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 Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 1  |  Issue : 1  |  Page : 16-19

Evaluation of the platelet cross-matching in oncology patients


From the Department of Blood Transfusion Services, Sri Balaji Action Medical Institute, New Delhi, India

Date of Web Publication3-Mar-2016

Correspondence Address:
Sadhana Mangwana
From the Department of Blood Transfusion Services, Sri Balaji Action Medical Institute, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2455-8893.178006

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  Abstract 

Context: Platelet transfusion is an essential part of managing cancer. Refractoriness to platelet transfusion poses great challenge in the treatment of thrombocytopenic patients.
Aims: The prospective study was undertaken to correlate and evaluate the result of the platelet cross-matching with posttransfusion count increment and to ascertain the effectiveness of routinely performing platelet cross-matching in Indian perspective.
Subjects and Methods: ABO compatible, leukoreduced, random-donor platelets were randomly transfused to 30 thrombocytopenic, oncology patients. Platelet cross-match and platelet antibody screen were performed using solid-phase red-cell adherence (SPRCA) techniques and corrected count increment (CCI) was ascertained.
Statistical Analysis: Statistical Package for Social Sciences version 16, Chi-square test were used for statistical analysis. Multivariate analysis and step-wise regression procedure were used to choose the set of best predictors.
Results: One hundred and twenty-two units (86%) were negative cross-matched while 20 units (14%) were positive platelet cross-matched. Mean CCI was 28,927 ± 23,007 which was more and statistically significant in females than in males. Four cases (13.33%) showed platelet refractoriness with CCI <5000 including three cases of leukemia (25% of hematological malignancies). Patients with low CCI showed positive cross-match and antibodies against platelets.
Conclusion: Platelet cross-match using SPRCA is an effective and rapid first-line approach for selecting compatible platelets as compared to human leucocyte antigen-matched platelets in the treatment of thrombocytopenic cancer patients. Platelet cross-match along with testing for anti-platelet antibodies should be an important component in the management of oncology patients which is less time-consuming and cost-effective than the molecular testing.

Keywords: Corrected count increment, platelet refractoriness, random-donor platelets, solid-phase red-cell adherence


How to cite this article:
Mangwana S, Simon N. Evaluation of the platelet cross-matching in oncology patients. Glob J Transfus Med 2016;1:16-9

How to cite this URL:
Mangwana S, Simon N. Evaluation of the platelet cross-matching in oncology patients. Glob J Transfus Med [serial online] 2016 [cited 2019 Aug 20];1:16-9. Available from: http://www.gjtmonline.com/text.asp?2016/1/1/16/178006


  Introduction Top


Platelet transfusion is a critical and an essential part of managing cancer, hematological malignancies, bone marrow failure, and hematopoietic stem cell transplantation.[1] Platelet transfusion is indicated for either a quantitative defect (thrombocytopenia) or a qualitative defect (dysfunctional platelets). In patients with cancer, patient's disease may directly cause thrombocytopenia via tumor involvement of the bone marrow, spleen, or both. In such cases, platelet transfusion is preferred to prevent and to treat hemorrhagic manifestations. However, between 30% and 70% of multiply transfused thrombocytopenic patients become refractory to random-donor platelets (RDPs).[2] Refractoriness to platelet transfusion is a complex process and poses a great challenge in the treatment of thrombocytopenic patients. Platelet refractoriness can be due to immune or nonimmune causes. Nonimmune causes such as fever, sepsis, splenomegaly, disseminated intravascular coagulation, graft-versus-host disease, drug-induced, and hemorrhages, are involved in 80% cases while immune causes consist mainly of sensitization to foreign class I A or B human leukocyte antigens (HLAs) through pregnancy, transfusion or transplantation. Two strategies are used to transfuse alloimmunized patients, matching donor-recipient HLAs, and cross-matching platelets.[1] HLA typing of patients as well as platelet donors is expensive and the long turn-around time decreases its utility in some clinical situations. In addition to these drawbacks, HLA matching requires the availability of large numbers of HLA-typed donors.[1] Platelet cross-matching assays are rapid alternative and a relatively low-cost to the HLA-matched option for the management of platelet refractoriness.[3],[4],[5]

Aim

The prospective study was planned to analyze the result of the platelet cross-matching with the posttransfusion count increment and to ascertain the effectiveness of routinely performing platelet cross-matching.


