Chapter 22: Autoimmune diseases, Pernicious Anemia, Hemolytic Anemia
PERNICIOUS ANAEMIA (PA)
This is megaloblastic anemia due to deficiency of vitamin B12, because of malabsorption, which is believed as an autoimmune phenomenon to gastric parietal cells and their products.
Age and Sex
PA is more common in a temperate climate. It affects both sexes equally. It is rare under the age of 30; the average presenting age is 60 years.
Signs and Symptoms
These are of severe anemia:
- The patient is pale and slightly jaundiced.
- Gastrointestinal manifestations are a result of vitamin B12 deficiency like a sore tongue, which appears as beef red.
- Neurological manifestations are serious. The patient may have paraesthesia, numbness, and ataxia.
Gastric biopsy Shows gastric atrophy affecting the acid and pepsin-secreting portion of the stomach and the antrum is unaffected.
- There are gastric parietal cell autoantibodies, virtually present in all patients. These are present in 20-30% of first-degree relative and 5% in the normal population.
- Autoantibody against intrinsic factor (IF) which are of two types, one is blocking, and second is a binding antibody. Blocking autoantibody reacts with the combining site for vitamin B12 on the intrinsic factor (IF) and is found in most patients (>70%). Binding autoantibody reacts with another epitope on the intrinsic factor (IF).
- Peripheral blood shows macrocytosis (MCV > 100ft).
- The reticulocyte count is low.
- Neutrophils are typically hypersegmented.
- Bone marrow is hypercellular and decreased myeloid: erythroid ratio. RBC precursors are large with immature nuclear morphology.
- Vitamin B12 estimation will show a deficiency.
- Schilling test will confirm the diagnosis.
Vit-B12 replacement therapy corrects all but not the neurological abnormalities.
Patients with PA develop gastric polyp very frequently and there are more chances to develop malignant tumors of the stomach.
AUTOIMMUNE HEMOLYTIC ANAEMIA (AHA)
Autoimmune Haemolytic Anaemia may be :
- Primary OR
- Secondary to other causes like malignancy or inflammatory diseases.
Autoimmune Hemolytic Anaemias are due to:
- Warm autoantibody, which reacts at 37Co.
- A cold antibody called cold autoimmune H.A, which reacts below 37Co.
- Warm-Ab Autoimmune Hemolytic Anaemiaare :
- Idiopathic warm AHA.
- Secondary types of AHA is due to :
- connective tissue diseases like SLE, Rheumatoid arthritis.
- Autoimmune hepatitis.
- Lymphoproliferative disorders like lymphocytic leukemia, Non-Hodgkin’s lymphoma.
- Viral infections like Hepatitis B-virus.
Cold-Ab Autoimmune Hemolytic Anaemia: This may be:
- Idiopathic cold AHA.
- Lymphoproliferative disorders e.g. chronic lymphocytic leukemia.
- Infections e.g. EBV, Mycoplasma Pneumoniae.
Management of Autoimmune hemolytic Anaemia can be summarized as follows
Mechanism of Hemolysis
- The majority of 80-90% has RBC autoantibodies and reacts with their target RBC.
- Warm AHA: – The circulating RBC are coated with IgG. Complement is activated. In addition, components of complement are present on RBC. A warm autoantibody is mostly against Rh-antigen.
- Typically, these coated RBC are sequestered in the spleen and occasionally in the liver.
Drugs induced hemolysis may lead to hemolytic anemia.
Mechanism:- There are three methods by which hemolysis can take place due to drugs.
- The most common cause of hemolytic anemia is by a drug a-methyldopa. Where IgG-type autoantibody to Rh-antigens is formed.
- The drug attaches to RBC surface antigens making them immunogenic. There will be a bypass of Th cell and B-L is activated and gives rise to anti-Rh Ab.
- In this method, the drugs act as haptens like penicillin and cyclosporins. These drugs attach to a protein on the RBC. Now, this becomes immunogen and cause immune damage.
- This mechanism is seen with the drug-quinidine (hapten), this binds to plasma protein to become immunogenic. This complex is absorbed on to RBC.