Although there are no natural anti-Rh antibodies, and they never develop spontaneously, they can be produced only in Rh –ve persons. This can happen in either of 2 ways: one, when an Rh –ve person is given Rh +ve blood, and two, when an Rh –ve mother carries an Rh +ve fetus.
1. In transfusions. When an Rh –ve person receives Rh +ve blood, there is no immediate reaction since there are no antibodies. But during the next few weeks/months, he/she may produce anti-Rh antibodies that will remain in the blood. (Even 0.5 ml of Rh +ve blood is enough to produce immune response). However, if within a few weeks, or even years later, a second Rh +ve blood is injected, the newly donated red cells will be agglutinated and hemolysed, thus resulting in a serious transfusion reaction.
2. In pregnancy. The most common problem due to Rh incompatibility may arise when an Rh –ve mother (phenotype dd) carries an Rh +ve fetus (phenotype DD or Dd).
Normally, no direct contact occurs between maternal and fetal bloods. However, if a small amount of Rh +ve blood leaks from the fetus through the placenta into the mother’s blood, the mother’s immune system will start to make anti-Rh antibodies.
This happens at the time of delivery when small amounts of fetal blood leak into the mother as the placenta separates from the uterine wall. As a result, some mothers develop high concentration of anti-Rh antibodies during the period following delivery. Therefore, the first-born baby will not be affected, unless the mother has previously received Rh +ve blood transfusion.
There are cases of fetal-placental bleeding during pregnancy itself when fetal blood may enter the mother’s circulation. During the first pregnancy, however, the anti-Rh antibody levels do not reach high enough levels to cause complications. However, during the second and subsequent pregnancies, the mother’s anti-Rh antibodies cross the placental membrane into the fetus where they cause agglutination and hemolysis. The clinical condition that develops in the fetus is called “hemolytic disease of the newborn (HDN)’ or “erythroblastosis fetalis”
Chief Clinical Forms of HDN The chief clinical forms (syndromes) of HDN are:
1. Hydrops fetalis. If the hemolysis in the fetus is severe, it may die in the uterus, or the fetus may develop anemia, severe jaundice, and gross edema.
2. Icterus gravis neonatorum (grave jaundice of the new born). Though the infant is born at term, there is jaundice (hemolytic jaundice), or becomes so within a day or so. Anemia may be absent for a few days though reticulocyte count is high, and many nucleated red cells (erythroblasts) are present (hence the term
“erythroblastosis fetalis”).
3. Kernicterus. In the adults, the bile pigments cannot cross the blood-brain barrier (BBB) but in infants the BBB is not fully developed so that these pigments may pass into the brain and get deposited in the basal ganglia, giving them a bright yellow color. The neurological syndrome of kernicterus is rarely a complication of “physiological jaundice of the new born” because there is no hypoxic stimulus. Also the bilirubin level is not as high as in HDN (The physiological jaundice is due to immaturity of the liver and disappears in a few days).
Q.18 If an Rh –ve mother carries Rh +ve fe-tus, what are the complications that are likely to occur?
See Q/A 17 above.
Q.19 When an Rh +ve mother carries Rh –ve fetus, why are there no complications?
The Rh +ve red cells of the mother cannot cross the placenta into the fetus. But even if small amounts of maternal blood do leak into the fetus as a result of placental hemorrhage at any time during pregnancy, the fetus cannot respond by forming anti-Rh antibodies. The reason for this is that the ability to respond to foreign antigens develops after birth. However, when it does develop in later life, transfusion of Rh +ve blood will evoke anti-Rh antibody production.
Q.20 What is hemolytic disease of the new-born? What are the forms in which this condition may be manifested?
See Q/A 17 above.
Q.21 What is the probability of the occurrence of hemolytic disease of the newborn when the father is Rh +ve and the mother is Rh –ve?
The blood group antigens are a result of gene action.
The gene related to D antigen is called D. When D
is absent from a chromosome, its alternate form (allelomorph), called d, takes its place. The Rh genes of a person are inherited from both parents. If the genes carried by the sperm and ovum are identical, the offspring is homozygous (DD or dd). Thus, if both carry D gene, all the offspring will be DD (homozygous D+; Rh +ve). If one carries D and the other carries d, the offspring will be heterozygous D+ (Rh +ve).
If both ovum and sperm carry d, the offspring will be homozygous D –ve (Rh –ve).
