Therapeutic Apheresis and Dialysis

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Direct adsorption of lipoproteins (DALI) apheresis is the first method for direct adsorption of lipoproteins from whole blood and is therefore an easy and rapid procedure. The majority of patients reaches >60% acute low-density lipoprotein cholesterol (LDL-C) reduction using either the DALI 750 or 1000 configuration. However, in patients with extremely high LDL-C levels or very large blood volumes, these configurations may lead to suboptimal results. The current study was performed to test the safety and efficacy of DALI 1250. In a severely obese patient (185 cm, 133 kg, blood volume 7.2 L, LDL-C 239 mg/dl), 11 L of blood (1.53-fold patient blood volume) was processed at a flow rate of 80 ml/min in 2.5 h; a combined heparin-plus-citrate anticoagulation regimen was used. Commercially available DALI 1250 and DALI hardware and disposables were manufactured by Fresenius HemoCare Adsorber Technology, St. Wendel, Germany. Twenty weekly sessions were performed. Clinically and technically, the apheresis sessions were completely uneventful. As compared to DALI 1000 (n = 4 sessions), the reduction rates by DALI 1250 (n = 20) improved for LDL-C (from 52% to 66%), lipoprotein (a) (Lp[a]) (53% vs. 66%), and fibrinogen (11% vs. 16%). There was a slight increase in high-density lipoprotein cholesterol (HDL-C) loss (20% vs. 24%). Moreover, the absolute amount of LDL-C removed per session increased from 5.06 g to 5.94 g. Laboratory safety parameters remained within the normal range, the anticoagulation was well controlled, and the pressure gradients over the adsorber remained constant. In this case report, DALI 1250 was perfectly safe and significantly increased the efficacy of LDL-C and Lp(a) elimination compared to standard DALI. Thus, this high-efficiency version of DALI may be used in patients with extremely high LDL-C levels and/or large blood volumes.
 
There has been a remarkable change in the scenario of therapeutic apheresis in the last 14 years in India. The crude method of manual removal of blood followed by separation of plasma by gravity, keeping it in the bottle for a long time, has now been totally replaced by plasmapheresis, centrifugation, membrane filtration, and immunoadsorption techniques. The indications for use have also changed from a list of limited indications in the beginning to include all immune complex disorders. The clinical beneficiaries have also increased from blood bankers to nephrologists and immunologists in addition to oncologists. Efforts are now underway with the help of the Indian Society for Apheresis (founded in 1985) to popularize the newer methods of cryofiltration, photopheresis and heparin extracorporeal low-density lipoprotein (HELP) and DALI apheresis systems besides the specialized techniques of immunoadsorption using filters, columns, or ligands. This is suggestive of a positive trend for the treatment of immune complex disorders.
 
Membrane differential filtration (MDF) (1,2) is a variety of cascade filtration. Three patients with primary hyperlipoproteinemia and coronary heart disease (2 patients with foregoing myocardial infarction) were treated with MDF for a period of 14 years. The mean treatment interval was 21 days. The basic level of low-density lipoprotein (LDL) cholesterol was about 450 mg/dl, and the level on LDL apheresis with comedication of statins was 180 to 200 mg/dl before treatment. Atherosclerosis progressed slowly during this period, and myocardial infarctions were avoided. However, in all 3 patients angiologic interventions became necessary. MDF is a well tolerated method that can be conducted without allergic hazards. The clinical results compare with those of other apheretic techniques.
 
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.
 
A patient with Bickerstaff's brain stem encephalitis (BBE) associated with anti-GQ1b antibody developed coma, severe weakness, and respiratory distress. The patient required ventilatory support. After having failed to improve on steroids, she was treated with plasmapheresis. She improved concomitantly with the plasmapheresis treatment and made a complete recovery. BBE associated with anti-GQ1b antibody is generally considered to be benign, and specific treatments have not been established. The results with this patient suggest that the condition is not always benign, and plasmapheresis may be beneficial in this disorder.
 
The developments in apheresis technologies and techniques and their clinical applications worldwide are technologically, sociologically, and economically driven. In the past, apheresis survey statistics have highlighted both the differences by geographical region in clinical practices and in the types of technologies utilized. While a national view of apheresis is critically important, an international view of apheresis may be more representative overall of this therapeutic modality than national results that are highly dependent on the local economics and the available technologies. These regional differences have provided a basis for the scientific and clinical assessments of these apheresis technologies and their clinical outcomes and have impacted the marketing and business developments of new technologies worldwide. The results of the International Apheresis Registry for 2000 reporting on 39 centers on 4 continents are presented. This survey collected data on 1,080 patients for a total of 15,257 treatments. Information gathered included patient demographics, medical history, treatment diagnoses, treatment specifics (type, methodology, access type, anticoagulants, drugs, equipment usage), side effects, clinical response, and payment provider. As in the prior International Apheresis Registry for 1983, the survey results highlighted the regional differences in apheresis usage and treatment specifics, indicating that an international overview of apheresis may be more representative of the impact of this therapeutic modality.
 