  Subjects and Methods Top


This study was performed on thirty oncology patients from September 2014 to February 2015 receiving multiple platelet transfusions. The pretransfusion platelet count of the patient was ascertained by automated 5-part Hematology Analyzer (LH 750, Beckman Coulter, USA). ABO compatible, leukoreduced, RDPs were randomly transfused. Blood samples were collected within 1-h of completing platelet transfusion for corrected count increment (CCI). The CCI was calculated using the following formula:



Patients were considered to be refractory when 1-h posttransfusion platelet count increment was <5000. Platelet cross-match and platelet antibody screen was performed using solid-phase red-cell adherence (SPRCA) techniques on Capture-P Solid-Phase System (Galileo, Immucor Inc, USA). Capture-P Solid-Phase System detects the unexpected anti-platelet antibodies in a patient or donor population. Patient or donor platelets are first bound to the surfaces of polystyrene micro plate wells. They are subsequently used to capture platelet antibodies from patient or donor sera. Serum is incubated briefly in platelet coated wells to allow antibodies, if present, to bind to the platelets. Unbound immunoglobulins (Igs) are then washed from the wells and replaced with a suspension of anti-IgG-coated indicator red cells. Centrifugation brings the indicator red cells in contact with antibodies bound to the immobilized platelets.

Negative test

Button of indicator red cells at the bottom of the test well with no readily detectable area of adherence.

Positive test

Adherence of indicator red cells to part or the entire reaction surface.

In the case of positive tests, adherence of indicator red cells to part or all of the reaction surface, the migration of the indicator red cells to the bottom of the wells is impeded as anti-IgG bridges are formed between the indicator red cells and the platelet-bound antibodies. As a consequence of such bridging, the indicator red cells will cover the immobilized platelets in a confluent monolayer. In contrast, in the absence of platelet antigen-antibody interactions, i.e., negative tests, the indicator red cells will not be impeded during their migration, and will pellet to the bottom of the wells as tightly packed, well-defined cell buttons. Results are reported as the number of incompatible (reactive) donor units.

Statistical analysis

The statistical analysis of data was performed using the Excel and Statistical Package for Social Sciences (SPSS) version 16 programs (SPSS Inc., Chicago, IL, USA). A multivariate analysis was performed to assess the factors predicting posttransfusion platelet increment (PPI) where, the set of independent variables were age, gender, body surface area (BSA), diagnosis, transfused platelet, history of transfusion, compatibility, and dosage of platelet transfusion. The step-wise regression procedure was used to choose the set of best predictors. A Chi-square test was used to correlate results of the cross-match with the posttransfusion counts. All P values are two-sided and P < 0.05 are considered statistically significant.

This study was approved by the Institutional Ethics Committee.


  Results Top


A total of 30 oncology patients received multiple platelet transfusions. Eighteen patients (60%) were males while 12 patients (40%) were females. The mean age of all patients was 46.87 ± 15.16 years with a range of 8–70 years. Male patient's age ranged from 28 to 70 years with mean age 46.28 ± 14.14 years while female patients age ranged from 8 to 70 years mean age 47.25 ± 17.2 years which is statistically insignificant (P = 0.07). Mean BSA of all patients was 1.60 ± 0.25 m 2 (range 0.88–2 m 2) without any statistically significant difference between males (1.67 ± 0.22 m 2) and females (1.51 ± 0.27 m 2).

Solid organ malignancies were seen more in females (10 of 18, 55.5%) than in males (8 of 18, 44.5%) while in hematological malignancies males were more affected (10 of 12, 83.3%) than females (2 of 12, 16.67%).

A total of 142 units of ABO compatible, whole blood-derived, leukoreduced, RDPs were randomly transfused to thirty patients with a mean of 4.73 ± 0.87 units of platelet transfusion per patient. One hundred and twenty-two of 142 units (86%) were negative platelet cross-matched while 20 units (14%) were positive cross-matched.

Mean platelet dose given was 2.29 ± 1.88 × 1011 with statistically insignificant difference between males (1.99 ± 2.29 × 1011) and females (2.07 ± 1.09 × 1011).

Characteristics of platelet transfusion events are shown in [Table 1]. The posttransfusion platelet count observed after platelet transfusion were 30.33 ± 26.59 × 109/L which were significantly higher in females (42.75 ± 24.63 × 109/L) than in males (22.05 ± 25.15 × 109/L) (P = 0.034). A multivariate analysis was performed to assess the factors predicting PPI where, the set of independent variables were age, gender, BSA, diagnosis, transfused platelet, history of transfusion, compatibility, and dosage of platelet transfusion. The step-wise regression procedure was used to choose the set of best predictors. The fitted model gave a joint explanatory power (R 2) =36.9% (P = 0.002). The significant predictors are found as gender (P = 0.020) and dose of platelet transfusion (P = 0.005).
Table 1: Characteristics of platelet transfusion events

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Mean CCI was 28,927 ± 23,007 which was more and statistically significant in females (36,865 ± 26,695) than in males (23,634 ± 19,176) with P = 0.009.

