2015 L2 Case 1 pregnant lady

Iron Deficiency Anaemia

A condition characterized by a gradual decrease of iron in the body leading to insufficient production of healthy red blood cells. Four main causes:

• Decreased Fe intake

• Increased Fe requirement

• Impared Fe absorption

• Chronic blood loss

Role of Iron

Haemoglobin, Nicotinamide adenine dinucleotide dehydrogenase.Average male = 4g in body, 75% in form of haemoglobin and myoglobin.

Iron absorptionMale : 12 - 31µmol/L

Female: 9 – 30 µmol/L

Iron absorption

As body has no way to discrete iron, regulation is done by regulating the absorption of iron from our diet. Regular, mixed diet contains ~18mg of iron.

Dietry iron either classed as inorganic iron or haem iron.

~2mg of iron lost per day.

How Hepcidin regulates iron absorption

• Low pH in stomach reduces inorganic Fe3+ into Fe2+ ions (absorbed by DMT-1)

• DMT-1 expression changes dependant on iron status

• Haem iron absorbed directly by specific duodenal enterocyte transporter (HCP-1)

• Hepcidin down regulates ferroportin levels when Fe levels are high

• Hepcidin is regulated by hypoxia and Fe deficiency

Iron Transport

Iron absorbed by duodenum is released into blood stream, then binds to transferrin. Transferrin binds to transferrin-receptors on developing erythrocytes and are internalised.

Fe2+ oxidised to Fe3+ by Hephaestin, then converted back by erythrocytes.

Iron storage

~25% of total body iron is in storage in two forms: Haemosiderin, Ferritin.

Haemosiderin - Collective name for variety of iron containing proetin deposits (visualised using Perl’s stain - blue).

Iron deficiancy anemia (I.D.A)

3 stages:

1. Progressive loss of stored iron - Minimal symptoms, RBC normal production

2. Stored iron & iron in transferrin is exhausted, - non-specific/ minimal symptoms. Hb level drop gradually

3. Frank anaemia

Fe deficiency impact

• Microcytosis

• Hypochromia

• Poikilocytosis

• Reticulocytopenia

• Target cells

Poikilocytosis

The presence of abnormal red blood cell shapes in the blood, often associated with different types of anemia.

Reticulocytopenia

A condition characterized by a decrease in the number of reticulocytes (immature red blood cells) in the blood, indicating reduced bone marrow activity in erythropoiesis.

Effects of Fe deficiency

Fe important for several enzymes, more systemic effects can be found, especially epithelial cells. Signs include:

• Glossitis: Smooth, inflamed tongue.

• Koilonychia: Spooning fingernails.

• Angular stromatitis: Lesions at the corner of the mouth.

• Pica.

• Behavioural difficulties.

Iron deficiency treatment

Can vary significantly. For most patients only minor interventions required:

• Dietry changes

• Vitamin C

Some patients requre supplementation

• Ferrous fumarate

Haemoglibinopathies

Inherited haemoglobin disorders (e.g. Thalassemia). The most common single gene disorders (7% population are carriers). Classified as:

• Structural defects

• Rate of synthesis defects

Mean Cell Volume (MCV)

A measure of the average volume of red blood cells, used in the evaluation of anemia.

Full Blood Count (FBC)

A common blood test that measures various components of blood, including red blood cells, white blood cells, and platelets.

Hepcidin

A hormone that regulates iron homeostasis in the body, affecting iron absorption and distribution.

Ferritin

A large globular protein that stores ~66% of bodily iron, reflecting the total body iron stores, each sphere holding 5000 iron ions. Transferrin is a B-globulin protein which can carry 2 Fe3+ ions per molecule. An acute phase reactant.

Female 10-150 μg/L

Male 25-350 μg/L

Hypochromia

A condition where red blood cells are paler than normal, often associated with iron deficiency. Hb <100g/L.

Also indicative of thalassemia.

Microcytosis

The presence of smaller than normal red blood cells, common in iron deficiency anemia and thalassemia. MCV <70fl (Reference range 83-100fl.

Erythropoiesis

The process of producing red blood cells from erythroid progenitor cells.

Reticulocyte

An immature red blood cell, indicating the activity of bone marrow in erythropoiesis.

Anaemia of Chronic Disorder

A type of anemia that occurs in the presence of chronic inflammation, leading to altered iron metabolism.

