دانلود مقاله انتقال پلاکت های نگهداری شده

چکیده
پس زمینه
روش ها
بحث
در دسترس بودن داده ها و مواد
اختصارات
مراجع

Abstract
Background
Methods
Discussion
Availability of data and materials
Abbreviations
References

چکیده
پیش‌ زمینه. پلاکت‌هایی که در دمای 1 تا 6 درجه سانتی‌گراد ذخیره می‌شوند، از نظر هموستاتیک فعال‌تر از پلاکت‌های استاندارد دمای اتاق (RTP) ذخیره‌شده در دمای 20 تا 24 درجه سانتی‌گراد هستند. مطالعات اخیر نشان می‌دهد که تبدیل RTP به پلاکت‌های ذخیره‌شده در سرد (پلاکت‌های ذخیره‌شده در سرد تاخیری، DCSP) ممکن است راه مهمی برای افزایش طول عمر پلاکت‌ها و افزایش عرضه پلاکت‌ها باشد و در عین حال پلاکت‌ها را برای درمان خونریزی حاد فعال و پرایمینگ کند. با این حال، داده های کارآزمایی بالینی کمی وجود دارد که از اثربخشی و ایمنی DCSP در مقایسه با RTP استاندارد پشتیبانی می کند.

روش‌ها .این پروتکل جزئیات طراحی یک کارآزمایی آزمایشی داخلی چند مرکزی، دو بازویی، گروه موازی، تصادفی، کنترل فعال، کور و آزمایشی داخلی است که در دو مرکز جراحی قلب در کانادا انجام می‌شود. این مطالعه 50 بیمار بزرگسال (بیش از 18 سال) را که تحت عمل جراحی قلب با حداقل متوسط ​​پیچیده با بای پس قلبی ریوی قرار می‌گیرند و نیاز به تزریق پلاکت دارند را تصادفی می‌کند تا RTP را طبق استاندارد مراقبت (گروه شاهد) یا DCSP (گروه مداخله) دریافت کنند. بیمارانی که به صورت تصادفی در گروه مداخله قرار گرفتند، پلاکت‌هایی مشابه ABO، پوشش بافی، کاهش‌یافته با پاتوژن، در محلول افزودنی پلاکتی که تا 4 روز در دمای 22 درجه سانتی‌گراد نگهداری می‌شود، سپس در دمای 4 درجه سانتی‌گراد به مدت حداقل 24 ساعت با انقضا قرار می‌گیرند. در 14 روز پس از جمع آوری. مدت مداخله از پایان بای پس قلبی ریوی تا 24 ساعت بعد با حداکثر دو دوز DCSP است. پس از آن، همه بیماران RTP دریافت خواهند کرد. هدف از این آزمایش، ارزیابی امکان‌سنجی RCT آینده با مقایسه اثر هموستاتیک DCSP با RTP (تعریف شده به عنوان تعداد کل فرآورده‌های خون آلوژنیک تزریق شده در 24 ساعت پس از CPB) و همچنین ایمنی است. به طور خاص، اهداف امکان سنجی این مطالعه آزمایشی تعیین (1) استخدام بیش از 15٪ بیماران واجد شرایط در هر مرکز در هر ماه است. (2) محصول پلاکتی مناسب برای 90٪ از بیمارانی که به طور تصادفی در گروه پلاکت نگهداری شده در سرد قرار گرفتند در دسترس است. (3) پایبندی به انتساب تصادفی (بیش از 90٪ از بیماران تجویز محصول اختصاص داده شده).

بحث. DCSP یک راه حل لجستیکی امیدوارکننده برای رسیدگی به کمبود عرضه پلاکت و یک گزینه بالقوه موثرتر برای مدیریت خونریزی فعال است. هیچ مطالعه بالینی آینده نگر در مورد این موضوع انجام نشده است. این مطالعه آزمایشی داخلی پیشنهادی امکان سنجی یک مطالعه قطعی بزرگتر را ارزیابی خواهد کرد

Abstract

Background
Platelets stored at 1–6 °C are hypothesized to be more hemostatically active than standard room temperature platelets (RTP) stored at 20–24 °C. Recent studies suggest converting RTP to cold-stored platelets (Delayed Cold-Stored Platelets, DCSP) may be an important way of extending platelet lifespan and increasing platelet supply while also activating and priming platelets for the treatment of acute bleeding. However, there is little clinical trial data supporting the efficacy and safety of DCSP compared to standard RTP.

