12. Differential diagnosis of thrombocytopenia in APS

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 observed in the peripheral smear.

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 always an easy task.

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

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 thrombocytopenia generally causes mild thrombocytopenia, usually >70 109 /L, from the mid-second or 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.