Amanita phalloides poisoning is the most common cause of lethal mushroom poisoning (lethality >20% in adults). A specific antidote against the amanitin toxins is not available. This retrospective study reports results in 21 patients (12 males, 9 females; ages 9-59 years) treated for amanita phalloides poisoning between 1984 and 1993. Plasmapheresis was carried out using a commercial plasma protein solution (Biseko, Biotest, Dreieich, Germany) in 17 patients, fresh plasma in 2 patients, and human albumin/Ringer's solution in 2 patients. Ancillary drugs, including penicillin and silibinin, also were used for detoxification, correction of blood-clotting deficiencies, and hepatic protection. One patient died of acute hepatic failure. The results, assessed using mortality (4.8% overall) and frequency of complications, indicate that plasmapheresis is a safe and effective treatment for amanita phalloides poisoning but that further investigations are needed, especially involving measurements of efficacy and the efficiency of toxin removal.
 
The aim of this study was to evaluate the in vitro activation in platelet suspensions collected with CS 3000 Plus and Cobe Spectra cell separators using platelet storage containers and the role of white blood cell (WBC) concentration of the suspension in this activation. Seventy-seven donors were subjected to automated platelet donations with 1 type of equipment (37 with Cobe Spectra and 40 with CS 3000 Plus). Blood samples were obtained immediately after separation and on the third day of storage at 22 degrees C in constant agitation. The WBC concentrations of these samples were studied before storage. Paraformaldehyde-fixed platelets were incubated with 2 murine monoclonal antibodies: CD42b and CD62. Murine monoclonal antibody immunoglobulin G was used as a negative isotypic control. Bound antibody was then quantitated by flow cytometry. On the third day of storage, a significant increase in CD62 expression rate was observed in platelet suspensions collected with both kinds of equipment. Mean expression rates for Cobe Spectra on Day 0 and Day 3 were 25.6 +/- 6.2% and 69.2 +/- 9.7%, respectively. Mean expression rates for CS 3000 Plus on Day 0 and Day 3 were 23.4 +/- 8.2% and 67.0 +/- 8.2%, respectively. The mean results for both devices were 22.8 +/- 4.56% for Day 0 and 68.7 +/- 13.2% for Day 3. There was no difference between CD42b mean fluorescence intensity on Days 0 and 3 for the 2 devices (p > 0.5). Mean WBC concentrations in the platelet suspensions for Cobe Spectra and CS 3000 Plus were 0.37 x 10(3)/microl and 0.42 x 10(3)/microl, respectively, and there was no relation between WBC concentration and increase in CD62 expression. Both kinds of equipment were found to be similar according to in vitro activation markers.
 
Because of a shortage of cadaver donors in Japan, ABO-incompatible living kidney transplantation has been carried out. Sixty-seven ABO-incompatible living kidney transplantations (LKT) were performed between January 1989 and December 1995 at our institution. In our previous report on the long-term results of ABO-incompatible LKT, graft survival of ABO-incompatible LKT up to 3 years was significantly lower than that of ABO-compatible LKT, but no significant difference was seen from 4 to 8 years. We removed anti-A/B antibodies by immunoadsorption and/or double filtration plasmapheresis before kidney transplantation. There was a significant difference between the anti-A/B antibody titers before and after plasmapheresis. The anti-A/B antibody titers also were well suppressed over the long term after transplantation.
 
Aregeneratoric anemia (AA) occurs rarely after ABO-incompatible allogeneic peripheral blood stem cell transplantation (alloPBSCT), and its management is generally difficult. Here, we present a 31-year-old white man with myelodysplastic syndrome who developed AA after receiving stem cells from his human leukocyte antigen (HLA) identical, but ABO-incompatible sibling. Because his anti-A antibody titers were high, therapy with conventional doses of erythropoietin and prednisolone failed to treat the AA. Following 8 cycles of plasma exchange and higher doses of erythropoietin and prednisolone as well as danazol administration, anti-A titers decreased, and his anemia improved significantly. In conclusion, to treat and obtain a low titer of antibodies in a patient with AA following an ABO-incompatible alloPBSCT, higher doses of erythopoietin and corticosteroids associated with plasma exchange have to be used.
 
