Hypertriglyceridemia: apheretic treatment.

Patients with extremely high triglyceride levels and associated lipemia are at high risk for acute pancreatitis. Two factors can increase triglyceride-rich lipoproteins; one is overproduction and other is a defect in clearance. Either mechanism can cause hypertriglyceridemia and both may exist simultaneously. Causes can be either primary or secondary. Plasmapheresis is efficacious for severe Hypertriglyceridemia in patients who have not responded to previous therapies. We have treated 15 cases of hypertriglyceridemia complicating the course of patients receiving Cyclosporin A after bone marrow transplantation. Five patients were treated with plasmapheresis, the other ten with cascade filtration. The removal rate for triglycerides was 58.0% for patients treated by cascade filtration and 63.5% for patients treated by plasmapheresis. The removal rates for triglycerides were low possibly as a consequence of early saturation of the filter.

Hypercholesterolemia and LDL apheresis.

Several trials have assessed the link between low-density lipoprotein cholesterol (LDL) and the development of coronary heart disease (CHD). LDL apheresis provides an effective role in treating patients with familial hypercholesterolemia (FH) and in preventing the progression of coronary artery disease (CAD). Five different techniques of LDL apheresis are in current use: immunoadsorption (IMA), dextran sulphate-cellulose adsorption (DSA), heparin extracorporeal LDL precipitation system (HELP), double filtration plasmapheresis (DFPP) or lipidfiltration and direct adsorption of lipoprotein using hemoperfusion (DALI). All methods are efficient,but their cost restricts LDL apheresis to the treatment of FH. Indications could include other diseases, but controlled trials are still lacking.

Double plateletpheresis (DPA) and tailored RBC collection with the Excel-Pro: preliminary results.

The Dideco Excel-Pro is frequently used for double plateletpheresis (DPA) when the platelet precount exceeds 280 x 10(3)/l. Platelets are collected as "dry platelets" and the resuspension solution is added when the procedure is over. Even when DPA is carried out the product volume prior to resuspension may be as low as 60 ml. As a result, a third product may be collected along with platelets. Our priority is to collect RBCs and, depending on the donor's BW, tailored RBC collections are carried out. This means that from 400 to 480 ml of PRBC (70% hct) are collected from donors whose BW exceeds 75 kg. The results of the last 27 DPA/tailored PRBC collections are: Donors gender and BW (kg), 19M/8F: 88.4 +/- 7.3 Hemoglobin (g/dl): 15.4 +/- 1.3 Platelet precount (x 10(3)/microl): 308 +/- 45 Volume of blood processed (1): 5.5 Procedure time (min): 81 +/- 3 Platelet yield (x 10(11)): 6.8 +/- 0.6 Avg Hemoglobin content of PBRC (g): 102.6 +/- 12.3 WBC contamination of the platelets: 6.8 +/ -10(5).

Cascade filtration (CF) with the Haemonetics MCS+: a new technical adaptation.

CF was introduced in clinical medicine in 1980. Up to now, exclusively two-vein procedures have been carried out with some limitations to expansion of this technique. In this report we describe the very first application of single-needle CF carried out with Haemonetics MCS + apparatus. Twenty procedures were completed without any untoward effect in patients suffering from TTP, post-hepatitic cryoblobulinemia, familial hypercholesterolemia and acute Guillan-Barrè Syndrome. From 1 to 4 sessions were carried out per patient with the expected laboratory and clinical results. The only limit is the procedure time that averages 231 +/- 48 min., approximately 40% longer than two needle procedures.

Lepromatous vasculitis successfully treated by plasma exchange (PE).

