2. Objectives
• Identify the clinical criteria required to make a
diagnosis of antiphospholipid syndrome.
• Review the workup of a patient with
antiphospholipid syndrome.
• Summarize the treatment and management
options available for antiphospholipid
syndrome.
3. Case 1
• 22 years old female patient from Hosh Issa,
single presented with spontaneous
ecchymosis, no bleeding from any other site
• Past medical history : free
• Menstrual history : no menorrhagia
4. • CBC:
HB: 11.5 normocytic hypochromic
PLT: 98
WBC: 6 with normal differential
PT, PTT: normal
5. • ANA , Anti ds DNA :negative
• Lupus anticoagulant :positive
• Anticardiolipin anticoagulant : positive
• ------ started treatment and lost follow up
• 7 months later : she got married, pregnant
then abortion (12weeks)
6. Case 2
• 38 years old female patient married with no
children from Hosh Issa presented with
generalized fatigue, bone pains, malar rash,
hair fall
• Past history: irrelevant
• Menstrual history: 3 abortions
8. Introduction
• Antiphospholipid syndrome (APS) is a
multisystemic autoimmune disorder.
• The hallmark of APS comprises the presence
of persistent antiphospholipid antibodies in
the setting of arterial and venous thrombus
and/or pregnancy loss.
9. • The most common sites of venous and arterial
thrombosis are the lower limbs and the
cerebral arterial circulation, respectively.
However, thrombosis can occur in any organ.
10. • The three known antibodies are:
• Anticardiolipin antibodies IgG or IgM
• Anti-beta-2-glycoprotein-I antibodies IgG or
IgM
• Lupus anticoagulants
11. Etiology
• Primary when there is no evidence of
autoimmune disease,
• Secondary to
1- Autoimmune processes like systemic lupus
erythematosus (SLE) in 40% of the cases
2- Infections such as borrelia burgdorferi,
treponema, HIV, leptospira and recently COVID19
3- Many drugs, including chlorpromazine,
procainamide, quinidine, and phenytoin.
• Low levels of APLA may also be normally present.
12. History and Physical
• Vascular Thrombosis
• APLS can cause arterial and/or venous thrombosis involving
any organ system.
• can be recurrent
• involve vessels unusual for other-cause-thrombosis (such as
upper extremity thrombosis, Budd-Chiari syndrome, and
sagittal sinus thrombosis).
• Venous thrombosis involving the deep veins of lower
extremities is the most common venous involvement and
may lead to pulmonary embolism resulting in pulmonary
hypertension.
• Any other site may be involved in venous thrombosis,
including pelvic, renal, mesenteric, hepatic, portal, axillary,
ocular, sagittal, and inferior vena cava.
13. • Arterial thrombosis may involve any sized arteries
(aorta to small capillaries).
• The most common arterial manifestation of APLS is
transient ischemic events (TIAs) or ischemic stroke,
• the occurrence of TIA or ischemic stroke in young
patients without other risk factors for atherosclerosis
shall raise suspicion for APLS.
• Other sites for arterial thrombosis may include retinal,
brachial, coronary, mesenteric, and peripheral arteries.
• The occurrence of arterial thrombosis carries a poor
prognostic value, given the high risk of recurrence in
these cases.
14. • Pregnancy Morbidity
• Pregnancy loss in patients with APLS is common,
especially in the second or third trimester.
• Besides pregnancy losses, other pregnancy-
related complications in APLS include pre-
eclampsia, fetal distress, premature birth,
intrauterine growth retardation, placental
insufficiency, abruptio placentae,
and HELLP syndrome (Hemolysis, Elevated Liver
enzymes, Low Platelet count)
15. • One or more unexplained fetal deaths of
morphologically normal fetus (normal fetal
morphology confirmed by ultrasound or direct
examination) at or beyond 10 weeks of gestation.
• One or more premature births of morphologically
normal neonate before the 34th week of gestation.
Prematurity must be secondary to eclampsia, severe
preeclampsia, or placental insufficiency.
• Three or more consecutive spontaneous abortions
before the 10th week of gestation after ruling out any
anatomic or hormonal abnormalities in the mother and
parental chromosomal causes.
16. • Cutaneous Involvement
• Several cutaneous manifestations have been reported,
although all are non-specific for APLS. Livedo reticularis
is the most common cutaneous manifestation seen in
APLS.
• Skin ulcerations, especially in lower extremities ranging
from small ulcers to large ulcers resembling pyoderma
gangrenosum, have been reported in APLS.
• Other cutaneous manifestations include nail-fold
infarcts, digital gangrene, superficial thrombophlebitis,
and necrotizing purpura.
17. • Valvular Involvement
• Cardiac valve involvement is very common in APLS. Mitral and
aortic valves are most commonly involved with thickening, nodules,
and vegetations evident on echocardiography. This may lead to
regurgitation and/or stenosis.
• Hematological Involvement
• Thrombocytopenia has been seen in more than 15% of APLS
cases. Severe thrombocytopenia leading to hemorrhage is rare.
Positive Coomb test is frequently seen in APLS, although hemolytic
anemia is rare.
• Neurological Involvement
• The most common neurological complication of APLS includes TIAs
and ischemic stroke, which may be recurrent, leading to cognitive
dysfunction, seizures, and multi-infarct dementia. Blindness
secondary to the retinal artery or vein occlusion can occur. Sudden
deafness secondary to sensorineural hearing loss has been
reported.
