Clinical perspectives of platelet transfusions: Defining the optimal dose

To halt bleeding in patients with severe thrombocytopenia due to bone marrow failure, it is desirable to achieve a post-transfusion blood platelet count of 40 × 10⁹/L by platelet transfusions. Based on calculations of corrected count increments, each 1 × 10¹¹ platelets transfused will increase the blood platelet count approximately 10 × 10⁹/L per each square meter of patient body surface area. Thus, the post-transfusion blood platelet count will be approximately 20 × 10⁹/L following transfusion of 3 × 10¹¹ platelets to a 5 foot, 8 inch patient weighing 170 pounds (2.0 m²), who is bleeding because of a pre-transfusion platelet count of 5 × 10⁹/L. The post-transfusion platelet count likely will be even lower in sick patients (sepsis, amphotericin B plus antibiotic therapy, splenomegaly, graft-vs.-host disease, etc.) or if platelets are lost from the unit by leukofiltration before transfusion. Although a dose of 3 × 10¹¹ platelets is acceptable, in a regulatory sense for product quality, it is inadequate to control bleeding in most thrombocytopenic adult patients. Adjusting dose for body size, bleeding patients with pre-transfusion blood platelet of <10 × 10⁹/L and weighing >120 pounds should receive approximately 6 × 10¹¹ platelets, those weighing 30 to 120 pounds should receive 3 × 10¹¹ platelets, and infants weighing <30 pounds (15 kg) should receive 5–10 ml/kg of platelet concentrate.     

降低预防性血小板输注剂量对慢性血小板减少症患者出血风险的影响

目的 探讨降低预防性血小板输注剂量对慢性血小板减少症(chronic thrombocytopenia)患者出血的影响.方法 选择2008年10月至2010年12月在本院住院的80例因造血干细胞移植(hematopoietic stem cell transplantation,HSCT)、血液系统肿瘤和实体瘤化疗引起...     

Clinical consequences of alterations in platelet transfusion dose: a prospective, randomized, double-blind trial

BACKGROUND: The dose-response relationship for platelet transfusion has become increasingly important as the use of platelet transfusion has grown. STUDY DESIGN AND METHODS: One hundred fifty-eight prophylactic apheresis platelet transfusions were administered to 46 patients undergoing high-dose therapy followed by hematopoietic progenitor cell transplantation in a prospective, randomized, double-blind, multiple-crossover study. Transfusions were administered in pairs, differing only in platelet content. Each pair consisted of a lower-dose platelet component (LDP) and a higher-dose platelet component (HDP) administered in random order to the same patient. LDPs contained a mean of 3.1 x 10(11) platelets (range, 2.3-3.5 x 10(11)), and HDPs contained a mean of 5.0 x 10(11) platelets (range, 4.5-6.1 x 10(11)). Patients with active bleeding and those who were refractory to platelet transfusions were excluded. RESULTS: The mean posttransfusion platelet count increment with LDP was 17,010 per microL, and that with HDP was 31,057 per microL (p<0.0001). Only 37 percent of LDPs resulted in platelet count increments of at least 20,000 per microL, whereas 81 percent of HDPs resulted in increments above this level (p<0.0001). The mean transfusion-free interval with LDP was 2.16 days, whereas that with HDP was 3.03 days (p<0.01). Administration of LDPs was associated with a 39 to 82 percent increase in the relative risk (per day) of requiring subsequent platelet transfusions (p<0.0001). CONCLUSION: As compared to the administration of HDPs, the administration of LDPs for prophylactic transfusion in hematopoietic progenitor cell transplant patients results in a lower platelet count increment, a lower likelihood of obtaining a posttransfusion platelet increment >20,000 per microL, a shorter transfusion-free interval, and a greater relative risk per day of requiring additional transfusions.     

