 2023

Narsoplimab for severe transplant-associated thrombotic microangiopathy.

BACKGROUND: Transplantation-associated thrombotic microangiopathy (TA-TMA) is an endothelial injury syndrome linked to the overactivation of complement pathways. It manifests with microangiopathic hemolytic anemia, consumptive thrombocytopenia, and microvascular thrombosis leading to ischemic tissue injury. Mannose residues on fungi and viruses activate the mannose-binding lectin complement pathway, and hence activation of the lectin pathway could be one of the reasons for triggering TA-TMA. Narsoplimab, a human monoclonal antibody targeting MASP-2 is a potent inhibitor of the lectin pathway. We describe the transplant course of a pediatric patient who developed TA-TMA following Candida-triggered macrophage activation syndrome and was treated with Narsoplimab. The data collection was performed prospectively. CASE PRESENTATION: The six-year-old girl underwent a human leucocyte antigen (HLA) haploidentical hematopoietic stem cell transplant using post-transplant Cyclophosphamide for severe aplastic anemia. In the second week of the transplant, the patient developed macrophage activation syndrome necessitating treatment with steroids and intravenous immunoglobulin. Subsequently, USG abdomen and blood fungal PCR revealed the diagnosis of hepatosplenic candidiasis. Candida-triggered macrophage activation syndrome responded to antifungals, steroids, intravenous immunoglobulin, and alemtuzumab. However, the subsequent clinical course was complicated by thrombotic microangiopathy. The patient developed hypertension in the 2nd week, followed by high lactate dehydrogenase (1010 U/L), schistocytes (5 per hpf), low haptoglobin (< 5 mg/dl), thrombocytopenia, and anemia in the 3rd week. Ciclosporin was stopped, and the patient was treated with 10 days of defibrotide without response. The course was further complicated by the involvement of the gastrointestinal tract and kidneys. She had per rectal bleeding with frequent but low-volume stools, severe abdominal pain, and hypoalbuminemia with a rising urine protein:creatinine ratio. Narsoplimab was started in the 5th week of the transplant. A fall in lactate dehydrogenase was observed after starting Narsoplimab. This was followed by the resolution of gastrointestinal symptoms, proteinuria, and recovery of cytopenia. The second episode of TA-TMA occurred with parvoviraemia and was also successfully treated with Narsoplimab. CONCLUSION: Lectin pathway inhibition could be useful in treating the fatal complication of transplant-associated thrombotic microangiopathy.

End-Stage Kidney Disease Resulting from Atypical Hemolytic Uremic Syndrome after Receiving AstraZeneca SARS-CoV-2 Vaccine: A Case Report.

Hemolytic uremic syndrome (HUS) is classically described as a triad of nonimmune hemolytic anemia, thrombocytopenia, and acute kidney injury. Atypical HUS (aHUS) is a rare variant of the disease, and it accounts for 5-10% of the cases. It has a poor prognosis, with a mortality rate exceeding 25% and a more than 50% chance of progressing into end-stage kidney disease (ESKD). Genetic or acquired dysregulation of the alternative complement pathway is highly implicated in the pathogenesis of aHUS. Multiple triggers for aHUS have been described in the literature, including pregnancy, transplantation, vaccination, and viral infections. Herein, we report a case of a previously healthy 38-year-old male who developed microangiopathic hemolytic anemia and severe kidney impairment one week after receiving the first dose of AstraZeneca SARS-CoV-2 vaccine. A diagnosis of aHUS was made after excluding other causes of thrombotic microangiopathies. Treatment with plasma exchange, prednisone, and rituximab (375 mg/m2) once weekly for four doses resulted in improvement of his hematological parameters. However, he progressed to ESKD.

Metabolism-Mediated Thrombotic Microangiopathy in an Older Patient Without Malnutrition.

Vitamin B12 deficiency can cause thrombotic microangiopathy (TMA)-like symptoms such as purpura caused by platelet reduction, general fatigue caused by anemia, and renal and hepatic abnormalities caused by malnutrition. TMA-like symptoms are known as metabolism-mediated TMA (MM-TMA). In MM-TMA, blood cell production is altered, and both pancytopenia and schistocytes appear. The initial presentation of MM-TMA makes it challenging to distinguish between primary and secondary TMA when patients do not present risk factors for malnutrition. We encountered an older female patient with a chief complaint of unconsciousness and loss of appetite for two days. Laboratory tests revealed pancytopenia with schistocytes. Moreover, the laboratory data revealed low serum levels of vitamin B12, indicating MM-TMA. The patient was successfully treated with intravenous vitamin B12 supplementation and discharged home. The patient had atrophic gastritis, which could have impeded the absorption of vitamin B12 from food. Among older patients without prolonged appetite loss, TMA-like symptoms should be investigated as MM-TMA induced by vitamin B12 deficiency, and prompt initiation of appropriate treatment is essential to differentiate between MM-TMA and true TMA.