Autoimmune Disease

name	description	evidence
Primary APS	occurs in the absence of any other related disease	TRUNCATED
Secondary APS	occurs with other autoimmune diseases, such as systemic lupus erythematosus	TRUNCATED
Asymptomatic APS	individuals with antiphospholipid antibodies but no clinical symptoms	TRUNCATED

0

subtype

Primary APS

population

Global

percentage

0.05

evidence

reference	supports	snippet	explanation
PMID:30957430	REFUTE	Among this cohort in 2000-2015, 33 cases of incident APS, as defined by the Sydney criteria, were identified... The estimated prevalence of APS was 50 (95% CI 42-58) per 100,000 population, and was similar in both sexes.	The prevalence of APS is reported as 50 per 100,000 population, which translates to 0.05%. However, this value is for all types of APS, not exclusively primary APS.
PMID:31951187	SUPPORT	28.4% of patients had primary while, 71.6% of patients had secondary APS.	The study notes that 28.4% of the cohort had primary APS, reaffirming the overall distribution of APS cases. Although it does not directly state the global prevalence per 100,000, it supports the distinction between primary and secondary APS.

0

phase

Onset

subtype

Primary APS

age_range

20-50

evidence

reference	supports	snippet	explanation
PMID:34634966	PARTIAL	We subdivided patients into two groups: youth- (15-24 years) and adult-onset (over 24 years) and compared them regarding demographic characteristics, criteria and non-criteria manifestations, cardiovascular risk factors, and aPL status.	The reference supports that primary APS can indeed onset within the specified age range of 20-50, but it does not provide sufficient evidence to conclude that progression specifically occurs within this exact range.
PMID:30957430	PARTIAL	The annual incidence of APS in adults ages >/=18 years was 2.1 (95% confidence interval [95% CI] 1.4-2.8) per 100,000 population.	This reference indicates that APS can onset in adults, which may include the age range 20-50, but does not specifically address the progression of primary APS within this age range.
PMID:26125104	NO_EVIDENCE	Current innovative treatment options include novel oral anticoagulants and the complement inhibitor eculizumab.	While discussing treatment options for APS, this reference does not address the specific age range of 20-50 or the progression of primary APS.

0

name

Antibody Production

description

The immune system produces antiphospholipid antibodies that target proteins associated with phospholipids in cell membranes.

cell_types

• B cell
• T cell

evidence

reference	supports	snippet	explanation
PMID:29867951	SUPPORT	The primary anti-phospholipid syndrome (APS) is characterized by the production of antibodies that bind the phospholipid-binding protein beta2 glycoprotein I (beta2GPI) or that directly recognize negatively charged membrane phospholipids.	This reference supports the statement by describing how the immune system produces antibodies that target phospholipid-associated proteins in cell membranes, a process involving the participation of both B cells and other immune cells.
PMID:30864219	SUPPORT	Antiphospholipid antibodies (aPL) are pathogenic autoantibodies in antiphospholipid syndrome (APS). ... In PAPS and SLE/APS patients, Th2, Th17, and plasmablasts were increased while regulatory T, memory B, and regulatory B cells were decreased compared to healthy controls.	This reference supports the statement by noting the involvement of T and B cells in the production of antiphospholipid antibodies, which are pathogenic in APS.
PMID:33722752	SUPPORT	It is now widely accepted that antiphospholipid antibodies (aPL) have direct pathogenic effects and that B cells, notably through aPL production, play a key role in the development of antiphospholipid syndrome (APS).	This reference further strengthens the support by indicating B cells' key role in the production of antiphospholipid antibodies in APS.
PMID:8968222	SUPPORT	Antiphospholipid antibodies are a heterogeneous group of antibodies with varying specificities. ... There are numerous potential links between antiphospholipid antibodies and coagulation disorders, including interaction of antiphospholipid antibodies and a cofactor, beta 2-glycoprotein I.	This reference supports the involvement of immune-produced antiphospholipid antibodies in APS and their interaction with cell membrane proteins.
PMID:22055541	SUPPORT	Diverse experimental evidence exists implicating the activation of various different cell surface receptors and intracellular pathways by antiphospholipid antibodies (aPL).	This reference discusses the cellular mechanisms activated by antiphospholipid antibodies, supporting the role of B and T cells in APS.

