Management of Inherited Bleeding Disorders in Pregnancy

Question 1

Haemophilia

What is the definition?

Answer 1

• Clinicians should be aware that haemophilia is an X-linked condition associated with reductionor absence of clotting factor VIII (haemophilia A) or IX (haemophilia B), causing bleedingsymptoms.

Question 2

Haemophilia

How should inheritance be assessed?

Answer 2

• Up to 50% of neonatal males with severe haemophilia have no previous family history. In thesecases, 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 haemophilia carriership in at-riskfemale family members.
• Females at risk of carrying haemophilia, particularly severe haemophilia, should be tested forthe genetic mutation present in affected family members, if available.

Question 3

Haemophilia

What are the different phenotypes and how is severity assessed?

Answer 3

• Clinicians should be aware of the different phenotypes and severities of haemophilia, as thisinfluences risk and required management.

Question 4

Haemophilia

What are the risks in pregnancy to mother and baby?

Answer 4

• Known or potential female carriers may have low factor VIII/IX levels. The levels should bechecked prior to an invasive procedure or in association with bleeding symptoms.
• Clinicians should be aware that carriers of haemophilia are at increased risk of bleeding withinvasive procedures, termination, spontaneous miscarriage and at the time of delivery.
• Male neonates with haemophilia are at increased risk of bleeding, including intracranialhaemorrhage (ICH) and extracranial haemorrhage (ECH).
• Male neonates with haemophilia are at risk of iatrogenic bleeding following delivery.

Question 5

Haemophilia

What is the prepregnancy management?

Answer 5

• The baseline factor level should be determined prior to onset of pregnancy.
• Before pregnancy, the general health of women who are carriers for haemophilia should beoptimised, including attention to weight and correction of any iron deficiency.

Question 6

Haemophilia

How should genetic counselling be provided?

Answer 6

• Genetic counselling should be provided to women at risk, ideally before pregnancy, byappropriately qualified and experienced clinical staff.
• Written informed consent should be obtained in advance of any genetic testing.

Question 7

Haemophilia

What are the options for prenatal diagnosis (PND)?

Answer 7

• Carriers of severe haemophilia should be offered preimplantation genetic diagnosis.
• Carriers of severe haemophilia with a male fetus confirmed to be affected by haemophiliashould be counselled to enable informed choices.
• All carriers of severe haemophilia should be offered fetal sex determination by free fetal DNAanalysis from 9 weeks of gestation.
• Pregnant carriers of severe haemophilia with a male fetus at risk of haemophilia should beoffered the option of PND with chorionic villus sampling at 11 –14 weeks of gestation.
• All carriers of haemophilia with male fetuses should be offered third trimester amniocentesis ifdiagnostic investigations have not previously been performed to determine haemophilia statusto inform options for delivery

Question 8

Haemophilia

What is the antepa rtum management?

Answer 8

• Antenatal care should be delivered in the context of a multidisciplinary team setting withhaematologists and obstetricians with expertise in this field.
• Maternal factor VIII/IX should be checked at booking, before any antenatal procedure and inthe third trimester; factor VIII levels rise in pregnancy, but factor IX tends to remain stable.
• Aim for factor VIII/IX levels of at least 0.5 iu/ml to cover surgical or invasive procedures, orspontaneous miscarriage. If treatment is required, factor levels of 1.0 iu/ml should be aimedfor and not allowed to fall below 0.5 iu/ml until haemostasis is secure.
• Tranexamic acid should be considered in combination with treatment for all those with levelsof less than 0.5 iu/ml or as sole therapy for those with levels above 0.5 iu/ml if clinicallyindicated. Following miscarriage, it should be continued until the bleeding settles.
• Desmopressin (DDAVP) can be used antenatally to raise factor VIII levels. Due to theantidiuretic effect, fluids should be restricted to 1 litre for 24 hours after use or, if not possible,electrolytes should be monitored.
• Recombinant factor VIII should be used if levels obtained with DDAVP are insufficient or in aknown nonresponder.
• Recombinant factor IX is required to cover invasive or surgical procedures in women withfactor levels less than 0.5 iu/ml.
• When giving treatment to raise clotting factor levels, it is important to monitor the response totreatment by measuring the plasma clotting factor concentration before and after infusion, and4–6 hours following treatment to facilitate dosing.
• Following any invasive or surgical procedure, a plan for ongoing treatment is required tomaintain the coagulation factor in the normal range for a suitable duration, determined by thenature of the procedure.
• A clear plan for the intrapartum care of a carrier and the baby should be available in advanceof 37 weeks of gestation. The woman should be seen in the anaesthetic clinic and theneonatologists should be informed of the intended delivery of a baby with haemophilia.
• If antenatal diagnosis has not been performed in a male fetus, then he should be managed asif he is affected.
• External cephalic version should be avoided in affected or potentially affected male fetuses andfemale fetuses who are obligate or possible carriers of severe haemophilia

