Pregnancy Treatment and Labour Management in Antiphospholipid Syndrome

NUSA PURNAWAN PUTRA 0861050031

MEDICAL STUDENT IN DEPARTMENT OF OBSTETRIC AND GYNAECOLOGY FACULTY OF MEDICINE, CHRISTIAN UNIVERSITY OF INDONESIA, JAKARTA

PRELUDE

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by the presence of arterial or venous thrombosis, pregnancy morbidity and the presence of a persistent increase in serum titer positive for antiphospholipid antibodies (aPL).

PRELUDE

In the United States noted that the prevalence of APS in the general population of the country reached 2-4%. In Singapore, 134 APS patients treated during 2004 to 2005, 43.3% had a positive outcome of LA, and 66.4% of aCL.
In Indonesia, there is no research data regarding the prevalence of women diagnosed with antiphospholipid syndrome (APS).

PRELUDE

Current first-line treatment for APS is lowdose aspirin (LDA) plus unfractioned heparin or with low molecular weight heparin (LMWH). However, in about 20% of cases of APS, the expected final destination, include live birth, can not be achieved.
Without treatment, the rate of miscarriage in subsequent pregnancies in these conditions was 90%.

PRELUDE
The

purpose of this paper is to investigate the pregnancy treatment and management of labour in antiphospholipid syndrome, so as to reduce the morbidity and mortality of both mother and fetus by selecting the appropriate treatment.

TREATMENT ANTIPHOSPHOLIPID SYNDROME

Nonmedically

Clinical and Laboratory monitoring during antenatal care

Management of labour

Medically

Anti coagulant
Anti aggregation Steroid HCQ

IVIG
Others

 Follow-up

before or during pregnancy, and after delivery, including fetal viability can be confirmed by transvaginal ultrasound.

Serial

ultrasound examinations to monitor fetal growth and amniotic fluid volume. Wave velocity of blood velocity in the uterine and umbilical arteries were also assessed.

The examination of platelets to monitor the occurrence of thrombocytopenia should be done routinely.
Primary assessment is the level of live-born infants, and the secondary assessment is excessive bleeding, thrombocytopenia, IUGR, pre-eclampsia, IUFD.

Timing of heparin can be initiated in the early stages of pregnancy, without waiting for the results of an ultrasound examination.
In another study from the Laboratory of

Hormonology, Maternity, and Haemostatis Unit, Geneva University Hospitals, Switzerland, heparin
administration begins when the heart starts activity seen on ultrasound (about 7-8 weeks).

 Aspirin

given in APS patients at a dose of 75 mg daily when the gestational sac (gestational sac) seen on ultrasound around 6 weeks gestation until the end of 35 weeks.

Large doses of corticosteroids (0.5-1 mg / kg per day) was associated with an increased risk of gestational diabetes, infections, hypertension due to pregnancy and preterm delivery. Side effects did not seem to occur when the dose of prednisone is used in low doses (10-20 mg per day).

 Hydroxychloroquine

(HCQ) annexin A5 can protect from disruption by antiphospholipid antibodies. clinical evidence is still limited to the successful outcome of them in the APS.

However,

 The

effectiveness of rituximab in combination with chemotherapy including plasmapahresis, has been widely used in the treatment of B cell malignancies, the clinical manifestations of APS or just to reduce the levels of aPL.

Department of Obstetrics and Gynecology, University of Utah Health Sciences Center and Intermountain Healthcare, USA, said that in the
handling of labor in patients with antiphospholipid syndrome, obstetric patients depending on their state of the pregnancy.

Indications for cesarean delivery is poor obstetric history, IUGR, pre-eclampsia, failure in the progress of labor, and breech presentation.

DISCUSSION

Department of Obstetrics and Gynecology in the University of Sheffield, UK, explained that Enoxaparin is used in a dose
of 20 mg subcutaneously produces 80% live birth rate. In line with the above result, the Department of Internal Medicine, Niguarda Hospital, Milan, Italy, reported the results of a study involving 27 patients APS. The use of subcutaneous heparin at a dose of 5000 IU twice a day recommended in this case, as well as oral administration of 100 mg aspirin.

DISCUSSION
Of

the 32 pregnancies studied 84.4% managed to deliver the baby alive and 15.6% had a miscarriage.
suggests that combination therapy produces slightly better results.

This

DISCUSSION

Another study from the Department of

Obstetrics and Gynecologic, Academic Medical Center, University of Amsterdam, Netherlands, involving 364 APS patients who
subsequently received treatment with 80 mg of aspirin combined with subcutaneous nadroparin (at a dose of 2,850 IU, started immediately after the diagnosis of pregnancy is established), 80 mg aspirin alone, or placebo.

DISCUSSION
In

these patients, the rate of live-birth was 69.1% in the combination therapy group, 61.6% in the aspirin only group, and 67.0% in the placebo group.
these results, it appears the level of live-birth of the three groups is not significant different.

