Keywords
guidelines - pregnancy - risk assessment - risk score - venous thromboembolism
Introduction
Pregnancy significantly increases the risk of venous thromboembolism (VTE) and may
be accompanied by placental vascular complications (PVCs), such as pre-eclampsia,
foetal growth restriction (intrauterine growth restriction [IUGR]), placental abruption,
intrauterine foetal death (IUFD) and pregnancy loss. Various national or international
recommendations concerning VTE prophylaxis during pregnancy are available[1]
[2]
[3]
[4] . However, their application is not always straightforward, particularly in patients
cumulating several identified risk factors for VTE and PVC, and the optimal strategy
for complex clinical cases remains unclear. Furthermore, their complexity may discourage
their routine use by primary care practitioners and gynaecologists less familiar with
VTE. Systematic risk assessment has been recommended since 2008,[5] and several risk-scoring systems have been published.[6]
[7]
[8]
[9]
[10]
[11]
[12] However, the clinical value of these scores is questionable due to their lack of
validation and compliance with international guidelines.
Using a Delphi approach, we developed an easy-to-use tool, the STRATHEGE score, enabling
individualized estimation of thrombotic risk during pregnancy and permitting implementation
of a risk-adapted strategy for anti-thrombotic prophylaxis during pregnancy and puerperium.[12] This score includes four sub-groups of items: personal and family history of thrombotic
events; acquired or inherited thrombophilia; personal history of PVCs; and other clinical
risk factors (see [Appendix A]). It was constructed by an expert panel of clinicians and biologists involved in
both VTE and pregnancy management, respecting the most recent international guidelines
in this area.
Appendix A
Final risk scoring system obtained at the end of the DELPHI method of development
and application
|
Past history of venous thromboembolic events
|
Score
|
Thrombophilia
|
Score
|
|
Multiple personal VTE events (including one proximal DVT or PE) or long-term anticoagulants
|
12
|
Anti-thrombin deficiency
|
10
|
|
Protein C, protein S deficiency
|
4
|
|
Single personal VTE event (*) – PE or proximal DVT
|
5
|
Factor V Leiden, factor II 20210 A polymorphism
|
|
|
– distal DVT
|
2
|
– Heterozygosity
|
3
|
|
(*) with a triggering factor
|
–2
|
– Homozygosity
|
5
|
|
(*) during pregnancy, post-partum or OC intake
|
+1
|
– Compound heterozygosity
|
4
|
|
1st degree relative, proximal VTE: idiopathic or multiple or severe
|
2
|
High factor VIII concentrations
|
0
|
|
Family history: non-severe VTE (distal DVT or triggering factor or > 60 y)
|
0
|
Hyperhomocysteinaemia
|
0/B
|
|
Past history of arterial thromboembolic events
|
|
LA / aPL antibodies ± placental vascular complications
|
9/A
|
|
Stroke, vasculitis, arterial embolism, symptomatic atherothrombosis
|
0/A
|
LA / aPL + arterial and/or venous thrombosis
|
12
|
|
Placental vascular complications
|
Score
|
Other risk factors
|
Score
|
|
IUFD
|
+2/A
|
Multiparity > 3, varicose veins, age > 35 y, obesity, post-phlebitis sequels, systemic
lupus erythematosus without LA
|
0
|
|
Recurrent miscarriages (≥ 3) or one loss ≥ 9 wk
|
0/A
|
|
|
Pre-eclampsia or HELLP syndrome or placental abruption
|
+1/A
|
|
IUGR
|
+2/A
|
Abbreviations: aPL, anti-phospholipid antibodies; DVT, deep vein thrombosis; IUFD,
intrauterine foetal death; IUGR, intrauterine growth restriction; LA, lupus anticoagulant;
LMWH, low-molecular-weight heparin; OC, contraception; PE, pulmonary embolism; VTE,
venous thromboembolism.
Note: The risk components finally retained are classified in four categories according
to their main characteristics. The final proposed treatment, detailed at the foot
of the figure, depends on the total value obtained after addition of the various components
of the risk.
Prophylaxis:
Graduated elastic compression stockings antepartum and during puerperium: all women
with at least one positive VTE risk factor.
