Iron-deficiency anemia (or iron-deficiency anaemia) is a common anemia (low red blood cell or hemoglobin levels) caused by insufficient dietary intake and absorption of iron, and/or iron loss from bleeding which can originate from a range of sources such as the intestinal, uterine or urinary tract.

Iron deficiency causes approximately half of all anemia cases worldwide, and affects women more often than men. World estimates of iron deficiency occurrence are somewhat vague, but the true number probably exceeds one billion people. This can result if:

The body does not make enough red blood cells Bleeding causes loss of red blood cells more

quickly than they can be replaced

The most significant cause of iron-deficiency anemia in developing world children is parasitic worms: hookworms, whipworms, and roundworms. Worms cause intestinal bleeding, which is not always noticeable in faeces, and is especially damaging to growing children.[ Malaria, hookworms and vitamin A deficiency contribute to anemia during pregnancy in most underdeveloped countries. In women over 50 years old, the most common cause of iron-deficiency anemia is chronic gastrointestinal bleeding from nonparasitic causes, such as gastric ulcers, duodenal ulcers or gastrointestinal cancer.

Anemia is one result of advanced-stage iron deficiency. When the body has sufficient iron to meet its needs (functional iron), the remainder is stored for later use in all cells, but mostly in the bone marrow, liver, and spleen. These stores are called ferritin complexes and are part of the human (and other animals) iron metabolism systems. Ferritin complexes in humans carry about 4500 iron atoms and form into 24 protein subunits of two different types.[4]

Signs and symptoms

Iron-deficiency anemia is characterized by the sign of pallor (reduced oxyhemoglobin in skin or mucous membranes), and the symptoms of fatigue, lightheadedness, and weakness. None of the symptoms (or any of the others below) are sensitive or specific. Pallor of mucous membranes (primarily the conjunctiva) in children indicates anemia with best correlation to the actual disease, but in a large study was found to be only 28% sensitive and 87% specific (with high predictive value) in distinguishing children with anemia [hemoglobin (Hb) <11.0 g/dl] and 49% sensitive and 79% specific in distinguishing severe anemia (Hb < 7.0 g/dl).[5] Thus, this sign is reasonably predictive when present, but not helpful when absent, as only one-third to one-half of children who are anemic (depending on severity) will show pallor. Iron-deficiency must be diagnosed by laboratory testing.

Because iron deficiency tends to develop slowly, adaptation occurs and the disease often goes unrecognized for some time, even years; patients often adapt to the systemic effects that anaemia causes. In severe cases, dyspnea (trouble breathing) can occur. Unusual obsessive food cravings, known as pica, may develop. Pagophagia or pica for ice has been suggested to be specific, but is actually neither a specific or sensitive symptom, and is not helpful in diagnosis. When present, it may (or may not) disappear with correction of iron-deficiency anemia.

Other symptoms and signs of iron-deficiency anemia include:

Anxiety often resulting in OCD-type compulsions and obsessions

Irritability or a low feeling

Angina

Constipation

Sleepiness

Tinnitus

Mouth ulcers

Palpitations

Hair loss

Fainting or feeling faint

Depression

Breathlessness

Twitching muscles

Pale yellow skin

Tingling, numbness, or burning sensations

Missed menstrual cycle

Slow social development

Glossitis (inflammation or infection of the tongue)

Angular cheilitis (inflammatory lesions at the mouth's corners)

Koilonychia (spoon-shaped nails) or nails that are weak or brittle

Poor appetite

Pruritus (itchiness)

Dysphagia due to formation of esophageal webs (Plummer-Vinson syndrome)

Insomnia

Restless legs syndrome [6]

Infant development

Iron-deficiency anemia for infants in their earlier stages of development may have greater consequences than it does for adults. An infant made severely iron-deficient during its earlier life cannot recover to normal iron levels even with iron therapy. In contrast, iron

deficiency during later stages of development can be compensated with sufficient iron supplements. Iron-deficiency anemia affects neurological development by decreasing learning ability, altering motor functions, and permanently reducing the number of dopamine receptors and serotonin levels. Iron deficiency during development can lead to reduced myelination of the spinal cord, as well as a change in myelin composition. Additionally, iron-deficiency anemia has a negative effect on physical growth. Growth hormone secretion is related to serum transferrin levels, suggesting a positive correlation between iron-transferrin levels and an increase in height and weight. This is also linked to pica, as it can be a cause.

