Solvent/detergent-treated Plasma Research Articles

Plasma Exchange Therapy Using Solvent Detergent-Treated Plasma: An Observational Pilot Study on Complement, Neutrophil and Endothelial Cell Activation in a Case Series of Patients Suffering from Atypical Hemolytic Uremic Syndrome.

Plasma exchange therapy (PEX) was standard treatment for thrombotic microangiopathy before eculizumab was available and is still widely applied. However, most PEX patients still ultimately progress to end-stage renal disease (ESRD). It has been suggested that infusion of plasma that contains active complement may induce additional complement activation with subsequent activation of neutrophils and endothelial cells, leading to exacerbation of organ damage and deterioration of renal function. This observational pilot study examines the effect of hemodialysis, eculizumab and PEX before and after treatment in plasma of aHUS patients on complement-, neutrophil and endothelial cell activation. Eleven patients were included in this pilot study. Six patients were treated with hemodialysis, 2 patients received regular infusions of eculizumab, and 3 patients were on a regular schedule for PEX. Patients were followed during 3 consecutive treatments. Blood samples were taken before and after patients received their treatment. Complement activation products increased in plasma of patients after PEX, as opposed to patients treated with hemodialysis or eculizumab. Increased levels of complement activation products were detected in omniplasma used for PEX. Additionally, activation of neutrophils and endothelial cells was observed in patients after hemodialysis and PEX, but not in patients receiving eculizumab treatment. In this pilot study we observed that PEX induced complement and neutrophil activation, and that omniplasma contains significant amounts of complement activation products. Additionally, we demonstrate that hemodialysis induces activation of neutrophils and endothelial cells. Complement activation with subsequent neutrophil activation may contribute to the deterioration of organ function and may result in ESRD. Further randomized controlled studies are warranted to investigate the effect of PEX on complement- and neutrophil activation in patients with thrombotic microangiopathy.

Comparison of ADAMTS13 and Von Willebrand factor levels and activities, and plasminogen levels, in plasma products currently available for the treatment of thrombotic thrombocytopenic purpura in South Africa

ObjectiveThrombotic thrombocytopenic purpura (TTP) results from a deficiency in the Von Willebrand factor (VWF) cleaving protease, ADAMTS13. Treatment involves plasma exchange (PEX) therapy with either fresh frozen plasma (FFP), cryosupernatant (CSP) or solvent/detergent-treated plasma (SDP), available in South Africa as Bioplasma FDP. The aim of the study was to generate in vitro data on these products, and to explore possible differences between the products that may offer treatment advantages. MethodsTwenty samples per product (FFP, CSP and Bioplasma FDP) were analysed for levels and activities of ADAMTS13 and VWF. Plasminogen levels, a proposed physiological back-up system for ADAMTS13, were also determined. FFP and CSP samples were subanalysed according to ABO blood group. Samples were analysed by means of commercially available ELISA assays. ResultsAll samples had normal/high ADAMTS13 activity (Median activity for SDP = 94.0%, CSP = 80.5%, FFP = 122.0%) and plasminogen levels. The VWF content was mostly normal for Bioplasma FDP, typically deficient for CSP and mostly deficient for FFP, which was an unexpected finding. Depending on the parameter, Bioplasma FDP was the most standardised, with coefficients of variation (CV) from 14.1% to 27.3%, while FFP showed great inter-individual variation (CV 24.6% to 208.6%). Statistically significant differences were found across products (P ≤ 0.0095), and ABO blood groups (P = 0.0001). ConclusionAll three products can be used for the treatment of TTP. The choice of product depends on the need for additional viral safety, costs, product availability and the perceived impact of within-product variations.

