Multiple crossmatch-incompatible red blood cell transfusions in a patient with anti-Yta (Cartwright) antibodies without hemolytic transfusion reactions: case report

Jazmine Ramos; William Nicholas Rose

doi:10.21037/aob-25-40

Case Report

Multiple crossmatch-incompatible red blood cell transfusions in a patient with anti-Yt^a (Cartwright) antibodies without hemolytic transfusion reactions: case report

Jazmine Ramos¹, William Nicholas Rose²

¹University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; ²Department of Pathology and Laboratory Medicine, Division of Transfusion Medicine, University of Wisconsin Hospital, Madison, WI, USA

Contributions: (I) Conception and design: Both authors; (II) Administrative support: Both authors; (III) Provision of study materials or patients: Both authors; (IV) Collection and assembly of data: Both authors; (V) Data analysis and interpretation: Both authors; (VI) Manuscript writing: Both authors; (VII) Final approval of manuscript: Both authors.

Correspondence to: William Nicholas Rose, MD. Department of Pathology and Laboratory Medicine, Division of Transfusion Medicine, University of Wisconsin Hospital, 600 Highland Ave, Madison, WI 53792, USA. Email: wrose@uwhealth.org.

Background: Anti-Yt^a is a relatively rare antibody directed against the high-prevalence Yt^a antigen in the Cartwright blood group system. Anti-Yt^a exhibits variable clinical significance, with documented reports of both hemolytic transfusion reactions (HTRs) and lack of clinical hemolysis following transfusion of Yt(a+) red blood cells (RBCs). The monocyte monolayer assay (MMA) has been shown to help predict the potential of an antibody to result in an HTR, but published clinical correlations are limited. This report describes a patient with anti-Yt^a who tolerated multiple Yt(a+) RBC transfusions without an evident HTR, consistent with his negative MMA results.

Case Description: A 72-year-old male underwent open surgical repair of a ruptured type IV thoracoabdominal aneurysm with subsequent need for RBC transfusions. Antibody screening on post-operative day (POD) 17 revealed anti-Yt^a after the patient already received 31 RBC transfusions. Given the variable clinical significance of anti-Yt^a, an initial MMA was performed to help predict the safety of Yt(a+) RBC transfusions. A repeat MMA was performed to ensure that subsequent Yt(a+) RBC transfusions remained safe. Despite indirect antiglobulin testing (performed as part of the MMA evaluation) demonstrating strong (up to 3.5+) immunoglobulin G (IgG) reactivity with Yt(a+) RBCs, both MMA results showed less than five percent reactivity, indicating low risk for HTR with antigen-positive crossmatch-incompatible blood. After negative MMA testing, the patient received four crossmatch-incompatible RBC units over three separate occasions without clinical or laboratory evidence of hemolysis, including stable post-transfusion hemoglobin and haptoglobin. The patient was discharged on POD 49, with no documentation of subsequent HTRs or additional RBC transfusions over the following 4 years.

Conclusions: This case contributes a well-documented instance of a patient with anti-Yt^a tolerating serial crossmatch-incompatible RBC transfusions, consistent with negative MMA results. This highlights an example of the utility of using the MMA to help guide transfusion decision-making in patients with anti-Yt^a.

Keywords: Anti-Yt^a; monocyte monolayer assay (MMA); red blood cell transfusions (RBC transfusions); incompatible transfusion; case report

Received: 20 September 2025; Accepted: 09 February 2026; Published online: 24 March 2026.

doi: 10.21037/aob-25-40

Highlight box

Key findings

• A patient with anti-Yt^a tolerated multiple crossmatch-incompatible red blood cell (RBC) transfusions without clinical or laboratory evidence of hemolysis, which validated the negative monocyte monolayer assay (MMA) result.

What is known and what is new?

• Anti-Yt^a is an uncommon antibody to a high-prevalence antigen. The hemolytic potential of anti-Yt^a has been shown to be variable, making transfusion decision-making challenging as Yt(a−) RBCs are of limited supply.

• This case adds an example of a patient with anti-Yt^a who tolerated multiple crossmatch-incompatible RBC units without evidence of hemolysis, guided by negative MMA testing.

What is the implication, and what should change now?

• This patient case demonstrates anti-Yt^a behaving in a clinically insignificant manner.

• The potential utility of negative MMA results to support the safe transfusion of crossmatch-incompatible Yt(a+) RBC units in patients with anti-Yt^a with close clinical and laboratory monitoring, should be considered.

