budd  chiari syndrome ( bcs ) is defined as obstruction of the hepatic venous outflow .
this obstruction might be located anywhere between the small hepatic veins to the suprahepatic inferior vena cava ( ivc ) .
the typical patient is a young woman presenting with abdominal pain , ascites , and hepatomegaly ; however , the clinical presentation varies .
usually patients show an underlying prothrombotic disorder , and in a substantial number of patients several risk factors are found .
the disease is mainly diagnosed by imaging , whereas therapeutic options comprise a step - wise approach with medication ( anticoagulation ) , minimally invasive procedures such as thrombolysis , percutaneous angioplasty , transjugular intrahepatic portosystemic shunting ( tips ) , but also surgical portosystemic shunting , and orthotopic liver transplantation ( ltx ) .
moreover , pregnancy in women with bcs is extremely rare ; pregnancy exerts a detrimental effect on the course of the disease .
here we report the case of a patient with bcs due to essential thrombocythemia ( et ) and tips which ended lethal within 19 months after delivery .
the university bonn medical school ethics committee allows publication without consent in such cases . additionally , we propose a score for risk classification of pregnancy in women with pre - existing bcs .
a stable course of disease could be achieved for 8 years by treatment with hydroxyurea , when acute bcs occurred with occlusion of all liver veins .
treatment consisted of lysis and veno - venous shunt ( palmaz - stent ) placement between left hepatic vein and ivc at a regional hospital ( figure 1 ) in conjunction with anticoagulant treatment using the vitamin k - antagonist ( vka ) phenprocoumon .
she remained stable for the subsequent 12 years with well - controlled hematologic disease and without thrombotic or portal hypertensive complications . at 36 years of age , progressive , recurrent ascites developed which was treated by creating a new tips using a baremetal and a covered stent .
( a ) invasive portography after left - sided tips placement demonstrating patent tips perfusion .
( b , c ) invasive tips - control demonstrating cavernous transformed portal occlusion and restored hepatopetal flow after tips elongation : ( 1 ) main portal vein ; ( 2 ) left portal vein ; ( 3 ) left hepatic vein .
this tips - tract was created from the ostium of the left liver vein , very close to the end of the palmaz - stent and the left portal vein branch .
the pressure gradient dropped > 50% ( portosystemic gradient decrease from 36 to 15 mm hg , see figure 1a ) , as usual during tips insertion . in the follow - up visits , the tips was patent and there was no need for invasive measurements until the patient conceived .
one year after tips revision , at the age of 38 , the patient conceived . during pregnancy ,
vka anticoagulation was replaced by therapeutic dose of the low - molecular - weight heparin ( lmwh ) enoxaparin with regular monitoring of anti - fxa ( axa ) activity ( peak axa - level : 1.0  1.2  u / ml ) , and hydroxyurea was discontinued due to its teratogeneity .
even though the recommendation in patients with high - risk et is to use interferon - alpha ( evidence level iii and grade b ) , we advised against it , as there are no controlled studies which show a clear benefit regarding teratogeneity , and , in particular , there is no experience in the situation of bcs .
tips patency was examined 4-weekly using doppler - ultrasound ; small amounts of ascites were first detected at a gestational age ( ga ) of 12 weeks .
first- and second - trimester ultrasound examinations including echocardiography and doppler examination of the fetal and uterine vessels were unremarkable .
g / l ) . despite axa - adjusted anticoagulation within the therapeutic range ( enoxaparin 60  mg qam , 80  mg qhs ) , thrombosis of the right subclavian vein occurred at ga 25 . therefore ,
testing for heparin - induced thrombocytopenia ( hit ) typical antibodies was performed , and medication was changed to fondaparinux ( 5  mg bd ) , as the anticoagulant and antithrombotic efficacy of fondaparinux at this dosage is superior .
a gradual deterioration of her general condition occurred ; she complained of increasing abdominal distension , pain , and dyspnea .
