Coombs-negative Hemolytic Anemia Research Articles

Post-COVID-19 complement-mediated TMA: A case report.

Systemic COVID-19 disease is associated with a variety of organ involvement in infected patients. A rarely reported complication is the induction of complement-mediated thrombotic microangiopathy (TMA). TMA is an extremely rare pathological condition that results in thrombosis in capillaries and small arterioles, due to an endothelial injury. It is often combined with thrombocytopenia, Coombs-negative hemolytic anemia, and end-organ damage. This case involves a patient who was admitted to our hospital for the purpose of diagnosis and treatment of acute kidney injury (AKIN 3) with severe proteinuria after a preceding SARS-CoV-2 infection. A 77-year-old male patient had COVID-19 pneumonia in January 2021 with the need of high-flow oxygen therapy in the intensive care unit. In March 2021, he was hospitalized again due to elevated serum creatinine levels and proteinuria. The patient exhibited normal vital parameters. A renal biopsy showed severe TMA. A diagnosis of COVID-19-associated TMA was made, and treatment with high-dose glucocorticoid therapy and plasma exchange was initiated. Additionally, therapy with eculizumab was established. Unfortunately, the kidney failure was initially progressive, so that hemodialysis (HD) was temporarily necessary. In May 2021, kidney function recovered to an estimated glomerular filtration rate of ~ 30 mL/min/1.73m2 corresponding to chronic kidney disease stage 3bA3 - 4A3. COVID-19-associated TMA is an extremely rare disease. TMA may be a possible long-term complication with the risk of end-stage renal disease if not properly diagnosed and treated.

A Case of Immune-Mediated Coombs-Negative Hemolytic Anemia in a Patient with Systemic Lupus Erythematosus

A Case of Immune-Mediated Coombs-Negative Hemolytic Anemia in a Patient with Systemic Lupus Erythematosus

Wilson Disease: Copper-Mediated Cuproptosis, Iron-Related Ferroptosis, and Clinical Highlights, with Comprehensive and Critical Analysis Update.

Wilson disease is a genetic disorder of the liver characterized by excess accumulation of copper, which is found ubiquitously on earth and normally enters the human body in small amounts via the food chain. Many interesting disease details were published on the mechanistic steps, such as the generation of reactive oxygen species (ROS) and cuproptosis causing a copper dependent cell death. In the liver of patients with Wilson disease, also, increased iron deposits were found that may lead to iron-related ferroptosis responsible for phospholipid peroxidation within membranes of subcellular organelles. All topics are covered in this review article, in addition to the diagnostic and therapeutic issues of Wilson disease. Excess Cu2+ primarily leads to the generation of reactive oxygen species (ROS), as evidenced by early experimental studies exemplified with the detection of hydroxyl radical formation using the electron spin resonance (ESR) spin-trapping method. The generation of ROS products follows the principles of the Haber-Weiss reaction and the subsequent Fenton reaction leading to copper-related cuproptosis, and is thereby closely connected with ROS. Copper accumulation in the liver is due to impaired biliary excretion of copper caused by the inheritable malfunctioning or missing ATP7B protein. As a result, disturbed cellular homeostasis of copper prevails within the liver. Released from the liver cells due to limited storage capacity, the toxic copper enters the circulation and arrives at other organs, causing local accumulation and cell injury. This explains why copper injures not only the liver, but also the brain, kidneys, eyes, heart, muscles, and bones, explaining the multifaceted clinical features of Wilson disease. Among these are depression, psychosis, dysarthria, ataxia, writing problems, dysphagia, renal tubular dysfunction, Kayser-Fleischer corneal rings, cardiomyopathy, cardiac arrhythmias, rhabdomyolysis, osteoporosis, osteomalacia, arthritis, and arthralgia. In addition, Coombs-negative hemolytic anemia is a key feature of Wilson disease with undetectable serum haptoglobin. The modified Leipzig Scoring System helps diagnose Wilson disease. Patients with Wilson disease are well-treated first-line with copper chelators like D-penicillamine that facilitate the removal of circulating copper bound to albumin and increase in urinary copper excretion. Early chelation therapy improves prognosis. Liver transplantation is an option viewed as ultima ratio in end-stage liver disease with untreatable complications or acute liver failure. Liver transplantation finally may thus be a life-saving approach and curative treatment of the disease by replacing the hepatic gene mutation. In conclusion, Wilson disease is a multifaceted genetic disease representing a molecular and clinical challenge.

