Download Managing patients with rare blood groups

Managing patients with rare blood groups
Dr. Ashish Jain
Associate Professor,
Department of Transfusion Medicine,
PGIMER, Chandigarh
Defining the rare blood group
 Most acceptable definition: International Society Blood
Transfusion (ISBT) – Working Party (WP) on Rare Donors
Frequency is less than 1:1000 population (0.1%)
 Variable: 4 : 1000 in France and
1 : 100 to 1 : 1000 in Japan
 ‘Very rare’: 1 person out of 10 000 (0·01%)
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Antibody against a High Frequency antigen (HFA)
Presence of multiple antibodies
High frequency antigens (HFAs)
 Also referred to as ‘high incidence’, ‘high prevalence’
and ‘public’ antigens.
 For HFA classification must have incidence of >90% but
majority have an incidence of >99%.
 Lack of a HFA = rare phenotype.
 ~189 red blood cell antigens classified as HFAs by the
ISBT
Blood group systems and RBC antigens
 35 blood group systems
 About 300 antigens
Other clinically significant systems and antigens
Rh system
– C,c,E,e
Kell system
– K, k
Kidd system
– JKa, JKb
Duffy system
– Fya, Fyb
Ss system
– S, s
Alloantibodies to HFAs (Ab-HFAs)
 Scarce publications on the transfusion support of patients
with Ab-HFA.
 prevalence in the general population,
 age, sex and racial distribution,
 the overall reactivity in standard serological procedures and
eventual difficulties regarding their specification,
 the relationship of Ab-HFA with/without transfusion hazards,
 the clinical complications
Heuft HG, Genth R, Wittmann G, Salama A. Alloantibodies directed against highfrequency red blood cell antigens. Infusionsther Transfusionsmed 1999;26:234-9.
Specificities of alloantibodies against high frequency antigens
(n = 133) and frequency of antibody mixtures
Serological characteristics and clinical complications
Heuft HG, Genth R, Wittmann G, Salama A. Alloantibodies directed against highfrequency red blood cell antigens. Infusionsther Transfusionsmed 1999;26:234-9.
Antibodies to HF Antigens May Decrease the
Quality of Transfusion Support
 Retrospective analysis - 52 hospitalized pts. with
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antibodies to HF antigens.
Admitted 5.2000 -12. 2001, Germany, Austria &
Switzerland.
133 compatible RBCs supplied for 26 pts.
104 antigen negative RBCs transfused to 22 pts.
Deviation from the standard transfusion policy occurred
in 23/56 (41%).
Seltsam A, Wagner FF, Salama A, Flegel WA. Antibodies to high-frequency antigens may decrease the
quality of transfusion support: an observational study. Transfusion 2003;43:1563-6.
Seltsam A et al. Transfusion 2003;43:1563-6
Identifying HFAs
Lysis of reagent red cells
during testing with fresh
serum:
Reactivity at room
temperature:
Anti-H, -I, -IH, -P, -PP1Pk (-Tja),
Anti-Ena, -LW (some), -Ge (some),
-Sda, or -Vel.
characteristic of anti-Vel, -P,
-PP1Pk (-Tja), -Jk3, and some anti-H
and -I.
Serologic
clues
Complement-binding
autoantibodies (anti-I and –IH),
or alloantibodies
(anti-Lub, -Vel, and –Yta),
may give similar results with
polyspecific AHG.
Reduced or absent reactivity
with enzyme treated RBCs:
anti-Ch, -Rg, -Ena, -Inb, -JMH, -Ge2, -Yta
(some).
Weak reactions in the AHG phase a/w
anti-Kna, -McCa, -Yka, and -Csa.
Panreactive
Equal
strength/
same
phase
AbHFA?
Autocontrol
negative
panel cell 10 is
negative for HFA Yta
ETHNIC CLUES
African
• Anti-U, -Jsb, -Hy,
-Joa, -Tca, -Cra,
and –Ata
European
• Anti-Kpb
Asian, South
American Indian &
Native American
• Anti-Dib
Getting the Rare phenotype donor
 In 1959, the American Association of Blood Banks
(AABB) set up a rare donor file to meet the transfusion
needs of patients with unusual blood group antibodies.
 The ISBT and World Health Organization (WHO)
lauched the collaborative program to generate data
from various sources (UK, USA and Japan).
 In 1985, the ISBT Rare donor Working Party (WP) was
established.
Getting the Rare phenotype donor
 ISBT-WP: Guidelines for testing, labeling, shipping of
rare blood, updating the data base, and coordinating
with the International Blood Group Reference
Laboratory (IBGRL), Bristol, UK.
 There is a well-established American Rare Donor
Program (ARDP) jointly managed by the American Red
Cross and AABB.