Introduction

The Cartwright blood group system initially consisted of two antigens, Yt^a and Yt^b, which are antithetical antigens differentiated by a single amino acid difference in the acetylcholinesterase protein. Yt^a is a high-frequency antigen present in approximately 99.8 percent of individuals, whereas the Yt^b antigen is encountered much less frequently (1). Although the immunogenicity of the Yt^a antigen is known to be very high, anti-Yt^a remains relatively uncommon in the context of the Yt^a antigen being a high-prevalence antigen (2). Overall, anti-Yt^a is present in about 0.3 percent of Yt(a−b+) individuals (3).

Most commonly, anti-Yt^a is identified during pretransfusion antibody screening in patients with a history of multiple transfusions. When anti-Yt^a is present, it poses a challenge as anti-Yt^a is considered to have variable clinical significance. While some patients with anti-Yt^a tolerate Yt(a+) red blood cell (RBC) transfusions without an adverse reaction, anti-Yt^a has caused delayed as well as acute hemolytic transfusion reactions (HTRs) in others (1,4,5). This variability poses a challenge in transfusion medicine, as withholding Yt(a+) RBC units unnecessarily to search for rare antigen-negative units can delay care in patients with an insignificant anti-Yt^a, while transfusion in others may risk an HTR in those with a significant anti-Yt^a. It is costly and challenging to locate compatible Yt(a−) RBC units, given that only one in 500 donors lacks the Yt^a antigen. This underscores the need to conserve these rare units for cases where their use is clearly indicated (4-6).

The monocyte monolayer assay (MMA) is an in vitro functional test used to predict the potential of an antibody to cause an HTR from an antigen-positive RBC transfusion by assessing the phagocytosis of antibody-coated RBCs by human monocytes. A monocyte phagocytosis index result greater than five percent suggests that an HTR may occur with the transfusion of antigen-positive RBCs (7). The MMA can help guide clinical decision-making about the safety and efficacy of transfusing Yt(a+) RBC units in a patient who is alloimmunized with anti-Yt^a (7-10). This case report describes a patient with anti-Yt^a who received crossmatch-incompatible RBCs without developing an HTR, highlighting the importance of understanding antibody significance in informing transfusion decision-making, particularly in the setting of a high-frequency antigen. We present this article in accordance with the CARE reporting checklist (available at https://aob.amegroups.com/article/view/10.21037/aob-25-40/rc).

Case presentation

The following is a case report on a 72-year-old male with O+ blood who was admitted in March of 2014 for open surgical repair of a ruptured type IV thoracoabdominal aneurysm and had a complicated post-operative course. The patient with a history significant for hypertension and ongoing tobacco use presented with an 11-hour history of left flank and back pain. He was in hemorrhagic shock and taken for emergent surgical repair. Per the operative note, the estimated blood loss was too large to quantify. His hemoglobin dropped from 15.2 to 7.5 g/dL over the day of surgery; he received 24 units of O+ RBCs, including 15 units given intraoperatively. He received an additional five units of O+ RBCs on post-operative day (POD) one and two more O+ units on POD three. Antibody screening on the day of surgery and POD four were both negative. On POD 17, an antibody screen was obtained in the setting of acute respiratory failure with hypotension requiring rapid response. The RBC antibody screen was positive for anti-Yt^a. This was the patient’s first positive antibody screening. The direct antiglobulin test (DAT) was negative for both immunoglobulin G (IgG) and C3d. An eluate was not performed when the DAT was negative, as it is generally not indicated because there would be insufficient antibody to characterize.

The American Red Cross (ARC) recommended an MMA and, in the meantime, transfusion of ABO/Rh-compatible units negative for the Yt^a antigen, given the variable clinical significance of anti-Yt^a. The patient received one unit of RBCs on POD 22 and two units on POD 24. These three units followed the ARCs recommendation of transfusing RBCs negative for the Yt^a antigen and were all crossmatch-compatible.

Further evaluation with an MMA using a sample from POD 17 was received on POD 26. The MMA, performed by the ARC Southern California Region Research Laboratory, showed a monocyte reactivity of less than five percent. This indicated a low risk of the Cartwright antibody causing an HTR (7). Thus, it was deemed acceptable to give the patient crossmatch-incompatible Yt(a+) RBCs. ARC also recommended reevaluation with additional MMA tests before further transfusions of Yt(a+) RBCs, as anti-Yt^a may change its characteristics after transfusions with Yt(a+) RBCs (11). Additionally, ARC recommended that crossmatch-incompatible RBC transfusions be followed with close clinical monitoring and laboratory follow-up for an immune process and hemolysis, including DAT and haptoglobin, respectively. As part of the MMA evaluation, indirect antiglobulin testing (IAT) using anti-IgG demonstrated IgG reactivity with Yt(a+) reagent RBCs (3.5+ without and 3+ with the addition of fresh normal serum as complement) and no reactivity with Yt(a−) RBCs.

