Biomedical subjects

W Jy

Publications and source records attributed to W Jy.

At least 19 recordsLinked to original sources

PubMed1998

Platelet activation in Alzheimer disease.

BACKGROUND: In light of recent reports of diminished platelet serotonin concentration and increased plasma serotonin levels in patients with Alzheimer disease (AD), we hypothesized that a state of heightened platelet activation might be present in AD. OBJECTIVE: To compare baseline activation of unstimulated platelets in patients with AD with that in control subjects. PATIENTS AND METHODS: Flow cytometry was used to measure platelet activation in 91 patients with probable AD and 40 age-matched control subjects. Groups were compared for percentage of circulating platelet aggregates, expression of CD62p, formation of leukocyte-platelet complexes, and presence of circulating platelet microparticles, controlling for effects of demographic, clinical, physiological, and logistical factors. RESULTS: Multiple analysis of covariance on ranked data revealed a 39.5% increase in percentage of platelet aggregates (P=.0001), a 59.3% increase in expression of CD62p (P=.001), and a 53.3% increase in leukocyte-platelet complexes (P=.0001) in the group with AD but no differences in the number of platelet microparticles, overall platelet count, plasma fibrinogen level, or plasma platelet factor 3. Activation was weakly correlated with sex, but was independent of age, severity of disease, duration of disease, depression, agitation, and family history of dementia. CONCLUSIONS: Platelets of patients with AD exhibit greater unstimulated activation than those of controls. Potential causes of such activation include possible stimulation of platelets by damaged cerebral endothelial cells or platelet activation induced by membrane abnormalities previously reported to be present in platelets of patients with AD. In light of recent evidence that platelets are the principal source of both amyloid precursor protein and beta-amyloid peptide in human blood, it is possible that AD platelet activation may reflect or even contribute to the pathogenesis of the disease.

Aged↗

PubMed1998

Platelet aggregates as markers of platelet activation: characterization of flow cytometric method suitable for clinical applications.

The present paper describes a flow cytometric method for assay of platelet aggregates (PAg) in blood. This method combines and simplifies previously reported techniques, simultaneously enumerating PAg formed upon platelet activation, their expression of activation marker CD62P (P-selectin), and their content of bound leukocytes (LPAg). The sensitivity of this method to low levels of agonists (ADP, collagen) is compared to conventional aggregometry and some features of platelet-leukocyte interaction are explored. The results were: (1) ADP or collagen induced a dose-dependent increase in PAg number and corresponding decline in free platelets. The ED50 for ADP (0.15 microM) and for collagen (0.2 microg/mL) was about 1/20 the ED50 found by aggregometry, indicating 20-fold greater sensitivity. (2) At higher concentrations, the fraction of PAg with bound leukocytes (LPAg) increased to 60-70%. This rise correlated with PAg size and CD62P expression, but not with the number of PAg formed. (3) The response of whole blood (WBD) to agonists was qualitatively different from that of platelet-rich plasma (PRP): in WBD the population of CD62P+ PAg was much higher than in PRP and the population of CD62P+ free platelets was much lower. This implies that leukocytes rapidly recruit activated platelets. (4) Desmopressin (DDAVP) at 5 nmol/L induced a significant rise in activated (CD62P+) PAg and platelets, even though no effect of DDAVP could be detected by conventional aggregometry; this further confirms that DDAVP acts directly on platelets. (5) Plasma samples from TTP patients induced a rise in PAg when added to normal PRP, though little or no effect could be detected by aggregometry. In summary, the flow cytometric method described here appears useful for detecting low levels of platelet activation and provides information on platelet leukocyte interaction, potentially important in identifying and differentiating thrombogenic states. Since it is rapid and economical, it is well suited for clinical implementation.

Biomarkers↗

PubMed1998

Thrombotic thrombocytopenic purpura plasma enhances platelet-leucocyte interaction in vitro.

