Can therapeutic plasma exchange be life-saving in life-threatening manganese intoxication?

We present a pediatric patient presenting with life-threatening severe neurological signs, chronic liver disease, and manganese intoxication who fully recovered from neurological signs and symptoms following chelation therapy and therapeutic plasma exchange (TPE). A 13-year-old female patient was admitted with abdominal pain. Loss of consciousness and decorticate posture (GCS;M:1,V:1,M:3) developed at the 5th hour of admission. She admitted to the intensive care unit intubated. No infectious etiology that could explain acute encephalopathy was detected. Abdominal ultrasound showed granular, heterogeneous liver parenchyma suggesting chronic hepatic disease, and TPE was administered for two days since Wilson's disease and autoimmune encephalitis could not be ruled out. Cranial MRI findings were consistent with a diagnosis of manganese intoxication. On Day 3 after admission, chelation therapy and TPE were administered based on a diagnosis of manganese intoxication. Blood manganese levels at admission, day 2, and day 5 were 46, 22, and 17.5 µg/dL (NR:4.7-18.3). Control MRI results showed reduced intracranial manganese deposition, and the patient regained full consciousness. TPE as an adjunct to chelation therapy may represent an effective therapeutic option in manganese intoxication.

Early therapeutic plasma exchange may improve treatment outcomes in severe acute toxic Hepatitis.

BACKGROUND AND OBJECTIVES: Acute toxic hepatitis can result in a different clinical course from a completely curable disease to subacute hepatitis, chronic hepatitis, and fulminant hepatitis failure, which is quite mortal. For this purpose, therapeutic plasma exchange (TPE) can be used for improving treatment outcomes by reducing the harmful substances caused with and/or without liver function in acute toxic hepatitis. We aimed to evaluate treatment outcomes in severe acute toxic hepatitis patients who applied early TPE procedure. MATERIALS AND METHODS: A total of 335 patients who received TPE between 2010-2021 were retrospectively screened and 59 (male/female, 30/29; min/max-age, 22-84) patients with acute toxic hepatitis who underwent TPE in the first 24 h were included in the study. TPE was performed in patients who had high total bilirubin level (>10 mg/dL). Laboratory parameters of the patients before and after the TPE procedure, number of patients developed complications of acute toxic hepatitis and mortality rates were evaluated for effectiveness of TPE. RESULTS: Acute toxic hepatitis was associated with hepatotoxic drugs in 44 (74.5 %), herbal medication 6 (10.2 %), mushroom poisoning 6 (10.2 %) and with substance abuse 3 (5.1 %) in patients. When the patients were compared based on INR, liver function tests, ammonia, lactate and Model For End-Stage Liver Disease (MELD) score at baseline, 48 h after TPE (independently of TPE number) and before final state a statistically significant decrease was observed in all parameters (p < 0.05). Fifty three (90 %) of patients improved without complications, the remaining 6 (10 %) patients were diagnosed with fulminant hepatitis. All these remaining patients died before liver transplantation (LTx) could be performed. CONCLUSION: TPE is a safe, tolerable therapy option and early TPE may improve treatment outcomes in severe acute toxic hepatitis.

Therapeutic plasma exchange in non-immune hemolytic anemia associated with henna ingestion: A case report.

Henna is a herb that is used in traditional medicine for medical purposes as well as in the field of cosmetic. It is one of the agents that can trigger hemolytic crisis in G6PD deficient patients but it is considered safe in patients with normal G6PD enzyme. Here we present a case of non-immune hemolytic anemia occurred after ingestion of a homemade solution containing henna powder. Therapeutic plasma exchange was performed daily for 3 subsequent days and the hemoglobin levels and hemolytic markers were improved dramatically. Laboratory test revealed a normal G6PD enzyme level six weeks after recovery. We would like to emphasize the possibility of unexpected adverse effects and undefined ingredients of herbal products. Therapeutic plasma exchange can be a promising treatment option in such cases.

A case of acute optic neuritis during pregnancy treated by membrane-based therapeutic plasma exchanges without systemic anticoagulation.

