Insights into abnormal hemostasis in the Quebec platelet disorder from analyses of clot lysis.

BACKGROUND: The Quebec platelet disorder (QPD) is inherited and characterized by delayed-onset bleeding following hemostatic challenge. Other characteristics include increased expression and storage of active urokinase-type plasminogen activator (u-PA) in platelets in the setting of normal to increased u-PA in plasma. There is also consumption of platelet plasminogen activator inhibitor-1 and increased generation of plasmin in platelets accompanied by proteolysis of stored alpha-granule proteins, including Factor V. AIMS AND METHODS: Although fibrinolysis has been proposed to contribute to QPD bleeding, the effects of QPD blood and platelets on clot lysis have not been evaluated. We used thromboelastography (TEG), biochemical evaluations of whole blood clot lysis, assessments of clot ultrastructure, and perfusion of blood over preformed fibrin to gain insights into the disturbed hemostasis in the QPD. RESULTS: Thromboelastography was not sensitive to the increased u-PA in QPD blood. However, there was abnormal plasmin generation in QPD whole blood clots, generated at low shear, with biochemical evidence of increased fibrinolysis. The incorporation of QPD platelets into a forming clot led to progressive disruption of fibrin and platelet aggregates unless drugs were added to inhibit plasmin. In whole blood perfusion studies, QPD platelets showed normal adherence to fibrin, but their adhesion was followed by accelerated fibrinolysis. CONCLUSIONS: The QPD is associated with "gain-of-function" abnormalities that increase the lysis of forming or preformed clots. These findings suggest accelerated fibrinolysis is an important contributor to QPD bleeding.

Intranodal myofibroblastoma: study of a case suggesting smooth-muscle differentiation.

A case of intranodal myofibroblastoma with amianthoid fibres was studied by histology, immunohistochemistry and electron microscopy, in a Canadian Caucasian male presenting with an inguinal mass which appeared following a sports injury. Tumour cells were spindled and formed haphazard interlacing fascicles with intervening areas of haemorrhage. They were positive for vimentin, alpha-smooth-muscle actin and HHF35. By electron microscopy, they displayed moderate numbers of rough endoplasmic reticulum cisternae, fine actin-sized filaments in cell processes, and discrete stretches of unambiguous lamina ('external' lamina), sometimes in association with short attachment plaques. The fibronectin fibrils and fibronexus junctions characteristic of myofibroblasts were not seen. The absence of fibronexus junctions and the presence of surface features typical of smooth-muscle cells (attachment plaques with overlying lamina) suggest that this tumour is not myofibroblastic but is exhibiting a degree of smooth-muscle differentiation. The findings confirm earlier observations suggesting that some intranodal myofibroblastomas are not myofibroblastic, but show a form of smooth-muscle differentiation.

Morphological analysis of microparticle generation in heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) with thrombosis is a serious complication of heparin use. HIT sera can generate platelet-derived microparticles, which are produced in a heparin-dependent manner and are hypothesized to be important initial pathological participants because they promote vascular occlusion. To date, microparticles have been studied using flow cytometric techniques. However, it is uncertain whether the small-sized material seen in flow cytometric studies represents true platelet microparticles shed from activated platelets or whether they are platelets that have contracted after releasing their internal components. This report describes a morphological investigation of platelet-derived microparticles in HIT using, among other techniques, confocal, scanning electron, and transmission electron microscopy. Following incubation with HIT sera, the existence of small membrane-bound vesicles in the milieu of activated platelets was demonstrated. A population of microparticles, expressing platelet-specific glycoproteins, was separated from platelets by centrifugation over a sucrose layer. These microparticles had identical flow cytometric profiles, size heterogeneity, and GPIb(alpha) and GPIIb/IIIa staining intensity as the microparticle population in unfractionated samples. When microparticles were generated in situ and fixed onto grids, they were demonstrated to be distinct membrane-bound vesicles that originated near the platelet body and terminal ends of pseudopods on activated platelets. These microparticles appeared to be generated by localized swelling, budding, and release. Collectively, these morphological studies document the existence of true microparticles in platelets activated by HIT sera. The microparticles may play an important role in the pathogenesis of HIT.

Sclerosing sweat-duct carcinoma (malignant syringoma) of the upper eyelid: a patient report with immunohistochemical and ultrastructural analysis.

Sclerosing sweat-duct carcinoma or malignant syringoma is a rare eyelid tumor. The authors report the first patient with sclerosing sweat-duct carcinoma involving the upper eyelid and present its immunohistochemical and ultrastructural features. The clinical features and the histopathologic and ultrastructural findings that distinguish this tumor from its benign counterparts are discussed. Sclerosing sweat-duct carcinomas are slow growing but locally invasive neoplasms that have a propensity to recur. Wide and deep surgical excision with frozen section evaluation of margins is recommended.