In thrombotic thrombocytopenic purpura (TTP), intravascular platelet aggregation and formation of platelet-rich thrombi impair the microcirculation. TTP plasma has been shown to induce aggregation of normal platelets in vitro. The present study investigates the formation of activated platelet aggregates (aPAg) induced by TTP plasma, with particular attention to their binding to leucocytes (LPAg). Results were compared with the effects of plasmas from normal controls (CTL) and from patients with immune thrombocytopenic purpura (ITP) or thrombosis (THR). Following addition of test plasma to normal whole blood (WB), aPAg and LPAg were assayed by flow cytometry using mAbs against CD41 (platelet marker), CD62p (platelet activation marker) and CD45 (pan-leucocyte marker), Compared to control plasma, TTP plasma was more potent than ITP or THR plasma in increasing aPAg: only TTP plasma significantly promoted leucocyte binding to give increased LPAg. Prior removal of neutrophils (PMN) from WB by beads coated with anti-CD15 mAb largely prevented formation of aPAg and LPAg. However, TTP plasma added to normal platelet-rich plasma significantly increased aPAg, which suggested possible hindrance of aPAg formation by erythrocytes and other leucocytes in PMN-depleted blood. We concluded that TTP plasma was most potent in the induction of aPAg and unique in promoting LPAg formation in WB. Neutrophils, and not other leucocytes, appear to be essential for LPAg formation. Enhanced PMN-platelet interaction in the microcirculation may facilitate platelet adhesion to vessel walls and promote the formation of platelet-rich microthrombi in TTP.

Adult↗

PubMed1998

Anti-CD36 autoantibodies in thrombotic thrombocytopenic purpura and other thrombotic disorders: identification of an 85 kD form of CD36 as a target antigen.

The presence of anti-CD36 antibodies in plasma of patients with thrombotic thrombocytopenic purpura (TTP), idiopathic thrombocytopenic purpura (ITP), and heparin-induced thrombocytopenia without/with thrombosis (HIT/HITT) has been examined by immunoblots, and a monoclonal antibody capture assay, the platelet-associated IgG characterization assay (PAICA). Results with PAICA showed that 73% (8/11) of patients with TTP were positive, and 71% (10/14) by immunoblots. With ITP, 20% (6/30) were positive by PAICA and 19% (3/16) by immunoblots; HIT, 30% (3/10) were positive by PAICA and 60% (6/10) by immunoblot; HITT, 50% (2/4) by PAICA and 100% (4/4) by immunoblot. Purification of CD36 by fast protein liquid chromatography (FPLC) from Triton X-100 extracts of normal platelet membranes resulted in the isolation of two different forms: the classic 88 kD form, and a second, lighter 85 kD form. Our data indicated that the patients' plasma autoantibodies reacted strongly with the 85 kD form. Conventional monoclonal and polyclonal antisera produced to the 88 kD form reacted strongly with the 88 kD form but weakly with the 85 kD form. These results confirm the possible importance of anti-CD36 antibodies in the pathophysiology of TTP and other thrombocytopenias and demonstrate the presence of a previously unrecognized target antigen for these antibodies.

Autoantibodies↗

PubMed1997

Danazol for paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal stem-cell disorder in which blood cells lack complement inhibiting membrane proteins, and become susceptible to complement-mediated injury, leading to chronic intravascular hemolysis and pancytopenia. Glucocorticoids have been a mainstay of therapy. For patients refractory to glucocorticoids and requiring blood transfusions, an alternative therapy is needed. We studied danazol therapy in 5 patients refractory to other treatments. Four of the 5 benefited, showing rise in hematocrit and eventual cessation of transfusion requirements. Remissions lasted > or =2 years in 3 and 10 years in 1 patient. Danazol was well-tolerated without serious side effects. Danazol appears to be a good alternative treatment in PNH.

Adolescent↗

PubMed1997

Platelet microparticles and calcium homeostasis in acute coronary ischemias.