Cause

A diagnosis of iron-deficiency anemia then requires further investigation as to its cause. It can be caused by increased iron demand / loss or decreased iron intake, and can occur in both children and adults. The cause of chronic blood loss should all be considered, according to the patient's sex, age, and history, and anaemia without an attributable underlying cause is sufficient for an urgent referral to exclude underlying malignancy. In babies and adolescents, rapid growth may outpace dietary intake of iron, and result in deficiency without disease or grossly abnormal diet. In women of childbearing age, heavy or long menstrual periods can also cause mild iron-deficiency anemia.

Parasitosis

The leading cause of iron deficiency worldwide is infestation with parasitic worms (hookworms, whipworms, roundworms). Estimates of infection in the world population vary from a minimum of a billion humans to as many as 5 or 6 billion. Paracitic worms cause both inflammation as well as chronic blood loss.

Blood loss

Blood contains iron within red blood cells. So if a person loses blood, he or she will lose some iron. There are several common causes of blood loss: Women with menorrhagia (heavy periods) are at risk of iron deficiency anemia because they lose a larger amount blood during menstruation than is replaced from their diet. Slow, chronic blood loss within the body — such as from a peptic ulcer, angiodysplasia, a colon polyp or gastrointestinal cancer — can cause iron-deficiency anemia. Gastrointestinal bleeding can result from regular use of some groups of medication, such as non steroidal anti inflammatory drugs (NSAIDs) e.g. Aspirin, anticoagulants such as clopidogrel and warfarin although these are required in some patients, especially those with states causing thrombophilia.

A lack of iron in the diet

The body regularly gets iron from the foods eaten. If a person consumes too little iron, or iron that is poorly absorbed (non-heme iron), over time the body can

become iron-deficient. Examples of iron-rich foods include meat, eggs, leafy green vegetables and iron-fortified foods. For proper growth and development, infants and children need iron from their diet, too.

An inability to absorb iron

Iron from food is absorbed into the bloodstream in the small intestine, especially the duodenum and proximal illeum. Many intestinal disorders can reduce the body's ability to absorb iron. There are different mechanisms that be present.

In cases where there has been a reduction in surface area of the bowel, such as in celiac disease, inflamatory bowel disease or post surgical resection the body can absorb iron, but there is simply insiffucient surface area.

If there is insufficient production of hydrochloric acid in the stomach, hypochlorhydria/achlorhydria (often due to chronic H. pylori infections or long-term proton pump inhibitor therapy) Ferrous and Ferric iron salts will precipitate out of solution in the bowel which are poorly absorbed.

In cases where systemic inflammation is present, iron will be absorbed into enterocytes, but due to the reduction in basolateral ferroportin molecules which allow iron to pass into the systemic circulation, iron is trapped in the enterocytes and is lost from the body when the enterocytes are sloughed off.

Depending on the disease state, one or both mechanism may occur.

Pregnancy

Without iron supplementation, iron deficiency anemia occurs in many pregnant women because their iron stores need to serve their own increased blood volume as well as be a source of hemoglobin for the growing fetus, and for placental development.

Other less common causes are intravascular hemolysis and hemoglobinuria.

Diagnosis

Anemia may be diagnosed from symptoms and signs, but when it is mild, it may not be diagnosed from mild nonspecific symptoms. Pica, an abnormal craving for dirt, ice, or other "odd" foods occurs variably in iron and zinc deficiency, but is neither sensitive or specific to the problem, so is of little diagnostic help

Anemia is often first shown by routine blood tests, which generally include a complete blood count (CBC) which is performed by an instrument which gives an output as a series of index numbers. A sufficiently low hemoglobin (Hb) by definition makes the diagnosis of anemia, and a low hematocrit value is also characteristic of anemia. Further studies will be undertaken to determine the anemia's cause. If the anemia is due to iron deficiency, one of the first

abnormal values to be noted on a CBC, as the body's iron stores begin to be depleted, will be a high red blood cell distribution width, reflecting an increased variability in the size of red blood cells (RBCs). In the course of slowly depleted iron status, an increasing RDW normally appears even before anemia appears.

