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PubMed1997

Energy-dependent expression of platelet-von Willebrand factor on the surface of unstimulated and stimulated platelets.

We have studied the energy requirements (adenosine triphosphate) for the expression of platelet-von Willbrand factor on platelets under conditions in which glycolysis and/or oxidative phosphorylation were inhibited. We found that platelet-vWf expression on the surfaces of both unstimulated and stimulated platelets required energy and was maximally decreased when metabolic ATP was maximally depleted. Platelet-vWf expression correlated directly with estimates of adenylate energy charge in both unstimulated and stimulated platelets. In addition, platelet shape change and agonist-induced intracellular Ca2+ flux were maintained at lower AECs than were either platelet aggregation or alpha-granule secretion. Our results indicate that the surface expression of platelet-vWf on unstimulated platelets is a dynamic process, and that energy is required to maintain basal amounts of platelet-vWf on the platelet surface. Our data also suggest that the metabolic ATP required to effect changes in platelet shape is less than that necessary to maintain basal platelet-vWf surface expression or to produce full alpha-granule secretion. We show that platelet-shape change in the absence of alpha-granule secretion can result in an increase in platelet-vWf surface expression.

2,4-Dinitrophenol↗
PubMed1986

A platelet alpha granule membrane protein that is associated with the plasma membrane after activation. Characterization and subcellular localization of platelet activation-dependent granule-external membrane protein.

We have identified and purified a platelet integral membrane protein (140,000 mol wt), using the KC4 monoclonal antibody specific for activated platelets, that is internal in resting platelets but exposed on activated platelets (Hsu-Lin S.-C., C.L. Berman, B.C. Furie, D. August, and B. Furie, 1984, J. Biol. Chem. 259: 9121-9126.). The expression of the protein on the platelet surface is secretion-dependent. This protein has been named platelet activation-dependent granule-external membrane (PADGEM) protein. PADGEM protein is distinct from the surface glycoproteins of resting platelets, but identical to the S12 antigen, GMP-140. Using immunofluorescent staining, resting platelets failed to stain for PADGEM protein with the KC4 antibody, but after permeabilization showed a punctate staining of the cell interior. Thrombin-stimulated intact platelets stained with a peripheral rim pattern thus demonstrating the translocation of PADGEM protein from an internal location to the cell surface. PADGEM protein expression on the platelet surface at varying thrombin concentrations correlated with alpha granule release, as measured by the secretion of platelet factor 4. Further evidence for an alpha granule localization of PADGEM protein was provided by nitrogen cavitation of resting platelets followed by metrizamide density gradient centrifugation; PADGEM protein codistributed with platelet factor 4. Using immunoelectron microscopy, the protein was localized to the alpha granule in frozen ultrathin sections of resting platelets labeled using rabbit anti-PADGEM protein antibodies, whereas in thrombin-activated platelets, the plasma membrane was labeled. These studies indicate that PADGEM protein is a component of the alpha granule membrane of resting platelets and is incorporated into the plasma membrane upon activation and secretion.

Antibodies, Monoclonal↗
PubMed1992

Stored platelets release nucleotides as inhibitors of platelet function.

It is well known that the function of platelets decreases progressively during storage of platelet concentrates at room temperature. To investigate this phenomenon in more detail, we have resuspended platelets that had been stored for 24 h or 72 h in fresh plasma, and we have measured the aggregation response and the ATP secretion. Conversely, the effect of plasma in which platelet concentrates (PC) had been stored for 24 h or 72 h, was tested on fresh platelets. Both the aggregation response to collagen and ADP and the collagen-induced ATP secretion of stored platelets partially recovered after incubation with fresh plasma (p < 0.05). The same parameters measured with fresh platelets incubated in stored PC-plasma were found to be significantly reduced in comparison with the response of fresh platelets in fresh plasma (p < 0.05). Finally, platelets were stored in a plasma-free medium, suitable for platelet storage and the supernatant was tested. This supernatant inhibited the function of fresh platelets in a storage time-dependent fashion. Boiling of these supernatants did not change the inhibiting capacities, whereas filtration over active charcoal did. Analysis of this supernatant revealed AMP and diadenosine tetraphosphate, which both inhibit platelet function. These data show that stored platelets release nucleotides that inhibit platelet function in a reversible manner. This phenomenon may contribute to the decrease of platelet function during storage and the recovery of platelet function after transfusion.

