Anemia: how it affects patients at different ages.

Every medical student and young doctor mentions anemia during a clinical examination of the patient. Here are some facts they need to understand.

When anemia is detected by a clinician at the bedside the hemoglobin has already fallen to 1/2 its normal value. Hence the doctor will miss anemia when the Hb is more than 7-8 gm/dl. Anemia is better detected in mucous membranes than skin. It is best looked for in the conjunctiva, on the surface of the tongue where a pale smooth tongue (loss of filiform papillae) is a give away. Compare the patient’s nail beds to your own to detect anemia. The skin of the palms is a poor place to look for anemia because many people have thick skin and callusses on the palm from the nature of manual work they do. If the palms are visibly pale (not pallor) then admit the patient for blood transfusion as the anemia is advanced!!! The palmar creases are not a good place to look for anemia as in pigmented races there is too much pigment in them and they are darker than the rest of the palm.  Remember that a low hemoglobin may be a factor in the manifestation of whatever other disease the patient is suffering from. A normal hemoglobin does not reflect a patient’s iron balance and they may still have a low serum iron and a low level of iron in the bone marrow. In an adult population anemia is rarely present by itself. When you find an anemic adult the first problem to be solved  is what has caused the anemia and then think what effect the anemia is having on the patient i.e. in a patient with ischemic heart disease anemia will precipitate or  worsen angina or heart failure and unless the anemia is corrected the patient will not respond to treatment.

Deficiency anemia in adult women of child-bearing age.

Many people with iron deficiency anemia have no symptoms at all. Of those who do, the most common symptoms include: Weakness. Headache. Irritability. Fatigue. Difficulty exercising (due to shortness of breath, rapid heartbeat). Brittle nails. Spoon shaped nails or koilonychia  are a sign of long-standing iron deficiency, it will rarely be seen in an urban population as any one with access to medical facilities will have been treated. Patients from rural areas or those living in abject poverty will exhibit this sign and the depressed nails persist for life even after correction of anemia. Sore tongue caused by accompanying vitamin B deficiency. Restless legs syndrome. Pica (an abnormal craving to eat non-food items, such as clay or dirt, paper products, or starch [eg, cornstarch]). Pagophagia (an abnormal craving to eat ice).

Girls and women are prone to iron deficiency on account of menstrual losses and iron loss during pregnancy. Multiple pregnancies, occurring very close together and accompanied by lactation, can cause iron deficiency even in those who have adequate access to food. Cumulative total requirements for expansion of the maternal RBC mass and fetal RBC production/fetoplacental growth are approximately 500 mg and 300 to 350 mg, respectively. Delivery results in the loss of approximately 250 mg. In the first trimester, approximately 1 to 2 mg/day of iron is needed due to normal gastrointestinal sloughing and the early pregnancy-related increase in RBC mass. By the second trimester, the demand increases to 4 to 5 mg/day due to requirements for increased maternal RBC production as well as fetal RBC production and fetoplacental growth. In the third trimester, the demand increases to approximately 6 mg/day due to ongoing maternal and fetal RBC production and fetoplacental growth.

In a 2018 series in which iron status was assessed in 299 healthy young women in the general population in Australia, 87 (29 percent) had iron deficiency. In a 2017 review of micronutrients deficiencies in the Middle East, the prevalence of iron deficiency in young healthy women ranged from 27 to 47 percent depending on the country. In a 2008 series of healthy young females in Italy, the prevalences of iron deficiency were 27 and 30 percent in athletes and non-athletes, respectively. So approximately 30% of healthy young women were deficient in iron in the bone marrow even when their hemoglobin was normal. The physiological requirement for iron in adult men and women is 1mg/day. Women require an additional .8 mg/day to make up for menstrual losses. In the poor countries of the world women cannot afford food like red meat to correct their losses coupled with the fact that men are given larger portion of all available food makes more than 50% of women iron deficient. To ensure replenishment of body iron stores please treat the patient for 3 months after the correction of anemia.