A low mean corpuscular volume (MCV) often appears next during the course of body iron depletion. It corresponds to a high number of abnormally small red blood cells. A low MCV, a low mean corpuscular hemoglobin and/or mean corpuscular hemoglobin concentration, and the appearance of the RBCs on visual examination of a peripheral blood smear narrows the problem to a microcytic anemia (literally, a "small red blood cell" anemia). The numerical values for these measures are all calculated by modern laboratory equipment.

Blood smear of a patient with iron-deficiency anemia at 40X enhancement

The blood smear of a patient with iron deficiency shows many hypochromic (pale and relatively colorless) and rather small RBCs, and may also show poikilocytosis

(variation in shape) and anisocytosis (variation in size). With more severe iron-deficiency anemia, the peripheral blood smear may show target cells, hypochromic pencil-shaped cells, and occasionally small numbers of nucleated red blood cells.[9] Very commonly, the platelet count is slightly above the high limit of normal in iron deficiency anemia (this is mild thrombocytosis). This effect was classically postulated to be due to high erythropoietin levels in the body as a result of anemia, cross-reacting to activate thrombopoietin receptors in the precursor cells that make platelets; however, this process has not been corroborated. Such slightly increased platelet counts present no danger, but remain valuable as an indicator even if their origin is not yet known.

The diagnosis of iron-deficiency anemia will be suggested by appropriate history (e.g., anemia in a menstruating woman or an athlete engaged in long-distance running), the presence of occult blood (i.e., hidden blood) in the stool, and often by other history.[10]

For example, known celiac disease can cause malabsorption of iron. A travel history to areas in which hookworms and whipworms are endemic may be helpful in guiding certain stool tests for parasites or their eggs.

Body-store iron deficiency is diagnosed by diagnostic tests, such as a low serum ferritin, a low serum iron level, an elevated serum transferrin and a high total iron binding capacity. A low serum ferritin is the most

sensitive lab test for iron deficiency anemia. However, serum ferritin can be elevated by any type of chronic inflammation and so is not always a reliable test of iron status if it is within normal limits (i.e., this test is meaningful if abnormally low, but less meaningful if normal).

Serum iron levels (i.e., iron not part of the hemoglobin in red cells) may be measured directly in the blood, but these levels increase immediately with iron supplementation (the patient must stop supplements for 24 hours), and pure blood-serum iron concentration in any case is not as sensitive as a combination of total serum iron, along with a measure of the serum iron-binding protein levels (TIBC). The ratio of serum iron to TIBC (called iron saturation or transferrin saturation index or percent) is the most specific indicator of iron deficiency, when it is sufficiently low. The iron saturation (or transferrin saturation) of < 5% almost always indicates iron deficiency, while levels from 5% to 10% make the diagnosis of iron deficiency possible but not definitive. Saturations over 12% (taken alone) make the diagnosis unlikely. Normal saturations are usually slightly lower for women (>12%) than for men (>15%), but this may indicate simply an overall slightly poorer iron status for women in the "normal" population.

Change in lab values in iron deficiency anemiaChange Parameter

Decrease ferritin, hemoglobin, MCVIncrease TIBC, transferrin, RDW

Iron-deficiency anemia and thalassemia minor present with many of the same lab results. It is very important not to treat a patient with thalassemia with an iron supplement, as this can lead to hemochromatosis

(accumulation of iron in various organs, especially the liver). A hemoglobin electrophoresis provides useful evidence for distinguishing these two conditions, along with iron studies.