1

name

Blood Clot Formation

description

Antiphospholipid antibodies increase the risk of forming clots in both arteries and veins, affecting blood flow.

evidence

reference	supports	snippet	explanation
PMID:22100379	SUPPORT	Antiphospholipid antibodies are a heterogeneous group of circulating autoantibodies associated with a risk of thrombosis.	This reference highlights the association of antiphospholipid antibodies with thrombosis risk, supporting the statement that they increase the risk of forming clots.
PMID:8968222	SUPPORT	It is clear that antiphospholipid antibodies are associated with an immune-mediated prothrombotic state.	This reference explains that antiphospholipid antibodies are linked to a prothrombotic state, indicating an increased risk of clots in both arteries and veins.
PMID:29867951	SUPPORT	The primary anti-phospholipid syndrome (APS) is characterized by the production of antibodies that... may contribute to arterial or venous thrombosis.	This reference supports the statement by elaborating on the role of antibodies in arterial and venous thrombosis.
PMID:12848964	SUPPORT	Despite the strong association between antiphospholipid antibodies (aPL) and thrombosis, the pathogenic role of aPL in the development of thrombosis has not been fully elucidated.	Although it acknowledges the mechanisms are not fully understood, it confirms the strong association between antiphospholipid antibodies and thrombosis.
PMID:24321419	SUPPORT	Antiphospholipid syndrome (APS) is associated with the risk of both arterial and venous thrombosis.	This directly supports the statement by indicating that APS is associated with both arterial and venous thrombosis.

2

name

Impaired Blood Flow

description

Blood clots obstruct normal blood flow, leading to complications depending on the clot's location in the body.

evidence

reference	supports	snippet	explanation
PMID:29339317	SUPPORT	antiphospholipid syndrome (APS) is an autoimmune condition characterized by the occurrence of recurrent arterial and/or venous thrombosis	The literature supports that APS is characterized by thrombosis, which aligns with blood clots obstructing normal blood flow.
PMID:33878780	SUPPORT	aPL induce excessive activation of the endothelium, monocytes, and platelets in consort with aberrations in hemostasis/clotting, fibrinolytic system, and complement activation.	The mechanism by which antiphospholipid antibodies induce thrombosis directly aligns with the provided statement.
PMID:33341301	SUPPORT	Thrombotic Antiphospholipid Syndrome (APS) is a condition affecting young individuals in whom a thromboembolic event occurs in the presence of circulating antiphospholipid antibodies (aPL).	The thromboembolic events described are consistent with blood clots obstructing normal blood flow.
PMID:21047408	SUPPORT	APLS comprises clinical features such as arterial or venous thromboses, valve disease, coronary artery disease, intracardiac thrombus formation, pulmonary hypertension and dilated cardiomyopathy.	Various cardiovascular complications consistent with blood clots obstructing blood flow are described.

3

name

Organ Damage

description

Clots in vital organs can impair function and cause significant damage.

evidence

reference	supports	snippet	explanation
PMID:22247356	SUPPORT	After a mean followup of 7.55 years, 29% of patients experienced organ damage and 5 died... Neurologic damage is the most common cause of morbidity.	The study details the incidence of organ damage in patients with APS, supporting the statement that clots in vital organs can impair function and cause significant damage.
PMID:27198137	SUPPORT	The kidney is a major target organ in both primary and secondary antiphospholipid syndrome... APSN is a vascular nephropathy characterized by small vessel vaso-occlusive lesions.	This reference supports the statement by explaining APS-induced damage in the kidneys through vascular blockage.
PMID:24741580	SUPPORT	Typically, neurological manifestations of APS include thrombosis of cerebral vessels leading to stroke.	This reference provides evidence of brain damage caused by APS-induced clots, corroborating the statement.
PMID:36575066	SUPPORT	Venous thromboembolism belongs to the most frequent clinical manifestation of this syndrome... we summarised basic pathophysiological mechanisms of venous thrombosis and lung embolism development.	This reference supports the statement by discussing lung damage caused by clots in patients with APS.
PMID:8968222	SUPPORT	Patients with the highest titers of IgG antiphospholipid antibodies have a relatively high risk of recurrent thrombotic events, especially stroke, deep venous thrombosis, and spontaneous abortion.	The mention of recurrent thrombotic events leading to stroke helps substantiate the role of APS in causing significant organ damage, especially in the brain.

