Antiphospholipid syndrome of Lupus patient

2. definition
 Antiphospholipid syndrome or antiphospholipid
antibody syndrome (APS or APLS or) is
an autoimmune,hypercoagulable state caused
by antibodies against cell-membrane phospholipids that
provokes blood clots (thrombosis) in
both arteries and veins as well as pregnancy-related
complications such as miscarriage, stillbirth, preterm
delivery, or severe preeclampsia.
 The syndrome occurs due to the autoimmune production
of antibodies against phospholipid (aPL) of the cell
membranes.
 In particular, the disease is characterised by antibodies
against cardiolipin(anti-cardiolipin antibodies)
and β2 glycoprotein I

3. Clinical types
 . The term "primary antiphospholipid syndrome" is used
when APS occurs in the absence of any other related
disease.
 APS however also occurs in the context of other
autoimmune diseases, such as systemic lupus
erythematosus (SLE), in which case the term "secondary
antiphospholipid syndrome" is used.
 In rare cases, APS leads to rapid organ failure due to
generalised thrombosis; this is termed "catastrophic
antiphospholipid syndrome" (CAPS) and is associated
with a high risk of death.

4. presentations
 APS presents in two major
ways:
1-thrombosis (venous or
arterial)
2-pregnancy loss.
 Thrombocytopenia, present
in about 20% of cases, canbe
an important clue.

5. EPIDEMIOLOGY
 Race
No defined racial predominance for primary APS has been documented,
although SLE is more common in African American and Hispanic
populations.
Sex
A female predominance has been documented, particularly for secondary
APS. This parallels the association of APS with SLE and other connective-
tissue diseases,
 Age
APS is more common in young to middle-aged adults; however, it also
manifests in children and elderly people. .[5]

6. EPIDEMIOLOGY
 In patients presenting with a deep venous thrombosis, up to 30%
will have the APS.
 In a person under age 50 with a stroke, up to 46% will have APS.
 About 8% of primary APS patients later develop SLE
 In SLE patients, about 30% have anticardiolipin and about 25% have
the lupus anticoagulant.
 The risk of venous thrombosis in a SLE patient with the lupus
anticoagulant is 50% by 20 years after diagnosis.

7. PATHOGENESIS
 The pathogenesis of APS is complex and
multifactorial, reflecting the fact that aPL bind to
plasma proteins and to endothelial cells involved in
multiple steps in coagulation.
 APL interfere with the activated protein C complex
and also bind to platelets.
 They bind to endothelial cells, leading to upregulation
of cytokines and tissue factor.

8. Clinical features
 Antiphospholipid syndrome (APS) is a heterogenous disorder in
terms of clinical manifestations and range of autoantibodies.
major clinical features may present:
 1-Vascular thrombosis
 One or more clinical episodes of arterial, venous, or small-vessel
thrombosis .
 Thrombosis may involve the cerebral vascular system, coronary
arteries, pulmonary system (emboli or thromboses), arterial or
venous system in the extremities, hepatic veins, renal veins, ocular
arteries or veins, or adrenal glands.
 2-Pregnancy morbidity
 One or more late-term (>10 weeks' gestation) spontaneous abortions
 Three or more unexplained, consecutive, spontaneous abortions
before 10 weeks’ gestation

9. Clinical features
History of any of the following should raise the
examiner's suspicion for APS:
1-Thrombosis (eg, DVT/PE, MI, transient ischemic attack [TIA], or CVA,
especially if recurrent, at an earlier age, or in the absence of other known
risk factors).
2-Miscarriage (especially late trimester or recurrent) or premature birth
3-History of heart murmur or cardiac valvular vegetations
4-History of hematologic abnormalities, such as thrombocytopenia or
hemolytic anemia
5-History of nephropathy
6-Nonthrombotic neurologic symptoms, such as migraine headaches,
chorea, seizures, transverse myelitis, Guillain-Barré syndrome, or dementia
(rare)
7-Unexplained adrenal insufficiency
8-Avascular necrosis of bone in the absence of other risk factors
9-Pulmonary hypertension

10. CLINICAL FEATURES
 livedo reticularis, a purplish
lacelike reticular
pattern,especially apparent
on the extremities.

11. Clinical features
 Catastrophic APS :
is a rare presentation with multiorgan thrombi .
Precipitants of catastrophic APS include infection,
surgery, pregnancy,exogenous estrogen, and
cessation of anticoagulation.
N.B:
 In the evaluation of APS, it is necessary to exclude
genetic and acquired causes of hypercoagulability
 Thrombosis can occur even in the presence of
thrombocytopenia

12. LABORATORY FEATURES
1-Lupus Anticoagulant
only 50% of patients with LA
have lupus.
To confirm the presence of an
LA, these criteria are required:

13. Lab features: lA
2. A sensitive activated partial thromboplastin time
(aPTT) is recommended for screening.
Prolongation of the clotting time must
be due to
an inhibitor (rather than a factor
deficiency). This is confirmed by demonstrating
that the prolonged clotting time does not correct
with a 1 : 1 or 4 : 1 mix with normal plasma.