单采新鲜血小板与冰冻血小板的输注效果分析．

[目的]探讨单采新鲜血小板与冰冻血小板的临床输注效果。[方法]76例血小板减少或血小板功能障碍患者输注单采血小板,随机分为两组,48例输注单采新鲜血小板,28例输注冰冻血小板,观察输注前后24h外周血血小板计数及出血止血情况。[结果]输注新鲜血小板组与输注冰冻血小板组在止血效果方面无明显差异,但在提高外周血血小板计数方面,新鲜血小板组明显优于冰冻血小板组。[结论]提倡新鲜血小板输注,冰冻血小板可以用于急救由于血小板减少导致的出血性疾病。     

Comparison of efficacy of low and high dose prophylactic platelet transfusion therapy in thrombocytopenic haemato-oncology patients

IntroductionTo determine an optimal platelet dose in thrombocytopenic patients is important for their judicious use. Transfusing platelets in different doses and comparing their post transfusion response can achieve this.AimTo compare the efficacy of low and high dose single donor apheresis platelets (SDAP) with standard dose transfusions in terms of Corrected Count Increment (CCI), Percent Platelet Recovery (PPR) and transfusion free interval.MethodIt was a prospective case control study done from January 2016 to April 2017. Twenty-eight hemato-oncology patients with CCI ≥5000 at 20–24 hours after standard dose (3 × 10¹¹/unit), received low dose (1.5 × 10¹¹ platelets/unit) and high dose (>4 × 10¹¹ platelets/unit) SDAP. CCI and PPR were calculated after 20 to 24 hours of transfusion. Transfusion free interval and bleeding episodes were also noted. Grading was done according to WHO bleeding scale.ResultThere was no statistical difference in CCI and PPR when standard dose was compared with low dose (CCI: p = 0.92, PPR: p = 0.89). When standard and high dose was compared, standard dose gave better results than the high dose in terms of CCI (p = 0.006) and PPR (p = 0.008) although the post transfusion increments were comparable (p = 0.938). High dose gave better (p = 0.005) platelet count increments than low dose but CCI (p = 0.04) and PPR (p = 0.05) was significantly less than the low dose. The difference in transfusion free intervals after three doses was not significant. Donor exposure to the patients was significantly (p = 0.000) reduced to 17.5%.ConclusionPossibility of low dose as an alternative to standard dose can be considered in view of comparable platelet response indicators and significantly reduced donor exposure.     

Platelet dose consistency and its effect on the number of platelet transfusions for support of thrombocytopenia: an analysis of the SPRINT trial of platelets photochemically treated with amotosalen HCl and ultraviolet A light

BACKGROUND: The SPRINT trial examined efficacy and safety of photochemically treated (PCT) platelets (PLTs). PCT PLTs were equivalent to untreated (control) PLTs for prevention of bleeding. Transfused PLT dose and corrected count increments (CIs), however, were lower and transfusion intervals were shorter for PCT PLTs, resulting in more PCT than control transfusions. PLT dose was analyzed to determine the impact of the number of PLTs transfused on transfusion requirements. STUDY DESIGN AND METHODS: Transfusion response was compared for patients with all doses of >or=3.0 x 10(11) and the complementary subset of patients with any dose of fewer than 3.0 x 10(11). Analyses included comparison of bleeding, number of PLT and red blood cell (RBC) transfusions, transfusion intervals, and CIs between PCT and control groups within each PLT dose subset. RESULTS: Mean PLT dose per transfusion in the PCT group was lower than in the control group (3.7 x 10(11) vs. 4.0 x 10(11); p<0.001). More PCT patients received PLT doses of fewer than 3.0 x 10(11) (n=190) than control patients (n=118; p<0.01). Comparisons of patients receiving comparable PLT doses showed no significant differences between PCT and control groups for bleeding or number of PLT or RBC transfusions; however, transfusion intervals and CIs were significantly better for the control group. CONCLUSIONS: When patients were supported with comparable doses of PCT or conventional PLTs, the mean number of PLT transfusions was similar. Lower CIs and shorter transfusion intervals for PCT PLTs suggest that some PLT injury may occur during PCT. This injury does not result in a detectable increase in bleeding, however.     