Babies born to anemic mothers will have iron deficiency themselves. Since the major source of iron in infancy is mother’s milk the babies will remain iron deficient in early life until weaned off milk and given iron rich solids. This is one reason for starting solid foods early. In mothers with iron deficient anemia, increasing severity of maternal anemia has been associated with decreasing neonatal hippocampal volume and production of brain-derived neurotrophic factor. Identifying and treating women with iron deficiency, who may not necessarily be anemic, may improve fetal/newborn ferritin levels. Hence the reccommendation that all women should be given oral iron and folic acid during pregnancy.  It may not be cost effective to check bone marrow iron in all prregnant women.Correlations between maternal and cord-blood ferritin levels have been observed, even in non-anemic mothers. In a longitudinal study of 185 individuals who were followed from infancy to the age of 19 years, those who had iron deficiency as infants for three or more months (or iron deficiency with severe anemia) had impaired cognitive functioning compared with those who did not have iron deficiency. The gap in cognitive functioning was greatest in those of low socioeconomic status, but persisted even in those with high socioeconomic status. This means low performance in school, poor ability to learn skills which will enable them to get better paid jobs. This means iron deficiency in the next generation. There is perpetuation of poverty and many youngsters are locked into the poverty cycle from their mother’s womb because of anemia in women.

Micronutrient deficiency is usually seen for multiple micronutrients. A common combination is iron and folic acid. Hence it is advisable to give oral iron and folic acid supplements to all women wishing to conceive and to those who are pregnant. It is advisable to give these supplements to lactating mothers as well. A gap of 2-3 years between pregnancies will help the mother to correct her deficiencies before the next child is conceived.

Grading Anemia.

  • Mild (Grade 1) – Hgb from 10 g/dL to the lower limit of normal
  • Moderate (Grade 2) – Hgb 8.0 to 9.9 g/dL
  • Severe (Grade 3) – Hgb 6.5 to 7.9 g/dL
  • Life-threatening (Grade 4) – Hgb <6.5 g/dL

When should the patient be evaluated for a cause other than iron deficiency? Promptly evaluate for other causes of anemia if there are any features of the anemia that suggest another condition or if testing for iron deficiency is negative (ie, if iron stores are adequate). Examples of features that suggest another cause include:

  • Extreme microcytosis (eg, mean corpuscular volume [MCV] <80 fL), suggestive of thalassemia
  • Macrocytosis (MCV >100 fL), suggestive of vitamin B12 or folate deficiency
  • Reticulocytosis due to hemolysis
  • Other cytopenias such as thrombocytopenia or neutropenia
  • Abnormally high white blood cell (WBC) count or platelet count
  • Abnormal RBC or WBC morphologies
  • Failure of the anemia to correct with iron supplementation

How much iron can food supply?

  • 3 ounces of beef liver, chicken or goat liver provides 3.5 mg of iron.
  • 1 cup of breakfast cereals enriched with iron, one cup of cooked beans one-half cup of tofu, 1 ounce of pumpkin, sesame, or squash seeds also provide 3.5 mg of iron.
  • 3 ounces of beef provide 2.1 mg or iron.
  • One-half cup of canned lima beans, red kidney beans, or chickpeas, one cup of dried apricots, one medium baked potato, one cup of cooked enriched egg noodles, one-fourth cup of wheat germ, 3 ounces of mutton, all provide 2.1gm of iron
  • An egg provides 1mg of iron.
  • 3 ounces of chicken, goats’ meat, fish, veal  provide .7mg of iron
  • .7 mg or iron is also provided by 1/2 cup of split peas (chanay ki daal), other lentils, one ounce of dried raisins, apricots, peanuts, roasted cashew, prunes and peaches, a cup of raw spinach, one medium stalk of brocoli, one cup of uncooked pasta, one slice of bread, one cup of brown rice.
  • Vegetables are a poorer source of iron. Cauliflower and cabbage provide .4 mg of iron.
  • Pomegranates, carrots, tomatoes and bananas all have .3 mg of iron in 3 ounces.
  • An apple is a poor source of iron 3 ounces or one large unpeeled apple  provides only .1 mg which resides in the peel!!! An orange has the same iron content,

This list gives vegetarian alternatives for people who do not eat meat. Vegetable food a relatively poor source of iron as the body may not be able to digest the iron from vegetables.