Spur Cell Anemia: A Rare and Under-Diagnosed Cause of Anemia in Alcoholic Patients with Advanced Liver Disease

Anemia in patients with alcohol use disorder (AUD) has a wide range of differential diagnoses, which can be challenging to interpret. It is often multifactorial, such as due to blood loss with or without coagulopathy, direct toxic effect of alcohol on hematopoietic cells, chronic inflammation, abnormalities in red blood cells (RBC) membranes, and nutritional deficiencies. Alcohol-induced liver disease may contribute to anemia through coagulopathy, splenomegaly, and hypersplenism. Macrocytosis is a common finding in patients with AUD due to B12 or folate deficiency or RBC membrane abnormality due to changes in lipid composition of RBC membranes. Patients with cirrhosis may have low haptoglobin due to impaired synthetic liver function. However, non-autoimmune hemolytic anemia and concomitant alcohol-induced liver damage should raise suspicion for spur cell anemia (SCA) and Zieve's syndrome. These medical conditions tend to be underreported or misdiagnosed. We describe a 44 year old male patient with a past medical history of AUD who presented with alcohol intoxication and was found to have newly diagnosed decompensated cirrhosis with severe macrocytic anemia with Hgb of 5.9 g/dl. Patient denied overt bleeding. Initial workup revealed high absolute reticulocyte count of 10.8% with retic index of 3, low haptoglobin of <15 mg/dl, elevated LDH of 275 u/l, negative Coombs test consistent with non-autoimmune hemolytic anemia, normal folate and B12 levels, and mixed direct and indirect hyperbilirubinemia. Peripheral blood smear showed anisopoikilocytosis, macrocytes, many spur cells, increased reticulocytes, but no schistocytes. Endo-colonoscopy showed grade 1 esophageal varices without evidence of recent bleeding. Given the history of heavy alcohol intake and cirrhosis, combined with Coombs-negative hemolytic anemia and peripheral blood smear findings of numerous spiculated red cells, our patient was diagnosed with SCA. At the time, due to active alcohol use, the patient was deemed not to be a candidate for liver transplant. This case report aims to aid physicians with the recognition of acute hemolytic anemia in patients with alcoholic liver injury and consideration of SCA and Zieve's syndrome as potential underlying causes. Prompt recognition and differentiation between these medical conditions are crucial as prognosis and treatment are different. Early recognition of SCA and timely consideration of liver transplantation can significantly improve patient outcomes.

Paroxysmal nocturnal haemoglobinuria presenting as cortical cerebral venous thrombosis

Abstract Paroxysmal nocturnal haemoglobinuria (PNH) arises as a consequence of mutation of phosphatidylinositol N-acetylglucosaminyltransferase subunit A gene that is required for synthesis of the glycosylphosphatidylinositol proteins to the cell surface of blood cells. Patients with PNH usually present with features of chronic unexplained anaemia, but can also present with bone marrow failure and thrombosis at unusual sites. We present the case of a 27-year-old who presented with complaints of headache and easy fatigability, on evaluation was found to have coombs negative haemolytic anaemia and brain magnetic resonance venogram revealed thrombosis in the left transverse and sigmoid sinuses. On further investigation, found to have PNH clone in both red and white blood cell lineages and diagnosed as PNH. Hence, any patient presenting with chronic non-immune intravascular haemolysis, unexplained anaemia and unusual thrombosis should alert the physician to consider PNH as a differential diagnosis to avoid delay in diagnosis and better management.

Overlapping features of thrombotic thrombocytopenic purpura and systemic lupus erythematosus, a diagnostic and a management challenge

Thrombotic thrombocytopenic purpura (TTP) is a rare, potentially fatal blood disorder that can be challenging for clinicians to identify in the setting of autoimmune diseases such as systemic lupus erythematosus (SLE). SLE can present with thrombotic microangiopathy (TMA) and differentiation between the two diseases can be quite difficult.
 In this case report we present a 62-year-old female with a history of SLE who was hospitalized with thrombocytopenia, dysarthria, dizziness, paresthesia and altered mental status. The laboratory results revealed direct Coombs negative hemolytic anemia, severe thrombocytopenia, significant elevation of lactate dehydrogenase, leukocytosis and presence of few schistocytes in the peripheral film. In addition, we also present evidence for circulating anti-ADAMTS13 antibody/ADAMTS13 antigen. Based on clinical, hematological, and biochemical findings, we concluded that it was a case of TTP-like microangiopathy associated with SLE and indicated treatment with methylprednisolone pulses and plasmapheresis. Later on, she developed psychosis and made plasmapheresis difficult to perform. We continued corticosteroids (dose 1mg/kg), RhoGAM, Chloroquine and Azathioprine, obtaining a satisfactory response after one week of treatment.