UNLABELLED: Elevation of free cytoplasmic calcium is the common pathway of platelet activation, leading to shape change, shedding of platelet microparticles (PMP), aggregation, and secretion of internal granules, including expression of CD62p on the surface. Platelet activation is well documented in unstable angina (UA) and acute myocardial infarction (MI). We investigated the following markers of platelet activation in 55 patients undergoing coronary angiography for suspected CAD: free cytoplasmic calcium, [Ca2+]cyt, PMP, CD62p expression, and platelet/leukocyte (P/L) interaction. [Ca2+]cyt was measured by Fluo-3 and the other measurements were by flow cytometry. Patients were classified into three groups: unstable angina (UA, n = 11), recent myocardial infarction (MI, n = 11), and patient controls (CTL, n = 33). Blood was drawn before infusion of heparin through femoral lines at the time of catheterizaton for assays. ( RESULTS: (1) PMP values were significantly higher in both UA and MI than in CTL, P < 0.05. There was no difference between UA and MI. (2) P/L interaction was significantly elevated only in UA, P < 0.05. (3) CD62p expression on free platelets did not differ significantly between any of the three groups. (4) The resting [Ca2+]cyt, thrombin-induced Ca2+ influx, and release of Ca2+ from internal stores were all significantly higher in platelets from the combined patient group (UA + MI) than in the patient control group, P < 0.001 CONCLUSIONS: Results on calcium hemostasis and PMP were significantly different in patients with acute coronary syndromes than those with stable angina or no coronary ischemia; this may reflect underlying pathophysiology of acute coronary ischemia. P/L interaction was higher only in the UA group, suggesting a role of leukocytes in UA.

Acute Disease↗

PubMed1996

Supplemental L-arginine HCl augments bacterial phagocytosis in human polymorphonuclear leukocytes.

That L-arginine (L-Arg) augments the host response to acute bacterial sepsis suggests that this amino acid intervenes early in the immune response, perhaps via the nitric oxide synthetase (NOS) pathway. The effect of L-Arg supplementation on in vitro phagocytosis of fluorescein-labeled, heat-killed Staphylococcus aureus by peripheral blood neutrophils (PMNs) from 12 normal human volunteers was studied. Separated PMNs were incubated for 2 h with labeled bacteria, with and without supplemental L-Arg, D-arginine, glycine, and/or the NOS inhibitors L-canavanine, aminoguanidine, or L-NG-nitroarginine methyl ester. PMNs were fixed and extracellular fluorescence quenched with crystal violet. By flow cytometry and confocal microscopy, L-Arg supplementation was shown to result in a highly significant increase in PMN bacterial phagocytosis, the maximal effect being seen with L-Arg 380 microM and falling off with higher concentrations. This augmentation was completely abrogated by NOS inhibitors in molar excess, but inhibitors alone did not suppress phagocytosis below that of unsupplemented controls. Neither D-arginine nor glycine affected phagocytosis; the L-Arg effect was stereospecific and not related to utilization of L-Arg as an energy source. L-Arg supplementation significantly enhances bacterial phagocytosis in human neutrophils, perhaps by effects on cytoskeletal phenomena, and this appears to be mediated through NOS activity. Phagocytosis by nonspecific immune cells which intervene early in the response to sepsis is critically important, and beneficial effects of L-Arg on the clinical course of sepsis may be due at least in part to augmentation of phagocyte function.

Arginine↗

PubMed1996

Involvement of CD44 and the cytoskeletal linker protein ankyrin in human neutrophil bacterial phagocytosis.

