A Case of Atypical Hemolytic Uremic Syndrome Successfully Treated with Eculizumab (original) (raw)
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Acta Scientific Medical Sciences, 2020
Atypical hemolytic uremic syndrome is a rare form of thrombotic microangiopathies resulting from various genetic mutations of the complement factors. Thrombotic microangiopathies include Thrombotic thrombocytopenic purpura, primary HUS further divided into typical HUS or Shiga-toxin related HUS, atypical HUS and secondary forms of HUS. The most common clinical features of the Hemolytic Uremic Syndrome are: kidney failure, thrombocytopenia resulting in hemorrhagic phenomena and also intravascular hemolytic anemia. Most commonly HUS is a diagnosis made from excluding all other plausible causes. HUS predominantly affects pediatric ages.
Nefrología, 2016
We present the case of a 23-year-old man with a 3-month history of headache, loss of vision, loss of appetite, and foamy urine. In the previous week, he had been bedridden, with sensory disturbances, oliguria, and dyspnoea. Upon initial assessment he appeared generally unwell, drowsy, disorientated, tachycardic, hypertensive, and tachypnoeic. He had asterixis, uraemic breath, jugular venous distension, breath sounds with bibasal rales, and oedema of lower limbs. Lab test on admission showed elevated nitrogen products, metabolic acidosis with a wide anion gap, evidence of non-immune microangiopathic haemolytic anaemia and thrombocytopenia (Table ). Further tests were requested, including ADAMTS13 activity, and infection and immune profiles, which were negative (Table ). Treatment was started with haemodialysis, parenteral labetalol, red cell transfusion, and plasma exchange. Once uraemia and hypertensive crisis were controlled, ophthalmological examination revealed a marked loss of visual acuity (RE: 20/400 + 1; LE: 20/150 -1) and hypertensive retinopathy. On day 7, haemolytic activity was controlled, which allowed discontinuation of plasma exchanges. However, the patient relapsed 48 h later, plasma exchanges were restarted and a definitive diagnosis was made of aHUS (Fig. ). Treatment with eculizumab was initiated, and plasma exchanges were stopped. The patient made adequate progress, with recovery of vision (20/30 in both eyes), however, dialysis had to be maintained. Genetic studies to detect complement mutations associated with aHUS were negative (Table ). At 9 month follow-up, the patient remained dialysisdependent; therefore, a diagnosis was made of end-stage renal disease (ESRD) secondary to aHUS, and the workup for renal transplantation was initiated. Atypical HUS is an extremely rare chronic genetic disease. It is caused by an abnormality in the regulation of complement and can lead to severe sequelae in multiple organs and even death. It is characterised by the triad of microangiopathic haemolytic anaemia, thrombocytopenia, and renal failure, though it can affect any organ. Our patient displayed renal, haematological, neurological, cardiovascular, and
Pediatric Nephrology, 2011
Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy associated with defective regulation of the alternative complement pathway. The prognosis for patients with aHUS is poor, and plasma exchange represents the first-line therapy. Eculizumab is a humanized monoclonal anti-C5 antibody that prevents the activation of the terminal complement pathway. Here, we report the case of a 9-year-old girl with frequent relapsing aHUS due to heterozygous factor H mutation who was initially treated with plasma exchange three times per week with 150% plasma exchange volume. This treatment frequently caused allergic reactions and school absences. Because any reduction in the frequency of plasma exchange immediately induced relapses of the aHUS, treatment with eculizumab, 600 mg every 2 weeks, was started and plasma exchange completely stopped. On this drug regimen the patient showed no evidence of disease activity during a period of more than 24 months. Renal function improved, proteinuria disappeared, the number of antihypertensive medications could be decreased, and the quality of life increased substantially. The inhibition of the terminal complement pathway by eculizumab was also confirmed by renal biopsy, which showed the absence of thrombotic microangiopathy 2 months after the initiation of eculizumab therapy. This case illustrates the long-term favorable outcome of aHUS with eculizumab treatment.
