兽研引言
红细胞（RBC）输注是兽医急诊和重症监护中常见的治疗干预措施。输注浓缩红细胞（pRBC）适用于改善继发于失血、溶血和/或红细胞生成受损的贫血患者的组织氧输送。然而，输血后的临床反应存在差异且不可预测，需要更多基于证据的剂量方案。多项人类和兽医研究评估了可能影响输血疗效和患者结局变异性的受血者相关、供血者相关和制品相关因素，包括输血触发时机的选择、供受者相容性和血制品储存时间。1,2 尽管人类理想的输血触发时机尚未确定，但宽松输血策略与更限制性输血策略（仅当血红蛋白<7-8g/dL时输血）之间并未显示出一致的死亡率获益。3,4 同样，在猫中，较高的输血前红细胞压积（PCV）（可能反映输血触发时机过于宽松）与较差的结局相关，但该物种的理想输血阈值仍未明确。1,5 跨物种而言，通常推荐采用个体化输血方案，综合考虑基础疾病过程、红细胞压积下降的速率和速度，以及是否存在可归因于贫血的临床症状。3,4
通过交叉配血优化供受者相容性已被提出作为减少输血相关并发症和提高输血疗效的策略，然而在猫中的结果并不一致。6–8 此外，输注较陈旧的血制品与人类和小动物较差的结局相关。9–13 与储存相关的生化和结构变化统称为红细胞储存损伤，可能损害红细胞变形能力、促进溶血并降低携氧能力，从而限制输血疗效。9,14 在储存过程中，氨和钾分别因细胞代谢和外流而蓄积。钾蓄积在储存的猫pRBC单位中可能较不明显，因为猫红细胞Na+/K+-ATP酶活性极低，因此细胞内钾浓度较低。15,16 供血者特异性因素也可能导致输血反应的变异性，但在兽医患者中研究甚少。本研究的主要目的是探讨供血单位PCV对猫输血疗效的影响。输血疗效定义为pRBC输注后受血者PCV的剂量归一化变化。另一个目的是评估各种红细胞储存损伤参数（包括供血单位钾和氨浓度）对输血反应的影响。本研究评估了较高的供血单位PCV是否与受血者PCV更大幅度的升高相关，以及储存相关变化是否对输血疗效产生不良影响。
鉴于储存血制品潜在的功能局限性，优化输血疗效具有临床意义。提高疗效可能减少重复输血的需求，从而限制红细胞储存损伤的累积暴露，并降低输血相关不良事件的风险，如过敏反应、输血相关肺损伤、输血相关循环超负荷和传染病传播。减少对异体血制品的血液暴露也可能转化为患者结局的改善。
材料与方法
这项前瞻性观察性研究于2021年12月至2024年4月在Schwarzman动物医疗中心进行。35只接受pRBC输注的客户拥有猫作为单一观察队列纳入。纳入标准为：未接受过输血、接受了pRBC输注，并在输血前和标准化输血后时间点获得了PCV测量值。排除标准为：患者既往接受过输血、输血量无法准确确定，或未采集输血后PCV测量值。鉴于样本量较小，在可能的情况下将缺失数据的受试者纳入分析。在这项观察性研究中，研究者和临床人员对患者或血制品特征未设盲。所有研究和治疗均在获得主人同意的情况下进行，并获得了Schwarzman动物医疗中心Caspary研究所内部机构动物护理和使用委员会的批准。作者确认遵守期刊的伦理指南并遵循兽医护理的最佳实践。
对每只入组患者，收集的数据包括信号特征、体重、通过血型鉴定卡（DMS Laboratories, Inc., Temple, AZ）测定的血型及交叉配血数据。在进行交叉配血时，由经过培训的人员按照实验室标准化程序进行主侧交叉配血，即将供体红细胞与受体血清混合并评估不相容性证据。交叉配血评估包括宏观和微观凝集。凝集或溶血的存在被认为提示不相容。还记录了贫血的原因或疑似原因。收集的输血特异性数据包括总输血量（mL）和计算的输血剂量（mL/kg）、输血持续时间以及住院期间实施的输血次数。
输血前测定的供体单位特征包括单位年龄（定义为从采集到输血的时间）、PCV、总固体（TS）、氨和钾浓度（Catalyst One, IDEXX Laboratories, Inc., Westbrook, ME）。 packed cell volume通过微量血细胞比容离心法测定，总固体使用折射法从血浆中测量。受体PCV在输血前即刻（基线）、输血后即刻（T0）、以及输血后12小时（T12）和24小时（T24）测量。液体治疗由主治临床医生根据患者需要酌情给予，未作为研究方案的一部分进行标准化。同时进行的液体给药未纳入PCV评估。
使用Shapiro–Wilk检验评估数据的正态性。参数数据以均值±标准差报告，非参数数据以中位数和范围报告。为评估输血疗效，将PCV测量值按输血剂量（mL/kg）标准化。为确定每单位输血血液的PCV增加量，ΔPCV计算为输血后与输血前PCV之差除以输血剂量（mL/kg），如下所示：
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新计算的参数称为ΔPCV0、ΔPCV12和ΔPCV24，代表评估的三个不同时间点。连续参数随时间的变化比较采用Wilcoxon符号秩检验。应用前向逐步线性回归分析评估测量变量之间的关联。通过似然比和卡方评估比较来评价模型和拟合优度，所有评估为具有统计学显著性的值均表明模型适当。使用Bonferroni校正控制多重比较。统计显著性设定为P值<0.05。所有统计分析均使用商业统计软件（StataSE 15.1, StataCorp LLC, College Station, TX）进行。
结果
三十五只猫符合纳入标准并入选研究。研究人群包括一只未去势雄性、21只去势雄性、13只绝育雌性，无未绝育雌性猫。代表性最高的品种为家养短毛猫（24/35），其余品种各有一只参与者。中位年龄为九岁（范围0.75–20岁），平均体重为4.2 ± 1.3 kg。大多数猫为A型血（34/35），一只猫分类为AB型血。所有猫均接受了血型特异性输血。13/35（37.1%）的猫在输血前进行了主侧交叉配血，其中11/13（84.6%）报告为相容，2/13（15.2%）为不相容。这两只猫交叉配血不相容的具体原因未确定。其余猫未进行输血前交叉配血。最常见的输血指征为红细胞生成减少（13/35），其次为混合病因（失血和生成减少的组合[7/35]）、失血（6/35）、未知原因（5/35）和溶血（4/35）。
