Thalassemia in PregnancyBassem Gerges

2nd of September 2014

The Basics - Haemoglobin• Main function to carry O2 to tissues and to return CO2 from the

tissues to the lungs

• Three types of haemoglobin Haemoglobin A (dominant after the ages of 3-6 months) Haemoglobin F Haemoglobin A2

• Normally 4 α-globin chains mapped to short arm of Chromosome 16 2 β-globin chains mapped to short arm of Chromosome 11

α-Thalassemia• Caused by deletions of one or more of the four α-globin genes

• α-Thalassemia trait is either α+ (three normal α-genes) or α0 (two normal α-genes) Usually asymptomatic Important to identify as may become anaemic in pregnancy

• α-Thalassemia major results if both parents have α0 and there are no functional α-genes (Hb Barts) Incompatible with life Foetus becomes severely hydropic

α-Thalassemia (cont’d)• Haemoglobin H disease

Three α-gene deletions Clinically mild disease May require occasional transfusion of RBC Not considered “transfusion dependent”

β-Thalassemia• Arise out of mutations in the β-globin genes

Decreased (β+) genes Absent (β0) genes As with α-thalassemia, in β-thalassemia the β-globin chains are structurally

normal but quantatively reduced

• β-Thalassemia trait (minor) Generally asymptomatic May become anaemic in pregnancy Clinically manifestations

Minimal hypochromic microcytic anaemia Increase in Haemoglobin A2 (α2δ2)

β-Thalassemia major• Inheritance of a defective β-globin gene from each parent

• Severe anaemia becomes apparent at 3-6 months after birth with the switch to β-chain production

• Fatal within a few years without regular transfusions

• Children can now survive to the second or third decade

• Also known as Mediterranean anaemia or Cooley anaemia

β-Thalassemia major (cont’d)• Clinical features

Marked anaemia from Modest decrease in haemoglobin synthesis Marked shortening of red cell life span due to aggregation of insoluble excess α-

chains Ineffective erythropoiesis Relative folate deficiency

Marked hepatic- and splenomegaly Excessive red cell destruction Extramedullary haemopoiesis Iron overload from repetitive transfusions

Distortion of skull, facial bones, and long bones because of erythroid marrow expansion

β-Thalassemia major (cont’d)• Clinical features (cont’d)

Thalassemic red cell morphology Marked microcytosis, hypochromia, target cells and extensive changes in size and

shape

Increased Haemoglobin F (α2γ2) Generalised haemosiderosis

Chronic haemolysis Ineffective erythropoiesis Repeated transfusions

Screening for Thalassemia• SOGC

FBC and HbEPG for all women from an ethnic background at increased risk Individuals with an MCV < 80 fL or MCH < 27 pg can have α- and/or β-thalassemia and/or iron

deficiency anaemia β-thalassemia trait can be reliably diagnosed by haemoglobin electrophoresis, with HbA2 and

HbF quantitation Patients with β-thalassemia trait have an elevated HbA2, i.e., > 3.5%

In patients with a low MCV, but with a normal Hb EPG and HbA2 and HbF quantitation, the differential diagnosis includes iron deficiency anaemia and α-thalassemia. A serum ferritin and a smear to screen for the H bodies of α-thalassemia are therefore required

HbEPG will allow identification of Hb variants, such as HbS, C, D, and E The finding of any abnormality requires screening of the partner

FBC, smear for H bodies, Hb EPG, and HbA2 and HbF quantitation If both partners are found to be carriers of haemoglobin mutations (i.e., any combination of

thalassemias and Hb variants), they should be referred for genetic counselling, ideally in the pre-conception period, or as early as possible in the pregnancy

Prenatal Diagnosis• Prenatal diagnosis by DNA analysis of chorionic villi or amniocytes should be offered to

all carrier couples at risk

• For couples at risk of severe α-thalassemia who decline invasive prenatal diagnosis, or who present after 20 weeks of gestation, ultrasound assessments in a tertiary centre to determine the foetal cardiothoracic ratio could be offered Shown to be a reliable mean of identification of a foetus with Hb Bart’s hydrops fetalis A cardiothoracic ratio level equal to or greater than 0.5 identifies all affected pregnancies and has

a false positive rate of 8%

• The finding of hydrops fetalis on ultrasound in the second or third trimester in women with an ethnic background that has an increased risk of α–thalassemia should prompt immediate investigation of the pregnant patient and her partner to determine their carrier status for α-thalassemia.

Management• Preimplantation genetic diagnosis with IVF

• Iron chelation therapy with desferrioxamine used by women with β-thalassemia should be ceased

• Check and optimise any endocrine and cardiac dysfunction prenatally

• Need iron and folate oral supplements throughout pregnancy Should not be given parenteral iron Consider IM folate if not responding Transfusion may be required prior to delivery

• Prenatal Diagnosis

• Continuation vs Termination of Pregnancy

References• Handbook of Obstetric Medicine, Catherine Nelson-Piercy

• SOGC Carrier Screening for Thalassemia and Hemoglobinopathies in Canada

• Essential Haematology, AV Hoffbrand, JE Pettit, PAH Moss

• Pathology, Board Review Series

• www.uptodate.com

Thank you