Association of Fibrinolytic Potential and Risk of Mortality in Cancer Patients.

Cancer is a leading cause of death, and the fibrinolytic system shows cooperative effects that facilitate the growth of tumors and the appearance of metastases. This prospective study aimed to evaluate the fibrinolytic potential in cancer patients and its association with mortality outcomes using the fluorometric method of simultaneous thrombin and plasmin generation. The study included 323 cancer patients and 148 healthy individuals. During the 12-month follow-up, 68 patients died. Compared to the control group, cancer patients showed alterations in thrombin production consistent with a hypercoagulability profile, and an increase in plasmin generation. Mortality risk was associated with two parameters of thrombin in both univariate and multivariable analysis: maximum amplitude (Wald 11.78, p < 0.001) and area under the curve (Wald 8.0, p < 0.005), while such associations were not observed for plasmin. In conclusion, this was the first study able to demonstrate the simultaneous evaluation of thrombin and plasmin generation in newly diagnosed untreated cancer patients. Patients with cancer have been observed to exhibit a hypercoagulable profile. During the study, two parameters linked to thrombin generation, MA and AUC, were identified and found to have a potential association with mortality risk. However, no associations were found with parameters related to plasmin generation.

Prolonged APTT of unknown etiology: A systematic evaluation of causes and laboratory resource use in an outpatient hemostasis academic unit.

BACKGROUND: A prolonged activated partial thromboplastin time (APTT) of unknown cause is one of the most frequent reasons why outpatients are referred for hemostasis consultation. Nevertheless, very few data are available on the relative contribution of individual causes of this common clinical scenario. Here, we present a systematic evaluation of all causes of APTT prolongation in a consecutive population of outpatients referred for specialized hemostasis consultation during a 14-year period. METHODS: All cases referred to an academic specialized hemostasis outpatient unit due to APTT prolongation of unknown etiology whose prolonged APTT was confirmed in the first visit were included in the study. Data were obtained from the electronic medical records. RESULTS: Among 187 consecutive patients, the most frequent causes were antiphospholipid antibodies in 22.6%, contact pathway factor deficiencies in 17.4%, other coagulation factor deficiencies in 11.6%, and vitamin K deficiency/liver disease in 11.6%. A definite cause was not identified in 22.1% of patients. Presence of antiphospholipid antibodies, and absence of bleeding symptoms were both associated with significantly longer APTT values compared to other categories/clinical scenarios. The investigation of each case required a mean of 18.2 additional tests per patient, with estimated costs ranging from US$191.60 to US$1055.60. CONCLUSIONS: Our results describe the main causes of APTT prolongation in outpatients, as well as estimates of resource use required to investigate this condition, thus providing evidence supporting the importance of measures to minimize the indiscriminate use of this assay.

Laboratory evaluation of patients with undiagnosed bleeding disorders.

The evaluation of patients with a bleeding tendency represents a challenge as the routinely available tests for evaluating bleeding disorders are limited, complicating the laboratory determination of the clinically observed bleeding tendency. As a result, some bleeding disorders remain undiagnosed. The aim of the study was to evaluate whether global coagulation tests would contribute to the laboratory analysis of patients with undiagnosed bleeding disorders. Patients were evaluated for coagulation and fibrinolysis activities by thrombin generation test and euglobulin lysis time. In addition, plasma activity of factor XIII, plasminogen, α-2 antiplasmin, plasminogen activator inhibitor-1, and thrombin-activatable fibrinolysis inhibitor was also obtained. Forty-five patients were included. Eight per cent presented a mild bleeding disorder and 20% a moderate bleeding disorder. The thrombin generation test results were similar between patients and controls. Euglobulin lysis time results, however, were lower in patients than in controls, both before (median 175 vs. 250 min, respectively; P = 0.003) and after (median 145 vs. 115 min, respectively; P ≤ 0.001) arm constriction, suggesting that they were experiencing hyperfibrinolysis. Interestingly, patients' median thrombin-activatable fibrinolysis inhibitor activity was higher than in controls (21.2 vs. 19.46 µg/ml; P = 0.016). However, plasminogen, α-2 antiplasmin, plasminogen activator inhibitor-1, and factor XIII activities did not differ between the groups. Global coagulation and fibrinolysis tests proved to be limited in detecting the hemostatic disorders in some patients with a relevant bleeding tendency and may not be adequate to address their bleeding risk. Bleeding scores are currently the available medical approach for the evaluation of these patients.