Gösta Berlin

A randomized controlled trial oftransfusion-related acute lung injury: is plasma from multiparous blood donors dangerous?

BACKGROUND: Transfusion‐related acute lung injury (TRALI) and other posttransfusion reactions may be caused by granulocyte and/or HLA antibodies, which are often present in blood from multiparous donors. The purpose of this study was to compare the effects of plasma from multiparous donors with those of plasma from donors with no history of transfusion or pregnancy (control plasma) in a prospective, randomized, double‐blind, crossover study.

Autologous Platelets Have No Effect on the Healing of Human Achilles Tendon Ruptures A Randomized Single-Blind Study

Background: Animal studies have shown that local application of platelet-rich plasma (PRP) stimulates tendon repair. Preliminary results from a retrospective case series have shown faster return to sports. Hypothesis: Autologous PRP stimulates healing of acute Achilles tendon ruptures. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: Thirty patients were recruited consecutively. During surgery, tantalum beads were implanted in the Achilles tendon proximal and distal to the rupture. Before skin suture, randomization was performed, and 16 patients were injected with 10mL PRP (10 times higher platelet concentration than peripheral blood) whereas 14 were not. With 3-dimensional radiographs (roentgen stereophotogrammetric analysis; RSA), the distance between the beads was measured at 7, 19, and 52 weeks while the patient resisted different dorsal flexion moments over the ankle joint, thereby estimating tendon strain per load. An estimate of elasticity modulus was calculated using callus dimensions from computed tomography. At 1 year, functional outcome was evaluated, including the heel raise index and Achilles Tendon Total Rupture Score. The primary effect variables were elasticity modulus at 7 weeks and heel raise index at 1 year. Results: The mechanical variables showed a large degree of variation between patients that could not be explained by measuring error. No significant group differences in elasticity modulus could be shown. There was no significant difference in heel raise index. The Achilles Tendon Total Rupture Score was lower in the PRP group, suggesting a detrimental effect. There was a correlation between the elasticity modulus at 7 and 19 weeks and the heel raise index at 52 weeks. Conclusion: The results suggest that PRP is not useful for treatment of Achilles tendon ruptures. The variation in elasticity modulus provides biologically relevant information, although it is unclear how early biomechanics is connected to late clinical results.

Guidelines on the use of extracorporeal photopheresis

After the first investigational study on the use of extracorporeal photopheresis for the treatment of cutaneous T‐cell lymphoma was published in 1983 with its subsequent recognition by the FDA for its refractory forms, the technology has shown significant promise in the treatment of other severe and refractory conditions in a multi‐disciplinary setting. Among the major studied conditions are graft versus host disease after allogeneic bone marrow transplantation, systemic sclerosis, solid organ transplant rejection and inflammatory bowel disease.

Photopheresis at onset of type 1 diabetes: a randomised, double blind, placebo controlled trial

BACKGROUND In recent years photopheresis, an extracorporeal form of photochemotherapy using psoralen and ultraviolet A irradiation of leucocytes, has been claimed to be an effective form of immunomodulation. AIM To evaluate its effect in type 1 diabetes we performed a double blind, controlled study using placebo tablets and sham pheresis in the control group. METHODS A total of 49 children, aged 10–18 years of age at diagnosis of type 1 diabetes were included; 40 fulfilled the study and were followed for three years (19 received active treatment with photopheresis and 21 placebo treatment). RESULTS The actively treated children secreted significantly more C peptide in urine during follow up than control children. C peptide values in serum showed corresponding differences between the two groups. The insulin dose/kg body weight needed to achieve satisfactory HbA1c values was always lower in the photopheresis group; there was no difference between the groups regarding HbA1c values during follow up. The treatment was well accepted except for nausea (n = 3) and urticaria (n = 1) in the actively treated group. There were no differences regarding weight or height, or episodes of infection between the two groups during follow up. CONCLUSION Photopheresis does have an effect in addition to its possible placebo effect, shown as a weak but significant effect on the disease process at the onset of type 1 diabetes, an effect still noted after three years of follow up.

