Hemophilia is a rare bleeding disorder manifested by the inability of the blood to clot. The disease occurs due to alterations in genes that regulate our body to stop bleeding. As we celebrate World Haemophilia today, The Pioneer brings to you a detailed write-up on Haemophilia. Haemophila A and B are the most common. It is caused by alterations or mutations in the F8 or F9 genes, respectively, on X chromosomes. The genes associated with hemophilia A and B, F8 and F9, respectively, provide instructions for producing clotting factors VIII and IX. Mutations in these genes result in reduced or non-functional clotting factors, leading to bleeding disorders. The severity of hemophilia in affected individuals can vary depending on the specific mutation and the level of clotting factor present in their blood. Haemophilia C, caused by a deficiency in factor XI located on an autosome, however, is rare.
Haemophilia A/B is an X-linked recessive genetic disorder. This means that the affected gene responsible for hemophilia is located on the X chromosome. Since males have one X and one Y chromosome (XY) and females have two X chromosomes (XX), haemophilia primarily affects males. Females can be carriers of the hemophilia gene if they inherit one normal X chromosome and one with a mutation, but they usually do not show symptoms themselves.
Dr. Dipanjana Datta, a BGCI Level II certified genetic counsellor at Renew Healthcare, shares that though hemophilia A and B have treatment in the form of factor and gene therapy, males affected by hemophilia suffer from various co-morbidities, including joint pain, bone-related issues, swelling, and internal bleeds, apart from excessive bleeding even in minor injuries. Undiagnosed, in the case of mild hemophilia, surgery or an accident can cause death! Thus, the diagnosis of the disease is of utmost importance. “Affected individuals are diagnosed through biochemical testing of the factors. Genetic testing can confirm the diagnosis of hhemophilia and help in understanding the specific type and severity of the condition. A carrier female will have normal factor levels in most cases. Thus, female family members may choose to undergo carrier testing by genetic studies to determine if they carry a mutation in the F8 or F9 gene, which could be passed on to their children. Biochemical testing is not a suitable method, as biochemistry might be normal.”
Hemophilia and pregnancy
Up to 50% of neonatal males with severe hemophilia have no previous family history. In these cases, there is a 90% chance that the mother is a carrier, with risk to the next male child.
A family tree should be constructed to assess the likelihood of hemophilia carriership in at-risk female families.
Risks in pregnancy for mother and baby:
The levels of clotting factors VIII and IX should be checked before an invasive procedure or in association with bleeding symptoms. Carriers of hemophilia are at increased risk of bleeding with invasive procedures, termination, spontaneous miscarriage, and at the time of delivery. Male neonates with hemophilia are at increased risk of bleeding, including intracranial hemorrhage (ICH), extracranial hemorrhage (ECH), and iatrogenic bleeding following delivery.
Dr. Kinjal Kothari, Associate Consultant Obstetrician Gynecologist, Manipal Hospital, shares, “The baseline factor level should be determined before the onset of pregnancy. Before pregnancy, the general health of women who are carriers of hemophilia should be optimised. Genetic counselling should be provided to women at risk. Carriers of severe hemophilia should be offered a preimplantation genetic diagnosis. Antenatal care should be delivered in the context of a multidisciplinary team setting with hematologists and obstetricians with expertise in this field. Maternal factor VIII/IX should be checked at booking, before any antenatal procedure, and in the third trimester. Drugs like tranexamic acid, desmopressin (DDAVP), and recombinant factor VIII/IX can be considered given the altered clotting factor profile. A clear plan for the intrapartum care of a carrier and the baby should be available in advance of 37 weeks of gestation. The woman should be seen in the anesthetic clinic, and the neonatologists should be informed of the intended delivery of a baby with hemophilia. A decision regarding the timing and mode of delivery should be agreed upon jointly between the woman and the multidisciplinary team.”
There needs to be a full assessment of the advantages and disadvantages of the mode of delivery and consideration of obstetric factors, maternal bleeding risk, patient preference, and reproductive expectations.
“Measures should be taken to ensure expertise and necessary resources are available at all times.
External cephalic versions and the use of ventouse and mid-cavity forceps should be avoided for male babies at risk of hemophilia. Experienced clinicians should be involved in decisions about whether or not to perform a central neuraxial anesthetic technique, and the woman should be given all the information she needs to make an informed choice based on the level of clotting factors.
To minimise the risk of postpartum hemorrhage (PPH), it is important to recommend or offer active management of the third stage of labour & management should be guided by the results of factor assays,” shares Dr. Kinjal.
Genetic testing involves analysing a person’s DNA to identify mutations in the F8 or F9 genes from blood or buccal swabs. In cases where there is a family history of hemophilia, invasive diagnostic methods like chorionic villi sampling and amniocentesis, followed by specific targeted genetic testing around 11 weeks (about 3 months) of pregnancy, can help determine the status of the fetus. This can help families make informed decisions about the pregnancy and prepare for the care of a child with hhemophilia. Aternatively, pre-implantation genetic testing can be performed by taking a biopsy of the embryos formed by IVF at 5th day and screening for the targeted mutation. This process is called PGT (M), which can help to identify healthy embryos without the trauma of repeated abortions after prenatal diagnosis.
Genetic testing and genetic counselling can play a pivotal role in diagnosis and management. Understanding the genetic basis and inheritance patterns helps predict recurrence risk and plan a healthy baby.
Haemophilia is a rare bleeding disorder, manifested by the inability of the blood to clot. The disease occurs due to alterations in genes that regulate our body to stop bleeding. As we celebrate World Haemophilia today, The Pioneer brings to you a detailed write up on Haemophilia.
