Transfusion and Apheresis Science - Articles in Press

Preparation of cryoprecipitate from riboflavin and UV light-treated plasma - Corrected Proof

2012-02-20

Abstract: Background and objectives: The Mirasol® pathogen reduction technology system for plasma is based on a riboflavin and UV light treatment process resulting in pathogen inactivation due to irreversible, photochemically induced damage of nucleic acids. This study was undertaken to evaluate the possibility of making pathogen reduced cryoprecipitate from riboflavin and UV light- treated plasma that meets the quality requirements specified by UK and European guidelines for untreated cryoprecipitate.Materials and methods: Cryoprecipitate was made from riboflavin and UV light-treated plasma. Plasma units were thawed over a 20h period at 4°C, and variable centrifugation settings (from 654g for 2min to 5316g for 6min) were applied to identify the optimal centrifugation condition. Plasma proteins in cryoprecipitate units were characterized on a STA Compact, Diagnostica STAGO and Siemens BCS analyzer.Results: Neither the centrifugation speed or time appeared to have an effect on the quality of the final cryoprecipitate product; however the initial solubilization of the cryoprecipitate product was found to be easier at the lower centrifugation setting (654g for 2min). Cryoprecipitate units prepared from Mirasol-treated plasma demonstrated protein levels that were less than levels in untreated products, but were on average 93IU/unit, 262mg/unit and 250IU/unit for FVIII, fibrinogen and von Willebrand ristocetin cofactor activity, respectively.Conclusion: Cryoprecipitate products prepared from Mirasol-treated plasma using a centrifugation method contain levels of fibrinogen, FVIII and von Willebrand ristocetin cofactor activity, that meet both the European and UK guidelines for untreated cryoprecipitate. Flexibility in centrifugation conditions should allow blood banks to use their established centrifugation settings to make cryoprecipitate from Mirasol-treated plasma.

Hydroxyethylstarch in cryopreservation – Mechanisms, benefits and problems - Corrected Proof

A. Stolzing, Y. Naaldijk, V. Fedorova, S. Sethe — 2012-02-20

Abstract: As the progress of regenerative medicine places ever greater attention on cryopreservation of (stem) cells, tried and tested cryopreservation solutions deserve a second look. This article discusses the use of hydroxyethyl starch (HES) as a cryoprotectant. Charting carefully the recorded uses of HES as a cryoprotectant, in parallel to its further clinical use, indicates that some HES subtypes are a useful supplement to dimethysulfoxide (DMSO) in cryopreservation. However, we suggest that the most common admixture ratio of HES and DMSO in cryoprotectant solutions has been established by historical happenstance and requires further investigation and optimization.

Editorial - Corrected Proof

Gail Rock — 2012-02-15

A very thought-provoking and stimulating group of papers, compiled by our Guest Editor, Urs Nydegger, MD, is the featured Theme Section for this first issue of Transfusion and Apheresis Science for 2012. We are pleased to bring you this extraordinary theme on innate immunity.

Symposium on fresh whole blood for severe hemorrhagic shock: From in-hospital to far forward resuscitations - Corrected Proof

2012-02-02

Abstract: This report is prepared for The Hemostasis and Oxygenation Research (THOR) Network and based on presentations of invited THOR investigators. In order to make it available to a larger group of interested readers it has been agreed to publish the report in TRASCI, as a “what is happening?” in view of its importance and novelty. On June 14th 2011 the first symposium on fresh whole blood (FWB) was held in Bergen, Norway. THOR network leadership, which includes Tor Hervig, PhD, MD, Geir Strandenes, MD, Erling Bekkestad Rein, MD, and Philip C. Spinella, MD, organized the event. It was sponsored by the Royal Norwegian Navy Medical Service, Norwegian Armed Forces Medical Services and Caridian BCT. The objective of this meeting was to bring together investigators from around the world who are interested in analyzing the efficacy and safety of FWB for patients with severe traumatic hemorrhagic shock and to determine the initial steps in developing a research program in this area. The THOR network is specifically interested in determining if FWB can improve morbidity and mortality in combat casualties with life threatening hemorrhagic shock. A three-year research proposal has been developed by the THOR network to determine (1) if FWB donation adversely affects donor performance of combat related skills, (2) the optimal storage solution, temperature, and acceptable storage duration for FWB, (3) the logistics of providing FWB in a combat environment safely to include optimal transport and administration methods. The symposium speakers were tasked with reviewing current data on; coagulopathy associated with massive traumatic bleeding, immunology of transfusion, outcomes associated with FWB use, logistic and medical issues of the use of FWB in far forward situations, training required for medics on FWB collection and administration, the risks of FWB and stored blood components and methods to mitigate these risks. The meeting concluded with a discussion of the THOR network’s three-year research program.