Gold standard

Conventionally, a definitive diagnosis requires a demonstration of depleted body iron stores obtained by bone marrow aspiration, with the marrow stained for iron. Because this is invasive and painful, while a clinical trial of iron supplementation is inexpensive and not traumatic, patients are often treated based on clinical history and serum ferritin levels without a bone marrow biopsy. Furthermore, a study published April 2009 questions the value of stainable bone marrow iron following parenteral iron therapy.

Treatment

Anemia is sometimes treatable, but certain types of anemia may be lifelong. If the cause is dietary iron deficiency, eating more iron-rich foods, such as beans, lentils or red meat, or taking iron supplements, usually with iron(II) sulfate, ferrous gluconate, or iron amino acid chelate ferrous bisglycinate, or synthetic chelate NaFerredetate EDTA, will usually correct the anemia. Alternatively, intravenous iron can be administered.

Recent research suggests the replacement dose of iron, at least in the elderly with iron deficiency, may be as little as 15 mg per day of elemental iron. An experiment

done in a group of 130 anemia patients showed a 98% increase in iron count when using an iron supplement with an average of 100 mg of iron. Women who develop iron deficiency anemia in midpregnancy can be effectively treated with low doses of iron (20–40 mg per day). The lower dose is effective and produces fewer gastrointestinal complaints. The body apparently adapts to oral iron supplementation, so iron is often effectively started at a comparatively low dose, then slowly increased.

The difference between iron intake and iron absorption, also known as bioavailability, can be great. Scientific studies indicate iron absorption problems are worsened when iron is taken in conjunction with milk, tea, coffee and other substances. A number of methods that can help mitigate this, including:

Fortification with ascorbic acid increases bioavailability in both presence and absence of inhibiting substances, but is subject to deterioration from moisture or heat. Ascorbic acid fortification is usually limited to sealed, dried foods, but individuals can easily take ascorbic acid with a basic iron supplement for the same benefits. The primary benefit over ascorbic acid is durability and shelf life, particularly for products like milk, which undergo heat treatment.

Microencapsulation with lecithin binds and protects the iron particles from the action of inhibiting substances.

Using an iron amino acid chelate, such as NaFeEDTA, similarly binds and protects the iron particles. A study by the hematology unit of the University of Chile indicated chelated iron (ferrous bis-glycine chelate) can work with ascorbic acid to achieve even higher absorption levels.

Separating intake of iron and inhibiting substances by a few hours

Using nondairy milk (such as soy, rice, or almond milk) or goats' milk instead of cows' milk

Gluten-free diets can resolve some instances of iron-deficiency anemia, if it is a result of celiac disease.

Heme iron, found only in animal foods, such as meat, fish and poultry, is more easily absorbed than nonheme iron, found in plant foods and supplements.[14][15]

Iron bioavailability comparisons require stringent controls, because the largest factor affecting bioavailability is the subject's existing iron level. Informal studies on bioavailability usually do not take this factor into account, so exaggerated claims from health supplement companies based on this sort of evidence should be ignored. Scientific studies are still in progress to determine which approaches yield the best results and the lowest costs.

If anemia does not respond to oral treatments, it may be necessary to administer iron parenterally using a drip or hemodialysis. Parenteral iron involves risks of fever, chills, backache, myalgia, dizziness, syncope, rash, and with some preparations, anaphylactic shock. The total incidence of adverse events is much lower than that with oral tablets (where the dose needs to be reduced or treatment stopped in over 40% of subjects) and blood transfusions.

A follow-up blood test is essential to demonstrate whether the treatment has been effective; it can be undertaken after two to four weeks. With oral iron, this usually requires a delay of three months for tablets to have a significant effect.

Iron supplementation and infection risk

Because one of the functions of elevated ferritin (an acute phase reaction protein) in acute infections is thought to be to sequester iron from bacteria, it is generally thought that Parenteral iron supplementation (which circumvents this mechanism) should be avoided in patients who have active bacterial infections bacteraemia. Replacement of iron stores is seldom such an emergency situation that it cannot wait for such infections to be treated, although occasionally cases will arise where this is not possible, such as chronic osteomyelitis.

