Haemoglobinopathies

1. Haemoglobinopathies

2. -inherited conditions • - haemoglobin is abnormal. • - a haem unit made up of an iron &protein. • - 97% of adult Hb (HbA) has two α- and two β-chains • -is HbA2 and is composed of two α- and two δ-chains. • -Fetal Hb (HbF) has two α- and two γ-chains

3. - by 6 months of age this has been replaced by adult haemoglobin. • -. Blood is examined by electrophoresi • Thalassaemia • -The basic defect is a reduced rate of globin chain synthesis in adult haemoglobin. • -ineffective erythropoiesis and increased haemolysis • - a low Hb and MCHC level but raised serum iron level.

4. - Definitive diagnosis DNA analysis. • - The severity of the condition depends on the number of abnormal genes. • . • - Types of thalassaemia and their inheritance • α-chains • α-thalassaemia major = four defective α genes • α-thalassaemia intermedia = three defective α genes • α-thalassaemia minor = two or one defective α genes

5. β-chains • β-thalassaemia major = two defective β genes • β-thalassaemia minor = one defective β gene • Alpha thalassaemia major • α-Thalassaemia major is incompatible with extrauterine life.

6. Beta thalassaemia major • -severe haemoglobin deficiency, which may result in cardiac failure and death in early childhood. • - the ineffective erythropoiesis and increased haemolysis cause hypersplenism. • -A splenectomy is often performed in order to increase RBC survival and reduce the need for frequent blood transfusions. • - Blood transfusions increase the possibility of survival to childbearing age.

7. Alpha and beta thalassaemia minor • -α- and β-thalassaemia minor is the most common problem encountered among pregnant women. • -This heterozygous condition produces an anaemia that is similar to iron deficiency in that the Hb, the MCV and the MCH are all lowered. • -A definitive diagnosis needs DNA analysis. • -no deficiency in iron

8. -. In pregnancy, oral iron and folate supplements are necessary in order to maintain the iron stores. • -Parenteral iron should never be given • - Blood transfusions may be required if the haemoglobin is thought to be inadequate for the stress of labour and blood loss at birth

9. Sickle cell disorders • -abnormal haemoglobin alpha or beta chains; the resulting Hb is called HbS. • - SCA) abnormal genes have been inherited from both parents, • - sickle cell trait (HbAS) only one abnormal gene has been inherited

10. Sickle cell anaemia • -increased fragility and shortened life span of 17 days • -chronic haemolytic anaemia and causes episodes of ischaemia and pain, known as attacks of pain or sickle cell crises. • -Sickling crisis may occur whenever oxygen concentration is low.

11. precipitating factors that affect oxygen uptake include • : • -sychological stress • - cold climate • - extreme temperature changes • - smoking-induced hypoxia • -strenuous physical exertion and fatigue • -respiratory disease • - infection • - pregnancy.

12. -sickle cells easily adhere to the vascular epithelium causing a reduced blood flow, vascular obstruction and hypoxia. • - This results in acute pain, particularly in the bones, joints and abdominal organs. • -Painful episodes last for a few hours to a few days

13. Effective management of sickle cell crisis can be achieved by: • • utilization of pain assessment tools to determine severity of the pain • • administration of effective analgesia within 30 min of admission to hospital starting with a non-opioid analgesia, e.g. paracetamol before moving to opioid analgesia for moderate/severe pain • • liaison with the acute pain management team to ensure adequate and continuing pain relief • • administration of oral and intravenous fluids to correct dehydration and electrolyte imbalance caused by pyrexia, vomiting or diarrhea • • pulse oximetry to assess oxygen saturation and the administration of oxygen therapy if indicated

14. antibiotic treatment if infection is suspected • • assessment of haematological indices and liaison with the haematology department • • keeping warm and promoting rest • • provision of social, psychological and physical support to alleviate symptoms associated with chronic pain. • -Blood transfusion therapy is key to the management of sickle cell anaemia as it increases the oxygen carrying capacity of blood by increasing the haemoglobin concentration and decreasing the percentage of sickle haemoglobin.

15. - However, due to the risk of developing red cell antibodies and iron overload • -the indications for the use of blood transfusion therapy include: • 1-acute chest syndrome, • 2- heart failure • 3- multiorgan failure • 4-,stroke • 5- splenic sequestration • 6- aplastic crisis.