The patient received one unit on POD 27 of O+ crossmatch-incompatible RBCs and two more units on POD 33 of O+ RBCs, with one crossmatch-incompatible unit and the other unit resulting as crossmatch-compatible. For all units crossmatched, only a binary compatible or incompatible result was given. In summary, the patient continued to test positive for anti-Yt^a antibodies without new antibodies detected and negative for DAT between POD 22 and 33. On POD 34, about eight hours after receiving a crossmatch-incompatible RBC unit, a DAT was positive for IgG (no elution was performed) and negative for C3d with a haptoglobin level within normal range. Elution studies are not routinely recommended for patients with a positive antibody screen, given their limited value in this setting (12). The patient remained clinically stable without signs or symptoms of an HTR, including jaundice, fever, or dyspnea, and exhibited an appropriate hemoglobin response following crossmatch-incompatible RBC transfusions (from 8.0 to 8.2 g/dL after one unit and from 7.2 to 8.4 g/dL after two units).

On POD 39 and 42, DAT was negative, and no new antibodies were detected on antibody screens. On POD 43, two more crossmatch-incompatible O+ RBC units were transfused without signs or symptoms of overt hemolysis. On POD 46, a DAT was performed and shown to be positive (+1) for IgG and negative for C3d, and subsequent elution revealed anti-Yt^a. Throughout his hospital stay, ABO/Rh typing was O+. All units transfused were crossmatched and O+ except for an O- unit on POD 24. Repeat MMA testing on POD 39 showed less than five percent, further supporting that the Cartwright antibody identified in this patient was more likely to be clinically insignificant and unlikely to cause overt hemolysis. The IAT demonstrated persistent IgG reactivity with Yt(a+) reagent RBCs (3+ without and 2+ with the addition of fresh normal serum as complement) and no reactivity with Yt(a−) RBCs. Overall, this patient tolerated multiple Yt(a+) crossmatch-incompatible RBCs without evidence of hemolysis or subsequent MMA positivity (Tables 1,2). He was discharged on POD 49 with no subsequent documented RBC transfusions or HTRs, and he was not seen again by transfusion medicine. The patient died more than 4 years later. The cause of death is not documented in the medical record.

Table 1

Timeline of antibody identification, monocyte monolayer assay testing, and blood transfusions

POD	Antibody screen	MMA result	RBC units transfused	Crossmatch status
0–4	Negative	–	31 units, O+	Not documented
17	Positive for anti-Yt^a	MMA sample collected	None	–
22	Positive for anti-Yt^a	Pending	1 unit, O+ Yt(a−)	Compatible
24	–	Pending	1 unit, O+ Yt(a−); 1 unit, O− Yt(a−)	Compatible
25	Positive for anti-Yt^a	Pending	None	–
26	–	Preliminary result: negative	None	–
27–29	Positive for anti-Yt^a	Final result: <5%	1 unit, O+	Incompatible
33	Positive for anti-Yt^a	–	2 units, O+	Mixed^†
39	–	Repeat MMA result: <5%^‡	–	–
42–46	Positive for anti-Yt^a	–	2 units, O+	Incompatible

^†, one unit crossmatch-compatible, one unit crossmatch-incompatible; ^‡, the sample for the repeat MMA was collected on POD 39, with final results received 24 days later. MMA, monocyte monolayer assay; POD, post-operative day; RBC, red blood cell.

Table 2

Timeline of hemolysis laboratory monitoring following crossmatch incompatible blood transfusions in a patient with identified anti-Yt^a

POD	Incompatible RBC units transfused	DAT	Hemoglobin (g/dL): pre-/post-transfusion^†	Haptoglobin (mg/dL)^‡
27	1 unit, O+	–	8.0/8.2	–
29	None	IgG: negative; C3d: negative	–	–
33	1 unit, O+^§	IgG: negative; C3d: negative	7.2/8.4	–
34	None	IgG positive	–	189
39–42	None	IgG: negative; C3d: negative	–	–
43	2 units, O+	–	7.6/8.9	–
46	None	IgG (+1) positive, elution: anti-Yt^a	–	–

^†, hemoglobin reference range, 13.6–17.2 g/dL; ^‡, haptoglobin reference range, 30–200 mg/dL; ^§, on POD 33, a second RBC unit was transfused and was crossmatch-compatible. DAT, direct antiglobulin test; IgG, immunoglobulin G; POD, post-operative day; RBC, red blood cell.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent for publication of this anonymized case report was not obtained from the deceased patient or his relatives after reasonable attempts were made.