中位输血量为29.7 mL（范围19.6–41.0），中位输血剂量为7.0 mL/kg（范围2.7–15）。二十九只猫在住院期间接受了单次输血，六只在住院期间某时接受了第二次输血，未纳入分析。
大多数输血可获得供体单位特征。表1总结了供体人群的特征。线性回归确定供体单位年龄与单位PCV和氨浓度均存在显著关联。平均单位年龄为12.6 ± 6.6天，单位年龄增加与较高的氨浓度（279.5 ± 109.4 µmol/L，95% CI：0.02–0.06）和较低的供体单位PCV（48.8 ± 5.7%，95% CI：−0.8-−0.1，p=0.0002，R2=0.44；n=34）显著相关。单位年龄与钾浓度（3.5 ± 0.8 mmol/L，95% CI：−2.9–3.7）或总固体（3.6 ± 0.6 g/dL，95% CI：−3.6–4.1）之间未发现显著关联。表1. 供体PRBC单位特征总结：储存PRBC单位的单位年龄、 packed cell volume、总固体、氨和钾的样本量、均值和标准差
本研究纳入猫的输血前中位PCV为17%（范围8–25%）。所有34只猫在输血后即刻均有输血后PCV测量值。至12小时，3只猫在PCV测量前已出院，1只猫未复查PCV，因此获得20只猫的12小时PCV测量值。至24小时，获得16只猫的PCV测量值，另有11只猫出院、1只死亡、1只安乐死、1只未复查24小时PCV。受血猫PCV在所有时间点输血后均显著升高（T0：21%，范围15–37，p<0.001；T12：23%，范围15–37，p<0.001；T24：24%，范围14–32，p=0.002）。本研究中各输血后PCV测量值之间未观察到差异。平均剂量归一化变化为ΔPCV0（0.86±0.7%/mL/kg，n=34）、ΔPCV12（1.1±1.2%/mL/kg，n=30）和ΔPCV24（0.95±0.6%/mL/kg，n=16）。任一时间点的ΔPCV与供体单位PCV、氨浓度、钾浓度或单位保存时间之间均未发现显著关联。
讨论
本研究评估了猫供体单位PCV及储存相关变量（包括单位保存时间、钾和氨浓度）对输血疗效的影响。优化pRBC输血疗效有可能减少患者血液制品暴露并改善患者结局。尽管输血导致受血猫PCV显著升高，但在对输血剂量进行归一化后，未检测到供体单位PCV或所评估的储存相关变量与该升高幅度之间的关联。这些发现提示，在本研究所评估的供体单位PCV范围内，输血反应可能反映了受血者、制品和供体相关因素的综合影响。
在人类医学中，已提出供体相关特征可能影响输血结局，尽管证据仍然有限且不一致。17有报道称，人类献血者的献血前血红蛋白水平与pRBC单位质量降低和单位血红蛋白含量减少相关。18然而，研究未能证明供体特征与受血者血细胞比容或PCV输血后变化之间存在一致关系。17人类血库实践旨在将单位PCV标准化为55–65%，理论上可使输血后PCV可预测地升高（约1–3%）。19这些估计基于过于简化的计算，未考虑供体单位PCV、按体重计算的输血剂量体积或受血者生理状态的变异性。20
Similarly, in veterinary medicine, commonly cited transfusion formulas aim to standardize dosing and predict post-transfusion PCV, with the general expectation that administration of 1 mL/kg of pRBCs will increase PCV by approximately 1%.19 Two commonly applied formulas in small animals include:
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pRBCs体积（mL）=1.5×期望PCV升高值（%）×体重（kg）
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pRBCs体积（mL）=（[期望输血后PCV–患者PCV]/供体单位PCV）×血容量（mL/kg）×体重（kg）20,21
尽管公式（b）纳入了供体单位PCV，但两种公式在预测输血后反应方面均表现不佳。8,21既往兽医研究报告，猫输血后PCV升高低于预期，交叉配血（0.75%/mL/kg）和未交叉配血（0.62%/mL/kg）患者中观察到相似反应，提示仅不相容性不能解释这种变异性。8此外，一项大型猫回顾性研究发现，尽管红细胞浓度存在差异，给予全血与pRBCs后PCV升高无差异。19这些发现提示，猫的输血反应可能无法仅通过供体单位PCV可靠预测。
人类研究还提出其他供体内在变量可能影响输血疗效，包括性别、红细胞酶活性差异、对氧化应激的易感性以及膜稳定性。21虽然在小动物医学中尚未明确定义类似的供体特异性变量，但有理由认为猫红细胞可能由于巯基数量更多、Heinz小体以及血红蛋白上可氧化硫醇残基更丰富而比其他物种更易受氧化应激影响，这可能促成该物种输血反应的变异性。5,22
与既往研究一致，本研究中供体单位存在明显的储存相关变化。单位保存时间增加与氨浓度升高和供体单位PCV降低相关，可能反映了持续的代谢降解和红细胞结构变化。16,23储存红细胞单位中氨的蓄积源于腺嘌呤核苷酸和细胞内蛋白质的分解，已被提出是不良输血事件的促成因素，而非输血疗效的决定因素。23,24观察到的供体单位PCV随保存时间降低可能归因于红细胞代谢和溶血时间增加。
