Remarkable elevation of fibrinolysis markers and procalcitonin associated with dabrafenib plus trametinib combination therapy: Uncommon adverse events

Abstract

21-45. 4 Koch M, Freundl AJ, Agaimy A et al. Atypical fibroxanthoma -histological diagnosis, immunohistochemical markers and concepts of therapy. Anticancer Res 2015; 35: 5717-5735.5 Ito A, Yamada N, Yoshida Y, Morino S, Yamamoto O. Myofibroblastic differentiation in atypical fibroxanthomas occurring on sunexposed skin and in a burn scar: an ultrastructural and immunohistochemical study.

Intracranial hemorrhage caused by dabrafenib and trametinib therapy for metastatic melanoma

“…Although MEKi cobimetinib and trametinib do not induce platelet dysfunction [17], Verzeroli et al [18] observed a downregulation of the hemostatic parameters' thrombin generation potential of plasma and D-dimer in patients who responded to BRAF-MEK inhibitor therapy. Furthermore, it has been demonstrated that BRAFi dabrafenib and MEKi trametinib downregulate tissue factor [19] and upregulate fibrinolysis markers [20] in BRAF V600E-mutated melanoma cells with a consequent inhibition of the coagulation cascade. In contrast, sudden elevation of plasma D-dimer levels along with disseminated intravascular coagulation induced by dabrafenib and trametinib has also been described [21], suggesting the ambiguity of the role of MEK in platelet function and primary haemostasis.…”

Extreme elevation of acute phase reactants and shock secondary to dabrafenib–trametinib

“…They are frequently ordered in critically unwell patients to assess the likelihood of infection, as results of microbiological cultures take time. Two such markers in routine practice are CRP and, more specifically, procalcitonin [6]. In normal healthy adults, the level of procalcitonin is low, but Nijsten et al [7] showed that procalcitonin could be induced as an acute-phase reactant.…”