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Antiphospholipid Antibody Syndrome (APS)
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 | Primary APS: no underlying systemic disorder |
| Secondary APS: presence of an underlying disease, most commonly SLE. |
|
| Antiphospholipid antibody: two main groups.
 | Lupus anticoagulants (LA): dRVVT used as both a
screening and confirmatory test. It is a sensitive assay, provides accurate results during
pregnancy. A prolonged dRVVT may be better than other tests for predicting arterial
thrombosis. |
| Anticardiolipin antibodies (ACA):
 | Predictive value probably rises with the titer. Both IgG and IgM ACA may
carry a risk, the correlation seems to be stronger with IgG antibodies. A mild increase involve very little risk. |
| No direct correlation between the concentration of
antibodies and extent of thrombosis.
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| Whether elevated cardiolipin, phosphatidylserine, or
phosphatidylethanolamine antibodies are a cause of stroke or are only a marker of the
presence of other precursors of stroke remains unknown.
|
| Associated laboratory abnormalities: may
include a prolonged activated partial thromboplastin time, false-positive VDRL, elevated
ANA, ESR, thrombocytopenia. |
| Finazzi et al: 360
patients with LACs or ACAs, followed prospectively for a median of 3.9 years. Two
independent risk factors for thrombotic events were identified: a previous history of
thrombosis and the presence of an IgG ACA titer exceeding 40 U/mL.
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| Clinical manifestation |
| Venous thrombosis:
| Most common: deep or superficial veins of the legs |
| Less common: inferior vena cava, iliofemoral, axillary, renal, portal,
hepatic, or retinal veins. |
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| Arterial thrombosis:
| Most common: Cerebral infarct, some strokes may be caused by cardiogenic
emboli. |
| Less common: Coronary, retinal, and visceral artery
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| Other symptoms
| Cutaneous: livedo reticularis, splinter hemorrhages, leg ulcer, skin
insarcts, blue toe syndrome |
| Neuro: multi-infarct dementia, chorea, transverse myelopathy, Pseudotumor
cerebri, cerebral venous thrombosis |
| Cardiac: Coronary artery disease, valve vegetations, intracardiac
thrombus |
| Hematologic: Thrmobocytopenia (40% of patients), hemolytic anemia |
| Obstetric: Late term pregnancy loss, intrauterine growth retardation. |
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| Hypertension, coronary artery disease, hyperlipidemia, cigarette smoking,
and a positive ANA are associated with an increased risk of stroke or TIA, whereas those
on aspirin plus dipyridamole were at a decreased risk. |
| Stroke recurrence rate may be as high as 10% per year. Usually large or
median branch artery infarcts and rarely causes lacunar infarcts.
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| The best independent predictor of a thrombotic event is a history of
thrombosis. |
| Cardiac valve thickening or vegetative lesions: may occur in > 30% of
patients with primary Antiphospholipid antibody syndrome. |
| Recurrent spontaneous fetal loss: more common in the second or third
trimester. Observed in 15% to 75% of Antiphospholipid antibody-positive women. |
| Livedo reticularis, a lattice-like pattern of skin discoloration: most
common cutaneous finding, seen in up to 80% of patients with Antiphospholipid antibodies. |
| Cutaneous ulcers, which may be refractory to treatment. |
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| APS & SLE |
| Up to 50% of patients with SLE have antibodies to phospholipids.
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| SLE patients with Antiphospholipid antibodies: 40% has thrombosis. SLE
without Antiphospholipid antibodies: 12% to 18%. |
| SLE patients have a higher incidence of cardiac valvular disease,
hemolytic anemia, leukopenia, and low C4 complement levels. |
| Tsokos et al: hemorrhagic stroke occurs more
commonly in active lupus. Thrombotic stroke, possibly related to the Antiphospholipid
antibody, is more common in quiescent phases.
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| Catastrophic Antiphospholipid antibody syndrome |
| A rare fulminant form of the APS. |
| Acute multiorgan system thrombosis of small and large vessels.
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| Cutaneous ischemia-gangrene, malignant hypertension, acute respiratory
distress syndrome, central nervous system deterioration, rapidly progressive renal
failure, infarction of the bowel, adrenal glands, or liver.
|
| High titer IgG Anticardiolipin Ab or lupus
anticoagulant. |
| Clinical manifestation may mimic thrombotic thrombocytopenic purpura,
disseminated intravascular coagulation, and active SLE.
