RESEARCH - most aPL patients who develop acute thromboses also have other risk factors

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Follow-up study shows most aPL patients who develop acute thromboses

also have other risk factors

Rheumawire

Aug 24, 2004

Janis

Cadiz, Spain - Antiphospholipid antibody (aPL) detected during routine

screening in otherwise asymptomatic patients is of limited clinical

relevance and is not a red flag predicting the need for long-term,

intensive anticoagulation, according to research in the August 2004

issue of the Journal of Rheumatology [1].

Dr A Giron- (Hospital Universitario Puerta del Mar, Cadiz,

Spain) writes, " Differences between patients [with the antiphospholipid

syndrome, APS] and asymptomatic carriers with aPL are at least partially

dependent on the proportion of coincident vascular risk factors. "

The problem of predicting which patients with APS are likely to develop

recurrent thromboembolism and which might be spared high-intensity,

long-term anticoagulant therapy remains a dilemma in clinical practice.

Antiphospholipid antibodies (aPL) are also present in about 2% of the

healthy population.

Giron- et al examined this problem in a prospective study of 404

subjects, 226 with primary or secondary APS and 178 of whom were

asymptomatic aPL carriers. Patients with APS and thrombosis were treated

with dicumarin to a target international normalized ratio (INR) of about

3.0. Asymptomatic carriers were treated with low-molecular-weight

heparin or aspirin only for prophylaxis during periods of increased

thrombosis risk, such as surgery, immobilization, or pregnancy. Patients

were followed for 36 months.

In the patients with secondary APS, the associated diseases were

systemic lupus erythematosus (n=37), primary Sjögren's syndrome (n=9),

progressive systemic sclerosis (n=5), rheumatoid arthritis (RA) (n=4),

mixed connective tissue disease (n=2), and other diseases (n=9).

Nineteen patients had infectious diseases, including 4 with human

immunodeficiency virus (HIV), 6 with chronic hepatitis virus C (HCV),

and 9 with both HIV and HCV. Patients with primary and secondary APS had

similar baseline percentages of venous and arterial thrombosis and of

recurrent fetal loss.

At the time of the first thrombotic event, 50% of patients with APS had

coincident risk factors for thrombosis vs 27.5% of those who were

asymptomatic aPL carriers (p<0.001). Venous thrombosis was the main

clinical finding in both primary and secondary APS. Those with venous

thrombosis were more likely to have had previous surgery or prolonged

immobilization, while those with arterial thrombosis were more likely to

have had hypercholesterolemia or arterial hypertension.

During the 36-month follow-up, 18 APS patients died, all within the

first 3 months. All 9 deaths among those with primary APS were related

to APS, but only 1 of the 9 deaths in those with secondary APS was

related to APS.

Of the 208 surviving APS patients, 3 had recurrences of deep vein

thrombosis of the lower extremities, all in the first 3 months and all

in the same extremity as the first event. In all 3 cases, the INR at the

time of the second event was lower than 2.5. Giron- notes that

no recurrent thromboses occurred in APS patients whose anticoagulation

reached the target level.

Anticoagulation was interrupted due to bleeding complications in 4

patients, including 1 fatal massive hemoptysis in a patient with

bronchiectasis. In all 3 cases the INR was 3.0-3.6 at the time of the

bleed.

The investigators monitored laboratory abnormalities over the 36-month

follow-up and found that the proportion of APS with persistence of

anticardiolipin antibodies (aCL) or lupus anticoagulant (LAC) decreased

steadily over that time, as did the same anti bodies in the patients

with asymptomatic aPL. " At the end of follow-up, only 84.6% of APS

patients and 78.0% of [asymptomatic aPL] patients maintained at least 1

aPL, " they report.

Giron- concludes, " In asymptomatic aPL carriers, a zero

incidence of thrombotic episodes could be predicted if these specific

measures of prevention are applied. " He proposes patients in whom the

disappearance of aPL has been maintained might be candidates for

something less intensive than indefinite anticoagulation.

In an accompanying editorial [2], Dr Mark A Crowther (McMaster

University, Hamilton, ON) notes that this study provides important new

information about APS but charges that the researchers have reached some

" unwarranted, potentially dangerous conclusions. " Crowther points out

that prospective cohort studies such as this " cannot provide evidence of

therapeutic efficacy. "

" t is wrong to conclude from this study that antithrombotic

prophylaxis prevented thrombosis: patients may not have been destined to

have this complication and, in fact, the use of inappropriately

intensive antithrombotic prophylaxis (for example, the use of high-dose

prophylaxis, 1 mg/kg, as described by the authors) may cause avoidable

bleeding complications in such patients, " Crowther warns. He points to

other recent studies showing that the overall risk of recurrent

thrombosis in APS patients was lower in those assigned to

standard-intensity warfarin (with a target INR of 2.0 to 3.0) than in

those given high-intensity warfarin.

Sources

Giron- JA, del Rio EG, C, et al.

Antiphospholipid syndrome and asymptomatic carriers of antiphospholipid

antibody: prospective analysis of 404 individuals. J Rheumatol 2004;

31:1560-1567.

Crowther MA. Antiphospholipid antibody syndrome:

Further evidence to guide clinical practice? J Rheumatol 2004;

31:1474-1475.

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org