Question 9

Haemophilia

What is the optimal mode an d timing of delive ry?

Answer 9

• A decision regarding the timing and mode of delivery should be agreed jointly between thewoman and the multidisciplinary team.
• The option of a planned lower segment caesarean section should be discussed for the deliveryof affected male babies, especially those with severe haemophilia and/or if the fetal status isunknown. However, there needs to be a full assessment of the advantages and disadvantagesof this mode of delivery and consideration of obstetric factors, maternal bleeding risk, patientpreference and reproductive expectations.
• If elective caesarean section is intended, this should be at 39+0completed weeks with a clearplan for the event of spontaneous labour occurring beforehand.
• For intended vaginal delivery, spontaneous labour is preferred, if no other obstetric concerns,to minimise the risk of intervention. Measures should be taken to ensure expertise andnecessary resources are available at all times. Planned induction of labour may be necessary incases where there are concerns about distance of travel to the specialist centre or if there areother obstetric concerns.
• The use of ventouse and midcavity forceps should be avoided for male babies at risk ofhaemophilia.
• Fetal blood sampling (FBS) and fetal scalp electrode (FSE) should be avoided in babies expectedto have severe or moderate haemophilia. In babies potentially affected with mild haemophilia,judicious use of FBS and FSE can be considered, in order to facilitate vaginal delivery and avoidmorbidity associated with caesarean section in labour. This decision should be made by a seniorobstetrician. Where FBS is used, sustained pressure under direct vision should be used toensure haemostasis.
• The plan for intrapartum management and the second stage of labour, involving a seniorobstetrician, should be documented.
• There is no evidence to recommend special measures for delivery in women carrying femalefetuses. A female fetus who is at risk of carrying severe haemophilia B may theoretically bemore at risk of ICH/ECH and this should be considered in the birth plan.

Question 10

Haemophilia

How can analgesia and anaesthesia be managed safely?

Answer 10

• Factor VIII/IX levels of more than 0.5 iu/ml are required for the insertion and removal ofepidural catheter and for spinal anaesthesia.
• Experienced clinicians should be involved in decisions about whether or not to perform acentral neuraxial anaesthetic technique, and the woman should be given all the informationshe needs to make an informed choice.
• The most suitable form of analgesia depends on the context of the delivery. All carriers shouldhave the opportunity to discuss analgesia with a senior anaesthetist prior to delivery. A clearplan for analgesia and anaesthesia should be available in the maternal records.
• Intramuscular injections should generally be avoided if factor Vlll/IX levels are less than 0.5 iu/ml.They may be used when a woman’s factor VIII/IX is maintained in the normal range by clottingfactor support or DDAVP.

Question 11

Haemophilia

What is the haemo static management during labour?

Answer 11

• If clotting factor levels are less than 0.5 iu/ml, DDAVP should be given to raise factor VIII, orfactor IX concentrate should be given to raise factor IX, aiming for 1.0 iu/ml.
• Tranexamic acid could be considered as sole therapy for women with low normal levels or inconjunction with DDAVP to increase factor VIII, or with substantive factor IX treatment.
• Treatment should be given as close to delivery as possible.

Question 12

Haemophilia

What is the postpartum management?