Anemia in adult men and post menopausal women.

Dietary deficiency of iron in an adult man is very unusual unless he has been institutionalised as in prison, psychiatric facilities or in a refugee or prisoner-of-war camp with nothing to eat but wheat or rice gruel. Try asking if he is out of  a job for some months. The same fate overtakes children in an orphanage as it does aged women living off family or stranger’s charity. Here is where a socio-economic history comes in.

Bleeding is the usual cause of anemia, in men and women ask about bleeding piles, and post menopausal bleeding in elderly women. Hidden or occult blood loss may occur because of the use of NSAIDs for arthritis, frozen shoulder etc. Symptoms of gastritis or reflux eosophagitis should also lead one to think of anemia. Use of aspirin or a platelet lowering drug can also cause sufficient blood loss from the gut. Fad diets such as the rice diet etc may also lead to anemia.

So what questions should you ask?

Do you feel unusually tired? How is your appetite? Have you made changes to your diet like stopping all red meat and eggs and avoiding chicken? Have you become a complete vegan? Have your economic circumstances declined: lost your job or your source of income? For women this happens when the husband dies or a son abandons her. Do you have someone to cook for you? For an elderly man the death of a spouse means no home cooked meals. Do you regularly take drugs for pain in your joints or frequent headaches? Are you bleeding from anywhere like bleeding piles, or frequent nose bleeds or bleeding from your gums? What color is your stool? Do you have heart burn specially on bending down or late at night after a heavy meal? Are you on blood thinners like aspirin or Lowplat?

When should suspect that in this case of anemia chronic kidney disease is on the hidden agenda? Often there are no recognizable renal symptoms. A 38-year-old woman was refered to my Dialysis unit for initiating dialysis and a work up for a renal transplant. She had unexplained anemia for 5 years unresponsive to hematinics. She came from a well to do family, had access to good food and did not have fads about her food. Her menses were regular and “no more than usual”. She had 3 children the youngest being 10 years old. Her husband was a doctor and had consulted various competent colleagues. A surgeon had suggested a pre-emptive hysterectomy! An astute physician noted that her reticulocyte count was always low and her serum uric acid was high. Serum creatinine was 1.4 mg/dl. In non-pregnant women a persistently high uric acid does not mean gout which is predominantly a male disease but it does mean that there is something wrong with the kidneys. Her Hb was 6gm/dl, creatinine clearance was 17 ml/min the ultrasound showed shrunken kidneys. Her physician decided on a blood transfusion, she had “panel reactive antibodies” and a matching donor was found with difficulty. She had an acute reaction to the transfused blood and went into acute-on-chronic renal failure. She was put on maintenance dialysis and received a kidney from her younger brother six months later and survived on immunosuppression for 22 years.

Kidney disease may be silent but try asking about a past history of nephrotic syndrome or swollen feet, persistent hypertension, recurrent UTI, renal stones that have been passed or operated upon or which are still there. Uncontrolled hypertension should alert you underlying renal disease ask about large kidneys or polycystic kidneys diagnosed in the past in the patient or a relative. All these may present as unexplained anemia.

Anemia may be detected when it affects a patient with ischemic heart disease or heart failure. For someone with angina either the onset of angina may coincide with the onset of anemia or the angina may become more frequent or last longer and the dosage of drugs required to control the angina is increased. So be suspicious if angina or heart failure become worse, and look for anemia.

