Oral Iptacopan Monotherapy in Paroxysmal Nocturnal Hemoglobinuria.

BACKGROUND: Persistent hemolytic anemia and a lack of oral treatments are challenges for patients with paroxysmal nocturnal hemoglobinuria who have received anti-C5 therapy or have not received complement inhibitors. Iptacopan, a first-in-class oral factor B inhibitor, has been shown to improve hemoglobin levels in these patients. METHODS: In two phase 3 trials, we assessed iptacopan monotherapy over a 24-week period in patients with hemoglobin levels of less than 10 g per deciliter. In the first, anti-C5-treated patients were randomly assigned to switch to iptacopan or to continue anti-C5 therapy. In the second, single-group trial, patients who had not received complement inhibitors and who had lactate dehydrogenase (LDH) levels more than 1.5 times the upper limit of the normal range received iptacopan. The two primary end points in the first trial were an increase in the hemoglobin level of at least 2 g per deciliter from baseline and a hemoglobin level of at least 12 g per deciliter, each without red-cell transfusion; the primary end point for the second trial was an increase in hemoglobin level of at least 2 g per deciliter from baseline without red-cell transfusion. RESULTS: In the first trial, 51 of the 60 patients who received iptacopan had an increase in the hemoglobin level of at least 2 g per deciliter from baseline, and 42 had a hemoglobin level of at least 12 g per deciliter, each without transfusion; none of the 35 anti-C5-treated patients attained the end-point levels. In the second trial, 31 of 33 patients had an increase in the hemoglobin level of at least 2 g per deciliter from baseline without red-cell transfusion. In the first trial, 59 of the 62 patients who received iptacopan and 14 of the 35 anti-C5-treated patients did not require or receive transfusion; in the second trial, no patients required or received transfusion. Treatment with iptacopan increased hemoglobin levels, reduced fatigue, reduced reticulocyte and bilirubin levels, and resulted in mean LDH levels that were less than 1.5 times the upper limit of the normal range. Headache was the most frequent adverse event with iptacopan. CONCLUSIONS: Iptacopan treatment improved hematologic and clinical outcomes in anti-C5-treated patients with persistent anemia - in whom iptacopan showed superiority to anti-C5 therapy - and in patients who had not received complement inhibitors. (Funded by Novartis; APPLY-PNH ClinicalTrials.gov number, NCT04558918; APPOINT-PNH ClinicalTrials.gov number, NCT04820530.).

Cancer-related thrombotic microangiopathy and disseminated intravascular coagulation in a patient with bone marrow carcinomatosis of unknown primary origin: A case report.

BACKGROUND: Cancer-related thrombotic microangiopathy (CR-TMA) is a rare type of Coombs-negative hemolytic anemia, which is caused by malignancy and has a poor prognosis. CASE: A 76-year-old female was referred to our hospital due to Coombs-negative hemolytic anemia, which was causing fatigue and dyspnea on exertion, accompanied by schistocytosis. A bone marrow examination demonstrated bone marrow carcinomatosis, and the tumor cells were morphologically suspected to be signet-ring cell carcinoma cells. As we failed to find the primary tumor site before the patient died, she was diagnosed with CR-TMA due to bone marrow carcinomatosis of unknown primary origin. Thrombotic thrombocytopenic purpura (TTP) was rapidly ruled out based on her PLASMIC score. In addition, immunohistochemical staining of a clot section of the bone marrow and tumor marker data were useful for narrowing down the likely primary tumor site. CONCLUSION: Although CR-TMA is an extremely rare phenomenon, clinicians who suspect CR-TMA should quickly rule out TTP and decide whether to provide appropriate chemotherapy or plan for palliative care.

Homozygous SPTA1-associated hereditary pyropoikilocytosis presenting as hydrops fetalis.

INTRODUCTION: Hereditary pyropoikilocytosis (HPP) is a heterogeneous inherited disorder of red blood cell (RBC) membrane and cytoskeletal proteins that leads to hemolytic anemia. HPP is characterized by marked poikilocytosis, microspherocytes, RBC fragmentation, and elliptocytes on peripheral blood smear. Mutations in SPTA1 can cause HPP due to a quantitative defect in α-spectrin and can lead to profound fetal anemia and nonimmune hydrops fetalis, which can be managed with intrauterine transfusion. CASE PRESENTATION: We present a case of a 26-year-old G4P2102 woman of Amish-Mennonite ancestry with a pregnancy complicated by fetal homozygosity for an SPTA1 gene variant (SPTA1c.6154delG) as well as severe fetal anemia and hydrops fetalis, which was managed with four intrauterine transfusions between 26 and 30 weeks gestation. Pre-transfusion peripheral smears from fetal blood samples showed RBC morphology consistent with HPP. The neonate had severe hyperbilirubinemia at birth, which has resolved, but remains transfusion-dependent at 6 months of life. DISCUSSION/CONCLUSION: To our knowledge, this is the first report that correlates homozygosity of the SPTA1c.6154delG gene variant with RBC dysmorphology and establishes the diagnosis of HPP.