Answer 12

• To minimise the risk of postpartum haemorrhage (PPH), it is important to recommend/offeractive management of the third stage of labour.
• Levels of factor VIII/IX should be maintained above 0.5 iu/ml for at least 3 days following anuncomplicated vaginal delivery or 5 days following instrumental delivery or caesarean section.Management should be guided by results of factor assays.
• Tranexamic acid should be continued postpartum until lochia is minimal.
• Pharmacological thromboprophylaxis should generally be avoided where the factor level is0.6 iu/ml or less, but will need to be considered in women with thrombotic risk factors, withcareful balance of risks.
• Following discharge from hospital, the haemophilia centre should maintain contact with thewoman who should be advised to report any increase in postpartum blood loss.

Question 13

Haemophilia

What is the neonatal management?

Answer 13

• A plan for diagnostic testing of the neonate following delivery, including cord blood sampling,should be included in the maternal pregnancy management plan.
• Coagulation results in neonates should be interpreted against age-adjusted reference ranges.
• Cord blood sampling and diagnostic testing is recommended for all male babies born tomothers who are carriers of haemophilia A/B although some mild cases may require retestingat 3 –6 months of age.
• Cord blood sampling and diagnostic testing of female babies born to mothers who are carriersof haemophilia is not recommended.
• Parents of neonates diagnosed with haemophilia should be informed of the diagnosis in atimely manner and arrangements should be made for neonatal follow-up at a haemophiliacentre.
• In a neonate with low factor levels, vitamin K should be administered by an oral regimen andfollowing neonate bloodspot screening, pressure should be sustained to avoid excess bleeding.
• Cranial ultrasound (US) should be considered prior to discharge in all neonates with severe ormoderate haemophilia.
• Cranial magnetic resonance imaging (MRI) should be undertaken in neonates with symptoms orsigns suggestive of ICH even in the presence of a normal cranial US.
• In neonates with haemophilia, information on the symptoms and signs of ICH should beprovided at the time of discharge.
• Short-term primary prophylaxis should be considered in severe and moderate haemophilia ininfants considered to be at increased risk of bleeding due to trauma at delivery or prematurity.
• Clinical bleeding events in neonates with haemophilia should be managed in accordance withtreatment guidelines.

Question 14

von Willebrand disease (VWD)

What is the class ification and inheritance?

Answer 14

• VWD is classified according to whether the deficiency of von Willebrand factor (VWF) is partialquantitative (type 1), qualitative (type 2) or severe quantitative (type 3). The classification isimportant for diagnosis, treatment and counselling of patients. However, it does not reliablypredict response to therapy and has a variable association with VWF gene mutations.
• Clinicians counselling these women should be aware that inheritance of VWD is autosomal andvariably dominant or recessive, depending on the VWD type.
• Genetic counselling about the risk of disease transmission, and its variable penetrance andexpression, should be provided for all women with VWD.

Question 15

von Willebrand disease (VWD)

What are the risks in pregnan cy to mother and baby?

Answer 15

• Clinicians should be aware that women with VWD have an increased risk of antepartum,primary and secondary PPH.
• All women should receive counselling about risks of increased bleeding, especially women withtype I VWD whose VWF level does not rise above 0.5 iu/ml by term, or type 2 or 3 VWD.

Question 16

von Willebrand disease (VWD)

What is the intrapar tum management?

Answer 16

• The timing of treatment should be as near to delivery as possible, and pre- and post-treatmentlevels of VWF activity and factor VIII levels should be measured and repeated after delivery, orif labour is prolonged.
• Tranexamic acid should be considered in combination with treatment for all those with VWFactivity less than 0.5 iu/ml, or as sole therapy for those with levels above 0.5 iu/ml if clinicallyindicated. This can be given orally or intravenously, and can be started prior to delivery.
• Platelet transfusions, as well as VWF factor replacement, may sometimes be required in type2B VWD.
• The mode of delivery should be guided by obstetric indications. Spontaneous labour andnormal vaginal delivery should be permitted if there are no other obstetric concerns, tominimise risk of intervention.
• For fetuses at risk of having type 2 or 3 VWD, FBS, external cephalic version, fetal scalpmonitoring, ventouse delivery and midcavity forceps should be avoided.

Question 17

von Willebrand disease (VWD)

How can analgesia and anaesthesia be safely managed?