14. Lab features
3-Anticardiolipin
Anticardiolipin (aCL) is actually an antibody directed
against negatively charged phospholipids bound to beta
2 glycoprotein I. Only medium-to-high titers of the IgG
or IgM isotype are accepted for the classification
criteria.
4-Anti–Beta 2 Glycoprotein I
Thus, anti-beta 2 GPI is rarely necessary to make the
diagnosis/classifi cation of APS.

15. Diagnostic CRITERIA FOR ANTIPHOSPHOLIPID
SYNDROME (sydney revision)
 One clinical criterion
 1-Thrombosis
Arterial Or Venous or Vasculopathy
2-pregnancy morbidity
a- 3 or more first trimester losses
b- or 1 or more late fetal losses
c- Or Severely preterm birth due to placental insufficiency
PLUS
One laboratory criterion: persistent over 3 months
 Lupus anticoagulant (present twice over 3 month) OR
 Moderate/high titer IgG or IgM anticardiolipin OR
 Moderate/high titer IgG or IgM anti–beta 2 glycoprotein I
SOURCE: From Miyakis S, et al. J Thromb Haemost 2006;4:295–306, by
permission of Journal of Thrombosis and Haemostasis.

16. complications
 Antiphospholipid syndrome (APS) complications
happen to only a minority of patients with aPL. Several
features are thought to increase the risk of thrombosis:
1-including the lupus anticoagulant (over aCL)
2- high titers of Acl
3- persistence of aPLs for longer than 6 months,
4-comorbid factors including estrogen, thalidomide,
nephrotic syndrome, bed rest, surgery, pregnancy,
and the postpartum period

17. treatment
 Asymptomatic Antiphospholipid Antibodies
Patients with aPL but no history of thrombosis or pregnancy
loss
1- should avoid medications that might contribute to
hypercoagulability, including oral contraceptives and hormone
therapy
2-. Other risk factors for hypercoagulability should be
minimized.
3- Low dose aspirin can be considered as a prophylactic
therapy, but efficacy has not been proven in clinical trials.
4- hydroxychloroquine can be considered as a possible
prophylactic intervention in SLE patients.

18. treatment
 Pregnancy Loss
For it ‘s prevention prophylactic doses of unfractionated or low-
molecularweight heparin plus low dose aspirin (81 mg)
This regimen causes less maternal and pregnancy morbidity than
the older regimens of prednisone and aspirin.
Unfortunately, the heparin and aspirin regimen is successful in
only 75% of pregnancies.
If unsuccessful, there is some scientific rationale to
the addition of intravenous immunoglobulin in the next
pregnancy.

19. Treatment
Thrombosis :
 The treatment of an acute thrombotic
event (thrombolysis and/or
heparin) .
 Because of the high risk of recurrence
of thrombosis in APS, a strong case
can be made for life-long
anticoagulation after a first
thrombotic event.
 If anticoagulation is stopped after 6
months,there is a recurrence rate of
20% or more .

20. Treatment
 The APS patient with thrombosis and thrombocytopenia
is of special concern.
 Thrombocytopenia does not protect the APS patient from
thrombosis.
 Most thrombocytopenia in APS is mild, in the range of 90 to
140,000.
 Profound thrombocytopenia, however, would greatly
increase the risk of bleeding with anticoagulation.
 The platelet count should be stable at above 50,000 before
chronic anticoagulation is begun, and the INR goal
would be 2.0 in such a patient.

21. Catastrophic Antiphospholipid
Syndrome
treatement is by heparin, plasmapheresis or intravenous
immunoglobulin, and high dose methylprednisolone
(the latter likely calms the cytokine storm produced
by the intense endothelial cell activation) .
Cyclophosphamide is not recommended as initial therapy
because of the increased risk of infection.
Mortality of catastrophic APS, even with intensive t
reatment in major academic centers, remains 50%.
Mortality RATE

22. Treatments under trials
 Statins have benefit for APS in animal models and
reduce thrombosis in clinical studies of non-APS
patients. However, they cannot be used in pregnancy
and have not been studied formally in APS.
 Rituximab depletes B cells, including B cells that
make aPL. However, the period of B-cell depletion is
variable, and long-lived plasma cells make aPL
survive.
Further studies are needed before it can be
recommended for APS.

