Antiphospholipid antibody syndrome

Learning objectives

Describe antiphospholipid antibody syndrome (APS)
Signs and symptoms and management of APS

Definition and mechanism

Antiphospholipid syndrome (APS) or Hughes syndrome is a disorder of the immune system that creates antibodies that attack tissues in the body by mistake
These antibodies can cause blood clots to form in arteries and veins, leading to a heart attack, stroke, and other conditions
Can result in miscarriage and stillbirth during pregnancy
Primary APS: the sole manifestation of an autoimmune process
Secondary APS: in association with another disease such as systemic lupus erythematosus
Antiphospholipid syndrome is more common in women than in men
Causes are not completely understood and include environmental or genetic factors or an existing autoimmune disorder
In very rare cases, blood clots can suddenly form throughout the body, resulting in multiple organ failures → catastrophic antiphospholipid syndrome (CAPS), or Asherson syndrome
- CAPS requires immediate emergency treatment with high-dose anticoagulants

Signs and symptoms

Vascular thrombosis	Arterial thrombosis	Stroke Transient ischaemic attack Myocardial infarction Venous thrombosis
	Venous thromboembolism	Venous thromboembolism Pulmonary embolism Small vessel thrombosis
Obstetric morbidity	≥ 1 unexplained fetal death at or beyond week 10 of gestation ≥ 1 premature birth due to severe pre-eclampsia, eclampsia, or consequences of placental insufficiency ≥ 3 unexplained consecutive spontaneous abortions before week 10 of gestation
Cardiac manifestations	Valvular heart disease Cardiomyopathies
Neurological manifestations	Cognitive dysfunction Headache or migraine Multiple sclerosis Transverse myelopathy Epilepsy
Dermatologic manifestations	Livedo reticularis Skin ulceration Pseudo-vasculitic lesion Distal gangrene Superficial phlebitis Malignant atrophic papulosis-like lesion Subungual splinter hemorrhage
Renal manifestations	Thrombotic microangiopathy Chronic vascular damage
Hematologic manifestations	Thrombocytopenia Hemolytic anemia

Risk factors

Pregnancy
Immobility
Surgery
Smoking
Oral contraceptives or estrogen therapy for menopause
High cholesterol and triglyceride levels
Systemic autoimmune diseases such as lupus

Complications

Kidney failure
Stroke
Cardiovascular problems
Pulmonary embolism
Pregnancy complications
- Miscarriages
- Stillbirths
- Premature delivery
- Slow fetal growth
- Pre-eclampsia

Treatment

Primary thromboprophylaxis for aPL carriers with no prior history of vascular thrombosis and/or obstetric events
- Low-dose aspirin (75-100 mg/d)
- Lifestyle changes: smoking cessation, weight loss, control of hypertension and hyperlipidemia
- A prophylactic dose of low-molecular-weight heparin (LMWH) in high-risk situations such as surgery, prolonged immobilization, and the puerperium
Secondary thromboprophylaxis for the prevention of recurrence after thrombotic and/or obstetric events in patients with a prior history
- Previous venous thrombosis:
  - Anticoagulation: target INR of 2.0-3.0
- Previous arterial thrombosis:
  - High-intensity anticoagulation: target INR of 3.0-4.0 or a target INR of 2.0–3.0 combined with low-dose aspirin
CAPS
- Combination therapy with glucocorticoid, heparin, and plasmapheresis or IV immunoglobulin, rituximab, cyclophosphamide, or eculizumab
Pregnant women
- Combination therapy:
  - Low-dose aspirin and unfractionated heparin or LMWH
- Withdraw oral anticoagulants as soon as pregnancy is confirmed to prevent teratogenicity
- Patients without a history of thrombosis:
  - Low-dose aspirin and a prophylactic dose of unfractionated heparin or LMWH are used for primary prevention
- Patients with a history of thrombotic events:
  - Low-dose aspirin and a prophylactic dose of unfractionated heparin or LMWH are used for secondary prevention
- After delivery:
  - Administer a prophylactic dose of LMWH for at least 6 weeks after delivery
  - Start warfarin as soon as possible after bleeding is controlled
  - Patients with APS who have not received any thromboprophylaxis before delivery and do not carry any risk factors for thrombosis, require LMWH for only 7 days following delivery