Therefore, if the father’s genotype is Dd, the offspring may be Rh +ve (Dd) or Rh –ve (dd), but if the genotype is DD, all offspring will be Rh +ve.
Thus, the probability of HDN when the father is Rh +ve will depend on whether he is Dd (Rh +ve) or DD (Rh +ve).
Q.22 How can hemolytic disease of the new-born be prevented? What is the treatment of severe HDN?
The hemolysis of red cells (HDN) is due to the crossing over of anti-Rh antibodies from the Rh –ve mother (through the placenta) into the Rh +ve fetus. The condition can be prevented by desensitizing all Rh –ve mothers by giving them injections of massive doses of anti-Rh antibodies called anti-Rh gamma globulin (RhoGAM) after every abortion, miscarriage, or delivery. These antibodies bind to and inactivate the fetal Rh antigens (on fetal red cells) present in maternal circulation. In this way, the Rh antigens from the mother’s blood are cleared (removed) before they have had time to stimulate production of anti-Rh antibodies.
(Fetal Rh typing is now possible with samples of amniotic fluid or chorionic villi, and treatment with a small dose of Rh immune serum can prevent sensitization of mother during pregnancy. It is not known how this is achieved but one effect of anti-D antibody is to inhibit antigen-induced B lymphocyte antibody production. It also attaches to D antigen sites on fetal red cells in mother’s blood).
Treatment of severe HDN. The best treatment for a severe case of HDN is to successively withdraw small amounts of fetal blood and to replace them with equal amounts of compatible Rh –ve blood. Of course, this exchange transfusion does not change the
inherited blood group of the infant. It only removes the red cells that are destined to be hemolysed.
Q.23 Why does the ABO-incompatibility rarely produce hemolytic disease of the newborn?
The ABO-incompatibility between the mother and fetus rarely causes HDN. The reason is that the anti-A and anti-B (anti-ABO) antibodies belong to IgM type of gamma globulins (cold antibodies) that do not cross the placenta.
Q.24 What is the incidence of blood types in Indian and a few other populations?
The frequency distribution of blood groups is shown in Table 1-4.
Table 1-4: Frequency distribution of blood groups
Q.25 What is the importance of blood group-ing?
Blood grouping/typing is important
in:-1. Blood transfusion for treatment purposes.
2. Determination of Rh incompatibility between the mother and child.
3. Paternity disputes. The ABO, Rh, and MNS blood grouping is used to settle cases of disputed paternity. Antigens A and B are dominant, whereas O is recessive. It is possible to prove that a person could not have been the father, but not that he was/is the father. (“DNA finger printing” is now a recognised procedure for settling such disputes.
It can prove fatherhood with 100% accuracy).
4. Choice of a donor in tissue/organ transplantation.
5. Genetic studies.
6. Medico legal use. Any red stain on a clothing may be claimed to be blood by a supposed victim.
Therefore, it is first confirmed that it really is human blood. Blood grouping of the extracted sample can then prove or disprove the claim of the
victim. In doubtful cases, the DNA fingerprinting can decide the claim one way or the other.
7. Susceptibility to disease. The people of blood type O are more susceptible to peptic ulcer. Blood type A is more commonly seen in carcinoma of stomach, and to some extent in diabetes mellitus.
Q.26 How is blood volume supplemented?
The total blood volume, plasma volume, or packed cell volume may be greatly reduced under certain circumstances. Thus, (i) The blood volume may be greatly reduced in cases of severe hemorrhage, (ii) plasma volume may be reduced in severe burns (plasma seeps out), prolonged vomiting or diarrhea, or excessive sweating, and, (iii) red cell volume may be reduced in cases of anemia. The blood volume can be supplemented by various solutions, plasma or whole blood (see Q/A 36).
Q.27 What are the indications for blood trans-fusion?
1. Acute hemorrhage. Acute loss of blood resulting from accidents, during surgery, ruptured peptic ulcer and aortic aneurysm, ectopic pregnancy, etc. are some of the conditions which may cause hemorrhagic shock, and therefore, need immediate blood transfusion. Cross-matched blood is always given, but if the situation is desperate, group O(Rh-ve) blood may be given to raise blood pressure. In burns, blood may be given though plasma is preferred.
2. Chronic anemias that cannot be treated with diet and drugs. Packed red cells (Hct about 70%) can be transfused when a quick restoration of Hb is required, as in pregnancy, emergency surgery, etc.