The leukocyte CD44 and CD45 cell surface receptors are associated via the linker proteins ankyrin and fodrin with the cytoskeleton, which itself is important in immune cell functions such as adherence, chemotaxis, and phagocytosis. The effects of rat antihuman CD44 and CD45 monoclonal antibodies on phagocytosis of fluoresceinated heat-killed Staphylococcus aureus 502A by normal human neutrophils (PMNs) during 2 hr incubation in RPMI-1640 was studied via flow cytometry and confocal microscopy. Flow cytometry was performed using an excitation wavelength of 488 nm, fluorescence being measured at 515-560 nm on 50,000 PMNs per sample. Confocal microscopy was performed on samples after further incubation with rhodamine-conjugated antiankyrin. Anti-CD44 resulted in an increase of 27-31% compared to control (P = 0.004) in the proportion of PMNs fluorescing, an increase of 17-24% (P = 0.001) in mean intracellular fluorescence per PMN, and an increase in total PMN fluorescence of 50-58% compared to control (P < 0.001). In contrast, anti-CD45 had little effect on phagocytosis. Colchicine (a microtubule-disrupting agent) enhanced, whereas cytochalasin-D (a microfilament inhibitor) inhibited bacterial phagocytosis; cytochalasin-D completely abrogated the effect of anti-CD44 on this PMN function. Hyaluronic acid augmented phagocytosis by an increment similar to that observed with anti-CD44. Two-color flow cytometry and confocal microscopy demonstrated that ankyrin always colocalized with ingested fluorescein isothiocyanate (FITC)-labeled bacteria. These data strongly suggest that CD44 is involved in bacterial phagocytosis, provide further evidence of CD44 receptor linkage to cytoskeletal elements in human leukocytes, and suggest that ankyrin has a significant role in the transport of phagosomes.

Ankyrins↗

PubMed1996

Association of murine splenocyte CD3 complex to the cytoskeleton: absence of modulation by exogenous fatty acids.

The cytoplasmic regions of the CD3 complex are presumably involved in signal transduction following ligand-receptor binding. We investigated the effects of incubating either stearic or oleic acid on the association of murine lymphocyte CD3 complex with the cytoskeleton. Both cytochalasin D, an inhibitor of microfilament formation, and W7, an inhibitor of calmodulin, inhibited capping of CD3. The association of CD3 with the cytoskeleton was confirmed by confocal laser scanning microscopy studies, which showed co-localization of the cross-linked CD3 receptors and the membrane attachment proteins ankyrin and fodrin. Although exogenous oleic acid increased plasma membrane fluidity, neither expression nor capping of CD3 receptors was increased. Nonetheless, oleic acid did increase uptake of tritiated thymidine after binding of anti-CD3 antibodies. Lymphoproliferation was progressively inhibited by both cytochalasin D and W7, confirming the importance of intact cytoskeleton for cellular activation.

Animals↗

PubMed1996

Fatty acid unsaturation increases expression and capping of murine lymphocyte CD44 and CD45.

We studied the effect of incubating murine lymphocytes with cis-unsaturated fatty acids on expression and capping of CD44 and CD45. Lymphocytes were incubated with stearic (18:0) or oleic (18:1 omega-9) acid bound to bovine serum albumin (BSA). After incubation with rat anti-CD44 or anti-CD45 monoclonal antibodies and then with fluorescent-labeled anti-rat antibody, mean fluorescence intensity (FI) was measured by using flow cytometry. Capping was measured after warning and fixation in paraformaldehyde. Steady-state fluorescence anisotropy (rs) was measured after the cells had been incubated with trimethylammoniumdiphenylhexatriene. Incubation with oleic acid, but not stearic acid or BSA alone, was associated with an increase in FI of CD44. Expression of CD45, however, was increased by both stearic and oleic acids to the same degree over BSA controls. CD44 and CD45 capping were both increased by incubation with oleic acid. Rs was decreased in cells incubated with oleic acid, suggesting an increase in membrane fluidity. We conclude that incubation with oleic acid increases expression of CD44 and increases capping of both CD44 and CD45. These findings were confirmed in feeding experiments, in which rs was reduced and CD44 capping increased by polyunsaturated fatty acid diets.

Animals↗

PubMed1996

Activated platelet aggregates in thrombotic thromboctyopenic purpura: decrease with plasma infusions and normalization in remission.

