Elsevier

Journal of Surgical Research

Volume 255, November 2020, Pages 99-105
Journal of Surgical Research

Society of Asian Academic Surgeons
Transplantation/Immunology
Human Leukocyte Antigen Class I Antibodies and Response to Platelet Transfusion in Patients Undergoing Liver Transplantation

https://doi.org/10.1016/j.jss.2020.05.029Get rights and content

Abstract

Background

Patients undergoing liver transplantation (LT) frequently receive platelet transfusion (PLT) to minimize their risk of hemorrhage. Alloimmunization to platelets may lead to refractoriness to PLT. Data on the implications of platelet alloimmunization in patients undergoing LT remain limited. We examined the effect of human leukocyte antigen class I (HLA-I) antibodies on PLT refractoriness and short-term outcomes after LT.

Methods

Peritransplant clinical and PLT factors were reviewed for all adult liver or simultaneous liver–kidney transplantations from 2012 to 2017. Sensitized patients (SE) with pretransplant HLA-I calculated panel-reactive antibody ≥20% were compared with unsensitized patients (US) with calculated panel-reactive antibody <20%. The mean follow-up was 21.4 mo.

Results

Alloimmunization was observed in 39% of the study cohort. SE (n = 28) received 272 PLTs, and US (n = 44) received 246 PLTs. History of pregnancy was higher among SE than US (P < 0.01); otherwise, both groups had similar clinical characteristics. SE had higher rates of PLT refractoriness (66% versus 47%; P < 0.01) than US. The mean platelet corrected count increment was lower among SE compared with US up to 100 min after PLT (P < 0.05). Alloimmunization and simultaneous liver–kidney transplantation independently predicted refractoriness on multivariate logistic regression (P < 0.05). Early allograft rejection and patient survival rates were comparable for both groups.

Conclusions

LT patients experienced high rates of HLA-I alloimmunization and PLT refractoriness. SE had higher rates of refractoriness and lower mean corrected count increment after transfusion compared with US. Our study suggests that further research to evaluate the utility of HLA-matched PLTs in HLA-I alloimmunized LT patients is warranted.

Introduction

Allogeneic blood transfusion introduces a multitude of foreign antigens and cells into the recipient, who mounts an immune response to the donor antigens (i.e., alloimmunization). Various clinical consequences may arise specific to the blood cells and antigens involved. The antigens most commonly implicated are classified as (1) human leukocyte antigens (HLA), divided into class I shared by platelets and most nucleated cells including leukocytes and class II present on antigen-presenting cells; (2) granulocyte-specific antigens; (3) human platelet antigens; and (4) red blood cell antigens.1, 2, 3, 4

Thrombocytopenia, defined as a platelet count <100 × 109/L, is a common complication in patients with end-stage liver disease (ESLD). Although the risk for clinically significant spontaneous bleeding because of thrombocytopenia is generally low in healthy individuals with a platelet count >20 × 109/L, ESLD patients exhibit increased risk for spontaneous hemorrhage and for iatrogenic bleeding from indicated invasive procedures (e.g., endoscopy, liver biopsy, paracentesis, etc.). As such, patients with ESLD frequently receive transfusions of platelet concentrates and other blood products to minimize their risk of hemorrhage. Alloimmunization against platelets may occur in up to 45% of patients receiving PLT and platelet refractoriness or inadequate response of the platelet count to transfusion, resulting from alloimmunization in 13%.5 Patients may develop platelet antibodies as early as 4 d after blood transfusion.6 Platelet refractoriness in ESLD patients undergoing liver transplantation (LT) increases patients’ risk for peri- and intra-operative hemorrhage, additional transfusion, and complications.7, 8, 9 Data on the incidence of platelet refractoriness because of HLA alloimmunization in LT patients and its impact on posttransplant outcomes remain limited. We sought to examine the effect of HLA class I (HLA-I) antibodies on refractoriness to PLT and short-term outcomes after LT.

Section snippets

Data collection

Using a prospectively collected transplantation database, we conducted a retrospective review of all patients aged ≥18 y who underwent LT or simultaneous liver–kidney (SLK) transplantation at the Froedtert and the Medical College of Wisconsin Transplant Center from October 2012 to September 2017. Patients were excluded if they (1) did not have HLA-I calculated panel-reactive antibody (cPRA) testing within 2 wk before or after transplantation, (2) suffered primary nonfunction of their hepatic

Patient characteristics

Of a total 145 LT and SLK transplantations performed during the study period, 72 patients met inclusion criteria and formed the study cohort. The mean age was 55.6 y. The most common etiologies of liver disease were hepatitis C and alcohol. Among the 26 female patients (36% of the study cohort), 19 patients (73%) had a history of pregnancy. Alloimmunization was observed in a total of 28 patients (39%) in the study cohort. The most commonly identified HLA-I antibody specificities in the study

Discussion

Although the impact of alloimmunization on platelet refractoriness has been well-described in hematology–oncology patients,5,14 the data on its clinical implications in solid organ transplantation remain limited. Our study reported the relationship between HLA-I alloimmunization and refractoriness to PLT in liver and SLK transplantation. We observed relatively high rates of both HLA-I alloimmunization, 39%, and refractoriness to PLT, 56%, in our cohort of LT and SLK transplantation patients. SE

Acknowledgment

The authors gratefully acknowledge Karen L. Pierce, B.S. C.H.S., and Lori A. Eggert, B.A., of the Versiti BloodCenter of Wisconsin Histocompatibility Laboratory for their help with coordinating the data collection.

This work was supported in part by The Kevin T. Cottrell Memorial Fund for Organ Transplantation Research.

Authors’ contributions: All authors contributed to study conception and design and analyzed the data. M.W., R.N., M.S., and A.P. contributed to acquisition of data. Drafting of

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