Carfilzomib-induced atypical haemolytic uraemic syndrome: a diagnostic challenge and therapeutic success

2021 ◽  
Vol 14 (2) ◽  
pp. e239091
Author(s):  
Alicia Darwin ◽  
Leonger Malpica ◽  
Jugraj Dhanoa ◽  
Hamza Hashmi
Keyword(s):  
Multiple Myeloma ◽  
Plasma Exchange ◽  
Haemolytic Anaemia ◽  
Haemolytic Uraemic Syndrome ◽  
Complement Protein ◽  
Diagnostic Challenge ◽  
Drug Induced ◽  
Therapeutic Success ◽  
Atypical Haemolytic Uraemic Syndrome ◽  
History Of

Haemolytic uraemic syndrome (HUS) is a thrombotic microangiopathy (TMA) that presents with renal insufficiency, thrombocytopaenia and microangiopathic haemolytic anaemia. Typical HUS is associated with Shiga toxin while atypical HUS (aHUS) is due to overactivation of the alternative complement pathway. aHUS has numerous causes, including drugs, with rare reports of carfilzomib, a proteasome inhibitor used in multiple myeloma, as causative agent. Cases vary in presentation, presenting a diagnostic challenge. Historically, TMAs were treated with plasma exchange. aHUS, however, is considered refractory to plasma exchange and best treated with eculizumab, a monoclonal antibody targeting C5, a terminal complement protein. We report a patient with history of multiple myeloma who presented with headaches, elevated blood pressure, petechiae, ecchymosis and haemolytic anaemia. His condition was determined to be carfilzomib-induced aHUS and he was successfully treated with eculizumab. Early detection and treatment of drug-induced aHUS is vital in reducing morbidity and mortality related to the condition.

scholarly journals Successful Subsequent Pregnancy in a Woman Receiving Eculizumab for Pregnancy-Associated Atypical Haemolytic Uraemic Syndrome

2019 ◽  
Vol 2019 ◽  
pp. 1-4 ◽  
Author(s):  
Samantha Bateman ◽  
Maleeka Ladhani ◽  
Shilpanjali Jesudason
Keyword(s):  
Renal Function ◽  
Haemolytic Uraemic Syndrome ◽  
Rescue Therapy ◽  
Significant Risk ◽  
First Trimester ◽  
Subsequent Pregnancy ◽  
Baby Girl ◽  
Successful Pregnancy ◽  
Atypical Haemolytic Uraemic Syndrome ◽  
History Of

Atypical haemolytic uraemic syndrome (aHUS) is a form of thrombotic microangiopathy precipitated by unopposed complement activation, the treatment of which has been revolutionised by the availability of the monoclonal anti-complement (C5) antibody, eculizumab. Historically, women with aHUS would be unable to achieve a successful pregnancy due to the severity of their renal disease and for the few who could conceive, recurrence of aHUS was a significant risk. In spite of this, parenthood remains a priority for many. Experience with eculizumab use in the management of aHUS during pregnancy is growing and with it comes a significant change in the course of the disease. We present the case of a 28-year-old woman diagnosed with severe aHUS in the first trimester of her first pregnancy. She received rescue therapy with eculizumab and had a return to normal renal function. While this pregnancy was lost, she strongly desired a family. We managed her through a subsequent pregnancy while receiving eculizumab. This pregnancy was uncomplicated and carried to term and she birthed a healthy 2500 g baby girl. The complexities of managing a pregnancy in a woman with a history of aHUS are vast but not insurmountable, as demonstrated by this case.

