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PubMed1993

Short-term and long-term role of platelet activating factor as a mediator of in vivo platelet aggregation.

BACKGROUND: Platelet activating factor (PAF) is a phospholipid released upon stimulation by a variety of cells and has been implicated in several pathophysiological events such as asthma and inflammatory diseases. However, although the ability to aggregate platelets in vitro was the first biological activity ascribed to PAF, its role in contributing to the in vivo formation of arterial thrombi has not been thoroughly clarified. METHODS AND RESULTS: Intravascular platelet aggregation was initiated in two different animal models of arterial stenosis and endothelial injury. An external constrictor was positioned around rabbit carotid arteries and canine coronary arteries. After placement of the constrictor, a typical pattern of flow developed in the stenotic vessels. This pattern of flow, characterized by progressive reductions of carotid or coronary blood flow followed by spontaneous or induced restorations of flow (cyclic flow variations, CFVs), is related to recurrent platelet aggregation at the site of the stenosis followed by dislodgment of the thrombus. After observing CFVs for 30 minutes, BN52021 (up to 1.2 mg/kg), a potent and selective PAF antagonist, was given intravenously to rabbits (n = 12) and dogs (n = 10). BN52021 completely inhibited CFVs in 10 of 12 rabbits, whereas it was relatively ineffective in abolishing CFVs in dogs (only 2 of 10 animals inhibited). This different effect of BN52021 was not explained by too small a dose of the drug to achieve a complete blockade of PAF receptors in dogs, since ex vivo platelet aggregation was completely inhibited in both rabbits and dogs in response to exogenous PAF at concentrations up to 10(-5) mol/L. In a second group of 10 dogs, the hypothesis that PAF may become an important mediator of CFVs in dogs only several hours after endothelial injury was tested. After 30 minutes of baseline CFVs, these animals received a bolus of BN52021 up to 1.2 mg/kg. After this treatment, CFVs were completely abolished in 2 of 10 animals. The remaining 8 dogs were followed for an additional 8-hour period, at the end of which a second bolus of BN52021 was given. At this time, BN52021 was effective, as CFVs were abolished in 6 of 8 animals. These effects of BN52021 at 8 hours were not the consequence of a cumulative dose of the compound, since ex vivo platelet aggregation in response to PAF returned to baseline values immediately before administering the second dose. To identify possible sources of PAF other than aggregating platelets at the site of arterial stenosis, dogs in a third group were killed after 30 minutes (n = 7) and after 8 hours (n = 8) of CFVs. Histological sections of the stenotic coronary artery showed a marked leukocyte infiltration in these arterial segments after 8 hours of CFVs, whereas sections from dogs killed after 30 minutes showed only moderate or no infiltration. CONCLUSIONS: These data demonstrate that PAF plays an important role as a mediator of platelet aggregation in vivo in rabbits and dogs. In the canine model, PAF appears to become more important after leukocyte infiltration of the arterial wall, as it may contribute to initiating enough platelet activation to lead to cyclic flow variations at sites of arterial stenosis and endothelial injury. Data from the present study suggest that PAF antagonists may be used as antiplatelet agents.

Animals↗
PubMed1984

Platelet membrane glycoprotein IIIa contains target antigens that bind anti-platelet antibodies in immune thrombocytopenias.

The precise pathogenic mechanism of platelet destruction in immune thrombocytopenias is not known, although many investigators have found that platelet-associated IgG is increased in these diseases. We report here the differentiation between specific binding of anti-platelet antibody, associated with platelet destruction, and the ubiquitous presence of nonspecific, platelet-associated IgG. Using an electrophoretic separation and antibody overlay technique, we have identified a specific membrane protein that bears target platelet antigens in immune thrombocytopenias. When posttransfusion purpura serum was studied, antibody binding to the PlA1 antigen on glycoprotein IIIa was readily distinguished from the nonspecific binding of immunoglobulin to a protein of 200,000 mol wt. After reduction of disulfide bonds, the PlA1 antigenicity was not observed, and IgG bound nonspecifically to a protein band with an apparent molecular weight of 45,000. We have also identified anti-platelet antibodies in patients with idiopathic thrombocytopenic purpura and determined their antigenic specificity. Antibodies which bind to a 100,000-mol wt protein were found in nine of thirteen patients with chronic disease. The antigens in three of these cases were studied in detail by using both reduced and nonreduced control and Glanzmann's thrombasthenic platelets. Target antigens were localized to glycoprotein IIIa, but are different from PlA1. The immune thrombocytopenic purpura antigenic system is clearly distinguished from nonspecific platelet-associated IgG. Sera from eight children with acute idiopathic thrombocytopenic purpura were also studied. In all cases, the nonspecific IgG binding to the 200,000-mol wt protein was observed. However, we were unable to demonstrate antibody binding to glycoprotein IIIa, which suggested that the acute childhood form of this disease may have a different pathogenic mechanism than that of the autoimmune chronic cases.