16. -New therapies include the use of drugs such as hydroxyurea, which inhibits the development of sickle cells by increasing fetal haemoglobin production. • - Bone marrow and stem cell transplantation can cure SCA • -Maternal and fetal effects; • . -antenatal and postnatal attacks of pain • -infections • - pulmonary complications • - anaemia • -pre-eclampsia • - and caesarean section. • - Fetal and neonatal complications include spontaneous abortion, pre-term birth, intrauterine growth restriction and perinatal death

17. Preconception care; • . All women should be offered haemoglobin electrophoresis in early pregnancy and for any with positive results it is important to have their partner tested. • counselling regarding prenatal diagnosis should be offered • . If both parents are carriers for HbS (i.e. heterozygous) there is a one in four chance that the fetus will inherit the more serious condition, sickle cell anaemia

18. Antenatal care: • Antenatal care aims to minimize the maternal and fetal complications • -women with SCA will experience sickle crises during pregnancy which requires hospital admission and treatment • -Monitoring of pregnancy is performed at frequent intervals by a multidisciplinary team involving a midwife, obstetrician, haematologist, specialist nurse and physician, • - Midwives have an important role in providing information and education about SCA and how it affects

19. pregnancy, particularly in emphasizing the factors that may precipitate sickle crisis. • - initial blood tests should include : • 1-screening for red cell antibodies • 2- haemoglobin electrophoresis • 3- serum iron • 4- total iron-binding capacity • 5- serum ferritin levels • 6-liver function tests, • 7-blood urea nitrogen and serum creatinine.

20. - Regular monitoring of the haemoglobin concentration is required throughout pregnancy; this is usually in the range of 6–9 g/dL. • -Fluid intake should be well maintained to prevent dehydration • - detect bacterial infections, particularly genitourinary and respiratory infections, at an early stage. • - Good nutrition and folic acid supplements • -The use of prophylactic blood transfusions to improve the outcome of pregnancy remains controversial.

21. - a policy of transfusing only when indicated, for example in : • symptomatic anaemia, • severe anaemia with a haematocrit <18%, • sickle crisis, • cardiac failure • or prior to caesarean section. • - Fetal assessment includes regular ultrasound scans to assess fetal growth. biophysical profiles and uterine Doppler blood flow studies

22. Intrapartum care: • . Timing and mode of birth is gauged according to maternal and fetal health • induction of labour or caesarean section should be performed for obstetric reasons. • Good pain relief • adequate hydration are essential to reduce the risk of a sickle crisis • an epidural is usually recommended.

23. Oxygen therapy via a nasal prong or mask is advised to maintain adequate oxygenation and improve cardiac function. • Prophylactic antibiotics may be considered to prevent infection. • Prolonged labour should be avoided and active management or a caesarean section may be advised • CTG monitoring is recommended, especially where there is intrauterine growth restriction.

24. Postnatal care. • Women with SCA are at a high risk of developing thromboembolic disorders • early ambulation • wearing anti-embolic stockings should be encouraged. • To prevent puerperal sepsis, antibiotic cover is continued throughout the postnatal period. • Neonatal screening of babies must be undertaken by obtaining a sample of neonatal capillary or venous blood at birth. • Those with positive results should be followed-up by a haematologist

25. -Sickle cell trait is usually asymptomatic. • -The blood appears normal • -although the sickle screening test is positive. • -The woman may be mildly anaemic in pregnancy and folate 5 mg daily is recommended to help erythropoiesis.

26. Other rare inherited disordersGlucose-6-phosphate dehydrogenase • Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked, hereditary genetic defect. • -G6PD is an enzyme necessary for the survival of the red cell; • - when it is deficient RBCs are destroyed in the presence of certain substances. • -These include fava beans, sulphonamides, vitamin K analogues, salicylates and camphor (found in products such as ‘Vicks VapoRub’). • - To prevent haemolysis these substances should be avoided

27. Spherocytosis • -the red cells are spherical instead of biconcave • - easily destroyed. • -In this disease the abnormal gene is dominant. • -Midwives need to be aware that women with this condition might have had a splenectomy