1.
A pilot randomized clinical trial of cryopreserved versus liquid-stored platelet transfusion for bleeding in cardiac surgery: The cryopreserved versus liquid platelet-New Zealand pilot trial
McGuinness S, Charlewood R, Gilder E, Parke R, Hayes K, Morley S, Al-Ibousi A, Deans R, Howe B, Johnson L, et al
Vox sanguinis. 2021
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Editor's Choice
Abstract
BACKGROUND AND OBJECTIVES Platelets for transfusion have a shelf-life of 7 days, limiting availability and leading to wastage. Cryopreservation at -80°C extends shelf-life to at least 1 year, but safety and effectiveness are uncertain. MATERIALS AND METHODS This single centre blinded pilot trial enrolled adult cardiac surgery patients who were at high risk of platelet transfusion. If treating clinicians determined platelet transfusion was required, up to three units of either cryopreserved or liquid-stored platelets intraoperatively or during intensive care unit admission were administered. The primary outcome was protocol safety and feasibility. RESULTS Over 13 months, 89 patients were randomized, 23 (25.8%) of whom received a platelet transfusion. There were no differences in median blood loss up to 48 h between study groups, or in the quantities of study platelets or other blood components transfused. The median platelet concentration on the day after surgery was lower in the cryopreserved platelet group (122 × 10(3) /μl vs. 157 × 10(3) /μl, median difference 39.5 ×10(3) /μl, p = 0.03). There were no differences in any of the recorded safety outcomes, and no adverse events were reported on any patient. Multivariable adjustment for imbalances in baseline patient characteristics did not find study group to be a predictor of 24-h blood loss, red cell transfusion or a composite bleeding outcome. CONCLUSION This pilot randomized controlled trial demonstrated the feasibility of the protocol and adds to accumulating data supporting the safety of this intervention. Given the clear advantage of prolonged shelf-life, particularly for regional hospitals in New Zealand, a definitive non-inferiority phase III trial is warranted.
PICO Summary
Population
Adult cardiac surgery patients who were at high risk of platelet transfusion, enrolled in the CLIP-NZ Pilot study (n= 89).
Intervention
Cryopreserved platelet transfusion (n= 49).
Comparison
Liquid-stored platelet transfusion (n= 40).
Outcome
The primary outcome was protocol safety and feasibility. Over 13 months, 89 patients were randomized, 23 (25.8%) of whom received a platelet transfusion. There were no differences in median blood loss up to 48 hours between study groups, or in the quantities of study platelets or other blood components transfused. The median platelet concentration on the day after surgery was lower in the cryopreserved platelet group (122 × 10(3) /μl vs. 157 × 10(3) /μl, median difference 39.5 ×10(3) /μl). There were no differences in any of the recorded safety outcomes, and no adverse events were reported on any patient. Multivariable adjustment for imbalances in baseline patient characteristics did not find study group to be a predictor of 24 hours blood loss, red cell transfusion or a composite bleeding outcome.
2.
A randomized, controlled pilot clinical trial of cryopreserved platelets for perioperative surgical bleeding: the CLIP-I trial
Reade MC, Marks DC, Bellomo R, Deans R, Faulke DJ, Fraser JF, Gattas DJ, Holley AD, Irving DO, Johnson L, et al
Transfusion. 2019
Abstract
BACKGROUND Cryopreservation extends platelet (PLT) shelf life from 5 to 7 days to 2 to 4 years. However, only 73 patients have been transfused cryopreserved PLTs in published randomized controlled trials (RCTs), making safety data insufficient for regulatory approval. STUDY DESIGN AND METHODS The Cryopreserved vs. Liquid Platelet (CLIP) study was a double-blind, pilot, multicenter RCT involving high-risk cardiothoracic surgical patients in four Australian hospitals. The objective was to test, as the primary outcome, the feasibility and safety of the protocol. Patients were allocated to study group by permuted block randomization, with patients and clinicians blinded by use of an opaque shroud placed over each study PLT unit. Up to 3 units of cryopreserved or liquid-stored PLTs were administered per patient. No other aspect of patient care was affected. Adverse events were actively sought. RESULTS A total of 121 patients were randomized, of whom 23 received cryopreserved PLTs and 18 received liquid-stored PLTs. There were no differences in blood loss (median, 715 mL vs. 805 mL at 24 hr; difference between groups 90 mL [95% CI, -343.8 to 163.8 mL], p = 0.41), but the Bleeding Academic Research Consortium criterion for significant postoperative hemorrhage in cardiac surgery composite bleeding endpoint occurred in nearly twice as many patients in the liquid-stored group (55.6% vs. 30.4%, p = 0.10). Red blood cell transfusion requirements were a median of 3 units in the cryopreserved group versus 4 units with liquid-stored PLTs (difference between groups, 1 unit [95% CI, -3.1 to 1.1 units]; p = 0.23). Patients in the cryopreserved group were more likely to be transfused fresh-frozen plasma (78.3% vs. 27.8%, p = 0.002) and received more study PLT units (median, 2 units vs. 1 unit; difference between groups, 1 unit [95% CI, -0.03 to 2.0 units]; p = 0.012). There were no between-group differences in potential harms including deep venous thrombosis, myocardial infarction, respiratory function, infection, and renal function. No patient had died at 28 days, and postoperative length of stay was similar in each group. CONCLUSION In this pilot RCT, compared to liquid-stored PLTs, cryopreserved PLTs were associated with no evidence of harm. A definitive study testing safety and hemostatic effectiveness is warranted.