[Sjögren's syndrome combined with cold agglutinin disease: A case report].

Sjögren's syndrome(SS)is a chronic autoimmune disease that affects exocrine glands, especially salivary and lacrimal glands. The main clinical manifestations are dry mouth and dry eyes, but also multi-organ and multi-system can be involved. Cold agglutinin disease(CAD)is an autoimmune disease characterized by red blood cell agglutination in the blood vessels of extremities caused by cold agglutinin at low temperature, resulting in skin microcirculation disturbance, or hemolytic anemia. Cold agglutinin disease is divided into two categories, primary cold agglutinin disease and secondary cold agglutinin disease. Primary cold agglutinin disease is characterized with cold agglutinin titer of 1 ∶4 000 or more and positive Coomb's test. However, the Coomb's test is not necessarily positive and the cold agglutinin titer is between 1 ∶32 and 1 ∶4 000 in secondary cold agglutinin disease. Here, we reported an elderly patient admitted to hospital due to fever. He was diagnosed with respiratory infection, but he showed incompletely response to the anti-infection treatment. Further laboratory tests showed the patient with positive ANA and anti-SSA antibodies. Additionally, the patient complained that he had dry mouth and dry eyes for 1 year. Schirmer test and salivate gland imaging finally confirmed the diagnosis Sjogren's syndrome. During the hospital stay, the blood clots were found in the anticoagulant tubes. Hemolytic anemia was considered as the patient had anemia with elevated reticulocytes and indirect bilirubin. In addition, further examination showed positive cold agglutination test with a titer of 1 ∶1 024, and cold agglutinin disease was an important type of cold-resistant autoimmune hemolytic anemia. Furthermore, the patient developed cyanosis after ice incubating at the tip of the nose. Hence, the patient was diagnosed as CAD and he was successfully treated with glucocorticoids instead of anti-infection treatments. Hence, the patient was diagnosed with SS combined with secondary CAD. SS combined CAD are rarely reported, and they are both autoimmune diseases. The abnormal function of B lymphocytes and the production of autoantibodies might be the common pathogenesis of them. Cold agglutinin disease can lead to severe hemolytic anemia, even life-threatening. In clinical practice, timely recognizing and dealing with CAD might promote the prognosis of the patient.

Atypical haemolytic uraemic syndrome in a postpartum patient.

A postpartum patient presented 1 week following uncomplicated pregnancy and elective repeat caesarean section with acute hypertension, severe anaemia and acute kidney injury. Her workup demonstrated microangiopathic anaemia, thrombocytopenia and liver enzyme elevations. Differential diagnoses included postpartum haemolysis-elevated liver enzyme-low platelet (HELLP) syndrome, haemolytic uraemic syndrome (HUS), and thrombotic thrombocytopenic purpura (TTP). She was treated initially with systemic corticosteroids, haemodialysis and plasmapheresis for presumed TTP while awaiting the results of ADAMSTS13 assay performed at an outside laboratory. When reported back as normal, the diagnosis of atypical HUS was established. Eculizumab was administered with rapid improvement of her condition.

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.

Idiopathic pulmonary haemosiderosis misdiagnosed as haemolytic anaemia: a case report.

Idiopathic pulmonary haemosiderosis is a rare disease primarily affecting children. The condition is characterized by widespread bleeding from alveolar capillaries, resulting in symptoms such as haemoptysis, shortness of breath and iron deficiency anaemia. However, it is not a specific disease and sometimes can manifest solely as anaemia, which may be easily overlooked and misdiagnosed. The purpose of this case report was to describe a 1-year-old boy who exhibited haemolytic anaemia as the only symptom of idiopathic pulmonary haemosiderosis, with the intention of offering clinical insights into the precise diagnosis and subsequent management of this rare and easily misdiagnosed disease. Clinicians should keep idiopathic pulmonary haemosiderosis in mind when evaluating children with haemolytic anaemia and promptly initiate testing and treatment to prevent misdiagnosis and improve outcomes.

