A 32-year-old woman comes to the emergency department due to chest pain and shortness of breath that woke her up this morning. The chest pain is sharp and worsens with inspiration. The patient has had no fever or cough but has had worsening right leg swelling over the past several days. Review of systems is positive for myalgias, joint pains, and facial rash brought on by sun exposure. Medical history includes 2 miscarriages at 12 and 16 weeks gestation. She takes no medications and does not use tobacco, alcohol, or illicit drugs. Temperature is 37.2 C (99 F), blood pressure is 152/86 mm Hg, pulse is 98/min, and oxygen saturation is 95% on room air. Physical examination shows clear lungs, normal heart sounds, and no abdominal organomegaly. The right lower extremity is swollen and tender to touch. CT angiography of the chest reveals pulmonary emboli. Which of the following additional laboratory findings is most likely to be present in this patient?
Diagnostic criteria for antiphospholipid-antibody syndrome (1 clinical & 1 laboratory criterion must be met) | |
Clinical | Vascular thrombosis
Pregnancy morbidity
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Laboratory |
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This patient has pulmonary emboli due to a right lower extremity deep venous thrombosis (DVT). Although risk of DVT is increased in several inherited and acquired conditions, this patient's history of fetal loss and signs of systemic lupus erythematosus (eg, myalgias, arthralgias, photosensitivity) suggest antiphospholipid-antibody syndrome (APS).
APS is characterized by the following:
Patients with antiphospholipid antibodies (particularly LA) generally have prolonged PTT because antiphospholipid antibodies bind the phospholipids used in most testing assays and prevent them from inducing coagulation. This laboratory artifact will not be fixed by a 1:1 mixing with normal plasma (unlike coagulation factor deficiency). However, adding phospholipids to the testing assay will eventually overcome the presence of the inhibitor and normalize the PTT. This is an indirect way of identifying LA antibodies; it is usually combined with other tests, such as the diluted Russell viper venom test or the kaolin clotting time test for diagnosis.
(Choice A) Patients with rheumatologic disease can develop autoantibodies to von Willebrand factor, leading to acquired von Willebrand disease (vWD). Acquired vWD is generally marked by easy bruising and mucosal bleeding (eg, epistaxis, gum bleeding, heavy menses), but fetal loss and thrombosis would be atypical.
(Choice B) D-dimer is a product of cross-linked fibrin degradation. Therefore, almost all patients (>95%) with ongoing thrombosis have elevated D-dimer levels. Low D-dimer would be highly unusual in the setting of pulmonary emboli and deep vein thrombosis.
(Choice C) Factor V Leiden mutation is an altered form of coagulation factor V that renders it resistant to the anticoagulant effects of activated protein C. Risk of thromboembolism and fetal loss is significantly increased, but factor V Leiden mutation is not linked with systemic lupus erythematosus and would not explain this patient's arthralgias, myalgias, and photosensitivity.
(Choice D) JAK2 mutation is present in most cases of polycythemia vera, which is associated with increased risk of thromboembolism. However, most cases occur in older individuals; in addition, it would not explain photosensitivity, myalgias, or arthralgias.
Educational objective:
Antiphospholipid-antibody syndrome is common in patients with systemic lupus erythematosus. It generally presents with thromboembolism and/or recurrent fetal loss. Positive testing for lupus anticoagulant (LA), anticardiolipin antibody, and/or beta2-glycoprotein-I antibody is diagnostic. Those with LA have prolonged PTT that does not improve with 1:1 dilution with normal serum (mixing test).