Clinical improvement of a patient with severe Wilson's disease after a single session of therapeutic plasma exchange

Here, we report a case of a 17‐year old female with Wilson's disease presenting with progressive Coombs' negative hemolytic anemia and hepatic cirrhosis who was treated with one session of therapeutic plasma exchange (TPE) and clinically improved. In clinical situations where multiple sessions of TPE may not be possible, the use of a single session of TPE in conjunction with conventional therapy may be of benefit in preventing further clinical deterioration. J. Clin. Apheresis, 2009. © 2009 Wiley‐Liss, Inc.     

Alternating therapeutic plasma exchange (TPE) with double plasma molecular adsorption system (DPMAS) for the treatment of fulminant hepatic failure (FHF)

Alternating therapeutic plasma exchange with double plasma molecular adsorption system can rapidly remove bilirubin and ammonia and supplement the essential substance from the blood, which could be used as an effective treatment for fulminant hepatic failure.     

Biochemical testing for the diagnosis of Wilson's disease: A systematic review

BackgroundWilson''s disease (WD) is a rare inherited disorder that leads to copper accumulation in the liver, brain, and other organs. WD is prevalent worldwide, with an occurrence of 1 per 30,000 live births. Currently, there is no gold standard diagnostic test for WD. The objective of this systematic review is to determine the diagnostic accuracy for WD of three biochemical tests, namely hepatic copper, 24‐hour urinary copper, and ceruloplasmin using the Leipzig criteria.MethodsAdhering to PRISMA guidelines, databases including PubMed/MEDLINE, CINAHL Plus, Web of Science, and Cochrane were searched. Studies that comprised of confirmed or suspected WD along with normal populations were included with adult and pediatric group. The sensitivity, specificity, negative predictive value and positive predictive value were computed using RevMan 5.4.ResultsNine studies were included. The best practice evidence for 24‐hour urinary copper test ranged from a cutoff value of 0.64–1.6 μmol/24 h (N = 268; sensitivity = 75.6%, specificity = 98.3%). Hepatic copper test was optimally cutoff based on the ROC curve analysis at 1.2 μmol/g yielding a power of 96.4% sensitivity and 95.4% specificity (N = 1,150); however, the tried and tested 4 μmol/g cutoff, with 99.4% sensitivity and 96.1% specificity, is more widely accepted. The ceruloplasmin test cutoff value was found to be ranging from 0.14 to 0.2 g/L (N = 4,281; sensitivity = 77.1%–99%, specificity = 55.9%–82.8%).ConclusionThis paper provides a large‐scale analysis of current evidence pertaining to the biochemical diagnosis of WD employing the Leipzig criteria. The laboratory values are typically based on specific subgroups based on age, ethnicity, and clinical subgroups. The findings of this systematic review must be used with caution, given the over‐ or under‐estimation of the index tests.     

血浆置换治疗32例肝衰竭患者的临床效果

目的探讨血浆置换治疗肝衰竭患者的临床效果。方法收集32例肝衰竭患者,在综合治疗的基础上,采用血浆置换技术对其进行治疗。分别于治疗前、后检测患者临床生化指标:天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、清蛋白(ALB)、总胆红素(TBil)、直接胆红素(DBil)、凝血酶原时间(PT)、肌酐(Cr)、国际标准化比率(INR)、总胆汁酸(TBA)。结果本组患者血浆置换治疗总有效率为78.13%。早期肝衰竭患者有效率94.73%,中期肝衰竭患者有效率70.00%,晚期肝衰竭患者全部无效死亡。生化指标AST、ALT、ALB、TBil、DBil、PT、Cr、INR、TBA治疗后较治疗前均有明显改善(P<0.05)。结论血浆置换治疗肝衰竭患者效果较好,越早治疗效果越好。     

