Clinical manifestations of antiphospholipid

syndrome
Authors: Doruk Erkan, MD, MPH, Stéphane Zuily, MD, MPH, PhD
Section Editor: David S Pisetsky, MD, PhD
Deputy Editors: Siobhan M Case, MD, MHS, Jennifer S Tirnauer, MD

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is
complete.

Literature review current through: Aug 2023. | This topic last updated: May 24, 2023.

INTRODUCTION

Antiphospholipid syndrome (APS) is an autoimmune multisystem disorder

characterized by arterial, venous, or small vessel thromboembolic events
and/or pregnancy morbidity in the presence of persistent antiphospholipid
antibodies (aPL) [1]. aPLs are a heterogenous group of autoantibodies which
are directed against phospholipid-binding proteins.

APS occurs as a primary condition or in the setting of an underlying systemic

autoimmune disease, particularly systemic lupus erythematosus (SLE).

The clinical manifestations of APS will be reviewed here. Pathogenesis,

diagnosis, and treatment of APS are presented separately. (See "Pathogenesis
of antiphospholipid syndrome" and "Diagnosis of antiphospholipid
syndrome" and "Management of antiphospholipid syndrome".)

Catastrophic APS (CAPS) and kidney manifestations of APS are discussed

separately. (See "Catastrophic antiphospholipid syndrome (CAPS)" and
"Antiphospholipid syndrome and the kidney".)
EPIDEMIOLOGY

In a large retrospective analysis including patients without known

autoimmune diseases, antiphospholipid antibodies (aPL) were present in
approximately 9 percent of patients with pregnancy losses, 14 percent with
stroke, 11 percent with myocardial infarction (MI), and 10 percent with deep
vein thrombosis (DVT) [2].

Estimates in the United States suggest that aPL are associated with
approximately 50,000 pregnancy losses, 110,000 strokes, 100,000 MIs, and
30,000 DVTs annually [2-8]. Epidemiologic studies done in the general
population from the United States and Italy determined a prevalence of
antiphospholipid syndrome (APS) ranging from 17 to 50 patients per 100,000
[9,10].

PRIMARY APS VERSUS APS WITH SLE

Approximately half of patients with antiphospholipid syndrome (APS) have

primary disease, while the other half have a concomitant systemic
autoimmune disease. Systemic lupus erythematosus (SLE) is the disease most
commonly associated with APS, which is present in approximately 35 percent
of cases [11].

Although many of the clinical manifestations of primary APS and APS

associated with SLE are similar [12], patients with SLE-associated APS are
more likely to have arthritis, livedo reticularis, heart valve disease,
thrombocytopenia, and leukopenia than patients with primary APS [13-15].
Another study found that the frequencies of arterial thrombosis, venous
thrombosis, and fetal loss were greater in patients with APS and SLE than in
those with primary APS [16]. However, traditional cardiovascular risk factors
and markers of early atherosclerosis are similar between patients with
primary and SLE-associated APS [17,18].

A separate issue regarding the relationship of APS and SLE is the frequency of
evolution of APS into SLE or lupus-like disease. Three studies involving 70 to
128 patients with APS found a variable rate of development of SLE over time:

● 0 percent at 5 years [19]

● 4 percent at 6.5 years [20]
● 13 to 23 percent at 9 years [21,22]

CLINICAL MANIFESTATIONS

In addition to the hallmark features of venous, arterial, and/or small vessel

thrombosis as well as specific pregnancy complications, other relatively
common clinical features of antiphospholipid syndrome (APS) include livedo
reticularis, thrombocytopenia, or transient ischemic attack [23].

Rarely, patients with APS can develop catastrophic APS (CAPS), with
widespread thrombotic disease and multiorgan failure ( table 1). CAPS can
also rarely be the initial presentation of APS. (See "Catastrophic
antiphospholipid syndrome (CAPS)".)

