9. Clinical significance of thrombocytopenia in APS

Interestingly, the presence of thrombocytopenia in patients with APS is not typically associated with haemorrhagic complications; rather it can trigger thrombotic events. Even more, it has been proven that the more severe the thrombocytopenia, the higher the probability of future thrombosis.

In a retrospective study 138 patients were enrolled with positive aPL without fulfilling clinical criteria for APS, after a mean follow-up of 146 60.3 months, 29.4% with thrombocytopenia developed thrombosis. They concluded that aPL-positive patients who develop thrombocytopenia have a potential risk of developing thrombosis [39].

Platelet activation plays an essential role in the development of atherosclerosis. In case of arterial thrombosis, the role of platelets is also essential. Continuous platelet activation in patients with APS may be involved, among other factors, in accelerated atherosclerosis. Moreover, atherosclerosis and its thrombotic complications may be mediated by local secretion of molecular effectors embedded or packed into microvesicles from the platelet surface [40].

A fundamental role of platelets and platelet activation in the process of thrombosis generation of APS patients has been supported by several data. These data suggest that aPL antibodies do not interact with circulating platelets in these patients. Instead, anti-β2-GPI-β2-GPI complexes bind exclusively to the platelet thrombus and not to the endothelium, a phenomenon leading to the amplification of platelet activation [29]. A possible explanation might be that aCL antibodies are able to bind the lipid component of platelet membrane only after platelet activation. In fact, major binding targets are the anionic phospholipids phosphatidyl-serine (PS), phosphatidylinositol (PI), and phosphatidyl-ethanolamine (PE), located in the inner surface of the platelet lipid membrane that becomes exposed and accessible to anti-β2-GPI antibodies after platelet activation.

Immune-thrombocytopenic purpura (ITP) is the most frequent cause of "megakaryocytic" thrombocytopenia. It is typically an exclusion diagnosis: when we cannot find any other reason of decreased platelet number, and there are megakaryocytes in the bone marrow we consider ITP. Thrombocytopenia is often experienced in pregnancy, affecting up to 10% of all pregnancies [44]. The causes of pregnancy-specific thrombocytopenia are gestational thrombocytopenia,

The most common cause of thrombocytopenia in pregnancy is gestational thrombocytopenia (75% of all cases) [45]. It may be difficult to differentiate from ITP, which also presents frequently during pregnancy, mainly in the first and second trimester. However, gestational thrombocyto-

third trimester, and is not related to adverse events for the mother and new-born. In some cases, pregnancy might lead to worsening of thrombocytopenia in patients with ITP [46]. This may be caused by the effects of the hormonal milieu of pregnancy on the reticuloendothelial system.

Thrombocytopenia is usually mild during pregnancy and is caused mainly by haemodilution. However, ITP, or SLE, even APS can start during pregnancy. Therefore complete examination of the patient, thorough laboratory checking, detailed medical history and careful follow-up is crucial.

The first task is to exclude concomitant SLE, or ITP, and ascertain whether thrombocytopenia refers to an increased activation of the coagulation system or an elevated tendency of bleeding. If it has been proven that thrombocytopenia is the manifestation of APS, it might have great

As thrombocytopenia is usually mild and if it predicts later thrombosis, usually APS can be treated by standard therapy. Patients can be given platelet aggregation inhibitors and/or anticoagulant therapy. Anti-thrombotic treatment should be stopped only in case of severe

In the presence of severe thrombocytopenia, rituximab represents a unique drug which can balance the effect of bleeding and thrombosis. By reducing the production of autoantibodies, rituximab can simultaneously raise the platelets and reduce the chance of thrombosis. Rituximab can supersede splenectomy as a second-line therapy in this group of patients [47]. In case of SLE-associated APS, when severe thrombocytopenia is generated by disease activation SLE should be treated with high-dose glucocorticoids, IVIG, immunosuppressive agents

CAPS is a life-threatening disease that requires very aggressive treatment. The treatment strategy is based on the combination of anticoagulation, glucocorticoids, plasma exchange and/or intravenous immunoglobulin, the so-called triple therapy. In refractory cases or in those with initial life-threatening situation, rituximab may be an effective option [15]. Recently, some cases of CAPS have been effectively treated with the addition of eculizumab to the triple therapy [50].

/L, from the mid-second or

Antiphospholipid Syndrome and Thrombocytopenia http://dx.doi.org/10.5772/intechopen.72509 61

pre-eclampsia, HELLP syndrome and acute fatty liver of pregnancy.

penia generally causes mild thrombocytopenia, usually >70 109

13. How to treat thrombocytopenia in APS?

importance: it can predict later thrombosis.

thrombocytopenia or bleeding [34].

and plasma exchange [48, 49].
