Coagulation cascade and fibrinolysis in patients with multiple-drug allergy syndrome.
BACKGROUND
Previous studies have shown that patients with multiple-drug allergy syndrome (MDAS) frequently have positive autologous serum skin test results, similar to patients with chronic urticaria (CU). Recent investigations have found that patients with CU show signs of thrombin generation and activation of the tissue factor pathway of the coagulation cascade.


OBJECTIVE
To study thrombin generation and fibrinolysis in patients with MDAS.


METHODS
Nine patients with MDAS underwent autologous plasma skin testing (APST) and measurement of plasma prothrombin fragment F(1 + 2) and D-dimer levels. Furthermore, the basophil histamine-releasing activity of plasma from patients with MDAS was evaluated. Plasma samples from 74 healthy control subjects and 13 patients with CU were used as negative and positive controls, respectively.


RESULTS
All 9 patients with MDAS had positive APST results, and 7 showed elevated plasma levels of fragment F(1 + 2). In patients with MDAS, the median F(1 + 2) level (339 pmol/L; interquartile range [IQR], 250-401 pmol/L) significantly exceeded that in healthy controls (159 pmol/L; IQR, 123-196 pmol/L) (P = .001) but did not significantly differ from that in controls with CU (292 pmol/L; IQR, 182-564 pmol/L; P = .38). Plasma D-dimer levels were normal in all the patients with MDAS and were significantly lower than in controls with CU (P = .009). Finally, the histamine-releasing activity of plasma from patients with MDAS was significantly increased and correlated with F(1+ 2) levels (r = 0.68; P = .04).


CONCLUSIONS
Positive APST results and thrombin generation indicate a common physiopathologic background in MDAS and CU. The lower D-dimer levels suggest that fibrinolysis occurs less intensely in MDAS than in CU.
Asero
Riccardo
R
Ambulatorio di Allergologia, Clinica San Carlo, Paderno Dugnano (MI), Italy. r.asero@libero.it
Tedeschi
Alberto
A
Riboldi
Piersandro
P
Griffini
Samantha
S
Bonanni
Erika
E
Cugno
Massimo
M
D000328:Adult; D000368:Aged; D001324:Autoantigens / Q000276:immunology; D015549:Basophil Degranulation Test; D001491:Basophils / Q000276:immunology / Q000378:metabolism; D001777:Blood Coagulation / Q000276:immunology*; D004342:Drug Hypersensitivity / Q000097:blood / Q000276:immunology / Q000503:physiopathology; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005342:Fibrinolysis / Q000276:immunology*; D006636:Histamine Release / Q000276:immunology; D006801:Humans; D008875:Middle Aged; D018777:Multiple Chemical Sensitivity / Q000097:blood* / Q000276:immunology / Q000503:physiopathology; D010446:Peptide Fragments / Q000097:blood; D011516:Prothrombin; D012882:Skin Tests; D013917:Thrombin / Q000378:metabolism; D014581:Urticaria / Q000097:blood / Q000276:immunology / Q000503:physiopathology
D001324:Autoantigens; D005338:Fibrin Fibrinogen Degradation Products; D010446:Peptide Fragments; C036309:fibrin fragment D; C045879:prothrombin fragment 1.2; D011516:Prothrombin; D013917:Thrombin