人工肝血浆置换术在药物性肝功能衰竭患者中的应用

目的 探讨药物性肝功能衰竭患者行人工肝血浆置换术治疗后的临床效果,并观察相关并发症的护理防治措施.方法 采用回顾性的研究方法,收集2012年7月至2015年7月在本院感染内科住院的100例药物性肝功能衰竭患者的临床资料,所有患者在给予常规方法治疗的基础上(如降酶、退黄、护肝等),进一步给予人工肝血浆置换术治疗.观察患者治疗前、治疗后的凝血功能、肝功能相关指标的动态改变及自觉症状(如纳差、恶心、腹痛等)的改变状况,并进一步归纳患者行人工肝血浆置换术后相关的并发症,探讨并发症出现的因素和相关护理防治方法.结果 大部分患者行人工肝血浆置换术治疗后,纳差、恶心、腹痛等不适症状明显减轻,生命体征较之前明显改善;人工肝治疗后患者的血清丙氨酸氨基转移酶、总胆红素明显降低,与治疗前比较,差异有统计学意义(P<0.05);治疗后,患者的血清白蛋白、凝血功能明显增高,与治疗前比较,差异有统计学意义(P<0.05);治疗后,相关并发症的出现率分别是:对血浆过敏11例(11%)、血压降低5例(5%)、插管处出血2例(2%).结论 药物性肝功能衰竭患者采用人工肝血浆置换术治疗,能显著改善患者的肝功能,大大提高了药物性肝功能衰竭患者的救治成功率,值得临床推广应用.     

Fibronectin replacement in patients with fulminant hepatic failure

Patients with fulminant hepatic failure have low levels of the plasma opsonizing protein fibronectin together with cardiovascular disturbances similar to those in septic shock where microembolization of capillary beds by particulate debris has been proposed to lead to multi-organ failure. Six patients with fulminant hepatic failure received a bolus injection of a concentrated fibronectin-rich preparation. The mean plasma immunoreactive fibronectin level increased from 53 +/- SE 12 micrograms ml-1 initially to 295 +/- 30 micrograms ml-1 (P less than 0.001) at 1 h after fibronectin administration. The in vitro plasma opsonic activity was also increased from 5.6 +/- 3.6% of control to 102 +/- 13% (P less than 0.005) at 1 h. No similar effect was observed with the clearance of microaggregated albumin, but as its clearance is probably not dependent on fibronectin it may reflect a different aspect of reticuloendothelial cell function. No significant changes were observed in cardiopulmonary function or oxygen utilization and it is possible this is because clearance of opsonized particles is limited by damage to Kupffer cells.     

Recent progress in the treatment of fulminant hepatic failure in Japan

Orthotopic liver transplantation is regarded as the only reliable treatment of fulminant hepatic failure in Western countries. The majority of hepatologists in Japan agree with this opinion. Liver transplantation is, however, only a symptomatic treatment of liver failure. The cause of fulminant hepatic failure is not taken into consideration in the decision of whether to proceed with liver transplantation. The term “fulminant hepatitis,” often used instead of “fulminant hepatic failure” in Japan, implies that the underlying liver disease is hepatitis in nature. Therefore, patients with fulminant hepatitis should be treated not only for the symptoms of liver failure, but for the underlying hepatitis as well. Such treatment includes antivirals and immunosuppressants for fulminant viral hepatitis, and immunosuppressants for fulminant autoimmune and drug-induced hepatitis. Using these treatment strategies, we have obtained a survival rate of 23/31 (74.1%) for the past 3.5 years in patients with fulminant hepatitis. We are currently attempting to cure all cases of severe hepatitis by predicting fulminant hepatitis and starting the treatment of hepatitis before the onset of coma.     

Fulminant hepatic failure associated with propylthiouracil: a case report with treatment emphasis on the use of plasmapheresis

Propylthiouracil is a commonly used medication for hyperthyroidism. Though propylthiouracil-induced hepatotoxicity is a rarely encountered problem, death due to fulminant hepatic failure may occur. In the English literature, only 34 cases have been described with severe hepatotoxicity secondary to this drug. Here we report a case of fulminant hepatic failure due to propylthiouracil and review the issues of treatment and management with special emphasis on the use of plasmapheresis in such situations.     