Methods
This protocol details the design of a multicentre, two-arm, parallel-group, randomized, active-control, blinded, internal pilot trial to be conducted at two cardiac surgery centers in Canada. The study will randomize 50 adult (≥ 18 years old) patients undergoing at least moderately complex cardiac surgery with cardiopulmonary bypass and requiring platelet transfusion to receive either RTP as per standard of care (control group) or DCSP (intervention group). Patients randomized to the intervention group will receive ABO-identical, buffy-coat, pathogen-reduced, platelets in platelet additive solution maintained at 22 °C for up to 4 days then placed at 4 °C for a minimum of 24 h, with expiration at 14 days after collection. The duration of the intervention is from the termination of cardiopulmonary bypass to 24 h after, with a maximum of two doses of DCSP. Thereafter, all patients will receive RTP. The aim of this pilot is to assess the feasibility of a future RCT comparing the hemostatic effectiveness of DCSP to RTP (defined as the total number of allogeneic blood products transfused within 24 h after CPB) as well as safety. Specifically, the feasibility objectives of this pilot study are to determine (1) recruitment of ≥ 15% eligible patients per center per month); (2) appropriate platelet product available for ≥ 90% of patients randomized to the cold-stored platelet group; (3) Adherence to randomization assignment (> 90% of patients administered assigned product).

Discussion
DCSP represents a promising logistical solution to address platelet supply shortages and a potentially more efficacious option for the management of active bleeding. No prospective clinical studies on this topic have been conducted. This proposed internal pilot study will assess the feasibility of a larger definitive study.

Background

Platelets are one of the most commonly used blood products and as such are frequently in short supply. Currently, platelets are stored at room temperature (20–24 °C) to retain post-transfusion circulatory longevity but at the cost of reduced shelf-life, which is part of the reason for the supply challenges. Cold storage (at 1–6 °C) of platelets prolongs their shelf-life while maintaining hemostatic effectiveness in acutely bleeding patients. Thus, converting room temperature-stored platelets (RTSP) before their shelf-life expires to cold-stored platelets may be a good strategy for extending their shelf-life and addressing the platelet supply challenges, but the safety and comparative effectiveness of this strategy in bleeding patients has not been robustly assessed. This pilot study will assess the feasibility of conducting a definitive comparative study of standard room temperature-stored platelets (RTSP) and delayed cold-stored platelets (DCSP).

Platelet transfusion is the primary therapy for platelet-related bleeding (i.e., excessive bleeding due to platelet deficiency or dysfunction). Platelets are one of the most commonly used blood products, particularly in major cardiothoracic surgery with cardiopulmonary bypass where platelet deficiency and dysfunction occur in all patients to varying degrees [1, 2]. As a result, approximately one in four cardiac surgical patients receive at least one platelet transfusion to treat active bleeding in the operating room or soon thereafter, with high levels of variability across institutions. Approximately 10% of the total platelet supply is directed to cardiac surgery alone [3,4,5]. Since the 1970s, standard international practice has been to store platelet units at room temperature (20–24 °C). This preserves the longevity of platelets post-transfusion but limits their storage shelf-life to 7 days for both pooled buffy-coat bacterially cultured and pooled buffy-coat pathogen-inactivated platelets [6]. The short shelf-life of room-temperature platelets (RTP) creates major supply challenges for blood suppliers and hospitals and leads to wastage of up to 30% of platelet units due to outdating [7]. Additionally, existing data suggests that storage at room temperature, while prolonging circulatory survival after transfusion, may in fact impair hemostatic function [8].

Discussion

Cold-stored platelets have been extensively studied in preclinical settings, and pilot trials in humans suggest at least comparable efficacy with no increased risk for adverse outcomes compared to room-temperature platelets [9, 18, 24, 39]. However, the safety and efficacy of cold-stored platelets have not been evaluated in large clinical trials and these products are not currently approved for use in Canada. Although they may have hemostatic superiority over conventional room-temperature platelets, there is a possibility that cold-stored platelets may increase the risk of thromboembolic events (as they are hemostatically more activated upon transfusion). However, this risk is largely theoretical and has not been demonstrated in prior studies [18, 40]. Nevertheless, we have taken several steps to minimize this risk and to identify it early should it occur. Additionally, while cohort studies have been published examining the impact on patient care of introducing delayed cold-stored platelets during times of shortages, large studies systematically measuring efficacy and safety are lacking [18].

The co-primary feasibility endpoints are adequate enrollment, adequate cold-stored platelet supply, and adequate clinician adherence to randomization assignment. We selected these outcomes because they will indicate what, if any, are the most important protocol modifications required before undertaking a large, definitive trial. Specifically, recruitment and protocol adherence are key common progression criteria for internal pilots of efficient RCTs [33], and confirming an adequate supply of cold-stored platelets at the time of transfusion is a critical metric for ensuring the feasibility of the definitive trial.

The planned primary outcome for the definitive study will be the mean number of ABCs transfused (including red cells, plasma, and platelets) within 24 h of CPB end. This outcome is an accepted measure of hemostatic efficacy that captures clinically relevant differences between study arms. It has been used as a primary outcome in a large randomized controlled trial comparing fibrinogen concentrate to cryoprecipitate in cardiac surgical patients in Canada [26, 28]. This outcome was used to support Canadian regulatory approval of fibrinogen concentrate in cardiac surgical patients, demonstrating its validity and importance for key regulatory stakeholders, and was a recommended outcome from the recent NHLBI Hemostasis Clinical Trial Outcomes Working Group [41].