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Identification of rare anti-f alloantibody in a tertiary care center in India

 Department of Transfusion Medicine, Medanta Lucknow, Lucknow, Uttar Pradesh, India

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Date of Submission13-Feb-2021
Date of Decision07-Jun-2021
Date of Acceptance12-Jun-2021
Date of Web Publication04-Jun-2022


A 68-year-old male known follow-up patient of nonalcoholic steatohepatitis and carcinoma stomach was admitted to hospital for further management. The patient was planned for radical gastrectomy and required two units of packed red blood cell (PRBC), due to low hemoglobin of 6.6 g/dl. The patient blood grouping and antibody screening (ABS) were done. Patient ABS was positive. On antibody identification, using eleven-cell identification panel, resolve Panel A (Ortho Clinical Diagnostics, Johnson and Johnson, USA), “anti-f” alloantibody was identified in the patient sample. Select cells, from another resolve panel were used to rule out remaining antibodies. Anti-f antibody is produced due to the exposure of “f antigen.” Anti-f antibody can cause hemolytic disease of fetus and new-born and possible hemolytic transfusion reactions. At our center, we successfully transfused two units of anti-human globulin compatible and “c-negative” units, to the patient without any adverse reactions. Thus, the patient having anti-f antibody can be managed by transfusing “c-negative” or “e-negative” PRBC units or units lacking both the “c” and “e” antigens.

Keywords: Antibody identification, antibody screen, anti-f antibody, c-negative, e-negative, f antigen

How to cite this URL:
Bhardwaj G, Tewari A, Tiwari D, Vishwakarma S. Identification of rare anti-f alloantibody in a tertiary care center in India. Asian J Transfus Sci [Epub ahead of print] [cited 2023 Mar 31]. Available from:

   Introduction Top

The Rhesus (Rh) blood group is the most complex of the blood group systems, comprising 54 antigens, numbered from RH1 to RH61, of which seven numbers are obsolete. The Rh antigens are encoded by two homologous, closely linked genes on the short arm of chromosome 1; RHD gene, producing the D antigen, and RHCE, producing the Cc and Ee antigens, respectively.[1] Some Rh antigens also, known as compound antigens, are only expressed when c and e or C and e or C and E or c and E are produced by the same RHCE gene.[1] The “antigen f” is included in a series of these compound antigens. It was previously referred to as cis-products to indicate that the antigen is expressed on the red blood cells (RBCs) when both c and e are present on the same haplotype. However, it is now known that “f antigen” is likely a single entity expressed on the Rhce protein resulting from conformational changes in the Rhce protein.[2]

Cases with anti-f alloantibody have been rarely reported in India. We report a case of successful identification of anti-f alloantibody in a male patient and providing him transfusion support with compatible units.

   Case Report Top

Clinical presentation

A 68-year-old male patient who was known hypertensive and was diagnosed to have nonalcoholic steatohepatitis along with carcinoma stomach was admitted for radical gastrectomy.

The initial complete blood count showed hemoglobin (Hb) of 6.6 g/dl. Owing to the transfusion requirement apart from preliminary investigations, samples for blood grouping and antibody screening (ABS) were sent to the blood center.

Laboratory workup

Column agglutination technology (CAT) was employed to perform patient blood grouping and ABS and antibody identification (ABID). As a routine procedure, patient ABS was performed using low-ionic strength solution-based CAT, the patient's plasma was screened for irregular antibodies using commercially available three-cell reagent panel (R1R1, R2R2, and rr phenotype; 0.8% Surgiscreen, Ortho Clinical Diagnostics, Johnson and Johnson, USA). Patient ABS was positive. The results are displayed in [Table 1].
Table 1: Initial Serological Tests

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This was followed by ABID using eleven-cell identification panel, resolve Panel A (Ortho Clinical Diagnostics, Johnson and Johnson, USA). The ABID was performed on anti-human globulin (AHG) Anti-IgG; anti-C3d; polyspecific cards (Ortho BioVue System, Ortho Clinical Diagnostics, Johnson and Johnson, USA). First, the panel cells were evaluated to exclude out the antibodies that could not be responsible for the reactivity seen. Then the panel cells were examined for the pattern of reactivity that matched and was suggestive of the presence of “anti-f” alloantibody, as shown in [Figure 1]. But, the existence of anti-Jka, anti-Lea, anti-S, and anti-M along with anti-f were not ruled, since none of these antibodies were excluded out even once in the homozygous state. Hence, select cells, from another resolve panel were used to rule out these remaining antibodies. The results of which are shown in [Figure 2].
Figure 1: Antibody identification panel

