Wai Khoon Ho

Introduction The antiphospholipid syndrome (APS) is characterized by thrombosis or pregnancy morbidity, and the detection in the blood of at least one of three antiphospholipid antibodies (lupus anticoagulant, or anticardiolipin or anti‐β₂‐glycoprotein I antibodies). Diagnosing APS is important so that secondary prophylaxis may be administered to reduce risk of recurrent thrombosis and/or pregnancy morbidity. In addition to APS‐defining antibodies, there may be additional autoantibodies that have a role in thrombosis and/or pregnancy morbidity. Furthermore, some patients have clinical manifestations highly suggestive of APS but are persistently negative for the APS‐defining antibodies (“seronegative APS”) and instead, have other autoantibodies. Antiannexin A5 (aANXA5) autoantibodies have been associated with increased risk of thrombosis and pregnancy morbidity; levels are also reportedly higher in patients with venous thrombosis compared with healthy controls. The prevalence of aANXA5 among patients with unprovoked venous thrombosis is not well‐documented and determination of the frequency of aANXA5 is the objective of this study. Methods We analysed sera from 148 patients with unprovoked venous thrombosis who had undergone routine laboratory testing for the present APS‐defining antibodies. Results aANXA5 IgG and IgM were present in 6% and 1%, respectively. Conclusion Prevalence of these antibodies in unprovoked venous thrombosis is comparable with frequencies reported in healthy individuals and is far lower than the prevalence in women with pregnancy morbidity. This may indicate lack of association with venous thrombosis, however, adequately powered case‐control studies will be required to resolve this and prevalence data from this study will assist in the design of such studies.

The anti-phospholipid syndrome (APS) is defined by the laboratory detection of at least one of three anti-phospholipid autoantibodies (lupus anticoagulant, or anti-cardiolipin or anti-β₂-glycoprotein I antibodies) in the clinical setting of thrombosis or pregnancy morbidity in a patient. Recognising APS and administering appropriate secondary thromboprophylaxis is important to reduce risk of recurrent thrombosis and/or pregnancy morbidity. In some instances, patients having clinical manifestations highly suggestive of APS are persistently negative for these antibodies but instead have other autoantibodies. Autoantibodies directed against prothrombin (PT) have been associated with increased thrombotic risk and comprise anti-prothrombin (aPT) and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies. Detection of aPT and aPS/PT may help stratify patients for more effective treatment, however, their prevalence among patients with unprovoked venous thromboembolism (VTE) is unknown and determination of their frequencies is the objective of this study. Sera from 148 patients with unprovoked VTE were analysed. Autoantibodies directed against PT collectively, aPT and aPS/PT were present in 24.3%, 14.9% and 13.5%, respectively. Prevalence of these autoantibodies in unprovoked VTE is much lower compared to cohorts comprising mainly patients with systemic autoimmune disorders. Detection of these autoantibodies in unprovoked VTE has potential therapeutic implications for patients including the duration of anticoagulation and administration, or otherwise, of direct oral anticoagulants. Data from this study will assist in the design of future clinical studies to estimate risk of recurrent VTE and to determine optimal management.

There is a significantly increased risk of pregnancy complications in women with anti-phospholipid syndrome (APS). The risk is further heightened in those with previous arterial or venous thromboembolism and so-called ‘triple positivity’ for anti-phospholipid antibodies (i.e., when lupus anticoagulant, and anti-cardiolipin (aCL) and anti-β₂ glycoprotein-I (anti-β₂Gp-I) antibodies are all detected). Management of these cases is extremely difficult and little is available in the medical literature to guide therapy. This report describes the use of regular plasma exchanges (PEx) to bring about a successful pregnancy outcome in a woman with secondary APS and previous recurrent miscarriages. The patient was also anticoagulated with enoxaparin and administered aspirin, prednisolone, azathioprine and hydroxychloroquine. Through regular PEx and immunomodulation therapy, levels of aCL and anti-β₂Gp-I antibodies were monitored and documented to fall as pregnancy progressed. Although the outcome in this case was successful, further experience is required before this regimen can be accepted as the standard of care for these patients at very high risk of pregnancy loss.

The clinical usefulness of laboratory testing of adult patients with venous thromboembolism (VTE) for heritable thrombophilia needs to be critically evaluated. At present, some clinicians use testin...

Venous thromboembolism, comprising deep vein thrombosis (DVT) and pulmonary embolism, is common in Australia and is associated with high morbidity. This article provides a summary of the risk factors for DVT of the lower limb and discusses the diagnosis of the condition using a diagnostic algorithm incorporating clinical assessment, D-dimer testing and imaging studies. It also briefly reviews the clinical significance of isolated distal lower limb DVT and superficial vein thrombosis. Many conditions in the lower limb mimic DVT. Diagnosing DVT on clinical grounds without objective testing is unreliable. Patients incorrectly diagnosed as having DVT may be subjected to unnecessary anticoagulation and its associated risks of bleeding. In contrast, there is a risk of thrombus extension and embolisation when DVT is missed or inappropriately treated.