Table Of ContentGroveretal.BMCPregnancyandChildbirth2013,13:16
http://www.biomedcentral.com/1471-2393/13/16
CASE REPORT Open Access
Pseudo (Platelet-type) von Willebrand disease in
pregnancy: a case report
Neetu Grover1, Vincent Boama2* and Munazzah Rifat Chou1
Abstract
Background: Pseudo (platelet-type)-von Willebrand disease is a rare autosomal dominant bleeding disorder caused
byan abnormal function of theglycoproteinlb protein; the receptor for von Willebrand factor. This leads to an
increased removalof VWF multimers from thecirculationas well as platelets and this results ina bleeding diathesis.
Worldwide, less than 50 patients are reported withplatelettypevon Willebrand disease (PT-VWD).
Case presentation: We describe the management ofplatelet typevon Willebrand disease inpregnancy of a 26
year old Caucasian primigravida. The initial diagnosis was made earlier following a significant haemorrhage post
tonsillectomy several years prior to pregnancy. The patient was managed under a multidisciplinary team which
included obstetricians,haematologists,anaesthetists and neonatologists.Careplansweremadefortheante-natal,
intra-partumandpost-partumperiodsinpartnershipwiththepatient.Thepatient’splateletcountlevelsdropped
significantlyduringtheantenatalperiod.Thisnecessitatedtheactiveexclusionofothercausesofthrombocytopeniain
pregnancy.Avaginaldeliverywasdesiredandplansweremadeforinductionoflabourat38weeksofgestationwith
plateletcoverinviewoftheprogressivefalloftheplateletcount.Thepatienthoweverwentintospontaneouslabour
onthedayofinduction.Shewastransfusedtwounitsofplateletsbeforedelivery.Shehadanunassistedvaginal
deliveryofahealthybaby.Thesuccessfulantenatalcounsellinghasencouragedthediagnosisofthesameconditionin
hermotherandsister.Wefoundthistobeaparticularlyinterestingcaseaswellaschallengingtomanageduetoits
rarity.PsuedovonWillebranddiseaseinpregnancycanbeconfusedwithanumberofotherdifferentialdiagnoses,
suchasgestationalthrombocutopenia,idiopathaticthrombocytopenia,thromboticthrombocytopenicpurpuraand
pre-eclampsia;allneedconsiderationduringinvestigationseveninacasesuchasthiswherethediagnosisofplatelet
typevonWillebranddiseasewasknownbeforepregnancy.
Conclusion:ManagementofpseudovonWillebranddiseaseinpregnancyinvolvestheco-operationof
multidisciplinaryteams,regularmonitoringofplateletlevelsandfactorVIIIandreplacementasappropriate.Thiscase
reporthighlightsthisrareconditionandtheneedtoexcludealltheotherdifferentialdiagnosesofthrombocytopenia
inpregnantwomenwiththrombocytopenia.
Keywords:VonWillebrand,Platelettype,Thrombocytopenia,Pregnancy
Background circulating platelets to the site of damage and binds to
VonWillebranddisease(VWD)isthemostcommonher- Factor VIII preventing its clearance from plasma. Presen-
editary coagulopathy which results from the deficiency or tation varies according to the extent of deficiency and
abnormalfunctionofvonWillebrandfactor(VWF)which ranges from abnormal menstrual bleeding, bleeding from
is required for platelet adhesion and aggregation. VWF gums,andnosebleedstohaemathrosis.
producedintheendotheliumisamultimericglycoprotein The three hereditary types of VWD described are type
which assists in platelet plug formation by attracting 1, type 2 and type 3. Type 1 is a quantitative defect and
type 2 is a qualitative defect. The severest form is type 3
*Correspondence:[email protected] whichisaquantitativedefectinwhichlevelsofVWFmul-
2DepartmentofObstetricsandGynaecology,RoyalCornwallHospital,Truro, timersmaybeundetectable.Type2BvonWillebranddis-
Cornwall,England,UK
ease was first described in 1980 and is caused by a
Fulllistofauthorinformationisavailableattheendofthearticle
©2013Groveretal.;licenseeBioMedCentralLtd.ThisisanOpenAccessarticledistributedunderthetermsoftheCreative
CommonsAttributionLicense(http://creativecommons.org/licenses/by/2.0),whichpermitsunrestricteduse,distribution,and
reproductioninanymedium,providedtheoriginalworkisproperlycited.
