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does protein s deficiency cause miscarriage

Nowrosjee Wadia Maternity Hospital, (NWMH) Parel, Mumbai, 400012 India

519, 520 Darshana Apts., 90 Ft Highway, Sane Guruji Nagar, Mulund (East), Mumbai, India

Nowrosjee Wadia Maternity Hospital, (NWMH) Parel, Mumbai, 400012 India

Nowrosjee Wadia Maternity Hospital, (NWMH) Parel, Mumbai, 400012 India



Protein S deficiency is a uncommon inherited thrombophilia usually related to fetal losses in being pregnant. It’s seen in roughly 1 in 500 to 1 in 3,000 individuals. Homozygous Protein S deficiency in neonates manifests as a catastrophic and deadly thrombotic complication termed Purpura Fulminans (PF).


Case Report

A 24-year-old third gravida with two neonatal deaths previously, offered to us in April 2006 for preconceptional counseling. Her first being pregnant in 2002 led to a preterm Cesarean part at 35 weeks of gestation in view of preterm untimely rupture of membranes with extended labor. She delivered a feminine child weighing 2.3 kg with outstanding, black pores and skin lesions all around the physique. Within the NICU, the neonate had necrosis and peeling of the pores and skin by the third day and died on the fifth day. The reason for loss of life couldn’t be decided from the historical past. Her second being pregnant in 2004 was additionally uneventful until 38 weeks of gestation, when she had antepartum hemorrhage adopted by an emergency LSCS. She delivered a feminine child with related outstanding black-colored pores and skin lesions. Equally, this neonate had necrosis and peeling of the pores and skin and died on the fifth day within the NICU. Once more the reason for loss of life was not recognized. The affected person had no different postoperative issues and was discharged with contraceptive recommendation. The investigations carried out on her within the interval interval revealed Lupus anticoagulant (LAC) constructive, CMV IgG, HSV IgG and Rubella IgG, +ve, ACL IgG and IgM unfavourable, Anti ds DNA, ANA and VDRL unfavourable, and regular sugars and parental karyotyping. The couple was then referred to the dermatology unit to establish a potential dermatological trigger for the neonatal losses. They recommended that neonatal PF secondary to Protein S or Protein C deficiency may have been the potential reason for the neonatal losses. Therefore, a Thrombophila profile of each the mother and father was carried out. Thrombophilia profile of the daddy was regular. Thrombophilia profile of the mom confirmed deficiency of Protein S–55 % (Regular vary = 70–140 %), with regular Protein C, Antithrombin III, and Issue V Leiden ranges. The couple was endorsed concerning the autosomal dominant nature of Protein S deficiency. The affected person was suggested periconceptional folic acid supplementation for six months and early antenatal registration with thromboprophylaxis in subsequent being pregnant.

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She conceived for the third time in September 2008, and registered on the antenatal clinic of NWMH at 9 weeks of gestation. Her baseline full blood depend and coagulation profile had been inside regular limits. In view of Protein S deficiency with constructive Lupus Anticoagulant in being pregnant, the affected person was began on low dose Aspirin (75 mg) as soon as every day and unfractionated Heparin (UFH) 5000 IU SC BD until 20 weeks. The doses of heparin had been elevated to 7500 IU SC BD from 20 weeks until 32 weeks, and afterward to 10,000 IU SC BD until supply. The affected person was monitored weekly with APTT ranges and platelet counts throughout being pregnant. She was given two intramuscular doses of Betamethasone at 28 weeks for lung maturity in anticipation of her previous historical past of preterm supply. Shade Doppler at 32 weeks confirmed good interval development with regular Doppler flows. She had weekly NST and Biophysical profile from 32 weeks onward for antepartum fetal surveillance. Aspirin was stopped at 34 weeks. At 36 weeks, the affected person complained of decreased fetal actions. NST was non-reactive and pressing biophysical profile confirmed sluggish fetal motion with fetal tachycardia. Heparin was stopped instantly, and 12 h later, an emergency LSCS was carried out below spinal anesthesia. She delivered a feminine little one of two.8 kg with good Apgar scores on August 21, 2009. The neonate was evaluated by the pediatrician and thrombotic profile of the infant was suggested. The mom was restarted on UFH 10,000 IU SC bd on the second postoperative day and in addition began on warfarin 1 mg od. The warfarin doses had been stepped up and adjusted as much as 5 mg OD with every day monitoring of PT/INR values. Heparin was discontinued as soon as the INR ranges had been within the vary of two–3. The affected person was suggested to proceed warfarin 5 mg OD for six weeks on discharge.

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Protein S deficiency is a uncommon inherited thrombophilia with autosomal dominant inheritance [1]. Protein S is a 69,000 MW vitamin-Okay-dependent pure anticoagulant protein. It capabilities as a cofactor to facilitate the motion of activated protein C on components Va and VIIIa. Neonatal PF is a manifestation of homozygous Protein S or Protein C deficiency. It’s a deadly syndrome of disseminated intravascular coagulation with quickly progressive hemorrhagic necrosis of the pores and skin on account of dermal vascular thrombosis [2]. Pregnant girls with Protein S deficiency are usually heterozygous. Companions of ladies with these defects must be provided screening to establish neonates who could also be homozygous or carry mixed defects, in whom prenatal analysis will be thought-about. Girls with genetic or acquired thrombophilias are at very excessive danger of antenatal and postpartum venous thromboembolism and will obtain thromboprophylaxis throughout being pregnant and puerperium [3, 4]. Subcutaneous unfractionated or low molecular weight heparins (LMWH) are the anticoagulants of alternative. Heparin doesn’t cross the placenta, and thus there isn’t a danger of teratogenesis or fetal hemorrhage. LMWH is the drug of alternative due to a greater side-effect profile, (decreased danger of osteopenia and thrombocytopenia) good security file for mom and fetus, and handy once-daily dosing for prophylaxis. Warfarin is related to teratogenic results and must be prevented in being pregnant. Regional analgesia is prevented for not less than 12 h after the final dose of LMWH [3]. Postpartum after 24 h, girls ought to resume warfarin with LMWH overlap till the INR is within the pre-pregnancy therapeutic vary [3, 4]. Heparin and warfarin will be safely administered to nursing moms [1, 4]. In conclusion, thrombophilia screening may be justified in girls with recurrent being pregnant loss [5], and satisfactory and acceptable thromboprophylaxis is a crucial a part of the administration of pregnant girls with inherited thrombophilias [4].

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