Polycythemia

(Definition/Aetiology)

Polycythemia causes

Polycythemia diagnostic criteria

• increase in the hemoglobin concentration above the upper limit of normal for the patient ’ s age and sex
• Erythrocytosis (absolute polycythemia) is likely when
• Hb > 18.5 g/dL or haematocrit > 0.52 in men
• Hb > 16.5 g/dL or haematocrit > 0.48 in women
• Once absolute is established, ix primary or secondary
• mutation of the cytoplasmic tyrosine kinase JAK2 gene
• JAK2-V617F (95%)
• JAK2 exon 12 mutations

• McLeod (XK) gene

• X chromosome (Males affected)
• codes for XK protein that carries Kx antigen, required for full Kell antigen expression

• McLeod - When XK not inherited, no Kx antigen, Kell antigen is weakly expressed – acanthocytes, anti-KL
• In Kell null, Kx antigen predominates. Anti-Ku produced. Decreased RBC survival

• McLeod syndrome
• RBC abnormality
• Elevated creatine kinase
• Neuropathy, cardiomyopathy.
• Associated with chronic granulomatous disease

• Clinical significance: yes

• Do not bind complement
• IgG binds at 37, agglutinate at AHG
• Destroyed by enzyme (Fya, Fyb, Fy6), resistant (Fy3, Fy5), no Fy4
• Antibody produced through exposure.
• HDFN+ (uncommon). DHTR+
• Dosage effect

• Chromosome 1
• Only present on RBC and body tissue
• Located on a glycoprotein, spans lipid bilayer multiple times

• Function: receptor for proinflammatory chemokines. Biologic sponge for excess chemokines
• Fya, Fyb – receptor for plasmodium vivax and knowlesi. Falciparum can freely enter regardless.

• Anti-Fya more common.

• Fy3 present whenever Fya/Fyb present. Anti-Fy3 produced in Fy(a-b-)
 Kidd Group

Lutheran Group

Lewis Group
 • Clinical significance: yes
• Some bind complement
• IgG binds at 37, agglutinate at AHG
• Enhanced by enzyme
• Antibody produced through exposure.
• Dosage effect
• Well developed at birth, occasionally cause mild HDN

• Chromosome 18

• Function: urea transporter

• Jk(a-b-) can be identified if resistant to 2M urea
• Antigen only found on rbc

• Jk3 present whenever Jka/Jkb present. Anti-Jk3 produced in Jk(a-b-), enhanced by enzyme

• Antibody do not store well in vitro. Weak reactivity in vitro.

• After stimulation antibody titre increases and quickly decreases to undetectable level
• Causes DHTR and extravascular hemolysis. Rarely activate complement and cause intravascular lysis

• Lua
• Clinical significance: no
• IgG and IgM
• Agglutination at RT (mixed field)
• Not affected by enzyme
• May present as naturally occurring antibody
• Poorly developed at birth
• Mild HDFN

• Lub
• Clinical significance: yes
• High incidence antigen, rare antibody
• IgG agglutinate at AHG (mixed field)
• Not affected by enzyme
• Mild HDFN

• Chromosome 19
• Located at membrane glycoprotein
• Function: adhesion properties, intra cellular signalling

• Clinical significance: no
• efficiently bind complement (hemolysis can be seen in vitro if fresh sample used)
• IgM agglutinate at IS, 37, and AHG. Agglutination is fragile and easily get dispersed.
• Enhanced by enzyme (Leb)
• Naturally occurring igM antibody. Usually in Le(a-b-) – anti-Lea and anti-Leb
• Can be neutralize by Lewis substance.
• No HDN

• Manufactured by tissue cells, secreted to body fluid, adsorbed to RBC

• Development of structure begin after birth [le(a-b-)] then [le(a+b+)] and completed at 6 years old [le(a-b+)]
• weakly expressed during pregnancy Lewis Le(a-b-) commonly seen, as hemodilution elutes Lewis off RBC.

