Background

Identifying antibodies to HLA (anti-HLA) by solid-phase assays is used to screen blood donors to mitigate transfusion-related acute lung injury risk. Various cutoffs for detection assays have been proposed in the literature; however, these do not take into consideration lot-to-lot variability of commercially available assays.

Study design and methods

Samples from 93 nontransfused males were tested using five different lots of a multiplex bead-based anti-HLA detection kit. A subset of 17 samples was tested on 5 days using a single lot. An additional 96 samples from donations with varied anti-HLA levels were tested using kits from two different lots. Results were reported as a normalized background (NBG) ratio.

Results

For the 93 nontransfused donors, NBG values generated using the reference lot were significantly higher than those obtained with three of the four comparator lots. However, for the 96 samples with low-, moderate-, and higher-level anti-HLA, Class I (CL-I) values were 1.4 times lower and Class II (CL-II) values were 1.2 times lower using the reference versus comparator lot. For CL-I antibodies the between-lot standard deviation (SD) was 1.36 (95% confidence interval [CI], 1.19-1.60), while the between-day SD was 1.27 (95% CI, 1.08-1.52). Similarly, for CL-II antibodies the between-lot SD was 0.81 (95% CI, 0.70-0.95), while the between-day SD was 0.50 (95% CI, 0.43-0.60).

Conclusions

There is interlot variability in the tested HLA detection assay as well as significant bias between lots. It may be reasonable to develop a new cutoff when a new lot is obtained.

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality. To determine TRALI incidence by prospective, active surveillance and to identify risk factors by a case-control study, 2 academic medical centers enrolled 89 cases and 164 transfused controls. Recipient risk factors identified by multivariate analysis were higher IL-8 levels, liver surgery, chronic alcohol abuse, shock, higher peak airway pressure while being mechanically ventilated, current smoking, and positive fluid balance. Transfusion risk factors were receipt of plasma or whole blood from female donors (odds ratio = 4.5, 95% confidence interval [CI], 1.85-11.2, P = .001), volume of HLA class II antibody with normalized background ratio more than 27.5 (OR = 1.92/100 mL, 95% CI, 1.08-3.4, P = .03), and volume of anti-human neutrophil antigen positive by granulocyte immunofluoresence test (OR = 1.71/100 mL, 95% CI, 1.18-2.5, P = .004). Little or no risk was associated with older red blood cell units, noncognate or weak cognate class II antibody, or class I antibody. Reduced transfusion of plasma from female donors was concurrent with reduced TRALI incidence: 2.57 (95% CI, 1.72-3.86) in 2006 versus 0.81 (95% CI, 0.44-1.49) in 2009 per 10 000 transfused units (P = .002). The identified risk factors provide potential targets for reducing residual TRALI.

Objective

Transfusion-related acute lung injury is the leading cause of transfusion-related mortality. A prospective study using electronic surveillance was conducted at two academic medical centers in the United States with the objective to define the clinical course and outcomes in transfusion-related acute lung injury cases.

Design

Prospective case study with controls.

Setting

University of California, San Francisco and Mayo Clinic, Rochester.

Patients

We prospectively enrolled 89 patients with transfusion-related acute lung injury, 164 transfused controls, and 145 patients with possible transfusion-related acute lung injury.

Interventions

None.

Measurements and main results

Patients with transfusion-related acute lung injury had fever, tachycardia, tachypnea, hypotension, and prolonged hypoxemia compared with controls. Of the patients with transfusion-related acute lung injury, 29 of 37 patients (78%) required initiation of mechanical ventilation and 13 of 53 (25%) required initiation of vasopressors. Patients with transfusion-related acute lung injury and possible transfusion-related acute lung injury had an increased duration of mechanical ventilation and increased days in the ICU and hospital compared with controls. There were 15 of 89 patients with transfusion-related acute lung injury (17%) who died, whereas 61 of 145 patients with possible transfusion-related acute lung injury (42%) died and 7 of 164 of controls (4%) died. Patients with transfusion-related acute lung injury had evidence of more systemic inflammation with increases in circulating neutrophils and a decrease in platelets compared with controls. Patients with transfusion-related acute lung injury and possible transfusion-related acute lung injury also had a statistically significant increase in plasma interleukin-8, interleukin-10, and interleukin-1 receptor antagonist posttransfusion compared with controls.