X-linked C1GALT1C1 mutation causes atypical hemolytic uremic syndrome.

Hemolytic-uremic syndrome (HUS), mostly secondary to infectious diseases, is a common cause of acute kidney injury in children. It is characterized by progressive acute kidney failure due to severe thrombotic microangiopathy, associated with nonimmune, Coombs-negative hemolytic anemia and thrombocytopenia. HUS is caused mostly by Shiga toxin-producing E. Coli, and to a lesser extent by Streptococcus pneumonia. In Streptococcus pneumonia HUS (pHUS), bacterial neuraminidase A exposes masked O-glycan sugar residues on erythrocytes, known as the T antigen, triggering a complement cascade causing thrombotic microangiopathy. Atypical HUS (aHUS) is a life-threatening genetic form of the disease, whose molecular mechanism is only partly understood. Through genetic studies, we demonstrate a novel X-linked form of aHUS that is caused by a de-novo missense mutation in C1GALT1C1:c.266 C > T,p.(T89I), encoding a T-synthase chaperone essential for the proper formation and incorporation of the T antigen on erythrocytes. We demonstrate the presence of exposed T antigen on the surface of mutant erythrocytes, causing aHUS in a mechanism similar to that suggested in pHUS. Our findings suggest that both aHUS caused by mutated C1GALT1C1 and pHUS are mediated by the lectin-complement-pathway, not comprehensively studied in aHUS. We thus delineate a shared molecular basis of aHUS and pHUS, highlighting possible therapeutic opportunities.

Hematologic Abnormalities After COVID-19 Infection: A Case of Coombs-Negative Hemolytic Anemia and Thrombocytopenia.

The occurrence of hemolytic anemia in patients with active SARS-CoV-2 infection has been documented in medical literature. While relatively uncommon, there have been instances where this condition presents as a Coombs-negative hemolytic anemia. In this research study, we report a distinctive case of Coombs-negative hemolytic anemia and thrombocytopenia in a patient with a known history of COVID-19 infection. The patient demonstrated a favorable response to treatment involving the administration of steroids and intravenous immunoglobulin (IVIG) therapy. This case adds to the existing body of evidence regarding the hematological manifestations of SARS-CoV-2 infection, highlighting the importance of considering and managing hematological complications in patients with COVID-19.

Peripheral blood smear diagnosis of G6PD deficiency in an 83-year-old man.

An 83-year-old male was admitted to the emergency department for abrupt onset of jaundice and asthenia. Vital signs were in range, and physical examination was unremarkable except for jaundice and hyperchromic urine. Full blood count on admission showed his hemoglobin concentration to be 81 g/L with no alteration in white blood cell (WBC) or platelets count. Biochemical tests were significant for high bilirubin level 417.07 μmol/L (indirect bilirubin 369.53 μmol/L) and abnormal lactate dehydrogenase level 1520 μmol/L. The hypothesis of hemolytic anemia was confirmed by further laboratory tests, which showed undetectable haptoglobin and increased reticulocyte count 196 × 109/L. Direct and indirect Coombs tests were both negative, suggesting a Coombs-negative hemolytic anemia. A first blood smear did not show schistocytes and the coagulation profile was in order. Medical history was negative for oxidant drugs assumption, prosthetic heart valves, and liver and kidney diseases. Chest radiography was normal, and a complete abdominal echography did not show hepatomegaly or splenomegaly. Meanwhile, the patient clinical course was complicated by pain and tightness in the chest and dizziness and an electrocardiogram was compatible with a non-ST-segment elevation myocardial infarction. A new set of lab tests showed severe anemia with 66 g/L of hemoglobin, and the patient undergone blood transfusion. In the suspicion of a hemolytic crisis in the context of glucose-6-phosphate dehydrogenase (G6PD) deficiency, an accurate anamnesis was collected and the patient confirmed the assumption of fava beans 3 days earlier after a long time. G6PD levels could not be assessed overnight, but a second blood smear was significant for bite, blister, and ghost cells (Figure 1 A and B), which are findings compatible with G6PD deficiency. Testing for G6PD was performed as soon as available and it revealed a significant G6PD deficiency (2.7 U/g Hb, normal range 8–14 U/g Hb, overestimated because of low Hb concentration). This is a case of G6PD deficiency diagnosed in 83-yer-old patient with no previous similar event in an unfavorable setting (emergency department by night). It highlights the necessity of high clinical suspicion of G6PD deficiency in the context of Coombs-negative hemolytic anemia, even in elderly patients. It is worth noting that different species of fava beans have a different capacity in inducing oxidative stress. Lastly, blood smear can still provide useful morphological data in supporting the diagnosis, regardless the immediate availability of G6PD test. Fabio Giglio conceived the study; D. Sannipoli, D. T. Clerici, and Fabio Giglio provided all clinical and hematological data; A. Boletini and P. Ronchi performed and analyzed morphology; D. Sannipoli and Fabio Giglio wrote the paper. All authors approved the paper. The authors declare no conflict of interest. Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.