Solvent-Detergent Plasma for the Treatment of Thrombotic Microangiopathies: A Canadian Tertiary Care Centre Experience

Solvent detergent-treated plasma (SDP) is a pathogen-inactivated blood plasma, which in comparison to frozen plasma is associated with lower rates of allergic reaction, transfusion-associated lung injury, and viral transmission. SDP has been available in Canada since 2012. Data on SDP use in Canada remains limited. We present a review of subjects receiving SDP at a large tertiary care centre primarily for thrombotic thrombocytopenic purpura and atypical hemolytic uremic syndrome, demonstrating the tolerability and safety of SDP.

Using SDP; and so it came to Canada.

A solvent/detergent-treated plasma (SDP) Octaplas®was first introduced in Germany by Octapharma in 1991 and subsequently was used in other European countries. In the US, another version of SDP was introduced by Vitex in 1998 and was distributed by the American Red Cross but production there ceased in 2002–2003. In 2006, Octapharma’s SDP was licensed in Canada andmore recently in the US in 2013. For the Canadian Apheresis Group (CAG) the withdrawal of the SDP made by Vitex marked the end of our national study designed to compare SDP to cryo-poor plasma (CSP) in patients with thrombotic thrombocytopenic purpura (TTP). At that time, we were aware of “another” i.e. Octapharma source of SDP but were unable to convince funding authorities to allow us to continue with the trial using this material and so, after the entry of 61 patients, 34 of whom received Vitex SDP and 27 CSP, the study was stopped. While wewere unable to complete the comparative study we did generate a good deal of information concerning the biochemical and clinical parameters of the patients and this information was published in a paper published in 2013 [1]. There have long been concerns in this patient population about the use of plasma since they receive such very large volume exchange fluid in a very short period of time. In a 2008 assessment by the CAG it was determined that the average TTP patient received 40 L of plasma over the first 7 days of treatment however, recent data indicate a considerable increase in the volume of plasma required and therefore an increase in donor exposures. Massive plasma infusion has the drawback of exposing patients to a great number of plasma donors, which increases the risk of transfusion-transmitted infections. A product which provides a higher level of safety and reduces the incidence of adverse reactions would clearly benefit these patients. So the CAG has long had an interest in and an active voice for the use of a pathogen inactivated plasma (PIP). However, not all of the currently available PI plasmas are the same. Studies from Spain have indicated that methylene blue plasma is problematic for use in TTP patients [2]. Interestingly, of the other products available, SDP plasma, psoralen-treated plasma and the Mirasol® (riboflaventreated) plasma there has not actually been a RCT to support their use in TTP. However, several forms of PI are in widespread use in Europe and have been used in the treatment of patients with TTP with reported success. In fact, the last decade has seen a slow but steady shift from FFP to SDP on the part of most European countries as the advantages of PI plasma over frozen plasma are realized. A recent report by our group showing that hepatitis E was transmitted through pooled plasma products in the form of the Vitex SDP shows the importance of using a truly pathogen inactivated solution in treating these patients [3]. This is particularly important because current therapy for refractory and relapsing TTP patients involves the use of Rituximab which acts to inhibit B cells. The resultant immune suppression will make patients far more susceptible to infection so a major concern will be to ensure that the safest product is used, therefore pathogen inactivated products should be used in this patient population. In 2012 we held a Working Group meeting in Canada to consider the introduction of SDP in this country. A review done by Marie Scully at the time very nicely described the * Tel.: +1 613 748 9613. E-mail address: cag@cagcanada.ca.

Relative concentrations of haemostatic factors and cytokines in solvent/detergent-treated and fresh-frozen plasma