INTRODUCTION: In acute optic neuritis, high dose steroid therapy as first - line treatment is contraindicated in early pregnancy, therapeutic plasma exchanges (TPE) represent an alternative. We report a case of a pregnant woman with progressive, acute optic neuritis subjected to membrane-based therapeutic plasma exchange with extracorporal citrate-based anticoagulation. CASE PRESENTATION: A 35 year-old second-time pregnant woman (4th week of gravidity) of Caucasian ethnicity complained of visual impairment of the right eye. She was hospitalized for suspected optic neuritis. In the eye exam central and peripheral scotoma of the right side were found. T2 weighted Magnetic-Resonance Imaging revealed an isolated, prechiasmal lesion of the right optic nerve, and the patient had a delayed p100 latency of visually evoked potentials of the right eye. Cerebrospinal-fluid investigation was unrevealing. The diagnosis of right sided optic neuritis was established. Due to early pregnancy, steroids were contraindicated. Visual disturbances further deteriorated by day 2 in hospital. For therapy, 5 sessions of membrane-based therapeutic plasma exchange with albumin solution were performed. An extracorporal anticoagulation using citrate with calcium substitution was applied. After the second session, there was a subjective improvement of symptoms. At discharge on day 14, visual acuity was no longer impaired, sensitivity to bright light remained. In eye exam at 3.5 months after discharge, the patient ha d a complete recovery. Follow-up gynecological exams were unrevealing. CONCLUSION: This case of unilateral acute optic neuritis supports the view that membrane-based therpautic plasma exchange without systemic anticoagulation represents a safe intervention in pregnancy.

Massive bee envenomation treated by therapeutic plasma exchange.

In the unfortunate event of massive envenomation and precipitation of multiorgan failure, therapeutic plasma exchange (TPE) can be considered as a modality for therapy. We present a patient case where TPE potentially allowed for removal of toxin with subsequent clinical improvement.

Double filtration plasmapheresis - 10-year pediatric experience as an alternative to plasma exchange.

BACKGROUND: Double filtration plasmapheresis (DFPP) is more selective at removing antibodies compared to plasma exchange (PE), thus reducing the need for replacement blood products. METHODS: We retrospectively analyzed the records of all pediatric patients whom DFPP had been performed. RESULTS: In total, 30 patients were treated with DFPP. Data were available for 436 sessions in 23 patients. Patients had a median of 6 (1-161) sessions. Age at start of treatment was 13.9 years (2.2-19.2) and weight 46 kg (13.4-82.8). Six patients were treated for antibody mediated rejection; 1 had full recovery, 1 CKD stage 4 and 4 required dialysis. Two patients were treated for recurrence of focal segmental glomerulosclerosis (FSGS) with good response. One successfully had an ABO-incompatible kidney transplantation. Five had anti-glomerular basement membrane disease; 3 had complete recovery, 1 CKD and 1 required transplantation. Three had granulomatosis with polyangiitis; 1 with full recovery, 1 had CKD and 1 required dialysis. Two had Type-2 Membrano-proliferative glomerulonephritis, 1 successfully treated, the other needing dialysis. One treated for rapidly progressive MPO-glomerulonephritis required dialysis. Other indications were Myasthenia Gravis, Guillain-Barré disease and autoimmune limbic encephalitis. Excluding FSGS patients (with >100 sessions), one patient had cryoprecipitate, 2 had blood transfusions, no other blood products were required. Minor complications were seen in 13 sessions (8.4%). No major complications were seen. CONCLUSION: DFPP is a safe, well tolerated form of apheresis that appears to have comparable outcomes to that of PE, without the routine need of replacement blood products.

Fructus Psoraleae-Induced Severe Liver Injury and Treatment With Two Artificial Liver Support Systems: A Case Series Study.