尽管储存相关变量出现了可测量的变化，但本研究中未发现这些因素与输血疗效之间存在关联。人类医学中也报道了类似发现，较陈旧的红细胞单位表现出溶血增加和红细胞压积降低，但未对输血结局产生一致的不良影响。18这些数据支持在公认的储存指南范围内继续使用现有的猫浓缩红细胞单位，而无需仅因单位储存时间而预期疗效降低。然而，这些发现不应被解读为供体年龄或储存相关特征在所有情况下均无临床重要性的证据。相反，在选择血液制品时，应将供体和制品相关特征与受血者特定的临床因素一并考虑。
与储存人血中所观察到的现象相反，猫浓缩红细胞单位中的钾未随储存时间延长而升高。在人类中，随着ATP水平下降损害ATP依赖性红细胞Na+/K+-ATP酶的功能，钾会发生蓄积。25,26然而，在猫和犬中，红细胞内钾浓度低且缺乏Na+/K+-ATP酶活性，这可能解释了为何未出现这种储存相关变化。27
独立于供体单位特征之外，受血者相关变量也可能在决定输血反应方面发挥重要作用。持续性失血或红细胞破坏可能减弱输血后PCV的预期升高，同时进行的液体治疗可能通过血液稀释降低所测得的PCV。炎症可能通过缩短红细胞存活时间、铁隔离和损害红细胞生成进一步导致PCV变化，正如在患有自然发生炎症性疾病的猫中所证实的那样。28这些因素在本研究所评估的异质性群体中尤为重要，在该群体中这些临床变量无法得到控制，并可能导致了输血后PCV的变异性。这可能掩盖了供体单位特征与输血疗效之间的关联。
此外，输血前交叉配血在猫中的作用仍然复杂且尚未完全明确。6–8交叉配血试验可通过识别针对非AB血型抗原（包括Mik）的抗体来改善供受体相容性，并可能降低输血反应风险、潜在提高疗效；然而，其对输血后PCV的影响并不一致。6–8一些研究报道交叉配血相容的输血后PCV升高幅度更大，而另一些则未发现此现象，这凸显了对于未接受过输血的猫常规进行交叉配血缺乏明确、基于证据的建议。1,6–8
本研究中的所有猫均接受了血型特异性输血，其中一部分进行了输血前交叉配血。在受检者中，大多数交叉配血相容。少数猫接受了交叉配血不相容的输血。鉴于交叉配血病例数量有限，未进行组间的正式比较分析。在临床实践中，初次输血前通常并非统一进行交叉配血，其对输血结局的影响仍不确定。
在本研究中，输血疗效定义为输血后PCV升高的幅度，这是通过增加循环血红蛋白改善携氧能力的常用替代指标。然而，PCV本身并不能反映输血的生理影响，包括对氧输送、微循环功能和红细胞存活的影响。直接评估输血后红细胞存活和功能可能更准确地衡量输血获益，但此类检测在临床上难以实施，且需要专业设备和先进方法。近红外光谱和专用磁共振成像等技术可评估组织和脑氧摄取，而红细胞生物素标记可评估输血后红细胞恢复和存活动力学。29这些方法在很大程度上仍处于实验阶段，需要进一步研究以确定其在兽医医学中的实用性。
本研究存在若干局限性。未进行先验样本量计算，且相对较小的样本量、显著的病例脱落（主要由于患者出院）以及供体单位PCV范围较窄，可能限制了检测细微关联的统计效能。这可能导致假阴性结果和脱落偏倚。此外，输血疗效仅基于PCV变化进行评估，其他临床相关结局（包括输血反应、炎症反应和患者存活）未予评价。交叉配血相容性、疾病严重程度和炎症、持续性失血和同时进行的液体治疗等潜在混杂因素也未得到控制。
尽管存在这些局限性，浓缩红细胞输血在所有评估的输血后时间点均导致PCV显著且持续升高，并在24小时内趋于稳定。这些发现支持浓缩红细胞输血在贫血猫中的临床实用性，然而，未识别出可预测输血反应的供体或储存相关变量。
结论
在本研究中，未检测到供体单位PCV或所评估的储存相关变量与以受血者PCV升高衡量的输血疗效之间存在关联。尽管储存时间与较高的氨浓度和较低的供体单位PCV相关，但这些变化在任何时间点均未转化为输血后PCV的临床相关差异。尽管未检测到单位储存时间与输血疗效之间的关联，但在选择猫pRBCs时，必须考虑储存期间氨的进行性蓄积，特别是对于氨负荷可能具有临床相关性的患者，例如肝性脑病患者。输血疗效可能是多因素的，并受供体、产品和受血者相关因素的共同影响。未来纳入更大规模、多中心人群以及输血疗效功能性指标的研究可能有助于进一步明确各种因素对输血反应的相对贡献。
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Introduction
Red blood cell (RBC) transfusion is a common therapeutic intervention in veterinary emergency and critical care. Packed red blood cell (pRBC) administration is indicated to improve tissue oxygen delivery in patients with anemia secondary to blood loss, hemolysis, and/or impaired RBC production. However, the clinical response to transfusion is variable and unpredictable and additional evidence-based dosing is needed. Several human and veterinary studies have assessed recipient-, donor-, and product-related factors that may contribute to variability in transfusion efficacy