Conclusions

In conclusion, transfusion-related acute lung injury produced a condition resembling the systemic inflammatory response syndrome and was associated with substantial in-hospital morbidity and mortality in patients with transfusion-related acute lung injury compared with transfused controls. Patients with possible transfusion-related acute lung injury had even higher in-hospital morbidity and mortality, suggesting that clinical outcomes in this group are mainly influenced by the underlying acute lung injury risk factor(s).

Objective

Transfusion-related acute lung injury is the leading cause of transfusion-related mortality. A prospective study using electronic surveillance was conducted at two academic medical centers in the United States with the objective to define the clinical course and outcomes in transfusion-related acute lung injury cases.

Design

Prospective case study with controls.

Setting

University of California, San Francisco and Mayo Clinic, Rochester.

Patients

We prospectively enrolled 89 patients with transfusion-related acute lung injury, 164 transfused controls, and 145 patients with possible transfusion-related acute lung injury.

Interventions

None.

Measurements and main results

Patients with transfusion-related acute lung injury had fever, tachycardia, tachypnea, hypotension, and prolonged hypoxemia compared with controls. Of the patients with transfusion-related acute lung injury, 29 of 37 patients (78%) required initiation of mechanical ventilation and 13 of 53 (25%) required initiation of vasopressors. Patients with transfusion-related acute lung injury and possible transfusion-related acute lung injury had an increased duration of mechanical ventilation and increased days in the ICU and hospital compared with controls. There were 15 of 89 patients with transfusion-related acute lung injury (17%) who died, whereas 61 of 145 patients with possible transfusion-related acute lung injury (42%) died and 7 of 164 of controls (4%) died. Patients with transfusion-related acute lung injury had evidence of more systemic inflammation with increases in circulating neutrophils and a decrease in platelets compared with controls. Patients with transfusion-related acute lung injury and possible transfusion-related acute lung injury also had a statistically significant increase in plasma interleukin-8, interleukin-10, and interleukin-1 receptor antagonist posttransfusion compared with controls.

Conclusions

In conclusion, transfusion-related acute lung injury produced a condition resembling the systemic inflammatory response syndrome and was associated with substantial in-hospital morbidity and mortality in patients with transfusion-related acute lung injury compared with transfused controls. Patients with possible transfusion-related acute lung injury had even higher in-hospital morbidity and mortality, suggesting that clinical outcomes in this group are mainly influenced by the underlying acute lung injury risk factor(s).

Background

Possible transfusion-related acute lung injury (pTRALI) cases by definition have a clear temporal relationship to an alternative recipient risk factor for acute respiratory distress syndrome (ARDS). We questioned whether transfusion factors are important for the development of pTRALI.

Study design and methods

In this nested case-control study, we prospectively identified 145 consecutive patients with pTRALI and randomly selected 163 transfused controls over a 4-year period at the University of California at San Francisco and the Mayo Clinic (Rochester, Minnesota).

Results

For pTRALI, we found evidence against transfusion being important: receipt of plasma from female donors (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.29-2.3; p = 0.70), total number of units transfused (OR, 0.99; 95% CI, 0.89-1.10; p = 0.86), and number of red blood cell and whole blood units transfused (OR, 0.78; 95% CI, 0.59-1.03; p = 0.079). In contrast, we found that risk for pTRALI was associated with additional recipient factors: chronic alcohol abuse (OR, 12.5; 95% CI, 2.8-55; p < 0.001), current smoker (OR, 4.2; 95% CI, 1.67-10.8; p = 0.0024), shock before transfusion (OR, 4.6; 95% CI, 2.0-10.7; p < 0.001), and positive fluid balance before transfusion (OR, 1.32/L; 95% CI, 1.20-1.44; p < 0.001).

Conclusion

Recipient risk factors for ARDS rather than transfusion risk factors predominate in pTRALI.