Vascular involvement is presently considered a "common pathway" in a number of diseases that is mediated by circulating immune complexes (CIC). CIC are found in the circulation when the disease is active and in single patients their level may parallel disease activity. Lepromatous leprosis is characterized by the presence of CIC and deposits of immunoglobulins and complement in vascular lesions of the different organs and an Arthus-like mechanism is considered as the basis for the clinical picture. The same mechanism is considered to play an essential pathophysiologic role in Lucio's phenomenon, which is characterized by lymphohistiocytic vascular infiltrates with or without thrombosis and secondary cutaneous infarction. Lepromatous vascular involvement is mediated by CIC whose antigen composition is known, the same as it is with HCV mediated cryoglobulinemia, HBV positive panarteritis nodosa, rheumatoid vasculitis, or Wagner's granulomatosis, which are usually treated by PE [1-3]. PE has been employed for lepromatous vasculitis since 1979 [4] and other cases have been successfully treated afterwards [5,6]. We report on another patient successfully treated by plasma exchange.

Acute intravascular hemolysis in two patients transfused with dry-platelet units obtained from the same ABO incompatible donor.

Since 1989 we have been collecting dry-platelets on a routine basis. Dry-platelets are those collected along with 25-30 ml of contaminating plasma cell with separators such as the Amicus, AS 104 and the Excel Pro. Platelets are resuspended in non plasma media for storage and for at least 60 hours their viability and functionality are not impaired. In this article we report on two hemolytic crises determined by two O Rh D + units of single donor platelets (SPD) taken from the same donor in a double-apheresis session. The two split units were administered to two A Rh D + patients suffering from metastatic breast cancer and severe aplastic anemia (SAA) respectively. In both cases the hemolytic reaction was of the intravascular type, with a drop in hemoglobin (Hgb) level from 8.6 to 5.4 and from 8.8 down to 5.3 g/dl respectively. From the patients' RBC only alpha agglutinins were eluted and donor's indirect antiglobulin test (IAT) was negative with extended panel RBCs. In the first case the clinical course after erythroexchange (Erex) was uneventful whereas in the second one, that suffering from SAA, after Erex, acute renal failure and shock did complicate the clinical course and the patient died seven days after the incriminated platelet transfusion.

Therapeutic hemapheresis as of 2000.

The main task of therapeutic hemapheresis remains doing the right thing and doing the right thing right. If objective results have been slow to take hold it is in large part because several physicians have resisted continuous improvement since therapeutic apheresis was considered so efficient to boomerang preventing elimination of unnecessary procedures and treatments. The right thing to do is treating patients who may respond in a specific phase of their disease, frequently along with the right drugs. Doing right the right thing is to take advantage of the new technologies and, medical culture which have led apheresis to the recent complexity and efficacy. In the following pages we are trying to update the state-of-the-art and new trends which characterize therapeutic apheresis at the beginning of 2000.

PCR testing for HCV in anti-HCV negative blood donors involved in the so called HCV +ve post-transfusion hepatitis.

UNLABELLED: Although it is infrequent, post-transfusion HCV infection may occur if the donors blood is collected in the window period between exposure and anti-HCV detectability by ELISA testing. STUDY DESIGN: In these last years, despite of routine application of anti-HCV testing, our blood transfusion center has been involved in 53 cases of alleged post-transfusion HCV hepatitis and look-back programs were set up with the goal of finding out the donors possibly involved in viral transmission. Most of these patients were hematological cases with multiple transfusions given because of aplastic anemia (3 cases), leukemia with or without bone marrow transplantation (5/4 cases) but necessitating long-term platelet support, leukemia and solid cancer patients undergoing autologous PBSC transplantation (3/4 cases) and TTP (2 cases). Only 32 patients were of the simple medical or surgical type, 9 transfused because of cardiac or vascular surgery, 8 because of spine surgery, 5 for different diseases and 5 for different types of cancer surgery. Donor's infectivity was determined by ELISA anti-HCV testing, by recombinant immunoblotting assay, and by nucleic acid testing. RESULTS AND CONCLUSION: No donors out of 267 traced of a total of 359 involved was found with anti-HCV seroconversion, or positive on PCR testing. This suggests that the responsibility for HCV transmission can only hypothetically be related to blood or blood components and that other transmission routes should be found out.

Dry platelets with the Dideco Excel apparatus.