In a series of 1000 patients with either primary or autoimmune disease-

associated APS, the various disease features were [24]:

● Deep vein thrombosis (DVT) – 32 percent

● Thrombocytopenia – 22 percent
● Livedo reticularis – 20 percent
● Stroke – 13 percent
● Superficial thrombophlebitis – 9 percent
● Pulmonary embolism – 9 percent
 ● Fetal loss – 8 percent
● Transient ischemic attack – 7 percent

Several studies have identified that particular combinations of features are

seen more often together or in a given patient over time (eg, stroke and
valvular heart disease, livedo and arterial thrombosis, thrombocytopenia and
small vessel thrombosis). A cluster analysis demonstrated that small vessel
thrombosis and pregnancy morbidity manifestations were found in patients
with non-criteria manifestations [25]. (See "Diagnosis of antiphospholipid
syndrome", section on 'Classification criteria'.)

In addition to those manifestations mentioned above, some of the other

possible antiphospholipid antibody (aPL)-related clinical manifestations
include cardiac valve disease, pulmonary hypertension, thrombocytopenia,
cutaneous ulcers and adrenal insufficiency due to hemorrhagic infarction,
and cognitive deficits [23,24,26-29].

Thrombotic events — Thromboses are the hallmark of APS, and venous

thromboses are more common than arterial thromboses [24]. The risk of both
venous and arterial thrombosis and/or thromboembolism is increased in
individuals with positive tests for lupus anticoagulant (LA) activity (odds ratio
[OR] 11) or with medium or high levels of anticardiolipin antibodies (aCL; OR
1.6) [30]. The risk of recurrent thrombosis or thromboembolism may be
further enhanced in those with positivity to three aPL, also known as "triple
positivity," (LA, aCL, and anti-beta2 glycoprotein [GP] I antibodies) upon
repeated testing [31].

Venous thrombosis — The deep veins of the lower extremities are the most
common sites of thrombosis, with estimates from large cohort studies
ranging from 20 to 30 percent of patients with APS [24,32]. Other sites of
venous thrombosis include the pelvic, renal, pulmonary, hepatic, portal,
axillary, subclavian, ocular, and cerebral sinuses, as well as the inferior vena
cava. Superficial vein thrombosis can also occur [33].

Arterial thrombosis — The most common site of arterial thrombosis is in

the cerebral vasculature, usually in the form of a stroke or transient ischemic
attack [24]. Occlusions in the retinal, coronary, renal, and mesenteric arteries
can also occur. Stroke in patients with APS is discussed in further detail below.
(See 'Neurologic involvement' below.)

Recurrent thrombotic events — The recurrence rate of thrombotic events

among patients with APS is highly variable among studies, with an annual
recurrent thrombosis risk ranging from 5 to 12 percent [11,31,33-36]. In
patients after a first unprovoked venous thromboembolism (VTE) for which
the anticoagulation was stopped, the annual risk of recurrent VTE can be
much higher, ranging from 10 to 20 percent [37]. The presence of LA or triple
aPL positivity is the main risk factors for recurrence [31,36,38,39].

Most, but not all, studies have indicated that an initial arterial thrombosis
tends to be followed by an arterial event and that an initial venous
thrombosis is usually followed by a venous event [40-42]. In a report in which
186 recurrences occurred in 101 patients, the site of recurrence was arterial
in 93 percent of those with an initial arterial thrombosis, and the site of
recurrence was venous in 76 percent of those with an initial venous
thrombosis [42]. The factors that determine the predilection for the venous or
arterial circulation are not known.

Neurologic involvement — Central nervous system abnormalities are a

common feature of APS that have been attributed to both vascular
thrombosis as well as direct injury to neuronal tissue by aPL [43]. Stroke and
transient ischemic attack are the most common neurologic manifestations of
APS. A thrombotic stroke occurring in a young patient with no overt risk
factors for cerebrovascular disease is a classic setting in which to suspect APS
[2].

Ischemic stroke may be a manifestation in situ thrombosis or due to

embolism arising from valvular heart disease. If routine transthoracic
echocardiography is normal, transesophageal echocardiography may be
indicated to assess for vegetations due to nonbacterial endocarditis. (See
'Cardiac involvement' below.)