3.
An 8-week course of 45mg of carbonyl iron daily reduces iron deficiency in female whole blood donors aged 18 to 45 years: results of a prospective randomized controlled trial
Marks DC, Speedy J, Robinson KL, Brama T, Capper HR, Mondy P, Keller AJ
Transfusion. 2014;54((3 Pt 2):):780-8.
Abstract
BACKGROUND Blood donation is known to contribute to iron deficiency in regular blood donors. This study investigated the safety and efficacy of postdonation iron replacement to mitigate iron deficiency in blood donors. STUDY DESIGN AND METHODS A total of 282 female whole blood donors aged 18 to 45 were prospectively randomized in a double-blinded placebo controlled trial to receive an 8-week postdonation course of carbonyl iron (45mg daily) or placebo. The primary endpoint was prevalence of iron deficiency (ferritin < 15ng/mL) at 12 weeks postdonation. Secondary endpoints were eligibility to donate based on capillary hemoglobin (Hb) and incidence of gastrointestinal (GI) complaints. RESULTS Ferritin levels at Week 12 were significantly higher in donors receiving carbonyl iron (17.0+10.9ng/mL) compared with those receiving placebo (10.6+8.4ng/mL; p<0.001). The proportion of iron-deficient donors was significantly lower in the carbonyl iron group (51.9%) compared to the placebo (80.5%; p<0.001). The mean Hb level in the carbonyl iron group (134.6+8.7g/L) was significantly higher than in the placebo arm (130.0+9.9g/L; p<0.001), significantly improving eligibility to donate at Week 12. Significantly more donors receiving carbonyl iron had at least one GI side effect (p<0.001). Importantly, 86.7% of donors receiving carbonyl iron indicated that they would take iron on an ongoing basis. CONCLUSION An 8-week postdonation course of 45mg of carbonyl iron significantly reduced iron deficiency and was well tolerated in female whole blood donors. Postdonation iron replacement may have a role in a broader strategy to optimize donor iron status. 2013 American Association of Blood Banks.
4.
A prospective trial assessing the safety and efficacy of collecting up to 840 mL of plasma in conjunction with saline infusion during plasmapheresis
Buzza M, Marks DC, Capper H, Cassin E, Badcock CA, Reid S, Kwok M, Yang H, Lee J, Corrigan C, et al
Transfusion. 2012;52((8):):1806-13.
Abstract
BACKGROUND The demand for plasma for manufacturing intravenous immunoglobulin and other plasma derivatives is increasing. A prospective study was conducted to determine whether up to 840 mL of plasma could be safely and effectively collected in conjunction with saline infusion during plasmapheresis. STUDY DESIGN AND METHODS Ninety-one plasma donors were enrolled in a modified 3 x 3 crossover study to assess the equivalence of three plasma collection methods: 750 mL of plasma with no saline (control, Method 1), 840 mL of plasma with a 250-mL saline infusion during and at the end of the donation (Method 2), and 800 mL of plasma with a 500-mL saline infusion at the end of the donation (Method 3). The primary efficacy endpoint was the total protein concentration of the collected plasma. Secondary efficacy endpoints were immunoglobulin (Ig)G and Factor (F)VIII plasma concentration and donors' acceptance of the new procedures. Safety was determined from the adverse event (AE) rate. RESULTS The total protein, IgG, and FVIII concentrations in plasma collected under Methods 2 and 3 were significantly lower than those in plasma collected under Method 1 (p < 0.0001). These variables were also significantly lower in plasma collected under Method 2 compared to Method 3. During the study, 75 AEs were recorded, 73 of which were mild to moderate. Significantly more donors (31%) preferred Method 2 compared to Method 3 (p = 0.006). CONCLUSIONS Saline infusion during plasmapheresis led to hemodilution of plasma proteins. However, the benefits to donor safety and satisfaction are compelling reasons to implement saline infusion during plasmapheresis. 2012 American Association of Blood Banks