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.

The effect of a fibrin sealant on knee function after total knee replacement surgery. Results from the FIRST trial. A multicenter randomized controlled trial.

BACKGROUND: Total knee replacement (TKR) is increasingly performed in short term hospital stay, making same day mobilization an important issue is after surgery. This implies little joint effusion by reducing intra-articular blood loss, which will enhance knee range of motion. The application of a topical fibrin sealant on the intraoperative bare bone and synovial tissue may contribute to better early full mobilization and thus improved functional outcomes. Since ambulation with a fully extended knee is less strenuous, we hypothesized that patients who received fibrin sealant would demonstrate improved early knee extension after six weeks compared to patients who received standard care. METHODS: A multicenter randomized controlled trial in a consecutive series of osteoarthritis patients scheduled for TKR surgery. Participants were randomized to receive fibrin sealant or not before closing the knee joint capsule. Primary outcome was change in knee extension angle(°) at short term (2 weeks) follow-up (cExt). Secondary outcomes were 6-week extension angle, knee flexion angle, hemoglobin loss, blood transfusion rates, complication rates, the Knee Society Score, and the KOOS and EQ5D questionnaires. RESULTS: When data on primary outcome became available from 250 patients, an interim analysis was performed by an independent Data Safety Monitoring Board for safety and effectivity assessment. This analysis showed that sufficient patients were included to detect a cExt of 10° between both groups. Inclusion was stopped however, all in the meantime included patients were treated according to their randomization. A total of 466 were available for analysis. Both groups were comparable in terms of baseline characteristics. The estimated mean cExt difference was 0.2° (95%CI -0.5 to 0.9). No differences in secondary outcomes were found. CONCLUSIONS: No beneficial effects or side effects were found of a topically applied fibrin sealant during TKR surgery. These results discourage the clinical use of a fibrin sealant in TKR. TRIAL REGISTRATION: Dutch Trial Register, NTR2500.

Incidence of alloantibody formation after ABO-D or extended matched red blood cell transfusions: a randomized trial (MATCH study).

BACKGROUND: Most incidentally transfused patients receive only ABO-D-compatible transfusions and antibodies are formed in up to 8%. The effect of extended (c, C, E, K, Fy(a) , Jk(a) , and S antigens) matched (EM) and ABO-D-matched red blood cell (RBC) transfusions on the incidence of new clinically relevant RBC antibody formation after a first elective transfusion event in surgical patients was studied. STUDY DESIGN AND METHODS: A multicenter randomized trial was performed in nontransfused patients who were scheduled to experience a single elective transfusion event of maximal 4 RBC units. The primary outcome was the incidence of newly formed warm reacting clinically relevant RBC alloantibodies measured in three follow-up (FU) samples taken at 7 to 10 days, 4 to 6 weeks, and 4 to 6 months posttransfusion. RESULTS: A total of 853 patients were randomized, and of these, 333 patients were transfused with a total of 1035 RBC units. At least one FU sample was available from 97% of transfused patients. In intention-to-treat analysis, new antibodies were detected in 10 of 155 ABO-D and seven of 178 EM patients, respectively. Per-protocol analysis including 190 patients showed a nonsignificant absolute risk difference (ARD) of 5.3% (95% confidence interval [CI], -1.4% to 12%) in alloimmunization between study arms. In a post hoc analysis of 138 patients who received RBCs but no platelet (PLT) transfusions the ARD increased to significance, 8.0% (95% CI, 0.4-16.0). CONCLUSION: Extended matching for selected antigens reduced the alloimmunization risk by 64% in surgical patients. Extended matching seems successful only if the patient did not receive accompanying nonmatched PLT transfusions.

Posttransfusion platelet increments after different platelet products in neonates: a retrospective cohort study.

BACKGROUND: In the Netherlands different platelet (PLT) products are used for neonatal transfusions: volume-reduced PLTs, PLT additive solution (PAS) II PLTs, and plasma PLTs. These are standard products at three different neonatal intensive care units where local transfusion guidelines apply. Here we assess the posttransfusion count increments with these products. STUDY DESIGN AND METHODS: We performed a retrospective cohort study of neonates who received, in the first month after birth, between January 1, 2007, and December 31, 2008, at least one PLT transfusion. Seventy-four neonates who received 197 volume-reduced PLTs transfusions, 68 neonates who received 105 PASII PLT transfusions, and eight neonates who received eight plasma PLT transfusions were analyzed. Early (within 8 hr after transfusion) and follow-up count increments (16-24 hr after transfusion) were evaluated for 191 and 81 volume-reduced PLTs, 77 and 56 PASII PLTs, and six and five plasma PLT transfusions, respectively, using a random-effects model. RESULTS: Volume-reduced PLTs were transfused at twice the dose in one-fifth the volume of PASII and plasma PLTs. The early posttransfusion count increment was higher for volume-reduced PLTs at 111 × 10(9)/L (95% confidence interval [CI], 86-135) compared to PASII PLTs at 62 × 10(9)/L (95% CI, 40-84; p = 0.000) and plasma PLTs at 47 × 10(9)/L (95% CI, 14-79). The follow-up count increment was also higher for volume-reduced PLTs at 60 × 10(9)/L (95% CI, 19-100) compared to PASII PLTs at 38 × 10(9)/L (95% CI, -0.2 to 77; p = 0.082) and plasma PLTs at 4 × 10(9)/L (95% CI, -38 to 46). CONCLUSION: Neonates who received twice the PLT dose by volume-reduced PLTs had twice as high early and follow-up count increment showing similar efficacy of products.

A comparison of volume-reduced versus standard HLA/HPA-matched apheresis platelets in alloimmunized adult patients.

BACKGROUND: Our blood bank prepares, on indication or request, a volume-reduced (VR) platelet (PLT) product with greater than 95% reduced plasma content and a 15-fold higher PLT concentration, potentially minimizing adverse reactions due to plasma, in particular for human leukocyte antigen (HLA)/human PLT antigen (HPA)-matched PLTs when minor ABO incompatibility cannot be avoided. Here we compared the clinical effectiveness of VR apheresis PLTs (APs) with standard APs. STUDY DESIGN AND METHODS: We performed a single-center cohort study among consecutive alloimmunized patients who received either HLA/HPA-matched standard APs and/or VR-APs between 1994 and 2008. The endpoints were corrected count increments (CCIs), time to next transfusion, and frequency of adverse reactions. The CCI of VR PLTs was calculated using the PLT dose before volume reduction. Using a random effects model, 851 transfusions to 68 patients were evaluated for CCI and 731 transfusions to 64 patients for time to next transfusion. The frequency of reported adverse reactions was compared between the groups. RESULTS: The 1-hour CCI was 23% (95% confidence interval [CI], 9%-42%; p < 0.001) lower and the 24-hour CCI was 17% (95% CI, -11% to 59%; p = 0.278) lower after VR-APs. The mean time to next transfusion was similar: standard APs, 3.1 days (95% CI, 2.7-3.5); and VR-APs, 2.8 days (95% CI, 2.5-3.2). Eight adverse reactions were reported: 4 of 619 in the standard AP group and 4 of 1202 in the VR-AP group. CONCLUSION: VR-APs showed lower 1- and 24-hour CCIs than standard-APs, which can be largely explained by the lower PLT dose of VR-APs. The benefits of plasma reduction should seriously be outweighed given these lower increments.