thromboplastin and Pemphigus

The main autoimmune blistering skin disorders are pemphigus vulgaris (PV) and bullous pemphigoid (BP). They differ in the inflammatory infiltrate, which is more intense in BP. Inflammation is known to activate coagulation in several disorders. Local and systemic activation of coagulation was evaluated in BP and PV. We studied 20 BP patients (10 active and 10 remittent), 23 PV patients (13 active and 10 remittent) and 10 healthy subjects. The coagulation markers prothrombin fragment F1+2 and D-dimer were measured by enzyme-immunoassays in plasma. The presence of tissue factor (TF), the main initiator of blood coagulation, was evaluated immunohistochemically in skin specimens from 10 patients with active PV, 10 patients with active BP and 10 controls. Plasma F1+2 and D-dimer levels were significantly high in active BP (P = 0.001), whereas in active PV the levels were normal. During remission, F1+2 and D-dimer plasma levels were normal in both BP and PV. TF immunoreactivity was found in active BP but neither in active PV nor in normal skin. TF reactivity scores were higher in active BP than in controls or active PV (P = 0.0001). No difference in TF scores was found between active PV and controls. BP is associated with coagulation activation, which is lacking in PV. This suggests that BP but not PV patients have an increased thrombotic risk. The observation that thrombotic complications occur more frequently in BP than in PV further supports this view.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Autoimmunity; Biomarkers; Blood Coagulation; Case-Control Studies; Eosinophils; Female; Fibrin Fibrinogen Degradation Products; Humans; Immunohistochemistry; Lymphocytes; Male; Middle Aged; Pemphigoid, Bullous; Pemphigus; Peptide Fragments; Prothrombin; Skin; Statistics, Nonparametric; Thromboplastin; Young Adult

Immunohistochemistry was used to investigate the expression of tissue factor (TF) as a coagulation factor and thrombomodulin (TM) as an anticoagulation cofactor in the epidermis. TM was expressed on Malpighian layer keratinocytes while TF was located on the supra-Malpighian layer. Epidermal shave extracts were biologically active for both factors. Keratinocytes cultured in high calcium, but not low calcium media, expressed both TF and TM. In pemphigus vulgaris pemphigus foliaceus and bullous pemphigoid, TF expression was increased on keratinocytes shielding the blister compared to the down-regulated TM expression by keratinocytes around the blister.

Topics: Biomarkers; Blood Coagulation; Blood Coagulation Factors; Culture Techniques; Epidermis; Humans; Immunohistochemistry; Keratinocytes; Pemphigus; Reference Values; Thrombomodulin; Thromboplastin