S2948 Challenges in Recognizing and Diagnosing Wilson Disease

Introduction: Wilson disease is a rare autosomal recessive disease leading to impaired copper homeostasis and accumulation in the liver, brain, and other organs. It is manageable, and physicians must familiarize themselves with the diversity of its presentation. Our case sheds light on the challenges; health care providers face in establishing the diagnosis. Case Description/Methods: A fifty-eight-year-old female was admitted to the hospital for altered mental status who had a dramatic hospital course with acute liver failure complicated by shock and multiorgan failure. Her past medical history is significant for COPD, liver cirrhosis. Family history is positive for Alpha-1 Antitrypsin deficiency. She presented with acute psychosis and altered mental status. Patient was admitted with suspected hepatic encephalopathy. She developed acute liver failure followed by shock and multiorgan failure. Her work up came back as Hg 6.7, Plt 27, INR 2.1, Haptoglobin < 8 mg/dl, Coombs negative, Ceruoplasmn 5.9, copper serum 32, 24 hours urine copper level 42 and urine copper level 351. Previously, she complained of tremor and slurred speech. She was evaluated by neurology team for seizure like activity, but it was found that her movements were compelling choreiform movements (Figure). Liver cirrhosis evaluation started on 2019 when she was evaluated for new onset ascites. Her exam showed abdominal distension and lower limb edema, labs showed ALP 247, AST/ALT 51/16, total bilirubin 0.7, ANA >1: 1280, alpha 1 antitrypsin low 72 with MZ phenotype, Ceruplasmin level 13. Liver Biopsy Showed findings consistent with moderately active steatohepatitis with cirrhosis. It was presumed that her liver cirrhosis was related to A-1AT deficiency/NASH. The low ceruplasmin has slipped and the diagnosis of Liver Cirrhosis secondary to A-1AT deficiency carried on. Discussion: Wilson disease caused by mutations in the ATP7B gene responsible for intracellular copper transporter's function, led to impairment in biliary copper excretion leading to the deposit of copper in several organs. The diagnosis is based on the score developed at the 8th International Meeting on Wilson Disease in Leipzig (8). If the score is ≥4, Wilson disease is highly likely. In our patient, points are given as follows: Neuropsychiatric symptoms suggestive of Wilson disease (2), Coombs-negative hemolytic anemia with high serum copper (1), Serum ceruloplasmin < 10 mg/dL (2) with a total score of 5 points, which made her diagnosis with Wilson disease is highly likely.Figure 1.: Kayser-Fleisher ring.

A Rare Case of Non-immune Hemolytic Anemia in a Stage IV Breast Cancer Patient Treated With Capecitabine

Incremental changes in the diagnosis of breast cancer leave drastic impacts on patients. There are detrimental shifts in cost, psychological disorders in terms of depression, and morbidities. Stage IV breast cancer has a high mortality rate and was afflicting our patient who was diagnosed with metastatic breast cancer estrogen receptor/progesterone receptor (ER/PR) positive, human epidermal growth factor receptor 2 (HER-2) neo negative, and low Ki-67. Among the various management modalities and effective treatments, capecitabine was selected because of its benefits; however, there are several commonly known adverse effects when using capecitabine including non-immune hemolytic anemia, a very rare and unexpected side effect despite the many research and clinical trials performed. Immune mediate or Coombs positive hemolytic anemia was reported with the usage of capecitabine, but this patient developed Coombs negative or non-immune hemolytic anemia. Capecitabine, a form of fluoropyrimidine, hypothetically affects the erythrocyte membrane structure resulting in the destruction of these cells. Additionally, discontinuation of capecitabine in the patient led to the resolution of the condition; this made us more aware of the precise diagnosis, also considering that the bone marrow biopsy came back negative.