The barrier of ABO-incompatible kidney transplantation is the presence of anti-A and anti-B antibodies in the recipient's circulating blood. Double filtration plasmapheresis (DFPP) is usually used to eliminate those antibodies. We tried cryofiltration apheresis (CRYO) in 2 recipients. Patient 1 was a 45-year-old male with B, Rh(+). The titers of IgM anti-A antibody were only reduced from x64 to x32 by the end of 3 sessions of standard CRYO. Renal allografting was not performed. Case 2 was a 29-year-old male with B, Rh(+). CRYO was introduced for 3 sessions. The initial IgM and IgG titers were x128 and negative, respectively. The standard CRYO system was modified by temperature, treated volume, and filter pore size. The IgM anti-A antibody titer was markedly reduced to x2 after the final session of CRYO. The donor was a 56-year-old father with A, Rh(+). Tacrolimus, azathioprine, methylprednisolone, and antilymphocyte globulin were used as the introductory immunosuppression therapy.
 
Infection, thrombosis, and stenosis are among the most frequent complications associated with blood contacting catheters. Because these problems are usually related to surface properties of the base catheter material, surface treatment processes such as ion implantation and ion beam assisted deposition (IBAD) (silver based coatings) can be used to mitigate such complications. Because these ion beam based processes affect only the near-surface region (approximately the outer 1 microm), there is little effect on bulk material properties. This study evaluated silver coated large bore catheters used for extracorporeal detoxification. In a 135 patient prospective study, 170 large bore catheters were inserted into the internal jugular or subclavian veins. Seventy-eight surface treated catheters (Spi-Argent, Spire Corporation, Bedford, MA, U.S.A.; n = 32 acute catheters, n = 46 long-term catheters) were inserted in 55 patients. Ninety-two untreated catheters placed in 80 patients served as controls (n = 40 acute catheters, n = 52 long-term catheters). After removal, the catheters were cultured for bacterial colonization using standard microbiologic assays. They also were examined using a scanning electron microscope (SEM). Bacterial colonization was observed in 7% of the treated catheters compared with 35.3% of untreated catheters. The SEM investigations showed all treated catheters to possess low thrombogenicity. Results of the study indicate that ion beam based processes can be used to improve thrombus and infection resistance of blood contacting catheters.
 
Central venous catheters provide at the present time the basic and ideal method to perform acute extracorporeal blood purification. Rapid launch of extracorporeal therapy is indicated in two situations: first, renal conditions presenting as a recognized acute organic renal failure (ARF) and acute decompensation of end stage renal disease (ESRD) without permanent vascular access; second, non-renal conditions presenting as urgent clinical situations requiring isolated ultrafiltration for chronic congestive heart failure, plasmapheresis or selective immunoadsorption for immune diseases, cytapheresis for hematological disease, and selective detoxification for certain types of poisoning. Central venous catheters are classified into 2 categories according to the duration of use: temporary catheter (less than 90 days) and permanent catheter (more than 90 days). A temporary catheter, including rigid (polyethylene, teflon) and semirigid (polyurethane) material, is indicated in emergency situations and for short-term use. A permanent catheter, made usually of soft silicone rubber with a subcutaneous anchoring system, has a subcutaneous tunnel and is indicated in medium and long-term use. Catheter design has benefited greatly from technical advances and material hemocompatability. However, catheter-related morbidity still remains high and is associated with an unacceptable incidence rate of infection and/or vein thrombosis. This article covers our present knowledge regarding catheter indications, technical aspects of catheter insertion and care, functional limitation of central venous catheters, and catheter-related complications. It is also our intent to provide the reader with optimal indication and catheter care in order to prevent and reduce the burden of catheter-related morbidity.
 
INTRODUCTION Guest Editor's Introduction: The most specific adsorption of antibody can be achieved by the application of antigen-antibody binding. The antibody is specific for a particular part of antigen called epitope rather than for the whole antigen molecules. Therefore, the immobilized epitope for target antibody could be used as the ligand of the adsorbent. Kuraray Co. developed a specific adsorbent for the anti-acetylcholine receptor antibody. The adsorbent consists of microporous cellulose beads for the base material which immobilized a synthetic peptide as the epitope ligand. This paper describes the basic design and in vitro characteristics of the adsorbent. This paper was printed in Therapeutic Plasmapheresis, vol 12, page 573–576 (1993), and reprinted here with permission.
 
