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There are limited data on the occurrence of criteria and noncriteria antiphospholipid antibodies (aPLs) in patients with malignancies of the female reproductive tract. Our observations confirmed the frequent presence of criteria and noncriteria aPLs in patients with uterine malignancies (UMs). We found significant differences in the occurrence of the particular aPLs between patients with UMs and those with noncancerous gynecological diseases (NCGDs). The noncriteria aPLs (against phosphatidic acid, phosphatidylserine, annexin V, and prothrombin) are more frequently observed in patients with UMs than in patients with NCGDs. However, the criteria aPLs did not significantly differ between the UM and NCGD groups.

Introduction

Thrombosis is a common complication observed in patients with malignancies.^1-3 Several factors responsible for the development of thrombosis have been identified. Interactions between cancer cells, coagulation mechanisms, and the immune system may play an essential role in initiating thrombotic processes accompanying tumors.^4-9

Women with reproductive tract malignancies, including uterine malignancies (UMs), are at high risk for thromboembolic complications also because of comorbidities, the advanced clinical stage of the disease at the time of diagnosis, disease duration, the scope of the surgery (performed via laparotomy or laparoscopy), and the need for long‑term postoperative immobilization.¹⁰

The role of the immune system in neoplasia and antitumor defense is well established.^11-15 Furthermore, there have been numerous reports on thrombotic complications associated with the presence of criteria antiphospholipid antibodies (aPLs) in patients with cancer.^16-19 Although the exact relationship between aPLs and malignancies is unclear, the presence of aPLs in cancer patients may contribute to an increased thromboembolic risk. There are limited data on the presence of aPLs and their association with thrombosis accompanying female reproductive tract tumors.^16,20

Antiphospholipid antibodies are serological markers of immunization and thrombotic risk in patients with antiphospholipid syndrome (APS). The diagnosis of APS usually involves the detection of criteria aPLs including immunoglobulin M (IgM) and immunoglobulin G (IgG) classes of anticardiolipin antibodies, anti–β2‑glycoprotein I antibodies, and lupus anticoagulants, as well as thrombotic complications.²¹

As emphasized in the literature, the assessment of the thrombotic complication risk should be supplemented with the detection of noncriteria aPLs, including anti–annexin V and anti‑phosphatidylserine / prothrombin complex, the presence of which may be associated with the increased risk of thrombosis.^5,16,22 To date, the role of noncriteria aPLs in the pathogenesis of thrombosis in the course of gynecological malignancies remains unclear.

In our study, we aimed to determine whether criteria and noncriteria aPLs are present in patients with UMs and related to the thrombotic risk, as compared with patients with noncancerous gynecological diseases (NCGDs).

Patients and methods

Our study involved 151 women admitted to the Department of Gynecological Oncology and Gynecology in the years 2015 to 2017. The study patients were admitted for the diagnosis and treatment of female reproductive organ lesions suggestive of cancerous or nonmalignant lesions of the adnexa. All patients were deemed eligible for surgical treatment.

The day before their scheduled surgery, a blood sample from each patient was collected in a clot tube. Each blood sample was centrifuged at 1008 relative centrifugal force for 10 minutes, and then the serum was frozen at –70 °C and stored for immunoassays for selected aPLs.

Surgery (via laparotomy or laparoscopy) was performed in 151 women, and the final diagnosis for each patient was based on the postoperative histological examination of the specimens. The postoperative histological diagnoses of the study patients are shown in Supplementary material, tables S1 and S2.

The patients were divided into 2 groups: the UM group of women with diagnosed UMs (n = 70) and the NCGD group of women with diagnosed nonmalignant genital organ pathology (n = 81). The mean (SD) age of the patients was 59.8 (12.6) years in the UM group and 45.1 (14.7) years in the NCGD group (P <0.001).

The comorbidities and thrombotic risk factors of the study patients are presented in table 1. In patients with UMs, hypertension, obesity, type 2 diabetes, and heart failure—the characteristic features of metabolic syndrome (MetS)–were more frequently recognized than in patients with NCGDs.