Adenosine Diphosphate↗
PubMed1990

Direct detection of activated platelets and platelet-derived microparticles in humans.

Flow cytometry was used to determine whether activated platelets and platelet-derived microparticles can be detected directly in whole blood after a hemostatic insult. Two different in vivo models of platelet activation were examined: (1) a standardized bleeding time, and (2) cardiopulmonary bypass. Platelets and microplatelets were identified with a biotinylated anti-glycoprotein (GP)lb antibody and a fluorophore, phycoerythrin-streptavidin. Microparticles were distinguished from platelets by light scatter. Activated platelets were detected with three fluorescein-labeled monoclonal antibodies (MoAbs): (1) PAC1, which binds to the activated form of GPIIb-IIIa; (2) 9F9, a newly developed antibody that is specific for fibrinogen bound to the surface of activated platelets; and (3) S12, which binds to an alpha-granule membrane protein expressed on the platelet surface after granule secretion. In nine normal subjects, bleeding times ranged from 4.5 to 7.5 minutes. Over this time, there was a progressive increase in the amount of PAC1, 9F9, and S12 bound to platelets in blood emerging from the bleeding time wound. With all three antibodies, platelet activation was apparent as early as 30 seconds after the incision (P less than .03). Activation was accompanied by a progressive decrease in the concentration of platelets in blood from the wound, while the concentration of microparticles increased slightly. In nine patients undergoing open heart surgery, 1 hour of cardiopulmonary bypass caused a 2.2-fold increase in the relative proportion of microparticles in circulating blood (P less than .001). Moreover, bypass caused platelet activation as evidenced by a mean two- to threefold increase in PAC1 binding to platelets. Although this increase was significant (P less than .02), PAC1 binding exceeded the normal range for unstimulated control platelets in only 5 of 9 patients, and 9F9 and S12 binding exceeded the normal range in only two patients. Taken together, these studies demonstrate that it is now feasible using flow cytometry to evaluate the extent of platelet activation and the presence of platelet-derived microparticles in the circulation of humans.

Adenosine Diphosphate↗
PubMed1989

Identification of and partial characterization of platelet vitronectin: evidence for complex formation with platelet-derived plasminogen activator inhibitor-1.

Vitronectin (VN; = complement S-protein), a plasma glycoprotein that is also associated with extracellular sites, was identified in washed human platelets contaminated with less than 0.05% of plasma VN. A specific enzyme-linked immunosorbent assay (ELISA) for VN has been developed and was used to detect and to quantitate VN in detergent extracts of washed platelets with 8.1 +/- 4.6 micrograms/10(9) platelets (n = 10), representing about 0.8% of the plasma VN pool. Platelet and plasma VN were similar by immunochemical criteria using Western-blot analysis, although platelet VN was mainly found as partially proteolyzed polypeptide. Total release of platelet VN occurred at optimal doses of Ca-ionophore 23187 or thrombin, whereas no VN was released by platelet treatment with digitonin or Staphylococcus alpha-toxin. During stimulation of washed platelets with various concentrations of thrombin, the nearly concomitant release of VN and plasminogen activator inhibitor-1 (PAI-1) together with platelet factor 4 indicated the association of VN with inner-platelet storage granules. Furthermore, platelet VN and PAI-1 in Ca-ionophore releasates comigrated during ultracentrifugation in high mol wt fractions of sucrose density gradients, indicating a possible association of both components. Complex formation of platelet VN and PAI-1 was verified by a sensitive enzyme-linked immunosorbent assay (ELISA) and accounts at least in part for a high molecular form of platelet VN. The identification of platelet VN and its binding to platelet PAI-1 raises the possibility that VN, in contrast to other adhesive proteins, may participate in localized regulatory functions of blood coagulation and fibrinolysis in platelet-matrix interactions and the protection of the matrix against proteolysis.