Comparative clinical studies of platelet concentrates: effects on clinical outcome and the use of healthcare resources. NBS Platelet Study Group

The Platelet Study Group are developing proposals to conduct a prospective randomised trial of different platelet products in the transfusion support of patients with haematological malignancy. All patients will receive prestorage leucodepleted red cells and will be randomised to receive either multiple donor non-apheresis buffy coat platelets which are non-leucodepleted (BCP), single donor apheresis platelets non-leucocyte depleted (SDP) or single donor (LD-SDP). All leucocyte depleted products will contain fewer than 5 x 10(6) WBC/transfusion. The primary objective of the study is to compare clinical efficacy, the incidence of adverse reactions treatment outcome and the use of healthcare resources.     

Hemostasis in patients with severe von Willebrand disease improves after normal platelet transfusion and normalizes with further correction of the plasma defect

BACKGROUND: A defective hemostatic effect of plasma concentrate infusion in patients with severe von Willebrand disease (vWD) has been ascribed to the absence of platelet von Willebrand factor (vWF) STUDY DESIGN AND METHODS: The role of platelet vWF in hemostasis of severe vWD was investigated. A plateletpheresis unit (4-5 × 10(11) platelets) from a normal compatible donor was transfused before any cryoprecipitate infusion to three type 3 vWD patients and to one patient with severe type 1 vWD with low levels of platelet vWF who required replacement therapy for bleeding episodes. Autologous platelets were transfused to one of the patients with type 3 vWD. RESULTS: Partial corrections of bleeding times (14-17 min vs. baseline>30 min) were observed in all patients after the transfusion of normal platelets. During cryoprecipitate infusion, bleeding times were normalized (<6 min), and bleeding episodes stopped when plasma levels of vWF activity ranged from 14 to 18 U per dL. Platelet interactions with the subendothelium increased in parallel with the correction of bleeding times. These results indicate that if approximately 20 percent of the total number of platelets have normal vWF antigen and if plasma vWF levels are at least 14 U per dL, then bleeding times will normalize and mucosal hemorrhages will stop. Transfusion of autologous platelets in one patient with type 3 vWD did not modify bleeding times or platelet adhesion on the subendothelium. CONCLUSION: The hemostatic effect of normal platelets in type 3 vWD seems to be related to the platelet vWF in the transfused platelets.     

重组人白细胞介素-11治疗急性髓系白血病巩固化疗后血小板减少的疗效观察和药物经济学评价

目的观察急性髓系白血病强化巩固治疗后使用重组人白细胞介素11(rhIL-11)对低血小板持续时间和血小板输注量的影响;评价rhIL-11治疗急性髓系白血病巩固化疗后血小板减少的药物经济性。方法对21例急性髓系白血病患者采用前后自身对照的方法,观察强烈化疗后用或不用rhIL-11,在严重血小板减少的发生率、血小板的最低值、低血小板的持续时间、血小板输注次数和输注量等方面的差异,并测算出使用rhIL-11后,患者治疗费用的变化。结果与对照组比较,rhIL-11组的低血小板持续时间明显缩短,每个疗程的血小板输注次数和输注量明显减少,差异均有统计学意义(t分别=4.23、2.28、2.30,P均<0.05);而两组的血小板最低值的差异无统计学意义(t=1.32,P>0.05);两组的严重血小板减少(低于10×109/L和低于5×109/L)的发生率比较,差异均无统计学意义(t分别=1.11、0.10,P均>0.05)。rhIL-11组的治疗费用较对照组平均每个疗程增加约1326.14元。结论急性髓系白血病巩固化疗后使用rhIL-11不能改善严重血小板减少的发生率和最低值,但是可以缩短低血小板持续时间并减少血小板的输注次数和输注量;与单纯输注血小板比较,使用rhIL-11增加了临床治疗费用。     

Collection of platelets with a new cell separator and their storage in a citrate-plasticized container