Circulating activated platelet aggregates (aPA) were assayed by flow cytometry employing mAb alpha-CD62p in eight patients with thrombotic thrombocytopenic purpura (TTP). Elevation of aPA was observed in all patients in active stages of TTP; aPA normalized in remission. Plasma infusions with plasmapheresis decreased aPA in responding patients. The rise and fall of aPA preceded relapses and improvements, respectively. These changes were seen prior to the traditional indicators, LDH, haematocrit, and platelet count. Incubation of plasma from TTP patients with normal whole blood induced formation of aPA; this effect was significantly greater than that of plasmas from ITP patient controls (P < 0.01), suggesting the presence of an aPA-promoting factor in TTP plasma. Parallel experiments using a platelet aggregometer failed to detect effect of TTP plasma on normal blood. In summary, aPA appear to be a marker of disease activity, rising with relapse, falling with plasma therapy, and normalizing in remission. The flow cytometric assay of aPA is more sensitive than aggregometry in detecting the putative aPA-promoting factor in TTP.

Flow Cytometry↗

PubMed1995

Platelet factor 3 in plasma fractions: its relation to microparticle size and thromboses.

Platelet factor 3 (PF3) was assayed by Russell's viper venom (RVV) in three plasma fractions, platelet-rich plasma (PRP), platelet poor plasma (PPP), and 0.1 microns particle-filtered plasma (PFP), in 42 healthy controls, 34 patients with recent cerebrovascular accidents (CVA) and 28 with recent ischemic events from coronary artery disease (CAD). Platelet microparticles (PMP) were assayed in PPP by flow cytometry. Relative to controls, the RVV clotting times were shortened in all three plasma fractions in both patient groups, p < 0.001. PMP were also elevated in both patient groups, p < 0.001. Linear regression analysis showed that the RVV times of PPP are inversely correlated with PMP, p < 0.005, in patient groups but not in controls. There was no correlation of RVV time with PT, APTT or FIB. After converting RVV times to units of PF3 activity, it could be shown that only about 1/4 of the total PF3 activity was contributed by platelets. The major contribution to the PF3 activity in controls was from microparticles < 0.1 microns but in patients was due mainly to microparticles > 0.1 microns. The RVV time was superior to routine coagulation tests in discriminating thrombotic patients from healthy controls.

Adolescent↗

PubMed1995

Desmopressin (DDAVP) acts on platelets to generate platelet microparticles and enhanced procoagulant activity.

Desmopressin (DDAVP), an analog of vasopressin (AVP), has wide clinical application as an anti-hemorrhagic (AH) agent. DDAVP in vivo releases vWF from endothelial cells but is reported to have little action on platelets. However, DDAVP is often used to improve hemostasis in platelet dysfunctions. We examined the effect of DDAVP on platelet microparticle (PMP) formation and procoagulant activity in vitro using platelets from normal volunteers and in vivo in six patients receiving DDAVP therapy. In the former, platelets were incubated with DDAVP (0.5 to 25 nM) and PMP released were stained with FITC-labeled MAb alpha-GP IIb/IIIa for flow cytometry. Procoagulant activity was measured in a clot-based assay using Russel's viper venom (RVV) calibrated with cephalin. A mean increase of 2-3 fold was observed in both PMP and procoagulant activity. Parallel to these observations was a dose-dependent rise in organelle-associated Ca2+. The assays were also performed on six patients prior to and at one hour after infusion of DDAVP, and similar but lesser effects were observed. We conclude that DDAVP acts on platelets in vitro, and that these effects may contribute to the hemostatic action of DDAVP in platelet dysfunctions in vivo.

Adult↗

PubMed1995

Danazol distribution in plasma and cell membranes as related to altered cell properties: implications for mechanism.

