Hemoglobinopathies are the first among genetic disorders for which a national guideline for prevention and control has been framed. The elements of the guidelines are guided by WHO directives and guidelines on hemoglobinopathies including Thalassemia and sickle cell disorders and WHO report on services for prevention and management of genetic disorders in developing countries. The NHM guidelines provide a framework based on strategies for prevention and management of hemoglobinopathies documented in publications of Thalassemia International Federation (TIF), various peer reviewed publications, reports of acknowledged groups and on experiences derived from implementing these strategies in public Health set up under NHM.

The guiding elements of NHM Guidelines on Hemoglobinopathies :

• Hemoglobinopathies are genetic disorders with an autosomal recessive inheritance implying that
      -  they are equally prevalent in males and females
      -  have a ‘carrier’ and ‘disease’ state
      -  the abnormal gene is passed on from one generation to another
• The carrier state refers to a person carrying only one abnormal gene. Such individuals do not have any disease and clinically have no symptoms.
• The disease state occurs when an individual’s both genes are abnormal, one abnormal gene being inherited from each of the parents..
• A couple where both the partners are carriers of an abnormal gene (mutated gene)r
      -  have a 25% risk in each pregnancy of giving birth to a child with disease state.
      -   have 25% chance in every pregnancy of having a ‘normal’ child
      -   have a 50% chance in each pregnancy to give birth to a ‘carrier’ child
     Thus, a carrier couple can have ‘normal’, ‘carrier’ or ‘disease’ affected children.
• Thalassemia Major, Thalassemia Intermedia and Sickle Cell Disease are the major disorders that require lifelong management and are to be considered for prevention. Hematopoietic Stem Cell Transplant (HSCT), commonly known as Bone Marrow Transplant (BMT), is the only curative treatment but is possible in very few patients due to high costs and non-availability of matched donors.
• Untreated Thalassemia Major is invariably fatal by 2-5 years of age. Commonly Thalassemia Major (TM) is managed by regular blood transfusions (Packed Red Blood Cells) and iron chelation therapy. Availability of leuko-depleted packed red blood cells (pRBC) and iron chelators are to be ensured for adequate management along with facilities for regular monitoring. Adequately treated patients can live a fulfilling life.
• It is possible to know whether the child to be born will be affected by disease, or be a carrier or normal by detecting the mutations of both parents in the fetal tissue. The process is called Prenatal Diagnosis (PND). As Thalassemia Major is a severe and life threatening disease, termination of pregnancy is permitted under Indian laws.
• Newborn screening can detect abnormal hemoglobin variants like HbS, both carriers as well as those with disease (HbSS ) states. On the other hand, thalassemia major is difficult to detect by newborn screening and can be detected hematologically mostly after 3-6 months of age and confirmed at one year of age. The screening is possible while doing CBC and doing confirmatory test with HPLC or electrophoresis.
• Carrier state is asymptomatic, but can be detected by relatively simple blood tests, which are available in the district hospitals , opening up the possibility of controlling hemoglobinopathies by preventing birth of affected children by
      -  Avoiding marriage between two carriers
      -   Prenatal diagnosis in pregnancies of couples where both partners are carriers, with the option of termination of pregnancy in case of an affected fetus.
• Cost effective population screening programmers are possible for detection of carriers, as low cost screening tests with high negative predictive value are available for detection of carriers of β-thalassemia (also referred to as β-Thalassemia Trait (BTT)), HbS Carriers (HbS Trait) and HbE carriers (HbE Trait).
• Genetic counseling, community education and awareness play a very important role in successful implementation of prevention programmes. Services and screening programmes should be sensitive to cultural and social practices and religious beliefs. Awareness of ethical and legal issues is required to avoid misuse of legal provisions, and be culturally sensitive.
• The time between initiation of implementation and visibility of impact is affected by the group that is chosen for carrier screening-adolescent, premarital, pre-conception or antenatal. Sustenance of preventive programmes for long periods of time extending to decades is required to achieve expected outcomes.