Four cases (13.33%) showed platelet refractoriness with CCI <5000, out of which three cases, were of myeloid leukemia; both acute and chronic (25% of hematological malignancies), and one case was of solid organ malignancy in a female (carcinoma ovary). All leukemia cases were males. These patients with low CCI showed positive cross-match and antibodies against platelets.

Using multivariate analysis, factors predicting PPIs were assessed. The significant factors were found as female gender (P = 0.020) and dose of platelet transfusion (P = 0.005).


  Discussion Top


Platelet transfusion therapy is life-saving for oncology patients, but platelet refractoriness always poses a challenge due to alloimmunization to HLA and human platelet antigens (HPAs). There are number of approaches to address the problem of platelet transfusion refractoriness. One of the most frequently used methods is HLA matching which is highly effective and routine approach to the management of refractory patients in number of institutions.[6] A commonly used alternative to HLA-matched platelets is the transfusion of cross-match - compatible platelets.[3],[5] Platelet cross-matching by SPRCA technique is simple less time-consuming and cheaper than HLA typing.[7] To the best of our knowledge, there is a paucity of Indian literature on platelet cross-match and platelet refractoriness in RDP transfusion in oncology patients.

The mean CCI of 28297 ± 23007 achieved in the study corresponds to PPI of 30.33 ± 26.59 × 109/L. In this study, patients receiving cross-matched platelets showed good increments. The response to compatible platelet seen in our study is consistent with previous studies [3],[8],[9],[10] which demonstrated significant improvement in CCI by using SPRCA method to cross-match platelets. Posttransfusion platelet count increment and CCI of >5000 were obtained in 86.66% of our cases. Our threshold for a good response (CCI >5000) is lower than commonly used threshold (CCI >7500) for successful transfusions which was consistent with those described by Rebulla et al.[3] and Salama et al.[9] who reported platelet recovery in 68% and 72.9% transfusions, respectively.

Frequency of refractoriness observed in this study (13.33%) was close to that reported in the literature which varied from 19% to 34%.[11],[12],[13],[14],[15] In our study, the incidence of platelet refractoriness was more in men (16.66%) than in women (8.33%) in contrast to the studies by Rebulla et al.[3] and Salama et al.[9] in which, 80% and 60% women respectively were refractory. In our study, platelet refractoriness was seen more in hematological malignancies (25%) than in solid organ malignancies (5.55%) which could be due to HPAs. In the study by Elhence et al.,[10] antiplatelet antibodies were responsible for incompatible cross-match in 41% of cases either alone (26.8%) or with anti-HLA antibodies while Rebulla et al.[3] found 15% patients having both anti-HLA and anti-HPA antibodies.

The 14% incidence of alloimmunization in this study was in concordance with multi centric TRAP study which showed 17–21% incidence of alloimmunization.[16] This could be due to use of leukoreduced, RDPs concentrates in our institution same as evidenced in multicentric TRAP study receiving leukoreduced components as compared to 45% incidence in patients receiving nonleukoreduced blood components.[16] Out of four cases showing alloimmunization, two patients had sensitization to previous blood transfusion or pregnancy leading to the development of platelet antibodies. Antibodies in other cases could be HPA antibodies, HLA antibodies, or autoantibodies. In other studies showing a high incidence of alloimmunization up to 40%, 56%, 66%, and 73.2%[9],[10],[11],[17] are due to formation of HLA antibodies in multi-transfused patients and transfusion of nonleukoreduced, RDPs [17] or single donor platelets.[10]

By using multivariate analysis, factors predicting PPIs were assessed, and significant factors were found as female gender and dose of platelet transfusion while in other studies,[9],[18] platelet cross-match was the most significant predictive factor for CCI.


  Conclusion Top


To conclude, blood services must be made aware of the importance of the development of measures to prevent alloimmunization and correct identification of refractoriness to provide adequate transfusion support for oncology patients. Platelet cross-match using SPRCA is an effective, useful tool and rapid, first-line approach for selecting compatible platelets from the local inventory as compared to HLA-matched platelets in the treatment of thrombocytopenic cancer patients. Further study is required to conclude and correlate the platelet compatibility with refractoriness. Platelet cross-match along with testing for anti-platelet antibodies should be an important component in the management of oncology patients which is less time-consuming and cost-effective than the molecular testing.