Concentrations of danazol in patient plasma and red blood cells (RBC) were assayed over a 6-month period in 75 patients on danazol therapy using a high-pressure liquid chromatography (HPLC) method more reliable than previous radioimmunoassay (RIA) methods. It was found that plasma danazol rose regularly for 15 days after the beginning of treatment, reaching a steady state plateau of 175 +/- 76 ng/ml in 20 patients on normal dose, and less for lower dose schedules. After stopping danazol, concentrations declined to near zero in a similar time frame. RBC concentrations on a packed volume basis were similar to plasma levels. However, the membrane ghosts of RBC contained about 50% of the total RBC danazol, implying about 100-fold higher concentration in membranes than in plasma. Similar distributions were obtained in vitro with both RBC and platelets, and were confirmed by 14-C-labeled danazol. These findings tend to support the hypothesis that the benefits of danazol in immune disorders may be attributable in part to its intercalation in the lipid bilayer of the plasma membrane, altering antigen/receptor expression to modulate immune reactions. This hypothesis was first suggested when it was observed that the RBC of patients on danazol therapy showed morphological changes and increased resistance to osmotic lysis. It was later shown that danazol in vitro reduces binding of autoantibodies, and protects against complement-mediated lysis, suggesting direct action of danazol on the membranes. This hypothesis is discussed, and danazol's effect in protecting against complement-mediated lysis is described.

Blood Platelets↗

PubMed1995

Platelet microparticles bind, activate and aggregate neutrophils in vitro.

The interaction of activated platelets with leukocytes are believed to play an important role in ischemic reperfusion injury and other thrombotic conditions. Upon activation, platelets shed platelet microparticles (PMP) and express activation markers CD62P expressed on activated platelets mediates adhesion of platelets to leukocytes, chiefly neutrophils, but little is known of the interaction of PMP isolated from stored platelets or thrombin activated platelets was incubated with leukocytes and binding assessed by flow cytometry. FITC-labeled alpha-CD41 was used to assess platelet material associated with WBC. Like platelets PMP bound preferentially to neutrophils rather than lymphocytes, and exhibited an absolute dependence on the presence of Ca2+. Binding was time-and concentration-dependent, reaching a plateau at 10 min at a ratio of PMP to neutrophils of 150:1. Fluorescence microscopy showed that most of the neutrophils were aggregated into clusters of 5-20 cells. Clustering of neutrophils was not observed to result form interaction with platelets. In these clusters the adherent PMP appeared to serve as bridges between the neutrophil. Addition of EGTA after brief incubation (5-10 min) released most of the bound PMP but if added after > 10 min, only approximately 60% of bound PMP were released. In contrast, nearly all bound platelets were released by EGTA at the same time of incubation. Incubation of neutrophils with PMP gave significantly higher percentage of CD41a(+)neutrophils than did platelets incubated at the same numerical ratio. PMP association with neutrophils was less markedly inhibited by alpha-CD62P (AC1.2) than platelets, but binding of both PMP and activated platelets was inhibited approximately 90% by antisialyl Lewis X. PMP binding to neutrophils induced a significant increase in both CD11b expression and phagocytic activity in a concentration-dependent manner. These findings suggest a possible role for PMP in addition to providing platelet factor 3, specifically, as an activator and mediator of neutrophils in ischemic injury, thrombosis, and inflammation.

Blood Platelets↗

PubMed1994

Complement-mediated fragmentation and lysis of opsonized platelets: ender differences in sensitivity.

It was reported that elevated levels of platelet microparticles (PMPs) in patients with immune thrombocytopenic purpura (ITP) were associated with decreased bleeding, and in some cases with small vessel thromboses (J Lab Clin Med 1992; 119:334). To investigate the possible role of complement in PMP production in ITP, an in vitro assay was developed to simulate ITP: platelets were opsonized with well-defined monoclonal antibodies against glycoprotein IIb/IIIa, of immunoglobulin G (alpha-CD41), and of immunoglobulin M (alpha-Plt-1) class, then exposed to serum as a source of complement. PMP generation and lysis were monitored by flow cytometer, by release of lactic dehydrogenase, and by generation of procoagulant activity. These effects were largely abolished by heating the serum (30 minutes, 65 degrees) or by incubation with alpha-C1q, confirming the role of complement. At low concentrations of serum, both monoclonal antibodies promoted PMP shedding in a concentration-dependent manner without loss of platelet population; at higher concentrations, extensive lysis occurred, but marked variations in resistance to lysis were observed in platelets from different individuals. The PMPs produced were associated with increased procoagulant activity, as measured by the Russell's viper venom test. The immunoglobulin M antibody was more potent than the immunoglobulin G antibody in promoting lysis, and the resulting PMPs had greater procoagulant activity. To clarify the variation seen in platelets from different donors, data was sorted on the basis of gender, with the finding that women's platelets are significantly more sensitive to complement-mediated damage than men's. This may explain in part why ITP is three to four times more prevalent in women than in men. We conclude that complement activation is the most likely explanation for the elevated level of PMPs often seen in patients with ITP and sometimes associated with thrombosis and that the determining factors are the concentration and nature of antibody as well as individual differences in sensitivity to complement-mediated damage. Because complement activation can occur without participation of antibody, complement activation may also be the cause of elevated PMP levels seen in other thrombotic disorders not involving platelet-specific antibodies.

