Effect of Low Molecular Heparin on Pregnancy Outcome With Protein S Deficiency

This is a parallel-group, multicenter, randomized controlled trial of 48 pregnancies with protein S deficiency in China. Patients are randomized into three groups to receive enoxaparin combined with aspirin, aspirin alone and no intervention. The primary outcome measure is livebirth rate.

Inclusion criteria

• Plasma activity levels of PS when not pregnant are below the lower limits of the adult reference values (generally about 60-70% for PS) without the use of warfarin. Or, free protein S antigen levels in the second and third trimesters are less than 30% and less than 24%, respectively
• Pregnant women who delivered from Aug 1st, 2024 to Oct 15th, 2027
• One or more family members exhibiting the same symptoms as the patient
• Past history of early onset thrombosis (age 50 or below)
• Repeated recurrence of thrombosis
• Thromboses in unusual sites
• New onset of thrombosis during current pregnancy or after delivery
• Patients with diagnosis confirmed by gene analysis Inclusion criteria 1 and 2 must always be met regardless of items of 3-8.
• Written informed consent

Exclusion criteria

• Thrombophilia other than Protein S deficiency
• Antiphospholipid syndrome, systemic lupus erythematosus, platelet abnormalities, vascular disorders, blood flow obstruction, paroxysmal nocturnal hemoglobinuria, malignant tumor and other conditions that tend to cause thrombosis
• Allergy/hypersensitivity to enoxaparin or aspirin
• Heparin-associated thrombocytopenia or thrombocytopenia (platelet count<75 × 10^9/L)
• Organ lesions at risk for bleeding such as acute stomach/bowel ulcers, cerebral hemorrhage, cerebral aneurysm
• uncontrolled hypertension or Severe hypertension (Systolic Blood Pressure >200mmhg and/or Diastolic Blood Pressure >120mmHg)
• Severe hepatic failure (INR >1.8)
• Serum creatinine greater than 80 umol/L (1.3mg/dl) and an abnormal 24 hour urine creatine clearance (<30ml/min)
• Abnormal uterine cavity on hysterosalpingogram/hysteroscopy