Factor V Leiden and Antiphospholipid Antibodies in Either
Mothers or Infants Increase the Risk for Perinatal Arterial
Ischemic Stroke
Michal J. Simchen, MD; Gal Goldstein, MD; Aaron Lubetsky, MD; Tzipi Strauss, MD;
Eyal Schiff, MD; Gili Kenet, MD
Downloaded from http://stroke.ahajournals.org/ by guest on June 15, 2017
Background and Purpose—The objective was to investigate the role of infant and maternal thrombophilia in a cohort of
mothers and infants presenting with perinatal arterial ischemic stroke.
Methods—Forty-seven infants with clinically and radiologically confirmed perinatal arterial ischemic stroke underwent
thrombophilia workup: factor V Leiden (FVL), PII20210A mutation, Methylene-tetrahydrofolate reductase 677T
polymorphism, protein C, protein S, antithrombin, FVIII, and antiphospholipid antibodies. Thrombophilia data were
available for 23 mother–infant pairs and compared with control populations to evaluate the risk for PAS.
Results—Thirty of 47 (64%) infants and 15 of 22 mothers (68%) had evidence of thrombophilia. In 18 of 23 (78%)
mother–infant pairs, there was at least 1 thrombophilic risk factor, but 15 pairs were mismatched in pathology. Among
infants, FVL, protein C deficiency, and presence of antiphospholipid antibodies prevailed (OR, 4.2; 95% CI, 1.5–11.3;
OR, 12.2; 95% CI, 2.5–59.9; OR, 4.1; 95% CI, 1.4 –12.2, respectively). Interestingly FVL prevailed in almost one-third
of mothers (OR, 8.5; 95% CI, 4.1–17.5) and 18% of mothers had antiphospholipid antibodies (OR, 3.8l; 95% CI,
1.5–10.0).
Conclusions—Maternal and neonatal thrombophilia, especially presence of FVL or antiphospholipid antibodies, may be
important in the pathogenesis of perinatal arterial ischemic stroke. The nature of thrombophilic mother–infant risk
potential interactions warrants further investigation. (Stroke. 2009;40:65-70.)
Key Words: antiphospholipid antibodies 䡲 FVL 䡲 perinatal ischemic stroke 䡲 thrombophilia
P
erinatal arterial ischemic stroke (PAS) is defined as a
focal (or multifocal) cerebral ischemic infarction, confirmed by radiographic or pathological assessment, attributable to an arterial event, and occurring between 28 weeks’
gestation and 28 days of postnatal age.1 Perinatal stroke
occurs in ⬇1 in every 4000 to 5000 live births,2,3 and in
settings with high frequency of neuroimaging may reach to 1
in 2300 live births.4,5 Most perinatal strokes involve the
middle cerebral artery. Cerebral arterial infarction in newborns either may present acutely during the neonatal period
with neurological symptoms such as seizures3,6 or may be
clinically asymptomatic until several months of age, when
signs of motor impairment or seizures are first noted, leading
to a delayed presumed diagnosis of PAS.6,7 PAS has received
increased attention as an important cause of cerebral palsy
and other neurological disabilities, including epilepsy and
cognitive impairment.8 –10
The pathophysiology of perinatal stroke is complex and
multifactorial. Risk factors may relate to both maternal and
placental problems, as well as fetal and neonatal disorders.
Maternal preeclampsia, chorioamnionitis, fetal cardiac anomalies, polycythemia, birth asphyxia, and systemic infection
are associated with PAS.8,11–13
The role of genetic and acquired thrombophilias in the
pathogenesis of PAS is quite controversial and not completely understood.14 –16 Maternal thrombophilias, both genetic and acquired, have been widely investigated in their
association with various pregnancy complications,17–21 but
their role in PAS is not clear.
Our aim in the present study was to investigate the role of
maternal and infant thrombophilia in a cohort of mother–
infant pairs in whom the infant has experienced a perinatal
ischemic stroke. This information may be important in
assessing predisposition to future potentially hazardous
thrombotic events.
Materials and Methods
Study Group
Pediatric patients with cerebral infarction diagnosed between April
1996 and October 2005 were entered into the Israeli Pediatric Stroke
Received May 29, 2008; accepted June 4, 2008.
From Department of Obstetrics and Gynecology (M.J.S., E.S.) and the Pediatric Coagulation Service (T.S., G.K., G.G.), National Hemophilia Center
and Institute of Thrombosis and Hemostasis (A.L., G.K.), Sheba Medical Center, Tel Hashomer, Israel, and Sackler Medical School, Tel-Aviv University, Israel.
