THE LUPUS ANTICOAGULANT

Franklin A. Bontempo, M.D., Medical Director, Coagulation Services

INTRODUCTION

Lupus anticoagulants (LA) are a heterogeneous group of clotting inhibitors that represent a clinical problem of growing importance.  These inhibitors are often discovered accidentally, such as when a prolonged partial thromboplastin time (PTT) is found during a pre-operative evaluation.  Most often, there are no clinical complications other than the need to explain the reason for the long PTT.  A minority of patients with LA have a hypercoagulable state manifested by recurrent thromboses or multiple spontaneous miscarriages.

definition

LA are anti-phospholipid antibodies, usually of the IgG or IgM type, that interfere with phospholipid-dependent coagulation tests.  Importantly, the clotting test abnormalities caused by LA are in vitro phenomena; the antiphospholipid antibodies of the LA react with the phospholipid preparations used to initiate clotting reactions.  In vivo clotting factor activities are not diminished and, except in extremely rare cases, there is no danger of a bleeding diathesis.  It should also be recognized that most patients with LA do not have lupus erythematosus or other systemic autoimmune disorders.

ETIOLOGY

The exact etiology of LA is unclear.  These antibodies are commonly found in asymptomatic elderly individuals.  Among patients with autoimmune disorders, those with SLE have the highest incidence (20-45%).  Patients with AIDS have an incidence of LA of at least 50%.  A number of drugs, most notably, procainamide (Pronestyl), hydralazine, INH, Dilantin, and phenothiazines, are known to induce LA.  The majority of affected patients, however, have no systemic autoimmune disease or any other underlying disorder and have no clinical manifestations.

LUPUS ANTICOAGULANTS & THROMBOSIS

A small percentage of patients with LA experience recurrent episodes of thrombosis, including cerebral, deep venous or renal vein thromboses, as well as pulmonary emboli, or arterial occlusions.  Depending upon the population studied, the incidence of thrombotic complications in patients with LA ranges from 5 to 20 percent.

LUPUS ANTICOAGULANTS & PREGNANCY

LA are associated with an increased risk of fetal loss, especially in the second trimester of pregnancy.  Placental infarction has been suggested as the cause of the failure to carry to term, but pathological analysis does not definitely support this contention.

LUPUS ANTICOAGULANTS & tHROMBOCYTOPENIA

An immune type thrombocytopenia has been observed in a small percentage of patients with LA; this may be due to reactions between antibodies and platelet membrane-associated phospholipids.

diagnosis

No single test is known to be definitive for a lupus anticoagulant.  As a result, a variety of tests and testing algorithms are used in an attempt to establish the diagnosis.  The typical screening test is a prolongation of the standard PTT that fails to correct when the patient’s plasma is mixed with normal plasma.  This suggests an inhibitor since normal plasma usually corrects any factor deficiency.  However, this screening alone is inadequate to establish the presence of an LA.  Many affected patients, especially pregnant women, have normal PTTs.  Conversely, occasional patients with a prolonged PTT that does not correct may have specific antibodies against individual clotting factors.  Thus, additional tests are needed both to establish and exclude the presence of LA. 

Other tests that aid in the recognition of LA include tests for antiphospholipid and anticardiolipin antibodies, the tissue thromboplastin inhibition index (TTI), the dilute Russell viper venom time (dRVV), the prothrombin time (PT), and the platelet neutralization procedure (PNP).  Standard clotting factor assays may also be performed; they can differentiate LA from the more clinically dangerous specific antifactor antibodies, such as antifactor VIII.

All of the forgoing tests either directly measure antiphospholipid antibodies or manipulate the amount of active phospholipid available to initiate the clotting cascade.  New tests for LA are currently being developed; they may be both more sensitive and more specific.

MANAGEMENT

When LA are found incidentally in asymptomatic patients, no therapy may be necessary.  In patients with drug-induced LA, discontinuing the agent will usually cause any abnormal clotting tests to revert to normal.

Several studies of small groups of non-randomized patients suggest that a combination of aspirin and prednisone or heparin alone may result in successful term pregnancy in women with recurrent fetal loss.  However, no randomized study has established the usefulness of either regimen.

Patients suspected of having recurrent thrombosis due to the “antiphospholipid antibody syndrome” may benefit from heparin, Coumadin, or aspirin and prednisone in an attempt to suppress any underlying autoimmune process.  The efficacy of this approach awaits further evaluation.

Copies of the Transfusion Medicine Update can be obtained by contacting Deborah Small at (412) 209-7320 or
by e-mail:  dsmall@itxm.org.