24. LUPUS AND MATERNAL OUTCOME
 Coexistence of other medical or obstetrical disorders.
 Whether there are an APA.
 About 40% experience flares, relatively mild in the form of
artheralgia and rash.

25. PREGNANCY OUTCOME IS BETTER IF
 Lupus activity has been quiescent for at least 6
months before conception
 There is no active renal involvement manifest by
Proteinuria or renal dysfunction.
 Superimposed preeclampsia does not develop.
 There is no evidence of APA activity.

26. CONDITIONS THAT SHOULD NOT BE PREGNANT
 Active Lupus
 Nephritis, nephrotic syndrome (esp. Cr >2)
 Other organ damages (e.g. cardio-pulmonary
involvement, anemia, thrombocytopenia, CNS
involvement, thrombosis)
 Still take high dose steroid and immunosuppressive
drugs

27. PREGNANCY COMPLICATIONS WITH SLE
1. Preeclampsia
2. Fetal Loss
3. Preterm Delivery
4. Low Birth Weight Infant (Glucocorticoids
causes growth restriction)
5. Venous Thromboembolic Disease

28. PREPARING FOR PREGNANCY WITH SLE
 Discuss desire to have child with Rheumatologist,
Obstetrician
 Women with Lupus nephritis are encouraged to delay
pregnancy until their disease is inactive for at least 6
months

29. MEDICATIONS DURING PREGNANCY
 Drugs to avoid (Immunosuppressant therapy)
 Mycophenolate mofetil
 Cyclophosphamide
 Methotrexate
 Biologic medications
 Etanerecpt, infliximab, anakinra
 Until more data is available, these meds should be avoided
 Drugs with small risk of harm
 Aspirin
 Prednisone/Glucocorticoids
 Azathioprine
 NSAIDs
 Drugs that are probably safe
 Antimalarials (hydroxychloroquine)
No evidence that antimalarials increases risk of miscarriages
or birth defects at normal doses

30. MANAGEMENT DURING PREGNANCY
 Assessment of severity using SLE-pregnancy disease
activity index (SLEPDAI).
 Serial hematological studies may detect changes in
disease activity, hemolysis, anemia, reticulocytosis,
thrombocytopenia, leucopenia.

32. MANAGEMENT DURING PREGNANCY
 Serum transaminase activity reflects hepatic
involvement, as does arise in serum bilirubin.
 Thrombocytopenia and Proteinuria resemble Lupus
disease activity
 The fetus should be closely observed for adverse effects.
 Screening for anti SS-A and anti SS-B antibodies, and is
found, fetal cardiac function should be evaluated.

33. RECOMMENDATIONS
 Delivery: will need stress dose steroid during active labor
 Breastfeeding: recommended even for women with SLE
 Birth control: OCP can be used but should be avoided

34. PHARMACOLOGICAL TREATMENT
 follow-up frequency is dependent on disease activity
 hydroxychloroquine is given to prevent flares
 Low dose aspirin is administered to prevent
preeclampsia
 If APLS positive or history of thrombosis or fetal
loss, treatment with heparin or LMWH and aspirin
100 mg per day.

35. PHARMACOLOGICAL TREATMENT
 Severe disease is managed with corticosteroid, such as
Prednisolone 1 to 2 mg/kg per day. or Chloroquine (250
mg/day)
 After the disease is controlled, this is tapered to a daily
dose of 10 to 15 mg each morning.
 Corticosteroid therapy can result in the development
Gestational or even Type 1 Diabetes.

36. CORTICOSTEROID
 In patient with positive anti SSA/Ro or anti SSB
antibodies no treatment was administered unless there
were intrauterine cardiac complication, in which case
Dexamethasone (4 mg/day) was given.

37. Neonatal Lupus syndrome
 generalized photosensitive rash
 thrombocytopenia and anemia
 giant cell hepatitis with severe cholestasis
 isolated complete heart block or cardiomyopathy
 Neonatal Lupus may appear up to 4 weeks after birth.

38. CONGENITAL HEART BLOCK
 The consequence of diffuse myocarditis and fibrosis in the
region between the Atrioventricular node and Bundle of
His
 CHB occurred almost exclusively in infants of women with
antibodies to the SSA/Ro or SSB/La antigen causes
unexplained stillbirth, arrhythmia is only 3%.
 The cardiac lesion is permanent, and pacemaker is
generally necessary.
 Long term prognosis is not good, and 1/3 of affected infants
die within 3 years.

39. THANK YOU!!!