Unusual Manifestations of the Antiphospholipid Syndrome

Abstract

The classical clinical picture of the antiphospholipid syndrome (APS) is characterized by venous and arterial thromboses, fetal losses and thrombocytopenia, in the presence of antiphospholipid antibodies (aPL), namely lupus anticoagulant (LA), anticardiolipin antibodies (aCL), or antibodies to the protein "cofactor" b2 glycoprotein I. Single vessel involvement or multiple vascular occlusions may give rise to a wide variety of presentations. Any combination of vascular occlusive events may occur in the same individual and the time interval between them also varies considerably from weeks to months or even years. Deep vein thrombosis, sometimes accompanied by pulmonary embolism, is the most frequently reported manifestation in this syndrome. Cerebrovascular accidents-either stroke or transient ischemic attacks-are the most common arterial thrombotic manifestations. Early and late fetal losses, premature births and pre-eclampsia are the most frequent fetal and obstetric manifestations. Additionally, several other clinical features are relatively common in these patients, i.e., thrombocytopenia, livedo reticularis, heart valve lesions, hemolytic anemia, epilepsy, myocardial infarction, leg ulcers, and amaurosis fugax. However, a large variety of other clinical manifestations have been less frequently described in patients with the APS, with prevalences lower than 5%. These include, among others, large peripheral or aortic artery occlusions, Sneddon's syndrome, chorea, transverse myelopathy, intracardiac thrombus, adult respiratory distress syndrome, renal thrombotic microangiopathy, Addison's syndrome, Budd-Chiari syndrome, nodular regenerative hyperplasia of the liver, avascular necrosis of the bone, cutaneous necrosis or subungual splinter hemorrhages. In this article, some of these "unusual" manifestations are reviewed.

Autoantibodies against the fibrinolytic receptor, annexin 2, in antiphospholipid syndrome

“…A large variety of other manifestations with prevalence lower than 5% has been described, including Sneddon syndrome, chorea, transverse myelopathy, adult respiratory distress syndrome, renal thrombotic microangiopathy, Addison syndrome, Budd-Chiari syndrome, nodular regenerative hyperplasia of the liver, avascular necrosis of the bone, cutaneous necrosis, and subungual splinter hemorrhages. 5 APS affects mainly young individuals, most of whom require lifelong anticoagulation. In the primary syndrome there is no evidence of underlying disease, 6 while the secondary syndrome exists mainly in the setting of systemic lupus erythematosus (SLE).…”

Chorea

“…Despite SLE or PAPS being described as the prototypes of autoimmune choreas (Quinn and Schrag, 1998), several reports show that chorea is seen in no more than 1--2% of large series of patients with these conditions (Asherson and Cervera, 2003;Sanna et al, 2003). Autoimmune chorea has rarely been reported in the context of paraneoplastic syndromes associated with anti-Hu and/or anti-CRMP5 antibodies in rare patients with small-cell lung carcinoma (Kinirons et al, 2003;Dorban et al, 2004).…”

Antiphospholipid syndrome in patients with systemic lupus erythematosus treated by autologous hematopoietic stem cell transplantation

“…In all 28 patients with APS, the type and number of pre-HSCT nonthrombotic APS-associated features included LSE (2), LR (3), calciphylaxis (2), thrombocytopenia (6), seizures (6), cranial nerve palsies (4), myelitis/transverse myelitis (4), ataxia (1), hallucinations (1), intractable headaches (2), multiple TIAs (1), and silent CVAs (1; Table 1). After HSCT, most nonthrombotic APS-related symptoms improved or stabilized (myelitis [3], ataxia [1], cranial nerve palsies [4], hallucinations [1], headache [1], calciphylaxis [2], LR [1]) and have not recurred (LSE [2], TIA [1], seizures [5], and thrombocytopenia [3]; Table 3). One patient with intractable headache and 2 with LR continue to manifest these APS features.…”

“…Other manifestations associated with APS but not part of the Sapporo criteria for definite APS include thrombocytopenia, hemolytic anemia, cardiac valve disease (Libman-Sacks endocarditis [LSE]), livedo reticularis (LR), and various neurologic manifestations including intractable headaches, migraines, seizures, chorea, transient ischemic attacks (TIAs), cerebrovascular accidents (CVAs), amaurosis fugax, dementia, psychosis, depression, transverse myelitis, and a multiple sclerosis-like disease. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] With the exception of anticoagulation, there is no standard therapy for APS. Current therapy for APS-related thrombosis is life-long anticoagulation with warfarin adjusted for an international normalization ratio greater than 2.0 to 3.0 to reduce the risk of recurrent thrombi despite the potential for serious bleeding complications.…”