although tips was patent at every control , recurrent paracenteses ( overall volume 15.4 l ) had to be performed to relieve these symptoms .
serial ultrasound of the uterine cervix revealed progressive shortening , prompting tocolytic therapy with atosiban and administration of corticosteroids for acceleration of fetal pulmonary maturity at 28 weeks of gestation . at ga 28  +  2 , abnormal fetal heart rate tracings and progressive cervical dilatation necessitated cesarean delivery , which was performed under general anesthesia .
percentile , apgar 8/9/10 , arterial ph 7.34 ) and transferred to the neonatal intensive care unit .
operation and postoperative surgical course was unremarkable ; several litres of ascites were drained after abdominal incision .
the further course was uncomplicated , and the baby was discharged home 8 weeks later .
post partum , ascites , and upper abdominal pain worsened despite continuous ascites drainage and medication .
upper gastrointestinal endoscopy was therefore performed on postoperative day 4 , which revealed grade ii esophageal and grade i gastric varices .
invasive tips - control demonstrated a foreshortening of the uncovered stent at the portal segment with associated cavernous transformed portal venous thrombosis .
subsequently , a covered stent elongation to a big portal varice was performed ( portosystemic gradient decreased from 12 to 6 mm hg , see figure 1b and c ) .
thereafter , the patient was stable on treatment with hydroxyurea and fondaparinux ; the latter was switched to rivaroxaban 2 weeks postpartum .
this time a tips revision with an adequate lowering of porto - systemic pressure gradient was not expected ; therefore , a spleno - renal shunt was created in order to treat the complications of portal hypertension ( see figure 3a ) . however
, within the course of the following weeks , the patient developed several flares of et with platelets around 800  g / l despite treatment .
when renal dysfunction was present as hepatorenal syndrome , she was listed for ltx 3 months later ( initial model for end - stage liver disease ( meld)-score 28 plus special request for non - standard exception [ nse ] ) .
bone marrow transplantation to cure et was discussed ; however , the patient did not fulfill the criteria . during this time
, the liver function deteriorated , and magnetic resonance imaging revealed a > 7  cm measuring central  tumor ,  which turned out to be a necrotic bcs - nodule ( see figure 3b ) . an organ allocation for ltx
unfortunately , the postoperative course was complicated by a primary nonfunction ( pnf ) of the first graft , and despite double retransplantation the patient succumbed 2 weeks later .
ct scan demonstrating stent in stent configuration and tips reocclusion . ct = computed tomography , tips = transjugular portosystemic shunt .
( a ) ct scan demonstrating occluded tips ( arrowhead ) , patent splenorenal shunt ( arrow ) , and cirrhotic liver disease with multiple regenerative nodules .
( b ) axial t2-weighted fat - suppressed mr image demonstrating a cirrhotic liver with siderotic nodules ( arrows ) and massive central liver fibrosis with edema ( arrowhead ) .
ct = computed tomography , mr = magnetic resonance , tips = transjugular portosystemic shunt .
with a prevalence of 1 in 100.000 to 500.000 , primary bcs is a rare disorder
. characterized by abdominal pain , hepatomegaly , and ascites , the temporal dynamics , site , and extent of obstruction determine its clinical course .
predisposing factors include , among others , inherited or acquired hypercoagulability and especially myeloproliferative diseases , as in our case .
pregnancy itself is also a risk factor for bcs ; however , usually additional risk factors are present . with a 3-year - lethality of 90%
treatment is based on expert consensus and consists of anticoagulation , interventional angioplasty , or tips stent with the aim to decompress the portal venous compartment .
in addition to the pregnancy - induced hypercoagulability , several changes inherent to pregnancy add to its detrimental effect on bcs .
these include blood volume expansion and hypoproteinemia ; the rise in intraabdominal pressure ; pressure of the gravid uterus on the ivc and other intraabdominal vessels , including the lymphatic system ; and the displacement of intraabdominal organs by the expanding uterus , causing changes in their respective anatomical relationship .