Answer 17

• For patients with type 1 VWD, where VWF activity has been normalised by pregnancy ortreatment, central neuraxial anaesthesia can be offered.
• For patients with type 2 disease, central neuraxial anaesthesia should be avoided unless VWFactivity is more than 0.5 iu/ml and the haemostatic defect has been corrected; this may bedifficult to achieve in type 2 and central neuraxial anaesthesia should not be given in cases oftype 3.
• For patients with type 2N VWD, central neuraxial anaesthesia should be avoided unlessfactor VIII level is more than 0.5 iu/ml.PPrior to delivery, all women should be given the opportunity to discuss analgesia with a seniorobstetric anaesthetist.
• In patients where an epidural catheter has been placed, consideration should be given to theneed for repeat treatment prior to catheter removal, as the risk of bleeding is no less thanwith insertion.
• Intramuscular injections and postnatal nonsteroidal anti-inflammatory drugs (NSAIDs) are onlysuitable in the short term when VWF activity and factor VIII are more than 0.5 iu/ml.

Question 18

von Willebrand disease (VWD)

What is the neonatal management?

Answer 18

• A plan for the diagnostic testing of the neonate following delivery, including cord bloodsampling, should be included in the maternal pregnancy management plan.
• Cord blood samples for VWF activity should be taken for babies at risk of type 2 and 3 VWD.
• For neonates at risk of type 2 or 3 VWD, vitamin K should be given orally, unless VWF activityis shown to be normal.
• Neonates with type 3 VWD should be considered for routine cranial imaging prior to dischargeand for short-term prophylaxis, with factor concentrate, if there has been significant potentialtrauma at delivery.

Question 19

Factor XI deficiency

What is the inheritance?

Answer 19

• Factor XI deficiency is an uncommon autosomal disorder which has both recessive anddominant inheritance patterns.
• The incidence in the non-Jewish population is 1/1 000 000; it is common in Ashkenazi Jews with heterozygosity in 8% and homozygosity in 0.2–0.5%.
• Clinicians should be aware that there is intra- and inter-individual variation in bleeding phenotype.

Question 20

Factor XI deficiency

What are the different phenotypes?

Answer 20

• Plasma levels of factor XI show poor correlation with bleeding symptoms.
• Spontaneous bleeding is rare, even with very low factor XI levels. However, these patients areoften at risk of bleeding following surgery or trauma.
• Heterozygotes have mild or moderate reduction in factor XI levels (more than 0.15–0.20 iu/ml).Most are asymptomatic, but patients with even mild reductions in factor XI (0.5– 0.7 iu/ml) mayhave a bleeding tendency.

Question 21

Factor XI deficiency

What are the risks in pregnancy to mother and baby?

Answer 21

• Factor XI does not usually increase during pregnancy; however, levels should be checked atbooking, in the third trimester and prior to invasive procedures.
• Women with factor XI de ficiency may suffer excessive bleeding after miscarriage ortermination, especially if they have a bleeding phenotype.
• There is increased risk of PPH in factor XI-deficient women, which is highest in those with a bleeding phenotype and of blood group O, and least in non-O blood groups with a nonbleeding phenotype.
• Patients with factor XI deficiency should be assessed for the presence of other potentiallycompounding factors, such as low VWF levels and platelet dysfunction.
• No special precautions for the baby are required for delivery unless the neonate is at risk ofhomozygosity or compound heterozygosity.

Question 22

Factor XI deficiency

What are the therapeutic options?

Answer 22

• Treatment options include tranexamic acid, factor XI concentrate and fresh frozen plasma (FFP),however, women with a nonbleeding phenotype or unknown status can often be managedexpectantly.
• Tranexamic acid should not be given simultaneously with prophylactic factor XI concentrate asthis is considered to increase thrombotic risk. For many women, it is likely that tranexamic acidalone will be sufficient to prevent PPH.
• f FFP is given to raise factor XI levels, solvent detergent (SD)-FFP should be used when available.
• Recombinant factor VIIa is not licensed for this condition and is generally not recommended,except if there is an inhibitor to factor XI.

Question 23

Factor XI deficiency

What is the antena tal, intrapartum and postpartum management ?