Sneddon syndrome, which is characterized by widespread livedo reticularis in

association with a stroke, has also been described among patients with aPL
[44,45]. In almost half of all cases, Sneddon syndrome is associated with
detectable aPL [44].

Cognitive deficits independent of stroke and/or white matter lesions have

been associated with APS [46,47]. The degree of reported cognitive deficits
ranges from subtle findings to transient global amnesia to permanent and
profound cognitive functioning. The cognitive deficits reported in APS are
sometimes but not always associated with white matter lesions. As an
example, cognitive deficits were evaluated in a study of 60 patients with
primary or secondary APS who underwent comprehensive
neuropsychological testing [26]. The APS patients were compared with 60
healthy controls, matched for age, sex, and education, and 25 disease
controls (systemic lupus erythematosus [SLE] and rheumatoid arthritis
patients who did not have APS). The following observations were made:

● Cognitive deficits were significantly more frequent in the patients with

APS (42 versus 18 and 16 percent of the healthy and disease controls,
respectively).

● Cognitive dysfunction in the APS patients was associated with livedo

reticularis on physical examination and with the finding of white matter
 lesions on brain magnetic resonance imaging (MRI).

● No relationship was detected between cognitive dysfunction and

previous central nervous system disease (eg, stroke).

Multifocal white matter lesions on MRI that are suggestive of a vasculopathy

are a common finding on MRI in APS patients [26]. These lesions may be
difficult to distinguish from those in multiple sclerosis [48,49].

Other less common neurologic disorders that have been reported in aPL-
positive patients include epilepsy, psychosis, chorea, and hemiballismus,
transverse myelopathy, sensorineural hearing loss, and migraine [24,26,50-
60]. However, no strong association has been established between these
manifestations and aPL.

Hematologic abnormalities — Thrombocytopenia can be observed in APS

patients and is discussed further below (see 'Thrombocytopenia' below).
Other hematologic abnormalities reported in patients with APS include
autoimmune hemolytic anemia, especially if there is widespread thrombosis;
and various thrombotic microangiopathic syndromes including thrombotic
thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) [61].
(See 'Other' below and "Evaluation of bone marrow aspirate smears", section
on 'Bone marrow necrosis'.)

Pulmonary involvement — Patients with APS may develop various lung

manifestations including pulmonary thromboembolic disease,
thromboembolic and non-thromboembolic pulmonary hypertension
(pulmonary arterial hypertension [62,63]), pulmonary arterial thrombosis,
pulmonary microthrombosis, acute respiratory distress syndrome, and
diffuse alveolar hemorrhage [24,64-69]. (See "The diffuse alveolar
hemorrhage syndromes" and "Clinical features and diagnosis of pulmonary
hypertension of unclear etiology in adults" and "Epidemiology, pathogenesis,
clinical manifestations and diagnosis of chronic thromboembolic pulmonary
hypertension".)

Cardiac involvement — Cardiac manifestations of APS most commonly

involve the valves, including valvular thickening and valve nodules (also
referred to as nonbacterial vegetations or Libman-Sacks endocarditis)
( picture 1) [24,70-75]. The mitral valve is most frequently involved, followed
by the aortic valve [76]. Involvement of the mitral and aortic valves can lead to
valvular regurgitation and, rarely, to stenosis [73-75]. Valve lesions, especially
aortic nodules, are highly associated with the risk of stroke [77,78]. The risk of
heart valve disease is higher in patients with LA or immunoglobulin G (IgG)
aCL (OR 6) than those with IgM aCL (OR 3) [79].

Patients with APS also have an increased risk for developing coronary artery
disease. Myocardial infarction may be due to coronary thromboembolism,
accelerated atherosclerosis leading to a plaque rupture, or microvascular
thrombosis (detected by MRI) with a normal coronary vascular bed [70]. One
study found that aPL (including lupus anticoagulant and anticardiolipin anti-
beta 2 glycoprotein (GP) 1 antibodies) was associated with a twofold
increased risk of myocardial infarction [80].