Iron deficiency protects against infection by creating an unfavorable environment for bacterial growth. Some studies have found iron supplementation can lead to an increase in infectious disease morbidity in areas where bacterial infections or where malaria are common. For example, children receiving iron-enriched foods have demonstrated an increased rate in diarrhea overall and enteropathogen shedding. Nevertheless, while iron deficiency might lessen infections by certain pathogenic diseases, it also leads to a reduction in resistance to other strains of viral or bacterial infections, such as Salmonella typhimurium or Entamoeba histolytica. Overall, it is sometimes difficult to decide whether iron supplementation will be beneficial or harmful to an individual in an environment prone to many infectious diseases; however, this is a different question than the question of supplementation in individuals who are already ill with a bacterial infection.

Epidemiology

Disability-adjusted life year for iron-deficiency anemia per 100,000 inhabitants in 2004.[16]   no data  less than 50  50-100

  100-150  150-200  200-250  250-300  300-350  350-400  400-450  450-500  500-1000  more than 1000

A moderate degree of iron deficiency anemia affected approximately 610 million people worldwide or 8.8% of the population.[17] It is slightly more common in female (9.9%) than males (7.8%).[17] Mild iron deficiency anemia affects another 375 million.

IRON RICH FOODS

The best way to prevent and treat anemia is to consume iron rich foods. The treatment of anemia may also be successful with the usage of iron supplements. When it comes to iron-rich nutrition, we can recognize two types of iron:

Heme iron: Iron found in hemoglobin in blood, therefore red meatNon-heme iron: Iron found in vegetables, dairy products and eggs

Non-heme iron: (iron found in vegetables) is harder to absorb than heme iron (found in meat) and that is why

vegetarians are at a greater risk of developing iron deficiency anemia.

Iron rich foods that are good sources of heme iron include: 

- Beef, chicken and pork liver

- Clams and oysters

- Fish and shrimp

- Turkey, chicken, beef and pork

 

 

 

 

 

 

 

Iron rich foods that are good sources of non-heme iron include:

- Fortified cereals, grains and pasta

- Beans and lentils

- Pumpkin seeds

- Canned beans

Today we are able to choose between a variety of iron rich foods and even the picky ones have an opportunity to have a healthy nutrition. First we will start by mentioning the best ones:

TOP TEN IRON RICH FOODS

- Red meat

- - Turkey and chicken

- Iron fortified foods (grains and cereals)

- Dark green vegetables such as spinach and kale

- Beans (kidney, lima, navy etc.) soybeans and lentils

- Liver

- Egg yolks

- Seafood such as fish, oysters, clams and shrimp

 

Not only do we have a plentiful of iron rich foods today but we also have iron fortified foods. These foods contain iron that has been added to them and they are especially good when it comes to “picky eaters” since

some of the natural resources of iron may sometimes appear tasteless. These foods include:

- Cereals

- Oatmeal

- Pasta

- Iron fortified bread

There are many other iron fortified foods as well, so make sure you look for them on labels while shopping for groceries.But why should we stop here. As we mentioned before there is a variety of choices when it comes to iron rich foods. For example: nuts, hazelnuts and almonds are a good source of iron and we can add curry, rosemary, cinnamon and sesame seeds to our daily diet to improve iron levels in our body. There are also many vegetables that can be added to this list of iron-rich foods and they include broccoli, parsley, brussel sprouts, swiss chard etc.

The biggest intake of iron is necessary during pregnancy, childhood and adolescence. These are the most sensitive stages of life and proper nutrition is the key for preventing anemia. Women in pregnancy, for example, need up to 27 mg of iron in their daily diet so it is crucial for them to eat iron rich foods, not only for them to be healthy, but for the baby’s development as well. Women who have two pregnancies close together or are pregnant with more than one child are at a greater

risk for having anemia if they are not careful during their pregnancy.

Iron from iron rich foods is best absorbed if those foods are consumed with vitamin C. And it is best if these two are combined together in your meals.