Total score:
1 to 3: Prophylactic LMWH during puerperium (6 wk).
4: Prophylactic LMWH during third trimester and puerperium.
5 to 11: Prophylactic LMWH antepartum and during puerperium.
≥ 12: Adjusted-dose LMWH.
A: Low-dose aspirin (if no adjusted-dose LMWH).
B: Folic acid.
As the clinical benefit of this STRATHEGE score-guided prophylaxis remained to be
prospectively demonstrated,[6] we conducted a before-and-after implementation clinical trial to show its effectiveness
in terms of the rate of thrombotic and vascular events in at-risk pregnant women (Clinicaltrials.gov
registry no. NCT00745212).
Materials and Methods
Study Design
This French multi-centre before-and-after implementation study was performed in maternity
units corresponding to levels I to IV obstetric care and comprised three successive
stages: before implementation of the scoring system (BEFORE stage), implementation
of this system and after its implementation (AFTER stage). In the BEFORE stage, eligible
adult women were consecutively included 24 hours after admission to the delivery unit,
thromboprophylactic regimens during puerperium being prescribed at the physician's
discretion. In principle, all relevant data required for calculation of the score
were recorded at the time of delivery, as were data on the treatment received. However,
as the scoring system was voluntarily finalized only at the end of the BEFORE phase
so as not to influence practices in that phase, certain additional data had to be
extracted retrospectively from medical records to complete the score (i.e. family
history of VTE). Symptomatic events occurring during pregnancy and the 6-week follow-up
after delivery were recorded.
In the implementation stage, all midwives and obstetricians in the maternity units
participating in the study were trained in use of the risk scoring system, designed
to identify women at risk of VTE and PVC and lead to a specific proposal for prophylaxis
based on the overall score (see [Appendix A]). This therapeutic approach comprised (1) identification of at-risk women using
a simple questionnaire, (2) addition of individual scores for identified risk factors
in the following four categories: personal or family history of VTE, presence of thrombophilia,
history of PVC and presence of other clinical risk factors and (3) use of our scoring
system to determine the optimal prophylactic regimen for each patient. Pocket-sized
cards presenting the scoring system were provided. This stage also included seminars
on VTE and PVC prophylaxis according to the Eighth American College of Chest Physicians
(ACCP) recommendations.[5]
In the AFTER stage, eligible adult women were consecutively included during any pregnancy-related
medical consultation and practitioners were asked to prescribe the thromboprophylactic
regimens suggested by the scoring system.
Patients
Adult women with at least one risk factor for VTE or PVC were eligible for inclusion.
According to the STRATHEGE scoring system,[6] risk factors included (1) personal history of VTE and family history of VTE; (2)
acquired or inherited thrombophilia including anti-thrombin deficiency, protein C
or S deficiency, heterozygous or homozygous factor V Leiden or pro-thrombin 20210A
polymorphism, lupus anticoagulant, anti-cardiolipin antibodies, anti-β2-glycoprotein
I antibodies, and hyperhomocysteinaemia; (3) history of PVC, defined as vascular IUFD
or repeated miscarriages > 2, pre-eclampsia, HELLP (haemolysis, elevated liver enzymes,
low platelet count) syndrome, placental abruption and IUGR (estimated foetal weight < 10th
percentile); and (4) high body mass index (> 30) or age above 35 years and two other
minor clinical risk factors. Patients were informed of the study design and gave their
oral consent to participate.
Exclusion criteria were unknown personal or familial history, non-vascular IUFD, presence
of mechanical heart valves requiring anticoagulation, any contraindication for anticoagulant
administration, such as known allergy to heparin, low-molecular-weight heparin (LMWH)
or aspirin and impossibility of follow-up.
STRATHEGE Score
The overall risk score for VTE and PVC was determined for each woman enrolled in the
BEFORE or AFTER stage and rates of concordance between the prophylactic regimens indicated
by overall risk scores and those actually implemented during pregnancy and puerperium
were recorded.
Endpoints
The primary endpoint was a composite endpoint including the occurrence of symptomatic
VTE and/or PVC during pregnancy or puerperium (defined as six completed weeks after
delivery).