and patient outcomes. These include transfusion trigger selection, donor-recipient compatibility, and blood product storage duration.1,2 Although the ideal transfusion trigger in people has not been determined, no consistent mortality benefit has been demonstrated between liberal versus more restrictive transfusion strategies (transfusing only when hemoglobin of <7-8g/dL).3,4 Similarly, in cats, higher pretransfusion packed cell volumes (PCVs) (potentially reflecting too liberal of a transfusion trigger) have been associated with worse outcomes, but ideal transfusion thresholds in this species remain undefined.1,5 Across species, individualized approaches to transfusion that incorporate underlying disease process, rate and rapidity of decline in hematocrit, and presence of clinical signs referable to anemia are generally recommended.3,4
Optimization of donor-recipient compatibility through crossmatching has been proposed as a strategy to reduce transfusion-related complications and improve transfusion efficacy, however, results in cats are inconsistent.6–8 Additionally, administration of older blood products is associated with worse outcomes in both people and small animals.9–13 Storage-related biochemical and structural changes, collectively termed the RBC storage lesion, may impair RBC deformability, promote hemolysis, and reduce oxygen carrying capacity, limiting transfusion efficacy.9,14 During storage, ammonia and potassium accumulate from cellular metabolism and efflux, respectively. Potassium accumulation may be less pronounced in stored feline pRBC units as feline erythrocytes have minimal Na+/K+-ATPase activity and consequently low intracellular potassium concentrations.15,16 Donor-specific factors may also contribute to variability in transfusion response but have been minimally investigated in veterinary patients. The primary objective of the current study was to investigate the influence of donor unit PCV on transfusion efficacy in cats. Transfusion efficacy was defined as the dose-normalized change in recipient PCV following pRBC transfusion. An additional objective was to assess the effects of various RBC storage lesion parameters, including donor unit potassium and ammonia concentrations, on transfusion response. The study evaluated whether a higher donor unit PCV was associated with greater increases in recipient PCV and whether storage-related changes adversely impacted transfusion efficacy.
