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
•Osmosis.org
•Special thanks to:
• Professor Nilofar Mustafa and Obs & Gynae Dept.
•Pathology Department