Dry platelets are required to prevent hemolytic and nonhemolytic febrile reactions after transfusion to ABO mismatched recipients, to reduce the risk of HLA immunization and to prevent allergic or anaphylactic reactions. Previously we have shown that the collection of single donor platelets almost free of plasma is possible with different cell separators. With the systems we described for the CS 3000+/Amicus and AS 104-204 apparatuses collection of dry platelets implies their resuspension in non plasma solutions after opening the circuit. With the new system developed by Dideco for the Excel apparatus this moreover is no longer required since the platelet bag can be connected to the resuspending medium through a dedicated line with an antibacterial filter. Platelets are collected cyclically and the resuspending solution is added when the procedure is over. In this study 53 collections were evaluated, 21 of which were erythrothrombocytapheresis. In 60-65 min 4.21 of anticoagulated blood (1/12) were processed with platelet collection automatically done after 6-700 ml cycles. The platelet yield averaged 4.67 +/- 0.7 x 10(11), with a platelet efficiency per minute of 7.18 +/- 0.9 x 10(9). The WBC contamination averaged 2.6 +/- 0.7 x 10(5) and contamination did not exceed 0.87 x 10(6). The quality of platelets was satisfactory as measured by aggregation, morphology score, and CD 62 membrane glycoprotein externalization. These results were comparable to those obtained with three other Excel apparatuses used in the conventional way to collect platelets resuspended in plasma or with the Amicus used to collect dry platelets using an open system.

Cascade filtration for TTP: an effective alternative to plasma exchange with cryodepleted plasma.

TTP remains enigmatic both in terms of etiology and management. The most recent approach is aggressive plasma exchange (PE) employing cryopoor plasma for replacement, based on the pathogenetic relevance given to exceedingly large Von Willebrand (VWF) multimers in the determination of the syndrome with normalization during remission. PE with fresh frozen plasma (FFP) is better than FFP infusion as shown by a recent Canadian study, supporting the theory that to treat TTP an offending circulating agent needs to be removed from the patient's plasma in contrast to the hypothesis that a missing factor is to be given along with FFP. A more recent hypothesis is supported by the results of studies published by the end of 1998 [Moake J, Chintagumpala M, Turner N et al. Blood 1994;84:490-97; Moake J, McPherson PD. Am J Med 1989;87: 3-9N] which would show that TTP is mediated by auto-antibodies to VWF-cleaving protease, or is the result of deficiency of the protease ascribed to abnormalities in its production, function or survival. Plasmapheresis without plasma infusion is relatively ineffective perhaps because it does not increase the protease activity. Cascade filtration (CF) is the autologous counterpart of plasmapheresis. It has been used by our group since 1980 to remove from patients plasma macromolecules such as VWF, fibrinogen, LDL and circulatory immune complexes (CIC). After secondary filtration, the autologous plasma has a composition which is very similar to that of allogeneic plasma after cryoprecipitation, a product which used in the management of TTP. Based on this knowledge, in 1994 we began to use CF in the treatment of TTP patients. In the beginning (7 patients) CF was combined with a decreasing number of conventional PEs using allogeneic plasma for substitution. Lately only CF with some plasma supplementation has been used in the last 9 cases. From a clinical point of view our 16 patients achieved remission after a number of treatments (11 +/- 7) that compares sufficiently well with those required by our historical control group of 47 cases (14 +/- 13). Of course the patient's exposure to allogenic plasma was significantly lower for patients in the CF only group (1.4 +/- 1.2 plasma U/session) compared to the PE + CF group (4.4 +/- 2.3 plasma U/session) or for the controls treated by PE only (10.8 +/- 4.6 plasma U/session). There were no deaths in the CF or PE + CF groups and no untoward effect was observed. On the contrary there were 5 deaths (1 on the day of presentation) in the PE group, and 1 HBV and 2 HCV infections as well as 4 severe allergic reactions to plasma proteins (or passive antibody infusion). We conclude that CF is presently the best treatment to offer to patients suffering from sporadic TTP and that CF may contribute to expanding the knowledge of the pathogenetic mechanisms of this uncommon multisystem disorder.