Financial Support and Sponsorship

Immucor.

Conflicts of Interest

There are no conflicts of interest.

 
  References Top

1.
Stroncek DF, Rebulla P. Platelet transfusions. Lancet 2007;370:427-38.  Back to cited text no. 1
    
2.
Heddle NM, Cook RJ, Sigouin C, Slichter SJ, Murphy M, Rebulla P; BEST Collaborative (Biomedical Excellence for Safer Transfusion). A descriptive analysis of international transfusion practice and bleeding outcomes in patients with acute leukemia. Transfusion 2006;46:903-11.  Back to cited text no. 2
    
3.
Rebulla P, Morelati F, Revelli N, Villa MA, Paccapelo C, Nocco A, et al. Outcomes of an automated procedure for the selection of effective platelets for patients refractory to random donors based on cross-matching locally available platelet products. Br J Haematol 2004;125:83-9.  Back to cited text no. 3
    
4.
Freedman J, Gafni A, Garvey MB, Blanchette V. A cost-effectiveness evaluation of platelet crossmatching and HLA matching in the management of alloimmunized thrombocytopenic patients. Transfusion 1989;29:201-7.  Back to cited text no. 4
    
5.
Rebulla P. A mini-review on platelet refractoriness. Haematologica 2005;90:247-53.  Back to cited text no. 5
    
6.
Petz LD, Garratty G, Calhoun L, Clark BD, Terasaki PI, Gresens C, et al. Selecting donors of platelets for refractory patients on the basis of HLA antibody specificity. Transfusion 2000;40:1446-56.  Back to cited text no. 6
    
7.
Vongchan P, Nawarawong W, Linhardt RJ. Modification of solid phase red cell adherence assay for the detection of platelet antibodies in patients with thrombocytopenia. Am J Clin Pathol 2008;130:455-66.  Back to cited text no. 7
    
8.
Gelb AB, Leavitt AD. Crossmatch-compatible platelets improve corrected count increments in patients who are refractory to randomly selected platelets. Transfusion 1997;37:624-30.  Back to cited text no. 8
    
9.
Salama OS, Aladl DA, El Ghannam DM, Elderiny WE. Evaluation of platelet cross-matching in the management of patients refractory to platelet transfusions. Blood Transfus 2014;12:187-94.  Back to cited text no. 9
    
10.
Elhence P, Chaudhary RK, Nityanand S. Cross-match-compatible platelets improve corrected count increments in patients who are refractory to randomly selected platelets. Blood Transfus 2014;12:180-6.  Back to cited text no. 10
    
11.
Ferreira AA, Zulli R, Soares S, Castro VD, Moraes-Souza H. Identification of platelet refractoriness in oncohematologic patients. Clinics (Sao Paulo) 2011;66:35-40.  Back to cited text no. 11
    
12.
Legler TJ, Fischer I, Dittmann J, Simson G, Lynen R, Humpe A, et al. Frequency and causes of refractoriness in multiply transfused patients. Ann Hematol 1997;74:185-9.  Back to cited text no. 12
    
13.
Novotny VM. Prevention and management of platelet transfusion refractoriness. Vox Sang 1999;76:1-13.  Back to cited text no. 13
    
14.
Slichter SJ, Davis K, Enright H, Braine H, Gernsheimer T, Kao KJ, et al. Factors affecting posttransfusion platelet increments, platelet refractoriness, and platelet transfusion intervals in thrombocytopenic patients. Blood 2005;105:4106-14.  Back to cited text no. 14
    
15.
Fabris F, Soini B, Sartori R, Randi ML, Luzzatto G, Girolami A. Clinical and laboratory factors that affect the post-transfusion platelet increment. Transfus Sci 2000;23:63-8.  Back to cited text no. 15
    
16.
Leukocyte reduction and ultraviolet B irradiation of platelets to prevent alloimmunization and refractoriness to platelet transfusions. The Trial to Reduce Alloimmunization to Platelets Study Group. N Engl J Med 1997;337:1861-9.  Back to cited text no. 16
    
17.
Bajpai M, Kaura B, Marwaha N, Kumari S, Sharma RR, Agnihotri SK. Platelet alloimmunization in multitransfused patients with haemato-oncological disorders. Natl Med J India 2005;18:134-6.  Back to cited text no. 17
    
18.
Heal JM, Blumberg N, Masel D. An evaluation of crossmatching, HLA, and ABO matching for platelet transfusions to refractory patients. Blood 1987;70:23-30.  Back to cited text no. 18
    



 
 
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