ANTI PHOSPHOLIPID ANTIBODY SYNDROME

ANTI-PHOSPHOLIPID ANTIBODY SYNDROME - Christopher S.Manasseh, MD
BASICS
DESCRIPTION
• An autoimmune thrombotic syndrome characterized by the presence of antiphospholipid antibodies in association with either recurrent venous or arterial thromboembolic events or repeated fetal loss
• Types
- Primary
 Occurs in patients without clinical evidence of another autoimmune disease
- Secondary
 Occurs in association with another disease such as systemic lupus erythematosus (SLE)
- Catastrophic antiphospholipid syndrome
 Differs from primary and secondary types in the caliber of vessels affected. Venous or arterial thrombosis of large vessels is less common, and patients present with acute thrombotic microangiopathy, kidney being the most commonly affected organ.
 Disseminated intravascular coagulation which does not occur in primary or secondary forms is seen in up to 25% of patients with the catastrophic type.
• Synonym(s): Hughes syndrome
ALERT
Geriatric Considerations
Atherosclerosis and cancer are more frequent causes of thrombosis than is antiphospholipid antibody syndrome.
Pregnancy Considerations
• Increased frequency of recurrent fetal loss
• Increased risk of premature delivery due to pregnancy related hypertension and uteroplacental insufficiency
GENERAL PREVENTION
In pregnant women with h/o recurrent fetal loss, use low dose unfractionated heparin 5000 U SQ b.i.d.
In all women with the syndrome and previous pregnancy loss, aspirin 325 mg/day may provide protection against future thrombosis.
Modification of secondary risk factors for atherosclerosis include control of hypertension, diabetes, hyperlipidemia, and smoking cessation.
EPIDEMIOLOGY
1/2 of all patients with the syndrome have the primary form of the disease.
Incidence
• 15% of women with recurrent pregnancy loss have this syndrome
• 63% of patients have at least 1 valvular abnormality on echocardiogram
Prevalence
1-5% of otherwise young healthy adults have antiphospholipid antibodies
50-70% of patients with SLE who have the antiphospholipid antibodies may develop this syndrome
RISK FACTORS
• Smoking
• Oral contraceptive use
• Surgery
• Immobilization
• Pregnancy
PATHOPHYSIOLOGY
Any organ can be involved, and the extent of involvement depends on the
• Nature and size of vessel involved
• Acuteness or chronicity of the thrombotic process
ETIOLOGY
Antiphospholipid antibodies promote thrombosis by any of the following hypotheses
• Activation of endothelial cells
• Oxidant-mediated injury of the vascular endothelium
• Interference with the phospholipid binding proteins involved in the regulation of coagulation
ASSOCIATED CONDITIONS
• SLE
• Malignant hypertension
• Nephrotic syndrome


DIAGNOSIS
SIGNS AND SYMPTOMS
• Arthralgia
• Livedo reticularis
History
• Family history of rheumatic illness
• Personal history of thrombosis
Physical Exam
Look for deep vein thrombosis of the legs.
Most common manifestation of the syndrome
TESTS
• ELISA test for anticardiolipin antibodies
• Clotting test for lupus anticoagulant
Lab
• Thrombocytopenia
• Leukopenia
Diagnostic Criteria
• The presence of at least ONE of the following clinical criteria
- Vascular thrombosis
 1 or more clinical episodes of arterial, venous, or small vessel thrombosis, occurring within any tissue or organ
- Complications of pregnancy
 1 or more unexplained deaths of morphologically normal fetuses at or after the 10th week of pregnancy OR
 1 or more premature births of morphologically normal neonates at or before the 34th week of pregnancy OR
 3 or more unexplained consecutive spontaneous abortions before the 10th week of pregnancy
• AND presence of at least ONE of the following laboratory criteria
- Anticardiolipin antibodies
 Anticardiolipin IgG or IgM antibodies present at moderate or high levels in the blood on 2 or more occasions at least 6 weeks apart
- Lupus anticoagulant antibodies
 Detected in the blood on 2 or more occasions at least 6 weeks apart
Pathological Findings
• Acute changes
- Capillary congestion
- Non-inflammatory fibrin thrombi
• Chronic changes
- Ischemic hypoperfusion
- Atrophy and fibrosis
DIFFERENTIAL DIAGNOSIS
• Other conditions that cause thrombotic microangiopathy, such as
- Hemolytic-uremic syndrome
- Thrombotic thrombocytopenic purpura
• Other thrombophilic conditions, such as
- Deficiency of protein C, protein S
- Deficiency of antithrombin III
- Mutation of factor V Leiden
- Prothrombin gene mutation
- Homocysteinemia
MEDICATION (DRUGS)
First Line
Warfarin treatment of moderate intensity (to achieve an international normalized ratio (INR) of 2-2.9) significantly reduces the rate of recurrent thrombosis.
• Duration of treatment is lifelong.
Second Line
Corticosteroids and azathioprine for treatment of symptoms of lupus in patients with secondary form of the syndrome
SPECIAL THERAPY
In patients who develop new thromboses despite moderate intensity anticoagulant therapy and for patients with catastrophic antiphospholipid syndrome
• Plasmapheresis
• IV immune globulin
FOLLOW-UP
PROGNOSIS
• Pulmonary hypertension, neurologic involvement, myocardial ischemia, nephropathy, gangrene of extremities, and catastrophic APS are associated with a worse prognosis.
• Most patients experience recurrences months or years after the initial event.
• Mortality rate is ~50% in patients presenting with the catastrophic type, and death is due to multi-organ system failure.
COMPLICATIONS
Discontinuation of warfarin results in increased risk of thrombosis (even death), particularly in the 1st 6 months after stopping treatment.
PATIENT MONITORING
As warfarin therapy is lifelong, patients need to have regular monitoring to maintain INR in the therapeutic range (between 2 and 2.9).
REFERENCES
1. Lockshin M. Antiphospholipid antibody syndrome. In: Ruddy S, Harris ED, Sledge CB, ed. Kelley's Textbook of Rheumatology. Philadelphia: Saunders Company; 2001;1145-1152.
2. Erkan D, Yazici Y, Sobel R, Lockshin MD. Primary antiphospholipid syndrome. Functional outcome after 10 years. J Rheumatol. 2000;27:2817-2821.
3. Levine JS, Branch DW. The antiphospholipid syndrome. N Eng J Med. 2002;10:752-759.
4. Crowther MA, Ginsberg JS, et al. A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with antiphospholipid syndrome. N Eng J Med. 2003;12:1133-1138.
ADDITIONAL READING
The decade of autoimmunity: edited by Y. Shoenfeld, publication date 1999.