Symptomatic VTE was defined as symptomatic pulmonary embolism (PE), deep or superficial
vein thrombosis (DVT or SVT) and cerebral venous thrombosis objectively confirmed
by ultrasonography (DVT and SVT), or positive ventilation/perfusion lung scan (PE),
or computed tomography scan or lower-limb venous ultrasonography (DVT or SVT), or
magnetic resonance imaging (cerebral venous thrombosis).
PVCs were defined as three or more consecutive pregnancy losses between 5 and 12 weeks
of amenorrhea (WA), one or more vascular IUFD after 12 WA (i.e. IUFD not explained
by malformation, chromosomal abnormality or infectious disease), pre-eclampsia, placental
abruption, HELLP syndrome or IUGR. Pre-eclampsia was defined as new-onset diastolic
blood pressure of at least 90 mm Hg after 20 weeks of gestation, controlled on two
occasions at least 4 hours apart, accompanied by significant proteinuria (> 0.3 g
in a 24-hour urine sample) or new-onset proteinuria in women with pre-existing hypertension.
Pre-eclampsia was defined as severe when associated with severe hypertension (diastolic > 110 mm
Hg or systolic > 160 mm Hg), eclampsia (seizures), pulmonary oedema, proteinuria ≥ 5 g
per 24 hours, renal insufficiency based on abnormal blood creatinine levels, abnormally
high liver enzyme levels (aspartate aminotransferase [ASAT] or alanine aminotransferase
[ALAT] ≥ 70 IU/L) with abdominal pain, low platelet counts (< 100 G/L) and/or delivery
at < 34 weeks of gestation. Placental abruption was diagnosed on detection of a circumscribed
depression on the maternal surface of the freshly delivered placenta, covered by dark
clotted blood; when placental abruption was very recent, signs and symptoms recorded
before delivery contributed to the diagnosis, particularly the association of vaginal
bleeding and uterine tenderness or back pain, or foetal distress or death, or uterine
hypertonus. HELLP syndrome was defined by the presence of haemolysis (characteristic
peripheral blood smear and serum lactate dehydrogenase ≥ 600 U/L or serum total bilirubin ≥ 1.2
mg/dL), elevated liver enzymes (serum ASAT or ALAT ≥ 70 U/L) and low platelet counts
(< 100,000 cells/µL). IUGR was defined as birth weight ≤ 10th percentile according
to AUDIPOG charts, taking into account maternal age, neonatal gender and gestational
age at delivery.
Secondary endpoints were post-partum haemorrhage and treatment-related complications.
Post-partum haemorrhage was defined as blood loss above 500 mL, necessitating examination
of the uterus, with any of the following: peri-partum haemoglobin drop of more than
20 g/L, transfusion, embolization, conservative surgical procedure, hysterectomy or
death. Treatment-related complications were defined as life-threatening bleeding or
bleeding requiring medical intervention, heparin-induced thrombocytopenia (defined
according to the ACCP guidelines), skin complications, heparin or aspirin allergy,
congenital anomalies or birth defects.
All events were validated by an independent central adjudication committee, unaware
of anticoagulant or anti-platelet treatment.
To avoid overlooking recorded events in the BEFORE stage, medical records and codes
from the International Classification of Diseases, 10th Revision, Clinical Modification:
O00-O99: (O03; O08; O12–16; O022; O087) were reviewed for patients included in this
stage.
Statistical Analysis
Based on a previous study, indicating a 5.6% incidence of VTE events among at-risk
women,[12] we assumed at least a 5% rate of VTE events plus PVC in our population before implementation
of our risk score. Assuming a 50% reduction in the primary endpoint with risk score-driven
thromboprophylaxis, and a two-sided type I error of 5%, we calculated that a sample
size of 900 patients per stage would have a 90% power to detect a difference between
the combined VTE and PVC rates observed before and after implementation of the score.
We therefore planned to recruit 2,000 patients in total to obtain 1,800 evaluable
patients.