• FUT1 (H) – type 2 RBC

• FUT2 (Se)
• type 1 secretion, adds fucose at terminal end
• very competitive compared to FUT3, to form H substance
• FUT3 (Lewis)
• type 1 secretion, add fucose subterminally
• Unmodifiable after that (steric hindrance) – form Lea
• Also add fucose to H substance (after type1 substance acted by FUT2) forming Leb

• Le(a-b+) do not produce anti-Lea

• Le(a+b-) rarely form anti-Leb

• Clinically insignificant as:

• transfused red cells shed their Lewis antigens and acquire the Lewis phenotype of the recipient
• Lewis antibodies are quickly adsorbed by free serum Lewis antigens
 I group

P group

MNS group
• Clinical significance: no
• Binds complement, c3d can be detected on RBC
• IgM cold autoantibody reacting at RT, avoided by pre warming technique
• Enhanced by enzyme
• Naturally occurring in most people

• Antigen present on precursor of ABH oligosaccharide chain closer to the membrane

• Can be found as soluble antigen in plasma or fluid
• i converted to I within 2 years of age
• I – branched chain
• i – linear chain
• Can be found as compound (clinically insignificant) anti-IH, stronger agglutination in O & A2 cells. (more H antigen)

• Autoanti-I – Mycoplasma pneumonia, cold agglutinin disease

• Autoanti-i – Infectious mononucleosis, lymphoproliferative disease, occasionally cold agglutinin disease.

• harmless autoanti-I of most people will not react above 10°-15°C, but some people have an autoanti-I that can react at RT

• Clinically significant anti-I occur in Cold Agglutinin Syndrome

• 1) Antibodies are of high titer (greater than 1000). Test the patient's serum against three group O adult cells
• 2) Have high thermal amplitude. (which are I positive-[pos]), three group O cord cells
• 3) Cause hemolytic anemia. (which are i positive-[weak]), and an autocontrol(pos).
Or prewarm prior test.

• Anti-P1
P1 - P1 P Pk
• Clinical significance: no, P1-pos RBC can be given if compatible at AHG
• IgM cold reacting P2 - P Pk
• Enhance by enzyme P1k – P1 Pk
• Detected in P2 individual P2k – Pk
• Naturally occurring P - none
• Commercial P1 substance can be used for neutralization.
Alloanti-P in Pk individual
• Autoanti-P
• Clinical significance: yes
• IgG biphasic hemolysin (Donath-Landsteiner antibody), binds P antigen at cold, and attach complement, hemolysis when
warm. – Paroxysmal Cold Hemoglobinuria
• Weak positive DAT (complement coated). Can supply P RBC, if pt&blood kept warm.
• Children after viral infection, adults with tertiary syphilis
• Confirmed with donath Landsteiner test.

• Anti-PP1Pk
• Hemolysis in vitro

• P antigen (globoside) is build on Pk,

• P1 is build on Type 2 precursor chain
• P1 antigen poorly developed at birth, expression decreases when stored.
• P1 - Soluble form detected in plasma and hydatid cyst fluid.

• Anti-M
• Clinical significance: no
• Naturally occurring IgG and IgM(usual)
• Some reacting at AHG after prewarming – is clinically significant
• destroyed by enzyme
• Rarely HDFN
• Dosage effect, also affected by pH. Enhanced at 6.5

• Anti-N
• Clinical significance: no
• IgM cold reacting
• destroyed by enzyme
• Dosage effect
• Can be found in dialysis patient.
• Does not cause HDN

• Anti-S,s,U
• Clinical significance: yes
• Causes HDFN
• IgG at AHG
• Dosage effect

• Chromosome 4

• When S or s inherited, U is present near to the base of membrane.

• S or s has antigenis similarity with N antigen. Prevent from formation of anti-N in MMSs.
Warm reacting antibody

Cold reacting antibody

Enzyme treatment
 Dosage

Cold reacting antibody

Enzyme treatment
Kell unaffected