Pembrolizumab-induced autoimmune haemolytic anemia in a patient with chronic lymphocytic leukaemia successfully treated with ibrutinib

We present a unique case of a patient with a long-standing history of indolent chronic lymphocytic leukaemia (CLL) who suddenly developed autoimmune haemolytic anaemia after starting immune checkpoint inhibitor therapy for bladder cancer. He had no clear indication to start CLL-directed treatment based on current clinical practice guidelines; however, targeted treatment of CLL with ibrutinib proved to be effective in treating the haemolytic anaemia.

Immune Checkpoint Inhibitors Induced Autoimmune Haemolytic Anemia: Case Series and Literature Review

Immune checkpoint inhibitors (ICIs) have brought a revolution to the anti-cancer treatment, however, they also triger a unique spectrum of immune-related adverse events (irAEs). Among irAEs, haemopoietic AEs are rarely reported and mostly severe or even life-threatening, especially autoimmune haemolytic anemia (AIHA). AIHA is presumed to relate to the abnormal formation of circulating autoantibodies against red cell membrane antigens. It usually cannot be discovered timely because of atypical symptoms. It is diagnosed according to presence of hemolysis evidences such as decrease of haemoglobin, increase of indirect bilirubin and lactate dehydrogenase (LDH), urobilinogen, and positive direct antiglobulin test (DAT). Treatments of AIHA are according to clinical experience and consensus, which have not been verified by prospective trial. Here we investigate previous reported ICIs induced AIHA cases including thirty detailedly documented patients. On the other hand, we report three patients who developed AIHA after three different anti-PD-1 antibodies. Most of them were aged patients with melanoma or NSCLC, developed AIHA by anti-PD-1 antibodies and relived with glucocorticoid. 43.3% of previous cases and all of our observed cases had anemia before ICIs treatment, which reminds us of anemia as a risk factor for ICIs induced AIHA. By screening parameters like complete blood examination, reticulocyte, liver function test or DAT test prior to immunotherapy, doctors could exclude pretreatment haemolytic anemia or be aware of post ICIs AIHA. Thus, it is possible to avoid the potentially life-threatening AIHA, or improve the level of pre-alarm and treatment ability of AIHA.

An unusual case of delayed and recurrent bleeding after renal biopsy in a patient with malignant hypertension

We report a 35-year-old Asian man who presented with symptomatic malignant hypertension with complications of acute kidney injury, thrombocytopenia and microangiopathic haemolytic anemia. A renal biopsy done led to recurrent bleeding needing repeated embolization. We highlight the importance of continued monitoring for post biopsy bleeding even weeks after the biopsy for high-risk cases and discuss the aspects of prevention of severe post biopsy bleeding. Keywords: Renal biopsy; Malignant hypertension; Embolization; Desmopressin.

Unusual manifestations of malaria in children

Background: Till recently, vivax malaria was being regarded as a “benign” disease. Falciparum malaria is known to be a serious illness with life threatening complications as cerebral malaria, jaundice, acute kidney injury, metabolic acidosis and bleeding diatheses. Recently, some other atypical presentations are also, being noted, which have hardly been discussed previously. The present report highlights the various unusual presentations of malaria in children.Methods: The study design was hospital based prospective observational study conducted over one year. Children between the ages of 1 month to 18 years admitted with a diagnosis of malaria confirmed by peripheral blood smear examination and/or rapid diagnostic test having unusual manifestations were studied. Patients with dengue fever, enteric fever, viral hepatitis, or any other infection were excluded. The various unusual manifestations of malaria, disease course and outcome were analysed.Results: 58 (27.1%) out of 214 patients studied were found to have atypical manifestations. The unusual features observed were ARDS in vivax malaria (n=11), fulminant hepatic failure (n=5), post malaria neurological syndrome (n=3), stroke (n=3), bilateral optic neuritis (n=1), abducens nerve palsy (n=1), autoimmune haemolytic anemia (n=1), nephrotic syndrome (n=1), splenic infarction (n=2), acute abdomen (n=2), hemiplegia (n=2), psychomotor agitation (n=7), sepsis (n=5), shock (n=3), disseminated intravascular coagulation (n=3) and urticaria (n=2). Six children with vivax presented in deep coma.Conclusions: Clinicians in endemic areas should be aware of unusual and varied presentations of malaria; failure of recognition of which may lead to delayed diagnosis resulting in increased mortality.