First diagnosis of thrombotic thrombocytopenic purpura after SARS-CoV-2 vaccine \u2013 case report

BackgroundWe report a case of a 25-year-old male patient, who developed acquired thrombotic thrombocytopenic purpura (aTTP) after receiving a first dose of mRNA-based SARS-CoV-2 vaccine Spikevax (mRNA-1273, Moderna Biotech, USA). While this is the first case in literature describing a case of aTTP after receiving the Spikevax vaccine, there are two other cases after mRNA-based Covid-19 vaccine and two after adenoviral SARS-CoV-2 vaccine.Case presentationThe patient presented with persisting malaise, fever, headache, word-finding difficulties, nausea, vomiting, petechial bleeding, and hematuria 13 days after receiving a first dose of vaccination. Laboratory testing showed low platelet count, Coombs-negative hemolytic anemia, and mild acute kidney injury. We excluded vaccine induced immune thrombotic thrombocytopenia (VITT) as another important differential diagnosis and the final diagnosis was established after ADAMTS-13 (A Disintegrin And Metalloproteinase with a ThromboSpondin type 1 motif, member 13) activity was found to be < 1% (reference range > 40%) and ADAMTS-13 antibodies being 72.2 IU/L (reference range < 12 IU/L).We initiated empiric therapy of plasmapheresis and corticosteroids on admission and started caplacizumab the day after. The patient’s thrombocyte count normalized 3 days after admission, hemolysis and acute kidney injury resolved after 2 weeks. The patient received 2 doses of rituximab (1 g each) after the diagnosis of immune TTP was established. One month after the initial presentation, the patient is in good overall condition, but still receives daily caplacizumab due to ADAMTS-13 activity of < 1%.ConclusionsLow platelet count after vaccination against SARS-CoV-2 has gained attraction after vaccine-induced immune thrombotic thrombocytopenia (VITT) has been described as a rare but severe complication of adenoviral-based vaccines. Thrombotic thrombocytopenic purpura (TTP) is an important differential diagnosis, but there are only few reports of TTP following SARS-CoV-2 vaccination. Despite pathophysiological and clinical differences of both entities, diagnostic uncertainty can result in the acute setting, since they share main symptoms such as headache and neurological alterations in addition to thrombocytopenia. In difference to other cases reported, this patient developed first symptoms of TTP as early as 4 days after vaccination, which suggests that vaccination merely acted as trigger for occult TTP, instead of truly inducing an autoimmunological process.

Comparison of Polybrene DAT and Conventional DAT in Cases of Suspected DAT Negative Autoimmune Hemolytic Anemia (AIHA)

Abstract Introduction/Objective A negative Direct Antiglobulin Test (DAT) is seen in approximately 1-5% of patients presenting with signs and symptoms of immune hemolysis. A well-performed ‘standard’ DAT detects ~100-500 molecules of bound IgG per red cell. A more sensitive polybrene DAT may be helpful in order to confirm a diagnosis of AIHA in patients whose samples have tested negative via standard DAT. However, there has been little reported on utility of the polybrene DAT in evaluating such cases with modern DAT reagents. We hypothesized that the polybrene DAT would not contribute substantially to the analysis of Coombs-negative hemolytic anemia (C-NHA), based primarily on our anecdotal observation. As such, we undertook a study to assess results of polybrene DAT in cases evaluated for possible (C-NHA). Methods/Case Report Two study sites were used for data analysis (Yale-New Haven Hospital, Site A, and VA Connecticut, Site B) over a five year period (2016-2021). During this time, standard DATs were performed at both study sites by the tube method using polyspecific antiglobulin and, if positive, reflex to anti-IgG and -C3. For cases of suspected C-NHA (which are reported to Blood Bank via a consult mechanism), conventioned DAT- samples are referred to our regional immunohematology laboratory (American Red Cross, Farmington, CT) for manual hexadimethrine bromide (Polybrene) DAT. Polybrene DAT is reported as negative with two sources of polyspecific AHG. Subsets of patients also underwent acid elution studies (Gamma ELU-KITII) as part of a C-NHA algorithm developed during the study period. Results of standard DAT, acId elution, and polybrene DAT were extracted from Blood Bank electronic records at both study sites. Results (if a Case Study enter NA) Evaluation for C-NHA was performed in 32 patients/cases over the study period. Amongst these individuals, 96.8% (31/32) underwent polybrene DAT assessment and none (0%; 0/31) demonstrated a positive polybrene DAT result. Notably, acid elution studies were performed in 90.6% (29/32) of traditional DAT negative cases. Of these, 10.3% (3/29) had reactive eluates. Conclusion Performance of the polybrene DAT appeared to be of no value in the assessment of suspected C-NHA. Given that nearly 10% of individuals with a negative conventional DAT had a positive acid elution, this testing step appears to be of greater value in potentially identifying an autoantibody in suspected cases of C-NHA.