Answer 23

• Factor XI or tranexamic acid is not usually required antenatally unless an invasive procedure isundertaken or if there is bleeding following miscarriage or surgical procedure.
• Delivery plans need to be individualised. Prophylactic factor XI replacement should beconsidered if homozygous/compound heterozygous, previous history of PPH or general bleedinghistory. Otherwise, management can be expectant, with tranexamic acid alone and factorreplacement reserved for excess bleeding.

Question 24

Factor XI deficiency

Can central neuraxial anaesthesia be given?

Answer 24

• Central neuraxial anaesthesia should not be given to women with low factor XI levels with a knownbleeding phenotype, where the phenotype is not clear or when there is a severe reduction in level.In those with a nonbleeding phenotype, discussion and counselling should be given regarding therisks and benefits of allowing neuraxial anaesthesia with or without factor replacement.

Question 25

von Willebrand disease (VWD)

What is the postpartum management?

Answer 25

• It is important to ensure that VWF activity and factor VIII levels are maintained at more than0.5 iu/ml for at least 3 days following uncomplicated vaginal delivery and at least 5 daysfollowing instrumental delivery or after caesarean section. Management should be guided byresults of laboratory investigations.
• Women with VWD should be considered for tranexamic acid for the postpartum period. Astandard dose is 1 g three to four times a day for 7–14 days. In some cases, prolongedadministration for 2 – 3 weeks or more may be necessary.
• If thromboprophylaxis is indicated, low-molecular-weight heparin (LMWH) may be given toinpatients with adequate correction of VWF:RCo and factor VIII levels. When pharmacologicalthromboprophylaxis is contraindicated, mechanical methods should be employed.
• Women with VWD should be made aware of the risk of delayed bleeding and be encouragedto report excessive bleeding. For women with more severe cases, HB should bemonitored and regular contact with the patient maintained for several weeks. Patients withtype 3 VWD may require treatment with VWF concentrate for 2–3 weeks or even longerfollowing delivery.

Question 26

Rare bleeding disorders

What are they?

Answer 26

• Clinicians should be aware that rare bleeding disorders include inherited deficiencies offibrinogen, factors II, V, VII, X, XI and XIII, combined factor V and factor VIII (factor V+VIII)deficiencies, and congenital deficiency of vitamin K-dependent factors.

Question 27

Rare bleeding disorders

What is the inheritance of factors II, V, VII, X and XIII, and combine d factor V+VIII deficiencies?

Answer 27

• Genetic counselling should be provided, with the understanding that most rare inheritedbleeding disorders are autosomal recessive in inheritance and heterozygote carriers are usuallyasymptomatic. For affected women or asymptomatic heterozygous carriers, consanguinity should be established to allow counselling, screening when possible and formulation of adelivery plan for a potentially affected baby.

Question 28

Rare bleeding disorders

What are the risks in pregnancy to mother and baby, and what are the treatment options?

Answer 28

• Clinicians should appreciate that coagulation factor levels can change during pregnancy.However, this is unlikely to influence haemostasis in women with severe deficiency.Management should take into account both the factor level and whether there is a clinicalhistory of bleeding.
• Treatment plans may need to be modified according to the nature of individual bleeds orprocedures, and to the background bleeding phenotype of each case. Factor replacement therapyis usually advised for delivery in women with severe coagulation factor deficiency and/ora bleeding history. Tranexamic acid at a dose of 15–20 mg/kg or 1 g four times daily alone can beused for minor bleeds and in combination with factor replacement.
• If the baby is at risk of severe deficiency, the delivery plan should include avoidance ofventouse, midcavity forceps, FBS and FSE.
• Central neuraxial anaesthesia, postpartum pharmacological thromboprophylaxis and NSAIDsshould usually be avoided in women with severe deficiencies as it may be difficult to guaranteeconsistent normalisation of haemostasis even after treatment. They may be used afterindividual assessment if adequate replacement therapy is confirmed.

