Antiphospholipid syndrome

Whereas (32 glycoprotein 1 ((J2-GPI) is the target of anticardiolipin antibodies, prothrombin is the antigen for most lupus anticoagulants. Both these antibodies are risk factors for both venous and arterial thrombosis. In addition, complications such as thrombocytopenia and recurrent miscarriages are manifestations of the so-called antiphospholipid syndrome (97). 

Although a mutation in an annexin has never been categorically proven to be the cause of a disease state, they have been implicated in pathologies as diverse as autoimmunity, infection, heart disease, diabetes and cancer. Annexinopathies were first described by Jacob H. Rand to describe the pathological sequelae in two disease states, die overexpression of annexin 2 in a patients with a haemorrhagic form of acute promyelocytic leukaemia, and the under-expression of annexin 5 on placental trophoblasts in the antiphospholipid syndrome. In this chapter we will outline some of the more recent observations in regard to these conditions, and describe the involvement of annexins in some other major causes of human morbidity... 

Cesarman-Maus, G., Rios-Luna, N.P., Deora, A.B., Huang, B., Villa, R., Del Carmen Cravioto, M., Alarcon-Segovia, D., Sanchez-Guerrero, J. and AK Hajjar, 2006, Autoantibodies against the fibrinolytic receptor, annexin 2, in antiphospholipid syndrome. Blood. 107(11) 4375—82. 

Lopez-Pedrera, C., Buendia, P., Cuadrado, MJ., Siendones, E., Aguirre, M.A., Barbarroja, N., Montiel-Duarte, C., Torres, A., Khamashta, M., and F. Velasco, 2006, Antiphospholipid antibodies from patients with the antiphospholipid syndrome induce monocyte tissue factor expression through the simultaneous activation of NF-kappaB/Rel proteins via the p38 mitogen-activated protein kinase pathway, and of the MEK-l/ERK pathway.Arthritis Rheum. 54(1) 301—11. 

Rand, J.H., Wu, X.X., Lapinski, R., van Heerde, W.L., Reutelingsperger, C.P., Chen, P.P., and T.L. Ortel, 2004, Detection of antibody-mediated reduction of annexin A5 anticoagulant activity in plasmas of patients with the antiphospholipid syndrome. Blood.l04(9) 2783-90. 

Dignat-George F, Camoin-Jau L, Sabatier F, et al. Endothelial microparticles A potential contribution to the thrombotic complications of the antiphospholipid syndrome. Thromb Haemost 2004 91 667-673. 

I 83 Wilson W, Gharavi AE, Koike T et al. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome, Arthritis Rheum 1999 42 1309-131 I. 

Antiphospholipid syndrome is a disorder of recurrent arterial or venous thrombosis, thrombocytopenia, hemolytic anemia, or a positive Coombs test, and in women recurrent idiopathic fetal loss, associated with raised concentrations of antiphospholipid antibodies. In systemic lupus erythematosus, the risk of this syndrome is about 40%, compared with a risk of 15% in the absence of antiphospholipid antibodies (539). However, only half of those with antiphospholipid antibodies have systemic lupus erythematosus, and the overall risk of the syndrome is about 30%. In patients who have antiphospholipid antibodies associated with chlorpromazine, there appears to be no increased risk of the syndrome. In contrast, in the primary antiphospholipid syndrome, the only clinical manifestations are the features of this syndrome. 

Lillicrap MS, Wright G, Jones AC. Symptomatic antiphospholipid syndrome induced by chlorpromazine. Br J Rheumatol 1998 37(3) 346-7. 

Kalashnikova LA, Nasonov EL, Stoyanovich LZ et al. (1994). Sneddon s syndrome and the primary antiphospholipid syndrome. Cerebrovascular Diseases 4 76-82 Kanter MC, Hart RG (1991). Neurologic complications of infective endocarditis. Neurology 41 1015-1020 Kaposzta Z, Young E, Bath PMW et al. (1999). Clinical application of asymptomatic embolic signal detection in acute stroke a prospective study. Stroke 30 1814-1818 Katzav A, Chapman J, Shoenfeld Y (2003). 

CNS dysfunction in the antiphospholipid syndrome. Lupus 12 903-907 Keung YK, Owen J (2004). Iron deficiency and thrombosis literature review. Clinical and Applied Thrombolysis and Hemostasis 10 387-391... 

Antiphospholipid syndrome (59) Antithrombin III deficiency Essential thrombocytosis Factor V mutation (39)... 

Pelletier, S., Landi, B., Piette, J.-C., Ekert, P, Coutellier, A., Desmoulins, C., Fadlallah, J.-R, Herson, S., Valla, D. Antiphospholipid syndrome as the second cause of non-tumorous Budd-Chiari syndrome. X Hepatol. 1994 21 76-80... 

Asymptomatic prolongation of the activated partial thromboplastin time associated with Inpus anticoagulant and a reduction in the coagulation activity of factors IX, XI, and XII occurred after 10 weeks of interferon alfa-2b and ribavirin in a 60-year-old woman with chronic hepatitis C (236). There were no arguments in favor of an antiphospholipid syndrome, and all the abnormalities normalized after withdrawal. 

Becker JC, Winkler B, Klingert S, Brocker EB. Antiphospholipid syndrome associated with inununo-therapy for patients with melanoma. Cancer 1994 73(6) 1621-4. 

A lupus-like syndrome with an antiphospholipid syndrome has been attributed to procainamide in a patient with pre-existing systemic sclerosis (54). 

The authors suggested that the pre-existence of systemic sclerosis in this case and the presence of allele HIA-DQBPl 0303 had increased the patient s susceptibility to the lupus-like syndrome and antiphospholipid syndrome. 

A lupus-like syndrome has occasionally been reported in patients taking quinidine (60,61,64). It usually presents with polyarthralgia, a raised erythrocyte sedimentation rate, and a raised antinuclear antibody titer. It can occasionally be associated with antihistone antibodies and a circulating coagulant. In two cases (65) the syndrome was associated with quinidine and not with procainamide. Lupus anticoagulant has been reported with the use of quinine and quinidine, and an associated antiphospholipid syndrome has been described (66). 

Lupus anticoagulant has been reported with the use of quinine and quinidine, and an associated antiphospholipid syndrome has been described (22). 

As discussed earlier, signs and symptoms such as fever, arthritis, and serositis are among the most common in patients with active disease. Therefore, in many patients with mild disease, initial treatment with a nonsteroidal anti-inflammatory drug (NSAID) is a logical choice. The choice of NSAlDs in SLE is empirical. The dose used should be adequate to provide anti-inflammatory effects, although low-dose aspirin may be useful in the management of patients with antiphospholipid syndrome. ... 

Lockshin MD, Sammaritano LR, Schwartzman S. Validation of the Sapporo criteria for antiphospholipid syndrome. Arthritis Rheum 2000 43 440-443. 

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