Summary
Erythromelalgia, a characteristic aspirin-responsive microvascular thrombotic complication
in essential thrombocythemia (ET), may develop despite oral anticoagulant treatment
or treatment with heparin, suggesting that the generation of thrombin is not a prerequisite
for its development. To study this, a cross-sectional comparison of the plasma levels
of thrombomodulin (TM), platelet factor 4 (PF4), β-thrombo-globulin (β-TG), prothrombin
fragment 1+2 (F1+2) and total degradation products of fibrin(ogen) (TDP) was made
between 5 ET patients suffering from erythromelalgia, 16 asymptomatic ET patients
and 20 control subjects, and after treatment with aspirin, respectively. Furthermore,
2 ET patients with a history of erythromelalgia were studied at regular time intervals
after discontinuation of aspirin until erythromelalgia recurred. As compared with
asymptomatic ET patients and control subjects erythromelalgia was characterized by
significantly higher β-TG and TM levels but no significant differences were detected
in either F1+2 or TDP levels. Treatment of erythromelalgia with aspirin resulted in
disappearance of erythromelalgic signs and symptoms, which was paralleled by a significant
decrease of β-TG and TM levels. Histopathologic and immunohistochemical analysis of
biopsies derived from erythromelalgic skin areas of 2ET patients showed that erythromelalgic
thrombi stained positively for von Wille-brand factor opposed to only a weak fibrin
staining. Our data suggest that erythromelalgia is caused by the intravascular activation
and aggregation of platelets with subsequent sludging or occlusion of the acral arterial
microvasculature. The generation of thrombin appears not to be essential for the formation
of these platelet thrombi, thereby giving a plausible explanantion for the inefficacy
of coumadin derivatives and heparin in the prevention and treatment of erythromelalgia
in essential thrombocythemia.
