ABNORMALITIES OF RED BLOOD CELLS

GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY

What is G6PD deficiency

• G6PD deficiency is a genetic disorder
• G6PD deficiency caused due to a deficiency of a chemical enzyme called glucose-6-phosphate dehydrogenase found in the RBC (red blood cells) causes red blood cells to break down prematurely.
• This syndrome is more common in males than females. Usually female became carrier.
• This deficiency did not show any symptom but after exposure to certain medicines, foods, and other infections, it causes severe injury to red blood cells by breaking the RBC's down
• Destruction of red blood cells is called hemolysis. If not properly treated, it will cause kernicterus.
• Once you get this disease, it can be either life long process or it could be cured.
• Typically,  easily curable with proper medicine

Symptoms of G6PD deficiency

• typically do not show any symptoms of the disorder until their red blood cells are exposed to certain triggers, which can be:

       Øillness, such as bacterial and viral infections

Øcertain painkillers and fever-reducing drugs

Øcertain antibiotics (especially those that have "sulf" in their names)

Øcertain antimalarial drugs (especially those that have "quine" in their names)

• In more serious cases
  Øpaleness (in darker-skinned children paleness is sometimes best seen in the mouth, especially on the lips or tongue)
  Øextreme tiredness
  ØRapid heartbeat
  ØRapid breathing and shortness of breath
  Øjaundice, or yellowing of the skin and eyes, particularly in newborns
  ØAn enlarged spleen
  Ødark, tea-colored urine

• Jaundice is one of the big side effects of G6PD deficiency. Newborn babies can have this disorder

ØThe main symptom of jaundice is a yellowish color of the eyes and mucous membrane.

ØG6PD causes jaundice by breaking down the red blood cells

Ø With jaundice, the baby's liver can not properly filter out toxins from the child's system, then lead to even more serious health problems

• For adult – if you get G6PD deficiency:

Ø You should avoiding eating beans – this food  increases the breakdown of red blood cells in this condition

Ø You should never use mothballs in your clothing or closets – these can exacerbate the disease

ØYou need proper medical treatment to make sure you have no lasting negative health effects 

Common affected of G6PD

• Distribution – most frequently in certain parts of Africa, Asia, and the Mediterranean
• An estimated 400 million people worldwide have glucose-6-phosphate dehydrogenase deficiency
• It affects about 1 in 10 African-American males in the United States

The gene related to G6PD

• G6PD is genetic disorder that related to mutations in the G6PD gene
• The G6PD gene provides instructions for making an enzyme called glucose-6-phosphate dehydrogenase.
• This enzyme functions as:

       Ø normal processing of carbohydrates

Øprotects red blood cells from the effects of potentially harmful molecules called reactive oxygen species - Reactive oxygen species are byproducts of normal cellular functions that building up to toxic levels within red blood cells

• If the G6PD deficiency by mutation, reactive oxygen species can accumulate and damage red blood cells
• Then, factor such as infections, certain drugs, or ingesting fava beans can increase the levels of reactive oxygen species causing red blood cells to be destroyed faster than the body can replace them. Afterward, it will cause hemolytic anemia
• carriers of a G6PD mutation may be partially protected against malaria, an infectious disease carried by a certain type of mosquito. Glucose-6-phosphate dehydrogenase deficiency occurs most frequently in areas of the world where malaria is common

How people inherit G6PD deficiency 

• This condition is inherited in an X-linked recessive pattern
• The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes
• In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition.
• In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder.
• Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females.
• A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons

Diagnosis and treating G6PD deficiency

• G6PD deficiency go undiagnosed until symptoms have been develop
• To confirm the diagnosis usually use blood tests and to rule out other possible causes of the anemia
• Treating the symptoms associated with G6PD deficiency is usually as simple such treating the illness or infection or stopping the use of a certain drug
• But, severe anemia may require treatment in the hospital to receive oxygen, fluids, and, if needed, a transfusion of healthy blood cells
• In rare cases, the deficiency can lead to other more serious health problems

Haemolytic disease of newborn (HDN)

•Is an alloimmune condition that develops in a fetus, 

 when the IgG molecules produced by the mother pass

 through the placenta

•This fetal disease ranges from mild to very severe,

 and fetal death from heart failure (hydrops fetalis) 

can occur

•Antibodies are produced when the body is exposed 

to foreign antigen 

•Some of the develeped antibodies can attack the body sistem
 and causing the reticulocytosis and eventually lead to anemia

•If present in the fetus, and may affect it in utero and 

persist after delivery 

•Rh disease is the most common form of severe HDN 

and it varies from mild to severe

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HOW TO DIAGNOSE

•The diagnosis of HDN is based on history and laboratory findings

•Blood tests done on the newborn baby

I.Biochemistry tests for jaundice

II.Peripheral blood morphology shows increase

reticulocytes. Erythroblasts (also known as 

nucleated red blood cells) occur in moderate and 

severe disease.

