Successful completion of pregnancy using apheresis and a balanced dose of coagulation factors in the presence of high thrombophilia and Lp(a) levels in a woman with two previous abortions.

A 26-year-old female patient was introduced to our lipid consultations for further diagnosis and treatment. She had two strokes, occurring at the age of 19 and 24, respectively. In addition, she was suffering from spastic tetraparesis as a consequence of perinatal asphyxia. Because of her history of strokes, a blood coagulation factor analysis was performed. Here, the following blood coagulation disorders were identified: von Willebrand disease type 1, protein S deficiency and increased levels of lipoprotein a (Lp(a)). In sum, these indicate a significantly increased risk of thrombophilia.

Recent research has shown two single-nucleotide polymorphisms in the LPA locus (6q26–27) to be strongly associated with increased Lp(a) levels as well as increased risks of coronary heart disease and stroke [1, 2]. A common genetic variant of LPA (rs10455872) was identified in the patient corresponding to her significantly increased Lp(a) levels.

Due to the patient's high-risk thrombophilia and taking into account considerably narrowed coronary vessels with a high risk of a cardiovascular event as determined by cardiac MRI, weekly lipoprotein apheresis treatment (LA) was initiated. Furthermore the patient was found to have a positive family anamnesis for different forms of thrombophilia (Table 1).

Table 1.

Family history for different thrombophilia disorders

Family member	Disorder	Clinical events
Mother 46 years	Factor V Leiden mutation with increased APC resistance (APCR)Homozygous plasminogen activator inhibitor (PAI) 4G/5G gene polymorphismHereditary protein S deficiencyHeterozygous methylenetetrahydrofolate reductase (MTHFR) C677T gene mutation	No
Father 48 years	No known disorders	No
Sister 23 years	Homozygous PAI 4G/5G gene polymorphismIncreased Lp(a)- and homocysteine levels	No
Brother 16 years	Heterozygous factor V Leiden mutationHeterozygous PAI 4G/5G gene polymorphismIncreased Lp(a) levels	No
Brother 15 years	Increased thyroid peroxidase (TPO) antibodiesHeterozygous PAI 4G/5G gene polymorphismHereditary protein S deficiencyHomozygous ACE D/D genotype polymorphismIncreased Lp(a)- and anti-nuclear antibody (ANA) levels at 10 years	Thrombosis
Sister 13 years	Heterozygous PAI 4G/5G gene polymorphismIncreased Lp(a) levels	No
Sister 12 years	Heterozygous factor V Leiden mutationHereditary protein S deficiencyHeterozygous PAI 4G/5G gene polymorphismHeterozygous MTHFR C677T gene mutation	Hemiparesis since birth
Brother hours	No known disorders	Died after delivery

Prior to the start of LA, the patient had been pregnant twice, but lost the fetus in the 6th and 9th gestation week, respectively, while exhibiting high levels of Lp(a) of around 200 mg/dL (480 nmol/L). It is known that Lp(a) levels may rise during pregnancy [3]. No further examination of the placenta had been carried out in the context of these miscarriages.

While receiving weekly LA the patient got pregnant again, but lost the fetus in the 14th gestation week. At the time, the recorded Lp(a) levels varied between 190 mg/dL (456 nmol/L) at the start and 56 mg/dL (134 nmol/L) at the end of an average apheresis procedure. A now conducted histopathological examination of the placenta revealed a fulminant microcirculatory perfusion disorder caused by multiple microthromboli.

The patient got pregnant again for the 4th time. Due to this course of events the therapy was intensified by doubling the LA rate to biweekly treatment. Here, thermofiltration (Diamed®; Köln; Germany), using a plasma volume of 4000 mL per treatment, was selected. This regimen allowed the decrease of LDL and Lp(a)-cholesterol levels by >75% when compared with the start of the apheresis treatment. Following LA procedures, Lp(a) was measured within the normal range [25 mg/dL (60 nmol/L)]. Regular thrombophilia screenings were made to regulate the administration of high-dose coagulation factors [von Willebrand factor: ristocetin cofactor (VWF:RCo), factor VIII and factor XIII]. The patient got pregnant again.

The pregnancy progressed normally and without complications. Due to the increasing risk of thrombosis, we decided to perform a premature delivery by Caesarean section in the 34th week of pregnancy. A thrombophilia screening of the umbilical cord blood could not be evaluated as of yet.

Even though coagulation factors were administered as necessary the patient suffered from smaller bleedings without clinical relevance in the area of the surgical wound. The newborn girl developed well and was able to leave the incubator on Day 14 after the delivery.

Up until now, no further clinically significant events have been reported for either the patient or the child.

This case illustrates how strong the association of thrombophilia [4] and increased Lp(a) levels [5] can be with regard to miscarriages. Only a high-rate extracorporeal Lp(a) elimination by LA and regular screening and substitution of coagulation factors allowed a pregnancy to be brought a successful end. Furthermore the importance of a well-coordinated interdisciplinary, patient-centred approach to the management of high-risk pregnancy is demonstrated. Whether the therapeutic strategy successfully employed here is transferable to other cases of patients with high-risk thrombophilia who desire children has to be investigated in future studies. Again, this clinical case suggests that Lp(a) is not only relevant to the known artherosclerotic processes (apoplexy of the patient) but seems to play an active role in the coagulation system, further increasing the risk of thrombophilia (in the placenta) as well.

Conflict of interest statement

None declared.