Adolescent↗
PubMed1984

Platelet interaction with rabbit subendothelium in von Willebrand's disease: altered thrombus formation distinct from defective platelet adhesion.

Blood interaction with the subendothelium of rabbit aorta was investigated in an annular perfusion chamber using patients with von Willebrand's disease, hemophilia, and afibrinogenemia. The vessels were exposed to nonanticoagulated blood for a range of flow conditions (wall shear rates of 650-3,300 s-1) and exposure times (1.5-10 min). The resultant platelet and fibrin interaction was quantified by the use of several morphometric techniques, one of which was developed to measure more precisely the dimensions (height and volume) of platelet thrombi attached to the subendothelium. A major finding was that under flow conditions in which little or no defect in platelet adhesion was observed in von Willebrand's disease, platelet thrombus height and volume in this disorder were significantly reduced as compared with normal controls or patients with hemophilia. Thus, Factor VIII/von Willebrand factor (VIII/VWF) may mediate not only the adhesion of platelets to subendothelium but also platelet-platelet attachments necessary for normal thrombus development. The level of Factor VIII:coagulant activity (VIII: C) was also observed to influence the resultant thrombus height and volume deposited on subendothelium, presumably through the generation of thrombin or some other procoagulant factor preceding fibrin formation, since normal values of thrombus dimensions were always observed in a patient with a fibrinogen deficiency. The influence of VIII:C became greater as shear rate was reduced, whereas as shear rate was increased, VIII/VWF was more dominant in determining the resultant platelet deposition on subendothelium. Thus, the deficiencies of VIII:C and VIII/VWF in hemophilia and von Willebrand's disease can lead to various abnormalities in platelet and fibrin association with subendothelium. The importance of a particular deficiency will depend strongly on the local blood flow conditions.

Adult↗
PubMed2004

Human bone marrow megakaryocytes and platelets express PPARgamma, and PPARgamma agonists blunt platelet release of CD40 ligand and thromboxanes.

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-activated transcription factor important in lipid metabolism, diabetes, and inflammation. We evaluated whether human platelets and megakaryocytes express PPARgamma and whether PPARgamma agonists influence platelet release of bioactive mediators. Although PPARgamma is mainly considered a nuclear receptor, we show that enucleate platelets highly express PPARgamma protein as shown by Western blotting, flow cytometry, and immunocytochemistry. Meg-01 megakaryocyte cells and human bone marrow megakaryocytes also express PPARgamma. Platelet and Meg-01 PPARgamma bound the PPARgamma DNA consensus sequence, and this was enhanced by PPARgamma agonists. Platelets are essential not only for clotting, but have an emerging role in inflammation in part due to their release or production of the proinflammatory and proatherogenic mediators CD40 ligand (CD40L) and thromboxanes (TXs). Platelet incubation with a natural PPARgamma agonist, 15d-PGJ(2), or with a potent synthetic PPARgamma ligand, rosiglitazone, prevented thrombin-induced CD40L surface expression and release of CD40L and thromboxane B(2) (TXB(2)). 15d-PGJ(2) also inhibited platelet aggregation and adenosine triphosphate (ATP) release. Our results show that human platelets express PPARgamma and that PPARgamma agonists such as the thiazolidinedione class of antidiabetic drugs have a new target cell, the platelet. This may represent a novel mechanism for treatment of inflammation, thrombosis, and vascular disease in high-risk patients.

