Experience with artificial liver support in 16 living related liver transplant recipients.

This study was a retrospective investigation about the indication and efficacy of artifical liver support for liver transplant recipients. Apheresis was performed in 16 of 41 patients subjected to living related liver transplantation (LRLTx) as articial liver support, including plasmapheresis (PP) in 13 cases, continuous hemodiafiltration (CHDF) in 7 cases, and plasma adsorption (PA) in 2 cases. One patient with cryptogenic liver cirrhosis was subjected to PP before the LRLTx, and the result was satisfactory. On the contrary, the results of PP and CHDF for graft, respiratory, or cardiac failure were not acceptable. Only 1 patient survived despite multiple organ failure. Both PP and PA for patients with hyperbilirubinemia were effective and improved their critical conditions. We conclude that apheresis for liver transplant patients is effective to treat hyperbilirubinemia, but it is not indicated for respiratory and cardiac failure nor for hepatic failure.     

Use of cellular and plasma apheresis in the critically ill patient: Part II: Clinical indications and applications

Apheresis is the process of separating the blood and removing or manipulating a cellular or plasma component for therapeutic benefit. Such procedures may be indicated in the critical care setting as primary or adjunctive therapy for certain hematologic, neurologic, renal, and autoimmune/rheumatologic disorders. In part I of this series, the technical aspects of apheresis were described and the physiologic rationale and clinical considerations were discussed. This review highlights the pathophysiologic basis, specific clinical indications, and treatment parameters for disorders that more commonly require management in the intensive care unit. The choice of plasma or cellular apheresis in these cases is guided by well-accepted, evidence-based clinical treatment guidelines. For some disorders, such as liver failure, severe sepsis, and multiple-organ dysfunction syndrome, apheresis treatment approaches remain experimental. Ongoing studies are investigating the potential utility of conventional plasma exchange, ex vivo plasma manipulation, and newer technologies for these and other disorders in severely ill patients.     

Successful treatment of drug‐induced acute liver failure with high‐volume plasma exchange

We report two patients with drug‐induced liver injury (DILI)‐related acute liver failure (ALF) who were successfully treated with high‐volume plasma exchange without liver transplantation. The first patient was a 66‐year‐old man admitted because of a perforated duodenal ulcer complicated with peritonitis and septic shock. After treatment with multiple antibiotics, the patient developed DILI and ALF. Grade 3 hepatic encephalopathy and profound jaundice were present. Symptoms and signs of ALF improved dramatically after initiation of plasma exchange. The patient was discharged uneventfully. The second patient was a 94‐year‐old man admitted for treatment of newly diagnosed pulmonary tuberculosis. DILI and ALF developed 5 days after initiation of anti‐tuberculosis treatment. Grade 4 hepatic encephalopathy was present. After plasma exchange, the patient's level of consciousness improved dramatically, and he recovered from ALF. These 2 cases show the potential of plasma exchange in the treatment of DILI despite occurrence acute liver failure. J. Clin. Apheresis, 28:430–434, 2013. © 2013 Wiley Periodicals, Inc.     

Therapeutic plasma exchange for fulminant hepatic failure secondary to Wilson's disease

Wilson's disease (WD) is an autosomal‐recessive disorder of impaired copper metabolism resulting in accumulation of copper primarily in the liver but ultimately in many organs and tissues. A small number of patients with WD initially present with fulminant hepatic failure (FHF), hypercupremia, and intravascular hemolysis. The therapeutic goals for these patients include quickly removing the copper and preparing the patient for liver transplantation. Here, we report on a 6‐year‐old male with WD in FHF with anemia, renal insufficiency, and coagulopathy. The patient received a series of therapeutic plasma exchanges (TPE) as adjunctive therapy to remove copper and stabilize his coagulopathy and anemia until a transplant was possible. A total of five single plasma volume (1500 mL) TPE were performed over the course of 11 days with plasma as the replacement fluid. Laboratory results demonstrated temporary improvement after each procedure. Liver transplantation was performed 12 days after beginning TPE and 35 days after admission to the hospital. TPE was a successful adjunctive therapy to bridge this patient with WD to transplantation. J. Clin. Apheresis 27:282–286, 2012. © 2012 Wiley Periodicals, Inc.     