A specific system for antibody removal from blood circulation in myasthenia gravis (MG) patients was devised by use of the immunoadsorbent bound to an acetylcholine receptor (AChR) peptide that was synthesized corresponding to the sequence of residues 183-200 of the AChR alpha-subunit (alpha 183-200), antibodies which prevent the binding of ACh to AChR. The alpha 183-200 peptide was confirmed to be immunogenic for induction of an animal model of the disease and for reactivity with MG autoantibodies. We then made use of these results for immunoadsorption therapy through the antigen-antibody reaction on the molecular level, having given patients relief from myasthenic weakness. The greatest care was taken for the selection of an antigenic region in the molecular structure among various myasthenogenic domains of AChR and for the antigenic conformation of synthetic peptide as the adsorbent to react with antibodies raised against the native protein.
 
A patient with acquired hemophilia complicated with chronic renal failure and lung tuberculosis was successfully treated by consecutive plasma exchange (PE). A 71-year-old man with serious bleeding tendency showed low coagulation factor levels and a high titer of factor VIII (FVIII) inhibitor, and he was diagnosed with acquired hemophilia. Because of the complication of active lung tuberculosis, instead of immunosuppressive therapy, he undertook a series of PE with fresh frozen plasma replacement for 3 months. After the start of PE, his bleeding symptoms and activated partial thromboplastin time (APTT) improved gradually according to the decrease in FVIII inhibitor levels. These results suggest that PE is an effective therapeutic tool for refractory acquired hemophilia.
 
Pooled therapeutic intravenous immunoglobulin (IVIg) is increasingly used for the treatment of autoimmune and systemic inflammatory diseases. The lack of a clear understanding of the mode of action of IVIg has been an obstacle to a more rational use and schedule of administration of IVIg and to the improvement of the existing IVIg preparations. Several nonmutually exclusive mechanisms have been proposed to account for the beneficial immunomodulatory effects of IVIg. These include the functional blockade of Fc receptors on phagocytes, inhibition of the deposition of activated complement components on target cells, modulation of the secretion of cytokines and cytokine antagonists, interference with T and B cell proliferation, neutralization of pathological autoantibodies, and long-term selection of immune repertoires.
 
Immunoadsorption therapy (IAT) is used in the treatment of autoimmune diseases. Although IAT has been reported to modify humoral immunity by inducing chemokines and activating complements, much remains unknown about the biological effects of IAT on cellular components in peripheral blood. To define the influence of IAT on leukocytes, we determined leukocyte L-selectin (CD62L) and Mac-1 (CD11b) as parameters for activation of leukocytes in peripheral blood during IAT. Peripheral leukocyte L-selectin and Mac-1 were determined continuously by flow cytometry in 6 patients with neuroimmunological disorders in whom IAT was conducted using a Plasma Flow OP-05 (Asahi Medical Corp., Tokyo, Japan) as a plasma separator and Immusorba TR-350 (Asahi Medical Corp., Tokyo, Japan) as an adsorption column. Expression of neutrophils (PMN) L-selectin was decreased 30 min after starting IAT, with the decreases particularly marked at the end of IAT, while expression of mononuclear cells (MNC) L-selectin slightly increased during IAT. Expression of PMN Mac-1 was markedly increased at the end of IAT, whereas expression of MNC Mac-1 did not change during IAT. Leukocyte counts decreased 30 min after starting IAT, and then increased to the initial level or higher in parallel with L-selectin downregulation and Mac-1 upregulation on PMN. L-selectin downregulation and Mac-1 upregulation on PMN suggested that activation of PMN associated with changes in peripheral leukocyte counts occurred during IAT and might play some role in modulating the human circulating blood and immune systems.
 
Activation of platelets during collection and storage has been implicated as a major cause of the platelet storage lesion. In this study, we investigated the effect of an automated plateletpheresis procedure on the in vivo platelet activation in 20 volunteer donors. Peripheral blood samples were collected immediately before and after plateletpheresis on the Haemonetics V50 Blood Cell Separator. Activation of platelets was determined by quantitating the amount of platelet P-selectin (CD62) expression using a whole blood method on flow cytometry. Adenosine diphosphate (ADP), collagen, and ristocetin induced platelet aggregations were also measured on a whole blood impedance aggregometer. Plateletpheresis caused a significant decrease in the CD62-positive platelet percentage and aggregation responses to 3 agonists. We concluded that the plateletpheresis procedure did not cause an increase in platelet activation in donors. Further studies are required to elucidate whether activated platelets are collected during the procedure or removed from the circulation of the donor and replaced by resting platelets, activated platelets bind to leukocytes or endothelial cells, and the plateletpheresis procedure is a powerful stimulus for platelet activation.
 
