Recurrent Miscarriages
(Anti-Phospholipid Syndrome)
Massiha Gulzar Ahmed, Roll # 71
Muhammad Asad, Roll # 75
Minahil Ahmed, Roll # 76
Muhammad Hannan Rana, Roll # 85
Supervisor : Prof Nilofar Mustafa
Tamgha-e-Imtiaz ( M
Patient Profile Married for
2.5 years.
Mrs. XYZ
28 Years old Non consanguineous
marriage
Doctor by
G4P0A3
profession
LMP 07 May 2018 EDD 14 Feb 2019
• Admitted on 4 January 2019 at 34 weeks for elective C-section
Background History
• Booked patient at CMH lahore
• Three consecutive 1st trimester miscarriages with
normal fetal morphology on USG
• Suspected clinical diagnosis of thrombophilic
disorder (Anti phospolipid Syndrome).
Past-obstetric history
First Miscarriage
• Early booking was done at CMH, Lahore.
• Folic acid taken pre pregnancy
• Spontaneous expulsion: 6th weeks gestation.
Second Miscarriage
•Booked at CMH Lahore.
•Spontaneous; after 4 months .
•She was on pre pregnancy folic acid.
•FCA appeared at 7 weeks.
•Missed miscarriage at 9 weeks .
•Suction evacuation was done
Postnatal Investigations
after 2nd Miscarriage
• Screened for diabetes and
thyroid dysfunction.
• OGTT: Normal
• TSH And Free T4: Normal
• USG: Normal Uterine Morphology
• Low dose aspirin 75mg (Loprin) &
Folic Acid 5 mg.
Reference :RCOG Green Top Guideline 17 , 2011
Third Miscarriage
•Booked at CMH Lahore:
• Spontaneous conception.
• Folic acid & Loprin continued
• FCA appeared at 6th weeks of gestation
• Missed miscarriage at 8 weeks.
Fetal morphology seemed normal
• Expectant management
• spontaneous expulsion.
Screening for Anti phospholipid Syndrome
•She was screened for
1. Lupus anticoagulant
2. Anti cardiolipin antibodies
Positive for anti cardiolipin antibodies.
Moderately high when repeated after 12 weeks.
Diagnosis
• Anti phospholipid Syndrome
• Plan to give LMWH for her fourth
pregnancy.
( Low molecular weight heparin)
History of present pregnancy
4th conception
First Trimester
• Booked at CMH Lahore
• Spontaneous planned
• Positive on urine dipstick test
• LMWH (Clexane 40 mg ) S/C x OD started
• Fetal cardiac activity confirmed on TVS: 6 weeks
• Advised to continue folic acid and loprin
Antenatal Investigations
Dating scan: 9 weeks of gestation.
EDD corresponded with LMP
Cervical length & Nuchal Translucency: Normal
Baseline investigations : Normal
1-Complete blood count
2-Blood sugar level fasting and 01 hour post prandial
3-Urine RE
4-HBsAg
5-Anti HCV screening
6-Rubella IgG ( positive)
Second Trimester
• Quickening: 5th month gestation
• Blood Pressure : Normal
• Anomaly scan: No anomalies
Uterine artery Doppler :
Bilateral uterine artery notch present
• CBC and Urine RE repeat were normal.
Treatment :
Clexane (40 mg) S/C x OD + Loprin (75 mg); continued
Iron and calcium supplements were started.
2nd Trimester continued
• Serial Growth Scans x 2 Weekly, 26th week
onwards.
• 26th Weeks Growth Scan:
-Fetal growth and AFI: Normal range
-Retroplacental haemorrhage of 74 ml
2nd Trimester continued
• Risks:
• Fetal growth restriction
• Preterm delivery
• Placental abruption
• Intra uterine fetal death
• 28 weeks x USG :
Fetal growth & AFI: Normal
Haemorrhage resolving on its own to
34 ml of blood.
Third Trimester
• At 32 weeks:
Inj. Betamethasone
USG : Fetal growth restriction
• Growth scan x 34 : Fetal growth restriction
• Family history:
No Hx of Diabetes, Hypertension, congenital
anomalies
• Medical history: insignificant
• Surgical history: insignificant
• Drug history: insignificant
• Socioeconomic:
– She has all basic facilities
– her dietary habits are satisfactory
Examination
• Pulse: 80 beats / minute
• BP: 120/80 mmHg
• Temperature: 980F
• Weight: 70 Kg
• Height : 5.4 ‘
( Early pregnancy BMI : 19 Kg /m2)
Examination
• Pallor: Nil
• Jaundice: Nil
• Thyroid: Not palpable
• Lymph Nodes: Not enlarged
• Edema: Mild bilateral pedal edema positive
Examination
• Chest Examination:
– Bilateral Normal Air Entry
• CVS:
– Normal 1st And 2nd heart sounds.
• Neurological System:
– Intact
Examination
Obstetric Examination:
– Inspection:
• Symmetrically distended abdomen, moving with
respiration with central umbilicus and stria gravidarum.