Discussion

This patient was positive for the anti-Yt^a antibody, was negative on the MMA, and tolerated multiple transfusions of Yt(a+) RBC units. This is evidenced by the normal haptoglobin level, stable hemoglobin levels, and lack of clinical signs or symptoms suggestive of an acute or delayed HTR after receiving crossmatch-incompatible Yt(a+) RBC units on three separate occasions. Interpretation of the DAT requires caution, as a positive DAT does not necessarily indicate hemolysis (13). The two positive DAT results on POD 34 and POD 46 did not correlate with clinical hemolysis or laboratory indicators of RBC destruction. This demonstrates a case where the negative result of the MMA test accurately predicted a low risk of an HTR in a patient with anti-Yt^a when given Yt(a+) RBC units. This highlights the use of a negative MMA as an adjunctive tool to guide safe transfusion of crossmatch-incompatible units in patients with anti-Yt^a.

There are limitations to this case report. Hemolysis assessment was limited in this retrospective report. Over the three separate days during which the patient was transfused with crossmatch-incompatible RBC units, a haptoglobin was obtained as a follow-up marker only once, reflecting clinician-directed testing. The rationale for the infrequent measurement of haptoglobin was not specified. Other laboratory markers of hemolysis, including lactate dehydrogenase, bilirubin, and reticulocyte count, were not obtained. Additionally, incompatible crossmatch results served as a proxy for Yt(a+) RBCs since the units were not specifically typed for the Yt^a antigen. However, these RBC units, along with the crossmatch-compatible RBC unit given on POD 33, were likely Yt(a+) as Yt(a−) RBCs are rare. The mixed crossmatch compatibility seen on POD 33 could be due to differences in antigen density on donor RBCs (14). Lastly, because the MMA was performed at an outside laboratory, detailed methodology was not available.

Although data on anti-Yt^a is limited, other research has shown similar findings of transfusing Yt(a+) RBC units in patients positive for anti-Yt^a without subsequent hemolysis (9,10,15,16). In the retrospective study by Wong et al., no patients with Yt^a antibody out of nine had a reported HTR when transfused with crossmatch-incompatible and likely Yt(a+) RBC units (15). This contrasts with other studies that have demonstrated the hemolytic potential of anti-Yt^a (4,5). In a case report by Raos et al., a patient with anti-Yt^a experienced an acute HTR when transfused with Yt(a+) RBCs (5). Six months later, the anti-Yt^a demonstrated negative MMA results. This supports the need for repeat MMAs to predict subsequent transfusion outcomes, as the properties of anti-Yt^a may evolve with time and following antigen exposure (11). Additionally, beyond standard pretransfusion screening, antibody screening should be repeated one to 3 months after transfusion to optimize detection of new alloantibodies (17,18).

Given the high frequency of Yt^a antigen in the population, there is a limited supply of Yt(a−) RBCs, which poses a logistical challenge to obtain. Due to a low MMA reactivity and absence of signs of hemolysis, crossmatch-incompatible Yt(a+) transfusions were eventually deemed acceptable. However, it took over a week for the MMA to return, resulting in an interim period of uncertain antibody hemolytic potential, and as 99.8 percent of the donor population is Yt(a+), crossmatches were likely to be incompatible regardless of the antibody’s hemolytic potential. This underscores the challenges of transfusion decision-making in patients with anti-Yt^a.

While IgG subclass testing was not performed in our patient, the difference in clinical significance of the anti-Yt^a antibody may be explained by its immunoglobulin subclass. Anti-Yt^a is largely of the IgG type with variations in subclass (15). While IgG1 and IgG3 are generally more effective at mediating hemolysis, IgG4 antibodies are typically associated with reduced hemolytic potential (19). Anti-Yt^a has been identified to be of the IgG4 subclass in some cases, which may contribute to its benign behavior in cases of crossmatch-incompatible transfusions (20). This concept may also explain the fluctuations of the DAT results in our patient. It is reasonable that the anti-Yt^a may be of an Ig subclass, like IgG4, that sufficiently binds antigen to cause a positive DAT result but may not efficiently activate phagocytes to result in clinically significant hemolysis.

Conclusions

This case describes a patient with anti-Yt^a who tolerated multiple crossmatch-incompatible RBC transfusions without clinical or laboratory evidence of an HTR, consistent with negative MMA results. This report underscores the potential utility of a negative MMA as an adjunctive tool to help guide safe transfusion of crossmatch-incompatible units in patients with anti-Yt^a.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://aob.amegroups.com/article/view/10.21037/aob-25-40/rc

Peer Review File: Available at https://aob.amegroups.com/article/view/10.21037/aob-25-40/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://aob.amegroups.com/article/view/10.21037/aob-25-40/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent for publication of this case report was not obtained from the patient or the relatives after all possible attempts were made.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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doi: 10.21037/aob-25-40
Cite this article as: Ramos J, Rose WN. Multiple crossmatch-incompatible red blood cell transfusions in a patient with anti-Yt^a (Cartwright) antibodies without hemolytic transfusion reactions: case report. Ann Blood 2026;11:4.