Description of the condition
Bleeding disorders can pose significant challenges during pregnancy and childbirth. Pregnancy is a hypercoagulable state, which means that the majority of bleeding disorders are not associated with a significant bleeding risk. However, some of the disorders will not be corrected by the hypercoagulable state induced by pregnancy, or this state will quickly wane post-delivery, thus requiring specific measures to prevent maternal and foetal bleeding complications especially during childbirth. Von Willebrand disease (VWD), haemophilia A and B, factor XI and factor VII deficiency account for almost 90% of the inherited bleeding disorders, whereas deficiency in fibrinogen, prothrombin factor, factor V, factor X, factor XIII are relatively rare (Chi 2007). Idiopathic thrombocytopenic purpura (ITP) is a commonly acquired bleeding disorder during pregnancy and accounts for 3% to 4% of the cases of thrombocytopenia detected at this time (Gill 2000); whereas HELLP (haemolysis, elevated liver enzymes, and low platelet count) syndrome is a rarer acquired bleeding disorder during pregnancy, occurring in approximately 1 to 2 per 1000 pregnancies (Geary 1997).
Von Willebrand disease is caused by a quantitative or qualitative defect in Von Willebrand factor (VWF). An increase in VWF (with levels in blood plasma up to normal plasma levels) is often seen during pregnancy in women with VWD (except type 3), but intrapatient variability is very wide (Conti 1986). A drastic fall in VWF following delivery in women with VWD causes these women to be prone to primary and secondary postpartum haemorrhage (PPH).
Congenital haemophilias are X-linked recessive bleeding disorders that result from deficiencies of the coagulation factors VIII and IX. Most female carriers of haemophilia have levels of factor VIII (or IX) within the normal range and are therefore protected against significant bleeding problems in day-to-day life (Giangrande 2009). Pregnant carriers of haemophilia A usually have low levels of factor VIII at the beginning of pregnancy, but have almost normal levels of factor VIII by the third trimester. In normal pregnancy, factor IX levels do not rise significantly (Stirling 1984). However, those with levels of factor VIII (or IX) under 50% (less than 0.50 IU/mL) are at increased risk of bleeding when facing haemostatic challenges (Lusher 1978). Female carriers of haemophilia A are at an increased risk of haemorrhagic complications, both early and late PPH, because of the rapid fall in the increased pregnancy-induced maternal clotting factor levels (FVIII) after delivery. The incidence of early and late PPH is increased among haemophilia A carriers (22% and 11%, respectively) (Kadir 1997) compared with the general population (5% and 0.7%, respectively) (Lee 1981). Risk of head bleeding in babies (cephalhaematoma, intracranial haemorrhage) is 3%, 64% and 15% following normal delivery, vacuum extraction and caesarean section (c-section) respectively (Ljung 1994)
Factor XI deficiency (haemophilia C) and factor VII deficiency are very rare inherited bleeding disorders in the general population but factor XI deficiency is very common in the Ashkenazi Jewish population (Bolton-Maggs 1988). Homozygous and compound heterozygous individuals with factor XI and factor VII deficiency develop haemorrhagic manifestations; heterozygous individuals are usually asymptomatic. Clinical prototypes vary from mild to severe and do not correlate with factor XI and VII levels. The levels of factor XI and factor VII do not change during pregnancy and there is a poor correlation between the level of factor XI and bleeding tendency (Bolton-Maggs 1988). For both factor XI and VII deficiencies, bleeding tendency is likely to be associated with levels of factor less than 15%, and varies in the same individual following different haemostatic challenges. Therefore, the unpredictable nature of these diseases makes their management during pregnancy and childbirth difficult.
Inherited fibrinogen abnormalities, factor II, factor V, factor X and factor XIII deficiencies are the rarest bleeding disorders; bleeding tendencies are low in heterozygous groups but life-threatening in the homozygous group due to PPH (Bolton-Maggs 1988; Fadel 1989).
Congenital platelet dysfunction disorders, being autosomal recessive disorders, are rare. Defects are in the platelet GPIb complex (Bernard-Soulier Syndrome) or the GPIIb-IIIa complex (Glanzmann thrombasthenia) or in the abnormal secretion and thromboxane synthesis. Bleeding tendencies are severe in Bernard-Soulier Syndrome and Glanzmann thrombasthenia, and need platelet transfusion. Bleeding is mild in platelet dysfunction disorders, which are due to abnormal secretion and thromboxane synthesis, but can be life-threatening following surgery or trauma (George 1990; Peng 1991).
Idiopathic thrombophilic purpura is a common cause of acquired bleeding disorder in pregnancy and occurs in 1000 to 2000 deliveries (Burrows 1990). The risk of spontaneous bleeding at birth in women with ITP is low and occurs particularly if the platelet count decreases to less than 20,000/µL (Webert 2003). The frequency of neonatal alloimmunisation thrombocytopenia (NAIT) is estimated at 1 to 2 cases per 1000 deliveries (Blanchette 1990). This disorder develops in foetal life, with 25% to 50% of foetal intracranial haemorrhages detectable on prenatal ultrasound prior to the onset of labour (Herman 1986).
