Global Journal of Transfusion Medicine

ORIGINAL ARTICLE
Year
: 2019  |  Volume : 4  |  Issue : 2  |  Page : 186--190

Platelet additive solution suspended apheresis platelets: A new perspective for safe transfusion practice in patients with liver disease


Suryatapa Saha, Deepti Sachan, Deepti Krishna, Raghuram 
 Department of Transfusion Medicine, Gleneagles Global Health City, Chennai, Tamil Nadu, India

Correspondence Address:
Dr. Suryatapa Saha
Department of Transfusion Medicine, Gleneagles Global Health City, Chennai, Tamil Nadu
India

Abstract

Introduction: Thrombocytopenia is one of the most common complications in chronic liver disease and perioperative transplant patients requiring multiple units of platelets transfusion. Aim: This study was undertaken to find out the effectiveness of platelet additive solution (PAS) suspended apheresis platelets in such patients and to compare the in vitro quality of PAS suspended, and plasma suspended apheresis platelets. Materials and Methods: This is a prospective study conducted in the Transfusion Medicine Department of multiorgan transplant center in South India from April 2016 to April 2017. AntiA and antiB isoagglutinin titers were analyzed in O group SSP+ suspended apheresis platelet concentrates (PCs) and response of both SSP+ suspended, and plasma suspended apheresis PCs were analyzed in patients by checking the corrected count increment (CCI). Results: Among 200 single donor platelet (SDP) products, 111 (55.5%) were SSP suspended and 89 (44.5%) were plasma suspended. There were no adverse transfusion reactions in SSP+ suspended PCs. Among 24 individuals with paired plasma suspended and SSP+ suspended SDP products, no statistically significant difference was found in CCI at 24 h. There was a statistically significant difference between pre- and post-anti-A and anti-B titers (P < 0.001). Ten donor units (23.2%) had titer ≥64 for anti-A and anti-B. Conclusion: The ex vivo storage of SDP in PAS offers several advantages in the harvesting of additional plasma for use as transfusable product and reduction of allergic reactions besides maintaining the quality control of platelets.



How to cite this article:
Saha S, Sachan D, Krishna D, Raghuram. Platelet additive solution suspended apheresis platelets: A new perspective for safe transfusion practice in patients with liver disease.Glob J Transfus Med 2019;4:186-190


How to cite this URL:
Saha S, Sachan D, Krishna D, Raghuram. Platelet additive solution suspended apheresis platelets: A new perspective for safe transfusion practice in patients with liver disease. Glob J Transfus Med [serial online] 2019 [cited 2019 Dec 7 ];4:186-190
Available from: http://www.gjtmonline.com/text.asp?2019/4/2/186/269384


Full Text



 Introduction



Tne of the most common complications of liver disease patients is thrombocytopenia requiring abundant usage of platelet concentrates (PCs) in such patients.[1] Although International guidelines recommend transfusion of group-specific PCs, group switchover is acceptable when group-specific PCs are not available due to a short shelf life of platelets. With increasing the usage of apheresis PCs, there have been adverse events reported due to minor ABO-incompatible platelet transfusion in patients. The proposed technique to prevent the adverse events by replacing incompatible plasma with either AB plasma is quite tedious and requires technical skills.[2]

Platelet additive solution (PAS) is an isotonic-buffered solution intended to store platelets. The storage of platelets in PAS not only provides more plasma to meet the patient needs or to fractionate into plasma-based products, but also it reduces red cell hemolysis from ABO-incompatible plasma and other adverse events due to low ABO titer.[3]

Others not much-mentioned advantages of PAS include having standardized composition, can be steam-sterilized, possess the ability to control the storage environment; the final PC contains less protein (van der Meer, 2016). Platelets can be stored in PAS by replacing 65%–80% of plasma. The Food and Drug Administration approved PAS in use is PAS-I (plasmalyte), PAS-II (T-Sol), PAS-III (Intersol), PAS-III M (SSP+), composol PAS-G, and M-Sol.[4]

Currently, PAS IIIM (SSP+™, Macopharma, Mouvaux, France) has been approved by the Drug Controller General of India (DCGI) for commercial use in our country.

