|Year : 2017 | Volume
| Issue : 1 | Page : 64-67
Kell alloimmunization in pregnancy: Lessons to be learnt
Department of Transfusion Medicine, Kovai Medical Center and Hospital, Coimbatore, Tamil Nadu, India
|Date of Web Publication||22-Mar-2017|
Department of Transfusion Medicine, Kovai Medical Center and Hospital, Coimbatore, Tamil Nadu
Source of Support: None, Conflict of Interest: None
With the introduction of anti-D prophylaxis, the incidence of RhD alloimmunization in pregnancy has been significantly reduced. RhD remains the most common cause of hemolytic disease of fetus and newborn (HDFN). Next to anti-D, anti-K and anti-c have been implicated in severe HDFN. Hereby, we report a case of Kell alloimmunization in pregnancy which is a leading cause of HDFN worldwide. This case highlights the need for tertiary care hospitals to establish a well-defined protocol for the management of Kell alloimmunization in antenatal females. Most commonly, Kell alloimmunization is secondary to previous transfusions, and hence, every attempt should be made for primary prevention, i.e., Rh-Kell-matched transfusions for women of reproductive age group.
Keywords: Hemolytic disease of fetus and newborn, Kell blood group, red cell alloimmunization, transfusion
|How to cite this article:|
Subramaniyan R. Kell alloimmunization in pregnancy: Lessons to be learnt. Glob J Transfus Med 2017;2:64-7
| Introduction|| |
The causes for red cell alloimmunization (RCA) include transfusions, pregnancy, and/or transplantation. RhD alloimmunization remains the most common cause of hemolytic disease of fetus and newborn (HDFN); however, non-Rh antibodies are also encountered in clinical practice as a cause of HDFN. The management of non-Rh alloimmunization in pregnancy is a challenging task because clear guidelines on the protocols to be followed do not exist. Herein, we report a case of Kell alloimmunization in pregnancy which is a leading cause of HDFN worldwide. This case highlights the need for tertiary care hospitals to establish a well-defined protocol for the management of Kell alloimmunization in antenatal females.
| Case Report|| |
A 24-year-old lady (G2P1L1A0 at 11 + 4 weeks period of gestation) visited our antenatal clinic to register her second pregnancy. Her blood group was A RhD negative. Her first pregnancy (G1) was 3 years ago and got registered in another hospital. She was informed that her red cell antibody screening was positive for anti-Kell. Paternal Kell phenotyping was not done at that time. She received antenatal anti-D prophylaxis at 28 weeks of gestation. Serial ultrasound doppler monitoring of peak systolic velocity of fetal middle cerebral artery was done. She delivered at 38+5 weeks due to premature rupture of membranes and no adverse neonatal outcome occurred. Previous medical history revealed that the patient had undergone surgery for septic arthritis 8 years ago, during which she received transfusion of one unit of group specific nonleukoreduced packed red blood cells (RBCs). The transfusion was uneventful. Posttransfusion, her hemoglobin levels raised to 8 g/dL.
In the current pregnancy (G2), red cell antibody screening was repeated using commercial cell panel (Diacell I-II-III, Biorad, Switzerland) by gel method and was found to be positive, autocontrol being negative. The antibody screen was negative in NaCl enzyme cards (Biorad, Switzerland). Direct Coombs test (DCT) was negative with monospecific (IgG and C3d) Coombs' gel card. Further, red cell antibody identification was done using commercial 11-cell panel by gel method (ID-Diapanel, Biorad, Switzerland) with specificity to anti-Kell antibody of IgG subtype. No additional alloantibodies were identified. The anti-Kell titers were 1:256. The husband's blood group was A Rh D positive. Extended Rh and Kell phenotyping of both the patient and her husband were done [Table 1]. Husband was also Kell antigen negative. Repeat antibody screen at 28 weeks was negative for additional alloantibodies. Subsequently, she was administered anti-D. The course of her pregnancy was uneventful. She delivered a male term baby at 38+2 weeks of gestation. The neonate's blood sample was Group A negative and DCT negative. There were no features of HDFN.