Multiorgan dysfunction accompanied with metimazole and thyroid storm - Corrected Proof

2012-01-27

Abstract: A 41-year-old man with a history of hyperthyroidism had been treated with methimazole and propranolol for the past 2months. He developed multiorgan dysfunction with acute liver failure, severe lactic acidosis, disseminated intravascular coagulation, heart failure and acute pulmonary edema with rapid deterioration of renal function. The patient had no history of alcoholism, drug abuse, blood transfusion, or exposure to hepatitis A, B, or C. Extrahepatic obstruction was ruled out with an abdominal ultrasonogram. Serologic studies and immunologic tests were negative. This case illustrates the sudden and abrupt deterioration of multiorgan dysfunction due to antithyroid drug administration and thyroid storm. The thyroid storm score of Burch and Wartofsky was 90/140. The multiorgan dysfunction was reversed by discontinuation of the methimazole and treat with hemodialysis, steroids, cholestyramine, nonselective beta-blocker, fresh frozen plasma infusion and supportive management in the intensive care unit. The patient was discharged from the hospital with normal coagulation parameters, renal and liver function tests.

Comparison of cryoprecipitate with fibrinogen concentrate for acquired hypofibrinogenaemia - Corrected Proof

A. Theodoulou, J. Berryman, A. Nathwani, M. Scully — 2012-01-09

Abstract: Background: The benefits of fibrinogen concentrate in hypofibrinogenaemia have been established in congenital and has been used in acquired disorders. Most European countries have already changed their practice, using fibrinogen concentrate.Methods: We compared the use of fibrinogen concentrate in acquired hypofibrinogenaemia to cryoprecipitate, which continues to be the standard of care in the UK. We undertook a retrospective analysis of fibrinogen increment in patients treated for acquired hypofibrinogenaemia.Results: Sixty four transfusion episodes receiving cryoprecipitate and 36 episodes receiving fibrinogen concentrate were compared. The median increment following 10 donor pools (two bags) of cryoprecipitate was 0.26g/l, compared to 0.44g/l following 2g of fibrinogen concentrate.Conclusion: With its superior safety profile from infectious diseases, this provides further evidence to support the use of fibrinogen concentrate.

Benefits and risks of IgA in immunoglobulin preparations - Corrected Proof

Urs E. Nydegger, Walter Fierz, Lorenz Risch — 2011-12-30

Abstract: The case of Immunoglobulin A (IgA) in transfusion medicine is unsettled: on one hand IgA is an important component of adaptive immunity and its deficiency may cause disease, on the other its presence in blood products might induce, in rare instances, allergy-like symptoms if not anaphylaxis.The practice with i.v. immunoglobulins currently changes as up to 10% concentrated preparations are given at fast rates hence even trace amounts of IgA contained in these IgG preparations can cause unexpected (side-) effects. Fortunately, the spectrum of sensitive IgA assays, along with anti-IgA screening assays now permits laboratories to narrow down IgA-dependent transfusion reactions to the real cases, in which IgA was the decisive trigger of anaphylaxis, proven or not by the presence of anti-IgA of the IgG or even IgE class. Tolerance to allogenic IgA has recently been reported. The known association of HLA with IgA deficiency (IgAD) has now been completed with an association to the nonsynonymous variant in IFHI1, allowing physicians to more precisely spot recipients at risk for an IgA-dependent transfusion reaction. Our review, along with our own experience here in Switzerland, allows us to conclude that IgA is a beneficial antibody rather than an allergen to be placed at the end of the list of non-infectious transfusion complications such as TRALI, febrile non-hemolytic reactions, purpura or volume overload.

Associations among birth weight, placental weight, gestational period and product quality indicators of umbilical cord blood units - Corrected Proof

Shu-Hui Wen, Wan-Ling Zhao, Py-Yu Lin, Kuo-Liang Yang — 2011-12-29

Abstract: Introduction: Numbers of CD34+ cell and total nucleated cell (TNC) and cord blood volume are commonly used as indicators for haematopoietic potential of umbilical cord blood (UCB) units. The purpose of this study was to investigate the relationship between donor-related factors and the quality indicators of UCB.Methods: Obstetric and neonatal clinical laboratory data of a total of 1549 UCB units were obtained from Buddhist Tzu Chi Stem Cells Center (BTCSCC) Cord Blood Bank. A retrospective multivariate analysis was conducted to analyze the data.Results: Our results showed that birth weight had positive correlations with each of the clinical features of CD34+ cell number, TNC count and unit volume of UCB, followed by the placental weight. Longer gestational period would decrease CD34+ cell number and volume of UCB. Female baby and mode of vaginal delivery of neonates were found to have larger amount of TNC in UCB.Conclusion: Our results would be helpful and beneficial in building up standard criteria for evaluating stored UCB units.

