Fw: Antiphospholipid Antibody Syndrome (APS)

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Subject: Antiphospholipid Antibody Syndrome (APS)

From pureheart@...Antiphospholipid Antibody Syndrome (APS) 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. 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. 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. Arterial thrombosis: Most common: Cerebral infarct, some strokes may be caused by cardiogenic emboli. Less common: Coronary, retinal, and visceral artery 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. 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. 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. APS & SLE Up to 50% of patients with SLE have antibodies to phospholipids. 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. Catastrophic Antiphospholipid antibody syndrome A rare fulminant form of the APS. Acute multiorgan system thrombosis of small and large vessels. 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. 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. 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. 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. 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. 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. Further Reading Antiphospholipid Antibody - definition & history - 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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