The composite primary endpoint (occurrence of VTE or PVC), as well as the other endpoints,
were compared before and after implementation of the score using the chi-square test;
absolute differences and relative risks (RRs) with their 95% confidence intervals
(CIs) were calculated. The number needed to treat (NNT) associated with the use of
the score was also estimated. To describe the concordance between the prophylactic
treatment indicated by the overall risk score and that actually prescribed, the Kappa
coefficient (with its 95% CI) was calculated. A Kappa coefficient close to 1 indicated
(almost) perfect agreement, while a coefficient close to 0 indicating disagreement.
Statistical analyses were performed using the SAS software, version 9.4 (SAS Institute,
Cary, North Carolina, United States).
Ethics
The study was approved by the Saint Etienne University Hospital Centre institutional
review board and ethics committee and by the local committee for the protection of
clinical trial participants (Comité de Protection des Personnes). It complied with the 2013 Helsinki Declaration (No. 08/120).
Results
From May 2008 to March 2013, 989 pregnant women at risk of VTE or PVC were enrolled
in the BEFORE stage of the trial, prior to implementation of the risk scoring system,
and 1,096 in the AFTER stage, following implementation of this system ([Fig. 1]). The study was conducted in 21 French maternity units, predominantly corresponding
to type III obstetric care (BEFORE stage: 62.4%, AFTER stage: 67.3%; [Table 1]). The mean gestational period at delivery was 37.4 and 37.7 weeks, respectively.
To allow comparison of the patients included in the two stages, we calculated a posteriori
the score for the BEFORE stage population. A risk score of 0 (corresponding to a recommendation
for no heparin treatment) was calculated for 51.3% of women in the BEFORE stage and
45.3% in the AFTER stage. According to the calculated risk score, 26.0 and 23.7% of
patients, respectively, required minimal prophylaxis (prophylactic treatment during
the 6-week puerperium; [Table 2]).
Table 1
Site and patient characteristics
|
Before intervention
(N = 989)
|
After
intervention
(N = 1,089)
|
|
Maternity type, %
|
|
|
|
I
|
11.9
|
12.6
|
|
II
|
25.7
|
20.1
|
|
III
|
62.4
|
67.3
|
|
Age (y), mean ± SD
|
32.0 ± 5.5
|
31.3 ± 5.1
|
|
Total no. of pregnancies, %
|
|
|
|
1
|
17.5
|
21.2
|
|
2
|
25.3
|
29.9
|
|
3
|
22.5
|
20.7
|
|
4
|
13.7
|
11.9
|
|
≥ 5
|
21.0
|
16.3
|
|
Parity, %
|
|
|
|
0
|
25.8
|
28.0
|
|
1
|
41.7
|
40.0
|
|
2
|
21.3
|
19.7
|
|
3
|
6.3
|
8.7
|
|
≥ 4
|
5.0
|
3.6
|
|
Delivery term (wk of gestation), mean ± SD
|
37.4 ± 3.7
|
37.7 ± 4.3
|
Abbreviation: SD, standard deviation.
Table 2
STRATHEGE risk scoring system and prophylaxis suggested by the overall score
|
Before intervention
(N = 989)
|
After
intervention
(N = 1,089)
|
|
Before
|
After
|
|
Anti-thrombotic prophylaxis
suggested by the overall risk score, %
|
Applied
a posteriori
|
|
|
0, No heparin treatment
|
51.3
|
45.3
|
|
1–3, Prophylactic heparin during PP (6 wk)
|
26.0
|
23.7
|
|
4, Prophylactic heparin during 3rd trimester + PP (6 wk)
|
2.9
|
2.7
|
|
5–11, Prophylactic heparin throughout pregnancy + PP
|
15.9
|
22.9
|
|
≥12, Weight-adjusted heparin prophylaxis during pregnancy + PP
|
3.9
|
5.5
|
|
Aspirin, %
|
13.0
|
42.9
|
Abbreviations: PP, puerperium; SD, standard deviation.
Fig. 1 Study design and calendar.
