Laboratory evaluation of patients with undiagnosed bleeding disorders

Abstract

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.

Characterization of a large cohort of patients with unclassified bleeding disorder; clinical features, management of haemostatic challenges and use of global haemostatic assessment with proposed recommendations for diagnosis and treatment

“…Recently, an algorithm to aid in the diagnosis of patients with a bleeding tendency has been published . Three studies have demonstrated that patients with UBD have evidence of fibrionlytic abnormalities with evidence of hyperfibrinolysis and fibrinolytic regulators . This may explain the efficacy of TxA that we observed at the time of haemostatic challenges.…”

“…[31][32][33] In two other studies with relatively large patient numbers, TG was unable to discern a difference between patients with UBD and controls. 34,35 Recently, the VBB has identified TG abnormalities including prolonged lag time, time to peak, decreased maximum TG, velocity index and area under the curve but these did not correlate with bleeding severity. 36 Routinely, we cannot recommend TG for routine use but we propose it may be of use in a research setting to further investigate these patients.…”

“…39 Three studies have demonstrated that patients with UBD have evidence of fibrionlytic abnormalities with evidence of hyperfibrinolysis and fibrinolytic regulators. 4,34,40…”

Investigation of patients with unclassified bleeding disorder and abnormal thrombin generation for physiological coagulation inhibitors reveals multiple abnormalities and a subset of patients with increased tissue factor pathway inhibitor activity

“…however, this may be due to study design or patient selection. 22,23 In addition, thrombin generation is not likely to be abnormal in all patients with UBD as many may have vascular/collagen, platelet or fibrinolytic defects which thrombin generation would not show.…”

Actualización clínica y molecular de la telangiectasia hemorrágica hereditaria en Salamanca

“…La evaluación de los pacientes con una tendencia a la hemorragia representa un desafío ya que las pruebas rutinariamente disponibles para evaluar los trastornos de la coagulación han sido limitadas hasta ahora, lo que ha complicado la determinación en laboratorio de la tendencia de sangrado clínicamente observada (136). Ya en 1994 se llevaron a cabo estudios para definir su etiología (130,128).…”