Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
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%) 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 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 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 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: 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 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 • • • • • • • • • 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.