Safety and Efficacy of 14-Day Cold Stored Platelets in Reversing Effects of Aspirin

Background: Aspirin is an antiplatelet therapy used to reduce the risk of vascular occlusive events. However, this therapy is associated with an increased risk of bleeding for which there is no antidote currently. Transfusion of 5-day room stored platelets (RSP) at 22°C can reverse the effect of aspirin but surprisingly, the recent randomized PATCH trial showed increased morbidity and mortality for patients who received RSP transfusion for intracranial hemorrhage while on aspirin. Prior studies have shown that cold stored platelets (CSP) at 4°C are mildly activated and may participate in clot formation immediately, thus may have the potential to reduce blood loss more rapidly than RSP in acutely bleeding patients. CSP also have the added advantages of decreased risk of bacterial contamination and longer shelf-life up to 14 days per current FDA variance. However, the function of 14-day CSP in plasma after transfusion is unclear and lacks high quality data. We aimed to evaluate the post-transfusion safety and efficacy of 14-day CSP in reversing the effects of aspirin therapy compared to that of 7-day RSP. Methods: Seven healthy human subjects were included in the analysis of this randomized, controlled, crossover study comparing transfusion of autologous 14-day CSP to 7-day RSP. Each subject participated in two study periods, which crossed over from one storage product to the other (CSP vs. RSP) according to randomization. For each study period, subjects underwent an apheresis platelet collection for autologous transfusion. Platelets were stored for either 14 days for CSP or 7 days for RSP. Subjects received a loading dose of aspirin 24 hours prior to transfusion. Blood was drawn at baseline, immediately pre-transfusion, at 1-hr, 4-hr, and 24-hr post-transfusion for an array of platelet function testing. After a washout period of 10-28 days, second study period commenced with similar sequence of events as the first study period using the other platelet storage product. The primary endpoint is the VerifyNOW Aspirin Reaction Units (ARU) at 1-hr after autologous transfusion. Secondary endpoints include ARU at 4-hr and 24-hr post transfusion, light transmission aggregometry in response to arachidonic acid and collagen, and the corrected count increment. Paired t-tests were used for statistical analysis between the two groups and, where appropriate, the change from pre-transfusion values were analyzed. Results: Transfusion of 14-day CSP and 7-day RSP units were well-tolerated by all subjects. Storage of platelets in the cold led to a non-significant trend for decreased platelet count, and the total platelet yield at the end of storage was significantly less in 14-day CSP compared to 7-day RSP (p=0.02). However, the corrected count increment did not differ significantly at 1-hr after transfusion. Platelet aggregation using the agonists, arachidonic acid 0.5mM and collagen 2.5ug/mL, did not reveal any significant difference between the two groups at any time points. The primary endpoint, platelet function testing by VerifyNOW, showed a larger change in platelet responsiveness at 1-hr post-transfusion in RSP than in CSP (p=0.03). Surprisingly, only RSP transfusion resulted in a significant change from the pre-transfusion VerifyNow measurements. Later time points showed a slight trend for improved platelet function as measured by VerifyNow with transfusion of both platelet products, but none were statistically significant. Conclusion: We report the first safety and efficacy data for 14-day cold stored platelets in in healthy humans. While prior in-vitro studies have demonstrated possible hemostatic superiority of cold stored over room temperature stored platelets, we observed inferior reversal of aspirin at early time points with CSP. This was in contrast to the results from our previous study, where 5 day-stored CSP were equivalent to RSP at early post transfusion time points. Further studies are needed to evaluate the maximal storage that provides functional equivalency between CSP and RSP. In addition, studies in actively bleeding patients are needed. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Platelet Refractoriness Evaluation after Platelet Concentrate Transfusion in Pediatric Leukemia