Correspondence to Gili Kenet, MD, Director, Thrombosis Unit, National Hemophilia Center, Sheba Medical Center, Tel-Hashomer, Israel, 52621.
E-mail [email protected]
© 2008 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org
DOI: 10.1161/STROKEAHA.108.527283
65
66
Stroke
January 2009
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registry. This is an ongoing prospective registry of pediatric stroke
patients, consecutively referred for thrombophilia workup. Children
between the newborn period and 18 years of age were entered into
the registry if cerebral arterial infarction was documented clinically
and objectively (by CT or MRI) and if parental consent was
obtained. PAS was diagnosed by demonstrating either onset of
symptoms during the perinatal period or late motor impairment,
accompanied by vascular ischemic lesions in the middle cerebral
artery distribution that cause hemiplegia, affecting tissue in the
hemisphere, the posterior limb of the internal capsule, and the basal
ganglia.22,23
The definition of perinatal stroke was applied by experienced
neuroradiologists, referring to porencephalic lesions, periventricular
cysts, volume loss, and brain atrophy as signs of nonacute strokes.
Children with symptoms beyond the perinatal period without radiographic confirmation of nonacute presumed perinatal stroke were
excluded. Among 136 registry patients, whose mean age at the
occurrence of stroke was 5.9⫾5.2 years, 58 children had perinatal
stroke diagnosed. Follow-up and outcome data were obtained from
medical records and assessment during visits at ambulatory clinics.
Children with seizures, hemiparesis, or other neurological abnormalities requiring speech or motor therapy or prolonged neurodevelopmental follow-up were defined as neurologically impaired, whereas
children with no such abnormalities were considered neurologically
intact. Children in the study group were consecutively referred for
laboratory evaluation of thrombophilic risk factors. All thrombophilia testing was performed in the same tertiary referral center
laboratory, using standard assays. Maternal thrombophilia evaluation
was also recommended in all cases, but not all mothers complied
with this request.
Control Group
As the rates of thrombophilia vary significantly between different
populations, we used as comparison groups the rates of thrombophilia from a locally derived pediatric population including 145
healthy neonates and children referred for complete thrombophilia
workup before elective surgery.24 We also used a previously published cohort of 631 healthy nulliparous pregnant women tested for
thrombophilia at our center.17
Coagulation Tests for Analysis of Thrombophilia
Blood samples were obtained on the first referral visit. Blood
samples were collected into 3.8% (9:1 ratio) trisodium citrate
anticoagulant in a 9:1 ratio (blood:citrate). Citrated blood was
centrifuged within 30 minutes of blood sampling at 2000g (20 min),
and plasma aliquots were stored at ⫺35°C until analysis. Prothrombin, partial thromboplastin, and thrombin times, as well as fibrinogen
assays, were performed using standard techniques. Protein C and
antithrombin activities were measured by chromogenic assays (Baxter Dade). Free protein S antigen was measured by enzyme-linked
immunosorbent assay (Gradipore ELISA test kit; Riverside Corporate Park). For children tested, only repeatedly-low-for-age values
established the diagnosis of a coagulation inhibitor deficiency.
Circulating anticoagulant was determined using 2 coagulation-based
tests: a PTT Lupus Anticoagulant (PTT-LA) test (Diagnostica;
Stago) and the dilute Russell viper venom test time expressing the
ratio of assay times using a poor phospholipids-containing reagent
(LA screen; Gradipore) as compared with a rich phospholipidcontaining reagent (LA Confirm; Gradipore). Prolonged ratios (⬎1.5
or 1.7 for Circulating Anticoagulant (CAC)-Russell viper venom test
and CAC-PTT, respectively) were repeated for confirmation at least
12 weeks after the initial tests. Anticardiolipin antibodies were
measured using Autoenzyme Anticardiolipin (ACL) Kit (Cambridge
Life Sciences). ACL were considered positive if medium-to-high
titers (⬎20 GPL or MPL units [IgG phospholipids units or IgM
phospholipids units]) were present on ⱖ2 occasions at least 6 weeks
apart. 〉-2 glycoprotein-1 anticardiolipin antibodies were measured
using a standard kit (Asco Diagnostica). Borderline (15 to 20 U/mL)
or higher values were repeated at least twice to confirm the
diagnosis.