No scar marks present.
– Palpation:
• Soft abdomen, non tender.
• Symphysio-fundal height (SFH) 32 cm
( SGA / FGR )
• Longitudinal lie, cephalic presentation
– Auscultation:
• Fetal heart rate 140 / min regular.
INVESTIGATIONS
Investigations
• Blood Group, Rh Factor: O Positive
• Complete Blood Count:
– Hb: 12.4 g/dl
– TLC : 7 x 10 9 /L
– Platelet: 190 x 10 9 / L
– MCV: 85.7 fL
– MCH: 29.1 pg
– MCHC: 34.0 g/dl
Investigations
• Blood Sugar Level, Fasting:
– 4.8 mmol/L ( 86 mg / dl)
• Blood Sugar Level 01 hour post-prandial:
– 7.5 mmol/L ( 135 mg / dl)
• Serum TSH, T3, T4
Normal
Investigations
• Urine Complete Examination: Normal
• HbsAg: Negative
• Anti HCV: Negative
Ultrasound
• Single Intra uterine pregnancy.
• Lie: Longitudinal Presentation: Cephalic
BPD : 8.4 cm FL: 6.4 cm ( 34 weeks)
AC: 28 cm ( 32 weeks )
FCA : Present
• Umbilical artery Doppler : SD ratio 2.6
• AFI: 5 (NV : 5 – 25)
• Placenta: Fundal , Post Placental bleed: 14 ml
Elective C section
• 34+5 Elective caesarean section planned
-Fetal growth restriction
-Oligohydramnios
POSTNATAL OUTCOME
Postnatal Outcome
• Elective C section at 34 weeks 5 days on 9th Jan ,2019
• Spinal anesthesia.
• Male baby of 1.8 kg.
• Admitted in nursery with jaundice.
• Discharged after 2 weeks.
• Clexane continued 1 week postpartum.
• Contraception plan was discussed
Case Discussion
Recurrent Miscarriages
Recurrent Miscarriages
Loss of three or more consecutive pregnancies
❖ Three or more first trimester miscarriage
❖ One or more second trimester miscarriage
Causes Of Recurrent Miscarriages
1. Thrombophilic Disorders:
a. Acquired
b. Inherited
2. Genetic factors
3. Anatomical factors
(uterine malformation, cervical weakness)
4. Endocrine factors
5. Infective agent
6. Epidemiological
RCOG Green-top guideline 17, 2011
Tests For Recurrent Miscarriages
1. Endocrine:
• HbA1C levels, OGTT
• TSH, free T4
2. Acquired Thrombophilia (APS):
• Lupus Anticoagulant
• Anti Cardiolipin , If Negative
• Beta 2 Glycoprotein Antibodies
3. Screening For Inherited Thrombophilias
4. Anatomical malformation:
• Ultrasound And HSG (Hysterosalpingography)
• Laparoscopy/ Hysteroscopy
5. Karyotyping:
If Placental Karyotyping Abnormal
RCOG Guideline No. 17, 2011
1)Thrombophilias
• Acquired
– Anti Phospholipid Syndrome
– Hyperhomocystinemia
– Activated Protien C Resistance
• Inherited
– Factor V Leiden Deficiency
– Protein C and S Deficiency
– Antithrobomin III Deficiency
– Prothrombin Gene Mutation
•Mechanism: Thrombosis of utero-placental circulation
•Treatment: LMWH or Loprin
2) Genetic Factors
• Parental chromosomal rearrangements:
Balanced reciprocal or Robertsonian translocation
• Embryonic chromosomal abnormality
• Treatment:
Genetic counseling
Preimplantation genetic diagnosis
IVF
3) Anatomical Factors
• Congenital uterine malformations:
Septate miscarry in 1st Trimester
Arcuate miscarry in 2nd Trimester
Septate Arcuate
uterus uterus
3) Anatomical Factors
• Cervical Weakness
– Second Trimester Miscarriage
Preceded by painless cervical dilation and
spontaneous rupture of membrane
• Treatment:
Septum Resection
Cervical Cerclage
4) Endocrinal Factors
• Diabetes : Increased HbA1C In 1st Trimester
• Thyroid : Autoimmune Thyroiditis
• PCOS:
Insulin Resistance
Hyperinsulinemia
Hyperandrogenem
ia
Treatment:
• Thyroid Hormone
Replacement Therapy
• Metformin
5) Infective Agents
• Bacteremia or viremia lead to sporadic miscarriages.
• Bacterial vaginosis :
2nd trimester miscarriages & preterm delivery
• Treatment:
Metronidazole
Clindamycin
6) Epidemiological Factors
• Advancing maternal age
• Obesity
• History of previous miscarriage.
• Heavy alcohol consumption.
Thrombophilia
s
Anti Phospholipid
Syndrome
Thrombophilia
• A n acquired or hereditary disorder marked
by an abnormal increase in the tendency of
blood to clot.