Platelet transfusion is being used in 67%-75% of hematology malignancies including leukemia. Platelet refractoriness is the failure to achieve satisfactory responses to platelet transfusions. Many transfusion centres use 1 hour and 24 hours after transfusion Corrected Count Increment (CCI) value to define platelet refractoriness. To analyze platelet refractory based on CCI-1h and CCI-24h value after Platelet Concentrate (PC) tranfusion in pediatric leukemia and the effect of non immune factors on platelet refractoriness. Subjects were evaluated for platelet count after 10-120 minutes and 18-24 hours of PC tranfusion to calculate CCI-1h and CCI-24h. Platelet Refractoriness was defined when CCI-1h <5×109/L and CCI-24h <4.5×109/L. Each subject was observed for non-immune platelet refractory factors. Interestingly, from 25 PC transfusion there was 20% platelet refractoriness of CCI-1h and 40% of CCI-24h. There was a significant difference CCI-1h and CCI-24h (p=0.027). Non immune factor had no effect for platelet refractoriness. Platelet count should be analyzed after 24 hours PC transfusion to diagnose platelet refractoriness. Further research including immune factor examination is needed.

Perbandingan Nilai Corrected Count Increment pasca transfusi Thrombocyte Concentratedengan Thrombocyte Apheresispada penderita Keganasan Hematologi

Introduction : Transfusion thrombocyte concentrate (TC) and thrombocyteapheresis (TA) is a form of use of blood components as supportive measures to increase the number of platelets of patients with hematological malignancies thrombocytopenia, platelet transfusion success rated the corrected count increment (CCI).1 Platelet transfusion refractoriness (PTR) or failure increase in platelet post platelet transfusion, defined as more than two times the transfusion episode or successively obtained the value CCI <7.5 at 1 hour post first transfusion or <4.5 at 18-24 hours post transfusion.31 Materials and methods : Research samples from hematologic malignancies patients with platelet counts <50,000 / mm3, enforced through inspection Bone Marrow punction (BMP), got 2 or more episodes of platelet transfusions in the form Thrombocyte Concentrate (TC) and Thrombocyte Apheresis (TA), aged 1-70 years, do a complete blood count, is hospitalized at Dr. Kariadi’s hospital Semarang during the study period, from the number of pre- and post platelet transfusion CCI value is then determined between the recipient TA and TC. CCI value between TA to TC compared to perform statistical analysis computer using Mann Whitney test Research result : A study of 82 patients with both men and women diagnosed with Hematologic Malignancies obtained Platelet refractoriness cases as much as 5 of the 41 patients who received a transfusion history of using TA (12.19%), and 30 of 41 patients who received a transfusion history using TC (73.17 %). Mann Whitney test showed the value of CCI in case the recipient PTR between TA and TC got significant differences (p <0.05). Conclusion : There is significant difference between the value CCI of TA resipients and TC resipients. The value CCI of TA recipient was significantly higher than the value CCIof TC recipients. Keywords : thrombocyte apheresis, thrombocyte concentrate, CCI, PTR Pendahuluan: Transfusi thrombocyte concentrate (TC) dan thrombocyteapheresis (TA)merupakan bentuk penggunaankomponen darah sebagai tindakan suportif untuk meningkatkan jumlah trombositpasien keganasan hematologi dengan trombositopenia, Keberhasilan transfusi trombositdinilai dengan corrected count increment(CCI).1Platelet transfusion refractoriness (PTR) atau kegagalan kenaikan trombosit post transfusi trombosit, didefinisikan sebagai lebih dari dua kali episode transfusi atau berturut-turut didapatkan nilai CCI < 7,5 pada 1 jam pertama post transfusi atau < 4,5 pada 18-24 jam post transfusi.31 Bahan dan metode: Sampel penelitian adalah penderita keganasan hematologidengan jumlah trombosit <50.000 /mm3, ditegakkan melalui pemeriksaan Bone Marrow Punction (BMP), mendapat 2 atau lebih episode transfusi trombosit berupa Thrombocyte Concentrate (TC) maupunThrombocyte Apheresis (TA), usia 1-70 tahun, dilakukan pemeriksaan darah lengkap, menjalani rawat inap di RSUP Dr. Kariadi Semarang selama periode penelitian, Dari jumlah trombosit pre dan post transfusi kemudian ditentukan nilai CCI antara resipien TA dan TC. Nilai CCI antara TA dengan TC dibandingkan dengan melakukan analisis statistik komputer menggunakan uji Mann Whitney Hasil penelitian: Penelitian terhadap 82 pasien laki-laki maupun perempuan dengan diagnosis Keganasan Hematologi didapatkan kasus Platelet refractoriness sebanyak 5 dari 41 pasien yang mendapatkan riwayat transfusi menggunakan TA (12,19%), dan 30 dari 41 pasien yang mendapatkan riwayat transfusi menggunakan TC (73,17%).Uji Mann Whitney menunjukkan nilai CCI pada kasus PTR antara resipien TA dan TC didapatkan perbedaan secara signifikan (p<0,05). Simpulan: Didapatkan perbedaan secara signifikan nilai CCI antara yang mendapatkan TA dan yang mendapatkan TC. Nilai CCI resipien TA secara bermakna lebih tinggi daripada nilai CCI resipien TC Kata kunci :thrombocyte apheresis, thrombocyte concentrate, CCI, PTR