Aims and objectives

There are not many studies from India involving the effectiveness of PAS suspended apheresis platelets in recipients. Therefore, this study was undertaken to assess the response of SSP+ suspended SDP transfusion in patients and also to compare the efficacy on the usage of O group SSP+ suspended SDP products in non-O group patients.

 Materials And Methods



The present prospective study was conducted in the department of transfusion medicine of multiorgan transplant center in South India from April 2016 to April 2017 and comprised of 200 apheresis PCs also known as single donor platelet (SDP). The patients included in our study were all liver disease patients. The etiologies were acute liver failure, chronic liver failure, and postliver transplant.

All the SDP donations were collected after screening the donors for apheresis donation as per the National Accreditation Board of Hospitals and DCGI standards with appropriate consents. The plasma suspended SDPs were collected in Trima Accel cell separator (Terumo BCT, Colorado, USA) whereas SSP suspended SDPs were collected in Fenwal Amicus Cell Separator (Fresenius, Germany). After the completion of the SDP collection in the Fenwal Amicus, the machine gave instructions to connect SSP followed by addition of SSP+ in an automated way in the ratio of 65:35 (as per the company's instructions).

To evaluate the efficacy of SSP+ suspended SDPs, corrected count increment (CCI) in 24 h period were compared between plasma suspended and SSP+ SDPs. In addition, patients receiving SDP transfusion were evaluated for the presence of any transfusion reaction.

Sampling and method for SSP suspended O group titer check

Samples for pre-preparation titer check for anti-A and anti-B titer in both IgG and IgM phases were taken from donor plasma from Pilot tube. IgG titer was checked after treating the donor sample with Dithiothreitol to break the IgM chains. Titers were tested using serial doubling dilution technique by tube method.

The assessment of corrected count increment

Control group (n = 29) comprised of patients receiving SSP suspended group-specific SDP transfusion. Our study group (n = 30) comprised of patients receiving SSP suspended group nonspecific transfusion. In both the groups, to note down the amount of platelet increment, CCI was calculated and compared. Further, to ensure equal comparisons of CCI, only those individuals (number of patients = 24) who received an equal number of both PAS (n = 70) and non-PAS SDP (n = 70) transfusion within a 5 days' period were evaluated.

CCI values were calculated utilizing the following equation:

CCI = (Postplatelet count − Preplatelet count) × 1011 × body surface area (m2).

The number of platelets transfused.

Recording of adverse transfusion reactions

Recipients of the entire 200 SDP units were included in the study. For patients having group nonspecific plasma suspended SDP transfusion, the incompatible plasma was replaced with AB plasma before issuing. The diagnosis of adverse transfusion reactions (ATRs) was documented after following the department's transfusion reaction reporting protocol. Patients were not given any premedication prior to transfusion.

Statistics

Data were reported as mean ± standard deviation. The data for pre- and post-titer levels of anti-A and anti-B were compared using paired t-test test to find statistical significance. Platelet increment in between the control group and study group was analyzed using a computerized statistical chart. Furthermore, to compare the CCI between the plasma suspended and SSP+ suspended, and plasma suspended SDP, Wilcoxon signed-rank test was performed.