Emergency ABO‐incompatible liver transplant secondary to fulminant hepatic failure: Outcome,role of TPE and review of the literature

The increasing demand for solid organ transplants has brought to light the need to utilize organs in critical situations despite ABO‐incompatibility. However, these transplantations are complicated by pre‐existing ABO antibodies which may be potentially dangerous and makes the transplantation prone to failure due to rejection with resulting necrosis or intrahepatic biliary complications. We report the clinical outcome of an emergency ABO‐incompatible liver transplant (due to fulminant hepatic failure with sudden and rapidly deteriorating mental status) using a modified therapeutic plasma exchange (TPE) protocol. The recipient was O‐positive with an initial anti‐B titer of 64 and the cadaveric organ was from a B‐positive donor. The patient underwent initial TPE during the peri‐operative period, followed by a series of postoperative daily TPE, and later a third series of TPE for presumptive antibody‐mediated rejection. The latter two were performed in conjunction with the use of IVIg and rituximab. The recipient's anti‐B titer was reduced and maintained at 8 or less 8 months post‐op. However, an elevation of transaminases 3 months post‐transplant triggered a biopsy which was consistent with cellular rejection and with weak C4d positive staining suggestive of antibody mediated rejection. Additional plasma exchange procedures were performed. The patient improved rapidly after modification of her immunosuppression regimen and treatment with plasma exchange. This case illustrates that prompt and aggressive plasma exchange, in conjunction with immunosuppression, is a viable approach to prevent and treat antibody mediated transplant rejection in emergency ABO‐incompatible liver transplant. J. Clin. Apheresis, 2012. © 2012 Wiley Periodicals, Inc.     

Therapeutic hemapheresis practitioners need to know about the treatment of thrombotic thrombocytopenic purpura.

In the field of therapeutic apheresis, thrombotic thrombocytopenic purpura (TTP) makes up a large percentage of the conditions treated by plasma exchange. The implementation of plasma exchange in the treatment of TTP has been shown to reduce the mortality rate for this group of patients significantly. Apheresis operators see many patients with acute symptoms, the "chronic" syndrome of TTP, and those with a "relapsing" TTP. The apheresis practitioner is with the patient for several hours during each treatment, and thus becomes an element of continuity in the care and assessment of the TTP patient. Progress in understanding the pathophysiology of this condition necessitates the frequent review of literature published regarding TTP, and continuing education of staff and physicians.     

Outcomes of previously healthy pediatric patients with fulminant sepsis-induced multisystem organ failure receiving therapeutic plasma exchange

Background: Fulminant sepsis‐induced multisystem organ failure (MSOF) in pediatric patients carries substantial morbidity and mortality. Therapeutic plasma exchange (TPE) has been reported to be beneficial in sepsis‐induced MSOF. We evaluated the outcomes of previously healthy children with fulminant sepsis‐induced MSOF receiving TPE. Materials and Methods: Previously healthy pediatric ICU patients who underwent TPE for MSOF due to fulminant bacterial sepsis were retrospectively reviewed. Eleven patients (three females and eight males) with age ranging 8 months to 14 years were identified (eight meningococcemia and three other infections). All patients received daily TPE with fresh frozen plasma (FFP) as replacement fluid. Organ failure index (OFI—maximum score = 6) was assessed daily for 7 days. Results: A median of 4 TPE (1–14) were performed. Improvements in organ function and platelet count occurred in most patients with 2–4 TPE treatments. All 10 patients who were alive had reduced OFI to 2 by day 7 of initial TPE and were all fully recovered (survival rate = 10/11, 91%). The only death occurred in a patient who died the same day after his first TPE treatment, which was initiated 24 h after development of MSOF. The 10 survivors underwent early initiation of TPE (median 5.3 h) after the onset of MSOF. Conclusions: > TPE may contribute to a better outcome in previously healthy pediatric patients with fulminant sepsis‐induced MSOF, especially if instituted early in the course of multiorgan failure. J. Clin. Apheresis, 2011. © 2011 Wiley‐Liss, Inc.     

The technique of therapeutic apheresis. Removal of abnormal blood elements may succeed when all else fails

Therapeutic apheresis is a generic term that refers to removal of abnormal blood cells and plasma constituents. The terms "plasmapheresis," "leukapheresis," and "erythrocytapheresis" describe the specific blood element that is removed. Apheresis therapies can be performed in the ICU to manage a number of neurologic, hematologic, and autoimmune disorders, including myasthenia gravis, Guillain-Barré syndrome, sickle-cell disease, and Goodpasture's syndrome. Apheresis procedures generally require two points of contact with the circulation--one for blood withdrawal and one for return; the withdrawal site should sustain a flow rate of at least 50 mL/min. Although apheresis is generally quite safe, hemodynamic instability, hypocalcemia, and dilutional coagulopathy can occur.     