To describe the clinical features and outcomes of patients with suspected Fructus Psoraleae (FP)-induced severe liver injury who underwent treatment with two artificial liver support systems (ALSSs). The cases of 12 patients with severe liver injury by FP were enrolled. We evaluated the tolerability of, and changes in biochemical parameters after treatment with plasma exchange combined with hemofiltration and double plasma molecular absorption system, and 6-month follow-up information were collected. The median age of the 12 patients was 60 years and nine (75%) patients were females. All patients had jaundice as the initial symptom. Two ALSS types were used to treat the patients. The group that underwent plasma exchange combined with hemofiltration showed remarkable improvements in ALT, AST, total bilirubin (TB), GGT and international normalized ratio levels (AST, TB, international normalized ratio, P < 0.01; ALT, GGT, P < 0.05), and the levels of AST, ALP, TB, and total bile acid decreased significantly in the double plasma molecular absorption system group after treatment (TB, P < 0.01; AST, ALP, total bile acid P < 0.05). During 6 months of follow-up, two patients died, two became chronic, and eight recovered to normal. FP can cause clinically severe liver injury, characterized by gastrointestinal symptoms and jaundice, which can lead to death or become chronic. Both ALSSs were safe and well tolerated in drug-induced liver injury patients. After ALSS treatment, the levels of biochemical indicators of liver function improved significantly, indicating that ALSS might be beneficial for patients with severe drug-induced liver injury.

Role of therapeutic plasma exchange in acute liver failure due to yellow phosphorus poisoning.

BACKGROUND: Therapeutic plasma exchange (TPE) has been utilized in various liver disorders. There is limited data on the efficacy of TPE in patients with acute liver failure (ALF). METHODS: Study group consisted of patients who underwent TPE for ALF due to yellow phosphorous poisoning (YPP) between 2015 and 2019. Demographic data and biochemical parameters were recorded before and after TPE. Overall survival and transplant-free survival (based on King's College Hospital Criteria [KCHC]) were analyzed. RESULTS: Forty-three patients underwent TPE for ALF due to YPP. Most of them were young males. Overall survival was 34 (79.06%). In our study population, 20 patients fulfilled KCHC (Group A) and 23 did not fulfill KCHC (Group B). Both the groups showed significant improvement in alanine aminotransferase, aspartate aminotransferase, and international normalized ratio (INR) after TPE (p < 0.05). In Group B, there was significant improvement in ammonia after TPE (p < 0.05) and all 23 patients (100%) survived after TPE. In Group A, 4 underwent liver transplantation (LT), 7 survived without LT, and the remaining 9 died without LT. Mean survival after completing TPE was 41.2 ± 44.5 days in Group A and 90 days in Group B. This difference was statistically significant (p = 0.001). There was statistically significant difference in post-TPE values of INR (p = 0.012) and ammonia (p = 0.011) between non-survivors and survivors. Adverse events such as hypotension (11.62%) and minor allergic reaction (4.65%) were managed conservatively. CONCLUSION: TPE is an effective procedure in ALF due to YPP, not fulfilling KCHC for LT. In KCHC fulfilled group, though it shows LT-free survival benefit, there is requirement of prospective, large volume, multi-center study to assess its efficacy.

Utilization of therapeutic plasma exchange for hyperbilirubinemia in a premature newborn on extracorporeal membrane oxygenation.

BACKGROUND: We report a case of a premature newborn girl with a hospital course complicated by suspected respiratory syncytial virus pneumonitis for which she was placed on veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Despite phototherapy, her total bilirubin steadily increased to a peak of 50.4 mg/dL with concern for bilirubin-induced neurologic dysfunction, kernicterus. STUDY DESIGN AND METHODS: Therapeutic plasma exchange (TPE) was achieved via connection with the VA-ECMO circuit. Our institution's standard apheresis procedural parameters were adjusted to account for the small body weight and thus the low blood volume of the neonate while on ECMO. These included calculating the total blood volume to include the patient as well as the ECMO circuit, priming of the apheresis instrument with packed red blood cells to limit the extracorporeal volume, using a lower inlet flow rate, the connection setup of the inlet and return line, and monitoring of ionized calcium and anticoagulation throughout the procedure. RESULTS: A total of three TPE procedures were performed over three consecutive days. This resulted in improvement and stabilization of the patient's bilirubin. CONCLUSION: This case emphasizes that TPE is feasible on a neonate with a suboptimal body weight and thus a low blood volume due to the increased blood volume provided while on ECMO. In the absence of ECMO, whole blood manual exchange transfusion is recommended as TPE would be unsafe due to significant extracorporeal volume that would occur during TPE in a pediatric patient with low body weight.