 Challenges in providing transfusion support:
 scarcity of compatible units,
 high transport and storage requirements, and
 the lack of experience on the part of many physicians in
treating these patients.
International Donor Panel (IRDP)
 IRDP: conceived under a joint WHO and ISBT initiative in
1965 to facilitate the rapid location and exchange of
rare blood between countries.
 The panel currently contains details of rare donors from
27 contributing countries and also frozen unit inventories
from frozen blood banks around the world.
 The compilation and maintenance of the IRDP is carried
out by the Red Cell Reference department of the IBGRL
in Bristol, UK.
International Donor Panel (IRDP)
Source: www.isbtweb.org
Strategies for compatible blood
 Correction of anemia, wherever possible
 Autologous pre-deposit (surgery)
 Cell salvage (for surgery)
 Calling up donors of known phenotype
 Mass screening of donations
 Consultation of National/International Frozen Blood banks
 Transfusing serologically incompatible or ‘least incompatible’
blood, with or without immunosuppression
 Testing the patient’s family members, specially the siblings
 Consultation of International Rare Donor Panel
Strategies for compatible blood
 Other factors to be considered are:
 Urgency of requirement
 Clinical diagnosis and patient’s bone marrow function
 Immunological status
 Strength and thermal amplitude of the antibody
 Class and subclass of the Ab
 In-vivo red cell survival
The availability of Rare Blood (ARDP)
Flickinger C, Petrone T, Church A: Review: American Rare Donor Program
Immunohematology 2004; 20 (4):239-244.
The availability of Rare Blood
 RBCs with some of the rare phenotypes are much more
difficult to find than others, for example:
 Knull, McLeod, U–, Vel–, Lan–, Bombay
 In France, not only donors but also patients with a rare
phenotype are registered; the idea being that patients
may become donors and vice versa.
Estimating the units………
 Determine the prevalence of compatible donors by
multiplying the prevalence of antigen-negative donors.
 If a serum contains anti-c, anti-Fya, and anti-S
 if the prevalence of antigen-negatives are
c-negative = 18%, Fy(a–) = 34%, and S-negative = 45%, then
 the prevalence of compatible units is:
0.18 × 0.34 × 0.45 = 0.028, or 2.8%
 If the patient is group O, the prevalence of group O donors (32%) is
factored into the calculation as follows:
0.028 × 0.32 = 0.009, or 0.9%.
Number of units to be tested = 1/0.009
= 111 units at least (in group O)
Indian Scenario
 Immunohematology Reference Laboratory at the
National Institute of Immunohematology, Mumbai, under
the aegis of the Indian Council of Medical Research
(ICMR), Government of India, maintains few rare donor
phenotype records.
 Lack of National data on the need for Rare phenotypes:
 in most of the blood banks, the antibodies of clinical
significance are either not detected by the available
serological technique, or if detected, are not identified.
 Unavailability of phenotyping sera
Rare phenotypes (India)
 “Bombay” (Oh) phenotype
 - D -/- D  In(a+b-)
 Co(a-b-)
 Weaker variants of A, B and H antigens
 I-i CdE/CdE (ryry)
Joshi SR, Vasantha K. A profile of rare bloods in India and its impact in blood transfusion service.
Asian J Transfus Sci 2012;6:42-3.
Rare phenotypes (India)
Bombay Phenotype (Oh ):
 First reported by Bhende et al in Bombay in 1952.
 Frequency estimated to be about 1 in 7600 in Bombay.
 Andhra Pradesh: 0.048%
 Tamil Nadu: 0.004%
 Karnataka : 0.005%
 1 for every 250,000 people worldwide.
 hh genotype
 No H antigens formed; therefore, no A or B antigens formed
 Phenotypes as blood group O
 Anti-A, anti-B, anti-A,B and anti-H present in the serum
 Only be transfused with blood from another Bombay (Oh)
 Prevalence in pregnant women and its effect on outcome is
scanty
Case – PGIMER, Chandigarh
 A 32 year old pregnant woman: referred to our institute at
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32 weeks gestation (difficulty in blood group) Blood group:
Bombay (Oh) RhD negative.
An IAT using a pool of red cells from two Bombay Rh (D)
positive blood donors gave negative result using the tube
as well as the gel technique: No anti-D
The anti- H titer: 16 (IgM)
Within the patient’s family, only one member (younger sister)
was of Oh phenotype (RhD negative).
No transfusion was required even in the post-partum period.
Jain A ,Kumwat V, Patil SS, Kumar P, Marwaha N, Sharma RR. Significance of serological
monitoring in a Bombay Rh (D) negative phenotype pregnant woman: A case report.
Transfus Apher Sci 2012;47:251-2.
Oh phenotype
Mallick S, Kotasthane DS, Chowdhury PS, Sarkar S. Bombay blood group: Is
prevalence decreasing with urbanization and the decreasing rate
of consanguineous marriage. Asian J Transfus Sci 2015;9:129-32.