locations

• brain
• kidneys
• lungs

4

name

Pregnancy Complications

description

In pregnant women, APS can cause miscarriages, stillbirths, and pre-eclampsia due to poor placental blood flow.

evidence

reference	supports	snippet	explanation
PMID:19665761	SUPPORT	Women with antiphospholipid syndrome (APS) and antiphospholipid antibodies (aPL) are at high risk for recurrent spontaneous miscarriage and late pregnancy complications, such as preeclampsia and preterm labor.	The literature mentions APS causing recurrent miscarriage and late pregnancy complications including preeclampsia.
PMID:20822807	SUPPORT	The antiphospholipid syndrome causes venous, arterial, and small-vessel thrombosis; pregnancy loss; and preterm delivery for patients with severe pre-eclampsia or placental insufficiency.	The article explicitly states that APS causes pregnancy loss and preterm delivery related to severe pre-eclampsia or placental insufficiency.
PMID:19557318	SUPPORT	In pregnant women, antiphospholipid syndrome (APS) is associated with an increased risk of preeclampsia, fetal intrauterine growth restriction, and other complications related to uteroplacental insufficiency.	This reference directly supports the statement by associating APS with preeclampsia and placental blood flow issues leading to complications.
PMID:17499708	SUPPORT	Antiphospholipid syndrome (APS) is frequently associated with complications during pregnancy... prematurity, intrauterine growth retardation, pregnancy-induced hypertensive disorders, and pulmonary hypertension can complicate pregnancy as well.	The reference lists various pregnancy complications associated with APS, such as prematurity and hypertensive disorders.
PMID:22784367	SUPPORT	In patients with the antiphospholipid syndrome (APS), the presence of a group of pathogenic autoantibodies called antiphospholipid antibodies causes arteriovenous thrombosis and pregnancy complications.	The literature points out that antiphospholipid antibodies cause pregnancy complications in APS, supporting the mechanisms described in the statement.

5

name

Chronic Complications

description

Persistent clotting episodes can lead to long-term damage to the affected organs.

evidence

reference	supports	snippet	explanation
PMID:38368768	SUPPORT	APS patients had a higher frequency of damage accrual. Microangiopathy and non-criteria manifestations were independent risk factors for damage accrual.	The study found that APS patients had a higher frequency of organ damage, supporting the statement that persistent clotting episodes can lead to long-term damage.
PMID:28572466	SUPPORT	A high proportion of patients experienced new thrombotic events and organ damage.	This study also confirms that patients with APS often experience organ damage due to thromboses, supporting the statement.
PMID:22247356	SUPPORT	After a mean followup of 7.55 years, 29% of patients experienced organ damage and 5 died.	This study describes morbidity, organ damage, and mortality in APS patients, confirming the association between persistent clotting episodes and long-term organ damage.

0

category

Thrombosis

name

Deep Vein Thrombosis

frequency

FREQUENT

diagnostic

True

sequelae

Pulmonary Embolism Stroke

evidence

reference	supports	snippet	explanation
PMID:36575066	SUPPORT	Venous thromboembolism belongs to the most frequent clinical manifestation of this syndrome.	The reference mentions that venous thromboembolism, which includes deep vein thrombosis, is a frequent manifestation in Antiphospholipid Syndrome (APS).
PMID:11534260	SUPPORT	The most common thrombotic events associated with ACLAs are deep vein thrombosis and pulmonary embolus (type I syndrome), coronary or peripheral artery thrombosis (type II syndrome), or cerebrovascular/retinal vessel thrombosis (type III syndrome).	The statement is supported, mentioning deep vein thrombosis, pulmonary embolism, and stroke as common thrombotic events in APS.
PMID:10961585	PARTIAL	In its classic presentation, the antiphospholipid syndrome manifests a combination of venous or arterial thrombosis... The manifestations often include a moderate thrombocytopenia and, less commonly, hemolysis.	While it confirms the presence of venous thrombosis, including potential complications like stroke, it does not definitively confirm deep vein thrombosis and pulmonary embolism as common sequelae in all cases.
PMID:12627666	SUPPORT	The relative frequency of ACLAs in association with arterial and venous thrombosis strongly suggests that they should be looked for in any individual with unexplained thrombosis; all three idiotypes (IgG, IgA, and IgM) should be assessed.	Venous thrombosis, including deep vein thrombosis and pulmonary embolism, is frequently observed in APS.