the occurrence of thrombosis despite full - dose and axa - adjusted anticoagulant treatment underscores the high thrombotic risk of et patients during pregnancy .
historical case series on bcs and pregnancy , reporting a 1-year maternal mortality of 50% are not suitable for risk assessment due to the advent of additional treatment modalities , in particular tips .
contemporary reports on pregnancy in bcs ( from 1990 onwards ) are restricted to 1 small series and 3 case reports .
even though there was no maternal mortality during pregnancy , delivery and follow - up , morbidity was considerable , including thrombosis , hemorrhage , and tips occlusion . likewise , fetal - neonatal outcome was poor , with a high rate of pregnancy losses and preterm births .
chiari syndrome we can not prove that the detrimental course of the disease could have been avoided if the patient had abstained from pregnancy .
the long time intervals with stable disease and the rapid downward trend during pregnancy and after delivery , however , point to a relevant contribution of pregnancy to the lethal course . in women with pre - existing cardiac disease , a classification has been developed , which is based on disease severity and anticipated impact of pregnancy on the underlying condition .
it allows the attending physician risk assessment , preconception counseling , and risk - adapted care during pregnancy and childbirth . in analogy , we suggest the classification of bcs into world health organization ( who ) classes i to iv as follows : class 1 : maternal mortality not increased ; no or only slight increase in maternal morbidity.class 2 : maternal mortality slightly increased ; maternal morbidity moderately increased.class 3 : maternal mortality significantly increased ; severe maternal morbidity .
interdisciplinary management before , during , and after pregnancy is mandatory.class 4 : extremely high maternal mortality , high risk of severe morbidity .
pregnancy is contraindicated , termination should be considered . in the case of continuation of pregnancy , management as for class 3 is required .
class 1 : maternal mortality not increased ; no or only slight increase in maternal morbidity .
pregnancy is contraindicated , termination should be considered . in the case of continuation of pregnancy , management as for class 3 is required .
allocation criteria may include the following : general : age ; time between diagnosis and pregnancy.history : presence and type of prothrombotic factors ; number of thrombosed veins ; complications of portal hypertension ; type and number of previous interventions.clinical findings : ascites , hepatosplenomegaly , esophageal varices ; cholangiopathy.laboratory results : liver function , kidney function , infection , coagulation.diagnostic imaging : ivc obstruction , collaterals.rotterdam , international prognostic score of thrombosis in world health organization - essential thrombocythemia ( ipset ) or other scores .
history : presence and type of prothrombotic factors ; number of thrombosed veins ; complications of portal hypertension ; type and number of previous interventions .
rotterdam , international prognostic score of thrombosis in world health organization - essential thrombocythemia ( ipset ) or other scores .
the usefulness of these and additional criteria , however , needs to be established . with numbers of women with
bcs seeking pregnancy expected to rise , the scoring system may help in preconception risk assessment and counseling ; furthermore , it may support in the establishment of treatment algorithms of bcs in pregnancy .
notwithstanding that , a favorable outcome of pregnancy in women with bcs requires an interdisciplinary team of specialists in gastroenterology , radiology , visceral surgery , hemostaseology , fetal medicine , obstetrics , and neonatology .
 abstractdue to its rarity , experience with pregnancy in budd  chiari syndrome ( bcs ) is limited . with the advent of new treatment modalities , transjugular 
 intrahepatic portosystemic shunt in particular , numbers of affected women seeking pregnancy with bcs are expected to rise . here 
 , we use a case that ended lethal within 2 years after delivery to discuss the effect of pregnancy on bcs and vice versa , and to highlight the necessity of a multidisciplinary teamwork . 
 additionally , a risk classification is proposed which may serve as a framework for preconception counseling and assist in the establishment and evaluation of treatment algorithms ; its criteria need to be defined and assessed for their applicability in further studies . 
INTRODUCTION
CASE
DISCUSSION