Cutaneous manifestations — APS has been associated with many

cutaneous abnormalities including splinter hemorrhages, livedo reticularis
and racemosa ( picture 2), cutaneous necrosis and infarction, digital
gangrene, skin ulcerations, lesions resembling vasculitis ("pseudovasculitic"
nodules, macules), and livedoid vasculopathy (with/without atrophie blanche)
[1,24,81-83]. (See "Livedoid vasculopathy".)

Livedo is the most common cutaneous manifestation of APS. Although livedo

reticularis is nonspecific, livedo racemosa can be associated with arterial
lesions and multiple thromboses in APS [84]. Livedo is present in more than
20 percent of SLE patients with aPL compared with 10 percent in SLE patients
without aPL. In the general population, prevalence of livedo is lower than in
patients with SLE [85]. In a series of 200 patients with APS, livedo reticularis
was associated with cerebral or ocular ischemic events (OR 10.8) [82]. By
contrast, livedo reticularis was observed with decreased frequency in patients
who experienced only venous thromboses (OR 0.2).

There is considerable ambiguity in the literature with regard to the terms

"livedo reticularis" and "livedo racemosa" [86]. Livedo racemosa is
characterized by a violaceous net-like pattern on the skin with irregular
and/or broken circles; livedo reticularis is characterized by unbroken circles
[87]. Livedo racemosa, named by Ehrmann in 1907 [88], is a more striking
cutaneous finding than livedo reticularis [86]. In addition, livedo reticularis
often occurs in physiologic settings rather than in disease states [89]. The
clinical significance of differentiating between livedo racemosa and livedo
reticularis was illustrated in a study of 111 patients with livedo racemosa and
32 patients with livedo reticularis [87]. The former were more likely to have
biopsy-proven cutaneous vasculitis; to be younger and male; and to have
arthralgia, higher levels of C-reactive protein (CRP), and antibodies to
phosphatidylserine prothrombin complexes. (See "Overview of cutaneous
lupus erythematosus", section on 'Vascular abnormalities' and "Clinical
manifestations and diagnosis of Raynaud phenomenon", section on 'Signs
and symptoms of Raynaud phenomenon'.)

As mentioned above, livedo reticularis in association with stroke is known as

Sneddon syndrome, and half of the time occurs in the presence of aPL. (See
'Neurologic involvement' above.)

Kidney disease — Kidney disease occurs in a minority of patients with

primary APS. Glomerular capillaries and other renal vessels, both arteries and
veins of all sizes, can be affected. The disease may be silent or may produce
acute or chronic kidney failure with proteinuria and hypertension. A detailed
discussion of kidney involvement in patients with APS, including those with
underlying SLE, is presented separately. (See "Antiphospholipid syndrome and
the kidney".)

Gastrointestinal involvement — Patients with APS may have ischemia

involving the esophagus, stomach, duodenum, jejunum, ileum, or colon
resulting in gastrointestinal bleeding, abdominal pain, an acute abdomen,
esophageal necrosis with perforation, or giant gastric or atypical duodenal
ulceration [90]. Splenic or pancreatic infarction may also occur [24]. In
addition, the liver may be involved; hepatic or portal venous thrombosis may
result in the Budd-Chiari syndrome, hepatic-veno-occlusive disease, hepatic
infarction, portal hypertension, and cirrhosis [90,91].

Ocular involvement — Amaurosis fugax, retinal venous [92] and arterial

occlusion, and anterior ischemic optic neuropathy have occurred in patients
with aPL [24,93,94].

Adrenal disease — Loss of adrenal function due to bilateral adrenal vein

thrombosis, resulting in hemorrhagic infarction, may occur in association
with APS, especially catastrophic APS [95,96]. An enlarged adrenal or an
adjacent mass may be apparent on a computed tomography (CT) scan, but
MRI is more effective in determining the age of adrenal hemorrhage and in
differentiating bleeding from other causes of adrenal gland enlargement.
Adrenal hemorrhagic infarction may present as abdominal, lumbar, pelvic, or
thoracic pain. (See "Causes of primary adrenal insufficiency (Addison
disease)", section on 'Hemorrhagic infarction'.)