The HELLP syndrome occurs in 10% to 20% of cases with severe pre-eclampsia (Geary 1997). Maternal mortality in pregnancy associated with HELLP syndrome is 1.1% (Sibai 1993) and the perinatal mortality is 34% before 32 weeks gestation, and 8% after this (Gul 2005). More common and serious maternal complications are placenta abruptio, disseminated intravascular coagulation (DIC) and subsequent severe PPH; whereas, prematurity, intrauterine growth restriction (IUGR) and abruptio placenta are the leading causes of neonatal death (Magann 1999). Hepatic rupture has a perinatal mortality that can reach 80% (Mihu 2007), the majority of which are observed during the antenatal period; whereas, about 30% of HELLP syndromes develop after birth, the majority within the first 48 hours with the time of onset ranging from a few hours to seven days following delivery (Barton 2004). Immediate delivery following stabilization of the maternal clinical condition is the primary choice of management in HELLP syndrome.
Description of the intervention
with a level less than 15% (i.e., less than 15% factor VII in factor VII deficiency;less than 15% factor XI in factor XI deficiency).
Pregnancy and childbirth management in women with bleeding disorders is a multidisciplinary approach consisting of obstetricians, haematologists, anaesthesiologists and neonatologists. Delivery is conducted in centres where resources for laboratory testing and clotting factor treatment are readily available. Relevant coagulation factor level is usually not measured at delivery, but is estimated during the third trimester. A deficient coagulation level has to be corrected to a safe level spontaneously or by supplementation in order to prevent bleeding during childbirth. Optimal management of delivery has to take into account the health needs and goals for both the mother and the newborn.
Delivery should be achieved by the least traumatic method and early recourse to c-section can be considered to minimise the risk of neonatal bleeding complications. Caesarean section is better for the foetus and not riskier for the mother, although the latter has not been proven in this context. Prolonged labour should be avoided whenever possible. Maternal genital and perineal trauma is minimised in order to reduce the risk of excessive bleeding at delivery (Kadir 1998; McMahon 2001).
Vaginal delivery is a safe mode of delivery in women with bleeding disorders and c-section section is mainly due to obstetric reasons (Lee 2006). Special attention to haemostasis is required to minimise bleeding during c-section. Administration of neuraxial or general anaesthesia are safe methods for labour and delivery. Risk of spinal epidural haematoma following administration of neuraxial anaesthesia may be increased with potential for permanent neurological injury, which is rare (Vandermeulen 1994). The decision for neuraxial anaesthesia is individualised and the procedure is better performed after optimum level of deficient clotting factor is achieved. When there is concern about spinal epidural haematoma, patient-controlled analgesia with fentanyl is an alternative option (Campbell 2003). Caesarean section under general anaesthesia is considered in cases where neuraxial analgesia is contraindicated. Instrumental delivery with low forceps is permissible, delivery by ventouse extraction or mid-cavity or rotational forceps delivery is not recommended and episiotomies and foetal scalp electrodes are avoided. Prophylactic replacement therapy is considered if maintaining the haemostatic level for at least five to seven days following either vaginal or c-section to prevent PPH is advisable. Prophylactic administration of a uterotonic drug (oxytocin, ergometrine, misoprostol, carboprost) along with active management of the third stage of labour is considered to prevent PPH.
Bleeding complications during delivery are 1% to 4% (intracranial haemorrhage, cephalhaematoma) in affected infants of inherited bleeding disorders and ITP, and commonly observed with traumatic delivery. However, these risks are not decreased by c-section (Fujimura 2002). Newborns affected by congenital coagulopathies are supplemented with oral instead than parenteral vitamin K. Similarly, for immunisation of affected newborn and neonates the intradermal or subcutaneous route is preferred.
How the intervention might work
Vaginal delivery is considered safer compared to c-section in women with bleeding disorders. It avoids surgical morbidity and anaesthesia-related complications. The safest method of delivery for foetuses at risk is controversial. Lack of data from the literature in relation to foetuses with rare bleeding disorders and knowledge is extrapolated from experience of newborns with common bleeding disorders such as haemophilia (Ljung 1994).The available data indicate that the risk of serious bleeding during normal vaginal delivery is small and delivery by c-section is not expected eliminate this risk (Ljung 1994). Low forceps delivery is considered less traumatic compared to c-section when the head is deeply engaged in the pelvis and easy outlet delivery is anticipated (Kadir 1998; McMahon 2001).
Why it is important to do this review
At present, there is ongoing debate about the best way to deliver in carriers of foetuses with, or at risk of, congenital bleeding disorders. The evidence from the comparison among vaginal and surgical delivery is scanty and there is equipoise which would justify controlled clinical trials being undertaken. This review will investigate which is the safe and more effective mode of delivery in women with bleeding disorders taking into account effects on both the mother and the foetus.