3. Exchange transfusion. It is employed in hemolytic disease of the newborn (consult Q/A 22).
4. Bleeding disorders. Fresh blood or platelet concentrates are given in purpura. Fresh frozen plasma, or cryoprecipitate is given in hemophilia and other clotting factor deficiencies.
5. Granulocyte transfusion. It is needed in cases of neutropenia (TLC < 500/mm3) with severe bacterial infection.
6. Bone marrow depression due to any cause and infiltration by carcinoma cells.
7. Autologous transfusion (see below; Q/A 28).
Q.28 What is autologous transfusion?
In addition to receiving blood from a donor, an individual may also receive one’s own stored blood, (i.e., during elective surgery on a preselected day in the future), a procedure called predonation. (The popularity of this procedure is that it avoids the hazards of AIDS, hepatitis, etc as well as risk of transfusion reaction).
Predonation (Predeposit). It is a form of autologous transfusion and is a common practice in some hospitals. After starting a course of iron tablets, two units of blood are collected, one 16 days before the operation, and the other eight days later. An important technical innovation is the cell-saver machine which sucks up blood from the wound during the operation, recycles it, and returns it to the patient’s body.
Q.29 What is blood doping? When is it em-ployed?
Blood doping is the procedure in which some athletes used to get a unit or two of their own blood (or red cells) removed and stored for a few weeks. It was then reinjected in 2–3 sessions a few days before an event. Since oxygen delivery to active muscles is the limiting factor, increased red cell count was expected to enhance their performance, especially in endurance events. The procedure was (and is) dangerous since it increases the load on the heart due to increased blood volume or viscosity. The International Olympic Committee has banned blood doping.
Q.30 What are the hazards (dangers) of blood transfusion?
1. Transmission of disease. The donated blood has the potential of transmitting some serious diseases. It is therefore mandatory to test the blood for HIV antibodies (for AIDS), hepatitis B surface antigen, HCV antibodies, syphilis (VDRL test), and malarial parasite.
2. Incompatibility due to mismatched transfu-sion This is the most serious and potentially fatal complication. Whether the transfusion reactions are immediate or delayed, as well as their severity is determined by the speed and extent of hemo-lysis of donated red cells.
i. Body aches and pains. Within a short time of starting the transfusion, the patient complains of severe pain in the back, limbs,
or chest, and a sense of suffocation and tightness in the chest. These symptoms are due to blockage of capillaries by clumps of agglutinated cells. Chills and fever generally accompany pains.
ii. Renal failure. Acute renal failure (kidney shutdown) appears to result from 3 main causes:
a. Substance of immune reaction and toxic substances released from hemolysing blood cause powerful renal vasoconstric-tion.
b. These substances and decrease in circu-lating red cells frequently cause circula-tory shock. The arterial blood pressure falls to very low levels, and renal blood flow and urine output decrease.
c. If the amount of free Hb in plasma is small, then whatever is filtered is reab-sorbed. If this amount is large, it gets precipitated in and blocks many tubules.
The result of all these factors is acute renal failure and death may occur in 8–10 days, if the shutdown is not resolved or treated with dialysis.
3. Faulty technique of transfusion. Cardiac ar-rhythmias, cardiac arrest, or circulatory overload may occur, especially in elderly patients of chronic anemia, heart or kidney diseases, if repeated transfusions are given, say, in 24 hours. Throm-bophlebitis may occur if the intravenous needle remains in the same site for many hours. Air embolism, i.e. entry of air into blood via the intra-venous needle is much less likely to occur because of the use of plastic bags (instead of glass bottles) which collapse down as they empty out of blood.
4. Allergic reactions. Reactions such as skin rashes and asthma may occur if the donor blood contains substances to which the patient is sensitive.
5. Pyrogen reactions. Reactions such as chills and fever are probably due to the presence of antibodies to leukocytes and platelets.
6. Tetany. With massive transfusions, the normal conversion of citrate to bicarbonate in the tissues may be delayed. This will result in fall in plasma ionic calcium and hence tetany.
7. Iron overload. Repeated transfusions in the absence of blood loss may lead to hemochromatosis.
Q.31 What precautions are taken while select-ing a blood donor?