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| Morbidity and mortality rates associated with the catastrophic
Antiphospholipid syndrome are high. |
| Treatment of patients with the catastrophic
APS relies on anecdotal reports.
| High-dose corticosteroids is generally ineffective. |
| Cyclophosphamide has been useful in some patients. |
| In view of the noninflammatory nature of the condition and the presence
of autoantibodies, therapy with anticoagulation and plasmapheresis is recommended. |
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Prevalence Of Antiphospholipid Antibodies:
| Presence of antiphospholipid antibodies does not
necessarily indicate an increased risk for thrombosis. |
| The presence of ACAs is considered a risk factor for stroke, but this
association may be true only in patients with SLE or other autoimmune disorders. |
| Many well-controlled studies have found no association between ACAs and
stroke in non-SLE patients |
|
| Normal healthy people |
| 1% to 14% - age related |
| Fields et al. found abnormal levels of IgG or IgM ACA in 12% of healthy
elderly persons. |
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| Infection |
| Syphilis, AIDS |
93% |
| Lyme disease |
39% |
| Mononucleosis |
20% |
| Tuberculosis |
20% |
| Protozoal infections, measles, chickenpox,
mumps, hepatitis A, leptospirosis |
? |
|
| Drug induced |
Phenothiazines, procainamide, chlorpromazine,
hydralazine, phenytoin, valproate, quinidine, propranolol, ethosuximide,
chlorothiazide, oral contraceptives. |
| Malignancy |
Melanoma, renal cell carcinoma, lung carcinoma,
thymoma, lymphoma, leukemia |
| Autoimmune diseases |
| SLE |
15%- 50% |
| Sjogren's syndrome |
42% |
| Rheumatoid arthritis |
up to 33% |
| Posoriatic arthritis |
28% |
| Scleroderma |
25% |
| Mixed Connective Tissue Disease |
22% |
| Giant cell arteritis, Polymyalgia rheumatica |
20% |
| Behcet's disease |
0% - 50% |
| Idiopathic Thrombotic Purpura |
30% |
| Juvenile chronic arthritis |
55% |
| Ankylosing spondylitis, polyarteritis nodosa,
relapsing polychondritis, Takayasu's arteritis, hemolytic anemia, Crohn's disease |
? |
|
| Neurologic diseases |
Myasthenia gravis (68%), multiple sclerosis (29%),
Guillain-Barre syndrome, transverse myelitis, Sneddon's syndrome, Dermatomyositis,
polymyositis. |
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| Treatment to prevent thrombosis |
| Treatment of patients with aPL Antibody is controversial. The problem
seems to be mainly an abnormal hypercoagulable state that predisposes to thrombosis of
arteries rather than true vasculitis. |
| Asymptomatic patient with Antiphospholipid Ab: reduce risk
factors for vascular disease.
| Those with high titers: avoid oral contraceptive. |
| Life style change: maintain ideal weight, cholesterol level and physical
activity. |
| Control blood pressure, avoid smoking. |
| ? Antiplatelet agents. |
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| Treatment after a thrombotic event:
| Rosove & Brewer: Patients on Warfarin did better. No recurrent
thrombotic event with INR > 2.6 |
| Derksen & al.: retrospective analysis.
| Anticoagulated: no recurrence of thrombosis |
| Anticoagulation stopped: 50% recurrence at 2 years, 78% recurrence at 8
years. |
|
| Khamashta: 147 patients with APS. Treatment with intensive Warfarin with
INR >3, more effective than low intensity Warfarin in preventing recurrent thrombosis. |
|
| Significant bleeding occurred in some patients with such high intensity
Warfarin treatment. |
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| Further Reading |
| Antiphospholipid
Antibody - definition & history - Thomas G. DeLoughery 1999 |
| Khamashta MA, Cuadrado MJ, Mujic F, et al: The management of thrombosis
in the antiphospholipid-antibody syndrome. N Engl J Med 332:993, 1995
|
| Pisetsky, DS., Gilkeson G., St. Clair, EW. Systemic Lupus Erythematosus.
Med Clin of N America. Vol 81. No1. Jan 1997 |
| Hinchey, JA. Sila, CA . Cerebrovascular complications of rheumatic
disease. Rheumatic Diseases Clin of N America. Vol 23. No 2. May 1997. |
| Thiagarajan, P. Shapiro, SS. Lupus anticoagulants and antiphospholipid
antibodies. Hematology/oncology Clin of N America. Vol 12. No. 6. Dec 1998. |
| Petri, M. Pathogenesis and treatment of the Antiphospholipid antibody
Syndrome. Med Clin of N America. Vol 81. No 1. Jan 1997. |
| Biller, J. Antiphospholipid Antibodies and Stroke. American Academy of
Neurology Annual Meeting. 1999. |
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