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Anderson JL , May HT , Knight S, et al. Association of Sociodemographic Factors and Blood Group Type With Risk of COVID-19 in a US Population. JAMA Netw Open. 2021;4(4):e217429. doi:10.1001/jamanetworkopen.2021.7429

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Association of Sociodemographic Factors and Blood Group Type With Risk of COVID-19 in a US Population

1 Intermountain Medical Center Heart Institute, Salt Lake City, Utah
2 University of Utah School of Medicine, Salt Lake City
3 Stanford University, Stanford, California

The observed variability in susceptibility to SARS-CoV-2 and severity of the ensuing COVID-19 have raised intense interest in their environmental and genetic risk factors. An early report from China 1 suggested that blood group A was associated with increased susceptibility and blood group O was associated with reduced susceptibility to SARS-CoV-2 infection. These reports motivated widespread interest in examining ABO blood groups as potential COVID-19 risk factors. Subsequent studies from Italy and Spain 2 reported that blood group A was associated with an increased risk of severe COVID-19 and blood group O was associated with a reduced risk. In contrast, a large Danish study 3 implicated disease susceptibility but not severity. However, observations from Boston, Massachussets, 4 and New York, New York, 5 did not confirm any specific associations between ABO blood group and disease. The controversy raised by these contrasting reports led to this case-control study.

Our objective in this case-control study was to independently test whether blood type is associated with SARS-CoV-2 susceptibility and COVID-19 severity. The study was approved by the Intermountain Medical Center institutional review board with a waiver of consent because the study represented no more than minimal privacy risk to individuals. This study is reported following the Strengthening the Reporting of Observational Studies in Epidemiology ( STROBE ) reporting guideline.

Intermountain Healthcare, a nonprofit, integrated health care system of 24 hospitals and 215 clinics in Utah, Idaho, and Nevada, generated a SARS-CoV-2 and COVID-19–specific electronic health records database. We searched this database for individuals who were tested for SARS-CoV-2 between March 3 and November 2, 2020, and had a recorded blood type. For individuals who underwent multiple tests, the first test with a positive result was chosen, otherwise the first test with a negative result was used. We compared positive vs negative test results, hospitalized vs nonhospitalized patients, and intensive care unit (ICU) vs non-ICU patients. Infectivity was determined by SARS-CoV-2–specific polymerase chain reaction testing of nasal swabs or saliva samples. Analysis of variance assessed associations across ABO groups. Odds ratios (ORs) between ABO groups were assessed by logistic regression adjusted for age, sex, and Rh factor. P values were 2-sided, and statistical significance was set at P < .167 for each of the 3 primary comparisons. Statistical significance was set at P = .006 for assessment of ORs because each set underwent 9 comparisons. Data were analyzed from November 20, 2020, to February 26, 2021.

A total of 107 796 individuals (mean [SD] age, 42.0 [17.8] years; 82 875 [76.9%] women) who had been tested for SARS-CoV-2 infection were included in the study. Further demographic characteristics of the studied population and ABO blood group associations are shown in Table 1 . Among individuals with COVID-19, hospitalization was associated with male sex (1165 men [50.1%] hospitalized vs 1871 men [20.5%] not hospitalized) and age (mean [SD] age among hospitalized patients, 57.0 [18.1] years vs 41.4 [14.9] years among nonhospitalized individuals). Admission to an ICU was also associated with male sex (426 men [61.8%] admitted to ICUs vs 725 men [44.8%] not admitted) and age (mean [SD] age among patients admitted to ICUs, 60.7 [158] years vs 55.4 [18.8] years in patients not admitted). Non-White race, which included African American, American Indian or Alaskan Native, Native Hawaiian or Pacific Islander, Asian, and unknown or declined to answer, was associated with viral positivity (1592 individuals [13.9%] with positive results vs 6610 individuals [6.9%] with negative results) and hospitalization (556 patients [23.9%] hospitalized vs 1036 individuals [11.3%] not hospitalized). Blood type was not associated with disease susceptibility or severity, including viral positivity, hospitalization, or ICU admission ( Table 1 ). Compared with type O blood, type A was not associated with increased viral positivity (OR, 0.97 [95% CI, 0.93-1.01]; P = .11), hospitalization (OR, 0.89 [95% CI, 0.80-0.99]; P = .03), or ICU admission (OR, 0.84 [95% CI, 0.69-1.02]; P = .08) ( Table 2 ). Similarly, types B and AB were not associated with worse outcomes than type O. Analyses restricted to White race produced similar results ( Table 2 ).

