**6. Antiphospholipid antibodies in cancer**

The relationship between thrombosis and cancer was first established by Trousseau in 1865. Since then, numerous studies have shown that thromboembolism is a common complication of cancer, occurring in 15% of all cancer patients [46, 47]. Despite extensive research and modern interventions, thromboembolic disorders are still a major cause of morbidity and mortality in these patients. The risk of thromboembolic events is four times higher in cancer patients than in the general population and this risk is further increased in patients undergoing chemotherapy [47, 48]. Much of this high risk is attributed to the cancer itself. However, patient-related factors such as age, performance status, body mass index, underlying comorbidities, and therapy are also the important factors. The biological origin of thromboembolic events is related to the pro-coagulant, hypoxic, and inflammatory state associated with tumors, especially in advanced stages [49]. Several mechanisms contribute to the hypercoagulable state observed in cancer, resulting in a complex interplay of various factors, including tissue factors, platelet and endothelial activation, coagulation abnormalities, procoagulants secreted by tumor cells, abnormal blood flow, and abnormal tumor angiogenesis [46, 50]. The question arises whether the presence of aPL further increases the thromboembolic risk in patients with malignancies.

A high prevalence of aCL, anti-β2GPI, LA, anti-phosphatidylcholine, antiphosphatidylserine, anti-phosphatidylinositol, anti-phosphatidylethanolamine, and anti-prothrombin antibodies has been observed in patients with various types of hematologic malignancies and solid tumors [47]. Therefore, the already increased risk of thrombosis in cancer patients is even higher for carriers of aPL. The reported prevalence of elevated aPL levels in cancer patients varies from less than 5%, which is similar to the prevalence observed in healthy individuals, to as high as 70% [47]. This dramatic range is due in part to different methods being performed, differences in study design, and inconsistent definitions of aPL positivity in the medical literature. In general, aPL tests are highly heterogeneous and poorly standardized. In addition, most studies examined the prevalence of aPL only once and did not repeat the test after 3 months, so the frequency may be overestimated. A recent systematic review of observational studies found an increased risk of developing aPL in patients with gastrointestinal, genitourinary, and lung cancer, leading to thromboembolic events and death [51]. In addition, a 17-year observational study of 1592 non-thrombotic women with three consecutive spontaneous abortions before the 10-week gestation or fetal death at or after 10-week gestation showed that the risk of cancer was significantly higher in women with a history of obstetric APS than in the general population [52]. Recently, one research group investigated the presence of criteria and non-criteria aPL in patients with uterine malignancies [53]. The authors found that non-criteria aPL (against phosphatidic acid, phosphatidylserine, annexin V, and prothrombin) are more common in patients with uterine malignancies (UM) than in patients with non-cancerous gynecological diseases (NCGD). In contrast, the criteria aPL did not differ significantly between UM and the NCGD group. It is interesting to note that several studies associate non-criteria aPL, especially antiprothrombin antibodies, with obstetric complications, while they could not confirm the association with either anti-β2GPI or LA [11, 12].

In conclusion, aPL levels appear to be elevated in patients with various malignancies, increasing their risk for thromboembolic events. In the future, it would be important to conduct well-designed large-scale population studies as well as longitudinal studies on patients with various cancers to determine the true risk and confirm whether the increased prevalence of aPL positivity is transient. Although aPL positivity may help assess the risk of blood clots, there are currently no strong data to recommend aPL screening in cancer patients.