Living related liver transplantation for acute fulminant hepatitis B: experience from two possible hyper-acute cases

Fulminant hepatic failure, which is represented by fulminant hepatitis, is fatal in most cases unless prompt liver transplantation is performed. Even if liver transplantation is performed, irreversible neurological damage is often complicated. In this case report, we describe two cases of fulminant hepatitis induced by acute hepatitis B virus infection, both of which were successfully rescued by living related liver transplantation without significant complications. The case 1 was a 45-year-old Japanese male. He complained general malaise and anorexia. His local physician diagnosed him as acute hepatitis B, and referred to our hospital. Due to severe coagulopathy, plasma exchange was performed 3 times. However, his hepatic coma progressed rapidly along with rapid decrease of both his direct/indirect bilirubin (D/T) ratio and serum blood urea nitrogen (BUN) levels. Living related liver transplantation was performed under the diagnosis of acute fulminant hepatitis B. The case 2 was a 34-year-old Japanese male. His complaints were fever and skin rush. He was referred to our hospital under the diagnosis of acute hepatitis B. On the second day after admission, he developed grade II hepatic coma, which deteriorated into grade III in spite of intensive therapy including plasma exchange. He also demonstrated rapid decrease of both D/T ratio and serum BUN level. Living related liver transplantation was performed on the next day. Both cases recovered without any evidence of neurological sequelae. In general, it is extremely difficult to rescue fulminant hepatitis by conservative treatments, particularly in cases with rapid progression. Although emergency liver transplantation may be an only option to rescue in such a case, living related liver transplantation has an advantage in view of urgent organ donation over cadeveric transplantation.     

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.     

Apheresis therapy for living-donor liver transplantation: experience for apheresis use for living-donor liver transplantation at Kyoto University.

Liver transplantation is a fundamental treatment for patients with end-stage hepatic failure. In order to perform living-donor liver transplantations under safer conditions, apheresis plays a major role in Japan due to the prevalence of living-donor liver transplantation wherein later retransplantation is difficult. In our department, the roles of apheresis in liver transplantation are as follows: as bridge therapy to liver transplantation (n = 45); as a supplement to the graft liver until the recovery of hepatic function (n = 77); as treatment for multiple organ failure including posttransplantation renal failure (n = 15); and as a means with which to reduce antibody titers for antibodies such as anti-A or anti-B in persons with ABO blood type = incompatible liver transplantation (n = 23). In our department, we have performed 822 liver transplantations at present. Of those cases, 183 were selected wherein apheresis was performed around the time of the operation. In all cases, transplantation with sufficient apheresis was performed before the surgical operation, however, 22 patients (48.9%) died after undergoing surgery. Among the patients who underwent the postoperative apheresis, those in the nonsurvivor group had lower grafted liver weights compared to those of the survivor group. The kidney was the organ that most frequently failed due to postoperative complications. In cases of ABO blood type-incompatible liver transplantations, patients with high preoperative anti-A/B IgM antibody titers sustained bile duct complications, patients with high preoperative anti-IgG antibody titers sustained hepatic necrosis, and patients with high postoperative anti-A/B IgM and anti-IgG antibody titers sustained hepatic necrosis most frequently.     

Therapeutic plasmapheresis as a bridge to liver transplantation in fulminant Wilson disease

Wilson disease is an autosomal recessive disorder of copper metabolism that leads to the accumulation of copper mainly in the liver, cornea, brain, and kidney. Rarely, Wilson disease can present as fulminant hepatic failure with direct antiglobulin test-negative hemolytic anemia and renal failure. In the absence of liver transplantation, this disease is uniformly fatal because medical therapy is ineffective. This report describes the successful use of plasmapheresis for a patient with fulminant Wilson disease as a bridge to transplantation. Five daily therapeutic plasmapheresis procedures using fresh frozen plasma as a replacement fluid were performed over 6 days. Serum copper, urinary copper excretion, and hemolysis were significantly reduced and renal function improved. The patient's clinical status improved and she remained clinically stable until a liver transplant was possible. Plasmapheresis can be a successful medical treatment in fulminant Wilson disease and should be considered as a therapeutic measure to stabilize a patient by decreasing serum copper, reducing hemolysis, and helping to prevent renal tubular injury from copper and copper complexes until liver transplantation is possible.     

