Anemia is a manifestation of underlying deficiency of hemoglobin, an iron containing pigment present inside the RBCs (red blood cells) and it is a laboratory diagnosis and can have myriad health consequences.

The normal hemoglobin for adult men is 13 to 17 g/dl, and for adult women is 12 to 15 g/dl. As per the WHO (World Health Organization) criteria anemia is defined as a hemoglobin level < 13g/dl for men and <12 mg/dl for women.

Hemoglobin is a complex of heme (an iron containing pigment) & globin (a protein substance) and has a vital role in the transport of oxygen in the blood from the lungs to the body cells. It also helps in bringing some of the carbon dioxide from the cellular level back to the lungs for expelling it out.

Normal RBC & hemoglobin physiology

The normal adult men contain about 5 – 6 million of RBCs per cubic millimeter & for women this number is about 4 – 5 millions similar units. The mature RBC is about 8 micrometer in diameter, biconvex and is synthesized in the bone marrow. The production RBCs require a hormone called as erythropoietin (EPO) that is secreted in the kidneys.

RBCs are produced from stem cells contained in the bone marrow. It begins with division of pluripotent hematopoietic cells that are capable of producing RBCs, WBCs (white blood cells), and platelets. From these stem cells erythroid line of cells are produced and these erythroid cells repeatedly divide and generate RBCs.  Hemoglobin is incorporated into the RBCs during their formation.

Types of anemia/ classification

Anemia can be diagnosed functionally (physiologically) into three major categories including;

* Hemorrhage/ hemolysis related
* Hypo-proliferative related (problem with bone marrow proliferation of RBCs)
* Maturational disorder related

Hemorrhage/ hemolysis related;

* Blood loss due to bleeding
* Intravascular hemolysis (destruction of RBCs in the blood vessels)
* RBC membrane abnormalities
* Metabolic defects
* Immune destruction of RBCs
* Hemoglobinopathies
* Fragmentation hemolysis etc

The hypo-proliferative

* Iron deficiency
* Bone marrow damage (e.g. infiltrative lesions)
* Decreased stimulation (e.g. Kidney diseases, inflammations)

Maturational disorders;

* Iron deficiency
* Thalassemia
* Sideroblastic anemia
* Vitamin B12 deficiency
* Folic acid deficiency
* Drug toxicities etc.

Clinical manifestations

Examination findings usually include;

* Pale skin and/or mucus membranes (nail beds, wrinkles of the palm etc)

Anemia makes the heart to pump more blood to compensate for reduced oxygen concentration in the blood and this will produce findings including;

* Strong arterial pulses (e.g. Radial pulse)
* Forceful heart beat
* A heart murmur (systolic type)

Diagnosis

A mild anemia may be missed clinically but moderate & severe grades of anemia are rarely missed clinically.  Irrespective of this certain investigations are necessary and they assist with;

* Laboratory confirmation of anemia &
* Help in detecting the cause of the anemia.

Investigations to confirm anemia include;

* Blood tests;

CBC (complete blood count)
Peripheral smear

The following CBC values are obtained including:

* Hemoglobin (normal: 13 g/dl for men & 12 g/dl for women)
* Hematocrit (normal: 45 to 52% for men & 37 to 48% for women)
* MCV (mean cell volume) – normal: 80 to 100 femtoliters
* MCH (mean cell hemoglobin) – normal: 27 to 32 picograms?* MCHC (mean cell hemoglobin concentration) – normal: 32 to 36%

MCV test gives an idea of the morphology of RBCs. For example small RBCs may be seen with conditions like iron deficiency & lead toxicity anemia, large RBCs (megaloblasts) are seen with conditions like Vitamin B12 or folate deficiency

Investigations to helping detecting the cause of anemia include;

* Peripheral smear
* Reticulocyte count
* Serum iron studies (total iron, ferritin, iron binding capacity etc)
* Vitamin B12, folate levels
* Thyroid tests (T4, T3, and TSH etc)
* Bone marrow studies etc.

A peripheral smear helps in identifying the morphological features of blood cells and also to look for specific anemic disorders like sickle cell anemia etc.

Reticulocytes are fresh batch of RBCs just released from the bone marrow. The normal range of these cells is around 1 to 2% of the circulating RBCs. A reticulocyte count is a key tool in the initial diagnosis of anemia. An increased reticulocyte count along with anemia indicates the bone marrow and the steps associated with RBC production are ok and that means the cause of anemia is hemolysis or blood loss.

A bone marrow examination is done when the reticulocute count is decreased, anemia is of normal size/shape and coloration (normocytic, normochromic) and iron storage of body is normal. These findings suggest strongly a bone marrow pathology like any infiltrative diseases, myelofibrosis etc.