Outcomes
Primary Endpoint
The primary endpoint was evaluable in all 989 patients BEFORE implementation of the
score and in 1,078/1,089 patients AFTER this (10 patients were lost to follow-up for
the post-partum period, and for one patient, the hospital record for one visit was
not found). The composite primary endpoint of VTE or PVC occurred in 190 (19.2%) patients
in the BEFORE stage and 140 (13.0%) patients in the AFTER stage ([Table 3]), yielding a RR reduction of 32% (RR = 0.68 [95% CI, 0.55; 0.83], p = 0.0001). The NNT associated with the use of the score was 16, meaning that using
the score in 16 patients would avoid the occurrence of one VTE or PVC. VTE was diagnosed
during pregnancy/puerperium in 37 patients (3.7%) BEFORE and 19 patients (1.8%) AFTER
implementation of the scoring system. The corresponding RR was 0.47 [0.27; 0.81],
p = 0.006. The NNT was 51. For VTE, the effect of implementing this scoring system
was mainly observed during pregnancy, the rate of VTE then being 2.7% for BEFORE and
0.9% for AFTER (RR = 0.34 [0.16; 0.69], p = 0.002; [Table 3]). PVC occurred in 16.3% of patients BEFORE and 11.5% of patients AFTER implementation
of the scoring system (RR = 0.71 [0.57; 0.88], p = 0.002). The NNT was 21, indicating that use of the score in 21 patients would avoid
the occurrence of one PVC. PVC mainly comprised IUGR with or without pre-eclampsia.
Table 3
Endpoints
|
Before intervention
(N = 989)
|
After intervention
(N = 1,089)
|
Absolute difference
(95% CI)
|
RR (95% CI)
|
p-Value
|
|
Composite primary endpoint
|
|
|
|
|
|
|
At least one VTE or PVC
|
190 (19.2%)
|
140 (13.0%)
|
–6.2% (–9.4; –3.1)
|
0.68 (0.55; 0.83)
|
0.0001
|
|
VTE
|
37 (3.7%)
|
19 (1.8%)
|
–1.9% (–3.4; –0.6)
|
0.47 (0.27; 0.81)
|
0.006
|
|
DVT
|
16
|
9
|
|
|
|
|
SVT only
|
16
|
5
|
|
|
|
|
PE
|
5
|
4
|
|
|
|
|
Cerebral venous thrombosis
|
0
|
1
|
|
|
|
|
VTE during pregnancy
|
27 (2.7%)
|
10 (0.9%)
|
–1.8% (–3.0; –0.6)
|
0.34 (0.16; 0.69)
|
0.002
|
|
VTE during puerperium
|
10 (1.0%)
|
9 (0.8%)
|
–0.2% (–1.0; 0.7)
|
0.83 (0.34; 2.02)
|
0.67
|
|
PVC
|
161 (16.3%)
|
124 (11.5%)
|
–4.8% (–7.8; –1.8)
|
0.71 (0.57; 0.88)
|
0.002
|
|
Intrauterine growth restriction
|
86
|
76
|
|
|
|
|
Pre-eclampsia
|
79
|
42
|
|
|
|
|
< 34 wk of gestation
|
46
|
29
|
|
|
|
|
Intrauterine foetal death
|
11
|
11
|
|
|
|
|
Placental abruption
|
8
|
4
|
|
|
|
|
Spontaneous miscarriage
|
0
|
9
|
|
|
|
|
Secondary endpoints
|
|
|
|
|
|
|
Post-partum haemorrhage
|
32 (3.2%)
|
48 (4.5%)
|
1.2% (–0.4; 2.9)
|
1.38 (0.89 ; 2.13)
|
0.15
|
|
Treatment-related complications
|
5 (0.5%)
|
3 (0.3%)
|
–0.2% (–0.8; 0.3)
|
0.55 (0.13 ; 2.30)
|
0.41
|
|
Bleeding
|
1
|
0
|
|
|
|
|
HIT
|
1
|
0
|
|
|
|
|
LMWH or UFH allergy
|
3
|
2
|
|
|
|
|
Minor bleeding (haemorrhoids)
|
0
|
1
|
|
|
|
Abbreviations: CI, confidence interval; DVT, deep vein thrombosis; HIT, heparin-induced
thrombocytopenia; LMWH, low-molecular-weight heparin; PE, pulmonary embolism; PVC,
placental vascular complications; RR, relative risk; SVT, superficial vein thrombosis;
UFH, unfractionated heparin; VTE, venous thromboembolism.