Acute ataxic neuropathy is characterized by sensory ataxia and areflexia. There is no established treatment. We tried immunoadsorption plasmapheresis 15 days after the onset for a 46-year-old woman suffering from this neuropathy. She could not walk even with assistance because of sensory ataxia. A sural nerve biopsy revealed active axonal degeneration and loss of myelinated fibers. We tried 5 sessions of plasmapheresis during 2 weeks. She could walk with assistance 12 days after the beginning of the plasmapheresis treatment. It took 3 months for her to be able to walk over 5 m without assistance, and she had severe sensory ataxia over a 17 month follow-up period. Immunoadsorption plasmapheresis started within 2 weeks after the onset of acute ataxic neuropathy may have beneficial effects if the axonal degeneration is mild. The plasmapheresis, however, should be continued for a longer period. A double blind study is necessary to clarify the effectiveness of this treatment on acute ataxic neuropathy.
 
Plasma exchange has gained widespread acceptance as an effective mode of blood purification in patients suffering from acute hepatic failure. However, it is still undetermined whether a single use of plasma exchange is capable of removing inflammatory cytokines completely or of preventing the development of citrate toxicity inherent with fresh frozen plasma. To clarify these issues we developed combined plasma exchange and continuous hemodiafiltration (CHDF) modality in which CHDF is performed in an opposite direction to plasma exchange. This study was designed to assess the effectiveness of combined modality therapy. Fifteen patients with acute hepatic failure were treated with plasma exchange (plasma exchange group) or plasma exchange and CHDF (plasma exchange + CHDF group), and various biochemical parameters were determined before and after treatment. Although citrate levels increased significantly after treatment compared with pretreatment levels in both the plasma exchange group and the plasma exchange + CHDF group, the percentage of the increase in citrate levels was significantly higher in the plasma exchange group than in the plasma exchange + CHDF group. Bilirubin levels were significantly lower after treatment in both the plasma exchange and plasma exchange + CHDF groups. There were no significant differences in tumor necrosis factor-alpha levels before and after treatment in the plasma exchange group, but they were significantly lower after treatment in the plasma exchange + CHDF group. Interleukin-6 (IL-6) levels increased significantly after treatment in the plasma exchange group, but there were no significant differences in the IL-6 levels before and after treatment in the plasma exchange + CHDF group. Interleukin-8 levels increased significantly after treatment in the plasma exchange group while decreasing significantly after treatment in the plasma exchange + CHDF group. These results indicate that combining plasma exchange and CHDF in a parallel circuit is an effective modality for suppressing the elevation of blood citrate levels and for removing inflammatory cytokines. This finding may have important implications for the development of an effective treatment for patients with acute hepatic failure.
 
We report two cases of hypertriglyceridemic necrotizing pancreatitis treated by plasma exchange (PE). The outcome of each case was quite different according to the timing of PE. A 36 year old man presented with abdominal pain, and a diagnosis of severe acute pancreatitis was made. His serum triglyceride (TG) level was 6,460 mg/dl. He did not undergo PE at first, however, his condition never improved and PE was performed 20 days after the onset of his illness. Finally, he died of multiple organ failure and sepsis. In contrast, a 52 year old man with acute necrotizing pancreatitis was referred to our department. He received PE quickly after hospital admission. His serum TG level, which was 3,540 mg/dl at hospital admission, dramatically returned to normal limits, and he was discharged from the hospital 62 days after admission. The prognosis of severe necrotizing pancreatitis due to hypertriglyceridemia is extremely poor. PE should be applied for the treatment of hypertriglyceridemic necrotizing pancreatitis immediately after its onset.
 
Complications of cardiopulmonary bypass (CPB) and acute inflammatory bowel disease (IBD) are associated with increased morbidity and cost. During reperfusion post-CPB, activated neutrophils adhere to microvascular endothelial cells mediated by cell adhesion molecules (CAMs) and cytokines/chemokines with subsequent myocardial damage caused by activated neutrophil-derived oxidants and enzymes. Leukofiltration was shown to reduce myocardial reperfusion injury and improve gas exchange as suggested by improvements in surrogate markers of inflammation and clinical end points. In acute IBD, characterized by rectal bleeding and protracted hospital stays, circulating neutrophils emigrate to the inflamed colon and adhere to microvascular endothelial cells by CAMs. Multiple treatments with leukofiltration in IBD were shown to induce long-term remission of acute IBD. Hence, leukofiltration may reduce reperfusion injury and rectal bleeding in CPB and IBD, respectively, and therefore decrease the morbidity and cost associated with these diseases.
 
