1. About antiphospholipid syndrome

Antiphospholipid syndrome (APS) is characterised by arterial and venous thromboembolic events and pregnancy morbidity (mainly, recurrent foetal losses), in the presence of antiphospholipid antibodies (aPLs). APS (or Hughes' syndrome) was first described by GR Hughes in 1983 [1]. APS is a non-inflammatory autoimmune disease, or autoimmune thrombotic disorder, because autoantibodies

© 2018 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and eproduction in any medium, provided the original work is properly cited.

are generated against different epitopes of the participant of the coagulation system (mainly against phospholipid-binding proteins) that result in thrombosis. These antiphospholipid antibodies are a heterogeneous group of autoantibodies. Lupus anticoagulant (LA), anti-cardiolipin antibodies (ACA) and anti-β2 glycoprotein 1 (aβ2GPI) are the most important among them [2].

risks is important as aPLs are prevalently observed in various diseases or elderly population. Current risk-stratification tools are largely limited to the antiphospholipid antibody profile

Antiphospholipid Syndrome and Thrombocytopenia http://dx.doi.org/10.5772/intechopen.72509 55

Novel biomarkers that correlate with disease activity and potentially provide insight into future clinical events include domain 1 specific anti-β2GPI antibodies, antibodies to other phospholipids, or phospholipid-protein complexes (such as antiphosphatidylserine/prothrombin antibodies (aPS/PT)), and functional/biological assays such as thrombin generation, com-

Clinical risk scores (antiphospholipid score (aPL-S) and the Global Anti-phospholipid Syn-

Diagnosis of APS is based on the Sapporo criteria (proposed in 1999 and updated in 2006 after

These include at least one clinical and at least one laboratory manifestation of APS. Clinical criteria include objectively confirmed venous, arterial, or small vessel thrombosis, and/or obstetric morbidity including recurrent miscarriage, stillbirth, or intrauterine growth retardation.

The laboratory criteria require demonstration of a persistent presence of lupus anticoagulant (LA), anti-cardiolipin (ACA) or anti-2GPI antibody (IgG or IgM). Antiphospholipid antibody positivity can be stated if at least one of these antibodies could be detected twice, 12 weeks apart. LA is measured by the help of coagulation tests, while ACA and anti-β2glycoprotein 1 (aβ2GPI) are determined by means of ELISA. LA results are expressed as qualitative data and only strong positivity carries clinical significance. In case of ACA and aβ2GPI, antibody medium/high titres of IgM and/or IgG subtype have important clinical value (Table 1).

Clinical symptoms of APS include thrombosis in any blood vessel of any organ. Typically, thrombosis may recur and can present both in arteries and in veins. Anti-phospholipid anti-

Although thrombosis due to APS does not differ from thrombosis caused by any other factors, some other symptoms and signs may accompany to the elevated blood clotting: for example, if a patient presents with thrombosis and also has livedo reticularis, it is very likely that throm-

Besides, there are only a few situations when arterious and venous thrombosis present on the same patient. This and the recurrence of the thrombotic event is very likely refers to APS.

There are the so-called "non-criteria" clinical features of APS, such as livedo reticularis, cardiac valve disease, haematological manifestations (thrombocytopenia and haemolytic anaemia),

Non-criteria manifestations mean that the presence of these characteristic features of the disease is not a requisite of the diagnosis, or with other words, they are not the sine qua non of

nephropathy and neurological manifestations (migraine, chorea and epilepsy).

bodies represent the strongest thrombophiliac factors, mainly LA.

plement activation, levels of circulating microparticles, and annexin A5 resistance [17].

drome Score [GAPSS]) may also have value in predicting clinical events [18].

and traditional thrombotic risk factors.

a conference in Sydney, Australia) [19].

bosis is a manifestation of APS.

the diagnosis.

2. Diagnosis of APS

APS may be a secondary disease, as it frequently associates to systemic autoimmune diseases such as SLE and also to malignant lymphoproliferative diseases and chronic hepatic disorders [3]. On the contrary, APS can appear without any underlying disease, and in this case, it is called primary antiphospholipid syndrome.

Neurologic involvement in APS is common and can be manifested by headaches, memory impairment, dizziness, epilepsy and blurred vision, but the most common presentations are transient ischaemic attacks and ischaemic strokes. Some of them are not thrombotic manifestations but are generated by connection of aPL antibodies and an antigen in the nervous system [4].

There is a special form of APS: the obstetric antiphospholipid syndrome (OAPS). It is characterised clinically only by obstetrical morbidity: at least two unexplained miscarriages, three non-consecutive miscarriages, preeclampsia, placental abruption, foetal growth restriction, stillbirth, premature birth, or two or more unexplained in vitro fertilisation failures [5, 6].

Catastrophic antiphospholipid syndrome (CAPS) is rare, but very serious form of APS. The mortality rate is very high. CAPS is characterised by thromboses generating in two or more organs in a few days. That leads to infarction and necrosis of the affected tissues causing multiple organ failures [7].

Standard care for thrombotic APS is indefinite anticoagulation with a vitamin K antagonist [8]. There is currently insufficient evidence to recommend the routine use of direct oral anticoagulants (DOAC) in thrombotic APS [9].

The 13th Task Force recommendation for primary thromboprophylaxis in APS supports the use of aspirin [10]. A recent meta-analysis conducted on a total of 1208 asymptomatic patients with persistently positive aPL has shown that low-dose aspirin (LDA) is associated with significant risk reduction in arterial but not in venous thrombosis when compared to placebo [11]. Aspirin with low molecular weight or unfractionated heparin may reduce the incidence of pregnancy loss in obstetric APS [12]. Aspirin alone is advised for treating patients with aPLassociated stroke or acute myocardial infarction [13].

Treatment regimens of APS further include hydroxychloroquine, statins, B-cell inhibitors, complement inhibitors, blocking of aPL/B2 GPI receptors on target cells and tissue factor inhibitors [14].

A combined therapy of anticoagulation, glucocorticoids, plasma exchange and intravenous immunoglobulin (especially in the presence of infection) can be used in complicated cases of multiorgan failure due to thrombosis as in CAPS. Cyclophosphamide can also be used in CAPS in the presence of secondary autoimmune disease such as SLE [15]. Rituximab can also be used in refractory cases after failure or inability to take the above-mentioned combined therapies or in the presence of micro-angiopathic haemolytic anaemia [16].

However, the majority of aPL-positive patients do not have thrombosis. That is why the stereotypical treatment for APS patients should be avoided and stratification of the thrombotic risks is important as aPLs are prevalently observed in various diseases or elderly population. Current risk-stratification tools are largely limited to the antiphospholipid antibody profile and traditional thrombotic risk factors.

Novel biomarkers that correlate with disease activity and potentially provide insight into future clinical events include domain 1 specific anti-β2GPI antibodies, antibodies to other phospholipids, or phospholipid-protein complexes (such as antiphosphatidylserine/prothrombin antibodies (aPS/PT)), and functional/biological assays such as thrombin generation, complement activation, levels of circulating microparticles, and annexin A5 resistance [17].

Clinical risk scores (antiphospholipid score (aPL-S) and the Global Anti-phospholipid Syndrome Score [GAPSS]) may also have value in predicting clinical events [18].