Adrenal involvement can also be seen in CAPS. (See "Catastrophic

antiphospholipid syndrome (CAPS)", section on 'Thrombosis and organ
involvement'.)
Osteonecrosis — Asymptomatic changes in the appearance of the femoral
heads of patients with primary APS have been noted on MRI. These findings
have been interpreted to indicate osteonecrosis. However, of the 30 patients
who were the subject of one report, none had changes on plain radiographs,
and none had progressive changes on subsequent MRIs [97]. Thus, the true
nature of the association between osteonecrosis and the presence of APS is
not clear.

PREGNANCY COMPLICATIONS

In addition to thrombotic events, pregnancy complications are the other

hallmark of antiphospholipid syndrome (APS). These complications include
fetal death after 10 weeks gestation, premature birth due to severe
preeclampsia or placental insufficiency, or embryonic losses (<10 weeks
gestation). Fetal loss in patients with aPL and the approach to women with
recurrent fetal loss are discussed in detail separately. (See "Antiphospholipid
syndrome: Obstetric implications and management in pregnancy" and
"Recurrent pregnancy loss: Evaluation".)

In aPL-positive patients with preeclampsia or the HELLP Syndrome

(hemolysis, elevated liver enzymes, and low platelet count in association with
pregnancy), the possibility of the evolving catastrophic APS (CAPS) must be
considered, particularly in patients with histories of thrombosis or
spontaneous abortions [98,99]. (See "HELLP syndrome (hemolysis, elevated
liver enzymes, and low platelets)" and "Catastrophic antiphospholipid
syndrome (CAPS)", section on 'When to suspect'.)

LABORATORY FINDINGS

In addition to the presence of antiphospholipid antibodies (aPL), some of the

other potential laboratory findings include thrombocytopenia, hemolytic
anemia, prolonged activated partial thromboplastin time (aPTT), a history of a
false-positive serologic test for syphilis, and low complement levels.

Antiphospholipid antibodies — The three major aPL tests that are

recognized by international classification criteria for antiphospholipid
syndrome (APS) ( table 2) are as follows:

● Anticardiolipin antibodies (aCL) immunoglobulin G (IgG) and/or IgM

enzyme-linked immunosorbent assay (ELISA)
● Anti-beta2 glycoprotein (GP) I antibodies IgG and/or IgM ELISA
● Lupus anticoagulant (LA) test

Generally, the diagnosis of APS is made in the presence of one or more of the
above aPL in the setting of a vascular thrombosis or a specific type of
pregnancy morbidity. Individuals with one or more aPL, but without a history
of thrombosis, pregnancy complications, or the other clinical manifestations
(see 'Clinical manifestations' above), may be at risk of developing APS. A
detailed discussion on diagnosis of APS is presented elsewhere. (See
"Diagnosis of antiphospholipid syndrome".)

An aPL may be present in some people who do not have APS and are
otherwise healthy, who have another autoimmune or rheumatic disease, or
who have been exposed to certain drugs or infectious agents. These and
other associations are discussed in more detail elsewhere. (See "Diagnosis of
antiphospholipid syndrome", section on 'Other conditions associated with
antiphospholipid antibodies'.)

The development of newer tests (antibodies directed against domain I of B2-

glycoprotein I or antiphosphatidylserine-prothrombin antibodies) will be
useful to identify high-risk APS patients for tailored management [100,101].

Thrombocytopenia — Thrombocytopenia can be observed in APS patients,

with an incidence ranging from 22 to 42 percent [61]. The frequency of
thrombocytopenia is higher in SLE-associated APS than in primary APS. The
degree of thrombocytopenia is usually moderate, with a platelet count
usually in the range of 100,000 to 140,000/microL, and is rarely associated
with hemorrhagic events. Thrombocytopenia is a predictive factor of APS-
related manifestations (thrombosis, pregnancy morbidity, hemolytic anemia,
or death) [102,103], and a decrease in platelet count frequently preceded an
episode of catastrophic APS [104].