Bacterial Toxins↗
PubMed2002

Development of a non-human primate sub-clinical model of heparin-induced thrombocytopenia: platelet responses to human anti-heparin-platelet factor 4 antibodies.

The purpose of this study was to characterize the responses of human and non-human primate (Macaca mulatta) platelets to anti-heparin-platelet factor 4 (AHPF4) antibodies. Due to the variations observed in the functionality and immunoglobulin isotypes in patients with heparin-induced thrombocytopenia (HIT), we used highly characterized human AHPF4 antibodies to study platelet activation responses. Using ELISA and 14C-serotonin release assay (SRA) systems, three patients' plasmapheresis fluid with similar responses to these assays were pooled. This pool was then used to study the platelet activation responses of human and primate platelets in the HIT platelet aggregation assay, a flow cytometry assay, and a variation of the aggregation assay in which glycoprotein IIb/IIIa inhibitors were supplemented. In the plasmapheresis fluid from three patients, the most significant AHPF4 immunoglobulin isotype present (based on optical density readings) was IgG, with less IgM (p < 0.001) and IgA (p < 0.001). The SRA yielded equivalent platelet activation results in all three patients. Using this pool in the platelet aggregation assay, without any heparin present, there was less percent aggregation (p < 0.001) with human platelets (11.8 +/- 2.35, n = 5) compared to the primate platelets (54.3 +/- 10.2, n = 9). In presence of 0.4 U/ml heparin, both platelet types had similar percent aggregations (p > 0.05). Three glycoprotein IIb/IIIa receptor inhibitors were used to evaluate the similarities in platelet activation. Eptifibatide was found to be a strong inhibitor of both species' platelet types at concentrations greater than 0.01 microg/ml. This was not the case with tirofiban which inhibited both human and monkey platelets at concentrations greater than 0.025 microg/ml. Abciximab inhibited aggregation at concentrations greater than 6.25 microg/ml. These data indicate that phylogenetic similarities in platelets of humans and primates may be used to further characterize the pathophysiology of HIT syndrome.

Abciximab↗
PubMed1992

Platelet-activating factor as an intercellular signal in neutrophil-dependent platelet activation.

The role of platelet-activating factor (PAF) in heterotypic cell to cell interactions in a rabbit neutrophil-platelet mixture model was investigated. Platelets were exposed to each of three chemotactic agonists: PAF, leukotriene B4 (LTB4), or FMLP. Only PAF stimulated aggregation, [3H]serotonin secretion, and cytosolic Ca2+ mobilization in platelets alone. However, platelets were stimulated by LTB4 and FMLP in the presence of neutrophils. This neutrophil-dependent platelet activation was blocked by pretreatment of platelets with PAF receptor antagonists, and was prevented by desensitization of platelets to PAF. Furthermore, the time-course of platelet activation showed a positive correlation with PAF production by neutrophils stimulated with either LTB4 or FMLP. The PAF-mediated neutrophil-platelet interaction was dependent on direct cell to cell contact, as demonstrated by experiments in which the majority of newly formed PAF was neutrophil associated (rather than released). Platelet activation did not occur when the neutrophil-platelet mixture was not stirred, minimizing cell to cell contact, or when platelets were challenged with a cell-free supernatant prepared from neutrophils activated with LTB4 or FMLP. Finally, the neutrophil-platelet interaction was abolished by SC-49992, a peptidomimetic of the fibrinogen binding sequence Arg-Gly-Asp-Phe, indicating a Arg-Gly-Asp-specific recognition mechanism. Our results demonstrate that neutrophil-generated PAF plays a crucial role in neutrophil-dependent platelet activation in this model system. This type of intercellular signaling event may be important in certain inflammatory or thrombotic processes.