18. • Pulmonary Involvement
• Pulmonary artery thromboembolism from deep vein
thrombosis is common and may lead to pulmonary
hypertension. Diffuse pulmonary hemorrhage resulting
from pulmonary capillaritis has been reported.
• Renal Involvement
• Hypertension, proteinuria, and renal failure secondary to
thrombotic microangiopathy is the classic renal
manifestation of APLS, although this is not specific to APLS.
Other renal manifestations reported include renal artery
thrombosis leading to refractory hypertension, fibrous
intimal hyperplasia with organized thrombi with or without
recanalization, and focal cortical atrophy
19.
20. Catastrophic Anti-Phospholipid
Syndrome (CAPS)
• CAPS is a rare but life-threatening complication of
APLS, with less than 1% of patients with APLS
developing CAPS. Mortality is very high (48%),
especially in patients with SLE and those with
cardiac, pulmonary, renal, and splenic
involvement.
• It is characterized by thrombosis in multiple
organs over a short period of time (a few days).
Small and medium-sized arteries are most
frequently involved.
21. • Clinical presentation varies depending on the
organ involved and may include peripheral
thrombosis (deep vein, femoral artery or radial
artery), pulmonary (acute respiratory distress
syndrome, pulmonary embolism, pulmonary
hemorrhage), renal (thrombotic microangiopathy,
renal failure), cutaneous (livedo reticularis, digital
ischemia, gangrene, skin ulcerations), cerebral
(ischemic stroke, encephalopathy), cardiac (valve
lesions, myocardial infarction, heart failure),
hematological (thrombocytopenia), and
gastrointestinal (bowel infarction) involvement.
22. The four criteria are:
• Involvement of three or more organs/systems/tissues
• Manifestations developing simultaneously or within
less than one week
• Histopathological confirmation of small vessel
occlusion in at least one organ/tissue
• Laboratory confirmation of the presence of APLA
Definite CAPS can be classified by the presence of all four
criteria, while probable CAPS can be classified if 3 criteria
are present and the fourth is incompletely fulfilled.
23. Diagnosis
• In addition to clinical criteria, the diagnosis of
APLS requires the presence of lupus
anticoagulant or moderate-high titers of IgG
or IgM anticardiolipin or anti-beta-2-
glycoprotein I antibodies. The criteria also
require a repeat LA test to be positive 12
weeks after the initial positive test to exclude
clinically unimportant or transient antibody.
24.
25. Treatment / Management
• Thrombosis Management
• In patients with a positive blood test for APLA but no prior
history of thrombotic events or pregnancy-related
outcomes, primary thromboprophylaxis is debatable.
• Patients with SLE with positive APLA are especially at higher
risk of developing thrombotic events, and
hydroxychloroquine is recommended in these patients,
which has been shown to be thromboprotective. Low dose
aspirin may also be considered.
• Prophylaxis for other patients with APLA who have high-risk
APLA profile such as triple positivity with other thrombotic
risk factors may be considered for low dose aspirin.
26. • In patients with a venous thrombotic event,
warfarin with an INR goal of 2.0 to 3.0 is
recommended for the longterm.
• Low molecular weight heparin can be used in
patients who are unable to tolerate warfarin, or
who show no response to warfarin.
• In patients who have recurrent thrombosis
despite adequate warfarin, the addition of aspirin
to warfarin, or high-intensity anticoagulation with
warfarin with the INR goal of more than 3.0 can
be considered.
27. • There are no randomized controlled trials to
demonstrate the efficacy of newer anticoagulant
agents, including clopidogrel, aspirin-
dipyridamole, argatroban, fondaparinux,
dabigatran, etc. These agents can only be used in
APLS with one venous thrombotic agent if there
is allergy/intolerance to warfarin. They are not
recommended in APLS, where warfarin use is
feasible or where there are recurrent events of
venous or arterial thrombosis.
28. • Pregnancy Management
• For pregnant females with positive APLA but no history of arterial
or venous thrombosis:First pregnancy: No treatment is indicated
• History of single pregnancy loss at gestation less than 10 weeks: No
treatment is indicated
• History of multiple pregnancy losses at gestation less than 10
weeks: Low dose aspirin in combination with prophylactic dose
unfractionated heparin or LMWH throughout pregnancy.
• History of one or more pregnancy losses at gestation more than 10
weeks: Low dose aspirin in combination with therapeutic dose
unfractionated heparin or LMWH throughout pregnancy. Aspirin
should be started before conception, and both aspirin and
heparin/LMWH can be discontinued 6 to 12 weeks postpartum.
29. • For pregnant females with positive APLA and
past history of arterial or venous
thrombosis:Low dose aspirin in combination
with therapeutic dose unfractionated heparin
or LMWH throughout pregnancy. After
delivery, these patients should be transitioned
to warfarin, which should be continued
lifelong with the INR goal of 2.0 to 3.0.
30. • Catastrophic Anti-Phospholipid Syndrome
(CAPS) Management
• There are no randomized controlled trials for
the management of CAPS. Anticoagulation
and high dose corticosteroids are used in
combination with IVIG, plasmapheresis,
rituximab, cyclophosphamide, or eculizumab.
