Anti-HLA antibody formation increases the chances of platelet refractoriness in platelet-transfused patients: a systematic review with meta-analysis

Cabral, Luana Joana Barreto; Lopes, Daniela Pereira; Martins Filho, Eduardo dos Santos; Valois, Rubenilson Caldas; Oliveira, Paula Christine Amarantes Justino; Mendonça-Mattos, Patrícia Jeanne de Souza

doi:10.1016/j.htct.2025.103821

person Luana Joana Barreto Cabral ⁎

schoolGraduate Program in Multiprofessional Residency in Hemotherapy and Hematology, Pará State University (UEPA), Belém, Pará, BrazilschoolMultiprofessional Residency in Hemotherapy and Hematology, Foundation Center of Hemotherapy and Hematology of Pará (HEMOPA Foundation), Belém, Pará, BrazilschoolLaboratory of Immunogenetics, Foundation Center of Hemotherapy and Hematology of Pará (HEMOPA Foundation), Belém, Pará, Brazil

0000-0002-1060-9317

person Daniela Pereira Lopes

schoolGraduate Program in Multiprofessional Residency in Hemotherapy and Hematology, Pará State University (UEPA), Belém, Pará, BrazilschoolMultiprofessional Residency in Hemotherapy and Hematology, Foundation Center of Hemotherapy and Hematology of Pará (HEMOPA Foundation), Belém, Pará, Brazil

person Eduardo dos Santos Martins Filho

schoolLaboratory of Immunogenetics, Foundation Center of Hemotherapy and Hematology of Pará (HEMOPA Foundation), Belém, Pará, Brazil

person Rubenilson Caldas Valois

schoolHemovigilance and Supervision Department, Foundation Center of Hemotherapy and Hematology of Pará (HEMOPA Foundation), Belém, Pará, BrazilschoolTeaching Staff, Pará State University (UEPA), Belém, Pará, BrazilschoolPreceptors of the State Program of Incentives to Qualification of Health Professionals - QUALIFICASAÚDE, Pará State University (UEPA), Belém, Pará, Brazil

0000-0001-9120-7741

person Paula Christine Amarantes Justino Oliveira

schoolTechnical Directory, Foundation Center of Hemotherapy and Hematology of Pará (HEMOPA Foundation), Belém, Pará, Brazil

person Patrícia Jeanne de Souza Mendonça-Mattos

schoolLaboratory of Immunogenetics, Foundation Center of Hemotherapy and Hematology of Pará (HEMOPA Foundation), Belém, Pará, BrazilschoolPreceptors of the State Program of Incentives to Qualification of Health Professionals - QUALIFICASAÚDE, Pará State University (UEPA), Belém, Pará, Brazil

0000-0001-6608-4954

person⁎ Corresponding author.
E-mail address:luanajbcabral@gmail.com (L.J.B. Cabral)

Conflicts of interest

The authors declare no conflict of interest.

Search strategy				Database
	AND	AND	AND	WOS	SCOPUS	PUBMED CENTRAL	LILACS	BVS BRAZIL	Medline (EBSCOhost)	SciELO Citation Index
("aplastic anemia "OR "myelodisplasic syndromes "OR "leukemias "OR “thrombocytopenic Patients" OR “thrombocytopenia" OR "anemia aplástica "OR "síndromes mielodisplásicas "OR "leucemias "OR "pacientes trombocitopênicos "OR "trombocitopenia "OR "síndromes mielodisplásicos "OR "pacientes trombocitopénicos "O "sindromi mielodisplasiche "OR "leucemie "OR "pazienti trombocitopenici")	(platelets OR platelet OR "platelet transfusion "OR plaquetas OR "transfusão de plaquetas "OR "transfusão de plaquetas "OR "transfusión de plaquetas "OR piastrine OR "trasfusione di piastrine")	(“polytransfused platelets” OR "platelet polytransfused" OR " ineffective platelet transfusion" OR transfusion OR "plaquetas poli-transfundidas" OR "politransfusão de plaquetas" OR " transfusão de plaquetas ineficaz" OR transfusão OR "transfusión ineficaz de plaquetas" OR transfusión OR "piastrine politrasfuse" OR " trasfusione inefficace di piastrine" OR trasfusione)	(“anti-HLA” OR “HLA antibodies” OR “anti-HLA antibodies” OR “Class I HLA” OR "HLA antibody" OR "anti-HLA" OR "anticorpos HLA" OR "anticorpos anti-HLA" OR "anticorpos HLA classe I" OR "anticorpo HLA" OR "anticuerpos anti-HLA" OR "Clase I HLA" OR "anticuerpo HLA" OR "anticorpi HLA" OR "anticorpi anti-HLA")	129	5	6	4	1	686	1