Factor 8:C (one stage clotting assay by Dade Behring) testing was
performed for mothers only and not for the children presenting with
PAS at least 3 months after delivery and repeated at least twice to
confirm activity levels ⬎160%.
Genomic DNA was extracted from EDTA-anticoagulated blood
samples using standard methods. Factor V Leiden (FVL) was
detected by polymerase chain reaction amplification of a 267-bp
fragment and MnlI digestion, as previously described.25 The C677T
polymorphism in the methylene-tetrahydrofolate reductase gene was
identified using the Hinfl cleavage of a 198-bp polymerase chain
reaction-amplified product.26 For identification of the G20210A
substitution in the factor II gene (FIIG20210A), a modification of the
method used by Poort et al27 was performed, as previously
described.28
Statistical Analysis
Frequencies and distribution of various thrombophilias were compared within the study group as well as to frequencies of genetic
thrombophilia in the population. The ␹2 tests and Fisher exact test
were performed as appropriate. A 2-tailed P⬍0.05 was considered
statistically significant.
Results
One-hundred thirty-six children fulfilling our inclusion criteria are registered to date in the Pediatric Stroke Registry. All
had evidence of ischemic stroke documented by computed
tomography or MRI before 18 years of age. Of these, 58
children had perinatal ischemic stroke diagnosed and all were
requested to undergo a complete thrombophilia workup.
All children (except for 1 child) had diagnoses during the
first year of life, with a mean age at diagnosis of 3.7⫾4.4
months. Of the 23 PAS patients, 13 presented with seizures
during the neonatal period, 9 had nonacute presumed perinatal stroke diagnosed because of late diagnosis of hemiparesis
or hemiplegia, and only 1 infant, who was examined for
increasing head circumference, had PAS diagnosed at age 2
years. This child has a brother with diagnosed PAS.
Thrombophilia workup results were available in 47 infants
and in 22 mothers. In 30 of 47 (64%) infants at least 1
hereditary or acquired thrombophilic risk factor could be
demonstrated. Twenty-five infants (53%) had genetic thrombophilia, whereas 11 (23%) had antiphospholipid antibodies
(APLA), either alone or in combination with genetic thrombophilia (Table 1).
Infant and Maternal Thrombophilia
To look at the contribution of maternal thrombophilia to the
risk for perinatal stroke, we examined mother–infant pairs for
whom a complete set of thrombophilia workup studies was
performed. Because only 22 mothers complied with our
request for testing, we studied 23 mother–infant pairs for
whom we had complete data sets (1 mother had 2 children
with PAS).
To look for potential selection bias in our analysis of this
subgroup of mother–infant pairs, we compared thrombophilia
risk factors between the group of infants for whom thrombophilia results were available for both infants and their mothers
(n⫽23) to those for whom no maternal information was
available (n⫽24). As can be seen in Table 1, the distribution
of thrombophilia risk factors was very similar, indicating lack
of any undesired selection.
Simchen et al
Maternal and Neonatal Thrombophilia in Perinatal Stroke
67
Table 1. Thrombophilic Risk Factors Among 47 Infants With Perinatal Stroke and Comparison Between
Infants With Perinatal Stroke With and Without Available Maternal Information
All Infants With
Perinatal Stroke,
N⫽47 (%)
Infants With
Maternal Information,
N⫽23 (%)
Infants With
No Maternal Information,
N⫽24 (%)
*P
At least 1 thrombophilic risk factor
30 (63.8)
14 (60.9)
16 (66.7)
0.67
Genetic thrombophilia (at least 1)
25 (53.2)
12 (52.2)
13 (54.2)
0.9
Decreased protein C activity
9 (19.2)
5 (21.7)
4 (16.7)
0.66
Decreased free protein S
6 (12.8)
2 (8.7)
4 (16.7)
0.43
0.43
10 (21.3)
6 (26.1)
4 (16.7)
FIIG20210A mutation
FVL mutation
3 (6.4)
2 (8.7)
1 (4.2)
0.55
MTHFR C677T
9 (19.2)
5 (21.7)
4 (16.7)
0.66
Acquired (APLA)
11 (23.4)
6 (26.1)
5 (20.8)
0.68
4 (13)
3 (12.5)
0.62
Combined genetic and acquired thrombophilia
7 (14.9)
*Comparison of thrombophilia distribution between infants with and without available maternal information.
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Of the mother–infant pairs, 14 (61%) infants had at least 1
genetic or acquired thrombophilic risk factor, of whom 12
infants had genetic thrombophilia markers. Four infants had
⬎2 genetic risk factors. Six infants had APLA, of whom 3
were also found to have genetic thrombophilia.