Secondary Endpoints
Overall, 80 patients experienced post-partum haemorrhage, without any statistical
difference between the BEFORE (32 patients, 3.2%) and AFTER (48 patients, 4.5%) periods
(RR = 1.38 [0.89; 2.13], p = 0.15; [Table 3]). Twelve of these patients had received LMWH during pregnancy, but discontinued
this treatment for delivery and epidural analgesia. The other 68 women experienced
post-partum haemorrhage without having received any pharmacological prophylaxis before
delivery. Five patients in the BEFORE stage and 3 patients in the AFTER period presented
another treatment-related complication ([Table 3]). No patient died in either period.
Anticoagulant and Anti-Platelet Prophylaxis
During pregnancy and puerperium, 584 patients (59.0%) in the BEFORE period and 766
(71.1%) in the AFTER period received anticoagulant prophylaxis. In the AFTER period,
compliance with the anticoagulant treatment suggested by the scoring system was 73.1%
overall and 42.1% for patients presenting VTE. Similarly, 283 (28.6%) and 491 patients
(45.5%) received aspirin in the BEFORE and AFTER period, respectively. In the AFTER
period, compliance with the aspirin treatment suggested by the risk score was 97.4%
overall. A similar compliance with the suggested aspirin treatment was observed for
patients presenting a PVC.
Other Data
Median birth weight was 3,070 and 3,160 g in the BEFORE and AFTER periods of the study,
respectively. The Appearance, Pulse, Grimace, Activity, and Respiration score and
other parameters did not differ significantly between the two periods (data not shown).
No treatment-related adverse events were observed in neonates.
Discussion
The results of this large multi-centre, controlled BEFORE and AFTER intervention study
show that implementation of the STRATHEGE risk scoring system and the proposed prophylactic
strategies significantly reduced the risk of VTE and PVC by 50 and 30%, respectively,
in at-risk pregnant women. It particularly reduced the rate of severe PVC. Overall,
use of our scoring system 16 times may avoid one event. However, the study design
does not allow resolution of this controversial issue.
Various risk stratification assessments and scoring systems have been proposed.[7]
[9]
[12]
[13] However, to the best of our knowledge, this is the first prospective validation
of a risk scoring system associated with a proposal of prophylactic strategies. Our
scoring system was established, using the DELPHI method, by 19 French experts actively
involved in both clinical management and research on VTE and PVC.[6] This score provides an individual estimation of the risk of thrombosis during pregnancy
and puerperium and suggests a corresponding prophylactic strategy. The scoring system
was developed before the eighth and ninth ACCP guidelines[1]
[5] and is no longer in total agreement with more recent guidelines and publications.
For example, we chose to associate VTE and PVC when developing our risk score, although
the development of a common prophylactic strategy for these two outcomes is still
a matter of debate.[13]
[14]
[15] However, use of our scoring system and its corresponding prophylactic strategies
seemed to similarly decrease rates of both VTE and PVC, thereby supporting our choice.
Other discrepancies with past ACCP guidelines (such as a family history of VTE) do
not concern the major recommendations, supported by a high level of evidence.
In the current ACCP guidelines, monotherapy with aspirin is recommended for women
with inherited thrombophilia and a history of pregnancy complications, except for
those with anti-phospholipid antibody syndrome.[1] According to our scoring system, some of these patients could receive LMWH on top
of aspirin. At the time when the scoring system was developed, this strategy was supported
by the results of several studies[16]
[17]
[18] suggesting a benefit of LMWH added to aspirin in the prevention of PVC. However,
Rodger et al recently failed to demonstrate a benefit of such an association on the
rate of pregnancy complications.[19] The benefits of such a prophylactic association are probably minor and are still
widely debated, and further trials are on-going.[13]
[15]
[17]
[20] It is worth noting that only 2.7% of our patients received this kind of association
based on the risk scoring system used.
LMWH prophylaxis initiated at the start of the third trimester is also controversial,
although VTE can occur in women at any time during pregnancy and puerperium.[21] In contrast to the ACCP guidelines,[1] French guidelines recommended initiation of LMWH at the start of the third trimester.[2] Other French investigators suffered from the same limitation in trial construction.[7] However, it is worth noting that this timing of the start of prophylaxis applied
to less than 3% of our patients.