1

category

Pregnancy-Related

name

Preterm Birth

evidence

reference	supports	snippet	explanation
PMID:26815583	SUPPORT	Antiphospholipid syndrome (APS) is the association of antiphospholipid antibodies with thromboses and/or obstetric morbidity. Obstetric morbidity includes recurrent first trimester loss, stillbirth, intrauterine death, preeclampsia, premature birth and fetal growth restriction.	The reference lists premature birth (preterm birth) as a form of obstetric morbidity associated with APS, supporting its categorization as a pregnancy-related phenotype.
PMID:36756665	SUPPORT	The pregnancy outcomes were not significantly different between NC-OAPS and OAPS groups.	The evidence suggests that patients with APS (OAPS) can experience similar pregnancy outcomes to those without the specific criteria of classical APS, which includes preterm birth.
PMID:34280554	SUPPORT	Patients with lupus anticoagulant positivity had an increased risk of preeclampsia (OR 2.10, p = 0.02, I(2) = 48%), SGA (OR 1.78, p < 0.01, I(2) = 0%) and preterm birth (OR 3.56, p = 0.01, I(2) = 48%).	The meta-analysis found that APS patients, especially those with lupus anticoagulant positivity, have an increased risk of preterm birth, supporting the statement that APS phenotypes include pregnancy-related complications such as preterm birth.

context

Pregnancy

2

category

Hematologic

name

Thrombocytopenia

evidence

reference	supports	snippet	explanation
PMID:8952756	SUPPORT	a variable degree of thrombocytopenia occurs in approximately 20-40% of the patients with APS	Thrombocytopenia is a hematologic phenotype observed in APS patients.
PMID:21303834	SUPPORT	This article summarizes the studies analyzed on thrombocytopenia and skin manifestations	Thrombocytopenia is mentioned as a manifestation studied in APS.
PMID:12217242	SUPPORT	Antiphospholipid antibody syndrome has been associated with [...] thrombocytopenia	Thrombocytopenia is listed among the associated conditions of APS.
PMID:20848817	SUPPORT	The manifestations often include a moderate thrombocytopenia	Moderate thrombocytopenia is identified as a feature of APS.
PMID:29316193	SUPPORT	Thrombocytopenia is the most common non-criteria hematological feature in patients with antiphospholipid syndrome (APS).	Thrombocytopenia is a significant hematologic feature observed in APS.

3

category

Cardiovascular

name

Cardiac Valve Disease

evidence

reference	supports	snippet	explanation
PMID:17916990	SUPPORT	Valvular involvement is the most common manifestation with a prevalence of 82% detected by transesophageal echocardiography. Symmetrical, nodular thickening of the mitral and/or aortic valves is characteristic.	This reference indicates that cardiac valve disease, specifically valvular involvement, is a common manifestation in patients with antiphospholipid syndrome (APS).
PMID:10852159	SUPPORT	Cardiac valve diseases and antiphospholipid syndrome.	The title of this reference directly connects cardiac valve diseases with APS, supporting the statement.
PMID:1733383	SUPPORT	Valvular involvement is frequently found in patients with the primary antiphospholipid syndrome.	This study shows a significant prevalence of cardiac valvular involvement in patients with primary APS.
PMID:30614053	SUPPORT	Most commonly mitral valve is affected followed by aortic and then tricuspid valve.	This report confirms that cardiac valve disease is a manifestation of APS, most commonly affecting the mitral valve.
PMID:1442504	SUPPORT	The earliest reports were of valvular disease, including verrucous endocarditis, as well as valvular thickening and insufficiency.	This review discusses various cardiac abnormalities associated with APS, including valvular disease.

