Other Blood Group Systems

More than 400 other blood group antigens exist. Even though blood is ABO and Rh compatible, a recipient of a transfusion may still develop an alloantibody to one or more of the hundreds of red blood cell antigens present. Any antigens that the patient does not possess are potentially immunogenic. Approximately 1.5-2.0% of hospital patients have detectable alloantibodies to red cell antigens caused by previous transfusion or pregnancy.

The most frequently detected antibodies in order of decreasing frequency are; D>K>E>CD>Fya>Jka>c>C>cE>e>DE>V>Jkb. Even components containing very few red blood cells, such as pooled random donor platelet concentrates can stimulate antibody formation. Multiply transfused patients have much higher incidences of RBC antibody formation. Thefrequency varies with age and disease state. Overall, approximately 10% of patients transfused with multiple units of red blood cells form antibodies against some of the non-ABO, non-D antigens. In those patients who produce 1 RBC antibody, about 33% will produce additional antibodies.

Frequency of RBC Antibodies in Multi-Transfused Patients

Population	Frequency (%)
Sickle cell children	8
Sickle cell adults	30
Thalassemia major - all ages	5
Chronic renal failure	7
Transplant recipients	10

Antibodies related to these antigens, like Rh antibodies, are unexpected and may interfere with compatibility testing. Some are immune, 37° reactive IgG antibodies and clinically significant because they are associated with transfusion reactions (TR) and HDN. Others are naturally occurring, cold reactive IgM antibodies and clinically insignificant because they are not usually associated with in vivo red cell destruction.

Clinical Significance of Most Common Blood Group Alloantibodies

Usually Clinically Significant	Sometimes Clinically Significant	Insignificant if not reactive at 37^oC	Generally Clinically Insignificant

A & B	Colton	A₁	P1
Diego	Dombrock	H	Sd^a
Duffy	Yt^a	M,N	Chido, Rodgers
Kell	Le^a		Cost
Kidd	Lutheran		Knops
Rh			Le^b
S,s,U

Common blood group antibodies and their reactivity are summarized in the table below.

Common Red Blood Cell Antibody Properties & Clinical Significance

Blood Group System	Antibody	Reactivity	TR	HDN	% Units Compatible	Transfuse
Rh	D	IAT	Yes	Yes	15	Antigen neg unit
	C	IAT	Yes	Yes	30	Antigen neg unit
	E	RT, IAT	Yes	Yes	70	Antigen neg unit
	c	IAT	Yes	Yes	20	Antigen neg unit
	e	IAT	Yes	Yes	3	Antigen neg unit
	C^w	RT, IAT	Yes	Yes	98	Antigen neg unit
Kell	K	RT, IAT	Yes	Yes	91	Antigen neg unit
	k	IAT	Yes	Yes	0.2	Antigen neg unit
	Kp^a	IAT	Yes	Yes	98	Antigen neg unit
	Kp^b	IAT	Yes	Yes	0	Antigen neg unit
	Js^a	IAT	Yes	Yes	100	Antigen neg unit
	Js^b	IAT	Yes	Yes	0	Antigen neg unit
Duffy	Fy^a	IAT	Yes	Yes	34	Antigen neg unit
Duffy	Fy^b	IAT	Yes	Yes	17	Antigen neg unit
Kidd	Jk^a	IAT	Yes	Yes	23	Antigen neg unit
Kidd	Jk^b	IAT	Yes	Yes	28	Antigen neg unit
Lewis	Le^a	RT,37, IAT	Rare	No	78	IAT XM compatible
	Le^b	RT,37, IAT	No	No	22	IAT XM compatible
MNSs	M	RT, IAT	Few	Few	22	IAT XM compatible
	N	RT, IAT	No	Rare	28	IAT XM compatible
	S	IAT	Yes	Yes	45	Ag neg unit
	s	IAT	Yes	Yes	11	Ag neg unit
P	P₁	RT	Rare	No	21	IAT XM compatible
Lutheran	Lu^a	RT, IAT	No	No	92	IAT XM compatible
Lutheran	Lu^b	RT, IAT	Yes	Yes	0.15	Medical decision