Fifteen of 22 (68%) mothers were positive for thrombophilia markers. Fourteen mothers had genetic thrombophilic
risk factors, whereas 4 mothers had APLA. Three mothers
had combined genetic thrombophilia risk factors, and 3 had
combined genetic and APLA. Six mothers had previous
thromboembolic episodes: 3 had previous strokes, 1 had a
transient ischemic attack during pregnancy, and 2 others had
previous episodes of deep vein thrombosis. One mother had 2
children with PAS and a previous pregnancy that ended in
stillbirth.
In 18 of 23 mother–infant pairs (78%), at least 1 thrombophilic risk factor could be identified for either mother or
infant (Table 2). Of the 18 thrombophilic pairs, matching
thrombophilia markers were found in 3 pairs, whereas a
partial match (in which either mother or infant had an
additional thrombophilia marker) were found in 7 additional
pairs. Eight mother–infant pairs had a complete mismatch in
thrombophilia markers. More than half of the cases of
nonsimilar thrombophilia patterns (8 of 15 cases) were
characterized by the presence of APLA in either mother or
infant. Five mother–infant pairs had no evidence of maternal
or infant thrombophilia.
Table 2.
Table 3 presents the distribution and relative frequencies of
thrombophilic risk factors in mothers and infants compared
with our control populations. In children with PAS, the
presence of FVL mutation, protein C deficiency, or APLA
exerted a significant risk for stroke as compared to our
controls. Interestingly, mothers carrying the FVL mutation or
APLA also increased the risk for PAS in their children. The
relative risk of mothers with FVL mutation was 8.5-times
(95% CI, 4.1–17.5) higher and the risk of APLA was
3.8-times (95% CI, 1.5–10.0) higher as compared to that of
control mothers (Table 3).
To test whether presence of thrombophilia had an impact
on the neurological outcome, we compared children with
residual neurological deficit to children who were neurologically intact after their stroke. Fifteen children had residual
neurological deficit; 10 of the 15 were carriers of thrombophilia (67%) compared to 4 of 9 (44%) children without
residual neurological damage. This trend was not statistically
significant (P⫽0.285).
Discussion
The role of genetic and acquired thrombophilias in the
pathogenesis of PAS is quite controversial and not completely understood. FVL mutation, the prothrombin mutation
(FIIG20210A), hyperhomocystinemia, and elevated Lp(a)
have all been described with increased frequency in infants
with PAS when compared with healthy control sub-
Relative Risks of Thrombophilia in Infants With Perinatal Stroke and Their Mothers Compared With Controls
Infants,
n⫽23
Prevalence
in Controls
Relative Risk
(95% CI)
Mothers,
n⫽22
Prevalence
in Controls
Relative Risk
(95% CI)
677T MTHFR homozygote
21.7% (5)
15.1%
1.4 (0.6; 3.5)
13.6% (3)
12.7%
1.1 (0.4; 3.1)
FVL-Het
26.1% (6)
6.25%
4.2 (1.5; 11.3)
31.8% (7)
3.8%
8.5 (4.1; 17.5)
8.7% (2)
3.6%
2.4 (0.5; 12.5)
9% (2)
4.2%
2.1 (0.5; 7.5)
21.7% (5)
1.8%
12.2 (2.5; 59.9)
0% (0)
NA
NA
8.7% (2)
0%
13.6% (3)
NA
NA
Risk Factor
FIIG20210A-Het
Protein C deficiency
Free protein S deficiency
Antithrombin deficiency
APLA
0% (0)
0%
21.7% (5)
5.4%
NA
NA
4.1 (1.4; 12.2)
0% (0)
18.2% (4)
NA
NA
4.7%
3.9 (1.5;10.0)
Relative risks are presented for infants vs controls (derived from Kenet et al24) and for mothers vs controls (derived from Salomon et al17), separately.
Het indicates heterozygous; NA, not available.
68
Stroke
Table 3.