Adenosine Triphosphate↗
PubMed2005

Platelet aggregation induces platelet aggregate stability via SLAM family receptor signaling.

Platelet aggregation is a dynamic entity, capable of directing its own growth and stability via the activation of signaling cascades that lead to the expression and secretion of various secondary agonists. Here we show that the signaling pathways triggered during platelet aggregation include an intrinsic pro-thrombotic activity mediated by 2 homophilic adhesion molecules, CD84 and CD150 (SLAM [signaling lymphocyte activation molecule]), which are tyrosine phosphorylated in a platelet aggregation-dependent fashion. The 2 CD84/SLAM adapter proteins, SAP (SLAM-associated protein) and EAT-2 (EWS-activated transcript-2), were found in platelets; only SAP, however, was found to immunoprecipitate with tyrosine-phosphorylated SLAM. The immobilized extracellular domain of CD84 promoted microaggregate formation, while SAP-deficient platelets demonstrated defective spreading on immobilized CD84, demonstrating a functional role in platelets for SLAM family interactions. Finally, analysis of SLAM-deficient mice revealed an overall defect in platelet aggregation in vitro and a delayed arterial thrombotic process in vivo. The data indicate that signaling of the adhesion molecules in the SLAM family, activated by proximity during aggregation, further stabilize platelet-platelet interactions in thrombosis.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Effects of marathon running on platelet activation markers : direct evidence for in vivo platelet activation.

We used the ADVIA 2120 Hematology System (Bayer HealthCare, Diagnostics Division, Tarrytown, NY) to study the effects of vigorous exercise on CBC count, WBC differential, RBC fragmentation, and platelet activation parameters in 32 healthy participants in a 26.2-mile (42.2-km) marathon. The runners demonstrated increases in hematocrit and platelet count consistent with dehydration and leukocytosis indicative of demargination of neutrophils or inflammation secondary to tissue destruction (eg, rhabdomyolysis). The number of RBC fragments was increased after the race (P = .008), consistent with exercise-induced hemolysis. The mean platelet component, a measure of platelet granularity, was decreased (P < .0001), and the number of platelet clumps was increased (P = .0026), providing evidence for in vivo platelet activation during the marathon. By using direct measurement of platelet granularity, our study confirms the in vivo activation of platelets by vigorous exercise and establishes the usefulness of automated cell counters for the assessment of platelet activation and of RBC fragmentation in this setting.

Adult↗
PubMed1999

Human platelets contain SNARE proteins and a Sec1p homologue that interacts with syntaxin 4 and is phosphorylated after thrombin activation: implications for platelet secretion.

In response to thrombin and other extracellular activators, platelets secrete molecules from large intracellular vesicles (granules) to initiate thrombosis. Little is known about the molecular machinery responsible for vesicle docking and secretion in platelets and the linkage of that machinery to cell activation. We found that platelet membranes contain a full complement of interacting proteins-VAMP, SNAP-25, and syntaxin 4-that are necessary for vesicle docking and fusion with the plasma membrane. Platelets also contain an uncharacterized homologue of the Sec1p family that appears to regulate vesicle docking through its binding with a cognate syntaxin. This platelet Sec1 protein (PSP) bound to syntaxin 4 and thereby excluded the binding of SNAP-25 with syntaxin 4, an interaction critical to vesicle docking. As predicted by its sequence, PSP was detected predominantly in the platelet cytosol and was phosphorylated in vitro by protein kinase C (PKC), a secretion-linked kinase, incorporating 0.87 +/- 0.11 mol of PO4 per mole of protein. PSP was also specifically phosphorylated in permeabilized platelets after cellular stimulation by phorbol esters or thrombin and this phosphorylation was blocked by the PKC inhibitor Ro-31-8220. Phosphorylation by PKC in vitro inhibited PSP from binding to syntaxin 4. Taken together, these studies indicate that platelets, like neurons and other cells capable of regulated secretion, contain a unique complement of interacting vesicle docking proteins and PSP, a putative regulator of vesicle docking. The PKC-dependent phosphorylation of PSP in activated platelets and its inhibitory effects on syntaxin 4 binding provide a novel functional link that may be important in coupling the processes of cell activation, intracellular signaling, and secretion.

