A consensus statement on the management of pregnancy and delivery in women who are carriers of or have bleeding disorders

Scott M Dunkley, Susan J Russell, John A Rowell, Chris D Barnes, Ross I Baker, Megan l Sarson and Alison M Street, on behalf of the Australian Haemophilia Centre Directors’ Organisation
Med J Aust 2009; 191 (8): 460-463. || doi: 10.5694/j.1326-5377.2009.tb02887.x
Published online: 19 October 2009

Women with inherited bleeding disorders (Box) are at risk of bleeding complications from haemostatic challenges during pregnancy and childbirth.1-5 Although several groups have published “evidence-based” guidelines on management of inherited bleeding disorders that include management of pregnancy, these guidelines are often voluminous and not user-friendly.1,2,6,7 The Australian Haemophilia Centre Directors’ Organisation (AHCDO) has developed practical guidelines for the management of pregnancy and delivery in women with bleeding disorders, with the aim of improving and standardising care, and these guidelines are available online ( However, as several different clinicians care for women with bleeding disorders (management involves a multidisciplinary team including, among others, an obstetrician, an anaesthetist and a haematologist), the AHCDO decided that the consensus statement would be valuable for the broader medical community.

All directors of haemophilia centres (adult and paediatric) throughout Australia are members of the AHCDO. The guidelines were developed initially by a working party (the listed authors) after extensive consultation, face-to-face meetings and revisions, and the final document represents a consensus opinion of all AHCDO members. Evidence-based literature and international guidelines were reviewed, and some are referenced. However, in many aspects of care in this area of medicine, evidence is lacking, and the recommendations are based on clinical experience and consensus opinion. The AHCDO recommendations are summarised at the beginning of each main topic.

Physiological response expected in pregnancy in women with bleeding disorders

In carriers of haemophilia A (carriers of the gene for factor VIII deficiency), coagulation factor VIII levels increase significantly during pregnancy, reaching a peak between 29 and 35 weeks.8,9 Although in a majority of these women, the levels will increase to within the normal range, the rise is variable and some may still have insufficient factor VIII levels for safe haemostasis at term.1,8,9 Similarly, in women with type 1, but not type 3, von Willebrand disease, levels of factor VIII and von Willebrand factor antigen (VWF:Ag) usually increase during pregnancy.1,8,9 In carriers of haemophilia B (carriers of the gene for factor IX deficiency), factor IX levels usually do not change significantly during pregnancy, and neither do factor XI levels in women with factor XI deficiency states.1,7,10,11

Because the rise in factor levels is unpredictable during pregnancy, the levels should be checked at presentation, and checked again before any invasive procedure, and during the third trimester.1,2,9,10 After delivery, factor levels usually return to baseline after days to weeks, but may drop earlier.1,8 It should be noted that women with normal factor levels may still be haemophilia carriers.

Management of pregnancy and delivery
During pregnancy

Women who are carriers of the genes for factor VIII or factor IX deficiency (haemophilia A and B, respectively) may have plasma factor levels outside the normal range and, particularly when these levels are < 30% (classified as mild haemophilia), they may be at increased risk of bleeding.7 A majority of carriers of haemophilia A will develop “normal” factor levels as pregnancy progresses, and thus will not require replacement therapy.1,7,12 However, in carriers with a moderate-to-severe deficiency, factor levels may not adequately correct during pregnancy.1,7,12 Women with rare bleeding disorders, such as fibrinogen or factor XIII deficiency, may require antenatal treatment to prevent fetal loss.

Women with type 1 von Willebrand disease (the most common and mildest form) also experience increased levels of factor VIII and VWF:Ag during pregnancy, with normal levels occurring in most women by delivery.1,7,13 Women with type 2 von Willebrand disease may also show an increase in factor VIII and VWF:Ag during pregnancy, but measures of VWF function (ristocetin cofactor and collagen binding assay) usually remain low.1,2,10 Further, thrombocytopenia associated with type 2B von Willebrand disease can worsen during pregnancy. Women with type 3 von Willebrand disease do not show any change in factor levels during pregnancy, and all require replacement therapy for delivery.1

Measurement of factor levels should be repeated in the third trimester (32–34 weeks’ gestation) to allow planning of the appropriate management of labour and delivery and the need for prophylactic therapy.1,6,7

The mother’s factor levels should also be checked before any invasive procedure, and, if below the normal range, replacement therapy should be provided.1,9,10 In general, normal equates to levels of factor VIII, factor IX and VWF:Ag being > 50 IU/dL for haemophilia A, haemophilia B, and type 1 von Willebrand disease, respectively. Bleeding in women with factor XI deficiency is highly variable and provision of replacement therapy should be individualised; however, it is required if factor XI levels are < 15 IU/dL.1,10,11 Treatment of women with rare bleeding disorders (see Box) should be individualised.