Purtscher-like retinopathy in systemic lupus erythematosus: clinical features, risk factors and prognosis.

BACKGROUND: Purtscher-like retinopathy (PLR) is a rare ocular manifestation in systemic lupus erythematosus (SLE) with poor prognosis, but its clear risk factors and treatment consensus are still lacking. AIM: To investigate the clinical features, risk factors and prognosis of PLR in SLE patients. DESIGN AND METHODS: A retrospective analysis was conducted on SLE patients with PLR admitted at Peking Union Medical College Hospital from 2013 to 2022. Clinical data, including demographic characteristics, lupus-related features, laboratory findings and ophthalmologic examinations, were collected and analyzed. The prognosis was evaluated based on best-corrected visual acuity and ophthalmologic outcomes. RESULTS: Seventeen SLE patients (32 eyes) diagnosed with PLR were included, along with a random selection of 100 SLE patients without retinopathy and 100 with retinal microvasculopathy as controls. Patients with PLR had a significantly younger age, a higher proportion of hemolytic anemia, a shorter duration of SLE, a higher SLE disease activity index-2000 (SLEDAI-2K) score, higher erythrocyte sedimentation rate (ESR) values and lower hemoglobin (HGB) values than the group without retinopathy (P < 0.05). They also had a significantly higher SLEDAI-2K score, higher ESR values and higher white blood cell values (P < 0.05) than the Microvasculopathy group. The majority of eyes (22/26, 84.62%) achieved stabilization at the last follow-up, with different therapeutic strategies, while a few (4/26, 15.38%) experienced complications or progression. CONCLUSION: This is the largest reported case series of PLR in SLE, which was associated with higher disease activity and poor visual prognosis. It was also associated with younger age, shorter SLE duration, concomitant hemolytic anemia, lower HGB and higher ESR value. Early recognition and prompt treatment are crucial for improving visual outcomes.

Methemoglobinemia in Hemodialysis Patients due to Acute Chlorine Intoxication: A Case Series Calling Attention on an Old Problem.

INTRODUCTION: Hemodialysis uses municipal water that must be strictly purified and sterilized to be used for that procedure. Large amounts of decontaminants are often used, such as chlorine, and if these compounds are not subsequently removed they can be transferred to the blood of patients causing complications including methemoglobinemia. METHODS: In this case series study, dialysis patients in one unit were evaluated. We reviewed clinical characteristics and laboratory findings obtained on the day when the water supply was disinfected with chlorine, with the aim to quantify methemoglobin concentrations. Our objective was to characterize the clinical presentation and management of patients who presented with methemoglobinemia on a specific index day. We also reviewed reported cases in the literature regarding this underreported complication. RESULTS: Eight patients who presented with chlorine intoxication were evaluated. The methemoglobin concentrations were between 1.3% and 7.9% (reference value 0-1%). We believe this to be caused by water containing 0.78 mg/L of total chlorine. Seven patients presented with cyanosis, 4 with dizziness, 6 with dark brown blood, 4 with dyspnea, and 4 with headache and hemolytic anemia. Subjects were treated with supplemental oxygen, methylene blue, intravenous vitamin C, blood transfusions, and increased doses of erythropoietin. No patient died, and all continued with their usual hemodialysis sessions. CONCLUSION: Acute chlorine intoxication transferred by the water used during hemodialysis sessions can present with methemoglobinemia accompanied by cyanosis, oxygen desaturation, and hemolytic anemia. Chlorine levels should be carefully monitored in the water used for hemodialysis treatment.

Mesenteric Ischemia in a Splenectomized Patient with Auto-Immune Hemolytic Anemia: Case Report.

Mesenteric ischemia is a serious complication that can occur after splenectomy for hemolytic anemia, potentially leading to lifelong intestinal problems such as ischemia and/or portal hypertension. We present the case of a 33-year-old man with a history of autoimmune hemolytic anemia and splenectomy who developed mesenteric ischemia. The patient experienced abdominal pain and diarrhea, and imaging studies revealed mesenteric vein thrombosis. Surgical intervention confirmed the diagnosis. This case significantly contributes to the existing literature by providing insights into the occurrence of mesenteric ischemia in younger individuals with predisposing factors, as well as its clinical presentation, diagnostic challenges, and severity. Moreover, it has implications for the future diagnosis and management of long-term mesenteric ischemia in patients who have undergone splenectomy for hemolytic anemia.

