人類白血球單一抗原抗體試驗對於血小板輸注無效病患尋找HLA配對相合血品之應用與成效評估徵

The Application and Outcome of HLA Single Antigen Flow PRA Test to Identify Compatible Platelet Units for Patients with Platelet Transfusion Refractoriness

背景：隨著醫療技術日漸發達，對於血液腫瘤病患、骨髓移植者之後續支持性治療或是先天血小板低下症狀者，血小板血品的輸注仍是能夠提升血小板計數並降低出血風險的方法。然而，隨著許多受血者須長期輸注血小板，也常造成血小板輸注無效（Platelet Tran sfusion Refractoriness，PTR）之狀況。臨床上為了避免血小板輸注無效造成醫療資源的浪費，通常有下列方法尋找因免疫性因素引發輸注無效之受血者適合輸注之血小板，例如：交叉相合（Cross-matched compat ible）血小板、人類白血球抗原配對（HLA-matched）血小板等。本研究應用HLA抗體鑑定於體內含有HLA抗體而使血小板輸注無效之受血者，藉由分析受血者血清HLA抗體分型，避開血品與受血者對應到之HLA抗體，選擇相容HLA型別提升尋找適合血品機率、並期望能夠提升輸血安全與減少醫療資源浪費。
方法：受試者進行HLA抗體鑑定並統計HLA抗體型別，依受試者本身HLA型別、抗體資訊預定血小板，並於血小板輸注前、後1個小時採集周邊血計算血小板上升指數，並評估血小板輸注成效。
結果：根據實驗數據統計，在參加本研究計畫受試者所輸注的所有HLA相合血小板血品或交叉配對血小板血品，A等級血品占約6%，而次等級B1U至B2UX血品占約59%，輸注成效依據CCI之計算結果（平均1-hr CCI>7500）成效良好。最後約35%為等級介於C至D之血小板血品，臨床上認為C等級以下血品輸注成效與隨機血小板（R）無顯著差異，但根據本研究結果顯示，若輔以HLA單一抗原抗體檢驗，能夠避開受血者血清中對應抗體且HLA型別不合的C等級血小板，也能夠有良好的輸注成效（平均1-hr CCI>7500）。
結論：我們能夠藉由本研究之結果觀察到HLA單一抗原抗體檢驗在血小板輸注尋找血品的過程中扮演良好的輔助角色，除了可以避免傳統僅尋找HLA型別一致血品耗時較長卻不敷臨床使用需求的缺點之外，也能夠追蹤受試者體內HLA抗體的變化，進一步避免使用傳統不靈敏方法尋找之交叉相合血小板造成輸注無效與醫療資源的浪費。

Background: With the development and innovation of medical technology, transfusion of platelet products is still a necessary treatment to prevent bleeding tendency and some adverse clinical outcomes for patients who get blood cancer or bone-marrow transplantation. However, the incidence of platelet transfusion refractoriness also gets raised due to long-term repetition of platelet transfusion to these recipients. Immune reasons such as ABO blood group incompatible, presence of HPA and HLA antibodies can show little to no increase in platelet count at 1 hour post transfusion while non-immune causes usually have decrease in platelet count post 24 hours. Recently, blood centers and medical technologists introduce single antigen flow panel-reactive antibodies test to identify antibodies against HLA in patients’ serum and HLA matchmaker software to calculate serologic “eplet score”. By the application of these methods medical technologists can obtain HLA antigen-restricted platelets which avoid the HLA antibodies that the recipients have in a “virtual”, “epitope- based” crossmatch.
Methods: This study applied human leukocyte single antigen antibody assay to recipients with pre-formed HLA antibodies, which made platelet transfusion refractoriness. By analyzing the HLA antibodies panel of the recipient’s serum, the HLA type of the donor can be avoided when looking for a compatible blood product. The CBC data was collected before platelet transfusion and post 1 hour of platelet transfusion to calculate the CCI value to evaluate the effectiveness of different platelet products.
Results: According to experimental data statistics, in all HLA-matched platelet products or cross-matched platelet products transfused to the participants of this research project, A-grade products accounted for about 6%, and B1U to B2UX grade products accounted for about 59%, with good transfusion efficacy according to the calculation results of CCI. Finally, about 35% were blood products of grades between C and D. In clinical practice, it is believed that the transfusion efficacy of blood products below grade C is not significantly different from that of random platelets (R). However, according to the results of this study, if HLA single antigen antibody testing is used in addition, the C-grade blood products that are not compatible with the HLA type of the serum of the recipient can also have good transfusion efficacy.
Conclusion: HLA single antigen antibody testing plays a good auxiliary role in the process of finding blood products for platelet transfusion. In addition to avoiding the disadvantage of traditional methods that only look for blood products with the same HLA type, which is time-consuming and cannot meet the clinical needs, it can also track the changes of HLA antibodies in the body of the participants. Further, it can prevent the transfusion failure and waste of medical resources caused by the cross-matched platelets found by the traditional insensitive methods.