Plasma exchange or immunoadsorption in patients with rapidly progressive crescentic glomerulonephritis : A Swedish multi-center study

A therapeutic removal of antibodies may be achieved by immunoadsorption (IA) or by plasma exchange (PE). The aim of this prospective randomised study was to compare the efficacy of these different techniques with regard to treatment of patients with rapidly progressive glomerulonephritis (RPG) having at least 50% crescents. Forty-four patients with a RPG were included for treatment either by IA or PE (with albumin as substitution for removed plasma). All patients were additionally treated with immunosuppression. A median of 6 sessions of PEs were performed in 23 patients compared with 6 IAs in 21 patients. Goodpastures syndrome (GP) was present in 6 patients (PE 3, IA 3). All of them started and ended in dialysis, two died. Among the remaining 38 patients (26 men, 12 women) 87% had antibodies to ANCA. Creatinine clearance for PE versus IA were at a median at start 17.1 and 19.8 ml/min, and at 6 months 49 and 49 ml/min, respectively. At 6 months 7 of 10 patients did not need dialysis (remaining: IA 0/5 and PE 2/5, n.s.). The extent of improvement did not differ between the groups. Three patients died during the observation period of 6 months (IA 2; PE 1, on HD). Although no difference was found between the IA or the PE group this study shows that the protocol used was associated with an improved renal function in most patients (except for Goodpastures syndrome) whereas 70% of them could leave the dialysis program.

Inadequate white cell reduction by bedside filtration of red cell concentrates

BACKGROUND White cell filtration of red cell concentrates is often performed at the bedside, in the ward, with the filter inserted in the blood administration line. The aim of this study was to evaluate the efficiency of this filtration method and compare it to filtration in the blood bank. STUDY DESIGN AND METHODS One-day-old, buffy coat-reduced, hard-packed red cell concentrates in saline-adenine-glucose-mannitol solution were filtered through different filters designed for bedside or laboratory use. With filters designed for bedside use, filtration of red cells was performed under laboratory conditions at fast flow (10 min) or under bedside conditions at slow flow (2 hours). The remaining white cells were counted microscopically. Filters designed for laboratory use were evaluated at fast flow, and the number of contaminating white cells was counted by flow cytometry. RESULTS With bedside filters, a significantly higher contamination of white cells was found in the units filtered at slow flow than at fast flow, regardless of the filter used. The number of units with > 5 x 10(6) white cells was 52 (78%) of 67 filtered at slow flow compared to 11 (23%) of 47 at fast flow, all filters taken together. This difference in white cell contamination was mainly due to an increase of polymorphonuclear cells in the red cell concentrates filtered at slow flow. With filters designed for laboratory use, 0 to 2 percent of units (n = 1448) were contaminated with > 5 x 10(6) white cells. CONCLUSION Bedside filtration for white cell reduction at slow flow is inefficient for 1-day-old, buffy coat-reduced red cell concentrates.

Measures to prevent transfusion-related acute lung injury (TRALI)

H. W. Reesink, J. Lee, A. Keller, P. Dennington, J. Pink, R. Holdsworth, H. Schennach, M. Goldman, T. Petraszko, J. Sun, Y. Meng, K. Qian, V. Rehacek, P. Turek, T. Krusius, E. Juvonen, P. Tiberghien, D. Legrand, G. Semana, J. Y. Muller, J. Bux, A. Reil, C. K. Lin, H. Daly, E. McSweeney, L. Porretti, N. Greppi, P. Rebulla, H. Okazaki, S. A. Sanchez-Guerrero, H. A. Baptista-Gonzalez, C. Martinez-Murillo, A. Guerra-Marquez, H. Rodriguez-Moyado, R. A. Middelburg, J. C. Wiersum-Osselton, A. Brand, C. van Tilburg, D. Dinesh, J. Dagger, P. Dunn, E. Brojer, M. Letowska, K. Maslanka, E. Lachert, M. Uhrynowska, E. Zhiburt, M. Palfi, G. Berlin, B. M. Frey, L. Puig Rovira, E. Muniz-Diaz, E. Castro, C. Chapman, A. Green, E. Massey, N. Win, L. Williamson, C. C. Silliman, D. J. Chaffin, D. R. Ambruso, N. Blumberg, P. Tomasulo, K. J. Land, P. J. Norris, O. C. Illoh, R. J. Davey, R. J. Benjamin, A. F. Eder, L. McLaughlin, S. Kleinman & S. Panzer