With contrasting reports from China, 1 Europe, 2 , 3 Boston, 4 New York, 5 and elsewhere, 6 we embarked on a large, prospective case-control study that included more than 11 000 individuals who were newly infected with SARS-CoV-2, and we found no ABO associations with either disease susceptibility or severity. The smaller sample sizes and retrospective, observational nature of many prior studies, in addition to their striking heterogeneity of ABO associations with disease susceptibility and severity, could be due to chance variations, publication bias, differences in genetic background, geography and environment, and viral strains. The ABO gene is highly polymorphic, and ABO blood groups are distributed differently across ancestries and geographies. Differing disease susceptibilities could be due to natural antibodies or prothrombotic effects with nongroup O. 6 The Utah population is dominated by Northern European ancestry, with a minority contribution of Hispanic/Latinx and other ethnicities. However, our results are similar among individuals of White race alone.

Given the large and prospective nature of our study and its strongly null results, we believe that important associations of SARS-CoV-2 and COVID-19 with ABO groups are unlikely and will not be useful factors associated with disease susceptibility or severity on either an individual or population level for similar environments and ancestries. Additional studies, closely controlled for genetics, geography, and viral strain, are required before accepting blood group as a determinant of predisposition to or severity of COVID-19.

Accepted for Publication: March 3, 2021.

Published: April 5, 2021. doi:10.1001/jamanetworkopen.2021.7429

Corresponding Author: Jeffrey L. Anderson, MD, Intermountain Medical Center Heart Institute, 5121 S Cottonwood St, Bldg 4, 6th Floor, Murray, UT 84107 ( [email protected] ).

Author Contributions: Dr May and Ms Bair had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Anderson, Muhlestein, Knowlton.

Acquisition, analysis, or interpretation of data: Anderson, May, Knight, Bair, Muhlestein, Horne.

Drafting of the manuscript: Anderson, May, Knight.

Critical revision of the manuscript for important intellectual content: Anderson, Bair, Muhlestein, Knowlton, Horne.

Statistical analysis: May, Knight.

Obtained funding: Anderson.

Administrative, technical, or material support: Anderson, Bair, Muhlestein, Knowlton, Horne.

Supervision: Anderson, Muhlestein, Knowlton, Horne.

Conflict of Interest Disclosures: Dr Muhlestein reported receiving a research endowment from Dell Loy Hansen Heart Foundation Heart Institute during the conduct of the study. Dr Horne reported receiving grants from Intermountain Research and Medical Foundation, AstraZeneca, and PCORnet; nonfinancial support in the form of in-kind donations from GlaxoSmithKline and CareCentra; serving on an advisory board for LabMe.ai; and licensing of intellectual property from Alluceo and CareCentra outside the submitted work. No other disclosures were reported.

Additional Contributions: Brianna Ronnow, MS (Intermountain Healthcare), assisted with manuscript submission and was not compensated for the work.

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The Correlation Between Blood Group Type and Diabetes Mellitus Type II: A Case-Control Observational Study From Pakistan

Simrah sharjeel, muhammad wasi, aliya jafri, fatima a raza, khizer shamim, kiran abbas.

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Kiran Abbas [email protected]

Corresponding author.

Accepted 2021 Nov 25; Collection date 2021 Nov.

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Introduction

Adult-onset type 2 diabetes mellitus (T2DM) is defined as a chronic hyperglycemic state, characterized by insulin resistance and declining islet B-cell function, eventually leading to islet B-cell function failure. The present study evaluated the association of T2DM with the type of blood group.