Hypercoagulability is a key contributor to acute cardiovascular syndromes and to various microcirculatory disorders. The use of heparin-mediated extracorporeal low-density lipoprotein/fibrinogen precipitation (HELP) apheresis makes a controlled, immediately effective reduction of clotting factors possible, and induces subsequent positive effects on plasma viscosity, erythrocyte aggregation, and microcirculation. Oxygen supply to an ischemic artery can thus be increased without hemodilution, qualifying the HELP system as a possible therapeutic tool in the treatment of acute cardiovascular syndromes and microcirculatory disorders.
 
The aim of this study was first, to evaluate the effects of continuous hemodiafiltration (CHDF) alone or combined with CHDF and polymyxin-B immobilized fiber (PMX) on survival rates of patients with sepsis and acute renal failure, and second, to evaluate the changes in plasma levels of inflammatory cytokines before and after treatment with CHDF and PMX and CHDF alone in these patients. Forty-eight patients with septic shock and acute renal failure were enrolled in this study. The survival rate of all patients at 28 days was 25% for those with CHDF and 75% for those with PMX and CHDF treatment. Combination treatment produced a significant reduction of plasma levels of endotoxin and interleukin-6 compared to the basal values and to the treatment with CHDF alone. From these data, it is suggested that the combined therapy with PMX and CHDF is effective in improvement of survival rate of patients with septic shock and acute renal failure.
 
A patient with acute hepatic insufficiency induced by a drug presented to our institution, and we performed a novel plasmapheresis that we call plasma dia-filtration (PDF). The patient was a 36 year old woman. She underwent 11 sessions of PDF for a duration of about 9 h for each procedure using the Evacure EC-2A filter together with 20 units of fresh frozen plasma and dialysate simultaneously. Serum levels of total bilirubin and prothrombin time were significantly improved after she underwent each procedure. However, after the third procedure the levels returned to the same level as on the previous day. Encephalopathy improved after the first procedure, and this improvement was maintained until the ninth procedure. The patient prepared to undergo liver transplantation after the tenth procedure because of the development of hepatic coma, but she died of respiratory insufficiency before undergoing the procedure. Accordingly in this case, PDF worked to maintain liver function in acute liver failure and may act as bridge therapy until the patient can undergo liver transplantation.
 
Improvement of hemorheology is one of the most important approaches in the treatment of acute ischemic stroke. We investigated the influence of extracorporal rheopheresis (ER) on cerebral blood flow in patients with acute ischemic stroke and evaluated its therapeutic effect. Thirty-three patients (rheopheresis group, 17; control group, 16; mean age 64 +/- 10 years) with acute ischemic stroke were included in our prospective randomized trial. The first treatment was started within 12 h after onset of symptoms, and treatment was repeated 3 times at an interval of 24 h. Hemorheological parameters were measured before and after each session. The cerebral blood flow was analyzed using 99mTc-ECD-SPECT. The functional and neurological outcomes were determined by follow-up investigations after 3 months. The hemorheological parameters were significantly different between the rheopheresis group (18% decrease of plasma viscosity, 55% decrease of red blood cell aggregation) and the control group (no decrease of both parameters). The single photon emission computed tomography (SPECT) analysis showed early reperfusion in 35% of the patients treated with rheopheresis and in 37% of the control group (NS). There were no differences in the neurological outcomes between the 2 groups. Extracorporal rheopheresis is practicable and safe. It rapidly and consistently improved the hemorheological parameters. Although this did not impact on cerebral perfusion or clinical outcome in patients with acute ischemic stroke in this report, we propose that ER deserves to be further evaluated by initiating the first treatment within 6 h post-insult.
 
We treated 2 patients with severe acute Guillain-Barré syndrome (GBS) with different apheresis methods. Sera from these patients in the acute phase contained a high titer of immunoglobulin (Ig)G anti-GM1 ganglioside antibody. One was a 57-year-old female treated with immunoadsorption (IA). IgG anti-GM1 antibody titer was reduced from 1:102,400 to 1:6,400 measured by ELISA after 1 month. However, her residual deficit was severe. The other patient was a 43-year-old male treated with plasma exchange (PE). IgG anti-GM1 antibody was reduced from 1:3,200 to 1:400 after 1 session of PE. After 1 month, he could walk independently. The better prognosis of the latter was possibly because of the patient's younger age and the plasma exchange that might have reduced such pathogenic factors as antiganglioside antibodies at the early stage of GBS.
 