• Among acquired thrombophilia,
Antiphospholipid Antibody Syndrome is the
most prevalent.
Anti Phospholipid Syndrome
INTRODUCTION
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Anti Phospholipid Syndrome
EFFECTS, SIGNS, SYMPTOMS
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Mechanisms of adverse pregnancy outcomes
1. Inhibition of trophoblast function.
2. Activation of complement pathways at the maternal–fetal
interface resulting in a local inflammatory response.
3. Thrombosis of uteroplacental vasculature
Effect of anti phospholipid antibodies on trophoblast
function and complement activation is reversed by heparin.
Effects of APS On pregnancy
• Increased risks of:
– Miscarriage (10-15%)
– second and third trimester fetal death
– Pre-eclampsia (10%) –severe and early onset
– Preterm delivery (30-40%)
– placental abruption
– FGR (30%)
– Fetal death (in APS)
– Deep Vein Thrombosis ( DVT )
Anti Phospholipid Syndrome
DIAGNOSIS
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Diagnosis
TREATMENT
Low Molecular Weight Heparin
• Prophylactic Dose:
– 0.6mg/Kg body weight :
Clexane 40mg OD (for 70 kg person)
• Therapeutic Dose:
– 1mg/Kg body weight
Clexane 40 mg BD (for 70 kg person)
– Titrate dose : 4hrs Post injection
Peak level of Anti Xa = 0.5- 1.0 IU/Ml
Reference
Management Of APS
(Without H/O Thrombosis)
• Pre Pregnancy :
Low-dose Aspirin:
-For all women with APS
-Because placental damage occurs early in gestation
-To prevent failure of placentation (throughout pregnancy)
Management Of APS
(Without H/O Thrombosis)
Pragmatic approach for aspirin therapy includes :
– < 3miscarriages:
• Offer Aspirin Alone ( live birth rate 42 %)
– If miscarriage occurs despite aspirin therapy:
• Offer LMWH + Aspirin ( live birth rate 71 %)
Handbook Of Obstetric Medicine, 4th Edition, Catherine Nelson Piercy
RCOG Greentop guideline 17
Management Of APS
(Without H/O Thrombosis)
• Antenatal Management:
– Use of LMWH (clexane) must be balanced against its
cost, inconvenience & the risk of osteoporosis (0.04%)
– Prophylactic dose : start as soon as pregnancy confirmed
– Monitoring with anti Xa level is not required
Management Of APS
(Without H/O Thrombosis)
• Antenatal Management:
–20 Weeks:
• Uterine Artery Doppler (If Pre-diastolic Notching +Ive)
–24 Weeks Onwards:
• Serial Growth Scan & Umbilical Artery Doppler
• Check BP and quantify proteinuria.
• Plan timely delivery to improve fetal outcome.
• Continue aspirin throughout pregnancy.
• Stop clexane 12 hours before delivery.
Management Of APS
(Without H/O Thrombosis)
• Antenatal Management:
– Ultrasound and doppler normal : no intervention till term.
– Absent/reverse flow and moderate abruption : deliver immediately
– Oligohydroamnios + FGR + normal doppler : deliver at 34 wk
Management Of APS
(Without H/O Thrombosis)
• Puerperium
– Start LMWH
• 4 hrs after GA
• 6hours after regional
– Prophylactic LMWH (40mg OD)
for 1-6 weeks(depending on other risk factors
e.g obese, smoker, age>35)
Reducing The Risk Of Thrombosis And Embolism During Pregnancy And The Puerperium, RCOG
Guideline 37a, 2009
Management Of APS (With H/O Thrombosis
Or Ischemic Stroke)
• Mostly these women are on Warfarin
(anticoagulation therapy)
• Change Warfarin to LMWH : prior to 6 weeks
gestation (after liason with haematologist)
• Full therapeutic anticoagulant dose.
• Titrate Dose : 4hrs Post Injection Peak Level Of Anti
Xa = 0.5- 1.0 IU /mL
• Stop 24 hours prior to delivery
Management Of APS (With H/O Thrombosis
Or Ischemic Stroke)
• Puerperium:
– Postpartum LMWH Or Warfarin ????
– LMWH switched to Warfarin After 5-7 Days Of Delivery in
women who are on lifelong anticoagulant therapy.
– Monitor INR when converting to warfarin (Till INR>2)
Contraception
Contraceptive Category
IUCD
1-Cu T 01
2- LNG IUS 02
Progestogens:
1- Progestogen only pill 02
2- DMP
3- Implanon
COCP 04
UK MEDICAL ELIGIBILITY CRITERIA
FOR CONTRACEPTIVE USE | UKMEC 2016
Thanks
Credits:
•Royal College Of Obstractic Guideline
• Handbook Of Obstetric Medicine, 4th Edition,
Catherine Nelson Piercy
•[Link]
•Special thanks to:
• Professor Nilofar Mustafa and Obs & Gynae Dept.
•Pathology Department