A new apheresis device using microprocessor control for the collection of a high-purity single-donor platelet concentrate was evaluated, as was the storage of platelets for up to 5 days in a citrate-plasticized polyvinylchloride blood bag. The study was conducted in three phases: collection of platelets for in vitro studies and determination of donor safety; autologous transfusion of platelets in healthy volunteers; and transfusion of platelets in patients requiring platelet transfusion therapy. Donors had mild hypocalcemia and minimal changes in blood counts except for a platelet count reduction from 288 +/- 50 x 10(3) (288 +/- 50 x 10(9)/L) to 217 +/- 43 x 10(3) per microL (217 +/- 43 x 10(9)/L). A mean of 3.36 +/- 1.24 x 10(11) platelets was collected in the mean volume of 214 mL with red cell and white cell contamination in the range of 10(7). Morphology and aggregation were as described previously in stored platelets. Platelet survival data in eight subjects showed a mean recovery of 61 +/- 11 percent and mean survival of 5.03 +/- 1.07 days by a weighted-mean model. Patients transfused with platelets had mean increments of 23,000 immediately and of 8000 at 24 hours; corrected count increments were 6000 at 1 hour and 4000 at 24 hours. The platelets were successful in providing hemostasis to these patients. Clinically useful 5-day-stored platelets are obtained by using this apheresis technology with a functionally closed system and a citrate-plasticized blood bag.     

Relationship between platelet count and bleeding risk in thrombocytopenic patients

Platelets are lost from circulation by 2 mechanisms: senescence and random loss. Approximately 7.1 x 10(3) platelets/microL/d are postulated to be randomly used in maintaining vascular integrity. Thus, in clinically stable patients, major bleeding is unusual unless the platelet count is 相似文献   

WBC-reduced platelet concentrates from pooled buffy coats in additive solution: an evaluation of in vitro and in vivo measures

BACKGROUND: The use of a platelet additive solution (PAS-II, Baxter) may have benefits over plasma for storage of platelets. It was the aim of this study to develop a method to produce WBC-reduced platelet concentrates (PCs) in PAS-II with >240 x 10(9) platelets and <1 x 10(6) WBCs per unit, which can be stored for 5 days at pH >6.8 and that will give sufficient platelet increments after transfusion: a 1-hour CCI of >7.5 and a 20-hour CCI of >2.5. STUDY DESIGN AND METHODS: PCs were made from five pooled buffy coats and 250 g of PAS-II. After centrifugation the PCs were WBC-reduced with a filter (Autostop BC, Pall Biomedical) and stored in a 1000-mL polyolefin container. CCIs were assessed in stable hemato-oncologic patients after 5-day old PCs were transfused. RESULTS: Routinely produced PCs contained a median of 310 x 10(9) platelets (n = 5,363) with 3.5 percent containing <240 x 10(9) platelets, in a median volume of 320 mL (n = 11,834). The median number of WBCs was <0.03 x 10(6) (n = 694). The WBC count exceeded 1 x 10(6) in three PCs, but it was always <5 x 10(6), giving 99-percent confidence that more than 99.5 percent of the units will contain <1 x 10(6) WBCs. The pH remained >6.8 on Day 8, provided the concentration was below 1.1 x 10(9) platelets per mL (n = 32). After 28 transfusions in 28 patients, the 1-hour CCI was 12.6 +/- 4.3 (mean +/- SD, with 2/28 CCIs <7.5) and the 20-hour CCI was 8.9 +/- 5.6 (with 4/28 CCIs <2.5). Limitations of this study include the absence of a control group of patients receiving platelets stored in plasma and of in vivo radiolabeled survival studies, but a comparison of these data with previously published data suggested that the in vivo survival of platelets stored in PAS-II is less than that of platelets stored in plasma. CONCLUSION: The WBC-reduced PCs conformed to specifications. These WBC-reduced PCs could be stored at least 5 days with maintenance of pH, and they gave sufficient increments after transfusion to patients.     