Plasma Exchange Can Be an Alternative Therapeutic Modality for Severe Cytokine Release Syndrome after Chimeric Antigen Receptor-T Cell Infusion: A Case Report.

BACKGROUND: Tumor immunotherapy with chimeric antigen receptor-T cells (CAR-T) is a promising new treatment for B-cell malignancies and has produced exciting results. However, cytokine release syndrome (CRS) is the most significant toxicity associated with this treatment and can be life-threatening. CASE PRESENTATION: A 23-year-old male patient had been diagnosed with relapsed and refractory B-cell acute lymphocytic leukemia. The patient was recruited into our CAR-T clinical trial, and 1 × 106/kg of engineered anti-CD19 CAR-T cells was administered. After infusion of CAR-T cells (day 0), the patient underwent a typical CRS reaction, with increases in fever, muscle soreness, and inflammatory cytokines. He was treated with antiallergic and antipyretic drugs, glucocorticoids, and tocilizumab (4 mg/kg, days 3 and 5). However, CRS was not under control, and his condition rapidly deteriorated. He was transferred to the intensive care unit, where dexamethasone 10 mg q6h was administered, and plasma exchange was performed, with 3,000 mL of plasma replaced by fresh frozen plasma per day for 3 consecutive days. His symptoms gradually improved, and the CRS-related symptoms were relieved. Additionally, a bone marrow smear showed no lymphoblast cells, and minimal residual disease was negative on day 28. The patient was eventually discharged in a normal condition. CONCLUSIONS: CRS is caused by an exaggerated systemic immune response, potentially resulting in organ damage that can be fatal. Although therapeutic plasma exchange is not included in CRS management guidelines, this case shows that plasma exchange is feasible in at least some patients with severe CRS.

Ayurveda metallic-mineral 'Bhasma'-associated severe liver injury.

Ayurveda Bhasma is a metallic-mineral preparation homogenised with herbal juices or decoctions and modified with heat treatment to apparently detoxify the heavy metals. It is widely recommended for the treatment of many disease conditions by practitioners of complementary and alternative medicine in the absence of good quality clinical trial evidence on its safety and efficacy. Heavy metal-induced liver injury is widely reported in the literature, and heavy metal adulteration of non-Bhasma-related Ayurveda and herbal products has been well described. We report a patient who developed severe liver injury requiring listing for liver transplantation for improved survival, after consumption of Bhasma for dyspepsia. This case describes the first documented case and toxicology analysis of Ayurveda Bhasma associated with severe drug-induced liver injury. Physicians must be alert regarding patient's use of supposedly safe Ayurveda Bhasma that may promote acute severe liver injury in the absence of other known aetiologies.

Therapeutic Plasma Exchange for Urgent Rivaroxaban Reversal.

Direct oral anticoagulants, which include the factor Xa inhibitor rivaroxaban, have some advantages over vitamin K antagonists in regard to stroke prevention in patients with atrial fibrillation. However, no antidotes to reverse the effect of oral anticoagulants are commercially available, which can complicate treating patients in whom reversal is urgent. We faced this challenge in a kidney transplant candidate, a 65-year-old man with end-stage renal disease who had been taking rivaroxaban for paroxysmal atrial fibrillation. When a deceased-donor kidney became available, we needed to rapidly reduce the patient's bleeding risk, while minimizing the cold ischemic time of the donor kidney. Therefore, we decided to take an experimental approach and perform therapeutic plasma exchange. The patient's plasma anti-factor Xa level decreased from 0.4 IU/mL immediately before treatment to 0.21 IU/mL afterward, indicating that rivaroxaban had been actively removed from circulation. Waste fluid showed significant anti-Xa activity, indicating that the risk of rebound anticoagulation had been mitigated. The patient subsequently underwent successful kidney transplantation. To our knowledge, this is the first report of therapeutic plasma exchange to reverse the effects of rivaroxaban in a patient undergoing urgent surgery. This treatment may also be suitable for patients who have life-threatening, large-volume bleeding, especially in the presence of substantial kidney or liver dysfunction.