Hypocomplementemia — Hypocomplementemia can be observed in

primary APS, similar to what is observed in patients with SLE [105,106]. As an
example, in an observational cohort that included 70 patients with primary
APS, nearly half presented with low complement levels [105]. However,
complement levels such as C3 and C4 are generally not used to trend disease
activity as they are sometimes used in SLE. (See "Acquired disorders of the
complement system", section on 'Increased consumption by immune
complexes'.)

Other — Other laboratory abnormalities include the prolongation of a blood

coagulation test (eg, aPTT), a hemolytic anemia [85], or a history of a false-
positive serologic test for syphilis. (See "Diagnosis of antiphospholipid
syndrome", section on 'When to suspect the diagnosis'.)

MORTALITY

Antiphospholipid syndrome (APS) is associated with increased morbidity and

mortality. A large, multicenter, prospective study of 1,000 APS patients found
a decreased survival rate of 90.7 percent at 10 years [11]. The main causes of
death during the 10-year follow-up included thrombosis (31 percent), sepsis
(27 percent), malignancy (14 percent), hemorrhage (11 percent), systemic
lupus erythematosus (SLE) involvement (8 percent), and catastrophic APS (5
percent). The mean age at death was 59, with a standard deviation of 14
years. There were no differences in the mortality rates in the presence of
underlying disease: 6.8 percent of patients with SLE-associated APS compared
with 7.1 percent of patients with primary APS died. Note, however, that
during the study period over 40 percent of patients were lost to follow-up.

The presence of antiphospholipid antibodies (aPL) in the serum of patients

with SLE has been identified as an independent risk factor for premature
death. This was illustrated in an observational study of 667 patients with SLE,
49 of whom died [107]. There was an increased risk of premature death in
patients with aPL, thrombocytopenia, and arterial occlusion. Other factors
associated with premature death were the intensity of anticoagulation
treatment, renal involvement, pleuritis, and disease activity.

Although some of the risk of early death is due to the increased propensity to
thromboembolic disease, in some settings, aPL may be a marker for a higher
mortality rate that is not due to thrombophilia per se. As an example, in a
study of 300 consecutive patients with a first ischemic stroke, stroke victims
with elevated levels of aPL (immunoglobulin G [IgG] anticardiolipin antibodies
[aCL] >20 units) had a higher mortality rate during approximately two years of
follow-up than those with lower or absent aCL levels (33 versus 18 percent
mortality, relative risk [RR] 1.94, 95% CI 1.05-3.67) [108]. However, the
increased mortality was not due to recurrent stroke but was associated with
other characteristics of those with aPL, including a higher rate of malignancy
and more prevalent risk factors for coronary heart disease.

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected

countries and regions around the world are provided separately. (See "Society
guideline links: Antiphospholipid syndrome".)
INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and
"Beyond the Basics." The Basics patient education pieces are written in plain
language at the 5th to 6th grade reading level and they answer the four or five
key questions a patient might have about a given condition. These articles are
best for patients who want a general overview and who prefer short, easy-to-
read materials. Beyond the Basics patient education pieces are longer, more
sophisticated, and more detailed. These articles are written at the 10th to 12th
grade reading level and are best for patients who want in-depth information
and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We
encourage you to print or e-mail these topics to your patients. (You can also
locate patient education articles on a variety of subjects by searching on
"patient info" and the keyword(s) of interest.)

● Beyond the Basics topic (see "Patient education: Antiphospholipid

syndrome (Beyond the Basics)").

