Preconception counselling
Women suspected of having a bleeding disorder or of being a carrier should have diagnostic testing before getting pregnant to allow for appropriate preconception counselling and early pregnancy management. This is especially important for women with severe bleeding disorders or those who could potentially carry a severely affected baby, such as carriers of severe haemophilia.
Preconception counselling has two benefits:
- It provides women and their family with adequate information on the genetic implications of their disorder, the available reproductive choices and options for prenatal diagnosis.
- It allows planning for pregnancy and establishing how and where the pregnancy can be best managed. Other aspects of preconception care include immunisation against hepatitis A and B for those likely to require blood transfusion and general advice such as folic acid supplementation. A DDAVP trial can also be carried out to assess response to this particular treatment option.
Psychological support should be available during all aspects of counselling. Women should also be offered the opportunity to speak with a paediatric haematologist regarding the care of a potentially affected child.
Prenatal diagnosis (PND)
PND is primarily considered in carriers of haemophilia because of the severity of the disorder in male offspring and because many affected families are already aware of the genetic defect. For each pregnancy in carriers of haemophilia, there is a 50% chance that a male child will have haemophilia and a 50% chance that a female child will be a carrier. In other bleeding disorders, prenatal diagnosis is considered only when the foetus is at risk of being affected with severe forms of the disorder. Since most bleeding disorders are autosomal recessive, this risk is more common in families and cultures with high rates of intermarriage.
Foetal sex determination
Foetal sex determination can be useful in the management of pregnancies at risk of haemophilia. This can be reassuring to the parents when the foetus is female, and invasive testing can then be avoided. It will also enable the management plan for labour and delivery to be refined to avoid instrumental deliveries and invasive monitoring techniques in male foetuses, which have a 50% chance of being affected.
Foetal sex may be determined in two ways:
1) Maternal blood test: The sex of the foetus can be determined from foetal DNA which can be extracted from a sample of the mother’s blood at approximately 9 weeks gestation.
2.) Ultrasound: Foetal sexing can be performed easily by ultrasound from the second trimester.
CVS, amniocentesis and cordocentesis
These procedures are associated with a risk of miscarriage / foetal loss. The causative genetic mutation must be known prior to CVS and amniocentesis.
CVS is the method most widely used today for prenatal diagnosis of inherited bleeding disorders. It is performed at 11 – 14 weeks gestation under ultrasound guidance. It has the advantage of earlier diagnosis compared to amniocentesis, which is performed at 15-20 weeks gestation. Both are associated with an approximately 1% risk of miscarriage. See glossary for further information on chorionic villus sampling and amniocentesis.
Cordocentesis (ultrasound guided foetal blood sampling) is performed at around 18-20 weeks gestation to obtain foetal blood for a clotting factor assay. The risk of miscarriage is higher with this procedure compared to amniocentesis or CVS. It is rarely performed today and may be an option for cases in which the causative genetic mutation cannot be identified. Women at risk for severe bleeding should receive prophylaxis (treatment) to normalise clotting prior to any invasive procedure.
Pre-implantation genetic diagnosis
Pre-implantation genetic diagnosis is a relatively new technique. Embryos created using in vitro fertilization (IVF) are tested to identify those that are unaffected by the bleeding disorder and these are then selectively transferred to the uterus. There have been reports of its success recently in carriers of haemophilia. This method will likely become a realistic option for some individual cases in the near future. However, further evidence on its efficacy and safety is still required. The cost and stress associated with IVF also need to be considered. Pre-implantation genetic diagnosis is not available in Ireland.
Access to prenatal diagnosis is available through the NCC, St. James’s Hospital, Dublin, Cork University Hospital and the National Centre for Medical Genetics at Our Lady’s Children’s Hospital, Crumlin.
Antenatal Management
Normal pregnancy causes increased concentrations of several coagulation factors including VIII, vWF and fibrinogen. Factor IX levels do not usually change significantly. These changes contribute to improved blood coagulation in women with bleeding disorders. Despite this improvement, however, women with bleeding disorders often do not achieve the same levels of clotting factors that other women do, and, therefore, are still at an increased risk of bleeding complications.
Miscarriage/ Pregnancy Complications
There is no evidence of a higher rate of miscarriage in carriers and women with other bleeding disorders than in the general population. However, women with certain factor deficiencies (such as factor XIII deficiency and fibrinogen deficiency) may be at greater risk of miscarriage and placental abruption (a premature separation of the placenta from the uterus that disrupts the flow of blood and oxygen to the foetus). Therefore, these women may require factor replacement throughout the pregnancy to prevent these complications.
Approximately 20% of all pregnancies are complicated by at least one bleeding episode, so bleeding in pregnancy may not be due to an underlying bleeding disorder. Obstetric causes should not be overlooked.
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Management of labour and delivery
The management of childbirth will depend on the needs of the mother and her potentially affected infant at the time of delivery. Women at risk of bleeding should ideally be referred for antenatal care and delivery to a centre, where in addition to specialist high risk obstetrics, there is a haemophilia treatment centre or a haematologist with expertise in coagulation. Laboratory, pharmacy, and blood bank support is essential.
If the mother is not near a haemophilia centre, the local hospital and medical team should be prepared beforehand for the woman’s and for the baby’s possible needs. Making decisions beforehand and having a written plan (birth plan) at home and at the hospital is important.