Question 29

Rare bleeding disorders

Prothrombin (factor II) deficiency

Answer 29

• If factor II activity is less than 0.2 iu/ml and there is significant bleeding, established labour orprior to caesarean section, give prothrombin complex concentrate 20–40 iu/kg to achieve factor IIactivity 0.2–0.4 iu/ml. Consider further prothrombin complex concentrate 10–20 iu/kg at 48-hourintervals to maintain factor II activity more than 0.2 iu/ml for at least 3 days. Women alreadyreceiving prophylactic prothrombin complex concentrate can continue it throughout pregnancy

Question 30

VWD

What is the prepregnancy and antenatal management?

Answer 30

• Prior to conception, the bleeding phenotype should be assessed, historical diagnosis reviewedand response to DDAVP established.
• Safe management requires a multidisciplinary approach.
• All women with VWD should have VWF antigen levels and activity, and factor VIII levelschecked at booking, in the third trimester and prior to any invasive procedures.
• Women with type 1 VWD who achieve normal VWF levels can be safely managed in standardobstetric units in collaboration with haemophilia centre staff.
• Women with types 2 and 3, or severe type 1 VWD should be referred for prenatal care anddelivery to a centre where there are specialists in high-risk obstetrics, as well as a haemophiliacentre. Facilities for laboratory monitoring of VWF and factor VIII levels are essential.
• Clinicians should aim for factor VIII and VWF ristocetin cofactor (VWF:RCo) activity levels of0.5 iu/ml or above to cover surgical procedures or spontaneous miscarriage
• Where invasive procedures are required, if VWF activity or factor VIII levels are less than0.50 iu/ml, women should receive haemostatic support in the form of DDAVP, whereresponsive, or VWF-containing concentrates.
• Treatment should be with DDAVP in preference to blood-derived factor concentrates wherepossible. This is safe for use in pregnancy and at delivery, but should be avoided inpre-eclampsia.
• Fluid intake should be restricted to 1 litre for 24 hours following DDAVP administration toprevent maternal hyponatraemia. If additional fluid is required, electrolytes should bemonitored.
• Clinicians should be aware that patients with type 2B VWD may develop thrombocytopeniafollowing DDAVP treatment.
• If VWF replacement therapy is required, a concentrate containing factor VIII and VWF,manufactured from a safe plasma source with adequate viral testing and inactivationprocedures should be used.
• Target peak VWF activity levels should be 1.0 iu/ml and levels maintained above 0.5 iu/ml untilhaemostasis is secured.
• For most antenatal procedures, a single preoperative treatment is sufficient, but in some cases,a second dose may be required at 12–24 hours, depending on the nature of the procedure and the measured levels.

Question 31

Rare bleeding disorders

Factor V deficiency

Answer 31

• For significant bleeding or delivery in women with factor V activity less than 0.2 iu/ml,15–25 ml/kg FFP should be considered once in established labour or before caesarean sectionto achieve factor V activity 0.2–0.4 iu/ml with further FFP 10 ml/kg at 12-hour intervals tomaintain factor V activity more than 0.2 iu/ml for at least 3 days. Where possible, SD-FFPshould be used to reduce infective risk.
• For severe bleeding or caesarean section, consider additional platelet transfusion

Question 32

Rare bleeding disorders

Severe factor VII deficiency

Answer 32

• For factor VII activity less than 0.2 iu/ml in the third trimester with prior history of bleeding,consider recombinant factor VIIa 15–30 micrograms/kg every 4–6 hours for at least 3 or 5 daysfollowing caesarean section. For all other women, recombinant factor VIIa 15–30 micrograms/kgis recommended only in response to abnormal bleeding. For mild bleeding, tranexamic acid(15–20 mg/kg or 1 g four times daily) can be used. For severe bleeding, recombinant factor VIIa15–30 micrograms/kg can be given and repeated if required every 4–6 hours, usually for aminimum of three doses.