Three different LDL apheresis columns efficiently and equally reduce lipoprotein(a) concentrations in patients with familial hypercholesterolemia and small apolipoprotein(a) particles - Corrected Proof

2011-12-29

Abstract: Introduction: High levels of lipoprotein(a) [Lp(a)] and apolipoprotein(a) [apo(a)] are associated with cardiovascular disease. In this study we determined apo(a) particle size and compared the Lp(a) reducing efficacy of three different LDL apheresis columns; DL-75, LA-15 and EC-50W in patients with familial hypercholesterolemia (FH).Results: Average Lp(a) concentration was reduced by 70%, 74% and 75% (all p<0.0001) for DL-75, LA-15 and EC-50W, respectively. No significant changes in the relative proportion of the isoforms of 14 and 32K 4 domains were observed after apheresis.Conclusion: Three different LDL apheresis columns reduced Lp(a) efficiently with preserved ratio between apo(a) isoforms.

Soluble CD40 ligand, high sensitive C-reactive protein and fetuin-A levels in patients with essential thrombocythemia - Corrected Proof

2011-12-26

Abstract: Background: CD40 ligand (CD40L) is expressed on the surface of activated platelets and activated T lymphocytes. Circulating soluble CD40 ligand (sCD40L) is formed from these molecules proteolytically. Fetuin-A is a potent antiinflammatory cytokine.Aim of the study: In this study, we aim to investigate sCD40L levels to determine whether there is platelet activation and to measure high sensitive C-reactive protein (hs-CRP) levels to demonstrate if this leads to an inflammatory process and also to study fetuin-A levels to see if there is any concomitant antiinflammatory event in patients with essential thrombocythemia (ET).Methods: We compared 30 patients with essential thrombocythemia with 30 control subjects and in these patients we measured levels of sCD40L, hs-CRP and fetuin-A.Results: sCD40L levels were significantly higher in the ET group compared to the control group (30.6±14.4 vs. 18.5±8.9, p=0.001). Although fetuin-A levels showed a slight trend to be increased in ET patients, the difference did not reach significance (4.5±4.2 vs. 3.2±2.1, p=0.158). There were no statistically significant differences in hs-CRP levels (24.6±4.9 vs. 25.0±5.2, p=0.750).Conclusion: sCD40L was significantly higher in patients with an ET without any association with an inflammatory process and we believe this may be a marker of platelet regeneration.

Quality-assessments of characteristics of placental/umbilical cord blood associated with maternal age- and parity-related factor - Corrected Proof

2011-12-23

Abstract: Umbilical cord blood (CB) has been widely used for unrelated allogeneic stem cell transplantation. It is important to determine the quality of CB units to avoid frequent problem of limited cell yields. However, no practical and/or optimum obstetric factors to predict them are yet available. This study analyzed the relationship between maternal/neonatal obstetric factors and the laboratory parameters of CB units to identify the optimum factors associated with a high yield of total nucleated cells (TNC). Primiparae in their early 30s may be one of the first selection criteria for CB donors to obtain higher yield of TNC.

One swallow doesn’t bring spring, reply to Khamesipour et al. - Corrected Proof

Seyed Moayed Alavian — 2011-12-22

I read with interest the published article by Khamesipour et al. in your journal recently. Occult hepatitis B virus (HBV) infection is a dilemma in transfusion medicine. Screening of anti-HBc Ab is an effective tool for finding previous contact with HBV infection, but the cost-benefit of exclusion of positive anti-HBc Ab in blood donors is a debate. The prevalence of occult hepatitis B (OHB) infection varies greatly among different countries and the discrepancy regarding its prevalence depends on the accuracy and performance of the tests. First of all, the HBV DNA load in OHB cases is usually extremely low (<200IU/ml) and this very low titer of HBV may not be infectious for recipients and thus implies a low impact on transfusion services . Secondly, since the serum HBV DNA levels of occult HBV subjects are expected to be very low, in order to reduce the chance of false-positive results due to contamination or real-time PCR noise signals as well as to enhance the detection rate of the PCR test, artus HBV DNA test should be performed three times on three separate occasions in all the samples. Definite OHB is defined as at least two of the three runs of assays showing detectable HBV DNA levels. But what the authors did does not comply with this guideline. They conducted the study in an anti-HBc Ab positive group and found one positive case of OHB. I would like to mention that OHB can be present in serum samples without any evidence of previous HBV infection that is called sero-negative occult HBV infection.