In the Kell blood group system, K is very immunogenic. K antigen occurs in only about 9% of Caucasians and 2% of African Americans. The Kp and Js antigens are products of linked loci.
In the Duffy blood group system, the usual alleles are Fya and Fyb. A third allele produces neither Fya nor Fyb. Approximately 70% of African Americans lack both Fya and Fyb.
In the Kidd blood group system, about 77% of Caucasians express Jka (27% Jka Jka & 50% Jka Jkb). The remaining 23% are Jkb Jkb. Most African Americans are Jka positive. Anti- Jka and Jkb are IgG antibodies, but they invariably bind complement and may give stronger reactions in an indirect antiglobulin test with anti-C3 than with anti-IgG. In identifying anti-Jka a dosage effect is common, so that positive results may be obtained only with homozygous Jka Jka cells.
Anti-Lewis a & b antibodies are usually IgM antibodies and are seldom clinically significant. They are commonly detected during pregnancy.
In the MNSs system, anti-M and anti-N are usually IgM antibodies and are rarely clinically significant. Numerous low frequency antigens have been described in this system, but they have little practical significance. Anti-S antibodies are often IgG and reactive at 37o C.
Almost all individuals are either P1 (75%) or P2. P2 persons frequently have anti-P1, which is usually an IgM antibody. Some anti-P antibodies behave as agglutinins at room temperature and as hemolysins at 37oC, which is termed biphasic hemolysis or Donath-Landsteiner antibodies. Anti-P autoantibody is associated with paroxysmal cold hemoglobinuria (PCH). Rare individuals with the p phenotype, who lack P1, P and Pk antigens, make an antibody against all three antigens, termed anti-Tja (anti-P1+P+Pk).
About 8% of Caucasians are Lua positive; almost all of them are LuaLub. The remaining 92% of the population are LubLub. Anti-Lua is not associated with increased red cell destruction. Anti-Lub is rarely a cause of a delayed hemolytic transfusion reaction, but not HDN.
Anti I is frequently associated with cold autoimmune hemolytic anemia (AIHA).

All detected antibodies are investigated and clinically significant ones are identified so that antigen negative blood can be provided for transfusion. If a patient has multiple antibodies, the percent of red cell units that will be compatible can be calculated in the following manner.

Find % units compatible for each antibody in table above.
Convert %compatible number to a decimal.
Multiply the decimal fraction of the 1st antibody by 2nd antibody and the 3rd antibody, etc.
Multiply the result by 100 and round off the result to the nearest whole number.
The answer is the percent of red cell units that will be compatible.

Example: A patient has anti-K (91% compatible), anti-E (70% compatible) and anti-Fya (34% compatible).

The % units compatible = 0.91 x 0.70 x 0.34 = 0.22 x 100 = 22%

Consequences Of Red Blood Cell Antibodies
Some antibodies, particularly IgM antibodies of the ABO blood group system, are capable of fixing complement to the red cell surface. Complement is a plasma protein cascade that is activated by some antigen-antibody reactions. Binding of the membrane attack complex disrupts the cell membrane, causing hemolysis. Hemoglobin is released into the plasma, resulting in hemoglobinemia and hemoglobinuria. This process is termed intravascular hemolysis.

Red cells coated with IgG antibody that does not fix complement are removed from the circulation following phagocytosis by reticuloendothelial cells. During phagocytosis, heme is metabolized to bilirubin, resulting in icterus. Hemoglobinemia and hemoglobinuria do not occur. This process is termed extravascular hemolysis.




ABO Blood Group System ABO Mismatched Allogeneic Transplants Albumin Autoimmune Hemolytic Guidelines Blood Administration Blood Component Transfusion Guidelines Blood Donation CMV Negative Blood Components Compatibility Testing Cryoprecipitate Factor IX Complex Factor VIIa Factor VIII Concentrate Factor VIII Inhibitors Fresh Frozen Plasma Granulocyte Transfusion Hemolysis Following Allogeneic BMT Informed Consent Irradiated Blood Components Leukocyte Reduced Red Cells & Platelets Massive Transfusion Neonatal Alloimmune Thrombocytopenia Nitric Oxide Banked Blood Other Blood Group Systems Pediatric & Neonatal Transfusion Practices Platelet Transfusion Prenatal & Perinatal Immunohematologic Testing RBC Transfusion Trigger Red Blood Cell Transfusion Rh Blood Group System RhIG for HDN Prevention RhIG for Treatment of ITP Saline Washed Red Blood Cells Sickle Cell Disease Transfusion Therapeutic Apheresis Thrombotic Thrombocytopenic Purpura Transfusion Reactions Transfusion Related Acute Lung Injury Trypanosoma Cruzi Donor Screening Umbilical Cord Blood Stem Cells von Willebrands Disease Warm Autoimmune Hemolytic Anemia