The quality of evidence (I-III) and classification of recommendations (A-E) are defined at the end of the "Major Recommendations."
- Carrier screening for thalassemia and hemoglobinopathies should be offered to a woman if she and/or her partner are identified as belonging to an ethnic population whose members are at higher risk of being carriers. Ideally, this screening should be done pre-conceptionally or as early as possible in the pregnancy. (II-2A)
- Screening should consist of a complete blood count, as well as hemoglobin electrophoresis or hemoglobin high performance liquid chromatography. This investigation should include quantitation of HbA2 and HbF. In addition, if there is microcytosis (mean cellular volume < 80 fL) and/or hypochromia (mean cellular hemoglobin < 27 pg) in the presence of a normal hemoglobin electrophoresis or high performance liquid chromatography the patient should be investigated with a brilliant cresyl blue stained blood smear to identify H bodies. A serum ferritin (to exclude iron deficiency anemia) should be performed simultaneously. (III-A)
- If a woman's initial screening is abnormal (e.g., showing microcytosis or hypochromia with or without an elevated HbA2, or a variant Hb on electrophoresis or high performance liquid chromatography) then screening of the partner should be performed. This would include a complete blood count as well as hemoglobin electrophoresis or high performance liquid chromatography (HPLC), HbA2 and HbF quantitation, and H body staining. (III-A)
- If both partners are found to be carriers of thalassemia or an Hb variant, or of a combination of thalassemia and a hemoglobin variant, they should be referred for genetic counselling. Ideally, this should be prior to conception, or as early as possible in the pregnancy. Additional molecular studies may be required to clarify the carrier status of the parents and thus the risk to the fetus. (II-3A)
- Prenatal diagnosis should be offered to the pregnant woman/couple at risk for having a fetus affected with a clinically significant thalassemia or hemoglobinopathy. Prenatal diagnosis should be performed with the patient's informed consent. If prenatal diagnosis is declined, testing of the child should be done to allow early diagnosis and referral to a pediatric hematology centre, if indicated. (II-3A)
- Prenatal diagnosis by DNA analysis can be performed using cells obtained by chorionic villus sampling or amniocentesis. Alternatively for those who decline invasive testing and are at risk of hemoglobin Bart's hydrops fetalis (four-gene deletion alpha-thalassemia), serial detailed fetal ultrasound for assessment of the fetal cardiothoracic ratio (normal < 0.5) should be done in a centre that has experience conducting these assessments for early identification of an affected fetus. If an abnormality is detected, a referral to a tertiary care centre is recommended for further assessment and counselling. Confirmatory studies by DNA analysis of amniocytes should be done if a termination of pregnancy is being considered. (II-3A)
- 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 alpha thalassemia should prompt immediate investigation of the pregnant patient and her partner to determine their carrier status for alpha-thalassemia. (III-A)
Definitions:
Quality of Evidence Assessment*
I: Evidence obtained from at least one properly designed randomized controlled trial.
II-1: Evidence obtained from well-designed controlled trials without randomization.
II-2: Evidence obtained from well-designed cohort (prospective or retrospective) or case–control analytic studies, preferably from more than one center or research group.
II-3: Evidence obtained from comparisons between times or places with or without the intervention. Dramatic results in uncontrolled experiments (such as the results of treatment with penicillin in the 1940s) could also be included in this category
III: Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.
Classification of Recommendations**
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a recommendation for or against use of the clinical preventive action; however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive action
L. There is insufficient evidence (in quantity or quality) to make a recommendation; however, other factors may influence decision-making
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on Preventive Health Care.
**Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force on Preventive Health Care.