Acute liver failure with hemolytic anemia in children with Wilson's disease: Genotype-phenotype correlations?

BACKGROUNDWilson’s disease (WD) is a rare autosomal recessive inherited disorder of copper metabolism. Acute liver failure (ALF) and hemolytic anemia represent the most severe presentation of WD in children. No clear genotype-phenotype correlations exist in WD. Protein-truncating nonsense, frame-shift, or splice-site variants may be associated with more severe disease. In contrast, missense variants may be associated with late-onset, less severe disease, and more neurological manifestations. Recently, a gene variant (HSD17B13:TA, rs72613567) with a possible hepatic protective role against toxins was associated with a less severe hepatic phenotype in WD.AIMTo analyze the possible genotype-phenotype correlations in children with WD presented with ALF and non-immune hemolytic anemia.METHODSThe medical records of children with WD diagnosed and treated in our hospital from January 2006 to December 2020 were retrospectively analyzed. The clinical manifestations (ALF with non-immune hemolytic anemia or other less severe forms), laboratory parameters, copper metabolism, ATP7B variants, and the HSD17B13:TA (rs72613567) variant were reviewed to analyze the possible genotype-phenotype correlations.RESULTSWe analyzed the data of 51 patients with WD, 26 females (50.98%), with the mean age at the diagnosis of 12.36 ± 3.74 years. ALF and Coombs-negative hemolytic anemia was present in 8 children (15.67%), all adolescent girls. The Kayser-Fleisher ring was present in 9 children (17.65%). The most frequent variants of the ATP7B gene were p.His1069Gln (c.3207A>G) in 38.24% of all alleles, p.Gly1341Asp (c.4021G>A) in 26.47%, p.Trp939Cys (c.2817G>T) in 9.80%, and p.Lys844Ter (c.2530A>T) in 4.90%. In ALF with hemolytic anemia, p.Trp939Cys (c.2817G>T) and p.Lys844Ter (c.2530A>T) variants were more frequent than in other less severe forms, in which p.His1069Gln (c.3207A>G) was more frequent. p.Gly1341Asp (c.4021G>A) has a similar frequency in all hepatic forms. For 33 of the patients, the HSD17B13 genotype was evaluated. The overall HSD17B13:TA allele frequency was 24.24%. Its frequency was higher in patients with less severe liver disease (26.92%) than those with ALF and hemolytic anemia (14.28%).CONCLUSIONIt remains challenging to prove a genotype-phenotype correlation in WD patients. In children with ALF and hemolytic anemia, the missense variants other than p.His1069Gln (c.3207A>G) and frame-shift variants were the most frequently present in homozygous status or compound heterozygous status with site splice variants. As genetic analysis is usually time-consuming and the results are late, the importance at the onset of the ALF is questionable. If variants proved to be associated with severe forms are found in the pre-symptomatic phase of the disease, this could be essential to predict a possible severe evolution.

Pediatric Wilson disease presenting as acute liver failure: Prognostic indices.