Mission: To improve care of all Thalassemia and Sickle Cell Disease patients for their better future and to lower the prevalence of hemoglobinopathies through screening and awareness strategies

NHM Guidelines for Prevention

Based on public health goal of reduction in the prevalence of hemoglobinopathies

• Community education and awareness programmes to remove any myths regarding transmission of disease, gender bias, stigma related to disease and carrier states and informing the community about appropriate prevention options and their availability through public health facilities.
• Installation of sustainable and cost effective carrier screening programmes at school level for adolescents backed by adequate and effective prescreening educative programmes on genetic disorders in general and hemoglobinopathies in particular and post screening non directive genetic counseling ensuring confidentiality and generating trust to enable expected outcomes.
• Establishing services at the community level for pre-marital and pre-conception screening backed by genetic counseling services.
• Extended family screening of all known and detected carriers and patients
• Implementation of strategies to achieve the public health goal of reduction in prevalence of these genetic disorders will be done in accordance with the guidelines laid down by WHO in its January 5-7,1999 Report on Genetic Disorders and Birth Defects emphasizing on preserving and respecting the social and cultural diversity and dignity and rights of the affected individuals and by voluntary genetic testing after informed consent. Excerpts from the WHO document are given below, to inform those who run the programme:
      -   These (public health) goals should never be set in ways to impose genetic tests or reproductive decisions on individuals.
      -   Accepted ethical guidelines of public health programs in genetics stipulate that genetic testing should always be voluntary, respecting the autonomous decisions of the patients, and should be preceded by proper information in the form of non-directive genetic counseling (WHO, 1998).
      -   Public health goals cannot override the cultural and personal values and beliefs of individuals and their reproductive rights, and oppose stigmatization and discrimination of affected persons (WHO, 1998).
      -   Governments should recognize that within any country there exists diversity of cultures and opinions about a number of issues relevant to genetics, such as human reproduction issues as well as about the significance of disabilities.

Based on the rights of prospective parents at risk of having a child with a serious genetic Disorder

• Establish carrier screening services for screening of pregnant women and their husbands, to prevent the birth of children with Thalassemia major or intermedia and Sickle Cell Disease in the district hospitals and below by doing CBC and confirmatory with HPLC / Electrophoresis.
• Availability of laboratory facilities for testing and confirmation of Hemoglobinopathy carriers at district level in the District hospital laboratory
• Establishment of loco- regional centers in States with facilities for prenatal diagnosis and laboratory facilities for DNA analysis. Increase feasibility of antenatal screening by training of personnel in sampling techniques with help of tertiary centers.
• Train Doctors /healthcare personnel for management and delivery of genetic counseling services for families at risk

NHM Guidelines for Management of Affected Children

Based on rights of patients for access to care

• Provide optimal care to all patients of thalassemia and sickle cell disease by establishing ICHH facilities (Integrated centres for hemoglobinopathies & hemophilia) facilities for transfusion and monitoring with the help of State health departments at the District Hospitals.
• Ensure availability of safe blood to children with thalassemia, strengthen existing Blood Banks/ blood storages to provide facilities for component and leuco-depletion, and help the States to set up new Blood Banks or blood storage facilities where there are none. Promotion of voluntary blood donation to fulfill the blood requirements.
• Provide financial support for obtaining medicines for iron chelation-an essential component of management without which blood transfusions given over the years will lead to iron-overload.
• Developing and implementing protocols for early diagnosis and intervention in cases of Sickle Cell Disease (SCD) and Thalassemia major (TM). Newborn screening for SCD – in order to provide timely intervention with prophylactic penicillin and vaccinations and targeted screening of children with anemia, to identify those having thalassemia trait or disease. Referral for Hematopoietic stem cell transplant (HSCT), also termed Bone Marrow Transplant (BMT) and facilitate establishment of more HSCT centres.
• Inform the community about appropriate treatment and management options and making these available through public health facilities.