Fulminant liver failure associated with clarithromycin

OBJECTIVE: To report a patient developing fulminant liver failure while being treated with clarithromycin for pneumonia. CASE SUMMARY: A 58-year-old white woman developed fulminant liver failure while being treated with the macrolide antibiotic clarithromycin for pneumonia. Comedication included N-acetylcysteine, atenolol, and isradipine. Other causes of liver failure, such as viral hepatitis, autoimmune hepatitis, toxins, and heart failure, were excluded by appropriate diagnostic means. All drugs were stopped, and the patient was transferred to another hospital for liver transplantation. She recovered spontaneously within several days, making transplantation unnecessary. A liver biopsy obtained 10 days after the initial presentation revealed centroacinar necrosis and beginning fibrous reorganization, compatible with recent centroacinar damage. DISCUSSION: Since no other cause could be identified, liver injury was considered to be drug related. Fulminant liver failure has not previously been described with concomitant use of atenolol and N-acetylcysteine. Although isradipine has been associated with hepatocellular injury, there are no reports of fulminant liver failure with this agent, and our patient had been treated for >2 years without signs of toxicity. The most likely cause of liver failure in this patient was, therefore, clarithromycin, which undergoes hepatic metabolism and has been reported to cause fulminant hepatic failure. A second possibility is an interaction between clarithromycin and isradipine, potentially increasing the hepatic toxicity of isradipine. CONCLUSIONS: Clarithromycin may be a cause of fulminant liver failure either alone or by inhibiting the metabolism of other drugs.     

Effective removal of copper by plasma exchange in fulminant Wilson's disease

BACKGROUND: Patients who present with fulminant hepatic failure due to Wilson's disease may develop hemolytic anemia and renal insufficiency. In this entity, acute hepatocellular necrosis triggers the release of copper ions into the circulation, which leads to toxic effects on red cell metabolic pathways and hemolysis. STUDY DESIGN AND METHODS: The utility of therapeutic plasma exchange to rapidly remove copper and reduce toxic serum copper levels was studied in two patients with fulminant Wilson's disease. RESULTS: Intensive plasma exchange using fresh-frozen plasma replacement removed substantial amounts of copper from the hypercupremic patients, resulting in a rapid reduction in serum copper levels and decreased hemolysis. The net copper removal was proportional to the serum level, ranging from 7,000 to 11,800 micrograms per procedure in one patient and from 3,700 to 6,800 micrograms in the other. CONCLUSION: Plasma exchange allows a rapid reduction in elevated serum copper levels in patients with fulminant Wilson's disease. This leads to an amelioration of hemolytic anemia and provides clinical stabilization until liver transplantation can be performed.     

The Italian registry of pediatric therapeutic apheresis: A report on activity during 2005

The results of the 2005 Survey of the Italian Society for Apheresis and Cell Manipulation (SIdEM) reporting on the pediatric procedures carried out in 18 Italian Apheresis Units are presented here. Utilizing a standardized questionnaire, the survey collected data on techniques, types of blood separators, clinical indications, and adverse events. A total of 1,693 apheresis procedures were carried out in 355 pediatric patients: 219 plasma‐exchange, 291 peripheral blood stem cell collections, 791 extracorporeal photochemotherapy (ECP), 265 LDL‐apheresis, 71 erythro‐exchange, 9 cytoreductive apheresis, 47 immunoadsorption sessions. Adverse events were registered in 94 procedures (5.6%), most of which of mild entity, e.g., insufficient flow rate (50.0%) and symptomatic hypocalcemia (24.4%). Our data indicate that all types of apheresis procedures can be safely carried out in children. ECP, utilized primarily for the treatment of graft versus host disease (GvHD) and rejection of solid organ transplantation, are burgeoning procedures in pediatric patients, whereas plasma exchange, which is a common treatment in adults, is infrequently utilized in pediatric medicine. J. Clin. Apheresis, 2009. © 2008 Wiley‐Liss, Inc.     

A survey of blood purification techniques.