name	presence	evidence
Antiphospholipid Antibodies	Positive	TRUNCATED
Lupus Anticoagulant	Positive	TRUNCATED
Anti-Cardiolipin Antibodies	Positive	TRUNCATED
Beta-2 Glycoprotein I Antibodies	Positive	TRUNCATED
Anti-Smith Antibodies	Negative	TRUNCATED

0

name

HLA-DR7

presence

Positive

evidence

reference	supports	snippet	explanation
PMID:12967526	NO_EVIDENCE	Multiple human leukocyte antigen-DR or -DQ associations with antiphospholipid antibodies have been described.	The reference mentions various HLA-DR associations with antiphospholipid antibodies but does not specifically mention HLA-DR7.
PMID:19758197	NO_EVIDENCE	We found that, as reported in the literature, the occurrence of DRB1*03 and DQB1*0201 alleles was higher in SLE patients than in controls, but these alleles were rare in the PAPS+SLE group.	This reference does not mention HLA-DR7 in the context of antiphospholipid syndrome.
PMID:7767340	SUPPORT	In conclusion, in PAPS patients from the South of Spain, HLA-DQ7 antigen showed the highest relative risk for PAPS, followed by DRw53.	Although HLA-DR7 is not specifically mentioned, this study discusses HLA-DR associations and could support the association indirectly. However, the mention of HLA-DR7 is more explicitly connected to diabetic retinopathy rather than APS.
PMID:11886709	NO_EVIDENCE	Our results suggest that the presence of HLA-DR7 protects against the development of proliferative disease in the diabetic Mexican population.	HLA-DR7 is discussed in the context of diabetic retinopathy and not antiphospholipid syndrome.

1

name

HLA-DR4

presence

Negative

evidence

reference	supports	snippet	explanation
PMID:7767340	REFUTE	Univariant analysis showed an association between PAPS and HLA-DQ7 (47% vs 25%l P = 0.3), DR4 (32% vs 16%; P = 0.08) and DQ3 (63% vs 39%; P = 0.04).	The literature suggests an association between primary antiphospholipid syndrome (PAPS), which is a form of APS, and HLA-DR4, contradicting the claim that HLA-DR4 presence is negative.
PMID:12967526	NO_EVIDENCE	Multiple human leukocyte antigen-DR or -DQ associations with antiphospholipid antibodies have been described.	This reference discusses HLA associations in general terms but does not provide specific evidence about HLA-DR4.

0

name

Smoking

presence

Positive

evidence

reference	supports	snippet	explanation
PMID:27377297	PARTIAL	A connection between cigarette smoking and anti-phospholipid antibodies (aPL) was first reported in the late 1980s. Systemic lupus erythematosus patients with aPL are more likely to be smokers than those without aPL. These patients have a particularly high frequency of vascular events.	The literature indicates there is some association between smoking and the presence of antiphospholipid antibodies, particularly in patients with systemic lupus erythematosus. However, it notes that the association has not been systematically examined and the connection is complicated by other factors. Therefore, it does not fully support a direct connection between smoking and antiphospholipid syndrome as an environmental factor.

1

name

Infection

presence

Positive

evidence

reference	supports	snippet	explanation
PMID:17531174	PARTIAL	An association between infections and antiphospholipid antibodies (aPL) has been reported in several epidemiologic and experimental studies. Infection-induced aPL have been traditionally regarded as transient and were generally not associated with clinical features of antiphospholipid syndrome.	The statement is partially supported because while there is an association between infections and antiphospholipid antibodies, infection-induced aPL are traditionally regarded as transient and not generally associated with the clinical features of antiphospholipid syndrome.
PMID:30301564	NO_EVIDENCE	An association between infections and heart valve involvement in antiphospholipid syndrome was not discussed.	This reference does not provide evidence regarding the association between environmental infections and Antiphospholipid Syndrome.
PMID:9087900	NO_EVIDENCE	The exact pathophysiologic mechanism in unclear but may be associated with an imbalance in the prostacyclin/ thromboxane ratio, which results in vasoconstriction and platelet aggregation.	This reference discusses antiphospholipid syndrome in the context of pregnancy loss and does not provide evidence regarding infections as an environmental factor.