SUMMARY AND RECOMMENDATIONS

● Definition – Antiphospholipid syndrome (APS) is an autoimmune
multisystem disorder characterized by arterial, venous, or small vessel
thromboembolic events and/or pregnancy morbidity in the presence of
persistent antiphospholipid antibodies (aPL). APS occurs as a primary
condition or in the setting of an underlying systemic autoimmune
disease, particularly systemic lupus erythematosus (SLE). (See
'Introduction' above.)
● Antiphospholipid antibodies – The three major aPL tests that are
recognized by international classification criteria for APS ( table 2) are
anticardiolipin antibodies (aCL) immunoglobulin G (IgG) and/or IgM
enzyme-linked immunosorbent assay (ELISA), anti-beta2 glycoprotein
(GP) I antibodies IgG and/or IgM ELISA, and the lupus anticoagulant (LA)
test. (See 'Antiphospholipid antibodies' above.)

● Clinical manifestations

• Thrombotic events – Thromboses are the hallmark of APS. The deep

veins of the lower extremities are the most common sites of venous
thrombosis, and the cerebral vasculature (stroke and transient
ischemic attack) is the most common site for arterial thrombosis.
Superficial vein thrombosis can also occur. (See 'Thrombotic events'
above and 'Neurologic involvement' above.)

• Neurologic involvement – Stroke and transient ischemic attack are

the most common neurologic manifestations of APS. Cognitive deficits
independent of stroke and/or white matter lesions have also been
associated with APS. (See 'Neurologic involvement' above.)

• Hematologic abnormalities – Thrombocytopenia can be observed in

APS, but the degree is usually moderate and is rarely associated with
hemorrhagic events. Other hematologic abnormalities reported with
APS include various thrombotic microangiopathy (TMA) syndromes
and autoimmune hemolytic anemia. (See 'Hematologic abnormalities'
above.)

• Pulmonary involvement – Patients with APS may develop various

lung manifestations including pulmonary thromboembolic disease,
thromboembolic and non-thromboembolic pulmonary hypertension
(pulmonary arterial hypertension), pulmonary arterial thrombosis,
 pulmonary microthrombosis, acute respiratory distress syndrome, and
diffuse alveolar hemorrhage. (See 'Pulmonary involvement' above.)

• Cardiac involvement – Cardiac manifestations of APS most commonly

involve the valves, including valvular thickening, and valve nodules
(also referred to as nonbacterial vegetations or Libman-Sacks
endocarditis), which can lead to valvular dysfunction. (See 'Cardiac
involvement' above.)

• Cutaneous manifestations – Livedo ( picture 2) is the most common

cutaneous manifestation of APS; while livedo reticularis is also
relatively common in the general population, livedo racemosa is more
specific for APS. Other cutaneous abnormalities that can occur in APS
patients include splinter hemorrhages, cutaneous necrosis and
infarction, digital gangrene, skin ulcerations, lesions resembling
vasculitis ("pseudovasculitic" nodules, macules), and livedoid
vasculopathy. (See 'Cutaneous manifestations' above.)

• Other manifestations – Other less common manifestations of APS

include ocular involvement, renal disease, adrenal insufficiency, and
gastrointestinal involvement. (See 'Ocular involvement' above and
'Kidney disease' above and 'Adrenal disease' above and
'Gastrointestinal involvement' above.)

● Pregnancy complications – Pregnancy complications are another

hallmark of APS. These complications include fetal death after 10 weeks
gestation, premature birth due to severe preeclampsia or placental
insufficiency, and/or multiple embryonic losses (<10 weeks gestation).
(See 'Pregnancy complications' above and "Antiphospholipid syndrome:
Obstetric implications and management in pregnancy".)
 ● Catastrophic APS – Rarely, patients with APS can develop catastrophic
APS (CAPS), with widespread thrombotic disease and multiorgan failure
( table 1). CAPS can also rarely be the initial presentation of APS. (See
"Catastrophic antiphospholipid syndrome (CAPS)".)

● Prognosis – APS is associated with increased morbidity and mortality.

Major causes of death include thrombosis, sepsis, malignancy,
hemorrhage, SLE involvement, and catastrophic APS. (See 'Mortality'
above.)
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