Eight patients with pancreatic abscesses secondary to acute necrotizing pancreatitis underwent drainage of their abscesses under laparotomy. Two of them died of acute pulmonary thromboembolism (PTE) within 1 week. Autopsy revealed a large thrombus at the main trunk of the pulmonary artery and in the left common iliac vein. Femoral catheter insertion/indwelling, immobilization, surgery, increased trypsin/kinin/kallikrein, increased endotoxin, and decreased antithrombin-III (AT-III) were present following drainage of the pancreatic abscesses. With respect to the bedside diagnosis of acute PTE, alveolar-arterial oxygen gradients obtained by blood gas analysis and mean pulmonary artery pressure estimated by pulsed Doppler echocardiography are very useful. In terms of the treatment, attention should be paid to the following to prevent deep venous thrombosis: prophylactic administration of low molecular weight heparin and administration of AT-III (AT-III > or = 80%), use of the subclavian vein whenever possible as blood access for apheresis therapy, as short a compression time as possible after removing the blood access catheter (< or =6 h), and application of intermittent pneumatic compression devices or elastic compression stockings on the lower extremities.
 
It has been accepted widely that excessive humoral mediators play important roles in the pathogenesis of organ failure in patients with severe acute pancreatitis (SAP) and that infection of the pancreas due to bacterial translocation (BT) is the most frequent cause of death in SAP. On the other hand, it has been reported that continuous hemodiafiltration (CHDF) removes humoral mediators on hypercytokinemic patients such as those with systemic inflammatory response syndrome. Furthermore, several clinical studies have demonstrated that selective digestive decontamination (SDD) effectively eliminates aerobic Gram-negative bacteria from the intestinal tract and reduces the incidence of septic complications in SAP. Herein we report a case of SAP who was treated successfully with intensive care including CHDF and SDD. Thus, this case report suggests that CHDF aimed at removing causative humoral mediators and SDD for the prevention of BT are useful new tools for the management of SAP.
 
Plasma viscosity (PV) and erythrocyte aggregation (EA) are determinants of microcirculation, especially under the compromised hemodynamic conditions resulting from atherosclerosis. Direct adsorption of lipoproteins (DALI) apheresis is the first method for direct adsorption of lipoproteins; it drastically reduces low-density lipoprotein (LDL)-cholesterol and lipoprotein (a) (Lp[a]), and may therefore improve PV and EA. The current study was performed to test the effect of DALI on hemorheology. Six hypercholesterolemic patients who had been on regular LDL apheresis for at least several months were treated on a weekly or biweekly basis, on average 5 times each by DALI. Before and after each session, PV was measured by a capillary tube plasma viscosimeter and EA by rotational aggregometry. Single DALI sessions (n = 31) acutely decreased PV from 1.18 +/- 0.04 to 1.06 +/- 0.3 mPa (-10%) while EA improved from 22.8 +/- 4.4 to 13.3 +/- 4.5 (arbitrary units) (-42%). LDL-cholesterol, Lp(a), and very-low-density lipoprotein (VLDL)-cholesterol were effectively reduced while the decrease of triglycerides and fibrinogen was only moderate. DALI apheresis exerted an acute positive effect on blood hemorheology which may have beneficial effects on microcirculation. This hypothesis is in accordance with the clinical observation that in some patients, improvement of angina and/or exercise tolerance can be observed after only a few DALI sessions where changes of coronary stenoses cannot be expected yet.
 
Both in children and adults, acute leukemia may present with extremely high blast counts; a phenomenon known as hyperleukocytosis. Respiratory failure, intracranial bleeding, and severe metabolic abnormalities frequently occur in acute hyperleukocytic leukemias (AHLs) and are the primary determinants of the high early mortality (20% to 40%) observed. The process leading to these complications has long been known as leukostasis, but the biological mechanisms underlying its development and progression have remained unclear. Traditionally, leukostasis has been attributed to overcrowding of leukemic blasts in the microcirculation, and its treatment has focused on prompt leukocytoreduction. However, it is becoming increasingly evident that leukostasis results from the adhesive interactions between leukemic blasts and the endothelium; a mechanism that none of the current therapies directly addresses. The endothelial damage associated with leukostasis is likely to be mediated by cytokines released in situ and by subsequent migration of leukemic blasts in the perivascular space. The adhesion molecules displayed by the leukemic blasts and their chemotactic response to the cytokines in the vascular microenvironment are probably more important in causing leukostasis than the cell number. This may explain why leukostasis may develop in some patients with AHL and not in others, and why some patients with acute leukemia without hyperleukocytosis (<50,000 blasts/mm(3)) develop leukostasis and respond to leukocytoreduction. Leukapheresis effectively reduces the blast count in many patients with AHL and is routinely used for immediate leukocytoreduction. However, the most appropriate use of leukapheresis in acute leukemia remains unclear, and the procedure may not prevent early death more efficiently than fluid therapy, hydroxyurea, and prompt induction chemotherapy. The use of cranial irradiation remains very controversial and is not generally recommended. The identification of the adhesion molecules, soluble cytokines, and chemotactic ligand-receptor pairs mediating endothelial cell damage in AHL should become a priority if better outcomes are desired.
 