BACKGROUNDAcute liver failure (ALF) can be a primary presentation of Wilson disease (WD). Mortality rates are high in WD with ALF (WDALF). Predictions of mortality in WDALF vary by model and are sometimes contradictory, perhaps because few patients are studied or WD diagnoses are questionable. AIMTo determine the outcomes among well-documented WDALF patients and assess mortality model performance in this cohort.METHODSWe reviewed the medical records of our pediatric WDALF patients (n = 41 over 6-years-old, single-center retrospective study) and compared seven prognostic models (King’s College Hospital Criteria, model for end-stage liver disease/pediatric end-stage liver disease scoring systems, Liver Injury Unit [LIU] using prothrombin time [PT] or international normalized ratio [INR], admission LIU using PT or INR, and Devarbhavi model) with one another.RESULTSAmong the 41 Han Chinese patients with ALF, WD was established by demonstrating ATP7B variants in 36. In 5 others, Kayser-Fleischer rings and Coombs-negative hemolytic anemia permitted diagnosis. Three died during hospitalization and three underwent liver transplantation (LT) within 1 mo of presentation and survived (7.3% each); 35 (85.4%) survived without LT when given enteral D-penicillamine and zinc-salt therapy with or without urgent plasmapheresis. Parameters significantly correlated with mortality included encephalopathy, coagulopathy, and gamma-glutamyl transpeptidase activity, bilirubin, ammonia, and serum sodium levels. Area under the receiver operating curves varied among seven prognostic models from 0.981 to 0.748 with positive predictive values from 0.214 to 0.429.CONCLUSIONWDALF children can survive and recover without LT when given D-penicillamine and Zn with or without plasmapheresis, even after enlisting for LT.

Coombs-Negative Haemolytic Anaemia, Direct Hyperbilirubinaemia and Splenomegaly: A Rare Amalgam.

Epstein-Barr virus (EBV) is notorious for its varied presentation in adults. Reactivation of EBV can occur at any time and is often due to weakened cellular immunity. Here we report the case of a young woman with no previous medical history who presented with cholestatic hepatitis, Coombs-negative haemolytic anaemia and splenomegaly. Due to the initial disjointed picture with no other localizing symptoms, she underwent extensive work-up for the same. EBV has been associated with many malignancies, autoimmune diseases and chronic fatigue syndrome. EBV causes elevated liver enzymes; however, cholestatic hepatitis is exceedingly rare, with only a few cases reported. Haemolytic anaemia is a common complication of EBV infection and is often Coombs positive. EBV testing should be considered before more invasive and expensive work-up in a patient presenting with multi-systemic abnormalities. Epstein-Barr virus (EBV) can have myriad manifestations in all age groups.Coombs-negative haemolytic anaemia can occur as a complication of EBV.EBV testing should be considered prior to more expensive work-up in anyone presenting with abnormalities in the reticuloendothelial system.

C3 glomerulopathy and atypical hemolytic uremic syndrome: an updated review of the literature on alternative complement pathway disorders.

The complement system plays a significant role within the pathological process of C3 glomerulopathy (C3GP) and atypical hemolytic uremic syndrome (aHUS). In daily practice, clinicians should differentiate the subgroups of C3GP because of they should apply different treatment modalities. In the past, C3GP was considered as a part of membranoproliferative glomerulonephritis (MPGN). MPGN is defined as glomerular capillary thickening secondary to the synthesis of the new glomerular basement membrane and mesangial cellular hyperplasia with mesangial matrix expansion. Atypical hemolytic uremic syndrome is an ultra-rare disease that can be outlined by the triad of Coombs negative microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Recent advances demonstrated that these diseases share common abnormalities of the control of the alternative complement system. Therefore, nowadays, most researchers advocate that there may be overlap in the pathogenesis of C3GP and aHUS. This review will provide recent novel mechanisms and treatment options in these diseases. For the purposes that we mentioned above and to help clinicians, we aimed to describe the etiology, pathophysiology, and treatment of C3GP and aHUS in this comprehensive review.

Wilson Disease-Induced Acute Liver Failure (NWI = 13) Salvaged without Liver Transplant by Plasmapheresis

AbstractWilson disease (WD) is a disorder of copper metabolism resulting in accumulation of copper in vital organs of the human body, predominantly in the liver and the brain. Acute liver failure in WD has a bad prognosis, especially with a score ≥11 in the revised WD prognostic index; emergency liver transplantation is considered the only life-saving option in this scenario. Here, we reported a girl patient with WD-induced liver failure and poor prognostic score who was rescued by plasmapheresis. She also manifested severe Coombs negative hemolytic anemia and acute kidney injury. This case report highlights the utility of an adjunctive modality besides liver transplantation for the management of fulminant liver failure caused by WD.