-D-/-D- phenotype
 The rare -D-/-D- phenotype of the Rh blood groups
lacks the Rh17 (all Rh antigens except D) that makes it
a high-frequency antigen-negative blood.
 Four patients:
 HDFN
 Multi-transfused (12 units) polytrauma and a cancer
patient who had an incompatibility
 Alloimmunized pregnant woman
 The D-negative phenotype:
European ancestry: 15-17%
African ethnicity: 3-5%
Asian ancestry: Rare (<0.1%).
 In Asian ancestry: mutations in RHD that are most often
associated with a Ce (r’) haplotype, (10-30% are
actually Del phenotype).
 Del phenotype: most common in Hongkong Chinese
population
Colton null phenotype
 Co(a-b-), very rare: only six cases recognized till date.
 Indian woman, a primipara, second gravida who
delivered a baby who developed a mild HDN.
 Compatibility test revealed a high titer alloantibody,
reacting with some high-frequency antigen, was
identified as anti-Co3.
 RBC typed as Co(a-b-).
 None of her family members were typed as Co(a-b-).
In(a+b-) phenotype
 Patient had severe transfusion reaction to an apparently
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incompatible blood.
High titer alloantibody that showed a remarkable
prozone phenomenon.
Anti-Inb; red cells were typed as In(a+b-)
Might have been immunized during pregnancies (two)
Sustained antibody level may presumably be due to a
constant stimulus through her underlying cancer as CD44
antigen is known to be a tumor antigen, and that Ina/Inb
are on CD44 molecules.
> 2000 blood units were screened: 2 compatible units
Her brother’s phenotype was compatible.
I-i- phenotype
 A newly recognized entity among certain adult RBCs:
- reacting as weak with anti-I as do the RBCs from
the newborn and
- reacting weak with anti-i like other adult RBCs.
 Always found in an association with blood group A1
and A1B and have a stronger expression of A1
 Serum has naturally occurring low-titer alloanti-I,
preferentially reacting at lower temperatures and may
cause nuisance in cross match test.
 Frequency of 1 : 1 000 in Mumbai population.
Towards the Rare Donor Registry
 Improved testing facilities:
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Antigen typing for other blood group systems
Antibody screening, Identification
Identifying and recruiting rare blood donors.
Retention of these rare blood donors.
Setting up national/regional reference centers to detect
and identify the rare phenotypes.
Upgrading the transfusion services where these rare blood
units can be stored in a frozen state.
Effective communication between various blood banks.
Strengthening the training and education programs for
technologists and clinicians.
Conclusion
 Blood of a rare type is mostly required for patients with Ab
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HFAs.
Identification of antibodies to HFAs is time consuming and
complex and delays transfusion.
Observing the clues is essential to a timely resolution.
Rare donor registry is a potential source for antigennegative compatible blood
Communication & Clinical judgment is the essential element in
blood management.
More studies required to determine the outcomes of
transfusion of incompatible RBCs in patients with rare blood
types and antibodies.
References
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Seltsam A, Wagner FF, Salama A, Flegel WA. Antibodies to high-frequency antigens may
decrease the quality of transfusion support: an observational study. Transfusion 2003;43:1563-6.
Flickinger C, Petrone T, Church A. Review: American Rare Donor Program. Immunohematology
2004;20:239-43.
Biale Y, Dvilansky A. Management of pregnancies with rare blood types. Acta Obstet Gynecol
Scand 1982;61:219-21.
Lynen R, Simson G, Quentin SH. Patients with anti-Vel: immunohematological characterization and
transfusion management. Beitr Infusionsther 1990;26:377-9.
Kaur R, Jain A. Rare blood donor program in the country: Right time to start. Asian J Transfus Sci
2012;6:1-2.
Bhende YM, Deshpande CK, Bhatia HM, Sanger R, Race RR, Morgan WT, et al. A “new” blood
group character related to the ABO system. Lancet 1952;1:903-4.
Shrivastava M, Navaid S, Peethambarakshan A, Agrawal K, Khan A. Detection of rare blood
group, Bombay (Oh) phenotype patients and management by acute normovolemic hemodilution.
Asian J Transfus Sci 2015;9:74-7.
Wagner FF, Bittner R, Petershofen EK, Doescher A, Müller TH. Cost-efficient sequence-specific
priming–polymerase chain reaction screening for blood donors with rare phenotypes. Transfusion
2008;48:1169-73.
Walker PS, Hamilton JR. Identification of antibodies to red cell antigens. In: Fung MR, Grossman
BJ, Hillyer CD, Westhoff CM, editors. Technical Manual. 18th ed. American Association of Blood
Banks; 2014. p.421.