Groveretal.BMCPregnancyandChildbirth2013,13:16 Page2of4
http://www.biomedcentral.com/1471-2393/13/16
functionally defective von Willebrand factor (VWF). It is Case presentation
an autosomal dominant bleeding disorder and results A 26 year old primigravida was referred to the antenatal
from a gain of mutation in the VWF gene, commonly clinic at 14 weeks gestation with a known diagnosis of
exon28codingfortheA1domain. pseudo (platelet type) von Willebrand disease. The pa-
Closelysimilartotype2Bistheplatelet-typeorpseudo- tient had been asymptomatic with this condition until
von Willebrand disease (PT-VWD). It is an autosomal diagnosis at the age of 16 following excessive haemor-
dominant disorder caused by gain of function mutations rhage immediately after a tonsillectomy. Haematology
of theVWF receptor on platelets. There is an abnormally clinical records indicate the following results at the ini-
enhancedbindingofnormalVWFtoanabnormalplatelet tial diagnosis: type of GP1BA mutation as Gly233Val,
glycoproteinIba(GP1ba)receptor[1]. VWF:Ag as 54 IU/dL, VWF:RCO as 38 IU/dL and Fac-
Mutation in the GP Iba gene(GP1BA) onchromosome tor VIII as 68 IU/dL. The results of VWF levels could
17 results in impairment of the haemostatic function of not be found and hence are not included. At the time of
VWFduetoacceleratedremovalofVWFmultimersfrom her antenatal booking, she was asymptomatic and was
thecirculation[2]. not undergoing any treatment for her condition. A truly
ThePhenotype of PT-VWD is as aresult of 4 reported multi-disciplinary team(MDT)wasinvolvedinherante-
mutations[3-6]: natal, intra-partum and postpartum care which included
haematologists, anaesthetists, neonatologists as well as
1)Gly233Valmutation. senior obstetricians.
2)Met239Valmutation. Thisplaysacriticalrole in
regulationofVWF binding, Antenatalcare
3)Gly233Sermutation, Theantenatalplanwasdiscussedwiththepatientduring
4)27basepairdeletion. several visits and the MDT. A plan was made for vaginal
deliveryat term. To facilitate a safe pregnancy and deliv-
Patients with PT-VWD and type 2bVWD have simi- ery, thefollowingcare planwasmade:
lar phenotypic parameters and clinical symptoms and
distinguishing between the two can be a diagnostic (cid:129)Regularantenatalfollowupat24,28, 32and 36
challenge. However, these two conditions have differ- weeksgestation
ent aetiology and require different treatment modal- (cid:129)FVIIIand plateletlevels tobe checkedat24 and32
ities [7]. A recent case series of platelet type von weeksgestation
Willebrand disease in pregnancy highlights the rarity (cid:129)HLA-matched plateletstobemadeavailableonsite
and importance of this condition [8]. The diagnostic fordelivery
criteria for PT-VWD can be challenging and current (cid:129)Anyadmissionassociatedwith theriskof bleeding
scientific literatures still debate it. An International shouldprompt arequest fortheappropriateplatelets
registry –based study [9] has reported less than 50
patients worldwide with PT-VWD. This important Intra-partumcareplan
study also provides the frequency of PT-VWD versus
type2BVWDinadditiontothepercentageofmisdiag- (cid:129)Traumaticdeliveryshouldbeavoidedasthebabyhas
nosis of PT-VWD. A clear diagnostic criterion is a50%chance ofinheritingthebleedingdisorder.
explainedinthispublication. (cid:129)Regional anaesthesia absolutelycontraindicated
Differentiation of the two conditions has important
therapeutic implications. Whereas some patients with Post-partumcareplan
type2B VWD can be treated with desmopressin, this is
generally avoided as it causes release of abnormal VWF (cid:129)Umbilical cordbloodforplateletcount aswellas
and worsens the bleeding condition. Ideally, patients VWFofthenewborn
are treated with platelet transfusion however the major-
ity require treatment with a plasma –derived VWF/fac- Routinedatingscanwasperformedbya sonographerat
tor VIII concentrates and cryoprecipitate. The use of 12 weeks gestation. A fetal anomaly scan was performed
cryoprecipitate in PT- VWD remains contentious, with at20weeks gestation.Noabnormalityofthefetusorpel-
increasing thrombocytopenia having been reported vic and genital structures was identified. No placental ab-
with these products .Partial correction of plasma VWF normalitieswerenoted.Serialfetal growthscansat28,32
level however has been effective in some patients as and36weeksindicatedanormalgrowingfetus.
