Biomedical subjects

T Wun

Publications and source records attributed to T Wun.

At least 19 recordsLinked to original sources

PubMed2002

Isolated cavernous sinus extramedullary relapse of chronic myelogenous leukemia following allogeneic stem cell transplant.

Isolated extramedullary relapse of chronic myelogenous leukemia (CML) after allogeneic stem cell transplant is rare. A case is reported of a patient who developed a granulocytic sarcoma of the cavernous sinus 7 months after allogeneic transplant for CML. He presented with neurologic deficits, and a mass lesion was found on imaging. No evidence of hematologic relapse was identified by bone marrow histology or cytogenetics. A premortem diagnosis was not possible, and the patient died 2 months later of an intracerebral hemorrhage after receiving various therapies directed against a presumed infectious etiology. Granulocytic sarcoma should be considered in the differential diagnosis of mass lesions presenting after allogeneic transplant for CML, even if there is no evidence of medullary disease.

Adult↗

PubMed2002

Filgrastim treatment of acute myelogenous leukemia (M7) relapse after allogeneic peripheral stem cell transplantation resulting in both graft-versus-leukemia effect with cytogenetic remission and chronic graft-versus-host disease manifesting as polyserositis and subsequent bronchiolitis obliterans with organizing pneumonia.

Filgrastim (granulocyte colony-stimulating factor) has recently been reported to successfully treat patients with leukemic relapse after allogeneic peripheral stem cell transplantation (PSCT). However, the majority of the patients who responded also developed graft-versus-host disease (GVHD). Polyserositis as a manifestation of GVHD is a rare phenomenon. We report the first case of polyserositis following the use of filgrastim to treat a patient with acute myelogenous leukemia (M7), who had relapsed after an initially successful allogeneic PSCT. The polyserositis manifested with effusions and was initially controlled with high doses of steroids and pericardial stripping; however, after a quiescent period the patient eventually developed bronchiolitis obliterans with organizing pneumonia that required additional immunosuppressive therapy. We review the literature on GVHD-associated polyserositis and offer potential explanations for its pathogenesis.

Adolescent↗

PubMed2001

Purified poloxamer 188 for treatment of acute vaso-occlusive crisis of sickle cell disease: A randomized controlled trial.

CONTEXT: Sickle cell disease (SCD) can cause severe painful episodes that are often thought to be caused by vaso-occlusion. The current therapy for these uncomplicated painful episodes includes hydration, oxygen, and analgesics. Purified poloxamer 188 may increase tissue oxygenation and thereby reduce inflammation, pain, and the overall duration of such painful episodes in patients with SCD. OBJECTIVE: To compare the duration of painful episodes in patients with SCD treated with purified poloxamer 188 to that of similar episodes experienced by patients who receive a placebo. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled, intention-to-treat trial conducted between March 1998 and October 1999 in 40 medical centers in the United States. PARTICIPANTS: Two hundred fifty-five patients with SCD (aged 9-53 years) who had a painful episode sufficiently severe to require hospitalization and narcotic analgesics. INTERVENTION: Patients were randomly assigned to receive an intravenous infusion of purified poloxamer 188, 100 mg/kg for 1 hour followed by 30 mg/kg per hour for 47 hours (n = 127), or a matching volume of saline placebo (n = 128). MAIN OUTCOME MEASURE: Duration of the painful episode, from randomization to crisis resolution. RESULTS: Mean (SD) duration of the painful episodes was 141 (42) hours in the placebo group compared with 133 (41) hours in those treated with purified poloxamer 188, a 9-hour reduction (P =.04). Subset analyses indicated an even more pronounced purified poloxamer 188 effect in children aged 15 years or younger (21 hours; P =.01) and in patients who were receiving hydroxyurea (16 hours; P =.02). Finally, the proportion of patients achieving crisis resolution was increased by purified poloxamer 188 (65/126 [52%] vs 45/123 [37%]; P =.02). Similar results were observed in children aged 15 years or younger (22/37 [60%] vs 10/36 [28%]; P =.009) and in patients who were also receiving hydroxyurea (12/26 [46%] vs 4/28 [14%]; P =.02). CONCLUSIONS: A decrease in the duration of painful episodes and an increase in the proportion of patients who achieved resolution of the symptoms were observed when the purified poloxamer 188-treated patients were compared with the patients receiving placebo. However, the difference between these groups was significant but relatively small. In subgroup analysis, a more significant effect on both parameters was observed in children and in patients who were receiving concomitant hydroxyurea. It is important to confirm both of these observations in further prospective trials.

Adolescent↗

PubMed2001

Correlation of abnormal intracranial vessel velocity, measured by transcranial Doppler ultrasonography, with abnormal conjunctival vessel velocity, measured by computer-assisted intravital microscopy, in sickle cell disease.