Question 33

Rare bleeding disorders

Severe factor X deficiency

Answer 33

• For delivery in women with factor X activity less than 0.3 iu/ml in the third trimester who havea history of bleeding and all those who require caesarean section, use prothrombin complexconcentrate 20–40 iu/kg (or factor X concentrate if available) to achieve factor X activity morethan 0.4 iu/ml. Consider further prothrombin complex concentrate 10–20 iu/kg once daily tomaintain factor X activity more than 0.3 iu/ml for at least 3 days. Antenatal prophylaxis maybe considered in women with a history of recurrent bleeding or adverse pregnancy outcomeusing prothrombin complex concentrate 20–30 iu/kg two or three times a week to maintaintrough factor X more than 0.01 iu/ml

Question 34

Rare bleeding disorders

Severe factor XIII deficiency

Answer 34

• During pregnancy, increased intensity prophylaxis is required using factor XIII plasmaconcentrate or recombinant factor XIII (if A-subunit deficiency). Dosing frequency should beincreased from every 28 days to every 14–21 days to maintain factor XIII more than 0.2 iu/ml.For delivery, consider additional factor XIII concentrate 10–40 iu/kg once in established labouror before caesarean section, depending on the interval since last prophylaxis.

Question 35

Rare bleeding disorders

Factor V+VIII deficiency

Answer 35

• For delivery in women with combined factor V+VIII deficiency, if factor V activity less than0.2 iu/ml in the third trimester, consider SD-FFP 15–25 ml/kg once in established labour orbefore caesarean section to achieve factor V activity 0.2–0.4 iu/ml. Consider further SD-FFP10 ml/kg once every 12 hours to maintain factor V activity more than 0.2 iu/ml for at least3 days. Consider additional recombinant factor VIII if the factor VIII activity is less than 0.5 iu/mlin the third trimester.

Question 36

Fibrinogen disorders

What is the nature and inheritance of afibrinogenaemia, hypofibr inogenaemia and dysfibrinogenae mia?

Answer 36

Clinicians should be aware that fibrinogen disorders can be autosomal recessive(afibrinogenaemia) or autosomal dominant (with quantitative and/or qualitative defects) andare associated with a variable clinical phenotype.

Question 37

Fibrinogen disorders

What are the risks in pregnancy to mother and baby?

Answer 37

• Clinicians should be aware that severe fibrinogen deficiency may be associated with bleeding,but quantitative and qualitative deficiency can also be associated with thrombosis andpregnancy loss.

Question 38

Fibrinogen disorders

What is the manage ment of pregnancy and delivery?

Answer 38

• If functional fibrinogen less than 0.5 g/litre, consider prophylaxis throughout pregnancy withfibrinogen concentrate initially 50–100 mg/kg twice per week, adjusted to maintain troughfibrinogen activity more than 1 g/litre. Higher doses of fibrinogen concentrate are likely to berequired to maintain fibrinogen activity as pregnancy progresses. Consider additional fibrinogenconcentrate for established labour to ensure fibrinogen activity more than 1.5 g/litre for atleast 3 days. Tranexamic acid can be used for minor bleeding.
• Because of the variable clinical phenotype associated with hypofibrinogenaemia anddysfibrinogenaemia, a personal and/or family history is required for management decisions. Ifthere is no personal or family history of bleeding or thrombosis, expectant management isrecommended for pregnant women or the neonate.
• Fibrinogen replacement therapy is associated with a high risk of thrombosis and requires vigilance.Pregnant women with a thrombotic phenotype or other risk factors for venous thrombosis, andwith a low risk of bleeding, should be considered for thromboprophylaxis with LMWH.
• Central neuraxial anaesthesia, NSAIDs and intramuscular injections should generally be avoidedfor women with severe fibrinogen deficiency, or a personal or family history of bleeding, due tothe difficulty in assuring correction with factor concentrate. They may be used after individualassessment if adequate replacement therapy is confirmed.
• The use of midcavity forceps, rotational forceps, ventouse, FBS and FSE should be avoided in ababy at risk of fibrinogen deficiency associated with a bleeding phenotype.

Question 39

Platelet function disorders

Answer 39

• Clinicians should be aware that the spectrum of bleeding in patients with platelet functiondisorders varies and may first present in pregnancy.
• Women known to have a platelet dysfunction disorder should receive prepregnancy counsellingfrom a multidisciplinary specialist team with expertise in caring for patients with plateletfunction disorders.

Question 40

Bernard Soulier Synd rome (BSS)

What is the aetiology?