Amino Acid Sequence↗
PubMed2000

Geldanamycin disrupts platelet-membrane structure, leading to membrane permeabilization and inhibition of platelet aggregation.

Geldanamycin (GA), a benzoquinoid ansamycin antibiotic, has been used as a tyrosine kinase inhibitor and an anti-tumour agent and is known to bind to heat-shock protein 90. In the present study on human platelets we have found that GA inhibited platelet aggregation induced by ADP, thrombin and the thrombin-receptor-activating peptide and caused platelet plasma-membrane damage, detected by leakage of adenine nucleotides as well as serotonin. Scanning electron microscopy (SEM) revealed that platelet exposure to GA led to the formation of holes or fenestrations in the platelet plasma membrane, confirming GA's ability to initiate membrane damage. In addition, GA itself caused both the dephosphorylation and phosphorylation of proteins in resting platelets and prevented agonist-induced phosphorylation of pleckstrin, the 20-kDa myosin light chain and other proteins. Another ansamycin, herbimycin A, also inhibited platelet aggregation, but caused minimal membrane permeabilization, as detected by (3)H release from platelets labelled previously with [(3)H]adenine, and much less membrane damage, revealed by SEM. Overall, GA is able to disrupt membrane structure and inhibit platelet aggregation, an ability which may be linked to alterations in the activity of protein kinases and phosphatases.

Adenine Nucleotides↗
PubMed1976

Clot retraction: evaluation in dilute suspensions of platelet-rich plasma and gel-separated platelets.

Suspensions of platelet-rich plasma (PRP) or gel-separated platelets (GSP) can be used to evaluate clot retraction subsequent to platelet aggregation and fibrin formation. PRP (200,000 per cubic millimeter) or GSP (200,000 or 100,000 per cubic millimeter) are diluted 1:10 (PRP) or 1:8 (GSP) in phosphate buffer, pH 7.4, and clotted with a high concentration (2.5 U. per milliliter) of thrombin. Human fibrinogen (25 mg. per cent) is added to GSP prior to dilution. Clot retraction is 91 to 100 per cent completed in 1 hour and is quantified by measurement of residual fluid volume. Test conditions are unfavorable for fibrinolysis. Very low concentrations of fibrin/fibrinogen degradation products D and E are detected in residual fluid, and no erythrocyte fall-out occurs. Furthermore, the extent of retraction in the dilute systems is related only to platelet numbers and platelet function. The dilute PRP and GSP methods allow evaluation of clot retraction in the presence of PGE1, the most potent inhibitor of platelet aggregation induced by conventional concentrations of collagen, ADP, epinephrine, and thrombin (0.1 to 0.5 U. per milliliter). High concentrations of PGE1 (to 6 x 10(-6) M) do not inhibit aggregation of GSP, fibrin formation, or platelet-fibrin interaction induced by 2.5 U. per milliliter of thrombin. In contrast, PGE1 concentrations as low as 1.5 to 3.0 x 10(-8) M inhibit clot retraction in both the dilute PRP and GSP systems. Thus, using dilute PRP or GSP the effects of platelet aggregation inhibitors on clot retraction can be determined independently of effects on platelet aggregation.

Blood Cell Count↗
PubMed2002

[Activation of random-donor platelet concentrates and platelet prepared from random-donor apheresis collections during storage].

The activation of random-donor platelet concentrates and platelets prepared from random-donor apheresis collections (plateletpheresis) during storage were studied. Percentage of CD62p staining and mean channel fluorescence (MCF) of CD41 of two kinds of platelets during storage on day 0, day 1, day 3 and day 5 were determined by flow cytometry. The results showed that percentages of CD62p staining and MCF of CD41 in plateletpheresis were (18.91 +/- 6.25)%, (19.48 +/- 8.27)%, (22.82 +/- 6.06)%, (56.71 +/- 11.79)% and (8.09 +/- 2.38)%, (8.13 +/- 2.45)%, (8.44 +/- 2.51)%, (19.87 +/- 6.13)%, while the results of platelet concentrates were (30.65 +/- 12.33)%, (31.46 +/- 11.86)%, (32.51 +/- 13.05)%, (63.55 +/- 13.27)% and (10.33 +/- 4.37)%, (11.09 +/- 6.61)%, (13.46 +/- 9.69)%, (24.41 +/- 10.15)%, respectively. The platelet count and pH value were also determined. The platelet number, pH value, percentage of CD62p staining and MCF of CD41 had no significant difference within 3 days of platelet storage. The platelet number and pH value decreased significantly (P < 0.001), while percentages of CD62p staining and MCF of CD41 increased significantly (P < 0.001) on day 5 of storage. It is concluded that the quality of plateletpheresis is better than platelet concentrate.