A complicated case of atypical hemolytic uremic syndrome with frequent relapses under eculizumab
Pediatric nephrology (Berlin, Germany), 2015
Atypical hemolytic uremic syndrome (aHUS) is a form of thrombotic microangiopathy characterized by uncontrolled activation of the alternative complement pathway with consecutive generation of the terminal complement complex. Mortality is increased, particularly in the first year of the disease. Therapeutic options include plasma therapy and terminal complement blockade using the anti-C5 monoclonal antibody eculizumab. Eculizumab prevents activation of the terminal sequence of the complement cascade and formation of the potentially lytic terminal complement complex (C5b-9). We report a 3-year-old boy with aHUS due to a novel heterozygous truncating complement Factor H mutation in combination with other changes known to be associated with an increased risk for aHUS. Despite eculizumab treatment and maximal suppression of the classical and alternative complement pathways, C3d and sC5b-9 remained consistently elevated and the patient showed repeated relapses. Not every patient with aHUS...
Hematology Reports
Atypical hemolytic uremic syndrome is a rare and progressive disease caused by uncontrolled alternative complement activation. Dysregulatıon of the complement activation results in thrombotic microangiopathy and multiorgan damage. A 29-yearold woman who was admitted with complaints of vomiting and headache was detected to have acute renal failure with microangiopathic hemolytic anemia (MAHA). After the diagnosis of atypical hemolytic uremic syndrome (aHUS), she was treated with plasma exchange (PE) and hemodialysis (HD). She has experienced hypertensionrelated posterior reversible encephalopathy syndrome (PRES) at the second plasma exchange. She was initiated on eculizumab therapy because of no response to PE on the 34th days. Her renal functions progressively improved with eculizumab treatment. Dependence on dialysis was over by the 4th month. Dialysis free-serum Creatinine level was 2.2 mg/dL [glomerular filtration rate (e-GFR): 30 mL/min/1.73 m2] after 24 months. Neurological inv...
Eculizumab Experince at a Patient With Atypical Hemolitic Uremic Syndrome
Kocaeli Medical Journal, 2018
Thrombotic microangiopathy discribes a specific pathologic lesion in which abnormalities in the vessel wall of arterioles and capillaries lead to microvascular thrombosis. Microangiopathic hemolytic anemia is a descriptive term for non-immun hemolytic anemia resulting from intravascular red blood cell fragmentation that produces schistocytes on the peripheral blood smear. Atypical hemolytic uremic syndrome is a type of primer thrombotic microangiopathy and using eculizumab in the early phase of therapy reduces the risk of irreversible renal damage. We mentioned both the importance of early diagnosis at the patients presenting with microangiopathic hemolytic anemia and thrombocytopenia like our patient and the benefit of eculizumab therapy at the early phase of atypical hemolytic uremic syndrome therapy.
American Journal of Kidney Diseases, 2013
Uncontrolled complement activation is central to the occurrence of atypical hemolytic uremic syndrome (aHUS) and can result in thrombotic microangiopathies (TMAs).These terms encompass a group of heterogenic inherited or acquired diseases that recent research suggests may be triggered by the complement cascade. Pathogenetic triggers of complement activation include immunologic disorders, genetics, infections, systemic diseases, pregnancy, drug administration, metabolic diseases, transplantation, or triggers of mixed cause. Hallmarks of aHUS and other TMAs include increased vascular endothelium thromboresistance, leukocyte adhesion to damaged endothelium, complement consumption, coagulation abnormalities, and vascular shear stress, whereas common end points of these mechanisms include hemolytic anemia, thrombocytopenia with microvascular infarction, and predisposition for decreased kidney function and other organ involvement. The central role of the complement cascade as a disease trigger suggests a possible therapeutic target. Eculizumab, a first-in-class humanized monoclonal anti-C5 antibody that has been successful in the treatment of paroxysmal nocturnal hemoglobinuria, a disorder of complement-induced hemolytic anemia, received approval for the treatment of aHUS in the United States and Europe in late 2011. We review the treatment of aHUS and other TMAs, focusing on the role of eculizumab, including its pharmacology, mechanism of action, and approved dosing recommendations and health economic considerations. Finally, the potential for future indications for eculizumab use in other complement-driven diseases is discussed. Am J Kidney Dis. xx(x):xxx.