From

DISCUSSION

The results also support from previous studies on combination therapy better than monotherapy, reported by the Department of Obstetrics and gynaecologic, Liverpool Women's Hospital, UK. This study involving 176 patients APS.
When analyzed, 53/67 (79%) live-born infants of women who had received aspirin and heparin, compared with 64/104 (62%) of women with APS who received aspirin alone.

DISCUSSION

In line with the research before, the study of the Laboratory of Hormonology, Maternity, and

Haemostatis Unit, Geneva University Hospitals, Switzerland, reported the APS patients with
anti-thrombotic therapy (aspirin 75 mg and 40 mg Enoxaparin inj.).

Of the 60 patients, 56 patients (93%) had a live birth.

DISCUSSION

Another study from the Department of

Obstetrics and Gynecology, University of Utah Health Sciences Center and Intermountain Healthcare, USA, APS involving 42 patients
treated with UFH and aspirin.

In this study, the live birth rate reached 85.7% in the treatment, and in previously untreated pregnancies, only reached 4.6%.

DISCUSSION

Another study by the Department of Obstetrics and Gynecology, University of Chicago, USA, reported on therapy with IVIG, of the 22 women in the IVIG group, only 10 women (45%) who had a live birth at term. In contrast to these findings, other studies of the Operative Unit of Gynecology, University of Rome, Italy, which did HIVIg therapy in 60 patients with therapy HIVIg APS (intact immunoglobulin type 20 g daily for 5 days, total dose 100 g), the live birth rate was 73.3% (44 / 60).

DISCUSSION

Maternal and Fetal Research Unit, King's College London, UK, in the study, 18 women
with antiphospholipid antibodies who have recurrent miscarriages therapy is given prednisolone (10 mg). before low-dose prednisolone given as treatment, 4 of the 97 pregnancies have resulted in live births (4% ).

Among the 23 pregnancies that comes with prednisolone, 9 women had 14 live births (61%).

DISCUSSION

The European Registry on Obstetric antiphospholipid syndrome (Europas) reported

194 patients with APS have done therapy with low molecular weight heparin (LMWH), with dose prophylaxis, low-dose aspirin combined well (LDA) and prednisone.

Overall, produce live births obtained in 174/194 (89.69%).

DISCUSSION

In another study, Department of Gynecology and

Obstetrics, New York University School of Medicine, New York, USA, APS reported on 87 patients treated
with prednisone and aspirin, live birth rate was 83.91% (73/87) and the rate of miscarriage fetus reaches 16.09% (14/87).

Of the 42 patients treated with prednisone and aspirin plus LMWH and IVIG, live birth rate was 97.62% (41/42) and fetal miscarriage rate was 2.38% (1/42).

DISCUSSION

From these studies, therapy in APS patients with a combination of aspirin, LMWH, prednisone, and IVIG, resulting in the live birth rate is very high compared with monotherapy or combination therapy to another, reaching 97.62%.

DISCUSSION

But according to the author, IVIG should not be included in the combination of the above due to the relatively high cost and the research about their effectiveness is still small and controversy. By simply using a combination of aspirin, LMWH, and prednisone was live birth rate can reach 89.69% based research that has been previously explained above.

DISCUSSION

Department of Obstetrics and Gynecology, University of Utah Health Sciences Center and Intermountain Healthcare, USA, reported the
study of labour management in patients with APS. A total of 7 (17.5%) of 40 patients in the study by through elective Caesarean section and 3 (7.5%) of 40 patients by emergency Caesarean section, the remaining 75% using a vaginal delivery.

DISCUSSION

This is in line with another study of the Department of

Obstetrics and Gynaecology, King's College, St Thomas' Hospital, London, UK, reported the study, from 39 APS
patients, 12 through childbirth by caesarean section (30.8%) and the rest are normal vaginal birth (69.2 %).

In contrast to the two studies above, Laboratory of

Hormonology, Maternitym and Haemostatis Unit, Geneva University Hospitals, Switzerland, reported that in 56 patients
with APS syndrome, 49 childbirth (87.5%) by caesarean section due to obstetric causes patients. The remaining 7 patients (12.5%) by vaginal delivery.

CONCLUSION
1.

Best management in patients with antiphospholipid syndrome is a combination of LDA (dose 75 mg, once daily beginning before conception and continuing through 36 weeks of gestation) plus LMWH (dose of 5000 IU or 40 mg once daily started when cardiac activity began to look at the ultrasound ( about 7-8 weeks) to gestational age 37 weeks) and prednisolone (10 mg dose, starting from a positive pregnancy test until 14 weeks gestation), which will reach 89.69% live birth rate.

CONCLUSION
2.

Handling of labor in patients with antiphospholipid syndrome still prioritizing vaginal delivery for live-birth that can reached 75%. It is actually not accompanied with poor obstetric morbidity.

Thank You
Nusa Purnawan Putra 0861050031
MEDICAL STUDENT IN DEPARTMENT OF OBSTETRIC AND GYNAECOLOGY FACULTY OF MEDICINE, CHRISTIAN UNIVERSITY OF INDONESIA, JAKARTA