Importance of Regular and Maintenance Therapy Adherence in Neuromyelitis Optica (NMO): Lessons from a Repeating Relapse Case.

BACKGROUND Neuromyelitis optica (NMO) is a rare demyelinating disease of the central nervous system; NMO predominantly affects the spinal cord and optic nerves. The diagnosis is based on history, clinical presentation, seropositive NMO-IgG antibody, and notably, exclusion of other diseases. Despite the absence of definitive therapeutic strategies for NMO, methylprednisolone pulse therapy and plasma exchange are used for acute phase treatment, while immunosuppressive agent(s) are recommended to prevent relapses and improve prognosis. Here, we report a repeating relapse NMO case due to lack of regular and maintenance therapy. CASE REPORT A 58-year-old female with chronic NMO presented with a three-day history of new-onset right leg weakness and pain. The patient was diagnosed with NMO three years ago and presented with her fourth attacks. During her initial diagnosis, she was initiated on steroids. One year later, she developed the first relapse and was treated with steroids and rituximab, leading to 1.5-year remission. After the second relapse, steroids and rituximab was still given as maintenance therapy, but was not followed. Thus, the third relapse occurred in five months. During this hospitalization, she received initially high-dose solumedrol (1 g daily for five days) in addition to gabapentin 100 mg (gradually increased to 300 mg) three times a day for muscle spasms. Due to worsening of paresthesia and hemiparesis, it was decided to place her on plasma exchange treatment. After two plasma exchanges, the patient's condition was improved and she regained strength in her lower extremity. She completed five more cycles of plasma exchange, and was then discharged on steroid therapy (prednisone 20 mg daily for 10 days then taper) as maintenance therapy and with follow-up in neurology clinic. CONCLUSIONS Over the span of three years, the patient has had three relapses since her NMO diagnosis where her symptoms have worsened. Steroid therapy alone seemed not insufficient in managing her more recent relapses. Nonadherence to NMO treatment likely increased her risk for recurrence, thus regular and long-term maintenance therapy is imperative to delay the progression and prevent relapse in NMO.

Treatment of severe leptospirosis with therapeutic plasma exchange in a pediatric patient.

Ekinci F, Yildizdas RD, Horoz ÖÖ, Alabaz D, Tolunay I, Petmezci E. Treatment of severe leptospirosis with therapeutic plasma exchange in a pediatric patient. Turk J Pediatr 2018; 60: 566-570. Leptospirosis is a common zoonotic disease caused by spirochetes of the genus Leptospira. Although it is mostly a tropical disease, some case reports have been published from temperate regions of the world. The disease presents with a wide spectrum; from asymptomatic self limited disease to a fatal illness characterized by multi-organ involvement. An 8-year-old girl presented with a 5-day history of fever, myalgia, fatigue, vomiting and diarrhea. She developed anuria, hypotension and became unconscious one day after admission and was referred to our pediatric intensive care unit for further evaluation and treatment. Initial physical examination revealed fever, jaundice, diffuse petecchiae on whole body, hepatomegaly and severe hypotension. Laboratory investigations showed elevated liver enzymes and bilirubin levels, elevated creatinine and creatine kinase levels and trombocytopenia. The diagnosis of Leptospirosis was detected by rapid IgM test and confirmed by microscopic agglutination test later. She was treated with mechanical ventilation, wide spectrum antibiotics, positive inotropic agents and penicillin G plus two days of continuous renal replacement therapy and five sessions of therapeutic plasma exchange performed daily. She recovered completely and was transferred to the pediatric ward on the 14th day of hospitalization. The exact role of therapeutic plasma exchange has not been well documented yet, it seems to have benefical effects on clinical and laboratory findings and survival as we observed in our patient and learned from experiences in adult patients presented as case reports.

[Apheresis Techniques]. / Tecniche di Aferesi.