MO107CLINICAL CHARACTERISTICS OF A PATIENT POPULATION WITH ATYPICAL HAEMOLYTIC URAEMIC SYNDROME AND MALIGNANT HYPERTENSION: THE GLOBAL AHUS REGISTRY ANALYSIS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Jean-Michel Halimi ◽  
Imad Al-Dakkak ◽  
Katerina Anokhina ◽  
Gianluigi Ardissino ◽  
Christoph Licht ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Haemolytic Uraemic Syndrome ◽  
Clinical Characteristics ◽  
Organ Damage ◽  
Malignant Hypertension ◽  
Symptom Presentation ◽  
Pathogenic Variants ◽  
Atypical Haemolytic Uraemic Syndrome ◽  
Before And After ◽  
History Of

Abstract Background and Aims Atypical haemolytic uraemic syndrome (aHUS) is a rare disease that manifests as complement-mediated thrombotic microangiopathy (TMA), which can lead to severe organ damage. Some patients with aHUS may present with malignant hypertension (MHT); both conditions can result in TMA. The objective of this analysis was to characterise patients with aHUS and MHT. Method In this analysis, patients from the Global aHUS Registry (NCT01522183) were included if they were diagnosed with MHT and were followed ≥90 days after initial aHUS symptom presentation or diagnosis date; patients were excluded if they withdrew from the registry or discontinued treatment with eculizumab due to a diagnosis other than aHUS. Demographics and clinical characteristics were evaluated. Results Seventy-one of 1903 registry patients were included in the analysis. Clinical characteristics are presented in the table. Seventeen patients (24%) had a paediatric (<18 years) onset of disease, and 54 (76%) were adults at aHUS diagnosis; female patients were slightly overrepresented (61%). Sixty-nine percent of patients were reported to have MHT at around the same time as aHUS diagnosis (+/-2 months), while 11% and 13% experienced MHT before and after aHUS diagnosis, respectively. aHUS triggering conditions were reported in 6/71 patients (8%) (Table). Cardiovascular (27%) and gastrointestinal (21%) symptoms were the most commonly reported extra-renal manifestations. Eight patients (11%) had a reported family history of aHUS and 40 patients (56%) had a complement pathogenic variant or an anti-CFH-antibody. Thirty-three patients (46%) had a kidney transplant; of these, 20 were prescribed eculizumab in the peri- or post-transplant period. Conclusion In this analysis of patients with aHUS and MHT, the observed high prevalence of pathogenic variants in complement genes or anti-CFH antibodies, alongside the high proportion of patients with extrarenal manifestations and/or requiring kidney transplant, indicate a high severity of presentation and poor prognosis of aHUS associated with MHT.

scholarly journals Adalimumab as a potential cause of drug-induced thrombocytopaenic microangiopathy

2020 ◽  
Vol 13 (3) ◽  
pp. e233526 ◽  
Author(s):  
Lorenzo Falsetti ◽  
Mattia Sampaolesi ◽  
Francesca Riccomi ◽  
Cinzia Nitti
Keyword(s):  
Internal Medicine ◽  
Emergency Department ◽  
Shiga Toxin ◽  
Haemolytic Uraemic Syndrome ◽  
Laboratory Tests ◽  
Severe Diarrhoea ◽  
Drug Induced ◽  
Medicine Department ◽  
Atypical Haemolytic Uraemic Syndrome ◽  
Count Recovery

We report the case of a 63-year-old male patient admitted to our emergency department for dyspnoea, peripheral oedema, severe diarrhoea and asthenia. History revealed Crohn’s disease (CD) submitted to several intestinal surgical resections in the previous years. He recently started a treatment with adalimumab for the control of CD. Laboratory tests at the admission revealed severe haemolytic anaemia and thrombocytopaenia. Haptoglobin levels were low, schistocyte count was markedly increased. In the suspect of thrombotic microangiopathy, he was admitted to our internal medicine department where we urgently started plasma exchange (PEX). We observed normal ADAMTS-13 activity in absence of Shiga toxin or enterotoxic Escherichiacoli at stool tests. Despite a diagnosis of atypical haemolytic–uraemic syndrome, we observed full platelet count recovery and schistocytes normalisation after the fourth PEX. We then put a diagnosis of adalimumab-induced thrombocytopaenic microangiopathy. Adalimumab was withdrawn. We did not observe relapses in the following 3 months.

scholarly journals Pregnancy-associated atypical haemolytic uraemic syndrome in the postpartum period: a case report and review of the literature

