RCOG World Congress 2025

Antithrombin III Deficiency in Pregnancy

A series of three cases

S Mahdasu and S Alomari

Introduction

Hereditary antithrombin deficiency is a thrombogenic

disorder associated with a 50–90% lifetime risk of

venous thromboembolism (VTE), which is increased

during pregnancy and the puerperium in these

patients. We present 3 cases of pregnant women

with antithrombin (AT) deficiency who presented with

a VTE and were treated with LMWH and antithrombin

concentrate according to individualised plan.

Case 1

A 31-year-old with Type 1 antithrombin (AT) deficiency

(antigen 0.32 U/mL, activity 0.33 U/mL) with a past history

of recurrent un-provoked venous thromboembolism (VTE)

was switched from warfarin to therapeutic-dose low-

molecular-weight heparin (LMWH) when she be-came

pregnant. Her past VTE events included two estrogen-

associated VTEs (oral contraceptive pill; ectopic

pregnancy and surgery) despite therapeutic warfarin.

While on once-daily weight-based LMWH, she developed

a new, symptomatic proximal deep vein thrombosis (DVT)

at 10 weeks gestation. She was subsequently treated with

AT concentrate and LMWH throughout her pregnancy,

with no further VTE recurrence and a successful delivery.

Case 2

19 year old primigravida with a known hereditary AT deficiency and

history of recurrent first trimester miscarriages , no personal history

of thrombosis but a strong family history of AT deficiency and

maternal postpartum VTE. The AT activity was 51% and the family

history confirmed the diagnosis .She was started on adjusted dose

of LMWH tinzaparin 14,000 IU daily from 12 weeks and that was

monitored monthly with AT activity and anti Xa level ;despite that Xa

activity remained subtherapeutic due to heparin resistance and

during the last trimester there was a further drop in AT levels .

Increasing the LMWH dose actually lowered the AT levels further so

the dose of 14,000 IU was resumed throughout pregnancy.

AT levels ranged from 33 to 57% during pregnancy; she was delivered

by a planned caesarean section at 39 weeks due to breech

presentation , the last dose of LMWH was given 24 hours before

surgery, 3 hours preoperatively , human AT concentrate infusion was

given intravenously .The caesarean section was uneventful and 8

hours post operatively , LMWH was resumed at 4500 IU/day she

delivered a healthy small for gestational age male baby weight 2615

grams .AT levels post infusion where 112% at 2 hours and 65%

trough next day . The AT infusion was planned to be given for 6 days ,

stopped at day 4 due to allergic reaction and the LMWH dose

increased back to 14,000 IU/day ;she was discharged on the day 6

post part of the continued to support in 4500IU daily for six weeks

Discussion

Case 3

G2P1+0 ,22 year old with AT deficiency .Her family history was

remarkable for AT deficiency in her father and sister. Her father had a

history of multiple thrombotic events beginning at the age of 23. At 31

he died from refractory progressive VTE related to small cell carcinoma

of the lung. In her past obstetric history 1st pregnancy was

uncomplicated. Prior to induction of labour she received LMWH during

her pregnancy and post-partum. She also received AT concentrate to

maintain AT activity at 80–120% of normal levels. After delivery,, she

was scheduled to receive prophylactic anticoagulation for 12 weeks

post-partum, she discontinued therapy at six weeks. However, she did

not experience any thrombotic events.

During her second pregnancy, she was prescribed prophylactic LMWH

daily .Despite that she developed a DVT in her right lower extremity at

13week .The DVT extended from the common femoral vein to the

popliteal vein. The LMWH dose was increased to therapeutic levels and

she received AT concentrate, targeting a peak AT activity of 120%.

Despite that she experienced progression of the DVT in her right lower

extremity to involve the common femoral vein, popliteal vein, and calf

veins. A multidisciplinary decision was made to proceed with IVC filter

placement. Anticoagulation management was escalated by the

addition of AT concentrate to therapeutic dosing of LMWH. LMWH was

discontinued 24 hrs prior to delivery and resumed 12 hrs after delivery.

There was no further progression of the DVT, and the baby’s vaginal

delivery was unremarkable.

The high risk of thrombotic events in pregnant patients

with hereditary AT deficiency has prompted

recommendation from a number of societies such as the

(RCOG) and (ACOG) supporting prophylactic LMWH use

in hereditary AT deficient patients with a personal or

family history of VTE [1,2]. However, patients may still

develop VTE despite being on LMWH. In selected

patients with previous pregnancy-associated VTE, AT

concentrates may be considered for secondary

prophylaxis of pregnancy-induced VTE. Pregnant

patients with hereditary AT deficiency who develop VTE

during pregnancy are often treated with both

anticoagulants and AT concentrate. There are no

guidelines regarding management of acute VTE in

pregnant patients with AT deficiency, and

recommendations are based on expert opinion and little

data is available on the appropriate timing of initiation,

dosing, and duration of AT concentrate during pregnancy

and the postpartum period. The two most common

indications for AT concentrate in pregnant women with

hereditary AT deficiency are for the management of

acute VTE during pregnancy despite therapeutic

anticoagulation and for prophylaxis in the antepartum,

peripartum, and/or postpartum periods. The indication is

less clear in women who develop VTE while receiving

prophylactic dose anticoagulation, who can potentially

be managed by increasing the dose of anticoagulation to