Transcript Thrombophylaxia in Antiphospholipid Antibody Syndrome

Thrombophylaxia in Antiphospholipid
Antibody Syndrome
The antiphospholipid syndrome (APS) is an
acquired
autoimmune condition. The clinical features are
thrombosis
(venous, arterial and microvascular) and/or
pregnancy
complications and failure
• Diagnosis of Antiphospholipid Antibody
Syndrome (APS)
Classification Criteria for the Antiphospholipid
Antibody Syndrome
Criteria
-----------------------------------------------------------------Clinical
------------------------------------------------------------------Thrombosis(Unexplained venous, arterial, or small vessel
thrombosis in any organ or tissue)
---------------------------------------------------------------------Pregnancy (One or more unexplained fetal losses after 10
weeks; three or more consecutive miscarriages before 10
weeks; or preterm delivery for severe preeclampsia or
placental insufficiency before 34 completed weeks)
Classification Criteria for the
Antiphospholipid Antibody Syndrome
Laboratory
------------------------------------------------------------Anticardiolipin antibodies (IgG or IgM isotypes in medium to
high titers at least 6 weeks apart)
-------------------------------------------------------------Lupus anticoagulant (Identified twice, at least 6 weeks apart)
Diagnosis of Antiphospholipid Antibody
Syndrome (APS)
• one of two clinical criteria, which include
vascular thrombosis or certain pregnancy
morbidity, must be present. In addition, at
least two laboratory criteria that include LAC
activity or medium- to high-positive specific
IgG- or IgM-ACAs must be confirmed on two
occasions 6 weeks apart.
• Phospholipids are the main lipid constituents
of cell and organelle membranes. Several
antibodies directed against these various
phospholipids and to proteins bound to
phospholipids . These antibodies include lupus
anticoagulant (LAC) and anticardiolipin
antibodies (ACAs). They may be of IgG, IgM,
and IgA classes, alone or in combination.
Cardiolipin is but one of many phospholipids
and is found in mitochondrial membranes and
Pathophysiology
Many patients with lupus have circulating
antibodies specifically directed either against
phospholipids or against phospholipid-binding
proteins such as ß 2-glycoprotein I
(apolipoprotein H).
Anticardiolipin antibodies apparently bind
directly to ß 2-glycoprotein I, and this protein
acts as a co-factor in this antigen-antibody
reaction
ß
2-Glycoprotein
I
• The major activity of this protein appears to
be its phospholipid-dependent anticoagulant
inhibition of prothrombinase activity of
platelets and ADP-induced platelet
aggregation . ß2-Glycoprotein I competitively
inhibits the binding of coagulation factors,
especially factor XII, and the prothrombinase
complex to phospholipid surfaces. This
prevents activation of the coagulation
cascade.
ß
2-Glycoprotein
•
ß
2-Glycoprotein
I
I is found in high
concentrations on the surface of the
syncytiotrophoblast. This seems intuitive
because the decidua is a critical area in which
to prevent coagulation.
ß
2-Glycoprotein
I
• In addition, ß2-glycoprotein I may be involved
in implantation because it is known that this
protein binds heparin. Moreover,
trophoblastic cells have heparin-like binding
sites.
ß
2-Glycoprotein
I
• Thus, a local loss ofß 2-glycoprotein I by an
antibody directed against it might prevent
implantation or result in intervillous space
thrombosis, or both.
Lupus Anticoagulant
• LAC appears to require a cofactor for its in
vitro anticoagulant function. Specifically, it
does not bind directly to negatively charged
phospholipids, but instead, LAC binds to
phospholipid-bound prothrombin
• Other phospholipid-binding proteins may be
involved in the pathophysiology of the
antiphospholipid antibody syndrome.
• These include protein C and protein S, which
are both endogenous anticoagulants, and
annexin V . The last is also known as placental
anticoagulant protein I or lipocortin V, and
annexin V coats the syncytiotrophoblast in
high concentration
• Tests for the LAC are nonspecific coagulation tests.
The partial thromboplastin time is generally
prolonged because the anticoagulant interferes with
conversion of prothrombin to thrombin in vitro. Tests
considered most specific are the dilute Russell viper
venom test (dRVVT) and the platelet neutralization
procedure. There is currently disagreement as to
which of these is best for screening. If either is
positive after addition of normal plasma, the
diagnosis is confirmed
• In general, among aPL, the specificity for
thrombosis is higher for LA than aCL or antib2GPI and greater for higher than lower titre
aCL
• When reporting the results, the method, cutoff value, and an interpretation as LA-positive
or LA-negative should be given
• Which tests should be done?
• LA is the most predictive test for thrombosis
and the presence of IgG aCL or IgG anti-b2GPI
in those who are La positive increases the
specificity
• In patients with thrombosis, measuring IgM
antibodies
does not add useful information (2B).
• In patients with pregnancy morbidity, the role
of IgM
antibodies is unclear (2C).
• Testing for IgA antibodies is not recommended
(1B).