Amino Acid Sequence↗
PubMed1993

[Effect of PAF (platelet-activating factor) on hemostasis. Studies on endothelial cells and platelets].

PURPOSE: To evaluate the direct action of PAF on the pro-coagulant activity of cultured vascular endothelial cells; to analyse by photometric methods the thrombogenic effect of PAF on platelets, and to assess platelet deposition on vascular endothelium. MATERIAL AND METHODS: Human endothelial cells were isolated from umbilical cord vein and incubated for three minutes at 22 degrees C with different PAF concentrations (10(9) M to 10(-7) M) in order to assess the influence of this lipidic mediator on the procoagulant activity of the cells. The effect of PAF on platelet aggregation was assessed by aggregation studies using arachidonic acid (AA) and different PAF and Lyso-PAF concentrations (10(-8) M to 10(-4) M). Serotonin (5-HT) release was tested in platelet rich plasma (PRP) samples highly sensitive to PAF. PRP samples were incubated for 30 minutes at 22 degrees C with 100 microCi 3H-5-HT. Platelets were activated with 10(-7) M to 10(-9) M PAF concentrations, the percentage of 3H-5-HT released into the extra-platelet medium being calculated. Baumgartner's continuous perfusion model was used to study platelet deposition on the vascular endothelium. The morphometric evaluation was carried out by a planimeter assembled to a data processor with a programme devised for analysing the platelet-subendothelium interaction. RESULTS: Evaluation of the procoagulant activity on the cell surface: The expression of the procoagulant activity showed no variations with respect to the controls under different concentrations of PAF. Platelet aggregation and release studies: Normal values of platelet aggregation (80% to 100%) were found when using AA, however, there were great case to case variations under different PAF concentrations. Serotonin release was less marked than aggregation itself. The use of Lyso-PAF failed to elicit platelet aggregation and serotonin release in any case. Morphometric evaluation: The results attained showed that perfusion carried out with 10(-8) M PAF concentration showed contact, adhesiveness and thrombus formation figures similar to those of control perfusion. CONCLUSIONS: Human platelets are not too sensitive to PAF activity, only high PAF concentrations being capable of inducing platelet aggregation and 5-HT release with ample variability. This suggests the existence of a heterogeneous platelet population with PAF receptors. Low PAF concentrations do not modify the haemostatic function, and only those PAF concentrations inducing maximal release and aggregations could reduce the interaction of platelets with vascular subendothelium and the formation of thrombi.

Blood Platelets↗
PubMedDate not supplied

Combination of platelet-derived growth factor-BB and insulin-like growth factor-I is more effective than platelet-derived growth factor-BB alone in stimulating complete healing of full-thickness wounds in "older" diabetic mice.