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Figure 2: Select cells to rule out remaining allo-antibodies

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By using select cells, anti-Lea was eliminated by selected cell number 1 and anti-M was eliminated by selected cell number 2. We could not find panel cells that were in homozygous dose for antigen Jka or antigen S and which should also, be simultaneously negative for antigen f. On performing extended antigen phenotyping of patient RBCs, with antisera's (Ortho Clinical Diagnostics, Johnson and Johnson, USA) anti-Jka, and anti-S were excluded out as the patient was serologically positive for Jka and S antigens [Table 2].
Table 2: Extended antigen phenotyping of patient's red cells

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Since anti-E and anti-Jkb were ruled out only once by resolve Panel A, therefore selected cell number 3, was used to exclude out these clinically significant antibodies once more.

As anti-f antisera are not available separately, selected cell number 9 was used to confirm the presence of anti-f, by testing against cells from another cell panel.

Anti-f alloantibody identification and RH phenotyping

Anti-f alloantibody was identified in the patient sample. The auto control and direct antiglobulin test were negative. The extended phenotyping for RH antigens were performed with antisera's (Ortho Clinical Diagnostics, Johnson and Johnson, USA). The patient was serologically C+E-c-e+ [Table 2].

Further management and follow up

On identification of anti-f antibody, the patient's past medical history was investigated to determine any history of blood transfusion. It was revealed that he has been transfused twice with packed RBCs (PRBCs), first time about a year ago and last transfusion about 4 months ago in a peripheral hospital. We received PRBC crossmatch request for two units. Random crossmatch was done with five units, of which two units were AHG compatible. Both the compatible units were c-negative. The results are shown in [Table 3].
Table 3: Phenotyping for antigen c and e in cross-matched units

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After transfusion of the first PRBC unit, patient Hb increased from 6.6 g/dl to 7.4 g/dl. No adverse transfusion reaction occurred.

Meanwhile patient developed some cardiac complications, with significant changes on echocardiogram and abnormal dobutamine stress echocardiogram (DSE). Since radical gastrectomy is a high-risk procedure, it was postponed in view of abnormal DSE investigation. Thereafter, the patient was advised for urgent coronary angiography + PCI and was shifted under cardiac team. The patient was managed under the supervision of critical care team and the second compatible unit of PRBC was transfused with no adverse reaction. Further rise in Hb, could not be monitored since patient attendants got patient discharged as they did not want any further treatment. The patient was being discharged and thus could not be further followed up.

   Discussion Top

The f antigen belongs to the Rh blood system with the International Society of Blood Transfusion symbol (number) RH6 (004006 or 4.6). It was reported in 1953 and named with the next letter of the alphabet when it was observed that c and e in cis were required for its expression. Its occurrence in Caucasians is 65%, Africans 92%, and Asians 12%.[3]

The f antigen expressed on RBC of individuals who have c and e genes present on the same haplotype. Previously, included in a list of so-called “compound antigens,” the “f antigen” is not really a “compound” antigen, since is not formed by the mere presence of c and e on the same red cell. However, rather it is formed by the action of the Rhce allele that also encodes both c and e. Hence, it better to state that Rhce codes for c, e, and f antigens.[4]

Phenotypically, when tested against the five major Rh antisera (Anti-D, Anti-C, Anti-E, Anti-c, and Anti-e) predicted genotypes Rzr (DCE/dce) could not be distinguished from R0r (DcE/DCe) and appeared the same. However, when tested with anti-f, only the DCE/dce shows positive reactivity, confirming the former genotype.[2] Anti-f is frequently a component of sera containing anti-c or anti-e and can be made by people with partial c and e antigens. Anti-f frequently fades in vitro and in vivo.[3]

Anti-f antibody is capable of causing hemolytic disease of the fetus and newborn[5] and transfusion reactions, thus, “f-negative” blood should be provided. Since anti-f is not commercially available as a reagent; however, c-negative or e-negative blood may be provided since all c-negative or e-negative individuals are also f-negative.[2]

The first two examples of anti-f (anti–ce) were detected in multi-transfused DCe/DcE patients.[6],[7] Anti-ce has also been implicated in a delayed hemolytic transfusion reaction.[8] In a case study by Jator and Pedde,[9] they identified anti-f antibody in a 24-year-old male, with no clear history of blood transfusion. The patient was transfused with two c-negative units, with no adverse reactions. A case report by Nakamura et al.,[10] showed identification of anti-f alloantibody in a male patient, having no history of previous blood transfusion, suggesting a naturally acquired anti-f alloantibody.