Author	Technique	Refractoriness^a		Anti-HLA antibodies^a		Total (n)	Rstudio program^b
Author	Technique	Present	Absent	Present	Absent	Total (n)	evtto	ntto	evcont	ncont
Wu et al.,²⁵	LCY (One Lambda) and PA (Payton associates)	6	3	6	3	9	6	6	0	3
Murphy et al.,²⁷	LCT (Mittal)	20	116	37	99	136	20	20	17	116
Godeau et al.,²⁸	LCT (Mittal) and MAIPA (Kiefel et al.²⁹	1	49	13	37	50	1	1	12	49
Novotny et al.³⁰	LCT and PRA ≥ 2 0% and MAIPA (HLA w6/32)	31	133	48	116	164	31	31	17	133
Bajpai et al.³¹	LCT ≥ 2 0% (Terasaki e McClelland) and PSIFT	18	32	30	20	50	18	18	12	32
Lin et al.³²	Flow Cytometry using donor platelet concentrates + kit FlowPRA™ (One Lambda)	31	13	28	16	44	28	31	0	13
Pai et al.³³	Luminex Assay (LifeScreen, Tepnel Lifecodes Corporation, Stamford, CT)	19	54	23	50	73	19	19	4	54
Jackman et al.³⁴	Luminex /LabScreen assay (One Lambda, Canoga Park, CA). Results with NGB. NGB > 10,8 (Class I HLA antibodies) and NGB > 6.9 (Class II HLA antibodies) were the cutoffs.	80	110	20	170	190	20	80	0	110
Enein et al.³⁵	FlowPRA screening kit, (OneLambda Canoga Park, USA). And CDC	13	7	6	14	20	6	13	0	7
Kumawat et al.³⁶	ELISA kit (Pakplus, GT diagnostic, USA) on three occasions (upon acceptance into the study, after 3 weeks or four transfusions, whichever occurred earlier, and at the end of 3 months)	21	9	18	12	30	18	21	0	9
Ramírez et al.³⁷	Microlymphocytotoxicity for identification of HLA antibodies and Polyethylene glycol 6000 method for identification of circulating immune-complexes	14	57	26	45	71	14	14	12	57
Hess et al.²²	CCI and PRA Class I HLA (FlowPRA Screening Kit, One Lambda Corp, Canoga Park, CA, USA);	102	614	40	776	816	40	102	0	614
Comont et al.²⁴	Luminex/ LABScreen Mixed and Class I HLA Single Antigen (One Lambda). Confirmed the most reactive with LCA-CDC using a 60-cell panel.	41	856	31	866	897	31	41	0	856
Peña et al.²⁶	Screening was performed with phenotyped beads from the LABScreen PRA (One Lambda Thermo Fisher; Luminex). If positive, single beads (LABScreen single antigen; One Lambda Thermo Fisher) were used. The strength of reactivity was reported as MFI. PRA was calculated using Fusion software (One Lambda Thermo Fisher). Overall, MFI≥1000 was considered positive, although standard reactivity was also considered. The percent of antibody reactivity panel calculation was determined by the online calculator optn.transplant.hrsa.gov/converge/resources/allocationcalculators.asp	7	20	7	20	27	7	7	0	20

Refractoriness^a		Anti-HLA antibodies^a		Total (n)	OpenEpi v. 3.01
Present n	Absent n	Present n	Absent n	Total (n)	Chi-square^b	R	NR
404	2073	333	2244	2577	anti-HLA+	333	2073
					anti-HLA-	404	2244
Yates corrected chi-square (2-tail)			Fisher's exact (2-tail)	Odds ratio	Confidence interval
p-value = 0.1662			p-value = 0.1659	0.8922	[0.7627, 1.044¹]

Authors	Anti-HLA antibody
Wu et al.,²⁵	A2 and X
Murphy et al.,²⁷	Multispecific (it was not possible to discriminate)
Godeau et al.,²⁸	Antibodies not specified, only said they were against Caucasian HLA antigens of cryopreserved lymphocytes
Novotny et al.,³⁰	Antibodies not specified
Bajpai et al.,³¹	Antibodies not specified
Lin et al.,³²	Common and rare HLA class I antigens, but not specified
Pai et al.,³³	Highly reactive public epitopes: 145QRT, 65QIA, 62QE, 127 K, and 163EW. Most common private epitope found: 151AHA (with HLA-A11 specificities)
Jackman et al.,³⁴	HLA Class I antigens, but not specified (samples from TRAP study included)
Enein et al.,³⁵	HLA Class I and Class II antigens, but not specified
Kumawat et al.,³⁶	HLA Class I antigens, but not specified. A significant association between HLA antibodies with (HPA)-5b/5b antibody (p-value = 0.033) associated with refractoriness was found
Ramírez et al.,³⁷	Antibodies not specified
Hess et al.,²²	HLA Class I antigens, but not specified
Comont et al.,²⁴	HLA Class I antigens, but not specified
Peña et al.,²⁶	From one patient (52 years old) with two remote pregnancies: a) Day 6 with routine PLT transfusions: HLA-B7 and HLA-B81; b) Day 22: mean fluorescence intensity stronger results of B7 and B81, followed by appearances of antibodies against A68, A69, A24, A2, A23 and B67