Apheresis may be performed with many different techniques. The basis for different therapeutic approaches lies in the pathophysiological processes present in the diseases that have to be treated. Over the years more sophisticated devices have been developed. The most frequent treatment is plasma exchange (plasmapheresis) using centrifugation or single filtration techniques. In addition cascade filtration and subsequent adsorption from plasma is done. Thereby removal is done by adsorption of molecules such as bilirubin, immunoglobulins (immunoadsorption), circulating immune complexes, various antibodies including those against blood types. Such adsorption technologies have also been developed to allow adsorption directly from a column perfused by whole blood (hemoperfusion). By combining various techniques, systems are available that allow bridging of patients with hepatic failure to transplantation (MARS, Prometheus). By adding e.g., hepatic cells to such systems, besides dialysis and adsorption, cells will help to degrade toxic molecules. Such bioreactors are in clinical use. Apheresis includes also the removal or retrieval of cells from blood for e.g., stemcell transplantation, polycythaemia or hemochromatosis. Removal of leukocytes from blood using leukocyte filters is indicated in inflammatory bowel diseases. By specifically irradiating lymphocytes and monocytes with UV light using the technique of extra corporeal photochemotherapy (ECTP) various immunological diseases are treated. On the other hand, various alternative techniques may be used for the same disorder. Thus for patients with high plasma LDL-cholesterol not responding to other lipid lowering strategic treatment, alternative therapy may be done either by cascade filtration, adsorption technology from plasma, heparin precipitation (HELP-system) or hemoperfusion. This article describes various techniques in clinical use.     

Therapeutic apheresis in Asia: An Indonesia single center experience

In developing countries, like Indonesia, apheresis is still a relative new procedure. Nowadays, therapeutic apheresis procedures are performed in the field of hematology and neurology, especially in the teaching hospitals in Indonesia. Therapeutic apheresis procedure, that is, leukocytapheresis, therapeutic plasma exchange (TPE), and thrombocytapheresis are already performed. In the period 2009–2013, 204 apheresis procedures in 137 patients to reduce the leukocytes, 72 TPE procedures in 17 patients, and 14 thrombocyte reductions were performed in the Sardjito hospital, Yogyakarta, Indonesia. In the future, to improve the therapeutic apheresis implementation, it is important to increase the insurance coverage and also should be considered to introduce the apheresis medicine into the curriculum of appropriate physician programs in Indonesia. Especially in Indonesia, a lot of efforts are still being needed to improve implementation of therapeutic apheresis. J. Clin. Apheresis 30:139–140, 2015. © 2014 Wiley Periodicals, Inc.     

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.     

Continuous hemofiltration/hemodiafiltration in critical care.

Continuous hemofiltration and continuous hemodiafiltration (CHF/CHDF) were developed as continuous renal replacement therapy for patients with severe conditons and has come to be widely performed mainly in critical care, taking the place of intermittent hemodialysis. The membrane pore size of a hemofilter used for CHF/CHDF allows passage of substances ranging from 30,000 to 50,000 Da, and the method for solute removal in CHF/CHDF employs the principle of convection, which is advantageous for removing middle- to high-molecular-weight substances. As apheresis therapy to remove pathogenic substances in blood, CHF/CHDF is therefore being investigated for its possible effect on various morbid conditions. It has recently been found that CHF/CHDF removes humoral mediators including cytokines, particularly in severe systemic inflammatory response syndromes such as septic shock and severe acute pancreatitis. CHF/CHDF is thus beginning to be performed for the prevention and treatment of organ dysfunction secondary to septic shock, trauma, or acute pancreatitis. CHF/CHDF is also efficacious as artificial liver support in preventing adverse effects caused by plasma exchange (PE) and for continuous removal of hepatic coma-inducing substances. CHF/CHDF is effective for various morbid conditions not only as renal replacement therapy, but also as apheresis therapy and is expected to be applied more widely in critical care in the future.     

Using the World Apheresis Association Registry Helps to Improve the Treatment Quality of Therapeutic Apheresis

Therapeutic apheresis (TA) is prescribed to patients that suffer from a severe progressive disease that is not sufficiently treated by conventional medications. A way to gain more knowledge about this treatment is usually by the local analysis of data. However, the use of large quality assessment registries enables analyses of even rare findings. Here, we report some of the recent data from the World Apheresis Association (WAA) registry. Data from >104,000 procedures were documented, and TA was performed on >15,000 patients. The main indication for TA was the collection of autologous stem cells (45% of patients) as part of therapy for therapy. Collection of stem cells from donors for allogeneic transplantation was performed in 11% of patients. Patients with indications such as neurological diseases underwent plasma exchange (28%). Extracorporeal photochemotherapy, lipid apheresis, and antibody removal were other indications. Side effects recorded in the registry have decreased significantly over the years, with approximately only 10/10,000 procedures being interrupted for medical reasons.ConclusionCollection of data from TA procedures within a multinational and multicenter concept facilitates the improvement of treatment by enabling the analysis of and feedback on indications, procedures, effects, and side effects.