Indications, efficacy, and safety of plasma products are highly debated. We compared the concentrations of haemostatic proteins and cytokines in solvent/detergent-treated plasma (SDP) and fresh-frozen plasma (FFP). Concentrations of the following parameters were measured in 25 SDP and FFP samples: fibrinogen (FBG), factor (F) II, F V, F VII, F VIII, F IX, F X, F XIII, von Willebrand factor (vWF), D-Dimers, ADAMTS-13 protease, tumour necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, IL-8, and IL-10. Mean FBG concentrations in SDP and FFP were similar, but in FFP, the range was larger than in SDP (P<0.01). Mean F II, F VII, F VIII, F IX, and F XIII levels did not differ significantly. Higher concentrations of F V (P<0.01), F X (P<0.05), vWF (P<0.01), and ADAMTS-13 (P<0.01) were found in FFP. With the exception of F VIII and F IX, the range of concentrations for all of these factors was smaller (P<0.05) in SDP than in FFP. Concentrations of TNF-α, IL-8, and IL-10 (all P<0.01) were higher in FFP than in SDP, again with a higher variability and thus larger ranges (P<0.01). Coagulation factor content is similar for SDP and FFP, with notable exceptions of less F V, vWF, and ADAMTS-13 in SDP. Cytokine concentrations (TNFα, IL-8, and IL-10) were significantly higher in FFP. The clinical relevance of these findings needs to be established in outcome studies.

Efficacy and Safety Profile of Solvent/Detergent Plasma in the Treatment of Acute Thrombotic Thrombocytopenic Purpura: A Single-Center Experience

Background: Thrombotic thrombocytopenic purpura (TTP) is a rare clinical disorder which was associated with poor prognosis for a long time. The outcome has been improved by the consistent introduction of thera-peutic plasma exchange (TPE) as standard treatment of TTP. Patients and Methods: We describe our experience in the use of solvent/detergent-treated plasma (SDP) for TPE in TTP. We retrospectively analyzed acute TTP epi-sodes in 8 patients (mean age = 27 years, range 18–44 years) treated with TPE using SDP with regard to tolerability and efficacy. Results: All 8 patients were positive for anti-ADAMTS-13 antibody. Seven out of 8 had a se-vere ADAMTS-13 deficiency. All patients responded rapidly to SDP TPE with an increase in platelet count to above 150 × 10⁹/l. Hemolytic anemia disappeared over the treatment period. Approximately 2,000 l SDP were used for more than 500 treatments. Treatment with SDP was well tolerated; none of the patients experienced an adverse drug reaction after exposure to SDP. No major complications occurred even after multiple TPE. Conclusion: Our investigations suggest that TPE using SDP as replacement fluid is an effective treatment for TTP. The data described also indicate that SDP might offer the benefit of reducing adverse drug reactions.

ADAMTS-13 Levels Do Not Predict Outcome in Thrombotic Thrombocytopenic Purpura: Protein S Levels Are Maintained during Plasma Exchange with Solvent Detergent Treated Plasma.

Introduction The ultimate therapy for TTP is not yet defined. While approximately 85% of patients respond to plasma exchange with FFP, the use of alternative solutions such as cryosupernatant plasma, which is deficient in the high molecular weight forms of vWF. has not been proven by appropriate randomized prospective sample trials. However, it is intellectually appealing. Additionally, the use of the ADAMTS 13 level either to predict disease or outcome has not been resolved.Methods Cryosupernatant plasma (CSP) was compared to solvent detergent treated plasma (SDP) over one cycle (nine days) of plasma exchange (PE) and subsequent procedures as required. Throughout treatment, ADAMTS 13 and protein S levels were followed.Results At the primary end point of one month, 3 of 35 of the CSP and 1 of 27 of the SDP patients died. The average platelet count was 184 × 109 per litre for CSP and 209 × 109 per litre for SDP. While vWF and FVIII were elevated in all patients at entry, no unusually large vWF multimers were seen at any time. At entry 9 patients had ≤ 0–10% ADAMTS 13 and 14 of 62 had normal levels with the rest in between. At presentation only 9 patients had 100% inhibitor activity with no inhibitor in 18 patients. Of the four patients who died, two who received CSP, had 100% enzyme activity at presentation whereas one had no ADAMTS-13 and another had 10%. All 4 patients died within 10 days. Fifteen patients with less than 10% enzyme activity had >1.5 vWF. However, elevated (>3u/mL) vWF was seen in the presence of normal ADAMTS-13 levels. Six months after remission, and in the presence of a normal platelet count, ADAMTS13 remained low in 5 patients and normal in 15.Protein S levels in 41/62 patients studied showed little variation during therapy with values on day 3 and 5, similar to those seen on entry.Conclusion In idiopathic TTP, ADAMTS 13 levels do not correlate with disease, and are not predictive of outcome. While protein S levels in the SDP were lower than those found in FFP, this did not appear to have clinical significance.