Some of our patients were possibly under-treated, although 59 (2.8%) women with a
history of thrombosis included in the BEFORE or AFTER phase belonged to this sub-group
and none relapsed. The 37 VTE events recorded during pregnancy affected mainly the
patients included in the BEFORE phase (27 vs. 10, p < 0.002), but only 30% of women received prophylaxis according to their overall risk
score, the others being under-treated. VTE events as a whole were greatly reduced
during pregnancy by use of our scoring system to guide prophylaxis (RR = 0.33 [0.16;
0.69]). This reduction was also evident for DVT and PE (0.37 [0.15; 0.89], p = 0.02) during pregnancy. Reflecting the study design, this reduction was observed
mainly during pregnancy rather than puerperium. As patients enrolled in the BEFORE
stage were included on the day of delivery, physicians had the opportunity to improve
prophylaxis during puerperium. This probably explains the absence of any significant
difference in puerperium event rates between the BEFORE and AFTER phases. Similarly,
275 PVC occurred, but PVC rates were significantly reduced by 25% in women who received
prophylaxis according to their overall risk score (comprising 40% of the total study
population). This reduction was particularly evident with respect to pre-eclampsia
(RR = 0.52 [0.36; 0.75]).
Our scoring system has been criticized for its potential to encourage excessive prophylaxis.[22] Concerning this issue, we emphasize that comparison of the BEFORE and AFTER periods
is difficult, because some of the score items were retrospectively collected for the
BEFORE phase (the scoring system was voluntarily finalized after this phase so as
not to influence practices). However, even in our high-risk population, when the scoring
system was applied (AFTER phase), heparin was recommended in only 31.1% of women during
pregnancy and 23.7% during puerperium.
Regarding safety, no significant treatment-related complications were observed. Post-partum
haemorrhage occurred following 3.9% of deliveries, a result in accordance with the
literature.[1]
[23] Overall, only 15% of the women affected had received LMWH and the incidence of post-partum
haemorrhage did not differ significantly between the BEFORE and AFTER phases or between
women in whom LMWH prophylaxis had been started during puerperium and those having
received LMWH during pregnancy. Furthermore, LMWH prophylaxis was discontinued for
delivery and peri-dural analgesia, aspirin being discontinued at 35 weeks. This pattern
is concordant with the results of many studies indicating the safety of LMWH during
pregnancy/puerperium, with no major bleeds.[1]
[24]
[25] No treatment-related adverse neonatal outcomes were observed.
Implementation studies (also called quasi-experimental studies) must often be conducted
under conditions in which randomized designs are difficult or impossible to put into
practice and bias cannot be avoided. Our study was not randomized, and bias may have
affected the results. However, the apparent similarity between patients included in
the BEFORE and AFTER phases, respectively, suggests minimal selection bias. Maternity
unit characteristics were also similar in the two phases. Another potential limitation
of this study is that we could not assess the influence of any individual element
of our intervention, as this would have necessitated a larger study. Finally, it is
important to note that we were able to show the impact of this intervention on both
VTE and PVC prevention.
Conclusion
This prospective before-and-after intervention study in more than 2,000 women at risk
of VTE and/or PVC showed that the use of our risk scoring system to guide prophylaxis
is safe and effective in reducing the risk of thrombotic events during pregnancy.
Use of the STRATHEGE scoring system, developed by experts actively involved in the
prevention of VTE and PVC, may be recommended.
What is known about this topic?
-
Venous thromboembolism (VTE) prophylaxis during pregnancy should be individualized.
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No evidence-based easy-to-use tool has been available to guide decisions on VTE prophylaxis
for the wide range of pregnant women seen in everyday clinical practice.
What does this paper add?
-
The clinical benefit of the STRATHEGE risk score-guided prophylaxis remained to be
validated. Our before-and-after-intervention study prospectively validated this approach
in at-risk women.
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The incidence of adverse vascular events during pregnancy was significantly reduced
by 32%.
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Use of the STRATHEGE score to guide thromboprophylaxis may be particularly valuable
for non-specialists.
