Platelet-associated Factors Research Articles

Blood‐borne factors possibly associated with post‐operative nausea and vomiting: an explorative study in women after breast cancer surgery

The pathophysiology behind post-operative nausea and vomiting (PONV) is still not fully understood, especially with respect to gender. According to PONV risk scores, female gender is the strongest predictor for PONV. The risk for PONV after general anaesthesia for breast cancer surgery is 50-80%. The aim of the present explorative study was to identify blood-borne factors that might be associated with the development of PONV in women undergoing breast cancer surgery as a basis for further studies. Fifty patients were enrolled prospectively in the study. A standardized sevoflurane-based anaesthetic was used. Blood samples for the analysis of vasopressin, gastrin, cholecystokinin, epinephrine, norepinephrine, dopamine, serotonin, platelet count and blood glucose were taken at six pre-determined time points peri-operatively, and PONV was assessed during 24 h. PONV was found in 27 of 47 patients completing the study. Patients with PONV had a larger variability of the platelet count (P = 0.001), a reduced platelet count on the first post-operative day (P = 0.02) and a less pronounced relationship between the platelet count and whole blood serotonin (P = 0.004) compared with non-PONV patients. A lack of a decrease in epinephrine levels in response to the induction of anaesthesia (P = 0.03) and increased levels of vasopressin (P < 0.001), epinephrine (P = 0.005) and blood glucose (P = 0.004) were observed in the early post-operative period in PONV patients. Three different platelet-associated factors and an altered epinephrine pattern were found to be associated with the occurrence of PONV after breast cancer surgery.

Platelet contribution to cancer cell growth and migration: the role of platelet growth factors.

Blood platelets contain several growth factors and inhibitors. The better known among them are named platelet-derived growth factor (PDGF) and transforming growth factor beta (TGF beta), active as modulators of growth of normal mesenchymal and epithelial cells. Cancer cell growth in vitro seems to be independent of the effects of exogenous peptides, but dependent on the cell ability to release autocrine growth factors, similar to PDGF or TGF beta. In addition, platelet-associated growth factors and inhibitors, which are able to induce a fibrotic response in connective tissue cells, might also play a role to modulate the desmoplastic reaction surrounding the tumor.

Migration of porcine endothelial and smooth muscle cells in response to platelet-associated factors.

A NeuroProbe multiwell microchemotaxis assembly has been used to study the migration of porcine aortic endothelial and smooth muscle cells in vitro in response to serum factors. Whole pig serum was found to be chemokinetic for endothelial cells but not smooth muscle cells. Chemokinetic activity was higher in platelet-enriched, plasma-derived serum (PDS) than in platelet-free PDS. The supernatant from washed, lysed pig platelets also showed chemokinetic activity both for endothelial and smooth muscle cells. Chromatography on Sephadex G-200 showed that the lysate contained a number of activities that act independently on the two cell types. The chemokinetic activity that we have detected appears to be distinct from the chemotactic effect of platelet-derived growth factor and platelet factor 4 on the basis of insensitivity to protamine sulfate and molecular size. The role of these platelet factors in pathological changes in vascular structure is currently under study.

Stimulation of DNA synthesis in primary cultures of adult rat hepatocytes by rat platelet-associated substance(s).

Experiments in whole animals have shown that normally quiescent adult rat hepatocytes are induced to proliferate by blood borne substances, which we are now probing in primary monolayer cultures. Under our conditions, freshly isolated adult hepatocytes do not proliferate actively in a defined medium, but are stimulated to synthesize DNA--an essential first step--by either serum or an EGF-hormone combination. Stimulation of [3H]thymidine incorporation into hepatocyte DNA by addition of dialyzed mouse, human, horse, or bovine (fetal, newborn, or calf) serum, whose activities are all similar, is regularly surpassed by an EGF-insulin mixture without serum. This, in turn, is exceeded by dialyzed normal rat serum, which is several times more potent than the other sera tested. Removal of blood platelets reduces the activity of normal rat serum by over 50%. Heat inactivation (56 degrees C) causes a similar loss, but heat treatment of platelet-poor serum fails to cause further reduction. The activity of mouse and human serum is not reduced by platelet removal. Serum from partially hepatectomized rats is not significantly more stimulatory than normal rat serum, and its activity is depressed in the same way by platelet deprivation and heat inactivation. Lack of enhancement by partial hepatectomy is not consonant with whole animal studies and requires further investigation. The heat-labile portion of the DNA synthesis-stimulating activity of rat serum appears to derive from platelets. This activity differs from the well-characterized heat-stable human PDGF. Its relation to other reported platelet-associated growth factors is still undetermined.

Plasma and platelet associated factors act in G1 to maintain proliferation and to stabilize arrested cells in a viable quiescent state: A temporal map of control points in the G1 phase

In medium supplemented with defibrinogenated, platelet-poor human plasma and a low molecular weight growth factor derived from human platelets (PDGF), Swiss 3T3 cells proliferate exponentially with the same cell cycle kinetics as cells cultured in medium supplemented with commercial calf serum. Removal of PDGF from the culture medium arrests proliferating cells in a stable, reversible G0 G1 quiescent state. This arrested state is similar to the known quiescent state induced by deprivation of calf serum in cell exit kinetics and cytoplasmic proteins synthesized. Cells are sensitive to PDGF deprivation only at the beginning of G1. Reduction of the plasma concentration in the culture medium also arrests cells in G1. The resulting arrested population is unstable and exhibits progressive cell death. Reduced levels of plasma block cellular transit through the cell cycle at a median time of approx. 2.1 h following mitosis, approx. 3.3 h prior to S phase initiation. In addition to being required by cycling cells, plasma associated factors are required to maintain G1 cells blocked by PDGF deprivation in a stable quiescent state. Establishment of a stable, viable G0 G1 growth-arrested state, therefore, apparently involves two distinct processes: arrest of cellular proliferation in G1 and stabilization of the arrested cells in a viable quiescent state. Together with previously reported findings on serum and isoleucine starvation, these results provide a temporal map of growth control points in the G1 phase.

Platelets and Fibrinolysis

SummaryBlood platelets play a crucial role in the response of blood to vascular injury through adherence to exposed subendothelial vessel wall structures, the subsequent release of substances which trigger platelet aggregation, and release-associated changes in platelet surface properties which facilitate the interaction of coagulation factors, leading to the formation of fibrin necessary for stabilization of the initial hemostatic plug. There is substantial evidence from in vitro studies to suggest that platelets may also affect the fibrinolytic plasminogen-plasmin system thought to be one of the important hemostatic regulatory mechanisms preventing inappropriate extension of the hemostatic plug which may lead to thrombotic vessel occlusion. In this paper, the published experimental evidence concerning the effects of platelets and platelet-associated factors on the activation and function of the plasminogen-plasmin system is reviewed. The experimental findings indicate that platelets may contribute to fibrin clot stabilization through the release of substances from their storage organelles which inhibit both plasminogen activation and the action of plasmin. The physiologic and pathophysiologic significance of platelet-mediated inhibition of fibrinolysis by plasmin, as well as other potentially important plasma and cellular fibrinolytic enzymes, is still largely subject to speculation and appears to be an important area for future investigation.