13. How to treat thrombocytopenia in APS?

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 anti-

Among aPL-positive patients, those with a low platelet count developed thrombosis more frequently than those without. Among aPL-negative patients, no difference was found in the

Beside thrombocytopenia, MCV alterations may have significant importance in APS. Though conformation of data is still lacking, there are evidences that platelets with increased MPV are more active than smaller platelets, with a greater pro-thrombotic potential because of higher levels of intracellular TXA2 and an increased pro-coagulant surface [41]. MPV is largely

MPV was found to be significantly higher in APS patients, especially in triple positive patients, as compared to controls. Moreover, the level of MPV above 7.4 fl was found to be an indepen-

Pseudo-thrombocytopenia should be excluded. Presence of fragmentocytes can refer to TTP. The observation of the characteristic "pentad" (fever, microangiopathic anaemia, thrombocytopenia, neurologic abnormalities and renal involvement) may strengthen the diagnosis.

Bone marrow examination can show out malignant haematological diseases such as multiple myeloma, or different kind of leukaemia, when there is no place for normal thrombopoiesis. In case of myelodysplastic syndrome (MDS), there are dysplastic features of the cells of megakaryocytic cell line and also morphological abnormalities of thrombocytes can be

Haemolytic anaemia is indicative of secondary APS due to SLE, or Evans syndrome. Otherwise, in case of SLE, not only haemolytic anaemia and thrombocytopenia may be found, but also aPL antibodies, without any clinical symptoms of APS. Other clinical symptoms of the systemic autoimmune disease or a history of thrombosis can help to differentiate, but it is not

bodies after platelet activation.

60 Thrombocytopenia

observed in the peripheral smear.

always an easy task.

10. Thrombocytopenia and risk stratification

11. Mean platelet volume (MPV) in APS

predictive value of thrombosis regardless of platelet count [29].

regarded as a useful surrogate marker of platelet activation [42].

dent predictor of thrombosis recurrence in patients with APS [43].

12. Differential diagnosis of thrombocytopenia in APS

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 importance: it can predict later thrombosis.

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 thrombocytopenia or bleeding [34].

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 and plasma exchange [48, 49].

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].

In case of pregnancy-associated APS, the health of the mother is considered always the more important. If there is a life-threatening situation, the pregnancy must be terminated. Pregnancy itself represents a higher thrombotic risk, so careful anticoagulation is extremely important. On the other hand, bleeding during delivery also should be avoided.

Conflict of interest

Author details

Budapest, Hungary

References

Klara Gadó<sup>1</sup>

There is no conflict of interest.

Medicine, Budapest, Hungary

1983;287:1088-1089

nology. 2015;6:205

\* and Gyula Domján<sup>2</sup>

\*Address all correspondence to: gadok@freemail.hu

of Physicians of London. 1994;28(4):301-304

1 Faculty of Health Sciences, Department of Clinical Studies, Semmelweis University of

Antiphospholipid Syndrome and Thrombocytopenia http://dx.doi.org/10.5772/intechopen.72509 63

2 Faculty of Medicine, 1st Department of Medicine, Semmelweis University of Medicine,

[1] Hughes GRV. Thrombosis, abortion, cerebral disease and lupus anticoagulant. BMJ.

[2] Pengo V, Tripodi A, Reber G, et al. Update of the guidelines for lupus anticoagulant detection: Subcommittee on Lupus Anticoagulant/antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and

[3] Petri M. Hughes syndrome: Antiphospholipid syndrome. In: Khamashta MA, editor. Hughes Syndrome Vol. 1. 2nd ed. London: Springer-Verlag London Ltd; 2006. pp. 22-28

[4] Hughes GR, Khamashta MA. The antiphospholipid syndrome. Journal of the Royal College

[5] Camarena Cabrera DM, Rodriguez-Jaimes C, Acevedo-Gallegos S, Gallardo-Gaona JM, Velazquez-Torres B, Ramírez-Calvo JA. Controversies concerning the antiphospholipid

[6] Levy RA, Dos Santos FC, de Jesús GR, de Jesús NR. Antiphospholipid antibodies and Antiphospholipid syndrome during pregnancy: Diagnostic concepts. Frontiers in Immu-

[7] Kazzaz NM, McCune WJ, Knight JS. Treatment of catastrophic antiphospholipid syn-

[8] Pengo V, Ruiz-Irastorza G, Denas G, et al. High intensity anticoagulation in the prevention of the recurrence of arterial thrombosis in antiphospholipid syndrome: 'PROS' and

Haemostasis. Journal of Thrombosis and Haemostasis. 2009;7(10):1737-1740

syndrome in obstetrics. Clinical Rheumatology. 2017;13(1):30-36

drome. Current Opinion in Rheumatology. 2016 May;28(3):218-227

'CONS'. Autoimmunity Reviews. 2012;11:577-580