Estimation of mean erythrocyte age using HbA1c or HbA1c/glycated albumin for evaluation of anemia severity.

BACKGROUND: Hemoglobin A1c (HbA1c) levels are low in patients with hemolytic anemia, as HbA1c reflects mean erythrocyte age (MRBC ). Erythrocyte creatine (EC) is a hemolytic indicator that also reflects MRBC . We previously reported an equation for estimating MRBC using EC (EC-MRBC ). AIMS: In this study, EC-MRBC was compared to the HbA1c level expressed in the International Federation of Clinical Chemistry and Laboratory Medicine units (iA1c) and to the iA1c/glycated albumin (GA) ratio to estimate MRBC . METHODS: This study included 238 subjects, including patients with hemolytic anemia and/or type 2 diabetes mellitus (T2DM). RESULTS: In non-diabetic individuals, both iA1c and iA1c/GA showed a strong positive correlation with EC-MRBC (p < 0.0001). The equations to estimate iA1c-MRBC and iA1c/GA-MRBC derived from the regression equations between EC-MRBC and iA1c, and EC-MRBC and iA1c/GA in nondiabetic individuals were 1.45 × iA1c and 20.0 × iA1c/GA, respectively. iA1c-MRBC and iA1c/GA-MRBC in non-diabetic individuals without hemolytic anemia were 57.6 ± 4.0 and 57.1 ± 6.4 days, respectively, and iA1c/GA-MRBC in T2DM patients without hemolytic anemia was 56.0 ± 8.8 days.; no significant difference was seen in the comparisons. CONCLUSIONS: The MRBC can be estimated using iA1c or iA1c/GA in non-diabetic individuals, and iA1c/GA in T2DM patients.

Severe autoimmune hemolytic anemia complicating hereditary spherocytosis treated successfully with glucocorticoids and cyclosporine: a case report.

BACKGROUND: Severe autoimmune hemolytic anemia complicating hereditary spherocytosis is life threatening and has not been described in a case report. Here, we report a case in which this intractable disease was treated successfully with glucocorticoids and cyclosporine. CASE PRESENTATION: A 25-year-old female patient with hereditary spherocytosis developed severe autoimmune hemolytic anemia after respiratory syncytial virus infection. Her hemoglobin level was 26 g/L and various anti-red blood cell antibodies were detected in her serum, making blood matching difficult. Glucocorticoid monotherapy was ineffective. With the addition of cyclosporine (50 mg/12 h), the patient's hemoglobin level increased significantly and the symptoms associated with anemia were greatly relieved. CONCLUSION: In patients with severe autoimmune hemolytic anemia, especially when the presence of multiple anti-red blood cell antibodies and alloantibodies interferes with blood matching, a glucocorticoid-cyclosporine regimen may be tried.

Pseudo-thrombotic microangiopathy due to folate deficiency.

Classically, deficiencies of vitamin B12 and folate are associated with megaloblastic anaemia. Additionally, vitamin B12 is able to cause a haemolytic anaemia in the form of pseudo-thrombotic microangiopathy (pseudo-TMA). Here, we present a case of a middle-aged woman with a history of Roux-en-Y gastric bypass who presented with dyspnoea and fatigue and was found to have thrombocytopenia and a non-immune haemolytic anaemia. Work-up for haemolytic uraemic syndrome, thrombotic thrombocytopenic purpura, paroxysmal nocturnal haemoglobinuria, infection, malignancy and autoimmune conditions was unremarkable. Her haemolytic anaemia and thrombocytopenia resolved with folate replenishment. She was diagnosed as likely having pseudo-TMA secondary to folate deficiency.

Thrombosis in Pregnant Women with Hemolytic Anemia.

Hemolytic anemias are a group of uncommon disorders affecting both genders, frequently occurring at the reproductive age. While a link between hemolysis and hypercoagulability has been suggested based on the elucidation of certain involved pathophysiological mechanisms, the extent of thrombotic risk in pregnant women with hemolytic anemia remains debatable. Due to the paucity of pregnancy-related data, risk assessment of gestations in women with hemolytic anemia is complicated. This review will highlight the latest advances in the diagnosis and management of these challenging disorders in pregnancy.

Circulating Levels of Hypoxia-regulating MicroRNAs in Systemic Lupus Erythematosus Patients with Hemolytic Anemia.

