Pernicious Anemia Associated Cobalamin Deficiency and Thrombotic Microangiopathy: Case Report and Review of the Literature

A 43-year-old Hispanic male without significant previous medical history was brought to emergency department for syncope following a blood draw to investigate a 40 lbs weight loss during the past 6 months associated with decreased appetite and progressive fatigue. The patient also reported a 1-month history of jaundice. On examination, he was hemodynamically stable and afebrile with pallor and diffuse jaundice but without skin rash or palpable purpura. Normal sensations and power in all extremities were evident on neurological exam. Presence of hemolytic anemia, schistocytosis, thrombocytopenia, and elevated lactate dehydrogenase (LDH) was suggestive of thrombotic thrombocytopenic purpura (TTP). However, presence of leukopenia, macrocytes, and an inadequate reticulocyte response to the degree of anemia served as initial clues to an alternative diagnosis. Two and one units of packed red blood cells were transfused on day 1 and day 3, respectively. In addition, one unit of platelets was transfused on day 2. Daily therapeutic plasma exchange (TPE) was initiated and continued until ADAMTS-13 result ruled out TTP. A low cobalamin (vitamin B12) level was evident at initial laboratory work-up and subsequent testing revealed positive intrinsic factor-blocking antibodies supporting a diagnosis of pernicious anemia with severe cobalamin deficiency. Hematological improvement was observed following vitamin B12 supplementation. The patient was discharged and markedly improved on day 9 with outpatient follow-up for cobalamin supplementation

The safety of intravenous iron sucrose use in the elderly patient

Background: This study was undertaken to assess the safety and tolerability of the use of intravenous (IV) iron sucrose in the therapy of iron-deficiency anemia in elderly, hemodialysis-dependent (HDD), chronic kidney disease (CKD) patients. Methods: This was a multicenter, open-label study in a large consecutive sample of 665 HDD-CKD patients (in 11 locations). Patients received IV iron sucrose therapy in treatment and maintenance dosing cycles over 10-week periods. There were 10 doses of 100 mg of iron sucrose in each drug cycle, and participants could receive multiple cycles of either or both regimens. Variables evaluated in the intent-to-treat population included adverse events (AEs), hemoglobin, and iron indices. Results: Of the 665 patients, 391 patients were under the age of 65 (younger adults) and 274 were 65 years of age or older (elder adults). Iron needs and erythropoietin dosing were similar in both the elder and younger adult patients. The incidence, severity, and nature of AEs and overall mortality were similar in both age groups. There were no drug-related deaths or drug-related serious AEs in either group. There were no hypersensitivity reactions or allergic reactions in either patient population, even among those with a prior history of intolerance to other parenteral-iron products. Comparison of the two age groups also revealed no differences in the efficacy of iron treatment as reflected by hemoglobin, transferrin saturation, and ferritin response. Conclusions: There is no apparent difference in the safety and efficacy of iron sucrose between elder and younger adults in the treatment of iron-deficiency anemia in HDD patients with CKD. © 2007, American Society of Consultant Pharmacists, Inc. All rights reserved

The safety and efficacy of ferumoxytol therapy in anemic chronic kidney disease patients

The safety and efficacy of ferumoxytol therapy in anemic chronic kidney disease patients.BackgroundAdministration of safe and effective iron therapy in patients with chronic kidney disease is a time consuming process. This phase II clinical trial studied ferumoxytol, a semi-synthetic carbohydrate-coated iron oxide administered by rapid intravenous injection to anemic chronic kidney disease patients (predialysis or undergoing peritoneal dialysis).MethodsInclusion criteria included hemoglobin ≤12.5 g/dL and transferrin saturation ≤35%. Twenty-one adult patients were randomized to receive ferumoxytol in a regimen of 4 doses of 255 mg iron in 2 weeks or 2 doses of 510 mg iron in 1 to 2 weeks. Ferumoxytol was administered at a rate of up to 30 mg iron/sec.ResultsThe maximum hemoglobin response following ferumoxytol administration occurred at 6 weeks, increasing from a baseline of 10.4 ± 1.3 g/dL to 11.4 ± 1.2 g/dL (P < 0.05). Ferritin increased from a baseline of 232 ± 216 ng/mL to a maximum of 931 ± 361 ng/mL at 2 weeks (P < 0.05), while the baseline transferrin saturation increased from 21 ± 10% to 37 ± 22% at 1 week (P < 0.05). Seven adverse events in 5 patients during this trial were deemed possibly related to ferumoxytol, none serious. These events included constipation, chills, tingling, a gastrointestinal viral syndrome, delayed pruritic erythematous rash, and transient pain at the injection site.ConclusionAlthough larger studies are required, this small study demonstrates that ferumoxytol can be safe and effective in increasing iron stores, is associated with an increased hemoglobin response, and is well tolerated at a rapid infusion rate