Blood Donors↗
PubMed2000

Anti-human platelet tetraspanin (CD9) monoclonal antibodies induce platelet integrin alphaIIbbeta3 activation in a Fc receptor-independent fashion.

OBJECTIVE: This study characterized the activation of platelet integrin alphaIIbbeta3 induced by two anti-human platelet tetraspanin monoclonal antibodies (mAbs), HI117 and SJ9A4. METHODS: Using 125I-labeled human fibrinogen(Fg), specific Fg binding to human platelets induced by HI117 and SJ9A4 was measured as indication of activation of platelet integrin alphaIIbbeta3 by the two mAbs. RESULTS: HI117 and SJ9A4 (10 microg/ml and 20 microg/ml) induced evident specific Fg binding to human platelets, suggesting that the two mAbs evoked activation of platelet integrin alphaIIbbeta3. Further study indicated that HI117 and SJ9A4 induced integrin alphaIIbbeta3 activation independent of platelet Fc-receptors, and that HI117 and SJ9A4-induced integrin alphaIIbbeta3 activation was inhibited by sphingosing, aspirin, apyrase, and/or PGI2. CONCLUSION: The anti-platelet tetraspanin (CD9) mAbs, HI117 and SJ9A4, can induce platelet integrin alphaIIbbeta3 activation independent of Fc-receptor. Three signaling pathways, i.e. thromboxane, secreted ADP, and cAMP pathways may be involved in the process, with protein kinase C activation presumably being the common step of the three pathways.

Antibodies, Monoclonal↗
PubMed2004

A rapid platelet function assay used to regulate platelet transfusion prophylaxis following cardiopulmonary bypass surgery.

Subsequent to cardiac surgery with cardiopulmonary bypass (CPB), patients are at risk of postoperative bleeding caused by acquired defects associated with the procedure. As such, many patients receive prophylactic blood product transfusion. The effectiveness of measuring platelet function using a near-patient platelet function analyzer for the purpose of regulating platelet transfusion and potentially modulating other blood products including fresh frozen plasma (FFP) and cryoprecipitate (CRYO) transfusion was evaluated prospectively in patients undergoing CPB. A 6-month prospective study was designed that encompassed all CPB patients at Aultman Hospital (Canton, OH) during 2001. Each patient was assessed postoperatively for platelet count and function using a point-of-care analyzer. Data were used to help determine whether a platelet transfusion would be administered. Transfusion of CRYO and FFP was also recorded. The data were then compared to the retrospective same 6-month period in the preceding year for the purpose of determining the value of this system in guiding transfusion triage. There were 1770 platelet packs transfused during the study period, representing a 34% reduction in platelet usage. Platelet transfusions were reduced by 51% (5.75 in 2001 vs. 11.75 in 2000) per patient. CRYO/FFP usage was also substantially reduced. During the study period, the patient caseload had increased by 72 (310 vs. 238). Monitoring platelet count and function as a result of CPB and administering an appropriate transfusion protocol can positively impact transfusion outcome.

Autoanalysis↗
PubMed2004

All platelets are not equal: COAT platelets.