 Results



Among 200 SDP products, 111 (55.5%) were SSP suspended and 89 (44.5%) were plasma suspended. One hundred and ninety-nine SDP products were issued to 61 liver disease patients. One unit was discarded due to expiry. The donor and patient characteristics are shown in [Table 1] and [Table 2]. Seventy-six (38%) of SDP donors were of group B followed by 74 (37%) group O, 36 (18%) group A, and 14 (7%) group AB, respectively. Most of the SDP donations were common in the age group of 21–29 years as 94 (47%) followed by 63 (31.5%) in the age group between 30 and 39 years, 25 (12.5%) in the age group between 40 and 49 years, 14 (2%) in the age group between 18 and 20 years, respectively.{Table 1}{Table 2}

Anti-A and anti-B titer levels of O group SSP suspended single donor platelet

Of 111 SSP suspended SDP, 43 (38.73%) were O group. The median tire for IgG and IgM of anti-A in all the donor samples was 16 and 32, respectively, whereas for anti-B, it was 32 and 64, respectively. The median titer for IgG and IgM for both anti-A and anti-B in PAS suspended O group SDP was 8 and 16, respectively. Geometric mean titer and range are represented in [Table 3]. There was a statistically significant difference between pre- and post-titers (P < 0.001). Ten donor units (23.2%) had titer ≥64 for anti-A and anti-B titers.{Table 3}

Comparison of corrected count increment

Mean CCI in the control group (n = 29) was 21944.40, whereas in the study group (n = 30), it was 44193.33 [Figure 1]. More than 70% of both plasma (75%) and PAS (72%) transfusions were above the CCI threshold of 7500. Furthermore, there was no significant difference in the CCI between the plasma suspended and PAS suspended SDP (P > 0.05) [Table 4].{Figure 1}{Table 4}

Adverse transfusion reaction

In our study, no significant ATRs was found in both the groups. We encountered only 1 (1.12%) out of 89 plasma suspended SDP transfusion. No ATR noted in PAS suspended SDP transfusion to both group-specific and nongroup-specific patients [Table 2].

 Discussion



The idea of storing platelets in plasma-free artificial media emerged in 1950s.[4] Initially, PAS was developed to remove plasma from PCs as plasma contains some enzymes which impose a negative effect on the quality of platelets. In addition, buffers could be added to keep the pH >6.0, a level below which platelets lose their clinical quality. Fast forward, further benefits were identified.[3]

Platelet transfusion is an established therapy for thrombocytopenia with both benefits and constraints.[5] PCs not only help in hemostasis and wound healing, but also induce hepatocyte proliferation by releasing hepatocyte growth factor and insulin-like growth factor-1,[6] thereby promoting liver regeneration and reducing liver fibrosis. Therefore, PCs are in demanding trend in liver disease patients requiring prolonged storage of platelets.[7] Over the past few decades, a variety of PASs was developed, which proved to be even better for storage of PCs than when stored in plasma. The formulations of PAS include sodium, potassium, magnesium, acetate, citrate, gluconate, and phosphate. The key to maintaining good platelet quality is the use of acetate as fuel for the platelets, which reduces the production of lactic acid due to a lower glucose metabolism, and it provides its own bicarbonate buffer, thereby preventing a pH drop and the platelet storage lesion. Saline maintains osmolarity of PAS, potassium, and magnesium have an inhibitory effect on platelet activation and metabolism, phosphate is added as a buffering agent.[8] There is a trend in Australia toward using SDPs rather than whole blood-derived pooled platelets to minimize the risk of alloimmunization from multiple donors.[9] Therefore, to be able to provide a standardized product with reduced plasma content is of utmost importance. In order to evaluate the clinical efficacy of PCs, CCI is to be recommended for frequent use. Although the right time to check CCI is 1 h posttransfusion, it is incorrect ethically to prick the patient exclusively for the study purpose. In our study, platelet increments in both the study group and control group receiving PAS were almost equivalent. Furthermore, we did not encounter any significant difference in between the CCI of plasma suspended, and SSP+ suspended SDPs [Table 4]. In a study by Larrea et al., there is no significant difference in the CCI after transfusion in between fresh and stored preparations of plasma suspended PCs and PAS suspended PCs.[10],[11] However, in the present study, we did not have resources to compare the CCI between fresh (1–2 days) and stored (3–5 days) preparations.