2011 ◽  
Vol 4 (2) ◽  
pp. 83-85 ◽  
Author(s):  
M Egbor ◽  
A Johnson ◽  
F Harris ◽  
D Makanjoula ◽  
H Shehata
Keyword(s):  
Case Report ◽  
Medical History ◽  
Postpartum Period ◽  
Haemolytic Uraemic Syndrome ◽  
Review Of The Literature ◽  
Atypical Haemolytic Uraemic Syndrome ◽  
History Of ◽  
Previous Medical History

Pregnancy has been reported to be a trigger in about 10% of all patients with atypical haemolytic uraemic syndrome (aHUS). However, in contrast to pregnancy-associated thrombotic thrombocytopaenic purpura, the presentation of pregnancy-associated aHUS remains ill defined and can therefore be difficult to diagnose and manage appropriately. Here we report a case of pregnancy-associated relapse of aHUS in a patient with a previous medical history of aHUS prior to pregnancy.

scholarly journals Co-Amoxiclav Induced Immune Haemolytic Anaemia: A Case Report

2020 ◽  
Vol 2020 ◽  
pp. 1-3 ◽  
Author(s):  
H. G. C. S. Karunathilaka ◽  
D. P. Chandrasiri ◽  
P. Ranasinghe ◽  
V. Ratnamalala ◽  
A. H. N. Fernando
Keyword(s):  
Haemolytic Anaemia ◽  
Rare Complication ◽  
Coombs Test ◽  
Igg Antibodies ◽  
Probability Scale ◽  
Drug Induced ◽  
The Third ◽  
Immune Haemolytic Anaemia ◽  
History Of ◽  
Symptoms And Signs

Drug-induced immune haemolytic anaemia (DIIHA) is extremely rare. We herein report a case of DIIHA due to co-amoxiclav. A 53-year-old male being treated for left-sided pyelonephritis with intravenous co-amoxiclav developed symptoms and signs of anaemia on the third day of treatment. He was found to have evidence of haemolysis with a positive Coombs test and IgG antibodies and C3d. Co-amoxiclav was identified as the probable culprit, using the Naranjo adverse drug reaction probability scale. Upon discontinuation of the drug and blood transfusion, the patient’s haematological parameters stabilised. Steroids were not required in the treatment. Diagnosis of DIIHA is made through a history of intake of co-amoxiclav, clinical and laboratory features of haemolysis, and a positive Coombs test. An autoantibody screen is most commonly negative. It is essential for clinicians to be aware about this rare complication caused by commonly prescribed drugs and be able to accurately diagnose and initiate treatment.

scholarly journals Non-Secretory Multiple Myeloma with Patchy Marrow Involvement and Aberrant Cytokeratin Expression

2021 ◽  
Vol 34 (13) ◽  
Author(s):  
Miguel Silva ◽  
Joana Martins ◽  
João Pinto ◽  
Teresina Amaro
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Bone Marrow Aspiration ◽  
Normal Serum ◽  
Bone Lesions ◽  
Diagnostic Challenge ◽  
Serum Free Light Chain ◽  
Cytokeratin Expression ◽  
History Of ◽  
The Right

Non-secretory multiple myeloma is a rare form of the disease that presents a diagnostic challenge. A 69-year-old woman presented to the emergency department with a pathological fracture of the right clavicle, along with a history of asthenia and middle back pain in the preceding three months. Workup revealed multiple focal lytic bone lesions in the clavicles, ribs, skull and thoracic- lumbar-sacral spine, without evidence of anemia, hypercalcemia or renal failure, with no abnormal immunofixation in the serum or urine and with normal serum free light chain ratios. The Iliac crest bone marrow aspiration and biopsy revealed a scarcely involved marrow, However, biopsy of one of the focal bone lesions revealed a hypercellular bone marrow with phenotypically abnormal plasmocytes, along with an intriguing, albeit aberrant, cytokeratin expression. Non-secretory multiple myeloma is in itself a rare diagnosis. However, the combination of a patchy marrow involvement and aberrant cytokeratin expression makes this a noteworthy presentation.

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