reviewed by Miller [2]. An individualised approach is Throughout the pregnancy the patient became in-
suggested for both treatment and prophylaxis in PT- creasingly thrombocytopenic, but remained asymptom-
VWD. atic and clinicallywell.Othercausesofthrombocytopenia
Groveretal.BMCPregnancyandChildbirth2013,13:16 Page3of4
http://www.biomedcentral.com/1471-2393/13/16
in pregnancy such as pre-eclampsia, gestational throm- 49onday1postpartum.Shewasfollowedupinthecom-
bocytopenia and thrombotic thrombocytopenia were munity by her general practitioner ( GP) and the haema-
considered and investigated in order to exclude their tologyteam.Herplateletcountwas81and175at2weeks
superimposition on PT-VWD. The following investiga- and6 weeks postpartum respectively. Thepatientand her
tions were performed to exclude the above differential family continue to be under the care of the GP and the
diagnosis:afullbloodcount,clottingscreen,abloodfilm, haematologyteam.
serumurea,creatinineandelectrolytes,24hoururinepro-
tein collection, liver function tests, regular blood pressure Conclusions
monitoring and a full clinical and neurological examina- In our patient, there was no diagnostic challenge in dis-
tions.Theresultsofalltheseinvestigationsremainednor- tinguishing it from type 2B VWD since the diagnosis of
mal throughout the pregnancy with the exception of the platelet type von Willebrand disease (PT-VWD) had
platelet count levels. At 32 weeks the worsening throm- been established pre-pregnancy. Bone marrow biopsy
bocytopenia (Table 1) prompted a change in the delivery was not performed as we did not find it an appropriate
plan. Discussion between the MDTand patient led to the investigation under the circumstances. Von Willebrand
followingnewplan: factor during the pregnancy were not checked since it
was felt by the team that it was not going to affect the
(cid:129)Induction oflabour at38 weeksinviewofworsening clinical management. The challenges faced in this case
thrombocytopenia. were determining when to institute platelet transfusion
(cid:129)Crossmatch 4unitsof bloodonadmissionatthe and whether to give cryoprecipitate and also when
timeofinductionoflabour . to induce labour in view of the significant drop in
(cid:129)Weekly platelet countuntilthe timeofdelivery. platelet count with advancing gestation. There were
also concerns about the wider differential diagnosis of
The patient was admitted at 38 weeks gestation for in- thrombocytopenia including superimposed preeclamp-
duction of labour. She however went into spontaneous sia, gestational thrombocytopenia, idiopathic throm-
labour on the day of her induction. She required 2 units bocytopenia and thrombotic thrombocytopenia which
of platelet transfusion before delivery. The active stage of were actively excluded. The rarity of this condition and
labourlastedabout8hours.Shehadanunassistedvaginal hence the relative lack of expertise in its management
delivery of a healthy male baby weighing 3.15 kg with an made it more challenging. The involvement of multi-
Apgar score of 9 in 1 minute and 10 in 5 minutes. The disciplinary senior team members resulted in a success-
total blood loss at delivery was 400ml. The paediatricians ful outcome for both the patient and the neonate. The
attending the delivery performed a comprehensive review opportunistic counselling that this patient received
of the neonate and also performed the cord blood tests during her pregnancy also led to the diagnosis under
for platelet count and VWF levels. We were informed by the haematologist of the same condition in both her
the paediatric team that the cord blood tests were all mother and sibling.
withinthenormalrange. Thisrarecasemayhaveeducationalvaluetomanyobste-
triciansandhaematologistsworldwidebecauseithighlights
Postnatal thehaemostaticcomplicationswithpregnancy.Werecom-
Thepost-partumperiodwasuneventfulandsheremained mendincludingPT-VWDintheinvestigationlistforevery
clinically well and asymptomatic. Her platelet count was pregnant woman who presents with thrombocytopenia for
Table1Bloodresults
Gestation Haemoglobing/dl Platelet RBC HCT MCV MCH Prothrombin APTT(S) FactorVIII(%)
10×9/l 10×12/l time(S)
Booking 13.6 171 4.55 0.434 88.3 29.9
24weeks 12.6 62 3.93 0.35 89.7 32.0 101
28weeks 13.1 38 4.07 0.37 92.3 32.3
32weeks 12.6 17 3.89 0.358 91.2 32.4 13 26 183
34weeks 12.5 35 3.93 0.365 93.0 31.9 12 25
36weeks 13.0 23 4.11 0.380 92.5 31.5
37weeks 13.5 40 4.21 0.388 92.3 32.0
38weeks 12.9 19 4.05 0.370 92.2 31.9
Day1postpartum 11.1 49 3.47 0.313 90.1 32.0
Groveretal.BMCPregnancyandChildbirth2013,13:16 Page4of4
http://www.biomedcentral.com/1471-2393/13/16
thefirsttime.Itistheopinionofsomehaematologyexperts
that Platelet type von Willebrand disease may be found to
be more common than current literature indicates if it is
sufficientlyinvestigated.