Here are some foods rich in vitamin C:

- Citrus fruit

- Green vegetables

- Apples

- Bananas

- Fortified juices

- Green vegetables

Proper nutrition is especially important for persons who have lost larger amounts of blood. This is why women need more iron during their periods. The dominating iron – rich foods in their nutrition should be fish, red meat, clams and oysters, dried fruit and beans. Some iron – rich foods are not only rich in iron, but they are

also rich in copper which helps enormously with the absorption of iron. These foods include seafood, liver, green vegetables, dried figs, apricots, etc.

You should note that it is best not to eat whole grains, which are rich in iron, in combination with other iron rich foods since they contain phytates that decrease iron absorption through food. The same note goes for spinach, which is rich in oxalate substances which decrease the absorption of iron.Unvarying nutrition, an exaggerated use of alcohol and coffee, vegetarianism, drastic diets for losing weight and an insufficient intake of iron through food are all possible causes of iron deficiency anemia. The consummation of groceries rich in vitamin C enlarges the absorption of iron, and it is highly recommendable to use vitamin C supplements (up to 2g daily). It would be best if every meal contained fish or meat and vitamin C.

Anemic persons should also spend much time in fresh air and walk at least one hour daily. Diverse nutrition, a regular intake of fresh fruits and vegetables as well as minimal consummation of alcohol, coffee, cocoa, aerated drinks and tea, are the best way to prevent anemia. If the iron intake through food is not sufficient, people suffering from anemia may also use supplements, which work best if taken on an empty stomach. Some may also use vitamin B and vitamin C supplements in addition to the corresponding therapy recommended by their doctor.

You can combine iron – rich foods into many delicious meals. You can take fresh apples beetroot and carrots and make a tasteful juice out of them by adding honey. Nettle is also very useful as you can make a salad out of it which you can combine with lemon juice and olive oil or you can drink nettle tea which is also very useful in fighting anemia.If you suspect that you have anemia, you should definitely talk to your doctor because sometimes an underlying illness may be the cause of your anemia. You should also be very careful with food allergies since some of the mentioned iron–rich foods may pose a threat of an allergic reaction. For example, many people are allergic to nuts and seafood and this is especially important to know when it comes to children since they are the most sensitive age group.

Children and toddlers also consume a lot of milk, and dairy products are not that good for the absorption of iron through iron–rich foods, so they are a risk factor for iron deficiency anemia. Toddlers need about 7 to 10 mg of iron a day which is a lot less from the needs of 18 mg in adults so you should be careful, when giving iron rich foods to your child, not to exaggerate since too much iron can be toxic and very dangerous for children.

IRON RICH BABY FOODS

The most important thing to remember when it comes to your child’s healthy nutrition is that iron is best absorbed when combined with vitamin C. Foods that are high in vitamin C help with the absorption of non heme iron and this is very useful, especially when it comes to children. Having this in mind, you can easily combine meals for your child. For example, cereals with fruit rich in vitamin C, or with vitamin C fortified juices is certainly a good choice for breakfast. Here you have iron from the cereals and vitamin C from the fruit or juice which makes it a great combination.At first, your newborn will receive all the amounts of iron it needs through breast milk which also contains vitamin C. Later your child will have the need for additional iron which can be compensated through iron fortified baby cereal. From this point your child will need extra iron which you can find in iron rich baby foods so make sure you check food labels in order to find the best of them. You can make iron rich baby foods in your own kitchen as well. Choose the best iron rich foods and turn them into mash or adjust the portions to your child’s needs.

Rho(D) Immune Globulin is a medicine given by intramuscular injection that is used to prevent the ..............................................................................................................................................................................

..........................................................................................