低温保存血小板的制备与质控效果的观察

本研究探讨建立系统的二甲亚砜 (DMSO)低温保存血小板的制备及质控的技术和方法 ,以保证低温保存血小板的质量。采取的方法 :①DMSO在使用前进行超滤替代消毒 ;②采血后 6小时内对血液进行离心 ,将血袋管道系于套桶上方 ;③以 4 80×g的相对离心力 ,离心加速 9档 ,减速 4档 ;④分离血小板时流速不能太快 ,80 - 10 0ml富含血小板血浆应在 1分钟左右分完 ;在加入DMSO时速度以 1毫升 /分钟为宜 ;加好DMSO后放入 - 80℃冰箱保存 ;临床输注前将血小板置于 38- 4 0℃的循环水浴中 ;⑤融化后进行血小板计数、白细胞和红细胞计数 ,检测HBsAg、抗 HCV、抗 HIV、梅毒特异性抗体 ,测定丙氨酸氨基转移酶 (ALT)并进行细菌培养。结果表明 :共制备14 80 0单位低温保存血小板 ,其中机采血小板 80单位。对其中 30 0单位进行质控。手工分离血小板计数≥ 2 .4×10 10 /单位 ,平均得率在 70 %以上。机采血小板计数≥ 2 .5× 10 11/单位。手工分离血小板红细胞污染数≤ 1× 10 9个/单位 ,白细胞污染数≤ 5× 10 7个 /单位。融化后进行细菌培养 ,无细菌生长 ;ALT均在正常范围内。患者输注后具有明显的止血作用。结论 :本方法制备的手工分离和机采低温保存血小板质量可靠 ,临床应用效果良好。     

Effects of in vitro adult platelet transfusions on neonatal hemostasis

Summary. Background: Thrombocytopenia is frequent among neonates, and 20–25% of affected infants are treated with platelet transfusions. These are frequently given for mild thrombocytopenia (platelets: 50–100 × 10⁹ L^?1), largely because of the known hyporeactivity of neonatal platelets. In tests of primary hemostasis, however, neonates have shorter bleeding and closure times (CTs) than adults. This has been attributed to their higher hematocrits, higher von Willebrand factor (VWF) concentrations, and predominance of longer VWF polymers. Objective: To determine whether the ‘transfusion’ of adult (relatively hyperreactive) platelets into neonatal blood results in a hypercoagulable profile. Methods: Cord blood (CB) and adult peripheral blood (PB) were separated (with a modified buffy coat method) to generate miniaturized platelet concentrates (PCs) and thrombocytopenic blood. PB‐derived and CB‐derived PCs (n = 7 per group) were then ‘transfused’in vitro into thrombocytopenic CB and PB. The effects of autologous vs. allogeneic (developmentally mismatched) ‘transfusions’ were evaluated with whole blood aggregometry, a platelet function analyzer (PFA‐100), and thromboelastography (TEG). Results: Adult platelets aggregated significantly better than neonatal platelets in response to thrombin receptor‐activating peptide, ADP, and collagen, regardless of the blood into which they were transfused. The ‘transfusion’ of adult platelets into thrombocytopenic CB resulted in shorter CTs‐EPI (PFA‐100) and higher clot strength and firmness (TEG) than ‘transfusion’ of neonatal autologous platelets. Conclusions: In vitro‘transfusion’ of adult platelets into neonatal blood results in shorter CTs than ‘transfusion’ with neonatal platelets. Our findings should raise awareness of the differences between the neonatal and adult hemostatic system and the potential ‘developmental mismatch’ associated with platelet transfusions for neonatal hemostasis.     