Platelet-derived growth factor and insulin-like growth factor-I have been shown to interact synergistically to enhance repair of skin wounds in normal healing swine. Platelet-derived growth factor alone has shown promise in treating human chronic ulcers. The objective of this study was to compare the wound healing effects of platelet-derived growth factor-BB alone with those of a combination of platelet-derived growth factor-BB and insulin-like growth factor-I in an improved model with the use of "older" animals with diabetes. Older diabetic (db/db) mice (>15 weeks of age) have less elevated insulin levels compared with young db/db mice. The serum insulin levels in the older animals is 1.0 to 2.5 times that of the nondiabetic animals, a similar increase to that which occurs in human patients with type II diabetes. Healing was evaluated in two studies involving a total of 104 animals. Treatment groups included the following: 4.0 microg/cm(2) of platelet-derived growth factor-BB, 40.0 microg/cm(2) of platelet-derived growth factor-BB, 4.0 microg/cm(2) of both platelet-derived growth factor-BB and insulin-like growth factor-I or vehicle. All growth factors were applied topically in a methylcellulose vehicle to full-thickness wounds every other day for 24 days. Efficacy end points were median and mean time to complete healing and rate of wound closure. The median time to complete healing for animals receiving the platelet-derived growth factor-BB/insulin-like growth factor-I combination was 38% and 33% faster (p < 0.001) than animals receiving 4.0 microg/cm(2) and 40.0 microg/cm(2) of platelet-derived growth factor-BB, respectively. The mean time to complete healing for platelet-derived growth factor/insulin-like growth factor-I treated animals was 31% and 29% faster (p < 0.001) than 4.0 microg/cm(2) and 40.0 microg/cm(2) platelet-derived growth factor-BB treated animals, respectively. Wounds treated with 4.0 microg/cm(2) platelet-derived growth factor-BB/insulin-like growth factor-I healed, on average, in 22 days compared with 31 days for 40.0 microg/cm(2) platelet-derived growth factor-BB alone and 38 days for vehicle. Also, platelet-derived growth factor-BB/insulin-like growth factor-I significantly improved the rate of wound closure throughout the duration of the studies compared with either dose of platelet-derived growth factor-BB alone (p < 0.005) or vehicle (p < 0.001). In conclusion, the data show that the combination of platelet-derived growth factor-BB and insulin-like growth factor-I is more effective than platelet-derived growth factor-BB alone at the doses tested or vehicle treatment in stimulating cutaneous wound healing in older, diabetic mice.

Journal Article↗
PubMed2002

Significance of platelet-reactive antibody screening for patients facing frequent platelet transfusions.

It is not clear whether platelet-reactive antibody screening is clinically significant for patients facing frequent platelet transfusions. On the basis of data from 96 patients who had been examined for platelet-reactive antibodies by the mixed passive hemagglutination method for a variety of reasons, we investigated the following three issues retrospectively: (1) the relationship between platelet-reactive antibodies and the occurrence of problems in platelet transfusions, such as refractoriness or nonhemolytic reactions; (2) the influence of a history of transfusion on the production of those antibodies; and (3) the effect of screening for those antibodies on the prompt administration of appropriate platelet components. More than half of the platelet transfusion-related problems were associated with platelet-reactive antibodies. For patients with a history of transfusion, the mean period before a clinical problem occurred with platelet transfusions was 9 days,compared with 66 days for those without such a history. Accordingly, during the period, patients with a history of transfusions received fewer units of platelets and had fewer donor exposures than did patients without such a history. On the other hand, most patients who had been screened in advance for those antibodies received appropriate platelet components without delay, whereas an average of 10 days was needed before those who had not been screened received compatible platelets. The patients who had not been screened were transfused with 68 units of random platelets on average during the period. When frequent platelet transfusions are anticipated, especially for patients with a history of transfusion, screening for platelet-reactive antibodies beforehand would be helpful for prompt administration of appropriate platelets, although problems, such as the cost of those platelets and the burden on donors, remain to be resolved.

Journal Article↗
PubMed1989

Platelet volume parameters as a diagnostic tool: the influence of anticoagulation and storage conditions on platelet impedance volume.

Rapid progress has been made in the design of aperture impedance cell counters, and parameters such as mean platelet volume and platelet distribution width have become routinely available to most physicians. Platelet volume is influenced by both platelet production in the bone marrow and platelet activation or sequestration in the circulation. In thrombocytopenic patients, it is often possible to differentiate between megakaryocytic and amegakaryocytic disease states on the basis of platelet volume analysis. In patients with thrombocytosis, a myeloproliferative disorder may be suspected if the platelet distribution width is high. However, the conditions of sample preparation and storage still give rise to considerable inaccuracy in the determination of platelet volume parameters. In this study, platelet impedance volume was strongly influenced by anticoagulation, storage time, and incubation temperature. Changes in platelet volume were more pronounced in whole blood than in platelet rich plasma. However, mainly large platelets were lost during the preparation of platelet rich plasma. Collecting blood directly into a mixture of citrate and low dose glutaraldehyde stabilized platelet volume for up to 2 h after venipuncture at room temperature. This method reduces platelet volume changes in vitro and is in this respect superior to the usual EDTA blood count or the use of platelet-inhibitory agents.