Apheresis therapies play an important role in the treatment of many pathologies, both as first-line and rescue therapies after drug failure or drug toxicity and, furthermore, when it is important to reach a therapeutic goal in a short time. Apheresis devices have evolved at an astounding rate over the last decades. Therapeutic apheresis are usually part of a treatment plan, so, a patient-centered approach to select the most appropriate treatment for each patient, balancing personal preferences, medication interferences and technological availability can significantly influence the choice of the protocol to be used. But, if the wide diversity of apheresis treatments may offer a tailored-patient approach, it can also create concerns on the right decision about the most appropriate protocol. Therapeutic apheresis - whose purpose is to cure diseases due to abnormality of blood cells or to toxicity of plasma substances - and, productive apheresis - whose purpose is to produce autologous or allogeneic therapeutic hemocomponents - are widely known as plasma-treatments and cytapheresis. The elementary techniques in apheresis are well represented by three physical separation methods of blood components: 1. differential centrifugation; 2. membrane filtration; 3. adsorption of proteins or cells, from whole blood or from plasma already separated. Starting from these three processes, several apheretic techniques have been developed to ensure, in expert hands, excellent therapeutic efficacy together with a low profile of adverse events.

Pro: High dose of therapeutic plasma exchange-mind the gap!

'Mind the gap' is a recorded warning phrase used in the London Tube since 1969. The following article is meant to be a warning of an increasing knowing-doing gap in routine practice of therapeutic plasma exchange (TPE), a treatment method that is used more and more throughout the world. The American Society of Apheresis recommendations, including the most recent ones from 2016, suggest using a TPE volume of 1.0-1.5 times the actual calculated plasma volume of the patient. There are only a few exceptions to that rule, such as the recommnded exchange volume in vasculitis or mushroom poisoning. The published literature suggests that in routine clinical practice in many institutions in several countries the exchanged volume might in fact be lower than recommended by the guidelines. In the following article we argue for a high dose of exchanged plasma volume, yet sketch different scenarios on how this time-averaged high dose can be delivered in various ways depending on the underlying disease, refuting a one-size-fits-all strategy that might facilitate the procedure but may result in 'underpheresis' in many patients. Further, the objectives underlying the use of smaller exchange volumes, especially the gap between the cost of blood products and the reimbursement of TPE are discussed. Lastly, the knowing-guiding gap is described, which can only be overcome by collecting high-quality data and conducting prospective clinical trials in the field of TPE.

A new prescription model for regional citrate anticoagulation in therapeutic plasma exchanges.

BACKGROUND: Regional citrate anticoagulation (RCA) is proposed for various extracorporeal purification techniques to overcome the risk of bleeding that might result from systemic anticoagulation. Yet, no individualized treatment protocol has been proposed for therapeutic plasma exchange (TPE) so far. The objective of this study was to assess the determinants of blood citrate concentration needed and to develop an individualized RCA protocol useful for clinical practice. METHODS: The study population included 14 patients who underwent a total of 47 TPE sessions. Citrate was infused pre-plasmafilter. Post-plasmafilter and systemic plasma ionized calcium concentrations were measured at standardized time intervals. An algorithm was proposed for the supplementation of calcium. During the discovery phase, citrate was infused at a fixed starting rate, and adapted accordingly to obtained post-plasmafilter ionized calcium levels. Using a mathematical approach, an algorithm was thereafter developed for individualized prescriptions of citrate. RESULTS: Pre-treatment values of hematocrit and plasma ionized calcium were the main determinants of the required rate of citrate infusion. These can be integrated into a final equation enabling to individualize the prescription. A prefilter ionized calcium concentration between 0.24 and 0.33 mmol/l prevented coagulation of the extracorporeal circuit. Significant hypocalcemia occurred in 8.5% of treatments. There were no significant acid-base disturbances. CONCLUSION: We propose a new protocol, which enables for the first time to individualize the prescription of regional citrate anticoagulation during TPE, in an efficient manner. The immediately obtained regional anticoagulation protects against both the risk of coagulation of the membrane and the exposure to an excess of citrate.

Therapeutic plasma exchange performed in tandem with hemodialysis without supplemental calcium in the apheresis circuit.