| Discussion|| |
Based on various studies conducted worldwide, the overall incidence of RCA in antenatal women is estimated to range 0.4%–2.71%. Second only to anti-D, the most common red cell alloantibodies implicated in HDFN are anti-K, anti-c, and anti-E. In 2%–4% of non-RhD alloimmunization pregnancies, HDFN is known to occur. The Kell blood group system has 24 antigens though Kell (K, K1) and cellano (k, K2) are considered clinically significant. They are potentially immunogenic, being implicated in severe HDFN. Kell antigen appears on fetal red cells by 10th week of life. Kell alloimmunization is mostly secondary to previous transfusions and rarely fetomaternal hemorrhage in pregnancy. When compared to Kell alloimmunization secondary to pregnancy, anti-K developing subsequent to transfusion seems to be less severe. Kell alloimmunization is considered important in pregnancy as the characteristics of HDFN due to anti-K are strikingly different from anti-D HDFN, namely, lesser amount of hemolysis (reduced reticulocytosis) and bilirubin levels in amniotic fluid and minimal postnatal hyperbilirubinemia. Fetal anemia caused by anti-Kell antibodies is due to the destruction of fetal erythroid progenitors in addition to hemolysis. It has been observed that anti-Kell titers >1:32 reflect the severity of hemolysis with 100% sensitivity although fetal anemia has been documented with anti-Kell titers of 8., Strategies for the management of Kell alloimmunization in pregnancy include basal assessment of antibody titers, paternal Kell antigen phenotyping and fetal Kell antigen status, ultrasonographic monitoring of the fetus for the signs of anemia and fetal hydrops and intrauterine transfusions if required.
Incidence of Kell antigen in our general population ranges from 4% to 6% (9% among Caucasians and 2% among African descents)., Incidence of Kell alloimmunization is estimated to be approximately 1 in 1000 pregnancies., In a study analyzing the specificities of non-RhD antibodies in 1,08,000 antenatal women, Kell antibodies were the most common with a prevalence of 0.5/1000 antenatal women (0.5%). In another study on Kell alloimmunization in pregnancy, Kell alloimmunization was identified in 10 out of 75 alloimmunized women. Out of 10, 3 had Kell positive fetuses and all presented with fetal anemia and further interventions were required. The prevalence of RCA in our antenatal patient population is estimated to range from 1.2% to 2.67%. In our patient population, non-RhD alloimmunization in pregnancy has been documented, mostly involving Rhesus, Kell, and MNS blood group systems. Kell alloimmunization rates, based on various studies, have been observed to be 1 in 3755 and 1 in 750 antenatal women., However, these values are hospital based and cannot be extrapolated for the overall incidence of RCA. These values should be confirmed by studies with larger sample size. In our patient, Kell alloimmunization was secondary to transfusion which was given several years before pregnancy. In up to 80% of antenatal women with anti-K, previous history of transfusion is present. In one study, history of red cell transfusion was present in 48% of pregnancies with non-RhD alloimmunization (most commonly, anti-K, anti-c, and anti-E). Koelewijn et al. studied the risk factors for the non-RhD alloimmunization in pregnancy and found that RBC transfusion is the most common independent risk factor for non-RhD alloimmunization. They also concluded that platelet transfusions, surgery, gravidity, hematological disease, and parity should be considered the additional risk factors. Prophylactic Rh-Kell-matched transfusions have been recommended for all women of reproductive age group as a primary prevention strategy. Several countries have incorporated the same in their transfusion policy. The scenario is different in most of the developing countries such as India, where red cell transfusions are matched only for ABO and RhD. Although the incidence of Kell alloimmunization is observed to be low, the prognosis is poor in such pregnancies with Kell positive fetuses., Anti-D remains the most common cause of RCA in antenatal women; nevertheless, the incidence has significantly reduced thanks to the worldwide implementation of anti-D prophylaxis. At the same time, the prevalence of non-RhD antibodies in antenatal women is increasing and estimated to be 0.2% to 0.3%. Koelewijn et al. concluded in their study that first trimester red cell antibody screening enables effective management of non-RhD alloimmunization with a detection sensitivity of 75%. Many developed countries have adopted red cell antibody screening in the first trimester for all antenatal women. At present, in India, we perform red cell antibody screening in RhD negative women only. RCA in pregnancy is an underestimated health care burden for a developing country like India. In the absence of a well-established antenatal screening program for such alloimmunized women, more than 50,000 fetuses would be lost every year. Red cell antibody screening in all pregnant women (irrespective of the RhD status) significantly helps in early identification of the “at risk” cases and further management. Hence, we recommend first trimester red cell antibody screening for all antenatal women (especially with previous history of transfusion) irrespective of the RhD status.
| Conclusion|| |
Considering the prognostic impact of Kell alloimmunization, every attempt should be made to implement primary prevention, i.e., prophylactic Rh-Kell-matched transfusions for women of reproductive age group. Secondary prevention involves red cell screening for all antenatal women irrespective of RhD status and close monitoring as described in [Figure 1]. Tertiary prevention includes close monitoring of the newborn with laboratory investigations such as DCT, bilirubin, hemoglobin, and exchange transfusion wherever necessary.
|Figure 1: Algorithm for the management of Kell alloimmunization. MCA-PSV: Middle cerebral artery-peak systolic velocity, MoM: Multiples of median|
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