Prior to delivery, all women with bleeding disorders should have the opportunity to meet with an anaesthetist. There is no consensus on the factor levels that are safe for epidural, but if levels are at least 0.5iu/ml and the rest of the coagulation studies are normal, epidural may be considered safe.
It is acceptable to use third trimester levels to devise an appropriate plan for delivery. If the factor level is low in the third trimester, prophylactic treatment may be necessary to prevent bleeding.
Desmopression (DDAVP) may be used to raise factor VIII and von Willebrand factor levels in carriers of haemophilia A and women with vWD prior to invasive procedures. It is generally thought to be safe for mother and foetus, but care must be taken in its administration at the time of childbirth. It should be used with caution if the mother has received intravenous fluids due to possible complications associated with fluid retention.
The foetus is also at risk of bleeding complications during the process of birth.
Invasive monitoring techniques (e.g. fetal scalp electrode, fetal scalp blood sampling) and instrumental deliveries (ventouse, midcavity or rotational forceps) should be avoided in pregnancies with potentially affected fetuses, as serious head bleeding may result from these procedures.
Normal vaginal delivery is not contraindicated in these pregnancies, but prolonged labour should be avoided and delivery achieved by the least traumatic method. Although caesarean section may not completely eliminate the risk of serious bleeding complications in the newborn baby, the early recourse to caesarean section should be considered to minimize the risk of neonatal bleeding complications.
Low forceps delivery may be considered less traumatic than caesarean section when the head is deeply engaged in the pelvis and an easy delivery is anticipated. Delivery in these cases should be performed by an experienced obstetrician.
Factor levels should be measured on a cord blood sample. A cord blood sample should be collected from newborns at risk of moderate or severe inherited bleeding disorders to assess coagulation status and clotting factor levels. This enables the early identification and management of newborns at risk of bleeding complications.
When assessing neonatal clotting factor levels, it should be appreciated that the levels of vitamin K-dependent factors (FII, FVII, FIX, and FX), correlate with gestational age due to liver immaturity and reach adult levels at six months of age. It is therefore not reliable to diagnose mild forms of inherited bleeding disorders at birth. Haemophilia A (FVIII deficiency), however, can be diagnosed at birth.
Intramuscular injections should be avoided in newborns at risk until the coagulation status is known.
If the factor level is reduced then the child should be referred to the Paediatric Haematologist on–call in Our Lady’s Children\’s Hospital, Crumlin or Cork University Hospital.
Any surgical procedures (e.g. circumcision) should be delayed until the coagulation status of the newborn baby is known.
Postpartum management
The most common causes of post partum haemorrhage (PPH) are uterine atony (inefficient uterine contractility), retained placenta or placenta pieces, and genital tract trauma. However, coagulation disorders are also a recognised cause of PPH. After the delivery, the elevated coagulation factors return to pre-pregnancy levels within 14 to 21 days of delivery. Therefore, the main risk of bleeding is after miscarriage or delivery. PPH may occur up to six weeks post delivery. Women with bleeding disorders, especially those with severe disorders, are at risk of primary and secondary PPH .
Primary PPH is blood loss of more than 500ml in the first 24 hours after delivery.
Secondary PPH is excessive bleeding occurring between 24 hours and six weeks post delivery.
Perineal/vaginal hematomas are rare complications of vaginal birth, but are also more likely to occur in women with bleeding disorders, especially after operative vaginal deliveries.
There may also be obstetric risk factors and causes of PPH in women with inherited bleeding disorders. Management of PPH in women with bleeding disorders requires close collaboration between haematologist, obstetricians and anaesthetists.
Reducing the risk of PPH
Prophylactic replacement therapy is recommended to cover labour, delivery, and the immediate postpartum period (at least three to four days for vaginal delivery and five to seven days for caesarean section) in women with low factor levels or inherited bleeding disorders. Recombinant products, if available, are the products of choice to avoid the potential risk of transmission of viral infection.
As the pregnancy-induced increase in coagulation factor return to pre-pregnancy levels, women with bleeding disorders are particularly vulnerable to secondary postpartum haemorrhage. Oral tranexamic acid or combined oral contraceptive pills can be used for the prevention and management of secondary PPH.
Breast Feeding
Breastfeeding increases factor VIII and von Willebrand factor levels in response to pregnancy hormones. Women who breastfeed may maintain the high hormone levels they had during pregnancy. This protects them from bleeding in the weeks following delivery. Desmopressin or tranexamic acid is passed through breast milk. Women with certain types of bleeding disorders can have bleeding problems postpartum whether or not they breast feed as they do not respond to pregnancy hormones.
Heel prick can be performed for Guthrie card analysis (screening for inherited disorders such as underactive thyroid). Pressure should be applied for five minutes and the site should be closely observed for 24 hours.
BCG can be administered as it is given into the skin.
Vitamin K should be administered by the oral and not intramuscular route.
All infants with bleeding disorders should have cranial ultrasound before discharge.
Transcranial ultrasound (through the fontanelle) should be done urgently on all newborns with possible bleeding disorder if delivery is traumatic or if there are signs suggestive of bleeding into the brain. Treatment with clotting factor concentrate may be necessary in such cases.
Definitive prenatal diagnosis can only be obtained with invasive tests in pregnancy, such as chorionic villus sampling.