Cryopreserved Platelets Fail Noninferiority Trial Compared With Liquid-Stored

Cryopreserved platelets failed to achieve statistical noninferiority compared with liquid-preserved platelets in patients undergoing cardiac surgery and at high risk for platelet transfusion, according to results of a new study published in JAMA.

The Cryopreserved versus Liquid Platelets II (CLIP-II) trial assessed the effectiveness and safety of platelets cryopreserved with dimethyl sulfoxide compared with liquid-stored platelets. The multicenter, randomized double-blind non-inferiority trial involved 11 Australian tertiary hospitals. Patients were eligible if they were at deemed high risk for platelet transfusion based on the Australian Cardiac Surgery Platelet Transfusion (ACSePT) score. Patients were also eligible based on clinician opinion that they were likely to require platelet transfusion.

Patients received up to three units of either cryopreserved group O apheresis platelets or conventional liquid-stored platelets either during surgery or in the first 24 hours in the intensive care unit (ICU).

While there was no difference in chest drain volume in the first 24 hours in the ICU — the primary outcome — noninferiority could not be concluded because the confidence interval crossed the prespecified noninferiority threshold. Median volume loss (interquartile range) was 610 mL (410 to 950) versus 523 mL (370 to 780); difference 87 (-50 to 280). The ratio of geometric means was 1.13 (95% CI. 0.96 to 1.34; P = .07). According to the authors, the confidence intervals indicate a potential increase in blood loss of up to 34%.

Noninferiority was defined prospectively as bleeding as no more than 20% greater bleeding within the first 24 hours of ICU admission.

The primary analysis included all randomized patients who received at least one study platelet unit. Of 388 randomized patients, 202 were determined to require platelet transfusion, with 104 receiving cryopreserved units and 98 receiving liquid-stored platelets.

More than 30% of patients required non-elective surgery. Patients were largely male (approximately 75% in each group) with a median age of 64 years. Liquid-stored platelets were 5.5 days old on average and were primarily from whole blood. The majority of patients (86.6%) received the first transfusion of study platelets during surgery. Importantly, the number of patients receiving open-label platelets after the first study unit but before all three units were transfused was greater in the cryopreserved group — 25% versus 3.1%, respectively.

Secondary outcomes were generally worse for patients receiving cryopreserved platelets, including intraoperative blood loss, chest drain volume at ICU admission and total postoperative blood loss. In addition, more platelets in the cryopreserved group received red blood cells — 74% compared with 59.3%, respectively. Fresh-frozen plasma and cryoprecipitate were also transfused more frequently in patients who received cryopreserved platelets.

The authors noted that the results of prespecified secondary outcomes “suggested that cryopreserved platelets were less hemostatically effective.”

In addition, mortality was greater for those who received cryopreserved platelets, though not significantly so, in the ICU, in-hospital and at 90 days. Intraoperative blood loss was 42% greater for the cryopreserved platelets group.

No difference was seen between the two groups in terms of prespecified or additional side effects, including local and systemic infections and core temperature greater than 102.2 degrees Fahrenheit. However, patients who received liquid-stored platelets were extubated sooner and went home earlier.

In an accompanying editorial, Mathew D. Neal, MD; Philip C. Spinella, MD; and Lucy Z. Kornblith, MD, pointed out that the inaccessibility of platelets has become a significant problem, creating “platelet deserts” in the United States and worldwide. In these areas, the risk of wastage of short-lived room temperature-stored platelet units (5-7 days) is a barrier to keeping them on-hand for emergency use in rural areas in the U.S. and in low- and middle-income countries. Finding a safe way to store platelets longer is an important research goal.

They also noted that unblinding may have impacted the results of this trial. “Given the overall poor performance of cryopreserved platelets compared with room-temperature platelets in bleeding indices, the potential of the treating clinician to react to worsening bleeding with open-label use of their standard product exists,” they wrote. “The dilution of cryopreserved platelets with room temperature liquid-stored platelets may have reduced observed differences between the study groups.”

Bleeding could have been worse in the cryopreserved group given this level of unblinded use of standard platelets, they said.