Therapeutic plasma exchange (TPE) and hemopoietic progenitor cell (HPC) collection are apheresis procedures that can safely be performed in tandem with hemodialysis. Despite the return of citrate-anticoagulated blood to the patient during HPC collection, it is not necessary to administer supplemental calcium during these procedures because the ionized calcium concentration is restored as the returning blood passes through the dialyzer. It is not known whether this applies to TPE, in which a mixture of blood and pharmaceutical albumin, an avid binder of plasma ionized calcium, is returned to the patient through the dialyzer. We report on three dialysis-dependent patients who required TPE and underwent tandem treatments without supplemental calcium in the apheresis circuit. Overall, ionized calcium fell 4-12% (P = 0.0.024) and patients reported no symptoms of hypocalcemic toxicity. Tandem hemodialysis/TPE can be performed without supplemental calcium in the apheresis circuit. J. Clin. Apheresis 32:154-157, 2017. © 2016 Wiley Periodicals, Inc.

Is aceruloplasminemia treatable? Combining iron chelation and fresh-frozen plasma treatment.

We report the case of a patient with hereditary ceruloplasmin deficiency due to a novel gene mutation in ceruloplasmin gene (CP), treated with fresh frozen plasma (FFP) and iron chelation therapy. A 59-year-old man with a past history of diabetes was admitted to our department due to progressive gait difficulties and cognitive impairment. Neurological examination revealed a moderate cognitive decline, with mild extrapyramidal symptoms, ataxia, and myoclonus. Brain T2-weighted MR imaging showed bilateral basal ganglia hypointensity with diffuse iron deposition. Increased serum ferritin, low serum copper concentration, undetectable ceruloplasmin, and normal urinary copper excretion were found. The genetic analysis of the CP (OMIM #604290) reported compound heterozygosity for two mutations, namely c.848G > A and c.2689_2690delCT. Treatment with FFP (500 mL i.v./once a week) and administration of iron chelator (Deferoxamine 1000 mg i.v/die for 5 days, followed by Deferiprone 500 mg/die per os) were undertaken. At the 6-month follow-up, clinical improvement of gait instability, trunk ataxia, and myoclonus was observed; brain MRI scan showed no further progression of basal ganglia T2 hypointensity. This case report suggests that the early initiation of combined treatment with FFP and iron chelation may be useful to reduce the accumulation of iron in the central nervous system and to improve the neurological symptoms.

Does therapeutic plasma exchange have a role in the treatment of prosthetic hip-associated cobalt toxicity? A case report and literature review.

BACKGROUND: Prosthetic hip-associated cobalt toxicity (PHACT) is an uncommon, but potentially devastating, complication for patients with metal-on-metal hip implants (MoMs). Clinical management of PHACT is poorly defined, with primary intervention being MoM explant followed by chelation therapy. Therapeutic plasma exchange (TPE) in cobalt toxicity has not been previously described. Given that cobalt is predominantly albumin bound, it should theoretically be removed by TPE. Here we report a case of PHACT and our experience using TPE to lower plasma cobalt levels. CASE REPORT: A 61-year-old woman developed deafness, blindness, ambulatory dysfunction, and endocrinopathies after MoM implant. Cobalt levels on admission were greater than 1500 µg/L. In an attempt to rapidly lower cobalt levels before MoM explant, hemodialysis and TPE were performed. Hemodialysis removed negligible amounts of cobalt. One session of TPE temporarily removed approximately two-thirds of measurable cobalt, but levels rebounded to pre-TPE values after 8 hours. It was only after MoM removal that cobalt levels plateaued below 300 µg/L and clinical symptoms improved. DISCUSSION: TPE removed cobalt from a PHACT patient, but a durable decrease in cobalt was only achieved after MoM explant. These findings are comparable to reports where chelation was employed in PHACT patients before MoM explant. The observed rebound phenomenon is likely from rapid equilibration between the immense extravascular tissue source (the MoM) and the intravascular compartment. CONCLUSION: TPE may serve as adjunctive therapy for PHACT patients whose cobalt levels remain high after explant, especially in patients with renal failure, in whom chelation is contraindicated.