Given the potential functional limitations of stored blood products, optimizing transfusion efficacy is clinically relevant. Improved efficacy may reduce the need for repeated transfusions, thereby limiting cumulative exposure to the RBC storage lesion and decreasing the risk of transfusion-associated adverse events such as hypersensitivity reactions, transfusion-related lung injury, transfusion-associated circulatory overload, and infectious disease transmission. Reduced blood exposure to allogenic blood products may also translate to improved patient outcomes.
Materials and Methods
This prospective, observational study was conducted at the Schwarzman Animal Medical Center between December 2021 and April 2024. Thirty-five client-owned cats that received pRBC transfusions were enrolled as a single observational cohort. Cats were included if they were transfusion naïve, were administered a pRBC transfusion, and had PCV measurements obtained prior to transfusion and at standardized post-transfusion timepoints. Cats were excluded if the patient had received a prior transfusion, if transfusion volume could not be accurately determined, or if no post-transfusion PCV measurements were not collected. Given the small sample size, subjects missing data were included in analyses where able. Investigators and clinical personnel were not blinded to patient or blood product characteristics in this observational study. All investigations and treatments were performed with owner consent and were approved by the internal institutional animal care and use committee of the Caspary Research Institute of the Schwarzman Animal Medical Center. The authors confirm compliance with the journal’s ethical guidelines and adherence to best practices of veterinary care.
For each enrolled patient, collected data included signalment, body weight, blood type determined via blood typing card (DMS Laboratories, Inc., Temple, AZ) and crossmatch data. When performed, major crossmatching was conducted by trained personnel using the laboratory’s standardized procedure in which donor RBCs were combined with recipient serum and evaluated for evidence of incompatibility. Crossmatches were assessed for both macroscopic and microscopic agglutination. The presence of agglutination or hemolysis were considered indicative of incompatibility. The cause or suspected cause of anemia was also recorded. Transfusion-specific data collected included total transfusion volume (mL) and calculated transfusion dose (mL/kg), duration of transfusion, and number of transfusions administered during hospitalization.
Donor unit characteristics measured prior to transfusion included unit age (defined as time from collection to transfusion), PCV, total solids (TS), ammonia and potassium concentrations (Catalyst One, IDEXX Laboratories, Inc., Westbrook, ME). Packed cell volume was determined by microhematocrit centrifugation, and total solids was measured from plasma using refractometry. Recipient PCV was measured immediately prior to transfusion (baseline), immediately following transfusion (T0), and then at 12 hours (T12) and 24 hours (T24) following transfusion. Fluid therapy was administered at the discretion of the attending clinician based on patient needs and was not standardized as part of the study protocol. Concurrent fluid administration was not incorporated into assessments of PCV.