Methodology

A case-control study was conducted from April 2020 to September 2021 in Karachi, Pakistan. An electronic questionnaire was used to determine if there is an association between ABO blood groups and type 2 diabetes mellitus. Our study involved two groups with an equal number of participants. The patient group contained participants who had been diagnosed with type 2 diabetes mellitus, whereas the control group contained participants who had never been diagnosed with type 2 diabetes mellitus. Information was collected through a self-administered electronic questionnaire which was circulated through social media.

The mean ± SD age was reported to be 25.98 ± 12 years. The study found a significant association between blood group B and type 2 diabetes mellitus (p=0.006), whereas a negative association was seen between the blood group O and type 2 diabetes mellitus (p=0.001). It should be noted, however, no significant association was found between the blood groups A and AB and type 2 diabetes mellitus (p>0.05).

The results of this study indicate that there is an association between type 2 diabetes mellitus and the ABO blood group system; a significant association was found between blood group B and risk of type 2 diabetes mellitus (T2DM). Nevertheless, we recommend regular screening for T2DM in individuals with a high-risk profile. Those at risk can adopt measures that are beneficial for them in the long run such as dietary control and physical exercise. Further studies using explorative techniques with a diversified population are recommended.

Keywords: endocrinology, diabetes mellitus, abo blood group, blood, adult-onset type 2 diabetes mellitus

Diabetes mellitus is a heterogeneous disease characterized by hyperglycemia due to vitiated insulin secretion by the beta cells of the pancreas and/or vitiated insulin action [ 1 , 2 ]. Adult-onset type 2 diabetes mellitus is defined as a chronic hyperglycemic state, characterized by insulin resistance and declining B-cell function, eventually leading to B-cell failure [ 3 ]. Even though type 2 diabetes mellitus is a multifactorial disease and is a result of both genetic and environmental factors (i.e., pollution, vitamin D deficiency, and damage to immune cells), regular physical activity can reduce its risk by improving glycemic control [ 4 ].

Some common symptoms of type 2 diabetes mellitus include excessive thirst, frequent urination, slow healing of sores, blurred vision, and fatigue. The global incidence of diabetes mellitus has been estimated to be 425 million in 2017, and the prevalence of type 2 diabetes mellitus is around 285 million which is approximated to grow to 438 million by 2030 [ 2 , 5 ]. However, the prevalence of type 2 diabetes mellitus in Pakistan is estimated to be 25 million [ 6 ].

Recent literature indicates a correlation between type 2 diabetes mellitus and the ABO blood group system. A study conducted in Turkey reported an increased risk of type 2 diabetes mellitus in participants with type A blood group [ 7 ]. A study published in the Libyan Journal of Medicine in 2010 was carried out among 70 patients with type 2 diabetes revealed that most participants with blood groups A and O did not have type 2 diabetes mellitus [ 8 ]. The A, B, and O blood groups, first identified by Karl Landsteiner, contain two antigens, A and B, and four phenotypes, A, B, O, and AB [ 9 ]. ABO antigens are carbohydrate structures bound to glycoproteins and glycolipids [ 10 ]. The Rhesus system is found in close association with the ABO blood group system, and Rhesus (or also known as Rh D) is an antigen that is found on the surface of red blood cells. The presence or absence of Rh antigen determines whether a person is Rh+ or Rh- [ 11 , 12 ].

Whether there is a relationship between blood group and the likelihood of acquiring diabetes is still uncertain. Therefore, the current study aimed to evaluate the significance of different blood groups as a predisposing factor for adult-onset diabetes mellitus type 2.

Materials and methods

A case-control study was conducted from April 2020 to September 2021 in Karachi, Pakistan. Ethical approval was obtained from the Institutional Review Board (IRB) prior to the study (JSMU/IRB/456). The study employed a nonprobability convenience sampling technique to select the participants. All participants with or without diabetes mellitus type 2 aged 18 or above were included in the study. Individuals who had hemoglobinopathies including thalassemia or sickle cell anemia were excluded from the study. Furthermore, those who were above 60 years and were never checked for diabetes mellitus were also excluded.