ADAMTS-13 levels in fresh, stored, and solvent detergent treated plasma

Background ADAMTS-13 is implicated in the pathophysiology of thrombotic thrombocytopenic purpura (TTP). Plasma exchange is thought to be effective through removal of a harmful substance or provision of a required material such as ADAMTS-13. As various methods are used to prepare plasma we determined the effects of storage and solvent detergent treatment on the ADAMTS-13 levels in plasma. Methods Samples from fresh plasma and fresh frozen plasma (FFP) were stored at 22 °C and ADAMTS-13 levels were measured at 0, 12, 24, 48 and 72 h. Samples were also taken from solvent detergent treated plasma (SDP) and cryosupernatant plasma (CSP). Total protein, albumin, fibrinogen and immunoglobulins were also measured. Results In fresh plasma, the levels of both the 175 and 140 Kd subunits of von Willebrand factor were consistent at 1.38 and 1.35 OD units from 0 to 48 h indicating normal ADAMTS-13 activity. The Vitex SDP produced slightly more of the 140 Kd subunit than did Octapharma SDP which gave equivalent fragments. Cryosupernatant plasma was the same as normal plasma. None of these values changed over 48 h. There was a 28% decrease in FVIII in fresh plasma over 24 h. Fibrinogen and albumin were unchanged. Conclusion ADAMTS-13 levels are not significantly decreased by storage of plasma at room temperature for up to 48 h. Both CSP and SDP also contained essentially normal levels of ADAMTS-13 and therefore could be used for treatment of patients with TTP.

Treatment of Thrombotic Thrombocytopenic Purpura Using Solvent Detergent Treated Plasma.

Background:Patients with Thrombotic Thrombocytopenic Purpura require immediate therapy with large volumes of plasma. They have been reported to respond well to plasma exchange (PE) with FFP (78%)1 and CSP (95%)2. We initiated a randomized prospective trial with CSP and solvent detergent treated plasma (SDP) intended to show non inferiority.Methods:Patients were randomized to receive either of the exchange fluids at 1.5 PV x 3 days then 1 PV x 4–6 days. Laboratory values were followed with ADAMTS-13 levels measured according to Furlan3. The primary end point was survival at 6 months.Results:A total of 62 of the required 280 patients entered the study then the supply of SDP was discontinued. 3/35 patients receiving CSP and 1/27 on SDP died before 1 month. These values are not significant but the study is underpowered so statistical analysis is not possible. FVIII and vWF levels were elevated in all patients at entry. 34/50 patients tested also had antibodies to CD36. 9 patients had no ADAMTS-3 at entry, 19 had between 5–50%, 9 patients had 50–100% and 15/62 patients tested had normal levels. Inhibitors were present at between 5–50% levels in 22/50 patients tested whereas 9 patients had complete inhibition of ADAMTS-13 and 18 had normal enzyme activity.Conclusions:Patients with TTP appear to respond well to SDP thereby offering a relatively safer therapeutic option for PE. An insufficient number of patients were entered to achieve statistical significance. Both the ADAMTS-13 and the inhibitor levels show great variation and are not prognostic.

The mantra of blood safety: time for a new tune?

The mantra of blood safety: time for a new tune?