EFFECTIVENESS OF SINGLE AND DOUBLED DOSES PLATELETS TRANSFUSIONS

Введение. Концентрат тромбоцитов — второй наиболее часто назначаемый компонент крови после эритроцитов. Тромбоциты способствуют свёртыванию крови, а также поддержанию целостности сосудов. Цель исследования. Сопоставить эффективность переливания единичных и множественных доз патоген-редуцированных тромбоцитов. Материалы и методы. В 15 клиниках Республики Башкортостан с 14 января по 30 сентября 2016 года выполнено 915 переливаний тромбоцитов: 831 единичных и 84 сдвоенных доз патоген-редуцированных тромбоцитов. Результаты. Установлена разная частота применения сдвоенных доз в разных клиниках, а также их преимущественное применение по пятницам. У реципиентов единичных и сдвоенных переливаний не выявлено различий следующих показателей: площадь поверхности тела, среднее количество трансфузий в анамнезе, доля первых переливаний тромбоцитов, частота профилактических и лечебных трансфузий, эффективность остановки кровотечения, скорректированный прирост тромбоцитов (СПТ). Заключение. Не получено доказательств различий в эффективности трансфузий сдвоенных и единичных концентратов донорских тромбоцитов. Прямая корреляция СПТ и исходной концентрации тромбоцитов свидетельствует об ограниченной диагностической значимости СПТ в качестве показателя эффективности переливания тромбоцитов. Introduction. Platelet concentrates are the second most commonly prescribed blood component after erythrocytes. Platelets promote coagulation and maintain the integrity of blood vessels. The aim of study: to compare transfusion effectiveness of single and multiple doses of pathogen-reduced platelets. Materials and methods. In 15 clinics of the Republic of Bashkortostan (from January 14 to September 30, 2016) 915 platelets transfusions were performed: 831 single and 84 double doses of pathogen-reduced platelets. Results. Frequency of doubled doses platelets transfusions varied in different hospitals, predominantly they used on Fridays. In recipients of single and doubled transfusions we revealed no differences in following parameters: body surface area, average number of transfusions in anamnesis, proportion of first platelets transfusions, frequency of preventive and therapeutic transfusions, effectiveness of bleeding stops, corrected count increment of platelets (CCIP). Conclusion. No evidences of difference in transfusion effectiveness of doubled and single donor platelets concentrates were received. Direct correlation between CCIP and initial platelets concentration shows the limited diagnostic significance of CCIP as an indicator of platelets transfusion effectiveness.