Informed consent was obtained from all the participants. The questionnaires were circulated by the researchers through social media sites such as Facebook, Instagram, WhatsApp, etc. In-person contact with the subject was avoided due to the ongoing pandemic situation. A total of 300 people were approached, of those 200 responded with a response rate of 66.67%. Six questionnaires were incomplete and were excluded from the analysis. One hundred ninety-four patients were included in the study with 97 participants in each group, i.e., case and control. A preformed proforma was used to collect sociodemographic data of the participants. The participant’s blood group, history of diabetes mellitus type 2, and other comorbidities were documented.

Participants were divided into two groups. Group A had participants with type 2 diabetes mellitus, whereas group B served as the control group. The Statistical Package for the Social Sciences (IBM SPSS, Chicago, USA) was used to analyze the data. All continuous variables were presented as mean and standard deviation, while for all categorical variables, frequency and percentages were evaluated. The Chi-square test was used as a test for significance with significant differences considered at a p-value of 0.05 or less.

A total of 194 participants with 97 in each group were included in the final analysis. The mean ± SD age was 25.98 ± 12 years. Forty-eight females (24.74%) and 49 males (25.25%) had type 2 diabetes mellitus (T2DM). Family history of T2DM was positive in 120 (61.90%) participants. One hundred twenty-nine participants (66.50%) reported being physically active, and 102 participants (52.60%) consumed a balanced diet. One hundred ten participants (56.70%) had no other comorbidities, and 127 (65.50%) participants never had a blood transfusion (Table 1 ). There was no statistical difference between case versus control with respect to the demographic profile of participants (p>0.05).

Table 1. Demographic Characteristics of Study Participants.

Upon cross-tabulation and application of appropriate Chi-square test, significant associations were found between blood group B (p=0.006) and blood group O (p=0.001) with type 2 diabetes mellitus (T2DM). This implies that patients with blood group B were more frequently diagnosed with T2DM, while individuals with blood group O were less frequently diagnosed with T2DM. It should be noted, however, no significant association was found between the blood groups A (p=0.631) and AB (p=1.000) and T2DM (Table 2 ).

Table 2. Association of Individual Blood Groups With Type 2 Diabetes Mellitus.

In our study, we reported that the majority of the population with blood group B had been diagnosed with type 2 diabetes mellitus (T2DM); however, only a small fraction of people with blood group O had been diagnosed with the disease. Our study coincides with existing literature [ 13 , 14 ]. Zaidi et al. reported a positive association between T2DM and the ABO blood group system; T2DM and the ABO blood group system are interrelated on a genetic immunologic basis; however, the study inferred that the individuals with blood groups type B and A have a higher frequency of T2DM [ 14 ]. In 2014, Qureshi and Bhatti found out that the incidence of T2DM among blood B was more common and the incidence of blood group O was the least common [ 9 ]. Bener and Yousafzai also supported these findings by concluding that blood group B was more common, whereas blood group O was the least common among diabetic populations [ 15 ]. Kamil et al. reported a higher frequency of participants with blood group B who had been diagnosed with T2DM compared with patients who had blood groups A and O [ 8 ]. Stern et al. revealed that there were statistically significant correlations between T2DM and RH blood type (p=0.0003) [ 16 ].

However, in contrast to the current findings, Alanazi et al. reported inconclusive findings [ 13 ]. A study conducted in Rawalpindi, Pakistan, reported that a smaller number of participants with blood groups A and B were seen among diabetic patients and a higher frequency of the blood group AB in the diabetic group [ 17 ]. Karagoz et al. explored the relationship between ABO blood groups with gestational diabetes mellitus. The authors revealed that those individuals with blood group AB were at augmented risk of developing gestational diabetes mellitus [ 18 ]. Fagherazzi et al. reported that individuals with blood group type O are more prone to developing endocrinological disorders [ 19 ]. According to Okon et al., patients with blood group A were more susceptible to T2DM [ 20 ]. A study conducted in Muzaffarnagar, India, in 2018 which included a total of 1,316 participants found an increased association of AB and O blood groups with type 2 diabetes mellitus [ 21 ]. Abegaz also supported this claim; in their review, they deduced that many studies have found significant relationships between several cancers, metabolic disorders, and other noninfectious disorders [ 22 ].