Author's reply: Solvent–detergent‐treated plasma: clinical evidence prior to economics

Vox SanguinisVolume 84, Issue 4 p. 334-335 Author's reply: Solvent–detergent-treated plasma: clinical evidence prior to economics M. Van Hulst, M. Van Hulst Department of Social Pharmacy, Pharmaco-epidemiology and Pharmacotherapy, GUIDE/GRIP, Groningen, the Netherlands Martini Hospital, Department of Clinical Pharmacy and Toxicology, Groningen, the Netherlands Search for more papers by this authorJ. T. M. De Wolf, J. T. M. De Wolf Department of Internal Medicine, University Hospital Groningen, Groningen, the NetherlandsSearch for more papers by this authorM. J. Postma, M. J. Postma Department of Social Pharmacy, Pharmaco-epidemiology and Pharmacotherapy, GUIDE/GRIP, Groningen, the Netherlands Search for more papers by this author M. Van Hulst, M. Van Hulst Department of Social Pharmacy, Pharmaco-epidemiology and Pharmacotherapy, GUIDE/GRIP, Groningen, the Netherlands Martini Hospital, Department of Clinical Pharmacy and Toxicology, Groningen, the Netherlands Search for more papers by this authorJ. T. M. De Wolf, J. T. M. De Wolf Department of Internal Medicine, University Hospital Groningen, Groningen, the NetherlandsSearch for more papers by this authorM. J. Postma, M. J. Postma Department of Social Pharmacy, Pharmaco-epidemiology and Pharmacotherapy, GUIDE/GRIP, Groningen, the Netherlands Search for more papers by this author First published: 20 May 2003 https://doi.org/10.1046/j.1423-0410.2003.00308.x M. van HulstDepartment of Social Pharmacy, Pharmaco-epidemiology and Pharmacotherapy Groningen University Institute for Drug Exploration/University of GroningenResearch Institute of Pharmacy (GUIDE/GRIP)Antonius Deusinglaan 19713 AV Groningenthe NetherlandsE-mail: m.van.hulst@farm.rug.nl Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume84, Issue4May 2003Pages 334-335 RelatedInformation

Manufacture and composition of fresh frozen plasma and virus-inactivated therapeutic plasma preparations: correlation between composition and therapeutic efficacy

The clinical efficacy of the therapeutic plasma used in the treatment of congenital and acquired severe coagulopathy depends on the potency of clotting factor and inhibitor activities. The composition of plasma strongly depends on the conditions under which it is produced. A low citrate anticoagulant-to-blood ratio, short intervals between donation and plasma separation and rapid freezing markedly improve the preservation of unstable coagulation factors. The influence of different leukocyte reduction filters on plasma quality still requires clarification. Recent trials on long-term storage conditions suggest that keeping plasma at −30 °C or colder over a period of 24–36 months prevents substantial decrease in clotting factor activities including factor VIII (FVIII). Three types of therapeutic plasma are currently available. Quarantine-stored fresh frozen plasma (FFP) contains physiological activities of therapeutically relevant plasma proteins, but carries a risk of transmitting blood-borne viruses that cannot be detected by human immunodeficiency virus (HIV) and hepatitis B and C screening. In contrast, solvent/detergent-treated plasma (SDP) and methylene blue/light-treated plasma (MBP) is virtually free of HIV and hepatitis C virus (HCV) subtypes. Virus inactivation procedures can have the consequence of reducing several clotting factors and inhibitors in SDP and MBP to varying degrees. However, pooling of plasma units before solvent/detergent (SD) treatment results in well-standardized protein levels of SDP. At least five prospective trials and four observational studies covering different clinical settings suggest that SDP and FFP do not substantially differ in their clinical efficacy or in their tolerance. By way of contrast, there is a lack of data about the clinical efficacy and tolerance of MBP compared to FFP.

Mortality risks, costs, and decision making in transfusion medicine.

