4. Role of platelets in APS

Thrombocytopenia is the most relevant non-criteria manifestation of APS.

≥1 clinical episode of arterial, venous or small vessel thrombosis.

≥1 unexplained death of a morphologically normal foetus ≥10 weeks of gestation

• severe preeclampsia or eclampsia defined according to standard definition;

For histopathological confirmation, thrombosis must be present without inflammation of the vessel

≥3 unexplained consecutive miscarriages <10 weeks of gestation, with maternal and paternal factors

Presence of antiphospholipid antibodies (aPLs), on two or more occasions at least 12 weeks apart and no more than 5 years prior to clinical manifestations, as demonstrated by ≥1 of the following:

• Medium to high-titre (>40 GPL or MPL, or >99th percentile) anticardiolipin IgG or IgM;

≥1 premature delivery of a morphologically normal foetus <34 weeks of gestation because of:

Thrombosis must be objectively confirmed.

• recognised features of placental insufficiency

• Lupus anticoagulant;

Table 1. Revised classification criteria for antiphospholipid syndrome [19].

(anatomic, hormonal or chromosomal abnormalities) excluded

• Anti-β2 glycoprotein-I (anti-β2GPI) IgG or IgM >99th percentile

activation, angiogenic imbalance and activation of immune cells [20].

prevalence is around 40–50 cases per 100,000 persons [24].

morbidity [16]. These data can underline the significance of APS.

diagnostic clinical criterion of APS.

wall

3. Epidemiology of APS

APS.

Vascular thrombosis

56 Thrombocytopenia

Pregnancy morbidity

Laboratory criteria

However, despite the pro-thrombotic nature of APS, thrombocytopenia is one of the most common non-criteria findings of the disease. Recently, thrombocytopenia is proposed to be a

In case of OAPS several disease processes may occur in the placentae of women with antiphospholipid syndrome due to the antiphospholipid autoantibodies, not only thrombosis and infarction, but also inflammatory events, mediated by cytokine release, complement

Presence of aPL Abs per se does not guarantee a patient will develop APS as only 8.1% of patients with aPL antibodies without a history of clinical thrombosis developed thrombosis during a 5-year follow-up period, suggesting that a patient needs an additional insult to develop the clinical disease [21, 22]. The prevalence of the antibodies increases with age [23]. Forty percent of patients with APS have SLE. The prevalence of ACA in SLE is from 12 to 30%, and LA is found in 5–34%. From the patients with SLE and aPL antibodies 50–70% progress to

The incidence of the APS is around five new cases per 100,000 persons per year, and the

The aPLs are positive in approximately 13% of patients with stroke, 11% with myocardial infarction, 9.5% of patients with deep vein thrombosis and 6% of patients with pregnancy Platelets play a key role in APS-related thrombosis due to the presence of multiple receptors that can interact with anti-β2-GPI antibodies (especially apolipoprotein E receptor 2<sup>0</sup> (apoER2<sup>0</sup> ) and glycoprotein Ibα (GPIbα)) with consequent release of different pro-coagulant mediators such as thromboxane B2, platelet factor 4 (PF4) and platelet factor 4 variant (CXCL4L1) [28].

In case of APS, thrombosis results from a hypercoagulable state caused by activation of endothelial cells, monocytes and platelets. It has been demonstrated that platelets are required for enhanced activation of the endothelium and fibrin generation by the anti-β2GP1 autoantibody/β2GP1 complex. Thus, the first event is the activation of thrombocytes, endothelial cells are activated indirectly [29].

Platelet activation, a major contributing factor of arterial thrombosis in APS, might play a role in APS-related thrombosis in at least two ways:

First, due to the presence of multiple receptors that can interact with antibodies, platelets can facilitate the dimerisation of β2-GPI enhancing the coagulation response.

Second, platelets provide a surface for coagulation reactions [30].

The role of thrombocytes in the pathogenesis of APS is supported by the fact that circulating platelet- and endothelial-derived microparticle level are elevated in patients with primary APS [31].

Mouse models of APS have shown that platelets are the first target for circulating anti-β2-GPIβ2-GPI complexes, and the enhancement of endothelium activation is also platelet thrombusdependent [29].
