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D variants and the other blood group systems

14 min

Skills you'll build2 skills
  • Choose the follow-up for a weak or discrepant D typing result
  • Judge whether a non-ABO antibody is significant from its thermal range and reactive phase

At the bench: Resolve a blood group discrepancy before selecting compatible components · Use the antibody workup to select suitable donor units

Try first

Try first

A 27-year-old pregnant patient is typed for the first time. Her red cells are nonreactive with anti-D at immediate spin and react 2+ in the weak-D test at the antiglobulin phase. The Rh control is nonreactive. How does the transfusion service classify her D status for now?

Keep going to see the reasoning.

Keep going to see the reasoning.

Right. Keep going to follow the reasoning.

Keep going to see the reasoning.

Keep going to see the reasoning.

Get the idea

Use the explanation to check your first decision.

Weak D and partial D

A deleted RHD gene is a common cause of D-negative red cells in people of European ancestry. Other RHD alleles make D antigen that reacts weakly, or that lacks some of its epitopes.1

PatternWhat the red cell carriesRecipient management
Weak D types 1, 2 and 3Every D epitope, at low densityManaged as D-positive
Partial DD with one or more epitopes missingCan form anti-D, so managed as D-negative
DELD below routine agglutination detectionTypes D-negative; adsorption-elution or genotyping shows the D

Weak D and partial D can give the same serologic pattern. Both may react weakly or not at all at immediate spin and more strongly at the antiglobulin phase.1

D typing for donors and recipients

A donor unit is labeled Rh positive when either the direct anti-D test or the weak-D test reacts. This prevents D-negative recipients from receiving D antigen.2

For a recipient, the question is whether she can form anti-D. Facilities that follow AABB standards may leave out weak-D testing for recipients.3 When a serologic weak D appears in a pregnant patient or another female of childbearing potential, RHD genotyping identifies the variant, and weak D types 1, 2 and 3 are managed as D-positive.4 Type 4.1 and other variants follow the genotype report and the service's adopted policy.5 An unresolved variant is managed as at risk, with D-negative red cells.1,4

Clinical significance of antibodies

An antibody is clinically significant when it can shorten the survival of antigen-positive red cells, cause a hemolytic transfusion reaction or cause hemolytic disease of the fetus and newborn. Its thermal range and reactive phase are the bench evidence.1

  • Rh, Kell, Kidd, Duffy, S and s antibodies are usually IgG. They react at 37 °C and the antiglobulin phase.
  • M, N, P1 and Lewis antibodies are usually cold IgM. They react at immediate spin or room temperature.

A cold antibody that also reacts at 37 °C or the antiglobulin phase may be clinically significant, so each antibody is assessed by its thermal range and phase.1 A clinically significant antibody requires antigen-negative red cells crossmatched through the antiglobulin phase.1,3

Follow the bench demonstration

Sources for this step
References
  1. Bloch EM, Campbell-Lee S, McKenna DH Jr, Montemayor-Garcia C, Schwartz J, Shaz B, Storry J, eds. Technical Manual. 22nd ed. AABB; 2026.
  2. Testing the blood, 21 CFR §640.5 (2026). Accessed September 27, 2026. https://www.ecfr.gov/current/title-21/chapter-I/subchapter-F/part-640/subpart-A/section-640.5
  3. Association for the Advancement of Blood & Biotherapies. Fundamental Standards for Blood Collection and Transfusion. 2nd ed. AABB; 2025. Accessed September 27, 2026.
  4. AABB, College of American Pathologists, American College of Obstetricians and Gynecologists, et al. Joint Statement on Phasing-In RHD Genotyping for Pregnant Women and Other Females of Childbearing Potential With a Serologic Weak D Phenotype. 2015. Accessed September 27, 2026.
  5. AABB. Association Bulletin #24-02: Use of Rh Immune Globulin and Considerations in the Setting of Supply Shortages and Limited Availability. July 15, 2024. Accessed September 27, 2026.

Watch one

Read each decision and its explanation.

Leah Vetter, 31, is typed before a planned cesarean delivery. She has no earlier D type on record.

  • Anti-D at immediate spin: 0
  • Weak-D test at the antiglobulin phase: 2+
  • Rh control: 0 at both readings

How is her D status recorded, and which red cells are allocated to her?

  1. Read the Rh control first. It is nonreactive at both readings, so the anti-D reactions are valid.

    A reactive control would make every anti-D reaction uninterpretable.

  2. Read the pattern. No reaction at immediate spin and 2+ at the antiglobulin phase is a serologic weak D.

    The antiglobulin phase detects D antigen present at low density or lacking epitopes.

  3. Serology cannot identify the variant.

    Weak D types 1 to 3 and partial D give the same reactions with serologic reagents.

  4. As a recipient, the question is whether she can form anti-D. Until the variant is known, she may be able to.

    The donor labeling rule protects D-negative recipients and does not address her own risk.

  5. Send RHD genotyping.

    She is of childbearing potential, and the joint statement recommends genotyping for this pattern.

  6. Allocate D-negative red cells until the report returns.

    An unresolved variant is managed as at risk for anti-D.