Future outlook in transfusion therapy - Corrected Proof

Kenneth E. Nollet — 2011-12-21

In Townsville, Queensland, a radio host for the Australian Broadcasting Corporation asked if there would ever be a day when blood substitutes would eliminate the need for human donors. I was visiting Townsville to speak at a meeting of medical laboratory professionals, and the interview was arranged in conjunction with an Australian Red Cross blood drive.

Management of cutaneous T-Cell lymphoma patients with extracorporeal photopheresis. The hellenic experience - Corrected Proof

2011-12-19

Abstract: Extracorporeal photopheresis (ECP) is an established therapy for cutaneous T-cell lymphoma (CTCL). The objective of this study was to further explore the clinical efficacy of ECP combined with immunomodulatory agents.Eighteen patients with histologically proven CTCL were followed-up after therapy with ECP, mainly combined with interferon-α or bexarotene.A total of 61% of patients responded to therapy (n=11; CR: 5, PR: 6). Median survival was 51months, progression free survival was 28months and response duration was 29±23.9months.ECP combined therapy was highly effective or had a palliative effect in CTCL resistant to previous treatments.

Response to letter from B.A. Badlou regarding H. Ohto and K.E. Nollet article entitled “Overview on platelet preservation: Better controls over storage lesion” Transfusion and Apheresis Science 44 (2011) 321–325 - Corrected Proof

Hitoshi Ohto, Kenneth E. Nollet — 2011-12-19

We thank Dr. Badlou for calling attention to research that adds flavor and detail to our modest review. The work of Dr. Badlou and colleagues has perhaps been under-recognized, and his thoughtful letter should be taken to heart by readers eager to advance platelet transfusion therapy.

Hemolysis upon intravenous immunoglobulin transfusion - Corrected Proof

Ruth F. Padmore — 2011-12-14

Abstract: Intravenous immunoglobulin (IVIG) is a mainstay of therapy in many disorders. An uncommon adverse side effect is IVIG-related hemolysis. Risk factors for IVIG-related hemolysis have been identified, including high dose IVIG given to non-O blood group recipients with an underlying inflammatory state. IVIG-related hemolysis has been linked to anti-A and anti-B hemagglutinins in the IVIG preparations and may involve both IgG and complement mediated hemolysis. A two-hit mechanism with threshold effect is proposed for IVIG-related hemolysis. Strategies exist to minimize or avoid IVIG-related hemolysis.

Colonization of recipient tissues with transplnted murine bone marrow cells - Corrected Proof

2011-12-14

Stem cell-based therapy has been one of the best documented approaches in regenerative medicine, promising cures for a multitude of diseases and disorders. This technique, known as endogenous cell homing, has the potential to provide new therapeutic options for in situ tissue regeneration .

International trends in transfusion therapy 2011 - Corrected Proof

2011-12-14

Drugs that inhibit complement - Corrected Proof

Hubert Schrezenmeier, Britta Höchsmann — 2011-12-14

Abstract: The complement system is an important part of the innate immune system. Complement plays a crucial role in the pathophysiology of many disorders.Despite the pivotal role of the complement system, an approved targeted inhibitor of a complement factor became available only recently. Eculizumab is a humanized monoclonal antibody that inhibits complement factor C5. It is a targeted, disease modifying, treatment of paroxysmal nocturnal hemoglobinuria (PNH). It was approved be the US FDA and the European Commission in 2007. In this review we will update the experience with eculizumab in PNH and discuss potential use of eculizumab in other disorders (e.g. cold agglutinin disease; atypical HUS) and new approaches to complement inhibition with drugs other than eculizumab.

Brief biography - Corrected Proof

2011-12-12

Rationale for plasma exchange turns to innate immunity - Corrected Proof

Urs E. Nydegger — 2011-12-12

The times during which plasma exchange (PE) was prescribed in the absence of robust evidence-based rationale are gone. A steadily increasing number of clinical conditions prolong the list of diseases for which we use PE as a primary or as adjuvant treatment.