Collagen- and thrombin-activated (COAT) platelets were first described in 2000 and have attracted considerable interest, changing the interpretation of the way in which platelets contribute to thrombin generation and how their procoagulant activity is organized. Platelets activated by two agonists coming from glycoprotein VI or Fc gamma-receptor IIA agonists on the one hand and thrombin on the other produce a population of approximately 50% highly procoagulant active platelets. This subgroup is formed by tissue transglutaminase and factor XIIIa linking of serotonin to the procoagulant proteins from granules or plasma, and these serotonylated proteins bind to fibrinogen or thrombospondin on the platelet surface. Serotonylation in the platelet cytoplasm has recently been shown to be an important regulating mechanism governing the activation of small GTPases and their function in granule release. Recent studies with Tph-/- mice in which the peripheral serotonin, including that in platelets, is very strongly reduced, have shown a prolonged bleeding time, suggesting it has an important hemostatic role in the release of platelet von Willebrand factor. More knowledge about how COAT platelets are formed will be important for a better understanding of the physiology and pathology of hemostasis.

Blood Coagulation Factors↗
PubMedDate not supplied

Platelet deposition on polyethylene. Dependence of second layer platelet attachment on von Willebrand's disease plasma.

The role of von Willebrand's factor (VWF) was examined in platelet deposition on polyethylene by exposing 3/16 inch diameter discs of polyethylene to 111In labeled platelets re-suspended in citrated blood from normal and severe von Willebrand's disease donors. Discs were oscillated for 30 and 60 min, washed, fixed, counted for 111In, and examined by scanning electron microscopy (SEM). Total platelet deposition in the 0% VWF group was significantly greater than control discs at 30 min (7.0 x 10(6) +/- 0.5 compared with 3.29 x 10(6) +/- 0.6 platelets/cm2). The SEM examination revealed patches of spread platelets, with platelets adhering to platelets in controls. A dense, uniform monolayer of platelets was found on the 0% VWF discs. At 60 min, control discs had significant increases in the platelet deposition with SEM examination revealing uniform coverage of the disc with additional platelets.

Biocompatible Materials↗
PubMedDate not supplied

Dipyridamole potentiates the inhibition of platelet aggregation by aspirin (in human platelet rich plasma and whole blood).

This study investigates the influence of dipyridamole on platelet aggregation as evaluated by a single agonist or a pair of agonists in human platelet rich plasma and whole blood. Dipyridamole up to 30 microM was not found to influence the platelet aggregation of platelet rich plasma or whole blood; aspirin (100 microM), on the contrary, did inhibit platelet aggregation. The inhibition of platelet aggregation by aspirin could be reversed by using high concentrations of agonists or pairs of agonists. In this model dipyridamole inhibited platelet aggregation in both platelet rich plasma and whole blood in a dose-dependent fashion. Thromboxane A2 was less than 10% of controls in aspirin-treated PRP stimulated with low or high concentrations of collagen or with a pair of agonists. This study suggests that dipyridamole has direct antiplatelet activity in platelet rich plasma and whole blood when the cyclooxygenase pathway is blocked by aspirin.

Adult↗
PubMed1977

Effects of prostaglandins, derivatives of cyclic 3':5'-AMP, theophylline, cholinergic agents and colchicine on clot retraction in dilute platelet-rich plasma and gel-separated platelet test systems.

In dilute suspensions of platelet-rich plasma (PRP) or gel-separated platelets (GSP), dibutyryl-cAMP (DBcAMP) and monobutyryl-cAMP inhibited platelet-mediated fibrin clot retraction in concentrations of 2--3 X 10(-6) M, with complete inhibition at 1--3 X 10(-4) M. Prostaglandin E1 (PGE1), which inhibited fibrin clot retraction in concentrations greater than 1.5--3 X 10(-8) M, was a more effective inhibitor than either PGE2 or PGF2 alpha. In the presence of theophylline (10-4 M), concentrations of DBcAMP, PGE1, PGE2 and PGF2 alpha necessary to inhibit fibrin clot retraction were reduced 50-fold for DBcAMP and 2.5 to 20-fold for the prostaglandins. In dilute PRP or GSP, inhibition of fibrin clot retraction does not result from inhibition of thrombin-induced platelet aggregation. Thus, compounds which increase platelet cAMP levels result in the inhibition of platelet-mediated fibrin clot retraction, and this inhibitory effect may be mediated, at least in part, through suppression of platelet contractility. Cyclic GMP, dibutyryl-cGMP and carbamylcholine-Cl (which stimulate guanylate cyclase) did not influence fibrin clot retraction, and did not prevent inhibition of fibrin clot retraction by DBcAMP and PGE1. Colchicine, in concentrations known to disrupt platelet microtubules (2.5 X 10(-6) M to 2.5 X 10(-3) M), had little inhibitory effect on either fibrin clot retraction or platelet (3H)-serotonin release.