Pathophysiology of Antiphospholipid
Antibodies in Pregnancy
• The combination of lupus anticoagulant and
high levels of ACAs is strongly associated with
decidual vasculopathy, placental infarction,
fetal-growth restriction, early-onset
preeclampsia, and recurrent fetal death.
Recommendation
We recommend that primary
thromboprophylaxis
should not be used in those incidentally
found to have
aPL (2B)
Adverse Pregnancy Outcomes
• the incidence of antiphospholipid antibodies in the
general obstetrical population is about 5 percent
• Increased rates of fetal wastage
• Approximately a third of women with APS will
develop preeclampsia during pregnancy
• In women with a history of recurrent pregnancy loss,
those with antiphospholipid antibodies had a higher
rate of preterm delivery
• Which patients with obstetric complications
should be
tested for aPL and how should the result affect
management?
Recommendations
• Women with recurrent pregnancy loss (3 pregnancy
losses) before 10 weeks gestation should be screened for
aPL (1B).
• For women with APS with recurrent (3) pregnancy
loss, antenatal administration of heparin combined with
low dose aspirin is recommended throughout pregnancy
(1B). In general, treatment should begin as soon as
pregnancy is confirmed.
• For women with APS and a history of pre-eclampsia or
FGR, low dose aspirin is recommended.
• Women with aPL should be considered for post-partum
thromboprophylaxis (1B).
Treatment Guidelines
• Aspirin
• Heparin
- Heparin binds toß 2-glycoprotein I, which coats the
syncytiotrophoblast. This prevents binding of
anticardiolipin and antiß-2-glycoprotein I antibodies
to their surfaces, which likely prevents cellular
damage
- Heparin also binds to antiphospholipid antibodies in
vitro and likely in vivo
Treatment Guidelines
• Immunotherapy
-Glucocorticoids likely should not be used with
primary APS—that is, without an associated
connective-tissue disorder.
- In instances of secondary APS seen with lupus
the dose of prednisone should be maintained
at the lowest effective level to prevent flares
Treatment Guidelines
• Immunoglobulin therapy has usually been
reserved for women with overt disease,
heparin-induced thrombocytopenia, or both.
It is used when other first-line therapies have
failed, especially in the setting of preeclampsia
and fetal-growth restriction
• Immunosuppressive therapy has also not been
well evaluated, but azathioprine and
cyclosporine do not appear to improve
standard therapies
Low-Dose Aspirin Plus Heparin
• Current data suggest the most efficacious
therapy to be low-dose heparin—7500 to
10,000 units administered subcutaneously,
twice daily—given concurrently with low-dose
aspirin, 60 to 80 mg once daily (American
College of Obstetricians and Gynecologists,
2007b). If active lupus coexists, then
prednisone is usually also given
Thrombophylaxia in Antiphospholipid
Antibody Syndrome
• Only positive Antiphospholipid Antibodies : 6
weeks Postnatal
Thrombophylaxia in Antiphospholipid
Antibody Syndrome
•
•
•
•
Antiphospholipid syndrome (previous VTE) :
very high risk,
Antenatal : High Dose Prophylactic
Postnatal: 6 weeks
Antiphospholipid syndrome (Recurrent
Miscarriage, IUGR/Pre-eclampsia) :
Antenatal :Prophylactic + Aspirin ,
Postnatal: 6 weeks
‫وضعيت بالينی‬
‫ترومبوفيلي اكتسابي)‪:‬‬
‫سندرم آنتي فسفوليپيد آنتي بادي‬
‫يعني وجود حداقل يك معيار‬
‫آزمايشگاهي وحداقل يك معيار‬
‫بالينی‬
‫(ترومبوفیلي اكتسابي)‪:‬‬
‫فقط وجود معیار آزمایشگاهي آنتي‬
‫فسفولیپید آنتي بادي بدون‬
‫وجود معیار بالینی‬
‫اقدام هنگام بارداري‬
‫اقدام پس از زايمان تا ‪ 6‬هفته‬
‫تجویزا‪intermediate)LMWH‬‬
‫تجويز‬
‫‪36‬تا(‪UFH+aspirin‬يا‪ LMWH‬یا)‪(Prophylactic‬یا‪UFH‬‬
‫)‪weeks‬‬
‫انتاکونیست ویتامین‪ K‬ا‬
‫هشدار و مراقبت‬
‫و مراجعه به موقع‪ ،‬بررسي دقیق‬
‫آموزش به مادر در مورد ‪DVT‬‬
‫عالئم‬
‫توسط پزشك در هربار مراجعه‪،‬‬
‫‪DVT‬و ‪VTE‬در صورت نیاز‬
‫شروع داروي ضد انعقادی‬
‫تجویز)‪UFH(Prophylactic‬‬
‫‪LMWH(Prophylactic or‬‬
‫یك هفته پس از ‪intermediate‬‬
‫زایمان نكته‪ :‬در صورتي كه در طي‬
‫بارداري داروي ضد انعقاد دریافت‬
‫شده‪ ،‬تا ‪ 6‬هفته پس از زایمان ادامه‬