In our case study, the patient had received blood transfusion on two separate occasions. First time it was approximately a year ago and second time around 4 months ago, in two different tertiary care hospitals. Since the patient was phenotypically “c negative” and “e positive,” at our hospital, we have issued and transfused the patient with two PRBC units, both were AHG compatible and “c” negative. The units which were positive for both “c” and “e” antigens were not compatible [Table 3].

Since the patient was RhD positive and we also performed extended phenotyping for RH antigens [Table 2], thus the patient was serologically D+C+E-c-e+. The possible genotype of the patient based on phenotype could have been R1R1 (DCe/DCe) or R1r' (DCe/dCe).

We did not perform adsorption– elution since anti-f could be identified with the help of RH antisera's and using select cells from another panel.

   Conclusion Top

We reported a rare case of anti-f alloantibody in India. The patient was successfully transfused with two AHG compatible and “c-negative” units, without any adverse reactions. Thus, timely identification and confirmation of anti-f antibodies in patients can be managed by transfusing “c-negative” or “e-negative” PRBC units or units lacking both the “c” and “e” antigens.

Limitation of the study

We were not able to follow-up the patient, after two units of RBC transfusion, since the patient was discharged against medical advice. Furthermore, due to the constraint of resources genotyping of patient RBCs could not be done.

Declaration of patient consent:

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient has given his consent for his images and clinical information to be reported in the journal. The patient understand that his name and initials will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

Daniels G. Human Blood Groups. 3rd ed. Chichester, United Kingdom: John Wiley and Sons; 2013. p. 182-211.  Back to cited text no. 1
Harmening DM. Modern Blood Banking and Transfusion Practices. 7th ed. Philadelphia: FA Davis Company; 2012. p. 163-4.  Back to cited text no. 2
Reid ME, Lomas-Francis C, Olsson ML. The Blood Group Antigen Factsbook. 3rd ed. SanDiego: Academic Press; 2019. p. 210-12.  Back to cited text no. 3
Glossary: f antigen – Blood Bank Guy Glossary. Available from: [Last Accessed on 2021 Feb 12]  Back to cited text no. 4
Levine P, White J, Stroup M, Zmijewski CM, Mohn JF. Haemolytic disease of the newborn probably due to anti-f. Nature 1960;185:188-9.  Back to cited text no. 5
Sanger R, Race RR, Rosenfield RE, Vogel P, Gibbel N. Anti-f and the “New” Rh antigen it defines. Proc Natl Acad Sci U S A 1953;39:824-34.  Back to cited text no. 6
Grundorfer J, Kopchik W, Tippett P, Sanger R. Anti-f in the serum of a CDe/cDE person: The second example. Vox Sang 1961;6:618-9.  Back to cited text no. 7
O'Reilly RA, Lombard CM, Azzi RL. Delayed hemolytic transfusion reaction associated with Rh antibody anti-f: First reported case. Vox Sang 1985;49:336-9.  Back to cited text no. 8
Jator EK, Pedde E. Anti-f in a 24-year-old male: A case study. Clin Lab Sci 2010;23:68-71.  Back to cited text no. 9
Nakamura Y, Ohsawa T, Furuta Y, Tokida M, Ichikawa K. Successful identification of anti-F alloantibody in a non-transfused male patient employing ID-micro typing system gel cards®. J Blood Disord Transfus 2015;6:2.  Back to cited text no. 10

Correspondence Address:
Gunjan Bhardwaj,
Department of Transfusion Medicine, Medanta-Lucknow, Sector-A, Pocket-1, Sushant Golf City, Amar Shaheed Path, Lucknow - 226 030, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ajts.ajts_22_21


  [Figure 1], [Figure 2]

  [Table 1], [Table 2], [Table 3]


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