Anticoagulants↗
PubMed1997

Platelets and inflammation: role of platelet-derived growth factor, adhesion molecules and histamine.

Despite the fact that the relationship between platelets and the inflammatory and immune responses has been reviewed previously, the allocation of platelets among the inflammatory cells is still at issue. Recent developments in our understanding of platelet-associated signalling events have offered new potential insights into platelet functions in inflammatory and immune-related diseases. In recent years, it has been established that a range of molecules, mainly associated with the platelet surface and/or the platelet granules, regulate the capacity of platelets to cross-talk with other inflammatory cells during the process of inflammation, and of vascular inflammation in particular. This is the case with platelet-derived growth factor (PDGF), secreted from platelet alpha-granules, with P-selectin, expressed on the platelet surface, and with platelet histamine, which is secreted from platelets in response to aggregatory and inflammatory stimuli. The nature and mechanism of action of these regulatory molecules, physiologically present in platelets and mobilised upon platelet activation and aggregation, is the subject of this review. The participation of platelets, through PDGF, P-selectin and histamine, is also discussed in overtly inflammatory disorders, such as acute respiratory distress syndrome, mesangial glomerulonephritis, chronic inflammatory bowel disease, disseminated intravascular inflammation, and allergic vasculitis, focusing on possible pharmacological interventions specifically active against growth factors, adhesion molecules and platelet histamine.

Animals↗
PubMed1994

Independent roles for platelet crossmatching and HLA in the selection of platelets for alloimmunized patients.

BACKGROUND: Although HLA-matched platelets are frequently requested for alloimmunized patients, recent evidence has indicated that 1-hour posttransfusion platelet increments in these patients are specifically sensitive to crossmatch compatibility. STUDY DESIGN AND METHODS: To determine the extent of advantage gained by use of single-donor apheresis (SD) platelets selected on the basis of HLA match when crossmatch-compatible SD platelets were available, a total of 220 platelet transfusions given in the absence of individually determined significant nonimmune factors were analyzed in a well-characterized cohort of platelet-refractory patients. Platelets were selected by solid-phase crossmatch from a small donor pool of relatively poor HLA matches or, upon request, ordered as HLA-matched and later crossmatched. RESULTS: Alloimmunized patients responded better to SD platelets selected on the basis of HLA than to pooled platelet concentrates or SD platelets selected at random, although most of the benefit was limited to the 57-percent subset of good HLA matches. Crossmatch-compatible SD platelets provided similar posttransfusion platelet increments independent of the HLA match. None of 31 crossmatch-incompatible SD platelets transfused provided an adequate increment, including 13 that were ordered as HLA-matched platelets. CONCLUSION: No benefit could be demonstrated from requesting that SD platelets be HLA-matched when crossmatch-compatible SD platelets were available.

Blood Grouping and Crossmatching↗
PubMed2002

Reticulated platelets predict platelet count recovery following chemotherapy.