Blood Coagulation↗
PubMed1990

Regulation of platelet heterogeneity: effects of thrombocytopenia on platelet volume and density.

We have examined the effects of variable degrees of acute thrombocytopenia on platelet levels, mean platelet volume (MPV), and buoyant density after induction of thrombocytopenia by platelet antiserum (PAS) in mice with or without spleens. Mice were studied serially 10-16, 36, 48, 60-64, 84, 108, 144, 180, 228, 276, 348-360, 372, and 516 h after PAS treatment. MPV and platelet count (PC) x 10(6)/microliters for normal intact mice (n = 136) were 4.7 +/- 0.3 fl (SD) and 1.69 +/- 0.52 (SD), respectively. Twelve hours after PAS-induced severe thrombocytopenia (PC less than 0.05 x 10(6)/microliters), MPV increased significantly (p less than 0.01) to 6.4 fl, was maximal at 36 h (8.2 fl), remained elevated until 144 h following PAS treatment, and then returned to normal. Platelet density decreased significantly (p less than 0.05) 64 h after PAS treatment and returned to normal at 144 h. Hematocrits of repeatedly bled intact control mice decreased from 45% to 30%, accompanied by thrombocytosis (maximal PC 2.24 x 10(6)/microliters) without significant changes in either MPV or platelet density. Moderate thrombocytopenia (PC 0.1-0.2 x 10(6)/microliters) in intact mice produced significantly (p less than 0.05) increased MPV, at 5.7 fl 12 h after PAS treatment, with a peak MPV of 7.6 fl (p less than 0.001) at 36 h; MPV returned to normal at 84 h. Platelet density decreased (p less than 0.001) 12 h after PAS treatment and returned to baseline at 228 h. Control splenectomized mice (n = 185) had an MPV of 5.0 fl +/- 0.7 fl and a PC of 2.14 +/- 0.6 x 10(6)/microliters. Comparably severe and moderate thrombocytopenia in splenectomized mice produced alterations in platelet count, MPV, and density similar to those in intact mice, although maximal MPV and the degree of rebound thrombocytosis after severe thrombocytopenia were more marked in splenectomized mice. In response to reduction of the platelet mass in both intact and splenectomized mice, MPV increased in proportion to the severity of thrombocytopenia, occurred as early as 4 h after induction, and persisted during early rebound thrombocytosis. Previous observations that megakaryocyte ploidy did not shift until 48 h after onset of thrombocytopenia confirm that both initial and maximal changes in MPV in response to this stimulus are regulated by processes other than alterations of megakaryocyte DNA levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Expression of fibrinogen receptors in platelets of migraine patients--correlation with platelet GPIIb content and plasma cholesterol.

Binding of fibrinogen to platelets washed from blood of migraine patients (n = 30) and control donors (n = 24) was compared. In addition, contents of platelet glycoprotein IIb and platelet fibrinogen were determined in both groups by radioimmunoassay. The receptor capacity for fibrinogen in platelets activated by ADP was significantly higher (p less than 0.01) in migraine patients (52,505 +/- 4,925) than in controls (33,881 +/- 3,965). The mean contents of GPIIb (3.51 +/- 0.34 micrograms/10(8) platelets) and fibrinogen (37.26 +/- 4.05 micrograms/10(8) platelets) in migraine platelets were also markedly increased (p less than 0.01 and p less than 0.001, respectively) when compared to controls (2.21 +/- 0.18 micrograms of GPIIb and 18.75 +/- 2.29 micrograms of fibrinogen per 10(8) platelets, respectively). There was a high correlation between the number of fibrinogen receptors exposed by ADP and the total amount of platelet GPIIb both in migraine patients (R = 0.69, p less than 0.01) and controls (R = 0.62 p less than 0.01), as well as plasma cholesterol in the case of migraine patients (R = 0.82, p less than 0.001).

Adult↗