Traditional quality-adjusted life year (QALY) cost analysis is complex and assigns arbitrary dollar values to catastrophic outcomes such as death. Analysis of transfusion medicine technologies by an alternative approach that focuses on costs to avoid fatal outcomes might be a useful adjunct to QALY analysis for allocating limited financial resources. We estimated the cost per death averted for the following interventions: apheresis platelets vs random platelets, solvent detergent-treated plasma vs untreated plasma, and leukocyte-reduced vs unmodified transfusions in cardiac surgery. As a control, similar data were calculated for current donor viral testing. The estimated incremental costs per death avoided were as follows: single-donor apheresis platelets, $15 million; solvent detergent plasma, $17 million; leukocyte-reduced transfusions in cardiac surgery, $11,000; HIV-1 antibody testing, $22,000; and HIV-1 antigen testing, $3.9 million. The estimated number of deaths averted per year in our hospital were as follows: apheresis platelets, 0.1; solvent detergent plasma, 0.044; leukocyte-reduced transfusions, 14; HIV-1 antibody testing, 6.0; and HIV-1 antigen testing, 0.033. HIV-1 antibody testing and leukocyte-reduced transfusions in cardiac surgery are comparably cost-efficient means of averting mortality in patients receiving transfusions. Solvent detergent plasma and apheresis platelets are comparatively expensive approaches to reducing mortality from transfusion complications.

Evaluation of Solvent/Detergent-Treated Plasma in Patients with a Prolonged Prothrombin Time

Objectives: To compare the laboratory and clinical outcome of patients who received solvent/detergent-treated plasma (SDP) and fresh-frozen plasma (FFP). Methods: A randomized, double-blinded study to assess the ability of SDP and FFP to reduce a prolonged prothrombin time (PT) to ≤15 s in patients with acquired coagulation deficits. Results: 45 patients (22 SDP vs. 23 FFP) were treated with 71 infusions. There were no significant differences in mean dose of plasma infused (7.8 ml/kg for SDP vs. 8.0 ml/kg for FFP, p = 0.46), percentage of patients who corrected their PT to ≤15 s (32% for SDP vs. 26% for FFP, p = 0.67), or percentage of patients whose bleeding ceased (27% for SDP vs. 22% for FFP). Conclusion: No clinical or statistically significant differences were observed after infusion with SDP or FFP in patients with acquired coagulation deficits.

Evaluation of Solvent/Detergent‐Treated Plasma in Patients with a Prolonged Prothrombin Time

Abstract Objectives: To compare the laboratory and clinical out‐come of patients who received solvent/detergent‐treated plasma (SDP) and fresh‐frozen plasma (FFP). Methods: A randomized, double‐blinded study to assess the ability of SDP and FFP to reduce a prolonged prothrombin time (PT to ≤ 15 s in patients with acquired coagulation deficits. Results: 45 patients (22 SDP vs. 23 FFP) were treated with 71 infusions. There were no significant differences in mean dose of plasma infused (7.8 ml/kg for SDP vs. 8.0 ml/kg for FFP, p = 0.46), percentage of patients who corrected their PT to ≤ 15 s (32% for SDP vs. 26% for FFP, p = 0.67), or percentage of patients whose bleeding ceased (27% for SDP vs. 22% for FFP). Conclusion: No clinical or statistically significant differences were observed after infusion with SDP or FFP in patients with acquired coagulation deficits.

Completely converting a blood service region to the use of safer plasma.

Three types of plasma are widely available for transfusion. Two plasma components, FFP donor retested (FFP-DR), and solvent/detergent-treated plasma (SDP), are now considered to be safer from infectious complications than FFP. A large regional blood center attempted to provide FFP-DR exclusively to all its 42 hospitals. Significant planning, increases in computer capabilities, and expansion of component storage areas were completed before initiation of this program. During the first 6 months of the FFP-DR program, the blood center was not able to supply the entire region exclusively with FFP-DR. Consequently, SDP was utilized to supplement the program and to successfully and completely convert the region's 42 hospitals to the use of safer plasma. Two new plasma components were utilized to completely convert a blood service region to the use of safer plasma.