OBJECTIVE: MicroRNAs are fine regulators for gene expression during the post-transcriptional stage in many autoimmune diseases. HypoxamiRs (miR-210 and miR-21) play an important role in hypoxia and in inflammation-associated hypoxia. Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease that would potentiate many pathological complications, including hemolytic anemia. This study aimed to investigate the role of hypoxamiRs in SLE/hemolytic anemia patients. METHODS: This work was designed to analyze the circulating levels of↱ the miR-210 and miR-21 expressions and hypoxia-inducible factor-1α (HIF-α) in SLE/hemolytic anemia patients. SLE activity was evaluated for all patients by SLE Disease Activity Index (SLEDAI). Clinical manifestations/complications and serological/hematological investigations were reported. HIF-α concentration was assayed by ELISA and expression of miR-21 and miR-210 was analyzed by qRT-PCR. RESULTS: The results indicated that the fold change of the miR-210/miR-21 expressions in plasma was significantly elevated in SLE/hemolytic anemia patients. A strong positive correlation between the miR-210 and miR-21 expression levels was also recorded. Among the associated-disease complications, hypertension, arthritis, oral ulcers, and serositis were associated with a high circulating miR-210 expression, while the occurrence of renal disorders was associated with the increased miR-21 expression. Furthermore, the HIF-α level was remarkably elevated in SLE/hemolytic anemia patients. A high positive correlation was recorded between the HIF-α concentration and miR-210/miR-21 expression levels. The occurrence of oral ulcers, arthritis, and hypertension was associated with the increased HIF-α concentration. On the other hand, SLEDAI and white blood cell count were positively correlated with miR-21/ miR-210. The erythrocyte sedimentation rate was positively correlated with miR-21. CONCLUSION: The dysregulation of the circulating miR-210/miR-210/HIF-1α levels in SLE/hemolytic anemia patients advocated that the hypoxia pathway might have an essential role in the pathogenesis and complications of these diseases.

Nmnat3 deficiency in hemolytic anemia exacerbates malaria infection.

Malaria is an infectious disease caused by Plasmodium parasites and has high mortality rates, especially among children in African and Southeast Asian countries. Patients with hemolytic anemia are suggested to adapt protective measures against malarial infection. Nicotinamide adenine dinucleotide (NAD+) is a crucial cofactor associated with numerous biological processes that maintain homeostasis in all living organisms. In a previous study, we had demonstrated that the deficiency of nicotinamide mononucleotide adenylyltransferase 3 (Nmnat3), an enzyme catalyzing NAD+ synthesis, causes hemolytic anemia accompanied by a drastic decline in the NAD+ levels in the erythrocytes. It is well known that hemolytic anemia is linked to a reduced risk of malarial infections. In the present study, we investigated whether hemolytic anemia caused by Nmnat3 deficiency is beneficial against malarial infections. We found that Nmnat3 deficiency exacerbated malarial infection and subsequently caused death. Moreover, we demonstrated that the NAD+ levels in malaria-infected Nmnat3 red blood cells significantly increased and the glycolytic flow was largely enhanced to support the rapid growth of malarial parasites. Our results revealed that hemolytic anemia induced by the deletion of Nmnat3 was harmful rather than protective against malaria.

Dual arterial thrombosis: A diagnostic enigma.

Cold agglutinin disease is a rare cause of arterial thrombosis leading to stroke, commonly encountered against a background of mycoplasma pneumonia infections. A 22-year-old patient presented with acute-onset left hemiplegia preceded by a short history of fever and cough. Magnetic resonance imaging (MRI) showed a right middle cerebral artery infarct. Serially repeated hemoglobin levels showed a progressive drop and peripheral smear showed evidence of hemolysis. Blood drawn for investigations would rapidly clot, suggesting a possibility of cold agglutinin-induced hemolysis. The patient was then worked up for all the possible causes of hemolytic anemia including secondary causes which were all negative except for significant immunoglobulin M mycoplasma levels with elevated cold antibody titers. The patient was then initiated on pulse steroids with azithromycin and doxycycline and hemoglobin levels stabilized. The patient also developed pulmonary thromboembolism which was managed with anticoagulation. The patient made a steady improvement, was discharged, and is on follow-up. Here, we present a unique case of mycoplasma associated cold agglutinin disease causing arterial thrombosis.

