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(EPCR) 23-bp insertion was detected by PCR amplification without any further restriction digestion.13
Plasminogen activator inhibitor (PAI)-1 4G/5G polymorphism was detected by allele-specific PCR
amplification using 2 sets of primers as described.14
All the thrombophilia markers were assessed at least
3 months after abortion or delivery.
Anticoagulation Regimen
Methods
Patients
We analyzed 32 consecutive pregnant women (mean
age = 24 years) with either DVT associated with
pregnancy or a history of recurrent fetal loss for
evaluation of thrombophilia and subsequent management during pregnancy. All the women had a
thorough investigation (ie, cytogenetic, hormonal,
anatomical, and infective causes for fetal loss) and
were negative for the above-mentioned causes.
Laboratory Monitoring
of Heparin Dosage
Activated partial thromboplastin time (APTT) was
performed once a week to keep the APTT 1.2 to 1.5
times the baseline of patients in cases of UFH therapy. The blood sample was taken once in every 2
weeks before the next dose of heparin until 30 weeks
of gestation and thereafter, every week when the
dose of UFH was increased to 7500 IU subcutaneous, twice daily. No anti-Xa or anti-IIa activity was
studied in the case of women treated with LMWH.
During each visit, a detailed history of bleeding was
taken from each patient. The patients had routine
blood counts during follow-up, with special reference to thrombocytopenia.
The heparin was injected subcutaneously
around the umbilicus by rotation using a 26-gauge
needle. All the deliveries were induced between 36
and 37 weeks and took place per via naturalis.
Results
The study group consisted of 32 women with thrombophilia.
Table 1 shows the characteristics of women with
recurrent pregnancy loss. The mean age of patients
was 24 years (range 20-37 years), and the mean
number of abortions in the group was 3.0 (range
2-9). Nine patients had only early pregnancy losses
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Table 1.
Characteristics of Patients With Recurrent Fetal Loss, Treatment Details, and Their Outcome
No
Patient
ID
Age
(y)
No of
Abortions
Time
of Loss
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
49
242
32
114
33
508
311
98
352
438
38
231
303
367
76
216
213
72
177
37
92
375
199
285
26
30
22
25
30
28
22
34
31
25
25
30
26
29
20
28
22
25
36
31
26
24
24
37
4
5
2
5
5
3
3
9
5
3
3
4
2
6
3
5
3
3
2
3
3
3
2
3
Early
Early
Early
Early
Early
Early
Early
Late
Late
Late
Early + late
Early + late
Early + late
Early + late
Early + late
Early + late
Early + late
Early
Early
Early + late
Early + late
Early + late
Early + late
Early + late
25
100
27
Early + late
Thrombophilia Marker
LA, ACA, FVL het
LA, ACA
ACA, fib448 het
LA, ACA
High fib (>800 mg/dL)
LA, ACA
ACA
ACA, 2GP1, weak annexin
High fib, MTHFR het
2GP1, EPCR het, weak annexin
LA, ACA, weak annexin
LA, ACA, PS def
ACA, antiannexin
High fib (>800 mg/dL)
ACA
LA, ACA
LA, ACA, 2GP1, PAI-1 4G/4G
LA, ACA, FVL het
FVL het
LA, ACA, 2GP1
LA, ACA, 2GP1
High fib (>800 mg/dL), high factor VIII
ACA
High fib (>800 mg/dL), antiannexin,
FVL het
LA, ACA, antiannexin
UFH/
LMWH
Live
Birth/Abortion
UFH
UFH
UFH
UFH
UFH
UFH
UFH
UFH
UFH
UFH
UFH
UFH
UFH
UFH
UFH
UFH
UFH
LMWH
LMWH
LMWH
LMWH
LMWH
LMWH
LMWH
Live birth
Live birth
Live birth
Live birth
Live birth
Abortion
Abortion
Live birth
Live birth
Abortion
Live birth
Live birth
Abortion
Live birth
Live birth
Abortion
Abortion
Live birth
Live birth
Live birth
Live birth
Live birth
Live birth
Live birth
LMWH
Live birth
NOTE: LA = lupus anticoagulants; ACA = anticardiolipin antibodies; FVL het = factor V Leiden heterozygous; fib448 het =
fibrinogen 448 Arg/Lys heterozygous; PS def = protein S deficiency; High fib = high fibrinogen; LMWH = lowmolecular weight
heparin; UFH = unfractionated heparin.
Table 2.
Characteristics of Patients With Deep-Vein Thrombosis During Pregnancy With or Without Fetal Loss,
Treatment Details, and Their Outcome
Patient
ID
Age
(y)
1
2
3
4
5
36
58
113
377
305
30
24
22
24
20
6
7
361
181
27
32
No
177
No of
Abortions
No
No
No
No
No
Time
of Loss
loss
loss
loss
loss
loss
2
1
Thrombophilia Marker
ACA, PS def
MTHFR het
LA, ACA, antiannexin
High platelets, FVL het
ACA,weak annexin, Fib448 homo,
PAI14G/4G
FVL het, weak annexin
High fib (>800 mg/dL)
Early
Early
UFH/
LMWH
Live
Birth/Abortion
UFH
UFH
UFH
LMWH
UFH
Live
Live
Live
Live
Live
birth
birth
birth
birth
birth
UFH
UFH
Live birth
Live birth
NOTE: LA = lupus anticoagulants; ACA = anticardiolipin antibodies; FVL het = factor V Leiden heterozygous; fib448 homo =
fibrinogen 448 Arg/Lys homozygous; PS def = protein S deficiency; MTHFR het = methylene tetrahydrofolate reductase heterozygous;
High fib = high fibrinogen; LMWH = lowmolecular weight heparin; UFH = unfractionated heparin.
18
17
Total Patients
16
Live Birth
14
12
10
6
5
6
4
2
0
RFL + UFH
RFL + LMWH
DVT + UFH
DVT + LMWH
Discussion
Lowmolecular weight heparin has become the routine treatment for women with fetal loss and with
acquired and heritable thrombophilias. However,
there are limited data on its utility in cases of recurrent fetal loss. Unfractionated heparin is an attractive alternative in a developing country such as India
because of the low cost; however, it has some side
effects and needs regular laboratory monitoring by
APTT assays. A recent systematic review,5 in which
the data on both LMWH and UFH were pooled,
showed that there was only a 35% reduction in pregnancy loss. However, most of the studies included in
178
Acknowledgment
The authors would like to acknowledge Gland
Pharma, Hyderabad, India, for providing LMWH
(Indeparin) for our patients.
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