III.Positive direct Coombs test (might be negative 

after fetal interuterine blood transfusion)

•Blood tests done on the mother

                  Positive indirect Coombs tests

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Biochemistry Test for Jaundice

•Jaundice is yellow discolouration of skin, sclera, mucous
membranes, and other tissues due to excess of bilirubin in the
blood.

•Occurs when there is too much bilirubin circulating in the
blood.

*Bilirubin is a compound produced when hemoglobin is broken down in the blood.

1. Examination of feces 

•The stools are dark colored in hemolytic jaundice due to

excessive bile pigment, whereas it is pale and chalky white (clay

coloured) in obstructive jaundice due to absence of bile. 

2. Serum bilirubin

•The total, conjugated and unconjugated fractions can be

estimated. This helps in assessing the severity of jaundice 

and also in identifying the type. 

Vandenberg reaction 

is a qualitative test used in detecting the type of bile pigment in 

the serum.Direct positive test is given by conjugated bilirubin,

unconjugated bilirubin gives rise to the indirect reaction. When 
both pigments are present the reaction is biphasic.

Positive Direct Coomb Test

•The direct Coombs' test is used to detect antibodies that are 

already bound to the surface of red blood cells.

•These antibodies sometimes destroy red blood cells and cause

anemia.

Normal result:No clumping of cells (agglutination).

                         indicating that there are no antibodies to red         

                         blood cells.

* mother have anti-D antibodies baby blood will test for anemia and jaundice

•This may occur when there is a baby-mother Rh
incompatibility.


•The most common cause of hemolytic disease of the newborn is
an ABO incompatibility between mother and baby, especially 
with mothers that are blood group O.

Indirect Coomb's Test

•The indirect Coombs test finds certain antibodies that are in the
liquid part of the blood (serum).


•A test to determine whether a woman has Rh-positive or Rh
negative blood (Rh antibody titer) is done early in pregnancy. If
she is Rh-negative, steps can be taken to protect the baby.

Normal result

      

      A negative indirect Coombs test for Rh factor (Rh antibody titer) in a pregnant woman means that she has not developed antibodies against the Rh-positive blood of her baby.

     This means that Rh sensitization has not occurred.

Abnormal result

      

      If the Rh antibody titer test is positive in a woman who is pregnant or is planning to become pregnant, it means that she Rh sensitizationhas antibodies against Rh-positive blood 

BLOOD CHEMISTRY TESTS

Rh ANTIBODY

•most of Rh antibody – IgG class

•can cause- haemolytic transfusion reaction/ haemolytic disease of newborn

•Its does not activate compliment

•Anti-D/ anti-c                  – can cause severe HDN

•Anti-C/ anti-E/ anti-e      – not cause HDN/only mild HDN

ANTIGEN SYSTEM

• Antigens defined as substances recognized by the body as foreign  and it cause the body to produce an antibody to react specifically with it
• In blood group system, the antigen system is ABO antigens
• The characteristic of ABO antigens are:

1. Glycolipid in nature – they are oligosaccharides attached   directly to lipids on red cell membrane
2. Stick out from red cell membrane and there are  many antigen sites per red blood cell (approximately 800,000)
3. soluble antigens are present in RBC, plasma, saliva, and other secretions
4. ABO antigens are only moderately well developed at birth

• The antigen system consists of 3 types of antigen:

          1. A antigens

          2. B antigens

          3. H antigens

• The production of A, B and H antigens are controlled by the action of transferases
• Transferases are enzymes that catalyze (or control) addition of specific sugars to the oligosaccharide chain.
• The H, A, or B genes each produce a different transferase – adds a different specific sugar to the oligosaccharide chain.
• Also, there are 2 types of precusor chain of sugars is formed which either Type 1 or Type 2 depending on the linkage site between the N-acetylglucosamine (G1cNAc) and Galactose (Gal)

•H gene causes L-fucose to be added to the terminal sugar of precursor chain, producing H antigen. In O group, the H antigen remaining unchanged

•A gene causes N-acetyl-galactosamine to be added to H substance, producing A antigen

•B gene causes D-galactose to be added to H substance, producing B antigen

Diagram showing the carbohydrate chains that determine the ABO blood group

Diagram showing the types of blood tag on antibody and antigen present

• Group A have antigen A plus antigen H
• Group B have antigen B plus antigen H
• Group AB have both antigen A and antigen B plus antigen H
• Group O only have antigen H