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VWF release and platelet aggregation in human melanoma after perfusion with TNFα
Author(s) -
Renard Nathalie,
Nooijen Peet T. G. A.,
Schalkwijk Lia,
De Waal Robert M. W.,
Eggermont Alexander M. M.,
Liénard Danielle,
Kroon Bin B. R.,
Lejeune Ferdy J.,
Ruiter Dirk J.
Publication year - 1995
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1711760310
Subject(s) - von willebrand factor , fibrin , platelet , pathology , medicine , perfusion , endothelium , immunostaining , fibrinogen , endothelial stem cell , chemistry , immunology , immunohistochemistry , biochemistry , in vitro
Twenty‐nine stage IIIA/B melanoma patients treated by isolated limb perfusion (ILP) with a high dose of recombinant human tumour necrosis factor alpha (rHuTNFα), interferon γ (IFNγ), and melphalan were histologically documented with emphasis on therapy‐induced changes of the tumour vasculature. Sequential biopsies were taken at various intervals before and after the treatment to compare the morphological changes. In order to visualize microvascular changes, immunostaining was performed for von Willebrand factor (VWF), type IV collagen, α‐smooth muscle actin, endothelial antigen PAL‐E, tissue factor, CD41 (thrombocyte marker), and fibrin. In biopsies prior to perfusion, necrosis, haemorrhage, and fibrin thrombi were not found. Within 3 h following triple combination therapy, a change in the distribution of VWF staining occurred, from a discrete endothelial pattern in the untreated lesions to a fuzzy perivascular and subepidermal pattern in the treated lesions. Within 24 h, this was accompanied by intravascular thrombocyte aggregation and erythrostasis, in the absence of tissue factor and fibrin deposits. These findings indicate that the thrombocyte aggregation observed is not caused by local procoagulant activity, but is rather the result of the therapy‐associated vascular damage or haemostasis. Although it is difficult to derive the dynamics of this process from static images, we assume that TNFα induced endothelial cell damage, leading to VWF release. Released VWF may play a role in the adhesion between thrombocytes and the damaged endothelium or the denuded subendothelium. As a consequence, the blood flow is impaired, leading to congestion and oedema, compatible with an early stage of haemorrhagic infarction.