Antiphospholipid Antibodies Associated with Malignancies: Clinical and Pathological Characteristics of 120 Patients

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Objective

To describe the different types of malignancies associated with antiphospholipid antibodies (aPL).

Methods

We performed a computer-assisted (MEDLINE, National Library of Medicine, Bethesda, MD) search of the literature from 1966 to 2003 to identify all cases of malignancies having aPL.

Results

One hundred twenty patients were found. The mean age was 56 ± 17 years (range 5 to 88). Sixty-two (52%) patients were men and 58 (48%) were women. A heterogeneous group of malignancies were found. Regarding hematological malignancies, 10 (8%) patients suffered from B-cell lymphoma, 8 (7%) from spleen lymphoma, 7 (6%) from chronic myeloid leukemia, and 6 (5%) from non-Hodgkin’s lymphoma (NHL). Regarding solid tumors, renal cell carcinoma was diagnosed in 7 (6%) patients, primary tumor with unknown origin in 7 (6%), lung adenocarcinoma in 6 (5%), breast carcinoma in 6 (5%), and melanoma in 6 (5%). The main aPL-related manifestations were thrombocytopenia (25%), cerebrovascular accidents (24%), deep vein thrombosis (19%), pulmonary embolism (15%), and heart valve lesions (9%). In 17 cases, catastrophic antiphospholipid syndrome was considered to be triggered by the malignancy. Seventy-one (63%) of 113 patients recovered or are still alive after cancer treatment. Twenty-three (35%) of 65 patients achieved aPL remission after proper treatment of the malignancy.

Conclusions

It is important to bear in mind, especially in elderly patients, that thrombotic events associated with aPL can be the first manifestation of malignancy. At the same time, the presence of aPL in patients with malignancies has important implications in their treatment and prognosis.

Section snippets

Patients and Methods

Patients were identified by a computer-assisted (MEDLINE, National Library of Medicine, Bethesda, MD) search of the literature to locate all cases of malignancies having aPL published in English, Spanish, French, German, and Italian. From 1966 to 1983, we included cases with malignancies and false-positive test for syphilis (BFP-STS) and/or LA. Since 1983 (when APS was first defined), we also included cases with aCL, and since 1990 through November 2003, we also included those cases with

General Characteristics

One hundred twenty patients were identified in the literature (12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96). The different types of malignancies associated with aPL are listed in Table 1, Table 2.

Discussion

Patients with cancer represent 20% of all patients in whom DVT and PE are diagnosed (98). In cancer, tumor cells can activate the coagulation system directly, through interactions with platelets, clotting, and fibrinolytic systems to generate thrombin. A series of endothelial factors, such as fibrin and tissue factor (TF), play a role in the clotting formation mediated via fibrin deposition and platelet activation. It has been postulated that aberrant TF expression plus disregulation of

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      A wide spectrum of malignancies are associated with APS, including both solid and hematologic malignancies. The largest review to date lists B-cell lymphoma and renal cell carcinoma as the most common malignancies, with 10 cases of B-cell lymphoma associated with APS and 7 cases of renal cell carcinoma associated with APS.5 In addition, the presence of antiphospholipid antibodies may presage a diagnosis of WM.7,8

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      Additionally, another patient developed breast cancer and eventually it was postulated that patients presenting the clinical manifestations of APS are at increased risk for developing malignancies [31]. This finding was later supported by Gómez-Puerta et al. [10] who observed that 34.1% and 41.6% of the patients with aPLs developed different types of haematological malignancies and solid tumours, respectively. Endler et al. [32] evaluated a large cohort of subjects (n = 4756) with positive-aCL antibodies where 184 subjects died (based on the Austrian Death Registry) where the cancer-related mortality was increased at 2.6-fold.

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