This study examined the efficacy of a different scoring system for multiple organ failure (MOF) patients treated by plasma exchange (PE). Twenty-five patients with MOF resulting from fulminant hepatitis who had been treated by PE for a total number of 91 PEs in a consecutive period of 22 months were included in our study. Data were collected from each patient to compute acute physiology and chronic health evaluation (APACHE) II and APACHE (AP) III scores. The sensitivity, specificity, and correct prediction of outcomes were measured. The correct prediction of outcomes was 86.5%in AP III and 77.5% in AP II. For the prediction of patient mortality, the AP III system seems to be more reliable than AP II.
 
Although widespread vascular thrombosis is common in thrombotic thrombocytopenic purpura (TTP), there have been no prospective studies on the extent of injury to specific organs. Following successful resuscitation and plasma exchange of an index patient with widespread organ dysfunction, cardiogenic shock, and elevated cardiac troponin-I levels, we prospectively studied and identified 2 more individuals (of 10 consecutive patients) with evidence of myocardial injury/infarction at presentation of acute TTP. These data suggest that cardiac troponin-I measurements should be considered during initial evaluation of all patients with acute TTP.
 
We tried to compare the efficacy of plasma exchange (PE) with that of intravenous immunoglobulin (IVIG) in patients with postinfectious polyneuritis (Guillain-Barré syndrome [GBS] and cranial neuritis). Fifteen patients with postinfectious polyneuritis were divided into 2 groups. The IVIG group included 5 cases of GBS and 2 cases of postinfectious cranial neuritis (ophthalmoplegic type). The PE group included 5 cases of GBS and 3 cases of postinfectious cranial neuritis (ophthalmoplegic type). The changes and incidences of improvement of muscle strength scores (MSSs) and ocular movement scores (OMSs) were evaluated before treatment and 1, 2, 3, and 4 weeks after treatment. No significant differences between the IVIG and PE groups were found in the MSSs or OMSs at any time after treatment. These data suggested that PE and IVIG had equivalent efficacy. In the IVIG group, the proportion of suppressor-inducer T cells significantly increased (p < 0.01) (before versus after treatment), and the proportion of suppressor-effector cells also increased but not significantly (before versus after treatment). In the PE group, the percentage of suppressor-inducer T cells significantly decreased (p < 0.05) (before versus after treatment) while the proportion of suppressor/cytotoxic T cells significantly increased (p < 0.05) (before versus after treatment). The percentage of suppressor-effector T cells also increased (before versus after treatment) but not significantly.
 
Chylomicronemia syndrome (CMS) is a rare disorder characterized by the presence of chylomicrons in the fasting state causing a milky appearance of plasma, eruptive xanthomas, and hepatosplenomegaly; an acute and potentially life threatening complication is severe acute pancreatitis. The underlying defects are inborn errors of metabolism such as deficiencies of lipoprotein lipase (LPL) or apoprotein C-II (apo C-II) as well as familial hypertriglyceridemia. Moreover, CMS can be precipitated when mild hypertriglyceridemia is exacerbated by additional factors such diabetes mellitus, ethanol abuse, or pregnancy. The purpose of the present study was to retrospectively analyze the results of therapeutic plasma exchange (TPE) in 5 patients transferred to our hospital for severe acute pancreatitis due to chylomicronemia syndrome. In a total of 7 TPE sessions, on average 3,286 +/- 247 ml of plasma (i.e., about 1 patient plasma volume) were treated per session. Triglyceride (TG) levels were decreased from 4,972 +/- 2,469 mg/dl on admission to 1,614 +/- 1,276 mg/dl (-70%) after the TPE sessions, and a further decrease was achieved by conservative treatment. Part of the TG reducing effect of the treatment was probably due to heparin induced lipolysis. Acute pancreatitis was resolved in all cases, and 1 pregnant patient delivered without problems at term. In summary, 1 or 2 TPE sessions sufficed to substantially decrease the bulk of triglycerides in acutely exacerbated chylomicronemia syndrome causing a rapid resolution of acute severe pancreatitis.
 
Top-cited authors
Tadao Akizawa
  • Showa University
Tadashi Tomo
  • Oita University
Masaaki Nakayama
  • St. Luke's International Hospital
Yoshiharu Tsubakihara
  • Osaka University
Masafumi Fukagawa
  • Tokai University