BACKGROUND: A laboratory measure that predicted the timing of platelet recovery after chemotherapy could guide prophylactic platelet transfusion. Reticulated platelets (RPs) are the youngest circulating platelets; an increased percentage of RPs is diagnostic of increased marrow platelet production, such as seen with idiopathic thrombocytopenic purpura, whereas a low percentage of RPs with thrombocytopenia indicates marrow suppression. This study examined whether the percentage of RPs, in combination with a newly devised measurement of "stress thrombopoiesis," the RP maturation index (RP-MI), could predict platelet count recovery following chemotherapy-induced thrombocytopenia. STUDY DESIGN AND METHODS: Platelet count nadirs were retrospectively determined in 35 chemotherapy-induced thrombocytopenia patients; percentage of RPs and RP-MI values were assayed at the early nadir (no imminent platelet recovery) and the late nadir (imminent platelet recovery). The latter was defined by a platelet count increase of 20 x 10(9) per L or more in the subsequent 48 hours without platelet transfusion. RESULTS: Early in the nadir (when platelet recovery did not occur in the subsequent 48 h after sampling), a low RP-MI and a low percentage of RPs were found in 29 of 35 patients. Late in the nadir, when recovery was imminent, 27 of 30 evaluable patients had elevated percentages of RPs or RP-MI values; the mean time from sampling to an increase of 20 x 10(9) per L or more was 42 hours. The positive and negative predictive values of this assay were 82 and 91 percent, respectively. Furthermore, when thrombocytopenia was severe (platelet count < or = 20 x 10(9)/L), an elevated RP-MI and/or percentage of RPs correctly predicted imminent platelet count recovery in five of five patients. CONCLUSION: This noninvasive, rapid, whole-blood assay of stress thrombopoiesis provides reproducible indices for timing platelet recovery following chemotherapy and the potential to optimize the use of prophylactic platelet transfusions in chemotherapy patients.

Adult↗
PubMed2004

Erythropoietin increases platelet reactivity and platelet counts in patients with alcoholic liver cirrhosis: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Patients with liver cirrhosis have a complex haemostasis disturbance including thrombocytopenia and abnormal bleeding time. Erythropoietin is the primary stimulator for erythrocyte production and also induces megakaryocyte formation. In healthy men erythropoietin increased platelet count and platelet reactivity. AIM: As patients with liver cirrhosis often undergo invasive procedures, we were interested to study whether erythropoietin could improve platelet function in addition to thrombocytopenia. METHODS: In total, 22 thrombocytopenic (platelet counts < 120 g/L) patients with alcoholic liver cirrhosis received either 100 IE/kg erythropoietin or placebo on days 1, 3 and 5 in a 2:1 randomized, placebo-controlled double-blind fashion. Platelet counts and platelet reactivity (activator-stimulated expression of P-selectin on platelets measured by flow cytometry) were determined on study days 1, 3, 5 and 9. RESULTS: Median platelet count was 80 g/L which is borderline for major elective surgical interventions. Baseline values were not different between groups (P > 0.05). Treatment with erythropoietin increased platelet count by 25% (P = 0.01) and platelet reactivity twofold (P < 0.01) vs. baseline. The increase in platelet count vs. baseline was more pronounced in patients with platelet counts <80 g/L. No significant effect was observed in the placebo group. CONCLUSIONS: Treatment with erythropoietin significantly increased platelet counts and platelet reactivity in patients with alcoholic liver cirrhosis. Preoperative treatment with erythropoietin is therefore expected to yield higher platelet levels and better platelet function.

Adult↗
PubMed1993

SIN-1 reduces platelet adhesion and platelet thrombus formation in a porcine model of balloon angioplasty.

