Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized Clinical Trial of Using Preconceptional Enoxaparin AND Low Dose Aspirin 81mg in Patient With Antiphospholipid Syndrome(APS)
Brief Summary: Preconceptional use of low molecular weight heparin (enoxaparin) and aspirin in patient with recurrent miscarriages with positive anti phospholipid antibodies increase the implantation rate and the duration of pregnancy with low complications to the mother and the baby.


Options:
A: Inclusion Criteria:

History of 3 or more consecutive miscarriages and positive antiphospholipid antibodies on at least two occasions more than 6 weeks apart before becoming pregnant and an unsuccessful pregnancy with aspirin + heparin with a karyotype of miscarriage either unavailable or normal (46XX/ 46XY).

Exclusion Criteria:

Abnormal karyotype of women or partner, previous thromboembolism, SLE, diabetes mellitus, hypertension, sensitivity to aspirin, heparin and prednisolone, multiple pregnancy.
B: Inclusion Criteria:

1. All women with recurrent first-trimester miscarriage and all women with one or more second-trimester miscarriage who screened before pregnancy for antiphospholipid antibodies.
2. To diagnose antiphospholipid syndrome it is mandatory that the woman has two positive tests at least 12 weeks apart for either lupus anticoagulant or anticardiolipin antibodies of immunoglobulin G and/or immunoglobulin M class present in a medium or high titre over 40 g/l or ml/l,or above the 99th percentile).

In the detection of lupus anticoagulant, the dilute Russell's viper venom time test together with a platelet neutralisation procedure is more sensitive and specific than either the activated partial thromboplastin time test or the kaolin clotting time test. Anticardiolipin antibodies are detected using a standardised enzyme linked immunosorbent assay.

Exclusion Criteria:

1. Age above forty years old .
2. Intrauterine abnormalities (as assessed by ultrasound, hysterosonography, hysterosalpingogram, or hysteroscopy).
3. Fibroids distorting uterine cavity .
4. Abnormal parental karyotype .
5. Other identifiable causes of recurrent miscarriages (tests initiated only if clinically indicated) e.g., diabetes, thyroid disease and systemic lupus erythematosus (SLE).
C: Inclusion Criteria:

1. Signed and dated informed consent form
2. Male or female of age 18-75 years
3. Triple aPL-positivity in the last blood sampling defined as:

   * aCL IgG/M (≥40 GPL or MPL, medium-to-high titer, and/or greater than the 99th percentile) and
   * aB2GPI IgG/M (≥40 U, medium-to-high titer, and/or greater than the 99th percentile) and
   * LA test positive based on the International Society of Thrombosis \& Hemostasis Recommendations.
   * Positivity of aCL and abeta2GPI must be of the same isotype.
   * To confirm triple positivity for aPL and to validate the laboratory diagnosis, plasma (at least 2ml prepared by double centrifugation at 2000g) from patients of each Center will be stored at -80°C and later on sent in dry ice and retested in a reference laboratory (Padua Thrombosis Centre). Expenses for shipment will be in charge to the coordinator Center.
4. History of thrombosis (objectively proven arterial, venous, and/or biopsy proven microthrombosis) and/or pregnancy morbidity according to Miyaki

Exclusion Criteria:

Subjects meeting any of the following criteria will not be enrolled in the study:

1. Severe hypersensitivity reaction to rivaroxaban
2. Calculated CLCR \<30 mL/min at the screening visit
3. Current pregnancy or breast feeding. Pregnancy is highly discouraged in these patients and if programmed patients are excluded from the study. If sexually active, be practicing an effective method of birth control (e.g., intrauterine device, double-barrier method, contraceptive patch, male partner sterilization) before entry and throughout the study
4. Concomitant treatment with other anticoagulants, such as unfractionated heparin, low molecular weight heparins (enoxaparin, dalteparin, etc.) heparin derivatives (fondaparinux), other oral anticoagulants (dabigatran etexilate, apixaban) in the case they can not be substituted with the study drugs.
5. Patients taking interfering medications: pharmacologic interactions may occur with strong inhibitors of p-glycoprotein and of CYP3A4, e.g., azole-antimycotics, such as ketoconazole, itraconazole, voriconazole, posaconazole, and HIV protease inhibitors; coadministration of rivaroxaban is therefore contraindicated in these cases. Several drugs used in neurological patients, such as phenobarbital, phenytoin, carbamazepine, and st john's wort (hypericum), are p-glycoprotein inducers and should be avoided. Whenever possible, it would be better to use levetiracetam and topiramate as antiepileptic therapy.
6. Hemorrhage Risk-Related Criteria

   * History of or condition associated with increased bleeding risk including, but not limited to:
   * Major surgical procedure or trauma within 30 days before the randomization visit
   * Clinically significant gastrointestinal bleeding within 6 months before the randomization visit
   * History of intracranial, intraocular, spinal, or atraumatic intra-articular bleeding
   * Chronic hemorrhagic disorder
   * Known intracranial neoplasm, arteriovenous malformation, or aneurysm
   * Planned invasive procedure with potential for uncontrolled bleeding.
   * Sustained uncontrolled hypertension: systolic blood pressure ≥180 mmHg
7. Known liver cirrhosis or ALT above three times the upper normal value.
D: Inclusion Criteria:

* Habenox 1: Three or more consecutive abortions of first trimester (ad h 12+6 wks) or two second trimester abortions (ad h 13 wks-23+6 wks) or one third trimester abortion (24 weeks or more) with one first-second trimester abortions and one thrombophiliatest positive: F V Leiden (heterozygote) or protein C or S deficiency, or anticardiolipin antibodies (low to moderate level), prothrombin gene mutation, or high level of F VIII.
* HABENOX 2: The thrombophilic tests above are negative.
* HABENOX 3:positive combined thrombophilia, F V Leiden (homozygote), anticardiolipin antibodies (high level \>40) , lupusanticoagulant, or AT III deficiency.

Exclusion Criteria:

* History of DVT or pulmonary embolism.
* Significant bleeding history.

Answer: B