Management

General measures of anemia management include;

* Stabilization of the patient
* Hospitalization if necessary
* Oxygen supplementation (if patient breathless)
* Avoiding strenuous activities
* Nutritious diet etc.

Specific measurements include;

* Iron deficiency anemia:

Oral iron supplementation (mild)
Parenteral iron supplementation (moderate to severe)

* Megaloblastic anemias:

Vitamin B12
Folic acid

* Chronic kidney diseases:

Recombinant EPO (erythropoietin)

* Many other conditions like myelofibrosis are appropriately treated

Blood transfusion/ packed RBCs may be required for severe anemia cases (especially related with blood loss type).

There are a number of coagulation factors in the blood, mostly proteins that are converted from inactive to active forms whenever the wall of a blood vessel is damaged.

Anyone who suffers from haemophilia is deficient in a factor, most commonly Factor VIII Haemophilia A, and is vulnerable to internal or external bleeding.

Symptoms often begin in infancy and continue through life. Their severity varies among individuals and milder forms of haemophilia may not be apparent until adulthood.

What causes haemophilia?
Haemophilia A is a genetic, or inherited, condition. It is an x-linked genetic defect, sometimes called sex-linked because it is passed on from a mother to her son. In almost every case, there will be a history of the disease within the family.

All of our inborn characteristics – our colour of hair, eyes and so on – are controlled by the action of one or more pairs of genes. Half of each pair comes from one parent, and the other half from the other parent. Every human being has vast numbers of these genes, which are contained in structures called chromosomes, and in each of us a few of the genes are faulty. This is what occasionally causes problems.

Most women have two x chromosomes, while men have one x and one y. In the most common from of x-linked inheritance, the female sex chromosomes of a mother who is unaffected carry one faulty and one normal gene. Her sons therefore have a 50/50 risk of inheriting her faulty gene and thereby inheriting the disorder themselves.

Each of her daughters has an equal chance of being a carrier like the mother – usually unaffected by the disease, but capable of transmitting it to her sons. x-linked disorders cannot be passed down from male to male, so a father who has haemophilia cannot pass it on to his sons.

This is the mechanism by which haemophilia is transmitted from one generation to the next. However, haemophilia will sometimes also appear spontaneously without any known family history of one disease.

How is haemophilia diagnosed and treated?
Apart from the clinical symptoms, laboratory blood analysis for Factor VIII remains the mainstay of haemophilia diagnosis. Treatment almost always involves the transfusion of concentrates of blood products which contain this coagulation factor. Extra transfusions generally have to be given if either surgery or dental care is needed.

What can I do myself?
Haemophilia sufferers must protect themselves adequately before engaging in sports, since a minor fall or blow could result in a severe bleeding episode. Contact sports are best avoided and can be replaced with lower risk, non-contact activities including walking, golf and swimming. Aspirin impairs the formation of blood clots, so it should not be taken.

When should I see my doctor?
Any episode of abnormal bleeding calls for medical consultation. People with severe haemophilia often have to seek emergency treatment over a minor cut or scrape, and some carry emergency supplies of Factor VIII to inject into themselves if necessary.

What will the doctor do?
Laboratory tests on a sample of blood will determine if coagulation is normal and will test the level of Factor VIII. Other tests may be done to see if another clotting problem is causing the symptoms. During a bleeding episode Factor VIII will usually be administered. Although frequent transfusions may also be needed, blood products are now treated to prevent the possibility of the transmission of hepatitis or AIDS viruses.

Is haemophilia dangerous?
Severe haemophilia can be life-threatening if not treated promptly. Even mild haemophilia can cause joint damage and disability if untreated.

Haemophilia can also lead to psychological problems. The parents of a child with haemophilia may become overly protective, making the child feel different from other children. In recent years, some people with haemophilia have suffered the effects of AIDS. Before blood tests for AIDS antibodies were developed, many haemophilia patients received blood products contaminated with the AIDS virus.

Symptoms of Haemophilia
*Serious bleeding or haemorrhaging from a trivial injury.
*Blood-filled swellings inside the skin.
*Blood in the urine.
*Bleeding into the joints, causing a painful arthritis.

What can I do to avoid haemophilia?
As it is an inherited condition you cannot avoid haemophilia, but you can avoid passing it on to your children. Men do not pass the disease on to their sons, but women – who do not appear to have haemophilia – can transmit it to their male offspring.

A simple blood test will identify those who are carriers of haemophilia. If any males in your family have had this condition and you are planning to have children, you may want to consider having this test. You may also wish to see a genetic counsellor for further information, so ask your GP to refer you.