Benefits of lower neonatal platelet transfusion thresholds

• Degree of thrombocytopenia is not a predictor of bleeding risk in neonates, yet most platelet transfusions are given prophylactically in non-bleeding premature infants.
• Recent data support a lower platelet transfusion threshold of 25 × 10⁹/L in non-bleeding premature neonates and indicate that higher transfusion thresholds may be associated with harm including increased risk of death and bleeding.
• The mechanism of increased adverse events with higher platelet transfusion threshold is unknown, but considerations include adult platelets disrupting the neonatal hemostatic balance of hypoactive platelets in a hypercoagulable and fragile environment and having a pro-inflammatory effect.

     

Identification of underlying and transfusion-related platelet qualitative alterations in the hemato-oncologic patient

Hemato-oncologic patients with chemotherapy-induced thrombocytopenia are one of the populations receiving platelet transfusions. The general practice with these patients is to give prophylactic platelet transfusions when platelet counts fall below 10 × 10⁹ PLT/L. However, in more than 40% of these patients, platelet transfusion does not prevent bleeding. The reason of the low efficacy of platelet transfusion in the context of chemotherapy patients is not entirely understood.We therefore aimed at immunophenotyping the expression of platelet surface and activation markers and thrombopoietin levels from hemato-oncologic patients before and after transfusion. A more detailed follow-up was performed in three patients that underwent autologous bone marrow transplantation.As previously reported, basal platelet activation was observed in hemato-oncologic patients. Based on flow cytometry parameters, i.e. the percentage of positivity and mean fluorescence intensity (MFI) distribution, our data provide an additional interpretation of platelet acquired qualitative changes in the hemato-oncologic patient. From our results we propose: first, the underlying activation of platelets in the hemato-oncologic patient is accompanied by loss of expression of the platelet receptors that are susceptible to protease-mediated shedding; second, soon after transfusion, the newly circulating donor platelets show additional activation, which may result in subsequent platelet receptor recycling and potential accelerated clearance of these activated platelets.In conclusion, the immunophenotype of circulating platelets changes after prophylactic platelet transfusion. Next to platelet count increment, exploration of this immunophenotype might help to explain transfusion refractory bleeding in hemato-oncologic patients. Eventually this may lead to personalization and improvement of the present platelet transfusion support regime.     

Compliance with prophylactic platelet transfusion trigger in haematological patients

The aim of prophylactic platelet transfusions in haemato-oncologic patients with thrombocytopenia is to prevent bleeding. Currently, a platelet transfusion trigger of 10 x 10(9) L(- 1) is considered to be safe. Transfusion compliance with this trigger can save costs. To investigate the compliance with this trigger of 10 x 10(9) L(- 1), we have evaluated 1447 platelet transfusions given during a period of 1 year to haematological patients. In half of the transfusions, there had been compliance with the trigger of 10 x 10(9) L(- 1). About three-quarters of all platelet transfusions were given at platelet counts < or =20 x 10(9) L(- 1). Transfusions at levels >20 x 10(9) L(- 1) were usually performed because of bleeding, scheduled interventions or concurrent anticoagulant therapy. We conclude that compliance with the prophylactic platelet transfusion trigger of 10 x 10(9) L(- 1) was about 50%; however, deviation from the trigger was partly explained by risk factors that justify a higher transfusion trigger.     

Platelet transfusion refractoriness responding preferentially to single donor aphaeresis platelets compatible for both ABO and HLA

Platelet transfusion refractoriness is challenging to manage. When human leucocyte antigens (HLA)‐sensitized patients fail to respond to HLA‐matched (HLA‐m) platelets, non‐immune destruction may be assumed, and collections of HLA‐m platelets abandoned. We report cases of highly HLA‐sensitized patients whose only satisfactory platelet transfusion responses were consistently associated with products compatible for both HLA‐ and ABO‐matched (HLA‐m/ABO‐m) platelets, and in whom unsatisfactory increments occurred if either form of major incompatibility was permitted (HLA‐u or ABO‐u). Absolute platelet increments (APIs) were measured and classified as satisfactory if ≥10 and unsatisfactory if <10. Patient 1, age 59 years, group O, with myelodysplastic syndrome/acute myelogenous leukemia (MDS/AML), was unresponsive to either fresh ABO‐m or HLA‐m platelets. Of 17 HLA‐m platelets, satisfactory responses occurred for 75% of HLA‐m/ABO‐m units, and failures for 100% of HLA‐m/ABO‐u, with mean API differing significantly (14·1 vs 1·1, P = 0·0059). Of 36 HLA‐m platelets given to patient 2, age 49 years, group O, Gravida 2 Para 2, with severe aplastic anaemia, a satisfactory response occurred with 75% of HLA‐m/ABO‐m units, and failures for 63% of the HLA‐m/ABO‐u (mean API 26·7 vs 7·6, P = 0·008). Increment failures from HLA‐m platelets need not imply intractable refractoriness. If resources permit, selection of HLA‐m/ABO‐m platelets may optimise the incremental response.     