Extracorporal liver support with molecular adsorbents recirculating system in patients with hepatitis B-associated fulminant hepatic failure

Hepatitis B virus (HBV) infection is the most prevalent cause of fulminant hepatic failure (FHF) in the Far East. HBV-associated FHF is characterised by rapidly progressive end organ dysfunction/failure and a very poor prognosis. To investigate how molecular adsorbent recirculating system (MARS) treatment impacts multiple organ system function in HBV-associated FHF. Ten consecutive patients were treated with MARS in a period of 12 months. Clinical, biochemical and haemodynamic parameters were assessed before and after MARS. Various disease severity scoring systems including model for end-stage liver disease, APACHE II, APACHE III, sequential organ failure assessment and organ system failure scores were also assessed. There were significant improvements in hepatic encephalopathy grading (p < 0.001), mean arterial pressure (p < 0.001), plasma renin activity (p = 0.027), bilirubin (p < 0.001), ammonia (p = 0.001) and creatinine levels (p < 0.001). There were also significant improvements in all the scoring systems evaluated. Meanwhile, platelet count was significantly decreased (p < 0.001). One patient was successfully bridged to liver transplantation. Three patients were alive at 3 months of follow-up. MARS can improve multiple organ functions in HBV-associated FHF. On the basis of these findings, randomised controlled studies are indicated and justified.     

Serum octopamine, coma, and charcoal haemoperfusion in fulminant hepatic failure

Serum octopamine levels were significantly higher in twenty patients with fulminant hepatic failure (FHF) during the first 48 h of grade IV coma than in health control subjects (3.38 +/- 0.20 ng/ml and 1.75 +/- 0.19 ng/ml respectively, P less than 0.001). Serial measurements in five patients who died without regaining consciousness showed serum octopamine to remain raised, and concentrations in the cerebrospinal fluid at death reflected serum levels. In five patients who regained consciousness, improvement in encephalopathy was associated with a significant reduction in serum octopamine. Renal failure in patients with FHF was found to contribute to raised serum octopamine but could not alone account for the observed levels. Patients given neomycin therapy did not have significantly lower serum octopamine levels than an untreated group. There was, however, a significant correlation between elevated serum octopamine and the occurrence of gestrointestinal bleeding during the previous 24 h. Charcoal haemoperfusion did not appreciably reduce serum octopamine levels.     

Therapeutic plasma exchange a potential strategy for patients with advanced heart failure

Background: Previous reports had emphasized the importance of humoral immunity in heart failure in humans, primarily determined by the presence of circulating antibodies. However, there is little or no information about the frequency of anticardiac antibodies present in failing human myocardium. Methods: Clinical data and myocardial tissue samples were analyzed to determine the role of humoral immunity in patients with chronic heart failure (CHF) in different settings. Results: Anticardiac antibodies were found present in failing hearts but not in normal control hearts. Further, the level of expression of these anticardiac antibodies changed with the severity of the disease state; and in patients with acute heart failure, we found selective activation of B cells. Finally, treatment of CHF patients with therapeutic plasma exchange, a strategy that removes circulating antibodies, resulted in a reduction in anticardiac antibody deposition and improvements in cardiac function. Conclusion: These data collectively suggest a role of humoral immunity in the progression of heart failure. J. Clin. Apheresis, 2010. © 2010 Wiley‐Liss, Inc.     

Therapeutic plasma exchange for acute inflammatory demyelinating syndromes of the central nervous system

Idiopathic inflammatory demyelinating diseases (IIDDs) of the central nervous system, of which multiple sclerosis is the prototype, represent a family of monophasic, recurrent or progressive diseases with overlapping clinical and pathological manifestations. While most patients recover spontaneously or following a brief course of high-dose corticosteroids, occasional patients, particularly those with fulminant severe IIDDs, such as the Marburg variant, do not respond to corticosteroids and have severe, residual neurological deficits. While it is widely believed that IIDDs are mediated by T lymphocytes, as is experimental allergic encephelomyelitis, additional, possibly humoral, factors may be essential to generate the extensive demyelination seen in these conditions. Anecdotal reports over the past two decades have suggested that patients with acute, severe neurological deficits resulting from IIDDs, who fail to improve after high-dose intravenous corticosteroids, may benefit from plasma exchange. A randomized, sham-controlled, crossover study has recently been completed at the Mayo Clinic, which addresses these observations. J. Clin. Apheresis 14:144–148, 1999. © 1999 Wiley-Liss, Inc.     