Acute Dapsone Intoxication: A Case Treated with Continuous Infusion of Methylene Blue, Forced Diuresis and Plasma Exchange

A case of massive dapsone poisoning (15 g) in a 26 year old man is reported. The patient exhibited high plasma dapsone concentration, marked methemoglobinemia, and signs of hemolysis. He recovered completely after intensive treatment with methylene blue, activated charcoal, forced diuresis, and plasma exchange. In order to avoid overdosage of methylene blue it is concluded that this substance should be given by continuous intravenous infusion in cases with severe methemoglobinemia. This way of administration caused a steady decrease in the methemoglobin concentration compared to intermittent administration. Plasma exchange was of minor benefit, probably due to the large distribution volume of dapsone.

Effects of different blood components on clot retraction analysed by measuring elasticity with a free oscillating rheometer

Free oscillation rheometry (FOR) using the ReoRox® 4 instrument makes it possible, at bedside, to study the coagulation process in blood over time and gives information on clotting time and coagulum elastic properties. In order to find out how various factors influence the FOR analysis we studied the coagulation process and change of elasticity over time in non-anticoagulated and citrated blood samples, plasma samples with various platelet concentrations (0–200 × 109/l) and blood samples with various haematocrit (0–40%). Blood samples supplemented with fibrinogen were analysed to elucidate the importance of fibrinogen on elasticity. The importance of the GPIIb/IIIa receptor on platelets was investigated by comparing the elasticity development in blood samples in presence and absence of a GPIIb/IIIa receptor inhibitor, abciximab. Anticoagulation with citrate did not have major influence on the viscoelastic properties of the coagulum. Increasing number of platelets and increasing fibrinogen concentration resulted in higher elasticity while increasing haematocrit gave lower elasticity. Blood samples with GPIIb/IIIa receptor inhibitor had very low elasticity indicating the importance of functional GPIIb/IIIa receptors. In conclusion we consider FOR to be a useful method to study the elastic properties of the coagulum. Various factors such as the number of red blood cells and platelets as well as the fibrinogen concentration should be taken into consideration when evaluating the results. The ReoRox® 4 instrument had excellent measuring range and unusually small artefactual effects on clot elasticity induced by the instrument in comparison with published results on other instruments.

Growth factor release during preparation and storage of platelet concentrates.

The platelet content of platelet‐derived growth factor (PDGF), a mitogen stored in the alpha‐granules, was studied during preparation and storage of platelet concentrates (PC) and compared to the growth‐promoting activity of platelets, β‐thromboglobulin (β‐TG) and lactate dehydrogenase (LD). We compared PC prepared from platelet‐rich plasma (PRP‐PC; n= 10) and from buffy coat. Two different pre‐preparation storage periods of the buffy coat were used: 4h (BC‐PC:4h; n = 10) and 24 h (BC‐PC: 24h; n = 5). The platelet content of PDGF and β‐TG was measured by a RIA technique and the growth‐promoting activity by incorporation of 3H‐thymidine in stimulated fibroblasts. The platelet content of PDGF, β‐TG and the growth‐promoting activity of the platelets decreased in a similar way during preparation and storage of PRP‐PC (31 ±2, 35±2 and 33±7%, respectively, at day 5 of storage; mean ± SEM). The release of LD was minor (3.9 ±0.5% at day 5). At day 1 of storage the platelet content of PDGF was significantly better preserved in BC‐PC:4h than in BD‐PC:24h (88±2 and 81 ±3%, respectively; p = 0.03). Comparing BC‐PC:4h and PRP‐PC we found a significantly better preservation of PDGF in BC‐PC:4h until day 3 of storage (80±2 and 75±1%, respectively at day 3; p = 0.046). In conclusion the preparation of PC according to the PRP method initially induces a higher loss of PDGF, and hence of the growth‐promoting activity, than the BC method.