BACKGROUND: Nitric oxide inhibits platelet adhesion and platelet aggregation in vivo. In this study, we investigated the effects of the nitric oxide donor SIN-1 on platelet adhesion and platelet-thrombus formation following experimental angioplasty. METHODS AND RESULTS: Bilateral carotid angioplasty was performed in 20 anesthetized pigs. Animals received either SIN-1 (3-morpholino-sydnonimine; 10 micrograms/kg/min; n = 8) or placebo (n = 8) before and during angioplasty. An additional control group of pigs received trimetaphan (n = 4), which induced hemodynamic changes similar to those that followed treatment with SIN-1. Platelet deposition was quantified by the injection of autologous 111In-labeled platelets. SIN-1 reduced platelet deposition after deep arterial injury compared with placebo (mean +/- SEM, 10.870 +/- 2.415 versus 40.326 +/- 9.889 platelets x 10(6)/cm2, p < 0.05). SIN-1 reduced platelet adhesion after superficial injury compared with both placebo and trimetaphan (2.231 +/- 0.333 versus 5.278 +/- 0.606 versus 5.022 +/- 1.136 platelets x 10(6)/cm2, respectively; p < 0.005). Scanning electron microscopy confirmed that platelets were deposited in the form of an adherent monolayer following superficial endothelial denudation and were reduced in number following treatment with SIN-1. The effects of SIN-1 on platelet function were associated with a significant increase in platelet cyclic GMP concentration from baseline (3.15 +/- 0.88 versus 1.58 +/- 0.73 pmol/10(9) platelets, p < 0.005). CONCLUSIONS: SIN-1 reduces platelet adhesion and platelet-thrombus formation following experimental angioplasty. The antiadhesive effects of SIN-1 are independent of changes in systemic hemodynamics. These results imply that the administration of a nitric oxide donor may prove effective in modifying the pathophysiological response to angioplasty injury.

Angioplasty, Balloon↗
PubMed2000

Imbalance between platelet vascular endothelial growth factor and platelet-derived growth factor in pulmonary hypertension. Effect of prostacyclin therapy.

Focal vascular injury and impaired endothelial function are features of pulmonary hypertension (PH) that lead to enhanced platelet endothelial cell interactions. Vascular endothelial growth factor (VEGF) is contained in platelets and released at sites of vascular injury to promote endothelial repair and wound healing in combination with platelet-derived nonspecific mitogens such as platelet-derived growth factor (PDGF). The overall balance between platelet VEGF and PDGF was investigated in 21 patients with primary PH, 8 with secondary PH, and 27 with chronic hypoxemic lung disease (CHLD), as well as in 29 control subjects. Platelet VEGF content was increased in patients with primary and secondary PH as compared with control subjects (518 +/- 89, 675 +/- 156, and 166 +/- 29 fg/10(5) platelets, respectively; p < 0.01), whereas platelet PDGF content was similar in the three groups (31 +/- 2, 36 +/- 4, and 33 +/- 3 pg/10(5) platelets, respectively; NS). Patients treated with a continuous prostacyclin infusion had a higher platelet VEGF but a similar platelet PDGF content as compared with untreated patients. Moderate increases in platelet VEGF and PDGF contents were observed in the CHLD patients. We conclude that patients with primary or secondary PH have an increase in platelet VEGF content, but not in platelet PDGF content, and that their platelet VEGF content increases further in response to prostacyclin infusion. We suggest that imbalance between platelet VEGF and PDGF is beneficial to patients with PH.

Adolescent↗
PubMed1987

Mechanisms of thrombocytopenia in chronic autoimmune thrombocytopenic purpura. Evidence of both impaired platelet production and increased platelet clearance.

Mechanisms of thrombocytopenia were studied in 38 patients with mild to moderately severe chronic autoimmune thrombocytopenia (AITP). 51Cr and 111In-labeled autologous platelet turnover studies and in vitro analysis of committed megakaryocyte progenitors (CFU-Meg) were used as independent measures of platelet production. Autologous 111In-labeled platelet localization studies were performed to assess platelet clearance. Although there was no increase in the frequency of marrow CFU-Meg, a specific increase in the CFU-Meg [3H]TdR suicide rate was seen which was inversely correlated with the platelet count (P less than 0.001). Platelet turnover studies showed significant numbers of patients had inappropriate thrombopoietic responses to their reduced platelet counts. Platelet-associated antibody levels correlated inversely with platelet turnover suggesting that antiplatelet antibody impairs platelet production. The circulating platelet count was best predicted by an index relating platelet production (i.e., turnover) to the spleen-liver platelet clearance that correlated directly with platelet survival (P less than 0.001). In summary, both depressed platelet production and increased platelet clearance by the liver and spleen contribute to the thrombocytopenia of AITP.

Autoantibodies↗