The following precautions are observed:
1. The donor should be healthy, and aged between 18 and 60 years. Pregnant and lactating women are excluded.
2. The donor should be screened for communicable diseases such as AIDS, hepatitis, syphilis, malaria, etc). The malarial parasite can survive at 4o C for 3 weeks.
3. The donor’s Hb should be within the normal range (usually above 12.5 g%). Its level is tested with the copper sulphate specific gravity method.
4. Professional donors must be discouraged for reasons that are well known.
Q.32 What are blood banks? How is donated blood stored? What is the fate of transfused citrate in the body?
With the modern surgical and medical procedures, the demand for blood has greatly increased. It is for this reason that blood banks were started where blood from voluntary donors could be stored, so that it was always available on demand. Most blood banks have lists of would-be donors so that they may be contacted when required.
Storage of blood. After a donor has been screened for donation, one unit of blood (450 ml) is collected, under aseptic conditions, from the antecubital vein directly into a special plastic bag containing 63 ml of CPD-A (citrate-phosphate-dextrose-adenine) mixture.
The blood bag is suitably sealed, labeled, and stored at 4o C, where it can be kept for about 20 days. (Faulty storage, i.e. overheating or freezing can lead to gross infection and hemolysis).
The citrate prevents clotting of blood, sodium diphosphate acts as a buffer to control decrease in pH, dextrose supports ATP generation via glycolytic pathway and also provides energy for Na+- K+ pump that maintains the size and shape of red cells and increases their survival time, and adenine provides substrate for the synthesis of ATP, thus improving post-donation viability of red cells.
Blood is stored at low temperatures for 2 reasons:
one, it decreases bacterial growth, and two, it decreases the rate of glycolysis and thus prevents a quick fall in pH.
Changes in red cells during storage. Changes occur due to decreased metabolism, and include increase in their Na+ and decrease in K+ concentration due to reduced Na+-K+ pump activity, the result being a net increase in total base and water content of the cells that swell and become more spherocytic.
The ATP content decreases and inorganic phosphate content increases.
Changes after transfusion. These changes occur within a day or so, the red cells lose sodium and gain potassium, with the volume, shape and fragility returning to normal. Their survival time increases if blood is given within a week of donation.
Fate of transfused citrate. The citrate (in the form of trisodium citrate) that is used to store blood can safely be injected intravenously (oxalates are toxic).
Within a few minutes, the liver removes citrate from blood and polymerizes it into glucose, or metabolizes it directly for energy. But if the liver is damaged, or if large amounts of citrate are injected too quickly, the citrate may lower the calcium level in blood to result in tetany, or even death from convulsions.
Blood substitutes Separate components of blood—
packed RBCs, whole plasma (fresh frozen plasma, FFP) to provide clotting factors, platelets, leukocytes, plasma and plasma expanders are now available.
Q.33 What is the only certain way of avoiding blood incompatibility?
1. The slides and containers must be properly labeled.
2. Cross matching is the only certain way of avoiding the dangers of mismatching.
3. Rh +ve blood should never be given to an Rh –ve female of any age before menopause.
Q.34 Name the precautions you will observe before and during blood transfusion?
1. Blood should be transfused only when absolutely required.
2. It should be confirmed that cross matching has been done to exclude mismatching of groups other than ABO system.
3. The blood bag should be checked for the blood type indicated on it.
4. It should be confirmed that the blood has been checked for infections especially AIDS.
5. Rh +ve blood should never be given to an Rh –ve person.
6. Blood should never be transfused at a fast rate—
usually not more than 20–25 drops per minute, unless otherwise indicated (as in acute and severe loss of blood where blood may have to be pumped into the patient). A rapid transfusion, under normal conditions, may cause chelation of calcium ions and tetany.
7. The condition of the recipient should be checked carefully for the first 10–15 minutes of starting the transfusion, and from time to time later on. The transfusion must be stopped if there is a rapid rise of temperature, (> 40°C), or any other reaction.
Q.35 What are the earliest effects of a mis-matched transfusion?
Within a short time of starting the transfusion (i.e.
when a few ml of blood have entered the recipient’s body), there may be severe pain anywhere in the body, a sense of suffocation and tightness in the chest. There may be chills and shivering, fever, etc.
(Consult Q/A 30 for details).
Q.36 Which blood substitutes may be used to restore blood volume if suitable donor blood is not available?
The blood volume may be reduced due to hemorrhage;
The blood volume may be reduced due to hemorrhage;