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BETWEEN A ROCK AND A HARD PLACE: THROMBOTIC RISK IN THE THROMBOCYTOPENIC PATIENT (CONSULTATIVE HEMATOLOGY) _________

Antiphospholipid antibody syndrome
Wendy Lim1
1

Department of Medicine, McMaster University, Hamilton, Ontario, Canada

The antiphospholipid antibody syndrome (APS) is defined by the persistent presence of antiphospholipid antibodies in patients with recurrent venous orarterial thromboembolism or pregnancy morbidity. Antithrombotic therapy is the mainstay of treatment given the high risk of recurrent thromboembolism that characterizes this condition. Despite the prothrombotic nature of APS, thrombocytopenia is present in a proportion of patients. which can complicate management and limit the use of antithrombotic therapy. The mechanism of APS-associatedthrombocytopenia is multifactorial and its relation to thrombotic risk poorly characterized. However, the presence of thrombocytopenia does not appear to reduce thrombotic risk in patients with APS, who can develop thromboembolic complications necessitating antithrombotic treatment. In these cases, treatment of the thrombocytopenia may be necessary to facilitate administration of antithrombotic agents.Clinical trials have demonstrated that patients with antiphospholipid antibodies and venous thromboembolism should be treated with vitamin K antagonists (warfarin); that ischemic stroke may be treated with aspirin or warfarin; and that women with recurrent pregnancy loss should receive prophylactic-dose heparin and aspirin. However, application of these trial results to patients with APS-associatedthrombocytopenia can be challenging since there are limited data on the optimal use of antithrombotic agents in this setting. Issues such as determining the platelet threshold at which antithrombotic agents can be safely used and managing patients with both bleeding and thromboembolic complications remain unresolved. Ultimately the risks and benefits of antithrombotic therapy, balanced against theseverity of the thrombocytopenia and its potential bleeding risks, need to be assessed using an individualized patient approach.

ntiphospholipid antibodies, including lupus anticoagulant (LA), anticardiolipin antibodies (aCL) and anti-β2-glycoprotein-1 (anti-β2-GP1) antibodies, are associated with an increased risk of arterial and venous thromboembolism. The antiphospholipid antibody syndrome(APS) is a prothrombotic condition characterized by the presence of these antibodies in patients with recurrent pregnancy morbidity and/or thromboembolic complications. Thrombocytopenia is a frequent finding in patients with APS, and balancing the need for anticoagulation when faced with significant thrombocytopenia can be a considerable challenge for clinicians managing such patients.

Aresults of clinical trials to an individual patient. It is notable that patients with APS may have other clinical characteristics, including thrombocytopenia, livedo reticularis, valvular heart lesions and nephropathy, but these features are not formally part of the consensus diagnostic criteria. Similarly, these patients may have antiphospholipid antibodies other than LA, aCL and anti-β2-GP1,including antibodies against prothrombin and other proteins or phospholipids that are not included in the current consensus criteria. Rarely, patients with antiphospholipid antibodies have multiorgan failure resulting from widespread thrombotic disease, known as catastrophic APS. Preliminary criteria for the classification of catastrophic APS have been published.2 The clinical manifestations,3 treatmentand prognosis4 of catastrophic APS are beyond the scope of this review.

Diagnosing APS
The diagnosis of APS is based on clinical criteria of pregnancy morbidity or thromboembolism, and laboratory findings of medium or high titer antiphospholipid antibodies that are present on two or more occasions at least 12 weeks apart (Table 1).1 These international consensus criteria were designed to...
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