Detrimental effects of nitric oxide inhibition on hepatic encephalopathy in rats with thioacetamide-induced fulminant hepatic failure

Hepatic encephalopathy is a complex neuropsychiatric syndrome seen secondary to acute liver failure, chronic parenchymal liver disease, or portal-systemic anastomosis. Vasodilatation induced by nitric oxide (NO) may be involved in the development of hepatic coma. However, there are no comprehensive data concerning the effects of NO inhibition on the severity of hepatic encephalopathy. Male Sprague-Dawley rats weighing 300-350 g were used. Fulminant hepatic failure was induced by intraperitoneal injection of thioacetamide (TAA, 350 mg kg-1 day-1) for 3 days. Rats were divided into two groups to receive either NG-nitro-L-arginine methyl ester (L-NAME, 20 mg kg-1 day-1 via intragastric gavage) or normal saline (N/S) from 2 days prior to TAA administration for 5 days. Severity of encephalopathy was assessed by counts of motor activity and neurobehaviour test scores. Plasma levels of endotoxin, tumour necrosis factor-alpha and nitrate/nitrite were determined by the chromogenic Limulus assay, enzyme-linked immunosorbent assay and colorimetric assay, respectively. Compared with N/S-treated rats, the mortality rate was significantly higher in rats receiving L-NAME (59% vs. 18%, P < 0.01). Inhibition of NO had detrimental effects on the counts of motor activities (P < 0.05) and neurobehaviour score (P < 0.01). Rats treated with L-NAME had significantly higher plasma levels of endotoxin (26.7 +/- 3.8 pg mL-1) and tumour necrosis factor-alpha (29.4 +/- 6.5 pg mL-1) compared with rats treated with N/S (13.2 +/- 2.7 pg mL-1 and 11.2 +/- 2.6 pg mL-1, respectively, P < 0.01). Plasma levels of endotoxin and tumour necrosis factor-alpha, but not of nitrate/nitrite, were significantly correlated with the severity of hepatic encephalopathy (P < 0.05). Chronic L-NAME administration had detrimental effects on the severity of encephalopathy in TAA-treated rats, suggesting a protective role of NO in the development of fulminant hepatic failure.     

Therapeutic plasma exchange for hyperviscosity syndrome secondary to high rheumatoid factor

Hyperviscosity syndrome (HVS) is most commonly associated with Waldenstrom’s macroglobulinemia, where it may be life-threatening. HVS may also occur in autoimmune diseases; data pertaining to efficacy of therapeutic plasma exchange (TPE) in HVS arising in non-malignant gammopathy are limited. We report a case of 71-year-old female with erosive rheumatoid arthritis with profoundly elevated rheumatoid factor (57,400 IU/ml; normal <35) who presented with findings consistent with HVS: profound weakness, headache, epistaxis and plasma viscosity (8.5 centipoise). She was successfully treated with pulsed high-dose steroids and TPE. Her symptoms of HVS have not recurred and the plasma viscosity has remained less than 3 centipoise. Given a slow onset of non-specific symptoms, HVS may be missed, incurring high risk of adverse effect. In symptomatic patients with high RF activity, a high index of suspicion for HVS is necessary to ensure timely identification and treatment with TPE, a safe and effective therapy.     

Therapeutic plasma exchange in antisynthetase syndrome with severe interstitial lung disease

Antisynthetase syndrome (ASS) is a rare condition characterized by interstitial lung disease (ILD), inflammatory myositis, fever, Raynaud phenomenon, mechanic's hand, and inflammatory polyarthritis in the setting of antibodies to amino acyl‐transfer RNA synthetases, with anti‐Jo‐1 antibody being the most common. Prognosis is very poor especially when there is associated ILD. To date, there is no standardized treatment for ILD associated ASS. Therapy is based on the use of steroids alone or in combination with other immunosuppressive agents, especially in severe or refractory cases. The role of therapeutic plasma exchange (TPE) in the management of this rare condition has not been established. Here, we report a case of severe ILD associated ASS in a 41‐year‐old woman who did not show clinical or laboratory response after six doses of high dose steroids and a dose of IV cyclophosphamide. Because of the aggressive nature of her disease and poor prognostic indices present, a decision was made to add TPE to her treatment. She underwent five sessions of TPE. At the end of the 5th session, the anti‐Jo‐1 antibody levels dropped to 3.6 AI (antibody index) and her creatinine kinase (CK) level from 875 to 399 U L^?1 (Units per liter) with overall improvement in her respiratory status. This case suggests TPE may be a promising treatment option in patients with ILD associated ASS refractory to steroids and other immunosuppressive therapy, particularly those with severe disease. J. Clin. Apheresis 30:375–379, 2015. © 2015 Wiley Periodicals, Inc.