January 2009
Patterns of Thrombophilic Risk Factors for Mother–Infant Pairs
Case
Infant
Mother
Mother–Infant Mismatch
Mat. Hx. Thrombosis
No
Thrombophilic risk factors: Infant negative,
mother positive
1
Normal
FVL*
Yes
2
Normal
PS,* factor VIII*
Yes
No
3
Normal
PS,* APLA*
Yes
No
4*
Normal
Factor VIII*
Yes
IUFD
5
MTHFR*
Normal
Yes
CVA @ 18 years
6
PC*
Normal
Yes
No
Thrombophilic risk factors: Infant positive,
mother negative
Thrombophilic risk factors: Infant positive,
mother positive, no match
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7
FVL, PT, PC,* PS,* APLA*
FVL, PT
Yes
No
8
PT, MTHFR, PC*
PT, MTHFR
Yes
No
9
MTHFR, PC,* APLA*
MTHFR
Yes
No
10
APLA
PS,* APLA
Yes
No
11
FVL
FVL, APLA*
Yes
No
12
FVL, APLA*
FVL
Yes
No
Yes
TIA in pregnancy
13
MTHFR*
APLA*
14†
APLA*
Factor VIII*
IUFD
15
FVL, PC,* PS*
FVL
CVA⫻2
16
FVL
FVL
No
No
17
FVL
FVL
No
No
18
MTHFR
MTHFR
No
No
Thrombophilic risk factors: Infant positive,
mother positive, match
19
Normal
Normal
No
DVT⫻2
20
Normal
Normal
No
DVT at 15 yr
21
Normal
Normal
No
No
22
Normal
Normal
No
No
23
Normal
Normal
No
No
*Mismatched pathologies.
†These 2 children are brothers.
APLA indicates antiphospholipid antibodies (anticardiolipin Ab IgG and IgM, lupus anticoagulant dilute Russell viper venom test, B2glycoprotein 1
IgG and IgM); CVA, cerebrovascular accident; DVT, deep vein thrombosis; IUFD, intrauterine fetal demise; MTHFR, 677T methyltetrahydropholate
reductase, only homozygotes were considered positive; PT, prothrombin mutation G20210A heterozygote; PC, Protein C deficiency; PS, Protein S
deficiency; Mat. Hx., maternal history.
jects.14,15,29 –32 In contrast, a recent cohort study found no
difference in the incidence of genetic polymorphisms between newborns with stroke and a random newborn control
sample.16 Although the role of infant thrombophilia in the
pathogenesis of PAS is still undergoing investigation, the role
of maternal thrombophilia in the pathogenesis of PAS has not
been studied extensively to date.
In our cohort of well-defined PAS cases, we found a high
rate of thrombophilia in both mothers and infants. Among
infants with PAS, we found at least 1 thrombophilic marker in
64% (30/47), and among mothers 68% (15/22) were found to
be thrombophilia carriers. These high rates of thrombophilia
are in concordance with a recently published study of 60
mother–infant pairs in whom the rates of thrombophilia
were 55% and 50% in mothers and infants with PAS,
respectively.33
Among our infants FVL, protein C deficiency, and presence of APLA prevailed as significant risk factors for PAS.
Twenty-six percent of our PAS infants were carriers of FVL
as compared to only 6.25% of controls. This prevalence of
FVL is much higher than the 5% rate reported in the recent
mother– child study by Curry et al,33 but quite similar to a
previously published Israeli case-controlled study in which
FVL and APLA prevailed among pediatric patients with
stroke34 and the rate of FVL carriership was 17.2%. FVL was
also recently reported as increasing the risk of arterial
ischemic stroke occurrence in children of Mediterranean
origin,35,36 in whom the rate of FVL carriership among
Simchen et al
Maternal and Neonatal Thrombophilia in Perinatal Stroke
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patients was 16.7% to 23.3%.35,36 Despite the fact that FVL
was definitely a significant risk factor for pediatric and
perinatal stroke in our study as well as in other Mediterranean
population studies, its role in the pathogenesis of arterial
thrombosis in the young remains to be elucidated.37
The contribution of APLA to the multifactorial nature of
PAS is not yet well-defined. In our study, 8 mother–infant
pairs had evidence of APLA, in either mother or child. More
than one-fifth of our PAS infants tested positive for APLA,
compared to 5.4% in controls. Again, this result is in
agreement with the Israeli study of pediatric stroke patients in
which 15.5% of patients were APLA-positive. These data
were not available in the study by Curry et al.33
Protein C deficiency was more prevalent in PAS infants
compared with controls (21.7% vs 1.8%, respectively), significantly increasing the risk for PAS. This was not observed
in our previous pediatric stroke study in which protein C
deficiency was found in 6.9% of older children with stroke.
We had no data on protein C prevalence in the mothers
control group; therefore, risk could not be estimated.