低温保存血小板在外科手术的应用

目的　研究低温保存血小板在外科应用的有效性和安全性。方法　输注对象为外科患者术中、术后出血或血小板减少引起出血以及有严重出血倾向患者。观察指标①输注前、后 2h出血时间 ;②输后伤口停止出血时间 ;③输注前、后 1h患者血小板计数 ;④根据①、②和③的结果判断输注低温血小板是否有效 ;⑤术前、术后血小板计数 ;⑥不良反应。结果　出血时间 :输前 (9± 3)min ,输后 (4± 2 )min(P <0 .0 1) ;输后 1h比输前血小板升高 (5～42 )× 10 9/L ;止血有效率为 95 % (2 2 6 / 2 38)。血小板计数 ,术后比术前下降 (130± 6 9)× 10 9/L。过敏反应 4例 ,发热反应 5例。结论　输注低温保存血小板具有明显止血和提高外周血血小板计数的效果。     

Reversibility of platelet P2Y12 inhibition by platelet supplementation: ex vivo and in vitro comparisons of prasugrel,clopidogrel and ticagrelor

Essentials

• Successful outcome of platelet transfusion depends on specific antiplatelet therapy in use.
• We assessed if ticagrelor, clopidogrel or prasugrel impacts on donor platelet activity ex vivo.
• Ticagrelor and/or its active metabolite in plasma or bound to platelets can inhibit donor platelets.
• This might compromise the effectiveness of platelet transfusion therapy.

Summary

Background

Platelet transfusion is the conventional approach to restore platelet function during acute bleeds or surgery, but successful outcome depends on the specific antiplatelet therapy. Notably ticagrelor is associated with inadequate recovery of platelet function after platelet transfusion. We examined whether plasma and/or platelets from ticagrelor‐treated patients influence donor platelet function, in comparison with clopidogrel and prasugrel.

Methods

Platelet transfusion was mimicked ex vivo by mixing naïve donor platelet‐rich plasma (PRP) or gel‐filtered platelets (GFP) in defined proportions with PRP, plasma or GFP from cardiovascular patients receiving standard care including medication with prasugrel, clopidogrel or ticagrelor (n = 20 each). Blood was taken 4 h after the previous dose. HLA2/HLA28 haplotyping let us distinguish net (all platelet) and individual patient/donor platelet reactivity in mixtures of patient/donor platelets, measured by flow cytometry analysis of ADP‐induced fibrinogen binding and CD62P expression.

Results

ADP responsiveness of donor platelets was dramatically reduced by even low (10%) concentrations of PRP or plasma from ticagrelor‐treated patients. Clopidogrel and prasugrel were associated with more modest donor platelet inhibition. GFP from ticagrelor‐treated patients but not patients receiving clopidogrel or prasugrel also suppressed donor GFP function upon mixing, suggesting the transfer of ticagrelor from patient platelets to donor platelets. This transfer did not lead to recovery of ADP responsiveness of patient's platelets.

Conclusion

Collectively, these observations support the concept that ticagrelor and/or its active metabolite in plasma or bound to platelets can inhibit donor platelets, which might compromise the effectiveness of platelet transfusion therapy.