.......immunological condition known as Rhesus disease (or hemolytic disease of newborn). The medicine is a solution of IgG anti-D (anti-RhD) antibodies that suppresses the mother's immune system from attacking Rh-positive blood cells which have entered the maternal blood stream from fetal circulation. In a Rhesus negative mother Rho(D) Immune Globulin can prevent temporary sensitization of the maternal immune system to Rh D antigens, which can cause rhesus disease in the current or in subsequent pregnancies. With the widespread use of Rho(D) Immune Globulin, Rh disease of the fetus and newborn has almost disappeared. The risk that a D-negative mother can be alloimmunized by a D-positive fetus can be reduced from approximately 16% to less than 0.1% by the appropriate administration of RhIG., Rho(D) Immune Globulin is composed of IgG antibodies and therefore is able to cross the placenta. In rare cases this can cause a baby to have a weakly positive DAT (direct antiglobulin test) due to sensitization of fetal cells from mothers who have received multiple doses of Rho(D) Immune Globulin. However, no treatment is necessary as the clinical course is benign.

History

The first Rho(D) Immuno Globulin treatment "RhoGAM" was introduced by Ortho-Clinical Diagnostics, a subsidiary holding of Johnson and

Johnson, and was first administered on May 29, 1968 to a woman in Teaneck, NJ.

In 1996 ZLB Bioplasma (part of CSL Behring) was given approval to sell Rhophylac in Europe, and in 2004 Rhophylac was approved in the United States.

Manufacturing and prion transmission

Rho(D) Immune Globulin is a derivative of human plasma. In the manufacturing process steps are taken to eliminate bacterial and viral contamination. The most common way anti-D products are manufactured is by a form of the Cohn cold ethanol fractionation method developed in the 1950s. Variations of the Cohn method developed in the 1950s may not completely clear aggregates of immunoglobulins, which can cause problems for patients if administered intravenously, and is a primary reason why most anti-Ds are for intramuscular use only. A non-Cohn manufacturing variation is ChromaPlus process approved by the U.S. Food and Drug Administration (FDA) that is used to make Rhophylac.[8] Rho(D) immune globulin may trigger an allergic reaction, and there is the possibility of transmission of Creutzfeldt-Jakob disease as a residual risk.

Antepartum Administration

In a pregnancy where the mother is D-negative and the father is D-positive, there is a 50% chance that the fetus will be D-positive and the mother is therefore at risk for

D alloimmunization. These women are candidates for RhIG prophylaxis.

The medication has an FDA Pregnancy Category C. It is given by intramuscular injection as part of modern routine antenatal care at about 28 weeks of pregnancy, as recommended by the American College of Obstetricians and Gynecologists (ACOG). The '28 weeks' recommendation comes from the fact that it has been observed that 92% of women who develop an anti-D during pregnancy do so at or after 28 weeks gestation.

RhIG should also be given after antenatal pathological events that are likely to cause a feto-maternal hemorrhage. Applicable 'pathologic events' include accidents which may induce fetomaternal hemorrhage (motor vehicle accidents, falls, abdominal trauma), following procedures during pregnancy, and following spontaneous or therapeutic abortions.

Postpartum Administration

A D-negative mother who is not alloimmunized to D should also receive an appropriate dose of RhIG after delivery of a D-positive infant. After delivery, a cord blood sample from infants born to D-negative mothers should be tested for the D antigen. If the neonate is D-negative, no further RhIG is needed. However, if the infant is D-positive, the mother should have a postpartum blood sample screened for fetomaternal

hemorrhage in order to determine the appropriate dosage of RhIG to be administered. (the presence of residual anti-D from antepartum RhIG administration does NOT indicate ongoing protection from alloimmunization- repeat administration of RhIG is necessary).

The rosette test (see: erythrocyte rosetting) is a sensitive method to detect fetomaternal hemorrhage of 10 cc or more. A rosette test will be positive if fetal D-positive cells are present in the maternal sample, indicating a significantly large fetomaternal hemorrhage has occurred. A rosette test may be falsely positive if the mother is positive for the weak D phenotype and falsely negative if the neonate is weak D. (See Rh Blood Group System section on Weak D: If the rosette test is negative, then a dose of 300 micrograms of RhIG is given (sufficient to prevent alloimmunization after delivery in 99% of cases)., The RhIG dose suppresses by up to 30 cc of whole blood.

