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Studies of thromboxane B2, platelet factor 4, and fibrinopeptide A in
bleeding-time blood of patients deficient in von Willebrand factor,
platelet glycoproteins Ib and IIb-IIIa, and storage granules
HJ Weiss and B Lages
Department of Medicine (Division of Hematology-Oncology), St Luke's-
Roosevelt Hospital Center, New York, NY 10019.
The blood volumes and concentrations of thromboxane B2 (TxB2), platelet
factor 4 (PF4), and fibrinopeptide A (FPA) were measured every 30 seconds
in bleeding-time blood in normal subjects and in patients with idiopathic
thrombocytopenic purpura (ITP), delta and alpha delta storage pool
deficiency (SPD), Bernard-Soulier Syndrome (BSS), thrombasthenia (TSA), and
von Willebrand's disease (vWD). Data were fitted to second-order (TxB2,
PF4, and FPA) or third-order (volumes) polynomials. Average values for
various parameters over fixed-time intervals were determined by numerical
methods. The bleeding time was greater than 15 minutes in all patient
groups and the initial bleeding, as reflected by the initial slope of the
fitted blood volume curves, was increased in ITP, BSS, and SPD (delta-SPD
in particular), but not in vWD and TSA. The increased values for both the
initial slope and the volume of blood collected after 2 minutes in SPD
suggest that vascular tone may be modulated, in part, by dense granule
substances such as adenosine triphosphate (ATP) or serotonin. In TSA,
uniquely, both platelet (TxB2 and PF4) and coagulation (FPA) values were
increased in early bleeding samples (initial slope). In vitro studies of
TxB2 production, together with previous flow studies of fibrin formation,
also suggest enhanced activation and coagulant properties of thrombasthenic
platelets. In other patients, reduced values of all substances at later
times may reflect impaired platelet-fibrin plug formation in the high-shear
regions at the ends of transected blood vessels. However, the initial
slopes of the fitted curves for both TxB2 and PF4 were normal in vWD,
suggesting that the early appearance of these substances may typically be
from platelets that are adherent to collagen within the lower shear
environment of the wound surface. The finding that FPA values were not
decreased initially in any patient group, including ITP, but were decreased
at later times (except for TSA), suggests that early fibrin formation
occurs independently of platelets in the low-shear environment of the wound
surface, whereas at later times fibrin is formed in a platelet-dependent
manner in the high- shear regions at the ends of transected vessels.
Volume 82,
Issue 2,
pp. 481-490,
07/15/1993
Copyright © 1993 by The American Society of Hematology
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