Plasma Circulating Levels of Soluble P-Selectin and Thrombospondin-1 (TSP1) Are Elevated in Patients with Cancer and a Shortened Activated Partial Thromboplastin Time (APTT) without Clinical Evidence of Thrombosis: An Inexpensive and Simple Test (APTT) To Be Considered for Its Clinical Value.

Abstract

There is evidence of shortening of the APTT in patients afflicted with and without cancer, and cancer is a well known underlying condition associated with hypercoagulability. Increased levels of coagulation factors such as VIII, IX, XI, II, and fibrinogen have been demonstrated as independent risk factors for venous thromboembolism (VTE). However, there is evidence that high levels of circulating factor VIII levels are not the only determinant for a shortened APTT (Blood 2004; 104:3631) and likely the same case for the other factors including fibrinogen levels. A shortened APTT in a patient with cancer with no evidence of a thrombotic event could be of clinical value in particular when the cost of measuring individual coagulation factors previously identified as risk factors for VTE would be very high. A lack of understanding of the underlying mechanism leading to a shortened APTT in the absence of VTE limit its clinical use, particularly for the clinical management of the patient presenting at admission with this phenomenon in association with cancer. In this case-control prospective study, we have investigated a potential mechanism associated with a shortened APTT in patients with cancer without evidence of thrombosis. The rationale for this study was a previous observation supporting a functional role of TSP1 in the generation of thrombin on a cell surface (Thrombosis Research 2005; 116: 533). The study was comprised of 69 human subjects subdivided in three separate groups, Group I, was constituted by 23 normal human volunteers, Group II included 23 patients without a shortened APTT and cancer, Group III was comprised of 23 patients with cancer with a shortened APTT (see table). Groups I and II were matched with group III by age and gender. In addition patients in Group II were matched with Group III by the type of cancer. Laboratory measurements included APTT, D-Dimer, soluble E, L, and P-Selectins as well as TSP1. Platelet and neutrophil counts were determined by automated methods. Laboratory measurements demonstrating a significant difference in Group III when compared with Group I and II were P-Selectin and TSP1. These results were independent of the platelet count in Group III. However the significant elevated circulating levels in plasma of P-Selectin in Group III are evidence supporting platelet activation. There was a trend for higher levels of D-Dimer in Group III (P < 0.17) when compared with Group II (P< 0.76), in accordance with previous studies reported in the literature. In summary, this prospective study demonstrates a potential association of a shortened APTT in patients with cancer with elevated circulating levels of soluble P-Selectin and TSP1. Our laboratory is currently investigating in more detail this interesting finding as well as the prospective clinical follow up of patients included in Groups II and III.Plasma DeterminationsParameterGroup IGroup IIGroup IIIP ValueaPTT29.3±2.728.2±2.323±1.00.01sP-Selectin23.2±425.4±944.0±110.001TSP1382±39871±4961246±2950.001Normal Range APTT: 24.2–35.3 seconds