Transfusion effect of random donor platelet and single donor platelet in thrombocytopenic patients at tertiary care hospital of South Gujarat

Background: Platelet transfusion plays a key role in therapy for the patients with thrombocytopenia. Superiority of Single donor platelet (SDP) over Random donor platelet (RDP) transfusions is largely assumed, but unproven. Platelet Rich Plasma-Platelet concentrate (PRP-PC) and Apheresis-PC were prepared and their therapeutic efficacy were assessed in thrombocytopenic patients.Methods: This study included 60 transfusion episodes consisting of 30 SDP and 30 RDP (147units of RDP). The post transfusion efficacy of transfused platelets was assessed at 1 hour and 24 hours by corrected count increment (CCI) and percentage recovery (PR). Paired ‘t’-test was used for statistical analysis and a probability of p<0.05 was used to reject null hypothesis.Results: The mean platelet dose of SDP (n=30) and RDP (n=30) was 2.86±1.05 x 1011 and 2.36±0.54 x 1011 respectively. The mean platelet increments of SDP at 1 hour and 24 hours were 38±18.1 x 103/μl and 37.3±20.7x 103/μl. The mean platelet increments of RDP at 1 hour and 24 hours were 28.5±11.4 x 103/μl and 26 ±11.6 x 103/μl. The mean CCI of SDP at 1hour and 24 hours were 21.4 ±7.3 x 103/μl and 20.8±7.4 x 103/μl respectively. The mean CCI of RDP at 1hour and 24 hours were 18.5±6.3x 103/μl and 17.4±7.6 x 103/μl respectively.Conclusions: Post-transfusion increments were significantly higher in patients who received SDP as compared to RDP, but the CCI and PR were comparable in both groups of patients.

Hubungan Antibodi Anti Trombosit terhadap Respon Transfusi Trombosit pada Pasien Hemato- Onkologi yang Mendapatkan Multitransfusi Trombosit di RS Dr. Cipto Mangunkusomo

Pendahuluan. Multitransfusi donor random dan paparan terhadap konsentrat trombosit yang termasuk non-leukocyte depleted diketahui sebagai faktor risiko terjadinya alloimunisasi (HLA dan HPA) yang dapat menjadi salah satu penyebab kegagalan transfusi. Oleh karena itu, perlu dilakukan penelitian mengenai hubungan antibodi anti trombosit tersebut dengan kegagalan respon transfusi trombosit pada pasien hemato-onkologi sehingga dapat dilakukan metode seleksi donor dan crossmatching trombosit donor dan resipien.Metode. Studi observasional dilakukan pada pasien hemato-onkologi dewasa yang mendapatkan multitransfusi trombosit di Rumah Sakit dr Cipto Mangunkusumo (RSCM) Jakarta. Pengamatan dilakukan pada respon transfusi dengan mengukur corrected count increment (CCI) 1 jam post transfusi dengan batas 7.500 m2/mL. Keadaan lain yang dapat mempengaruhi CCI dieksklusi dari penelitian. Antibodi (Ig G) dideteksi dari serum pre transfusi terhadap antigen HLA kelas 1, epitop GP IIb/ IIIa, Ib/IX dan Ia/IIa dengan teknik ELISA secara kualitatif. Pengukuran ini menggunakan kit ELISA komersial Pak-2 LE. Analisis statistik dilakukan dengan uji chi-square dan regresi logistik untuk ditentukan PR dengan IK 95%.Hasil. Selama periode Maret–Juni 2008 terkumpul 36 transfusi yang diberikan pada 21 pasien dengan berbagai diagnosis hemato-onkologi. Sebanyak 33,3% memberikan respon transfusi yang tidak memuaskan (CCI <7.500). Dari seluruh transfusi, ditemukan antibodi HLA kelas 1 positif sebanyak 38,9% dari pasien, sedangkan antibodi GP IIb/IIIa hanya ditemukan pada 1 orang (2,8%). Didapatkan hubungan antara antibodi HLA kelas 1 dan kegagalan respon transfusi dengan nilai PR 4,7 (IK 95% 1,535–14,474, p=0,003) dan adjusted PR 11,4 (IK 95%, 2,219–58,557, p=0,004)Simpulan. Pasien yang memiliki antibodi HLA kelas 1, memiliki kecenderungan kegagalan transfusi trombosit 11,4 kali lebih besar. Namun, hubungan antibodi GP IIb/IIIa dengan respon transfusi belum dapat ditentukan, sehingga dibutuhkan studi lanjutan dengan sampel yang lebih besar.