Thalassaemia

An inherited blood disorder (haemoglobinopathy) that affects the production of hemoglobin, often resulting in microcytic, hypochromic anemia.

Classified by which globin genes are implicated and how many:

• Alpha Thalassaemia

• Beta Thalassaemia

Beta Thalassaemia

Most clinically “important” Thal class. Caused by beta global gene mutations:

• Point muations

• mRNA disruption

Three recognised forms:

• Beta Thalassaemia minor.

• Beta Thalassaemia intermedia.

• Beta Thalassaemia major

Beta Thalassaemia Minor

Mildest form, sufferers often unaware. Inheritance of a single mutated gene. Analysis reveals:

• Microcytic, hyprochromic red cells

• Elevated red cell count

Differential

Mean cell haemoglobin parameters are key (27-31 pg/cell), In B Thal value = <27

Serum ferritin also useful:

• 10-300 ng/ml in adult females, 25-350 ng/ml in adult males.

• Reduced levels in iron deficiency

• Normal/ raised levels in thalassemia

Beta Thalassaemia Major

Inheritance of two defective Beta-globin genes. Patients present:

• Severe anaemia

• Hepatosplenomegaly

• Skeletal deformaties

FBC reveals:

• Microcytic, hypochromic red cells.

• Elevated red cell count.

• Evidence of haemolysis.

• Normoblast

Variant Haemoglobins

Due to defects in beta-globin gene synthesis it is possible for other globin chains to be synthesised - HbF is a common finding in Beta Thal Major.

• Hbα2γ2

• 98% of total Hb

Variant haemoglobin can be detected using Hb electrophoresis

Beta Thalassaemia Intermedia

Includes cases of beta-thal which exhibit symptoms of disease but do not require regular transfusion (Hb levels stable ~70 g/L.

Different mechaninisms behind intermedia:

• Mild Beta Thal mutations.

• Co-inheritance of increased γ-globin synthesis mutation.

• Co-inheritance of alpha thalassaemia mutations

Alpha Thalassaemia

Mutations within alpha globulin genes. Four phenotypic groups:

• Silent carriers.

• Alpha thalassaemia trait.

• Haemoglobin H disease.

• Barts Hydrops fetails.

Alpha globulin gene loss often due to deletion (9 large scale deletions associated, each linked to particular ethinc groups).

Improper meiotic cross-over is the cause of many alpha-thal mutations.

Silent carrier

Caused by loss of single alpha globin gene. Routine haematology analysis would not reveal any abnormality.

DNA analysis required to completely identify silent carriers (multiplex PCR).

Cooley's Anaemia

Another name for Beta Thalassaemia Major, characterized by severe anemia and splenomegaly in affected infants.

HbH disease

Deletion of 3 globin genes (common is SE asian populations. Moderately anaemic (80g/L). Microcytic, hypochromic anaemia.

Red cell inclusion bodies, HbH (5-35% of all Hb), demonstrated using redox dyes.

HbH is a functionally useless haemoglobin tetramer.

Barts hydrops fetalis

Most severe alpha thal (deletion of 4 alpha globin genes). No functional Hb produced after 10 weeks gestation.

Functionally useless tetramers produced:

• Hb H

• Hb Barts (4 γ globin genes)

Barts pregnancy usually terminates in third trimester

Haemoglobinopathies management

No current practical cure. Transfusion support is required: Maintain Hb 100-120 g/L, Helps suppress erythropoiesis. Two main complications:

• Iron overload

• Transfusion reactions

Transfusion reaction

An adverse response of the immune system to transfused blood products, which can be severe.

Glossitis

Inflammation of the tongue, which can be a symptom of iron deficiency.

Koilonychia

A nail disease that leads to spoon-shaped nails, often associated with iron deficiency.

Antenatal care

Healthcare provided to pregnant women to monitor and improve maternal and fetal health.

Chronic blood loss

A slow and often undetected loss of blood over time, which can contribute to iron deficiency.

Transferrin

A blood plasma protein that binds iron and transports it throughout the body.

Hepatosplenomegaly

Enlargement of both the liver and spleen, often associated with blood disorders.

Dietary iron

Iron obtained from foods, categorized as haem iron from animal sources and non-haem iron from plant sources.