Her D status is recorded as a serologic weak D with RHD genotyping pending. She receives D-negative red cells in the meantime. If the report shows weak D type 1, 2 or 3, she will be managed as D-positive.

Practice this skill

Your turn

Problem 1 of 3 · Hints available

Why can a recipient with a partial D phenotype form anti-D after transfusion of D-positive red cells?

Incorrect. That describes weak D types 1, 2, and 3, which keep the complete D epitope set and are managed as D-positive.

Incorrect. Absent Rh-associated glycoprotein from an RHAG defect produces the regulator Rhnull phenotype, which lacks all Rh antigens. An immunized Rhnull patient forms anti-Rh29.

Correct. Donor D carries the epitopes the recipient lacks, so the recipient can respond to them. A recipient with a partial D variant capable of anti-D formation is managed as D-negative and generally receives D-negative red cells.

Hint
  1. Two of the options describe other Rh phenotypes. Name each one.
  2. Ask what on the donor's D could look foreign to this recipient.

Review D expression and variants

Problem 2 of 3 · Hints available

A pregnant patient's D typing shows a serologic weak-D pattern that has not been resolved. Which result lets the transfusion service classify her as D-positive or as at risk for anti-D?

Correct. Weak D types 1, 2, and 3 keep the complete epitope set, and the 2015 AABB and CAP statement supports D-positive management for them. Other variants follow the genotype report and the service's adopted policy. An unresolved variant is managed as at risk.

Incorrect. A repeat serologic test can confirm the weak reactivity, but weak D types and partial D variants can give the same serologic pattern.

Incorrect. The screen shows only that she has not formed anti-D so far. Whether her variant can form it depends on which variant she carries.

Hint
  1. Ask which test can distinguish the variants.
  2. Weak D types and partial D variants can give the same pattern in routine serologic D typing.

Review D expression and variants

Problem 3 of 3 · On your own

A patient's panel identifies anti-M. With M-positive cells it reacts 2+ at immediate spin, 1+ at 37 °C and 1+ at the antiglobulin phase. The autocontrol is nonreactive. How does the transfusion service treat the antibody?

Many examples of anti-M are cold IgM. This one reacts at 37 °C and the antiglobulin phase, so it may be clinically significant.

Dismissed an antibody because it is usually cold-reactive

Anti-M and anti-N are usually cold IgM, but some examples react at 37 °C or in the antiglobulin phase and are clinically significant. Dismissing one by its specificity, without checking its thermal range and phase, can let antigen-positive red cells be issued.

Reactivity at 37 °C and the antiglobulin phase shows the antibody binds at body temperature. M-negative units with an antiglobulin crossmatch protect the patient.

Papain and ficin destroy M. A treated panel loses the reaction and gives no information about its thermal range.

Review MNS, Kell, Kidd, Duffy, and Lutheran

Use it

Read the case evidence, then make each decision. The step is complete without it.

  • Odette Glass, 34, a pastry chef, is 26 weeks pregnant. MRN 4418207.
  • Her prenatal type shows anti-D at immediate spin 0 and a weak-D test at the antiglobulin phase 1+. The Rh control is 0.
  • Her antibody screen reacts, and the panel identifies anti-Lea.
  • The anti-Lea reacts 2+ at immediate spin. It is nonreactive at 37 °C and the antiglobulin phase. The autocontrol is 0.
Decision 1 of 3

How is her D status handled today?

Her serologic weak D could be a weak D type or a partial D. Genotyping identifies it, and she is managed as at risk until then.

The weak-D rule applies to donor units. As a recipient she could carry a partial D and form anti-D.

Applied donor weak-D rules directly to a recipient

Donor units are labeled D-positive when any weak-D test reacts, which protects D-negative recipients. A recipient with a partial D variant can form anti-D, so calling that patient D-positive from a weak reaction exposes them to D-positive red cells. Recipient results are resolved by genotype and the transfusion service's adopted policy.

Her weak-D reaction shows D antigen. Genotyping may find a weak D type 1, 2 or 3, which is managed as D-positive.

Review D expression and variants

Decision 2 of 3

What does the anti-Lea's reaction pattern show?

Reactivity at immediate spin with nothing at 37 °C or the antiglobulin phase fits a cold IgM antibody.

Clinical significance is judged by thermal range and phase. This antibody shows no reactivity at body temperature.

It reacts only at immediate spin. Laboratory policy may allow crossmatch-compatible red cells for an antibody judged clinically insignificant by its testing and history.

Review MNS, Kell, Kidd, Duffy, and Lutheran

Decision 3 of 3

The genotype report returns weak D type 1. What changes?

The genotype now explains the weak reaction. Weak D type 1 carries every D epitope.

Weak D type 1 carries every D epitope at low density. The 2015 joint statement supports D-positive management for types 1, 2 and 3.

Partial D is missing epitopes. Weak D type 1 has the complete set.

Review D expression and variants

Both decisions in this case were based on the phase of each reaction. Her D reacted only at the antiglobulin phase, so genotyping was needed before she could be managed as D-positive. Her anti-Lea reacted only at immediate spin, the pattern of a cold antibody.

For reference

Sources checked