The structure and growth of valve-pocket thrombi in femoral veins

Abstract

SYNOPSISThe structure of 50 small thrombi in femoral valve pockets and the microscopic contents of 35 apparently empty pockets were studied in an attempt to ascertain the nature of the microscopic nidi from which thrombi form and their manner of growth to visible thrombi. Sixteen thrombi had little or no cellular invasion. Most of these recent structures had two main regions, red areas restricted distally in the pocket by the vein wall, and larger white regions comprising most of the thrombus length and often covering the red areas. Red areas are the early sites of cellular adhesion and invasion and the likely sites of origin of most thrombi. They were usually dominated by red cells and fibrin. White zones, which represent propagation growth, are characterized by many foci of platelets with fibrin borders (platelet-fibrin units). Some red areas also contained platelet-fibrin units but they were few and tiny; platelets were not seen in others and one small wholly red thrombus was devoid of platelets. Degenerative changes in platelet-fibrin units were observed, and it is postulated that many become purely fibrin structures. There was no significant evidence of preceding intimal damage in the vein wall. Therefore nidi are laid down on normal endothelium probably on the vein wall near the apex of the pocket. Some pockets, empty of thrombi, contained condensed foci of red cells or tiny fibrin fragments surfaced by endothelial cells and considered to be the remnants of aborted thrombi; a few contained clumps of platelets or leucocytes. It is postulated that any of these may represent the nidi from which thrombi grow. Several thrombi also incorporated large fat droplets, numerous in two. Fat embolic globules derived from fractures are their likely source.Small isolated thrombi in valve pockets (valve sinuses) are not infrequent in major deep veins of the thigh (fig 1) and calf, especially in middle-aged and elderly subjects at bed rest

P-selectin mediates the adhesion of sickle erythrocytes to the endothelium

“…22 Erythrocyte adhesion to P-selectin also suggests possible molecular mechanisms for the adherence of activated platelets to sickle cells, 57 cooperative heterocellular interactions in sickle cell vaso-occlusion, [57][58][59][60] and the retention of erythrocytes in red thrombi. 61,62 The modest adherence that we noted of nonsickle cells to P-selectin does not diminish the importance of sickle cell adherence. Indeed, our finding is consistent with previous reports of a lesser degree of nonsickle RBC adherence to endothelial cells.…”

A Mathematical Model of Venous Thrombosis Initiation

“…They can grow to be centimeters long, and much of their volume appears to consist largely of fibrin and trapped red blood cells (4). The belief that many venous thrombi originate in VVPs comes from studies of excised veins (generally postmortem) (4,5) in which early-stage thrombi were found in the VVPs in the legs. These thrombi have been variously reported to be located on the vein wall within the pocket or on the side of the valve leaflet that faces the valve pocket (5,7), but never on the side of the valve leaflet that faces the vein lumen (6).…”

“…It is a serious cause of mortality and morbidity, especially in older persons. A preponderance of human VT that is not associated with cancer, sepsis, or other systemic challenges is associated with prolonged immobility and occurs in the pockets behind (downstream) of venous valves in the legs or pelvis (1)(2)(3)(4)(5). Venous valves normally make possible the one-way flow of blood toward the heart driven by contractions of leg muscles.…”

“…These ''white'' early thrombi are described as ''granular'' and ''friable'' (7) and have a consistency that is very different from that of the larger later-forming ''red part'' of the thrombus. The endothelial surfaces from which the early thrombi emanate seem to be devoid of injury (4,5,8,9).…”

An MRI study of the differences in the rate of thrombolysis between red blood cell‐rich and platelet‐rich components of venous thrombi ex vivo

“…However, it is generally believed that such inclusions can rarely be found in venous thrombi. In fact, prevalence of platelet inclusions in thrombi may be higher than anticipated by the conventional histological observations (9), which may be due to the poor availability of efficient high-resolution noninvasive techniques for thrombi investigation. MRI is a powerful tool for the characterization of the layered pulmonary emboli structure (10).…”