If a fetomaternal hemorrhage in excess of 30 cc has occurred, additional testing is mandatory in order to determine the appropriate dosage of RhIG to prevent alloimmunization. A positive rosette test should be followed by a quantitative test such as the Kleihauer-Betke test (acid/elution) or an alternative approach such as flow cytometry. See article on Kleihauer-Betke test for details on how the volume of fetomaternal hemorrhage is calculated.

The dosage of RhIG is calculated from the volume of fetal hemorrhage (in mL). Ex: 50 mL fetal hemorrhage / 30 ml = 1.667 (round up to 2) then add 1 = 3 vials of RhIG.

Postpartum RhIG should be administered within 72 hours of delivery. If prophylaxis is delayed, the likelihood that alloimmunization will be prevented is decreased. However, ACOG still recommends that RhIG be administered because partial protection still occurs., If the D-type of a newborn or stillborn is unknown or cannot be determined, RhIG should be administered.

Immune Thrombocytopenia (ITP)

Primary Immune Thrombocytopenia (ITP) is an acquired immune mediated disorder characterized by isolated thrombocytopenia, defined as a peripheral blood platelet count less than 100 x 109/L, and the absence of any obvious initiating and/or underlying cause of the thrombocytopenia. Symptoms of ITP include abnormal bleeding and bruising due to the reduction in platelet count. Rho(D) Immune Globulin Intavenous [Human; Anti-D] is indicated for use in non-splenectomized, Rho(D)-positive children with chronic or acute ITP, adults with chronic ITP, and children and adults with ITP secondary to HIV infection. Anti-D must be administered via the intravenous route when used in clinical situations requiring an increase in platelet count. The mechanism of action of anti-D is not

fully understood however, after administration the anti-D coated red blood cell complexes saturate Fcγ receptors sites on macrophages, resulting in preferential destruction of red blood cells (RBCs), therefore sparing antibody-coated platelets.[21] Anti-D is recommended as a first-line therapy for ITP, along with corticosteroids and intravenous immune globulin (IVIG).[22][23] WinRho SDF is an anti-D manufactured, distributed and marketed by Cangene Corporation in the US.

Contraindications

The following females are NOT candidates for RhIG:

D-negative females whose infant is known to be D-negative

D-negative females who have been previously alloimmunized to D (they have an anti-D antibody)

Any D-positive females (NOTE: women who test positive for the weak D phenotype should be considered D-positive and not receive RhIG.

Rhophylac manufactured by CSL Limited Brand names

. RhoGAM and MICRhoGam are brand names of Johnson and Johnson. Other brand names are: BayRHo-D, Gamulin Rh, HypRho-D Mini-Dose, Mini-Gamulin Rh, WinRho SDF (Cangene), Partobulin SDF (Baxter) and Rhesonativ (Octapharma). RhesuGam (NBI)

Routes of Administration

RhIG can be administered either by either intramuscular (IM) or intravenous (IV) injection, depending on the preparation. The IM-only preparation should never be administered IV due to the risk of complement system activation. Multiple IM doses should be given at different sites or at different times within the 72 hour window. Or, multiple IV doses can be administered according to the instructions in the package insert.

RhoGAM (rhod immune globulin human) ® and MICRhoGAM (rhod immune globulin human) ® Rho(D) Immune Globulin (Human) are sterile solutions containing IgG anti-D (anti-Rh) for use in preventing Rh immunization. They are manufactured from human plasma containing anti-D. A single dose of RhoGAM (rhod immune globulin human) contains sufficient anti-D (approximately 300 μg or 1500 IU)* to suppress the immune response to 15 mL (or less) of Rh-positive red blood cells. A single dose of MICRhoGAM (rhod immune globulin human) contains sufficient anti-D (approximately 50 μg or 250 IU)* to suppress the immune response to 2.5 mL (or less) of Rh-positive red blood cells.

Rho(D) Immune Globulin (Human) intended for intramuscular use and prepared by cold alcohol fractionation has not been reported to transmit hepatitis or other infectious diseases.7