Answer 40

• Clinicians should be aware that BSS is caused by genetic abnormality of an important plateletadhesion receptor (glycoprotein [GP] Ib-IX-V receptor) and is often associated with a severebleeding phenotype.

Question 41

Bernard Soulier Synd rome (BSS)

What is the inheritance?

Answer 41

• BSS is an autosomal recessive disorder. In areas of high consanguinity, it may be prudent totest the father using platelet flow cytometry for GP Ib surface density.

Question 42

Bernard Soulier Synd rome (BSS)

What are the maternal risks?

Answer 42

• BSS is associated with significant risk of primary and secondary PPH, and wound haematoma.Management of delivery, therefore, requires careful planning with the multidisciplinary team.
• Peripartum haemostatic management should be guided by assessment of the individualphenotype.
• Patients with a bleeding history should be given a platelet transfusion prophylactically atdelivery or before caesarean section, in combination with tranexamic acid. Platelets should behuman leucocyte antigen (HLA)-matched where possible to reduce the risk of alloimmunisationand platelet refractoriness.
• Tranexamic acid should be given at the onset of labour and continued regularly through thepostpartum period until lochia is minimal.
• DDAVP has variable efficacy and is unlikely to be useful as sole therapy in BSS.
• Central neuraxial anaesthesia should be avoided

Question 43

Glanzmann’s thrombasthenia (GT)

What is the aetiology?

Answer 43

• Clinicians should be aware that GT is a disorder of platelet function with autosomal recessiveinheritance and is often associated with severe bleeding tendency.

Question 44

Glanzmann’s thrombasthenia (GT)

What are the maternal risks?

Answer 44

• GT is associated with significant risk of intrapartum and PPH, and a careful plan ofmanagement is needed for women preparing for labour and delivery.
• HLA-matched platelet transfusions and/or recombinant factor VIIa should be givenprophylactically, at delivery, for patients with a history of bleeding. Repeat doses may berequired depending on the clinical picture.
• DDAVP has not been shown to be effective in GT and is unlikely to be helpful.
• Tranexamic acid should be given from the onset of established labour and continued regularlythrough the postpartum period until lochia is minimal.
• Central neuraxial anaesthesia should be avoided.

Question 45

Glanzmann’s thrombasthenia (GT)

What are the risks to the fetus?

Answer 45

• Maternal alloimmunisation to paternally-derived fetal platelet antigens (GP IIb/IIIa) may causefetal thrombocytopenia and risk of ICH and other fetal bleeding.
• If fetal-maternal alloimmunisation does not occur, there is no need to restrict aids to delivery.

Question 46

Glanzmann’s thrombasthenia (GT)

What are the treatment options?

Answer 46

• Women should be monitored for platelet-specific alloantibodies at booking, and at 28 and34 weeks of gestation.
• If fetal-maternal alloimmunisation occurs, management should involve a fetal medicine unitwith experience of these conditions, and treatment with intravenous immunoglobulin with orwithout steroids should be considered.
• Amniocentesis with platelet typing may be considered in cases of paternal heterozygosity.
• If the baby is at risk of homozygous GT or fetomaternal alloimmune thrombocytopenia,restrictions to delivery should be applied, as for all babies at risk of ICH. This includesavoidance of ventouse, midcavity forceps, FSE and fetal scalp sampling. Depending on risk, anelective caesarean section may be considered.
• Neonatal care of potential alloimmunisation requires a cord platelet count and withholdingintramuscular vitamin K until the result is known, or administering it orally. A platelet countbelow the normal range should be repeated at day 3–5 when the platelet nadir is reached, dueto development of the neonatal spleen. Platelet transfusion should be given if the plateletcount is less than 30 3 109/litre

Question 47

Other congenital platelet function defects

What are the therapeutic options?

Answer 47

• Women with mild platelet function disorders may require treatment to cover delivery.
• DDAVP and/or tranexamic acid can be used to cover delivery.
• Tranexamic acid should be continued postpartum until lochia is minimal.
• Central neuraxial anaesthesia should only be given if the risks are considered to be outweighedby the benefits and the haemostatic defect has been corrected. A platelet transfusion may benecessary beforehand and epidural catheter should not be left in situ.