Introduction of Biosimilar Therapeutics Into Nephrology Practice in the United States: Report of a Scientific Workshop Sponsored by the National Kidney Foundation

Biosimilars are biologic medicines highly similar to the reference product with no meaningful clinical differences in terms of safety, purity, and potency. All biologic medicines are produced by living cells, resulting in an inherent heterogeneity in their higher order structures and post-translational modifications. In 2010, the US Congress enacted legislation to streamline the approval process for biosimilars of products losing patent protection, with the goal of decreasing costs and improving patient access to therapeutically important but expensive biologic agents. In 2015, the US Food and Drug Administration approved the first biosimilar agent through this pathway. Approval of additional biosimilar agents in the United States, including those used by nephrologists, is anticipated. Given the relative lack of knowledge regarding biosimilars and their approval process and a lack of trust by the nephrology community regarding their safety and efficacy, the National Kidney Foundation conducted a symposium, Introduction of Biosimilar Therapeutics Into Nephrology Practice in the U.S., September 17 to 18, 2015. Issues related to manufacturing, the regulatory approval process, interchangeability, substitution/switching, nomenclature, and clinician and patient awareness and acceptance were examined. This report summarizes the main discussions at the symposium, highlights several controversies, and makes recommendations related to public policy, professional and patient education, and research needs

Introduction of Biosimilar Therapeutics Into Nephrology Practice in the United States: Report of a Scientific Workshop Sponsored by the National Kidney Foundation.

Biosimilars are biologic medicines highly similar to the reference product with no meaningful clinical differences in terms of safety, purity, and potency. All biologic medicines are produced by living cells, resulting in an inherent heterogeneity in their higher order structures and post-translational modifications. In 2010, the US Congress enacted legislation to streamline the approval process for biosimilars of products losing patent protection, with the goal of decreasing costs and improving patient access to therapeutically important but expensive biologic agents. In 2015, the US Food and Drug Administration approved the first biosimilar agent through this pathway. Approval of additional biosimilar agents in the United States, including those used by nephrologists, is anticipated. Given the relative lack of knowledge regarding biosimilars and their approval process and a lack of trust by the nephrology community regarding their safety and efficacy, the National Kidney Foundation conducted a symposium, Introduction of Biosimilar Therapeutics Into Nephrology Practice in the U.S., September 17 to 18, 2015. Issues related to manufacturing, the regulatory approval process, interchangeability, substitution/switching, nomenclature, and clinician and patient awareness and acceptance were examined. This report summarizes the main discussions at the symposium, highlights several controversies, and makes recommendations related to public policy, professional and patient education, and research needs

Iron sucrose in hemodialysis patients: Safety of replacement and maintenance regimens

Background. Parenteral iron replacement and maintenance are frequently required in hemodialysis patients. However, serious adverse events have been reported after single doses of some intravenous iron products. This multicenter phase IV clinical trial examined the safety of iron sucrose for the treatment of iron deficiency and for the maintenance of iron sufficiency in hemodialysis patients. Methods. In this safety study, iron sucrose was given in two dosing regimens. Iron deficient patients were treated with intravenous iron sucrose, 100 mg, during 10 consecutive hemodialysis sessions (replacement regimen). Iron replete patients were given iron sucrose, 100 mg intravenous (iv) over 5 minutes, weekly for 10 weeks (maintenance regimen). At the end of each 10-dose cycle, iron status was reassessed, and dosing during the subsequent cycle was based on the adequacy of iron stores as per Dialysis Outcome Quality Initiative (K/DOQI) Guidelines. With each dosing regimen, adverse events, if any, were recorded and described. Results. Six hundred and sixty-five hemodialysis patients, including 80 who had experienced previous intolerance to other parenteral iron preparations, received a total of 8583 doses of iron sucrose. One hundred eighty-eight patients received more than one iv iron cycle (replacement, maintenance, or both). There were no serious or life-threatening drug-related adverse events. Conclusion. Iron sucrose is safe when given as treatment for iron deficiency or for maintenance of iron stores