Current data on the association between type 2 diabetes mellitus and the ABO blood group system are contradicting as some studies show a positive association, whereas others offer a negative association. It may be noted, however, that the contradictory results can be due to differences in ethnicity and sociodemographic changes affecting the genetic expression of the disease.

The current study serves as a helpful tool for raising awareness among the public regarding the possible association of certain blood group types and T2DM. Those at risk can adopt measures that are beneficial for them in the long run such as dietary control and physical exercise. The current study had some limitations. For instance, the data acquisition was hindered by the ongoing global pandemic and data collection was limited to electronic interviews. Another limitation was the self-reported blood groups and diabetes mellitus diagnosis. Finally, other causes of diabetes mellitus such as the family history of obesity were not taken into consideration; therefore, these factors may play a role in the increased prevalence of T2DM in blood group B participants. Further research exploring how genetic blood composition affects the likelihood of acquiring diabetes mellitus is needed.

Conclusions

The results of this study indicate that there is an association between type 2 diabetes mellitus and the ABO blood group system; a significant association was found between blood group B and type 2 diabetes mellitus (T2DM). Nevertheless, we recommend regular screening for T2DM in individuals with a high-risk profile. Those at risk can adopt measures that are beneficial for them in the long run such as dietary control and physical exercise. Further studies using explorative techniques with a diversified population are recommended.

The content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus.

The authors have declared that no competing interests exist.

Human Ethics

Consent was obtained or waived by all participants in this study. Jinnah Sindh Medical University issued approval JSMU/IRB/456. This is to inform you that the study topic entitled "The Correlation Between Blood Group Type and Diabetes Mellitus Type II: A Case-control Observational Study From Pakistan" has been approved by the committee.

Animal Ethics

Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue.

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Blood Bank Case Study: “What’s Your Type?”

The general public doesn’t always know a lot about laboratory testing in general, but most people know a little about blood types, even if it’s what they have learned from TV! Blood types do seem to come up in casual conversation. We might hear a conversation about blood type after someone has donated blood, or between family members comparing notes, who ask “What’s your type?” Yet, even with medical technologists, there can still be some confusion about blood types and blood typing, particularly if one has not worked in Blood Bank in many years. I recently received an email from a colleague who had a few questions about blood types, as she has not worked in Blood Bank for over 40 years. I always tell my students that no question is a bad question, and indeed, she asked some very good questions, which I will address with this case study.

What blood type is listed on a patient’s chart if they type “O Du”?

What blood type is recorded on a donated unit of blood typed “O Du”?

What type of blood does an “O Du” patient receive?

Can an “O Du” patient have a transfusion reaction if they are transfused with O positive blood? Would she need to receive O negative blood in a transfusion?

Does an “O Du” patient need to receive RhoGAM if she pregnant and her husband is Rh positive?

If you have ever wondered or can’t remember details about any of these questions, you’re in the right place. So, what’s new, if anything, with blood types?

Landsteiner discovered the ABO blood group system in 1901, and identified A, B and O blood types, using experiments performed on blood from coworkers in his laboratory. The discovery of the codominant AB blood type soon followed, but it was not until around 1940 that the Rh blood group was first described. In 1946, Coombs and coworkers described the use of the antihuman globulin (AHG) to identify weak forms of Rh antibodies in serum. For us old blood bankers, the original name for this test was the Coombs’ test. (You will still find physicians ordering a Coombs’ test!) The current and proper name for this is the direct antibody test (DAT), which is used to detect in vivo sensitization of RBCs. AHG can also be used to detect in- vitro sensitization of RBCs using the 2 stage indirect antibody test (IAT).

Since Landsteiner’s work, we have not discovered any new blood groups that are part of the routine blood type. The ABO and Rh blood groups are still the most significant in transfusion medicine, and are the only groups consistently reported. However, we currently recognize 346 RBC antigens in 36 systems. 1 Serological tests determine RBC phenotypes. Yet, today we can also determine genotype with family studies or molecular testing. This case study and 2 part blog reviews some terminology in phenotyping, some difficulties and differences encountered, and explores the possibility of RHD genotyping to assess a patient’s true D status.