In our study 15 of 23 (65%) infants had some form of
neurological impairment during follow-up. This high rate of
neurological impairment is common. In other studies cerebral
palsy developed in 68% of children with PAS,9 epilepsy was
common among PAS patients presenting with seizures,10 and
some neurological sequelae were documented in 38% to 58%
of mother– child pairs study.33 We found no significant
association between neurological outcome and thrombophilia, although infants with impaired neurological outcomes
tended to test positive for thrombophilia more often when
compared to the unimpaired infants (67% vs 44%,
respectively).
Thrombophilia was documented in more than two-thirds of
the mothers who underwent thrombophilia screening. We
found that maternal carriership of FVL or presence of APLA
significantly increased the risk of PAS in their offspring. In
our study 31.8% of mothers were heterozygous carriers of the
FVL mutation compared with only 3.8% in a large cohort of
nulliparous pregnant women17 and with 8.2% of the mothers
in the study by Curry et al.33 We also found that infants of
mothers carrying APLA had an increased risk for stroke.
APLA was found in 18.2% of mothers compared with 4.7%
of control mothers. A potential association of maternal APLA
with fetal thrombophilias leading to an increased risk of PAS
has already been raised by Nelson et al;1 however, studies of
the outcome of infants born to mothers with APLA syndrome
and of studies of children with primary APLA syndrome
revealed very rare cases of perinatal stroke.38,39 The presence
of APLA in neonates with PAS may therefore represent an
acquired comorbid trigger, increasing the risk for stroke,
especially when other thrombophilic risk factors coexist.40 To
our knowledge our study is the first to report such significant
associations.
The importance of demonstrating the presence of thrombophilia in cases of PAS extends further beyond the index
pregnancy, because children with thrombophilia as well as
their mothers, apart from carrying an increased risk for PAS,
may be predisposed to higher risks of thrombosis or further
pregnancy complications throughout their lives.
69
There are several possible therapeutic implications of
thrombophilia testing are several, including the need for
anticoagulation required after initial diagnosis, the length of
anticoagulation, and potential prophylaxis required in subsequent life events such as surgery or prolonged immobilization. Moreover, for mothers who tested positive for thrombophilia, special additional therapeutic considerations include
management during subsequent pregnancies or hormonal
treatments (ie, oral contraceptives).
Our study has several limitations. We did not have complete thrombophilia information on all of our patients. Among
47 PAS patients in our registry for whom we have thrombophilia results, we had information on only 22 mothers.
Nevertheless, we found no difference in the distribution of
thrombophilia risk factors between PAS patients for whom
maternal thrombophilia was available and those for whom it
was not; therefore, we believe our results are valid to the
group as a whole. Furthermore, selection of severe cases can
be ruled out because the neurological outcome of the 23
infants tested is not different from that of previously published reports.
Another limitation of our study is the relatively small
number of cases. This could potentially limit our ability to
accurately estimate the magnitude of risk factors for PAS.
Effort is currently being made to enlarge the group to
strengthen our conclusions.
We have not evaluated the potential role of paternal
thrombophilic on PAS risk. We found several cases of
mismatch in mother and infant thrombophilias in our cohort.
The presence of other genetic thrombophilic factors in the
infant implies a possible contribution of paternal thrombophilia to perinatal ischemic thrombosis. A similar finding was
reported in by Curry et al.33 Therefore, it would be prudent to
investigate both parents for possible prothrombotic tendencies as part of the workup in cases of neonatal thrombosis.
In summary, we found that both maternal and infant
thrombophilia may contribute to the higher prevalence of
PAS. Both FVL and APLA have been identified as potential
risk factors for PAS in the Israeli population of infants and
mothers studied, as compared with controls.
We believe that thrombophilia testing should be performed
on any child with PAS and that both parents should be tested
as well. Positive tests may eventually lead to therapy-related
considerations to reduce the risk of PAS in future pregnancies
of FVL carriers. Large prospective studies of perinatal stroke
are currently lacking and, according to our results, we believe
this issue deserves further attention.
Disclosures
None.
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Factor V Leiden and Antiphospholipid Antibodies in Either Mothers or Infants Increase
the Risk for Perinatal Arterial Ischemic Stroke
Michal J. Simchen, Gal Goldstein, Aaron Lubetsky, Tzipi Strauss, Eyal Schiff and Gili Kenet
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Stroke. 2009;40:65-70; originally published online October 16, 2008;
doi: 10.1161/STROKEAHA.108.527283
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