Desmopressin (1-desamino-8-D-arginine vasopressin [DDAVP]) is a synthetic analogue of vasopressin that increases the plasma levels of VWF and factor VIII. DDAVP has been used in the treatment of women with haemophilia A and type 1 von Willebrand disease during pregnancy;1,7,14 it has a category B2 safety warning for use in pregnancy in Australia.15 However, DDAVP can stimulate uterine contraction and cause premature labour, as well as hyponatraemia.13 Importantly, in most patients with type 1 von Willebrand disease, who would respond to DDAVP, factor levels will have risen during pregnancy, but in patients with type 2 and type 3 von Willebrand disease, who have the greatest need for elevation of VWF, the response to DDAVP is generally poor.16 As such, if treatment is needed, the AHCDO recommends administration of VWF-containing concentrates in the antenatal treatment of von Willebrand disease, although DDAVP may be a suitable alternative in women who are carriers of haemophilia A.

Labour and delivery

Normal vaginal delivery is recommended for women with inherited bleeding disorders.1,2,6,7,9-13 Caesarean section does not eliminate the risk of cranial haemorrhage in the neonate, and elevates the risk of bleeding and the factor replacement requirements of the mother.1,7 In some series, the risk of cranial bleeding was in fact higher with caesarean section compared with vaginal delivery.1,7 However, the use of vacuum extraction is contraindicated because of the unacceptably high risk of cranial haemorrhage (about 60%). Also, the use of forceps and a prolonged labour should be avoided.1,7,17 The mode of delivery should ultimately be determined on obstetric grounds.

A normal factor level in the mother (or, in women with von Willebrand disease, results of quantitative and functional assays for VWF) is desirable for delivery and, if the factor level is abnormal (see previous section), replacement therapy may be required.1,7,9,10

Management of neonates
Infants at risk of a severe bleeding disorder

Testing of cord blood for inherited bleeding disorders is recommended in the guidelines of the Haemophilia Centre Doctors’ Organisation in the United Kingdom and is very useful in excluding severe disease.1 However, its value in milder disease (particularly haemophilia B) is controversial, and results should be confirmed by peripheral blood testing. In addition, adult levels of vitamin-K-dependent clotting factors and factor XI may not be present until after 6 months of age.

The risk of intracranial haemorrhage is around 4% in newborns with severe haemophilia.1,7,17 In haemophilia, predelivery ultrasound determination of the sex of the fetus is useful, because female infants do not ordinarily have an elevated risk of cranial haemorrhage. The risk of cranial haemorrhage is also increased in neonates with severe forms of von Willebrand disease,2 but is very rare in infants with factor XI deficiency.11

The AHCDO recommends that neonates with a bleeding disorder receive a transfontanel ultrasound examination soon after birth to check for intracranial haemorrhage. Because intracranial haemorrhage may be delayed (median time after delivery is 4.5 days), mothers should be made aware of potential symptoms, such as vomiting, seizures and poor feeding.26

Prophylactic factor replacement therapy should not be routinely given and may be associated with an increased risk of inhibitor development in children with haemophilia (inhibitor development is an immune response inhibiting factor replacement from stopping a bleeding episode).1,3,27 Similarly, the use of prophylactic recombinant factor VIIa has not been shown to improve clinical outcomes.3

In neonates with haemophilia or severe subtypes of von Willebrand disease, vitamin K should be given orally or subcutaneously.1 Immunisation should be given subcutaneously or intradermally.1,3

  • Scott M Dunkley1,2
  • Susan J Russell3
  • John A Rowell4
  • Chris D Barnes5
  • Ross I Baker6
  • Megan l Sarson2
  • Alison M Street7
  • on behalf of the Australian Haemophilia Centre Directors’ Organisation

  • 1 Institute of Haematology, Royal Prince Alfred Hospital, Sydney, NSW.
  • 2 Australian Haemophilia Centre Directors’ Organisation, Melbourne, VIC.
  • 3 Centre for Children’s Cancer and Blood Disorders, Sydney Children’s Hospital, Sydney, NSW.
  • 4 Haematology Department, Royal Brisbane Hospital, Brisbane, QLD.
  • 5 Henry Ekert Haemophilia Treatment Centre, Royal Children’s Hospital, Melbourne, VIC.
  • 6 Thrombosis and Haemophilia Service, Royal Perth Hospital, Perth, WA.
  • 7 The Alfred Hospital, Melbourne, VIC.

Competing interests:

None identified

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