Our case study involves a 31 year old woman who is newly married. She is not currently pregnant, has never been pregnant, is not scheduled for surgery but has had a prior surgery 15 years ago, and has never received any blood products. She and her husband recently donated blood and, as first time blood donors, just got their American Red Cross (ARC) blood donor cards in the mail. The husband noted that his card says that he is type O pos. The woman opens her card, and, with a puzzled look on her face, says “My card says I’m an O Pos, too. There must be a mistake.” She knows she has been typed before and checks her MyChart online. Sure enough, her blood type performed at a local hospital is listed in her online MyChart as O negative. She further checks older printed records and discovers that 15 years ago, before surgery, she was typed at a different hospital as “O Du”. She is very upset, wondering how she can have 3 different blood types. She is additionally concerned because they are planning to have children and recalls being told that because she is Rh negative, that she would need Rhogam. Is she Rh negative or positive, and what does Du mean? Will she need Rhogam when pregnant? She has many questions and calls the ARC donor center for an explanation.

What is happening here, what is this woman’s actual blood type, and what testing can be done to ensure accuracy in Rh typing? From the patient reports, it appears that this woman has what today we call a “weak D.” Du is an older terminology that should no longer be used, and that has been replaced by the term “weak D.” But, why does she have records that show her to be an O neg, a type O, Du (today, this would be written O weak D), and now, a card from ARC stating she is O pos?

RhD negative phenotypes are ones that lack detectable D antigen. The most common Rh negative phenotype results from the complete deletion of the RHD gene. Serologic testing with anti-D is usually expected to produce a strong 3+ to 4+ reaction. A patient with a negative anti-D at IS and at IAT would be Rh negative. If the patient has less than 2+ strong reaction at immediate spin (IS), but reacts at IAT, they would be said to have a serologically weak D. 1 Historically, weak D red blood cells (RBCs) are defined as having decreased D antigen levels which require the IAT for detection. Today’s reagents can detect many weak D types that may have been missed in the past, without the need for IAT. However, sometimes IAT is still necessary to detect a weak D. When this is necessary is dependent on lab SOPs and whether this is donor testing or patient testing. The reported blood type of this patient also depends on the SOPs of the laboratory that does the testing. And, the terminology used for reporting is also lab dependent. It is not required by AABB to test patient samples for weak D (except for babies of a mother who is D negative). There is also no general consensus as to the terminology to be used in reporting a weak D. Some labs would result this patient as O negative, weak D pos. Some labs may result O pos, weak D pos. Others may show the individual reactions but the resulted type would be O pos. Labs who do not perform weak D testing would report this patient as O, Rh negative. The following chart explains why this patient appears to have 3 types on record.

What blood type is recorded on a donated unit of blood typed “O Du?”

AABB Standards for Blood Banks and Transfusion Services requires all donor blood to be tested using a method that is designed to detect weak D. This can be met through IAT testing or another method that detects weak D. If the test is positive, the unit must be labeled Rh positive. This is an important step to prevent alloimmunization in a recipient because weak D RBCs can cause the production of anti-D in the recipient. This also explains why the ARC donor card this patient received lists her type as O pos.

Historically, weak D red blood cells (RBCs) were defined as having decreased D antigen levels which require the IAT for detection. A patient who is serologic weak D has the D antigen, just in fewer numbers. This type of weak D expression primarily results from single-point mutation in the RHD gene that encodes for a single amino acid change. The amino acid change causes a reduced number of D antigen sites on the RBCs. Today we know more about D antigen expression because we have the availability to genotype these weak D RBCs. More than 84 weak D types have been identified, but types 1, 2, and 3 represent more than 90% of all weak D types in people of European ethnicity. 2 An Rh negative patient has no D antigen and should, under normal circumstances, only receive Rh negative blood. Yet, there has been a long history of transfusing weak D patients with Rh positive RBCs. 90% of weak D patients genotype as Type 1, 2 or 3 and may receive Rh positive transfusions because they rarely make anti-D. 2

It is now known that weak D can actually arise from several mechanisms including quantitative, as described above, position effect, and partial D antigen. Molecular testing would be needed to differentiate the types, but, with the position effect, the D antigen is complete and therefore the patient may receive Rh positive blood with no adverse effects. On the other hand, a partial D patient may type serologically as Rh negative or Rh positive and can be classified with molecular testing. It is important to note that these partial D patients are usually only discovered because they are producing anti-D. If anti-D is found, the patient should receive Rh negative blood for any future transfusions.