Covid-19 in Lupus Nephritis

COVID-19 outbreak is currently being concerned for managing patients withimmunological disorders nowadays, including SLE. Lupus is a complexautoimmune disease characterized by the presence of autoantibodies that againstcell nucleus involved many organs in the body. Patients with SLE will increaserisk of severe infection because the intrinsic respond attack with their immunerespond though immunosuppressive drugs consumption, and will potentiallydamage some organs target associated with their disease. Lupus have multipleclinical manifestations with a fluctuating symptom. Patient who come with thesymptom ofbreathlessness will getworse day by day. The symptom could be felt inthe same time as fatigue, joint pain, hair loss, malar rash, oral ulcer, pleuraleffusion and swollen feet. There's a patient with antinuclear antibody positive foranti-smith and anti-Ro/SS-A. She was diagnosed with COVID-19, SLE withnephritis, haemolytic anemia, vasculitis and pleural effusions. The clinicalmanifestations of this patient indicate a COVID-19 with lupus nephritis that hassevere disease. She was being treated with methylprednisolone andhydroxychloroquine for SLE and azithromycin plus oseltamivir as a therapy forCOVID-19. The effect of hydroxychloroquine on SARS-CoV-2 was better seen inpatients with SLE who gotthe medication regularly. Patients went home after 24days of hospitalization after negative RT-PCR results and clinical improvement ofLES.

Covid-19 in Lupus Nephritis

COVID-19 outbreak is currently being concerned for managing patients withimmunological disorders nowadays, including SLE. Lupus is a complexautoimmune disease characterized by the presence of autoantibodies that againstcell nucleus involved many organs in the body. Patients with SLE will increaserisk of severe infection because the intrinsic respond attack with their immunerespond though immunosuppressive drugs consumption, and will potentiallydamage some organs target associated with their disease. Lupus have multipleclinical manifestations with a fluctuating symptom. Patient who come with thesymptom ofbreathlessness will getworse day by day. The symptom could be felt inthe same time as fatigue, joint pain, hair loss, malar rash, oral ulcer, pleuraleffusion and swollen feet. There's a patient with antinuclear antibody positive foranti-smith and anti-Ro/SS-A. She was diagnosed with COVID-19, SLE withnephritis, haemolytic anemia, vasculitis and pleural effusions. The clinicalmanifestations of this patient indicate a COVID-19 with lupus nephritis that hassevere disease. She was being treated with methylprednisolone andhydroxychloroquine for SLE and azithromycin plus oseltamivir as a therapy forCOVID-19. The effect of hydroxychloroquine on SARS-CoV-2 was better seen inpatients with SLE who gotthe medication regularly. Patients went home after 24days of hospitalization after negative RT-PCR results and clinical improvement ofLES.

A CASE OF A CHRONIC LYMPHOPROLIFERATIVE DISORDER PRESENTING AS AUTOIMMUNE HEMOLYTIC ANEMIA

Lymphoproliferative disorders encompass a group of diseases with a highly variable clinical course. This is a case report of a patient who presented with haemolytic anemia initially and was subsequently diagnosed as a chronic lymphoproliferative disorder. He was treated with Rituximab to which he showed a favourable response.

Rare hereditary nonspherocytic hemolytic anemia caused by novel homozygous mutation, c.301C>A, (Q101K) in the AK1 gene in an Indian family

BackgroundAdenylate kinase (AK) deficiency is an uncommon form of congenital non-spherocytic haemolytic anaemia. To date, only 13 families have been affected by this disorder exhibiting symptoms like chronic anaemia supported by recurrent blood transfusions, jaundice, hepatosplenomegaly, and mental and psychomotor retardation in exceptional cases. This study aimed to identify a pathogenic mutation in the undiagnosed case of haemolytic anemia and to offer a parental diagnosis in the subsequent pregnancy.MethodNext-generation sequencing (NGS) was performed to identify pathogenic variants in the patient. Prenatal diagnosis during the second pregnancy was performed on genetic testing was performed on chronic villus sample (CVS) collected in 11 weeks of pregnancy from the mother and intravenous blood was drawn from both the parents.ResultsNovel causative mutation (p. Gln101Lys) in the AK gene was identified in a 5-year-old male child with severe transfusion-dependent hemolytic anemia. Bioinformatics tools predicted the deleterious effect of the novel variant on the structure of the protein. Prenatal diagnosis of the fetus was found to be heterozygous for the mutation. Both the parents were heterozygous for the variant c.301C > A, p. Gln101Lys.ConclusionWe have presented a review of the literature and novel mutations in the AK1 gene (p. Gln101Lys) associated with adenylate kinase deficiency. It is first a prenatal diagnosis AK deficiency report from India where heterogeneity is too high in the population and custom of intra-community marriages are prevalent.