Data was assessed for normality using the Shapiro–Wilk test. Parametric data are reported as mean ± standard deviation, and non-parametric data are reported as median and range. To assess transfusion efficacy, PCV measurements were normalized to transfusion dose (mL/kg). To determine the increase in PCV per unit of transfused blood, the ΔPCV was calculated as the difference between the post-transfusion and pre-transfusion PCV divided by the transfusion dose (mL/kg) as follows:
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\documentclass[12pt]{minimal} \usepackage{wasysym} \usepackage[substack]{amsmath} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage[mathscr]{eucal} \usepackage{mathrsfs} \DeclareFontFamily{T1}{linotext}{} \DeclareFontShape{T1}{linotext}{m}{n} {linotext }{} \DeclareSymbolFont{linotext}{T1}{linotext}{m}{n} \DeclareSymbolFontAlphabet{\mathLINOTEXT}{linotext} \begin{document}$$\mathrm{\Delta PCV{\mathrm{ }} = {\mathrm{ }}\left({post - transfusion\,{\mathrm{ }}PCV{\mathrm{ }}-{\mathrm{ }}pre - transfusion\,{\mathrm{ }}PCV} \right)/transfusion\,{\mathrm{ }}dose{\mathrm{ }}\left({mL/kg} \right)}$$\end{document}The new, calculated parameters are referred to ΔPCV0, ΔPCV12, and ΔPCV24 to represent the three different time points assessed. Comparisons between continuous parameters over time were performed by Wilcoxon signed rank test. Forward, stepwise linear regression analyses were applied to assess for associations between measured variables. The model and goodness of fit were evaluated by likelihood ratio and comparison to chi-square assessment and all values evaluated as statistically significant demonstrated appropriate models. Bonferroni correction was utilized to control for multiple comparisons. Statistical significance was set at a P value of < 0.05. All statistical analyses were performed by commercial statistical software (StataSE 15.1, StataCorp LLC, College Station, TX).
Results
Thirty-five cats met the inclusion criteria and were enrolled in the study. The study population consisted of one intact male, 21 castrated males, 13 spayed female, and no intact female cats. The most highly represented breed was domestic shorthair (24/35), and the remaining breeds included a single participant each. The median age was nine years (range, 0.75–20 years) and mean body weight was 4.2 ± 1.3 kg. Most cats were blood type A (34/35) with one cat classified as blood type AB. All cats received type-specific transfusions. Major crossmatching was performed in 13/35 (37.1%) cats prior to transfusion, of which 11/13 (84.6%) were reported as compatible and 2/13 (15.2%) as incompatible. The specific cause of crossmatch incompatibility in these two cats was not determined. The remaining cats did not undergo pretransfusion crossmatching. The most common indication for transfusion was decreased erythropoiesis (13/35), followed by mixed etiology (combination of blood loss and decreased production [7/35]), blood loss (6/35), unknown cause (5/35), and hemolysis (4/35).
The median transfused volume was 29.7 mL (range, 19.6–41.0) and the median dose of transfusion was 7.0 mL/kg (range, 2.7–15). Twenty-nine cats were administered a single transfusion over the course of hospitalization, and six received a second transfusion at some point during hospitalization, which was not included in analysis.
Donor unit characteristics were available for most transfusions. Table 1 summarizes the characteristics of the donor population. Linear regression identified significant associations between donor unit age and both unit PCV and ammonia concentration. The mean unit age was 12.6 ± 6.6 days and increasing unit age was significantly associated with higher ammonia concentration (279.5 ± 109.4 µmol/L, 95% CI: 0.02–0.06) and with lower donor unit PCV (48.8 ± 5.7%, 95% CI: −0.8-−0.1, p=0.0002, R2=0.44; n=34). No significant associations were found between unit age and potassium concentration (3.5 ± 0.8 mmol/L, 95% CI: −2.9–3.7) or with total solids (3.6 ± 0.6 g/dL, 95% CI: −3.6–4.1).
Table 1. Donor PRBC Unit Summary Characteristics Sample Size, Mean and Standard Deviation for Unit Age, Packed Cell Volume, Total Solids, Ammonia and Potassium for Stored PRBC Units
| Sample Size | Mean | Standard Deviation | |
|---|---|---|---|
| Unit age (days) | 34 | 12.6 | 6.6 |
| Donor PCV (%) | 34 | 48.8 | 5.7 |
| Donor TS (g/dL) | 34 | 3.6 | 0.6 |
| Donor Ammonia (µmol/L) | 33 | 279.5 | 109.4 |
| Donor Potassium (mmol/L) | 33 | 3.5 | 0.8 |
The median pre-transfusion PCV in cats enrolled in the study was 17% (range, 8–25%). Post-transfusion PCV measurements were available for all 34 cats immediately following transfusion. By 12 hours, three cats had been discharged prior to PCV measurement and one cat did not have a PCV rechecked, resulting in 12-hour PCV measurements for 20 cats. By 24 hours, PCV measurements were available for 16 cats as 11 additional cats were discharged, one died, one was euthanized, and one did not have a 24-hour PCV rechecked. Recipient PCV increased significantly following transfusion at all timepoints (T0: 21%, range 15–37, p <0.001; T12: 23%, range 15–37, p<0.001; T24: 24%, range 14–32, p=0.002). No differences were observed between any post-transfusion PCV measures in the study. Mean dose-normalized changes were ΔPCV0 (0.86 ± 0.7%/mL/kg, n=34), ΔPCV12 (1.1 ± 1.2%/mL/kg, n=30), and ΔPCV24 (0.95 ±0.6%/mL/kg, n=16). No significant associations were identified between ΔPCV at any time point and donor unit PCV, ammonia concentration, potassium concentration, or unit age.