Consent
Written informed consent wasobtained from thepatient
for publication of this Case report. Acopy of the written
consentisavailableforreviewbytheSeriesEditorofthis
journal.
Competinginterests
Wedeclarethatwehavenocompetinginterestsasauthorsofthiscase
report.
Authors’contributions
NGwasinvolvedintheclinicalmanagementofthispatient.NG,MRCandVB
contributedequallytothewriteupofthiscasereport.Allauthorshaveread
andapprovedthefinalmanuscript.
Authordetails
1DepartmentofObstetrics&Gynaecology,EastSurreyHospital,RedhillRH1
5RHTEngland,UK.2DepartmentofObstetricsandGynaecology,Royal
CornwallHospital,Truro,Cornwall,England,UK.
Received:13June2012Accepted:13January2013
Published:17January2013
References
1. WeissHJ,MeyerD,RabinowitzR,PietuG,GirmaJP,VicicWJ,RogersJ:
Pseudo-vonWillebrand'sdisease.Anintrinsicplateletdefectwith
aggregationbyunmodifiedhumanfactorVIII/vonWillebrandfactorand
enhancedadsorptionofitshigh-molecular-weightmultimers.NEJM1982,
11;306(6):326–333.
2. MillerJL,CunninghamD,LyleVA,FinchCN:Mutationinthegene
encodingthealphachainofplateletglycoproteinIbinplatelet-typevon
Willebranddisease.ProceedingsoftheNationalAcademyofSciencesofthe
USA1991,88:4761–4765.
3. EnayatMS,GuilliattAM,SurdharGK,JenkinsPV,PasiKJ,TohCH,Williams
MD,HillFG:AberrantdimerizationofvonWillebrandfactorastheresult
ofmutationsinthecarboxy-terminalregion:identificationof3
mutationsinmembersof3differentfamilieswithtype2A(phenotype
IID)vonWillebranddisease.Blood2001,98:674–680.
4. TakahashiH,MurataM,MorikiT,AnboH,FurukawaT,NikkuniK,ShibataA,
HandaM,KawaiY,WatanabeK,etal:SubstitutionofValforMetat
residue239ofplateletglycoproteinIbalphainJapanesepatientswith
platelet-typevonWillebranddisease.Blood1995,1;85(3):727–733.
5. RussellSD,RothGJ:Pseudo-vonWillebranddisease:amutationinthe
plateletglycoproteinIbalphageneassociatedwithahyperactive
surfacereceptor.Blood1993,81(7):1787–1791.
6. OthmanM,NotleyC,LavenderFL,WhiteH,ByrneCD,LillicrapD,
O'ShaughnessyDF:Identificationandfunctionalcharacterizationofa
novel27-bpdeletioninthemacroglycopeptide-codingregionofthe
GPIBAgeneresultinginplatelet-typevonWillebranddisease.Blood2005,
1;105(11):4330–4336.
Submit your next manuscript to BioMed Central
7. EnayatMS,GuilliattAM,LesterW,WildeJT,WilliamsMDH,HillFG:
Distinguishingbetweentype2Bandpseudo-vonWillebranddiseaseand and take full advantage of:
itsclinicalimportance.BrJHaematol2006,13:664–666.
8. O’ConnorD,LesterW,WilloughbyS,WildeJT:Pregnancyinplatelet-type • Convenient online submission
VWD:acaseseries.ThrombHaemost2011,106(2):386–387.
• Thorough peer review
9. HamiltonA,OzeloM,LeggoJ,NotleyC,etal:Frequencyofplatelettype
versustype2BvonWillebranddisease.AnInternationalregistry-based • No space constraints or color figure charges
study.ThrombHaemost2011,105(3):501–508. • Immediate publication on acceptance
• Inclusion in PubMed, CAS, Scopus and Google Scholar
doi:10.1186/1471-2393-13-16
Citethisarticleas:Groveretal.:Pseudo(Platelet-type)vonWillebrand • Research which is freely available for redistribution
diseaseinpregnancy:acasereport.BMCPregnancyandChildbirth2013
13:16.
Submit your manuscript at
www.biomedcentral.com/submit