Adult↗

PubMed1993

Elevated platelet microparticles in transient ischemic attacks, lacunar infarcts, and multiinfarct dementias.

Platelets release microparticles (PMP) upon activation. Elevated levels of PMP were observed in patients with immune thrombocytopenic purpura (ITP), sometimes associated with a syndrome resembling transient ischemic attack (TIA), suggesting a thrombogenic potential for PMP. To determine if this association applies to TIA and other cerebrovascular accidents (CVA) without ITP, we studied PMP profiles in 71 patients with ischemic CVA: 28 with small vessel CVA (SCVA), either lacunar infarcts or TIA; 24 with large vessel CVA (LCVA); 19 with multiinfarct dementia (MID); 12 with Alzheimer's dementia (AD); and 31 healthy controls. The mean PMP values were: MID = 3.71 +/- 0.51; SCVA = 3.48 +/- 0.63; LCVA = 1.97 +/- 0.28; AD = 1.19 +/- 0.27; controls = 0.88 +/- 0.09, (all units x 10(7)/mL). PMP values in all groups except AD were significantly above normal (p < 0.01). However, the elevation in SCVA was more marked than in LCVA (p < 0.01). Administration of the calcium channel blocker, nifedipine, to 11 TIA patients reduced PMP significantly.

Adult↗

PubMed1992

Clinical significance of platelet microparticles in autoimmune thrombocytopenias.

Platelet microparticles (PMPs) are vesicles derived from platelet membranes that are too small (less than 0.5 micron) to be detected in routine platelet counting. They arise in association with platelet activation and other unknown causes. Elevated PMPs have been observed in idiopathic thrombocytopenic purpura (ITP), a disorder in which autoantibody interacts with platelets and the opsonized platelets are destroyed by macrophages. However, the clinical significance of PMP has been unknown. Using flow cytometry, we examined PMP concentrations in 62 patients with ITP and in 33 normal control subjects to assess the clinical significance of PMP in ITP. When compared with PMP levels in control subjects, PMP levels were significantly higher (p less than 0.005) in patients with ITP, but considerable variation among individual patients was observed. Patients with platelet counts less than or equal to 60,000 were evaluated for correlation of PMP levels with manifestations of thrombocytopenias; patients without symptoms (free of petechiae or mucosal bleeding) are found to have significantly higher PMP levels (p less than 0.05) than patients with symptoms, suggesting hemostatic protection by PMP. Additionally, we identified a group of patients with ITP who experienced neurologic complications resembling transient cerebral ischemic attacks (TIAs): recurrent episodes of dizzy spells or weakness in mild cases, and coma, seizure, or progressive dementia in advanced cases. Small cerebral infarcts were demonstrated by computed axial tomography scan or magnetic resonance imaging in spite of severe thrombocytopenias. Patients with this syndrome are often found to have higher PMP levels (p less than 0.005) when compared with the group free of neurologic complications. It is concluded that PMPs play an important role in hemostasis in patients with thrombocytopenia, and that high concentrations of hemostatically active PMP can be thrombogenic in certain clinical settings. Quantitation and characterization of PMP is important in assessment and management of patients with thrombocytopenia.

Aged↗