Discussion
This study evaluated the impact of feline donor unit PCV and storage-related variables, including unit age, potassium, and ammonia concentrations, on transfusion efficacy. Optimizing pRBC transfusion efficacy has the potential to reduce patient exposure to blood products and improve patient outcomes. Although transfusion resulted in a significant increase in recipient PCV, after normalization for transfusion dose, no association was detected between the donor unit PCV or the evaluated storage-related variables and the magnitude of this increase. These findings suggest that, within the range of donor unit PCVs evaluated in this study, transfusion response may reflect the combined influence of recipient-, product-, and donor-related factors.
In human medicine, donor-related characteristics have been proposed to influence transfusion outcomes, although evidence remains limited and inconsistent.17 It has been reported that pre-donation hemoglobin levels in human blood donors are associated with reduced pRBC unit quality and decreased unit hemoglobin content.18 However, studies have failed to demonstrate a consistent relationship between donor characteristics and post-transfusion changes in recipient hematocrit or PCV.17 Human blood banking practices aim to standardize unit PCV at 55–65%, theoretically resulting in predictable increases in PCV (~1-3%) following transfusion.19 These estimations are based on oversimplified calculations that do not account for variability in donor unit PCV, transfusion volume per body weight dose, or recipient physiology.20
Similarly, in veterinary medicine, commonly cited transfusion formulas aim to standardize dosing and predict post-transfusion PCV, with the general expectation that administration of 1 mL/kg of pRBCs will increase PCV by approximately 1%.19 Two commonly applied formulas in small animals include:
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Volume of pRBCs (mL) = 1.5 x desired increase in PCV (%) x body weight (kg)
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Volume of pRBCs (mL) = ([desired post-transfusion PCV – patient PCV] / donor unit PCV) x blood volume (mL/kg) x body weight (kg)20,21
Although formula (b) incorporates donor unit PCV, neither formula performs well in predicting post-transfusion response.8,21 Prior veterinary studies report lower than expected increases in PCV following transfusion in cats, with similar responses observed in both crossmatched (0.75%/mL/kg) and uncrossmatched (0.62%/mL/kg) patients, suggesting that incompatibility alone does not explain this variability.8 Additionally, a large retrospective study in cats found no difference in PCV increase following administration of whole blood versus pRBCs, despite differences in red cell concentration.19 These findings suggest that transfusion response in cats may not be reliably predicted by donor unit PCV alone.
Additional intrinsic donor variables, including sex, differences in red cell enzyme activity, susceptibility to oxidative stress, and membrane stability, have been proposed to affect transfusion efficacy in human studies.21 While analogous donor-specific variables have not been clearly defined in small animal medicine, it is reasonable to consider that feline erythrocytes may have greater susceptibility to oxidative stress due to higher numbers of sulfhydryl groups, Heinz bodies, and a greater abundance of oxidizable thiol residues on hemoglobin compared to other species, which may contribute to variability in transfusion response in this species.5,22
Consistent with prior studies, storage-related changes were evident in donor units in the present study. Increasing unit age was associated with higher ammonia concentrations and lower donor unit PCV, likely reflecting ongoing metabolic degradation and RBC structural changes.16,23 Ammonia accumulation in stored RBC units results from the breakdown of adenine nucleotides and intracellular proteins and has been proposed as a contributor to adverse transfusion events, rather than as a determinant of transfusion efficacy.23,24 The observed decrease in donor unit PCV with age is likely due to increased time for RBC metabolism and hemolysis.
Despite measurable changes in storage-related variables, no association was identified between these factors and transfusion efficacy in the present study. Similar findings are reported in human medicine, with older RBC units demonstrating increased hemolysis and reduced hematocrit without consistent adverse effects on transfusion outcomes.18 These data support the continued use of available feline pRBC units within accepted storage guidelines without expectation of reduced efficacy based solely on unit age. However, these findings should not be interpreted as evidence that donor age or storage-related characteristics are clinically unimportant under all circumstances. Rather, donor- and product-related characteristics should be considered in conjunction with recipient-specific clinical factors when selecting blood products.