Thus, 3 scenarios can come from typing the same patient. With a negative antibody screen, and because 90% of weak D patients have been found to be Type 1, 2 or 3 when genotyped, many labs do not routinely genotype patients and will report the blood type as Rh pos and transfuse Rh pos products. However, depending on the lab medical director and the lab’s SOPs, these same patients may be labeled Rh neg, weak D and receive Rh negative products. There is no general consensus on the handling and testing of weak D samples. The 3 rd scenario is that many labs do not test for weak D in patients at all, and a negative D typing at IS would result in reporting the patient as Rh neg, with no further testing. In this case, the patient would be transfused with Rh negative products.

This question was covered somewhat in the above discussion. Policies regarding the selection of blood for transfusion are lab dependent, dictated by the lab medical director, and are based on the patient population, risk of developing anti-D, and the availability or lack of availability of Rh negative blood products. Anti-D is very immunogenic. Less than 1 ml of Rh pos blood transfused to an Rh negative person can stimulate the production of anti-D. However, not all patients transfused with Rh positive blood will make and anti-D. As discussed above, 90% of weak D patients are types 1, 2 or 3, would be unlikely to become alloimmunized to anti-D. If a weak D patient with a negative antibody screen receives a unit of D pos RBCs, there is a very small possibility that they are a genotype who could become alloimmunized to the D antigen and produce anti-D. However, as stated above, the majority of weak D patients can be transfused with D positive RBCs. Thus, with few exceptions, from a historical perspective, one can safely classify the weak D as D positive.

This question gets a little trickier when dealing with females of childbearing age. We particularly want to avoid giving Rh positive blood to females to avoid anti-D and the complications of Hemolytic Disease of the Fetus and Newborn. Therefore, when dealing with these patients, lab policies and physicians tend to be more conservative in their approach to transfusion. The consequences, however, in males and older females are less serious and these patients could be given Rh positive blood if there exists a shortage of Rh negative units. Any patient who becomes alloimmunized to the D antigen, would thereafter be transfused with Rh negative products.

This, again, would be up to the medical director, the lab’s SOPs or the patient’s physician. Depending on lab practice, the lab may or may not perform weak D testing. If the lab does not perform weak D and results this patient as Rh neg, the patient would get Rhogam. If the lab does do weak D testing and finds a weak D phenotype, the decision whether or not to give Rhogam would be up to lab practices and the practitioners involved. The lab’s policy on terminology used in resulting the type may also reflect the decision whether or not to give Rhogam. This brings up a lot of questions in the lab because we know that a patient who would not make anti-D would not need Rhogam. So, what is the best course of action? Read my next blog to learn more about troubleshooting and resolving D typing discrepancies!

From the discrepancies in reported type in this individual, and putting all the pieces of the puzzle together, we can conclude that this patient is a weak D phenotype. However, the type reported and the terminology used varies from lab to lab. Molecular testing is available, yet most labs are still using serological testing for blood types for both donors and patients. This is based on several factors within the lab setting. Stay tuned for my next Blood Bank blog exploring D typing discrepancies and the financial aspects of performing genotype on pregnant patients to clarify Rh type.

-Becky Socha, MS, MLS(ASCP) CM BB CM graduated from Merrimack College in N. Andover, Massachusetts with a BS in Medical Technology and completed her MS in Clinical Laboratory Sciences at the University of Massachusetts, Lowell. She has worked as a Medical Technologist for over 30 years. She’s worked in all areas of the clinical laboratory, but has a special interest in Hematology and Blood Banking. When she’s not busy being a mad scientist, she can be found outside riding her bicycle.