Résumé La maladie à l'agglutinine froide est une cause rare de thrombose artérielle conduisant à un accident vasculaire cérébral, couramment rencontré dans un contexte d'infections à la pneumonie des mycoplasmes. Un patient de 22 ans a présenté une hémiplégie gauche aiguë précédée d'une courte histoire de fièvre et de toux. L'imagerie par résonance magnétique (IRM) a montré une infarctus de l'artère cérébrale moyenne droite. Les niveaux d'hémoglobine répétés en série ont montré une baisse progressive et le frottis périphérique a montré des preuves d'hémolyse. Le sang prélevé pour les investigations allait rapidement, suggérant une possibilité d'hémolyse induite par l'agglutinine froide. Le patient a ensuite été élaboré pour toutes les causes possibles de l'anémie hémolytique, y compris des causes secondaires qui étaient toutes négatives, sauf pour des niveaux d'immunoglobuline M de Mycoplasma significatifs avec des titres élevés d'anticorps froid. Le patient a ensuite été initié sur des stéroïdes d'impulsion avec de l'azithromycine et des niveaux de doxycycline et d'hémoglobine stabilisés. Le patient a également développé une thromboembolie pulmonaire qui a été gérée avec l'anticoagulation. Le patient a fait une amélioration constante, a été libéré et est sur le suivi. Ici, nous présentons un cas unique de maladie d'agglutinine à froid associée aux mycoplasmes provoquant une thrombose artérielle. Mots-clés: Maladie d'agglutinine à froid, accident vasculaire cérébral, thrombose pulmonaire.

Zieve Syndrome: A Clinical Triad, or Perchance a Quartet?

Zieve syndrome presents with a triad of hemolytic anemia, unexplained jaundice, and hyperlipidemia secondary to alcohol use/alcohol-induced liver injury, highlighting hemolytic anemia as the hallmark feature. Zieve syndrome is more common than originally perceived as its incidence is estimated to be 1 in 1600 admissions, but its mechanism is still poorly understood. This is a case of a 29-year-old man who developed Zieve syndrome shortly after admission for pancreatitis secondary to alcohol use disorder. Early diagnosis is important to reduce unnecessary tests and interventions. Further studies should be considered to evaluate the association between Zieve syndrome and pancreatitis.

Systemic lupus erythematosus with trisomy X: a case report and review of the literature.

BACKGROUND: The cause of systemic lupus erythematosus is not completely clear so far, but the prevalence of systemic lupus erythematosus is significantly increased in people with additional X chromosomes. CASE PRESENTATION: We report a 17-year-old Chinese female patient with systemic lupus erythematosus complicated with trisomy X, accompanied by lupus nephritis, pancytopenia, hemolytic anemia, and multiserous effusion. The patient recovered well after treatment and returned regularly. We review the previously reported cases to summarize the clinical characteristics of these patients. CONCLUSION: The additional X chromosome is related to the development of systemic lupus erythematosus. Whether it is a subtype of systemic lupus erythematosus remains to be further confirmed.

Microangiopathic Hemolytic Anemia Is a Late and Fatal Complication of Gastric Signet Ring Cell Carcinoma: A Systematic Review and Case-Control Study.

BACKGROUND: Microangiopathic hemolytic anemia (MAHA) is a rare paraneoplastic syndrome that has been reported in patients with gastric signet ring cell carcinoma (SRCC). Clinical and prognostic features of MAHA in this setting have been poorly described. MATERIALS AND METHODS: We conducted a systematic review in 8 databases of gastric SRCC complicated by MAHA and performed a case-control study assessing factors associated with survival in patients with gastric SRCC and MAHA in our pooled cohort compared with age-, sex-, and stage-matched cases of gastric SRCC from the Surveillance, Epidemiology, and End Results (SEER) database. Descriptive analyses were performed and multivariable Cox-proportional hazards regression modeling was used to determine factors associated with overall survival. RESULTS: All identified patients (n = 47) were symptomatic at index presentation, commonly with back/bone pain, and dyspnea. Microangiopathic hemolytic anemia was the first manifestation of gastric SRCC in 94% of patients. Laboratory studies were notable for anemia (median 7.7 g/dL), thrombocytopenia (median 45.5 × 103/µL), and hyperbilirubinemia (median 2.3 mg/dL). All patients with MAHA had metastatic disease at presentation, most often to the bone, bone marrow, and lymph nodes. Median survival in patients with gastric SRCC and MAHA was significantly shorter than a matched SEER-derived cohort with metastatic gastric SRCC (7 weeks vs 28 weeks, P < .01). In multivariate analysis, patients with MAHA were at significantly increased risk of mortality (HR 3.28, 95% CI 2.11-5.12). CONCLUSION: Microangiopathic hemolytic anemia is a rare, late-stage complication of metastatic gastric SRCC and is associated with significantly decreased survival compared with metastatic gastric SRCC alone.