In contrast to what is observed in stored human blood, potassium did not increase with storage in feline pRBC units. In people, potassium accumulation occurs as declining ATP levels impair the function of ATP-dependent RBC Na+/K+-ATPase.25,26 In cats and dogs, however, erythrocytes have low intracellular potassium concentration and lack Na+/K+-ATPase activity, which likely explains the absence of this storage-related change.27
Independent of donor unit characteristics, recipient-related variables likely also play a substantial role in determining transfusion response. Continued blood loss or erythrocyte destruction may attenuate the expected increase in PCV following transfusion, and concurrent fluid administration may decrease measured PCV through hemodilution. Inflammation may further contribute to changes in PCV through decreased RBC survival, iron sequestration, and impaired erythropoiesis, as demonstrated in cats with naturally occurring inflammatory disease.28 These factors are particularly relevant in the heterogenous population evaluated in the present study, in which these clinical variables could not be controlled for and may have contributed to variability in post-transfusion PCV. This may have obscured associations between donor unit characteristics and transfusion efficacy.
In addition, the role of pre-transfusion crossmatching in cats remains complex and incompletely defined.6–8 Crossmatch testing may improve donor-recipient compatibility by identifying antibodies to non-AB blood group antigens, including Mik, and may reduce the risk of transfusion reactions and potentially improve efficacy; however, its impact on post-transfusion PCV is inconsistent.6–8 Some studies report greater increases in post-transfusion PCV with crossmatch-compatible transfusions, while others do not, underscoring the lack of clear, evidence-based recommendations for routine crossmatching in transfusion naïve cats.1,6–8
All cats in this study received type-specific transfusions, and a subset underwent pre-transfusion crossmatching. Among those tested, the majority were crossmatch compatible. A small number of cats received crossmatch-incompatible transfusions. Given the limited number of crossmatched cases, formal comparative analyses between groups was not performed. Crossmatching is generally not uniformly performed prior to initial transfusion in clinical practice, and its impact on transfusion outcomes remains uncertain.
In the present study, transfusion efficacy was defined as the magnitude of increase in post-transfusion PCV, a commonly used surrogate for improved oxygen-carrying capacity through increased circulating hemoglobin. However, PCV alone does not reflect the physiologic impact of transfusion, including effects on oxygen delivery, microcirculatory function, and red blood cell survival. Direct evaluation of RBC survival and function following transfusion would likely provide a more accurate measure of transfusion benefit, but such tests are difficult to perform clinically and require specialized equipment and advanced methodologies. Techniques such as near-infrared spectroscopy and specialized magnetic resonance imaging can assess tissue and cerebral oxygen extraction, while biotin labeling of RBCs allows for evaluation of post-transfusion RBC recovery and survival kinetics.29 These approaches remain largely experimental and require further investigation to determine their utility in veterinary medicine.
There are several limitations to this study. An a priori sample size calculation was not performed and the relatively small sample size, significant attrition (mostly due to patient discharge), and narrow range of donor unit PCVs may have limited the statistical power to detect subtle associations. This may have resulted in false-negative findings and attrition bias. Additionally, transfusion efficacy was assessed solely based on PCV change, and other clinically relevant outcomes, including transfusion reactions, inflammatory response, and patient survival, were not evaluated. Potential confounding factors such as crossmatch compatibility, disease severity and inflammation, continued blood loss and concurrent fluid therapy, were also not controlled for.
Despite these limitations, pRBC transfusion resulted in a significant and sustained increase in PCV at all assessed post-transfusion timepoints, with stabilization occurring within 24 hours. These findings support the clinical utility of pRBC transfusion in anemic cats, however, donor- or storage-related variables predictive of transfusion response were not identified.
Conclusion
In this study, no association was detected between donor unit PCV or the storage-related variables evaluated and transfusion efficacy as measured by increase in recipient PCV. Although storage duration was associated with higher ammonia concentrations and lower donor unit PCV, these changes did not translate into clinically relevant differences in post-transfusion PCV at any timepoint. Although no association was detected between unit age and transfusion efficacy, progressive ammonia accumulation during storage must be considered when selecting feline pRBCs, particularly for patients in which an ammonia load may be clinically relevant, such as those with hepatic encephalopathy. Transfusion efficacy is likely multifactorial and influenced by a combination of donor-, product-, and recipient-related factors. Future studies incorporating larger, multicenter populations and functional measures of transfusion efficacy may help further define the relative contributions of various factors to transfusion response.