Ideally, it is always better to transfuse group compatible platelets to obtain a good optimal CCI.[12] However, it is practically impossible in times of urgent need of SDPs, which in turn leads to switching to group nonspecific SDP transfusion. Various studies have reported the existence of potential risk with transfusion of ABO-incompatible platelet units containing “high titer” of anti-A and anti-B antibodies.[13] The risk is even greater when group nonspecific O group PCs are transfused. It has been recently reported that the presence of high-titer anti-A, anti-B, and anti-AB antibodies in the plasma of O group SDP donors, have the potential to hemolyze the red cells of a nongroup O recipient (minor ABO incompatibility). In the present study, there was a significant reduction of titer (P < 0.001) for both anti-A and anti-B postpreparation. Critical titers depend on the method of determining titer and can include the following >1:16 forin vitro hemolysis assays, >1:64–1:100 for IgM, and >1:256–1:400 for IgG.[14] In the present study, we preferred group-specific transfusion for high-titered post-SSP+ addition of O group SDP donated units. Although strategies to reduce platelet associated hemolytic reaction are varied and includes the screening of donor plasma for “high-titer” antibodies, volume reduction-substitution, washed platelets and setting a maximum volume of incompatible plasma to be transfused to a patient in a defined period. All of these mentioned strategies are quite cumbersome and requires both specialized equipment and time besides a trained technician. As PAS effectively reduces the plasma from a platelet donor, it may also reduce the incidence of hemolysis due to incompatible plasma.[3],[8]

In our study, we encountered only 1 of 89 (1.12%) plasma suspended SDP transfusion. This might be contributed to the limited number of transfusion of plasma-suspended SDPs due to the benefits mentioned above. Tobian et al. demonstrated 46% reduction in allergic reaction by the usage of PAS suspended platelets.[15] Although the pathophysiology of ATR due to SDPs has not been fully exemplified, both donor plasma and recipient components play a key role in ATR. The presence of biogenic amines, eosinophil, and neutrophil chemotactic factors, enzymes, leukotrienes, prostaglandin, platelet-activating factor, and cytokines are all being found to implicate in ATRs.[16] Further understanding of the pathophysiology of ATRs could provide new preventive strategies.

Majority of the studies involving the effectiveness of PAS in SDP used selection of apheresis donors based on human leukocyte antigen (HLA) and human platelet antigen (HPA). Weiss et al. in his review cited the importance of HLA- and HPA-matched platelets to prevent refractoriness. In our center, we lacked those methods to select an apheresis donor.[10] This might contribute to the platelet refractoriness of the patients who had CCI <7500 after repeated SDP transfusion. Besides some studies have shown that it is difficult to find HLA compatible donors who are also ABO identical for patients with refractory thrombocytopenia.

As platelet transfusion significantly improves some of the indicators of liver function in liver disease patients in transplant setting, prolonged storage of SDP with minimal side effects and better improvement of CCI in patients demands utmost attention.

Availability of safe blood component is a critical element in improving health care. In any multi-organ transplant center, patient requiring intensive care is in constant need of platelets. Arranging group-specific inventory is a challenge in today's era due to the unpredictable needs of liver transplants and short shelf life of platelet products. A switch from plasma to PAS for platelet storage is also cost-effective by reducing the allergic reactions as well as saving a unit of plasma especially in a liver transplant center with high load of plasma exchange and transfusion.

To summarize, the usage of PAS, especially in SDPs, proves to be clinically beneficial in transplant centers.

 Conclusion



The usage of SSP+ for SDPs in our setting eliminated the need for group-specific platelets due to the above-mentioned benefits. No adverse reactions were encountered from transfusion of PAS suspended SDPs. The ex vivo storage of SDP in PAS offers several advantages in the harvesting of additional plasma for use as transfusable product and reduction of allergic reactions. Papers on the SSP+ usage in the Indian subcontinent are limited. Larger studies on the clinical efficacy and quality of PAS suspended PCs for 7 days' survival will benefit the implementation of PAS suspended SDPs universally.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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