Allogeneic and autologous serum eye drops: a pilot double-blind randomized crossover trial.

PURPOSE: Serum eye drops (SEDs) are used to treat a variety of ocular surface defects. Serum eye drops (SEDs) are normally produced from the patient's blood. However, not all patients can donate sufficient or suitable blood, and logistics can be challenging. Allogeneic blood from voluntary blood donors does not have these disadvantages. Our aim was to evaluate whether autologous and allogeneic SEDs have comparable efficacy and tolerability. METHODS: In a prospective, double-blind crossover trial, patients with severe dry eyes were randomized to first receive autologous SEDs for one month, followed by one-month washout, before receiving allogeneic SEDs for 1 month; or receive the SED preparations in reverse order. The Ocular Surface Disease Index (OSDI) was the primary endpoint, and various secondary endpoints were determined. A linear mixed model with random intercept for each patient was applied per treatment group to compare the pre- and postoutcome measurements. RESULTS: Nineteen patients were enrolled, of whom 15 completed the trial. When autologous SEDs were used, the mean ± SD OSDI improved from 62 ± 19 to 57 ± 18. For allogeneic SEDs, the OSDI changed from 59 ± 20 to 56 ± 23. The estimated mean difference (95% confidence interval) was -4.2 (-9.5 to 1.2) for autologous and -4.5 (-9.8 to 0.9) for allogeneic SEDs (both, not significant). Adverse events were mild and resolved completely. CONCLUSION: Autologous and allogeneic SEDs have comparable efficacy and tolerability for use in patients with severe dry eyes. Allogeneic SEDs are therefore an attractive alternative for patients who need SEDs but are clinically or logistically unable to donate blood.

Activation, function and content of platelets in burn patients.

Burn injury has severe impact on the physiologic homeostasis. Platelet counts show a distinct course post-burn injury, with a nadir at day 3 followed by a thrombocytotic period with at peak at day 15, with a gradual return to normal. So far, it is unknown how the functionality and activational status of platelets develop post burn. In this study, we investigated if the function, activation and growth factor content of platelets of burn patients are affected and how this evolves in time. Six burn patients with over 15% total burned surface area were followed during 1 month. Standard hematological and coagulation analyses, thromboelastography (TEG), platelet-function analyzer-100 (PFA), several platelet activation parameters (CD62P-CD63, AnnexinV) and growth factors (TGFb1, VEGF, PDGF-AB/BB, EGF, TGFb2, FGF-2, PDGF-AA) analyses were performed. TEG analyses showed procoagulant changes. PFA-100 analyses were nearly all within normal range. CD62P and CD63 and Annexin-V indicated no clear activation of platelets. Growth factor content followed the same course as the platelet count, reflecting a constant growth factor per platelet ratio. Concluding, platelets post burn-injury appears to be functional and not overly activated. However, burn patients seem to remain in a procoagulant state for an extensive period, which may impact their pathology.

Platelets from donors with consistently low HLA-B8, -B12, or -B35 expression do not undergo antibody-mediated internalization.

Patients refractory to platelet transfusions because of alloimmunization require HLA-matched platelets, which is only possible if a large HLA-typed donor pool is available. However, even then, patients with broad immunization or rare haplotypes may not have suitable donors. In these patients, transfusions with platelets showing low HLA class I expression may be an alternative to fully HLA-matched transfusions. In this study, we quantified the proportion of donors with consistently low HLA-B8, -B12, and -B35 expression on platelets using human monoclonal antibodies specific for these antigens. Furthermore, as model for in vivo clearance, antibody-mediated internalization of these platelets by macrophages was investigated. The expression of HLA-B8, -B12, or -B35 on platelets was extremely variable between individuals (coefficients of variation, 41.4% to 73.6%). For HLA-B8, but not for HLA-B12 or -B35, this variation was in part explained by zygosity. The variation was most pronounced in, but not exclusive to, platelets. Expression within one donor was consistent over time. Remarkably, 32% of 113 HLA-B8, 34% of 98 HLA-B12, and 9% of 66 HLA-B35 donors showed platelet antigen expression that was not or only minimally above background. Antibody-mediated internalization of platelets by macrophages correlated with antibody opsonization and antigen expression and was absent in platelets with low or minimal HLA expression. In conclusion, our findings indicate that a substantial proportion of donors have platelets with consistently low expression of specific HLA class I antigens. These platelets may be used to treat refractory patients with antibodies directed against these particular antigens, despite HLA mismatches.

Effects of storage time of red blood cell transfusions on the prognosis of coronary artery bypass graft patients.

BACKGROUND: In different centers for cardiothoracic surgery throughout the world, different policies are followed concerning the maximum storage time of to-be-transfused red blood cells (RBCs). The aim in this study was to investigate the possible role of the storage time of RBC transfusions on the outcome of coronary artery bypass graft (CABG) surgery patients. STUDY DESIGN AND METHODS: In a single-center study, all patients who had undergone CABG surgery in the period 1993 until 1999 were identified. Only those patients who had received standard, allogeneic, buffy coat-depleted, unfiltered RBCs in saline-adenine-glucose-mannitol were entered in the analyses (n = 2732). Endpoints were 30-day survival, hospital stay, and intensive care unit (ICU) stay. Storage time of the perioperative RBC transfusions was analyzed in the following four ways: 1) mean storage time of all perioperative RBC transfusions; 2) storage time of the youngest RBC transfusion; 3) storage time of the oldest RBC transfusion; and 4) comparing outcome in patients receiving only RBCs with a storage time below the median storage of 18 days with patients receiving only RBCs with a storage time above the median. RESULTS: The univariate analyses showed a strong correlation between storage time and the endpoints survival and ICU stay, but also a correlation with an established risk factor such as the number of transfusions. The multivariate analyses showed no independent effect of storage time on survival or ICU stay. CONCLUSION: In these analyses, pertaining to 2732 CABG patients, no justification could be found for use of a particular maximum storage time for RBC transfusions in patients undergoing CABG surgery.