Coombs-negative haemolytic anaemia in pregnancy: A case report

We present a rare case of Coombs-negative autoimmune haemolytic anaemia in a multiparous woman in secondary care. There were no known underlying medical or obstetric risk factors for haemolytic anaemia. Following extensive investigation and a therapeutic trial of oral corticosteroids, a diagnosis was made. Autoimmune haemolytic anaemia is potentially fatal, and prompt diagnosis with haematology input is essential to ensure maternal and fetal safety in pregnancy and the puerperium. With only a small number of cases of Coombs-negative autoimmune haemolytic anaemia reported in the literature, we present this rare case for discussion. We highlight the importance of thorough investigation of refractory anaemia in pregnancy and consider the associated challenges.

PULMONARY MUCORMYCOSIS: A RARE CAUSE OF HYDROPNEUMOTHORAX

SESSION TITLE: Medical Student/Resident Chest Infections Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Mucormycosis is a rare but often fatal fungal infection. These fungi are ubiquitous in nature and most commonly cause rhino-orbital-cerebral infections. Patients who are immunocompromised are at higher risk (1). CASE PRESENTATION: A 76 year-old never-smoker with a medical history significant for type 2 diabetes (HbA1c 5.8%) and Coombs negative hemolytic anemia was admitted with 3 months of progressive dyspnea. She had an associated nonproductive cough for 10 days. She denied fevers, night sweats, chest pain or hemoptysis. Two months prior to presentation, she started prednisone 60 mg daily for hemolytic anemia. Prednisone was slowly tapered to 30 mg daily at the time of presentation. She received one dose of Rituximab due to persistent anemia. Evaluation 2 weeks prior to presentation revealed a right upper lobe, 5 cm cavitary lesion on chest CT. On arrival she was tachycardic (heart rate 110) and tachypneic (respiratory rate 32) without hypoxemia. Labs were notable for a hemoglobin of 9.5 g/dl, WBC of 13.6, and creatinine of 1.85 mg/dl. Chest x-ray showed a loculated right hydropneumothorax. Chest CT showed the right hydropneumothorax with progression of the right upper lobe cavitary lesion. A 14 French pigtail catheter was placed at bedside via ultrasound guidance. Pleural studies demonstrated exudative fluid with negative cytology and cultures. She underwent CT-guided biopsy of the cavitary lesion, which revealed inflammation, necrosis, and numerous broad-ribbon-like, pauci-septate hyphae favoring mucormycosis. IV liposomal amphotericin and posaconazole were initiated. Thoracic surgery declined operative intervention due to her age and comorbidities. She developed respiratory and renal failure and passed away 1 month after presentation. DISCUSSION: This patient developed pulmonary mucormycosis in the setting of glucocorticoid and Rituximab therapy. The diagnosis of mucormycosis can be difficult due to nonspecific symptoms (1) and lack of serologic tests. Commonly used fungal antigen tests such as 1,3-beta-D-glucan are traditionally negative (2). Chest CT findings are nonspecific with the classic halo or reversed halo sign present in only a minority of cases (1). A definitive diagnosis is made with histopathology (1). Successful treatment requires early diagnosis, reversal of predisposing factors, surgical debridement, and prompt initiation of antifungal therapy (3). Liposomal amphotericin is first-line pharmacologic therapy (1); however, antifungal therapy without surgical debridement is unlikely to be successful. CONCLUSIONS: Our patient presented with an unusual case of pulmonary mucormycosis; a high suspicion and histopathology are required to make the diagnosis. CT findings are non-specific and common fungal antigen tests can be negative. Early diagnosis and prompt initiation of antifungal therapy with surgical debridement improves the chance for survival. Reference #1: Farmakiotis D, Kontoyiannis DP. Mucormycoses. Infect Dis Clin North Am 2016; 30:143. Reference #2: Ostrosky-Zeichner L, Alexander BD, Kett DH, et al. Multicenter clinical evaluation of the (1-->3) beta-D-glucan assay as an aid to diagnosis of fungal infections in humans. Clin Infect Dis 2005; 41:654. Reference #3: Spellberg B, Walsh TJ, Kontoyiannis DP, et al. Recent advances in the management of mucormycosis: from bench to bedside. Clin Infect Dis 2009; 48:1743. DISCLOSURES: No relevant relationships by Meghan Hill, source=Web Response author/editior relationship with UpToDate Please note: $5001 - $20000 Added 04/01/2020 by David Midthun, source=Web Response, value=Royalty No relevant relationships by Kelly Pennington, source=Web Response