Anemia and the size of RBCs. Once you have asked for a blood complete picture a persistent picture of microcytosis should make you think of thalassemia. If the RBCs are large then it is known as macrocytosis. This is not synonomous with macrocytosis which is diagnosed when there is a persistence of nucleated and binucleated RBCs along with a large size. This shows lack of synchrony between maturation of an RBC, reduction in size and loss of the nucleus. This maturation synchrony depends on the presence of adequate amounts of vitamin B12 and folic acid. So megaloblasts caused by low B12 levels are seen in pernicious anemia in the elderly, because of lack of intrinsic factor in the stomach wall, in young people from tuberculosis or ulcerative colitis affecting the terminal ileum and interfering the absorption of B12 and intrinsic factor complex, and drugs interfering with B12 or folate metabolism.

Megaloblastic anemia is seen with the following drugs:  Antacids, Azathiaprin, Cytosine arabinoside, Cladrebine, Cemetidine and other H2 receptor blockers,  Fludarabine, Fluorouracil, Gadolinium, Gemcitabine, Allopurinol, Capecitabine, Lamivudine, Leflunomide, Mercaptopurine, methotrexate, Mycophenolate mofetil, Zidovudine.

Macrocytosis is seen in: Aminosalicylic acid, Ampicillin and other penicillins, Chloramphenicol, Dapsone, Estrogens and other hormone contraceptives, Erythromycin, Metformin, Phenytoin, Nitrofurantoin, Thoguanine, Valproic acid.

Drugs which can cause hemolysis in the presence of G-6-PD deficiency are: Dapsone (hemolysis in individuals with G6PD deficiency), Methylene blue, Nitrofurantoin, peglioticase, Primaquine.

Thiamine responsive megaloblastic anemia. There is a form og megaloblastic anemia which responds to the administration of thiamine rather than folic acid or Vitamin B12.

Multifactorial anemia occurs in many diseases caused by absence of or inability to utilise vitamins for example: Alcohol, Liver disease, Human immunodeficiency virus infection (and therapy), Myelodysplastic syndrome, Hereditary stomatocytosis, Hypothyroidism, Pregnancy, Aplastic anemia, Multiple myeloma, Bariatric surgery, Down syndrome, Copper deficiency.

Anemia may be the harbinger of something sinister.

The cause of anemia in a malignancy is usually multifactorial. There may be bleeding from thrombocytopenia sometimes caused by bone marrow infiltration and or the production of immunoglobulins secreted by the tumour. There may be external bleeding, internal bleeding, impaired intake of nutrients or malabsorption of nutrients. The use of anticoagulants to prevent or treat deep vein thrombosis may be a cause.

Bone marrow replacement — Leukemias, lymphomas, and plasma cell dyscrasias are hematopoietic malignancies that commonly involve bone marrow, supplanting normal hematopoiesis and resulting in myelophthisis with anemia and other cytopenias. Solid tumors can also produce anemia by involving the bone marrow space through metastasize.

Both solid tumors and hematologic malignancies may give rise to MAHA (microangiopathic hemolytic anemia). However, in contrast to leukemia-associated MAHA, which is generally due to DIC with risk of hemorrhage from consumptive coagulopathy (as in acute promyelocytic leukemia), solid tumor-associated MAHA is generally thrombotic, with an increased risk for thrombotic complications and renal failure. The solid tumors most commonly associated with MAHA are mucinous adenocarcinomas (eg, gastric, breast, pancreas, prostate, lung).

Remember anemia may be the main factor you are treating or it is a factor which is making the prognosis worse and has to be dealt with. Even when correcting the anemia does not improve the length of survival it does improve the quality of life.

 

 

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shaheenmoin

I am a Professor of Medicine and a Nephrologist. Having served in the Army Medical College, Pakistan Army for 27 years I eventually became the Dean and Principal of the Bahria University Medical and Dental College Karachi from where I retired in 2016. My passion is teaching and mentoring young doctors. I am associated with the College of Physicians and Surgeons Pakistan as a Fellow and an examiner. I find that many young doctors make mistakes because they do not understand how they should answer questions; basically they do not understand why a question is being asked. My aim is to help them process the information they acquire as part of their education to answer questions, pass examinations and to best take care of patients without supervision of a consultant. Read my blog, interact and ask questions so that I can help you more.

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