Angioedema: Patients experience and treatment relief - Corrected Proof

Martha Kaeslin, Andreas R. Huber — 2011-12-12

Abstract: Angioedema is defined as a swelling of the skin, mucosa and submucosa of the respiratory tract. It may also impair the intestinal epithelium and other mucous membranes. It can be potentially life-threatening if the upper respiratory tract is involved. In these cases emergency treatment is often required in particular if the pharynx and larynx are swollen. Beside the well-known etiologies of allergic angioedema, many forms of nonallergic angioedema are known and in the majority of these forms increased plasma and tissue concentrations of bradykinin play a critical role.

Thrombotic thrombocytopenic purpura and its look-alikes: A single institution experience - Corrected Proof

Michael Bellone, Jason Chiang, Tahmeena Ahmed, Dennis Galanakis, Lisa Senzel — 2011-12-08

Abstract: At presentation, variant or “look-alike” conditions can resemble TTP. We reviewed charts of 26 consecutive patients treated for presumed TTP. Of 15 classic TTP patients, 11 were tested for ADAMTS13; all showed severe deficiency, and inhibitor levels correlated with probability of relapse. The variant TMA group consisted of 8 patients who had active clinical disorders which overlapped with TTP. Variant TMA patients had higher creatinine and worse prognosis than classic TTP patients. “Look-alike” disorders included ITP with intravascular hemolysis following administration of WinRho™, and human granulocytic anaplasmosis. These conditions had not been previously described as TTP look-alikes.

Beliefs underlying blood donors’ intentions to donate during two phases of an avian influenza outbreak - Corrected Proof

Barbara M. Masser, Katherine M. White, Kyra Hamilton, Blake M. McKimmie — 2011-12-06

Abstract: Using a Theory of Planned Behavior (TPB) framework the current study explored the beliefs of current blood donors (N=172) about donating during a low and high-risk phase of a potential avian influenza outbreak. While the majority of behavioral, normative, and control beliefs identified in preliminary research differed as a function of donors’ intentions to donate during both phases of an avian influenza outbreak, regression analyses suggested that the targeting of different specific beliefs during each phase of an outbreak would yield most benefit in bolstering donors’ intentions to remain donating. The findings provide insight in how to best motivate donors in different phases of an avian influenza outbreak.

Evaluation of cell death after treatment with extracorporeal photopheresis - Corrected Proof

2011-12-06

Abstract: The aim of our study is to assess the mortality of leukocytes during extracorporeal photopheresis. Sixty-three photopheresis performed on 13 patients affected by chronic GvHD were evaluated. Samples were analyzed using a FACSCalibur flow cytometer. Apoptosis and necrosis of limphomononuclear cells dramatically increased after the apheretic procedure. We found a further increase of apoptotic and necrotic limphomononuclear cells after treatment with 8-MOP and UVA (p⩽0.05). Our data suggested that the immunomodulatory effects of extracorporeal photopheresis, triggered by circulating apoptotic or necrotic cells, could play an important role in the treatment of GvHD with this procedure.

The role of the extracorporeal photopheresis in the management of the graft-versus-host disease - Corrected Proof

Panayotis Kaloyannidis, Despina Mallouri — 2011-11-28

Abstract: Over the last decades significant advances have been made in the field of donor selection, alternative transplant sources, immunosuppressive treatment and supportive care, as well as in the better understanding of the immunobiology of allogeneic hematopoietic stem cell transplantation (alloTx). Nevertheless, several factors still affect unfavorably the outcome of the procedure. Graft-versus-host disease (GvHD) remains the leading cause of morbidity, non-relapse mortality and treatment failure post alloTx. So far, steroids are the widely used 1st line treatment for GvHD achieving considerable response rate however, patients who fail to respond to the initial therapy have a dismal prognosis and no standard treatment is well established for them to date. In recent years, extracorporeal photopheresis (ECP) has been proposed as an efficacious and safe treatment for steroid refractory GvHD. Overall responses of 75% have been reported in the cutaneous and mucosal involvement and 45–65% in other organ manifestations (lung, liver and intestinal), allowing reduction and even discontinuation of steroids, thus contributing towards a significant reduction of morbidity. Although the mechanism of action of ECP is not fully understood, it seems that it has an immunomodulatory rather than an immunosuppression effect and induces immunotolerance, preserving the beneficial graft-versus-tumor effect. Given these very promising results in steroid-refractory or steroid-depended GvHD, currently, extracorporeal photopheresis is being investigated as both first-line and prevention therapy also.