The Stroke Prevention Trial has confirmed that utilization of transcranial Doppler ultrasonography (TCD), which examines blood flow in large intracranial vessels, can identify children with sickle cell disease (SCD) who are at high risk of developing a premature stroke. It is not known to what extent the vasculopathy in SCD involves small vessels and whether the abnormalities, if present, correlate with large-vessel vasculopathy. Eighteen children with SCD were examined with TCD to determine middle cerebral artery (MCA) velocity and computer-assisted intravital microscopy (CAIM) to determine bulbar conjunctival vessel velocity during the same visit for vasculopathy correlation. High MCA velocity (> or = 200 cm/sec) was found by TCD in 4 patients who also showed abnormal conjunctival velocity (< 0.2 mm/sec or intermittent trickle flow) by CAIM. Three patients had conditional (> or = 170 cm/sec and < 200 cm/sec) MCA velocity: 2 showed abnormal (trickle) and 1 showed normal conjunctival velocity (1.9 mm/sec). One patient with unmeasurable MCA velocity had abnormal (trickle) conjunctival velocity. Of the remaining 10 patients who had normal MCA velocity, 2 showed abnormal (0.05 mm/sec and 0.1 mm/sec) and 8 showed normal conjunctival velocities (1.1-2.4 mm/sec). The MCA velocities correlated significantly with bulbar conjunctival flow velocities (P < or =.008, Fisher exact test). A correlation exists between MCA (large-vessel) and conjunctival (small-vessel) flow velocities. CAIM is a noninvasive quantitative technique that might contribute to the identification of SCD patients at high risk of stroke. Small-vessel vasculopathy might be an important pathological indicator and should be further explored in a large-scale study. (Blood. 2001;97:3401-3404)

Adolescent↗

PubMed2001

Prospective evaluation of cancer clinical trial accrual patterns: identifying potential barriers to enrollment.

PURPOSE: Well-conducted cancer clinical trials are essential for improving patient outcomes. Unfortunately, only 3% of new cancer patients participate in clinical trials. Barriers to patient accrual in cancer clinical trials must be identified and overcome to increase patient participation. MATERIALS AND METHODS: We prospectively tracked factors that potentially affected patient accrual into cancer clinical trials at the University of California Davis Cancer Center. Oncologists seeing new outpatients were asked to complete questionnaires regarding patient characteristics and the physician's decision-making on patient eligibility, protocol availability, and patient opinions on participation. Statistical analysis was performed to correlate these parameters with subsequent protocol accrual. RESULTS: There were 276 assessable patients. At the initial visits, physicians did not consider clinical trials in 38% (105/276) of patients principally because of a perception of protocol unavailability and poor performance status. Physicians considered 62% (171/276) of patients for participation in clinical trials. Of these, only 53% (91/171) had an appropriate protocol available for site and stage of disease. Seventy-six of 90 patients (84%) with available protocols met eligibility criteria for a particular study. Only 39 of 76 patients (51%) agreed to participate in cancer clinical trials, for an overall accrual rate of 14% (39/276). The remainder (37/76, 49%) declined trial participation despite meeting eligibility criteria. The most common reasons were a desire for other treatment (34%), distance from the cancer center (13%), patient refusal to disclose reason (11%), and insurance denial (8%). Patients with private insurance were less likely to enroll in clinical trials compared to those with government-funded insurance (OR, 0.34; P =.03; 95% CI, 0.13 to 0.9). CONCLUSION: Barriers to cancer clinical trial accrual can be prospectively identified and addressed in the development and conduct of future studies, which may potentially lead to more robust clinical trials enrollment. Investigation of patient perceptions regarding the clinical trials process and the role of third party-payers is warranted.

Adolescent↗

PubMed2001

Comparison of the L10M consolidation regimen to an alternative regimen including escalating methotrexate/L-asparaginase for adult acute lymphoblastic leukemia: a Southwest Oncology Group Study.

The effectiveness of intensive post-remission chemotherapy regimens for adult patients with acute lymphoblastic leukemia (ALL) is limited by both a high rate of disease recurrence and a substantial incidence of treatment toxicity. To evaluate a potentially more effective and less toxic approach, we conducted a multicenter phase III trial of consolidation therapies comparing the standard L10M regimen with one combining the brief, intensive L17M regimen and escalating methotrexate (MTX) and L-asparaginase (L-asp). Patients over age 15 with previously untreated ALL were eligible. Induction therapy included vincristine, prednisone, doxorubicin, cyclophosphamide and intrathecal methotrexate administered over 36 days. Patients who achieved complete remission (CR) were randomized to receive consolidation with either the L10M regimen or with DAT (daunomycin, cytosine arabinoside, 6-thioguanine) and escalating MTX and L-asp. The randomization was stratified by age, WBC and Ph chromosome status. Maintenance therapy was the same in both arms. Of 353 eligible patients, 218 (62%) achieved CR and 195 were randomized. The treatment arms did not differ significantly with respect to disease-free survival (DFS; P= 0.46) or overall survival (P= 0.39). Estimated DFS at 5 years was 32% (95% confidence interval (CI) 23-42%) in the L10M arm and 25% (95% CI 16-33%) in the DAT/MTX/L-asp arm. In each arm, 4% of patients died of toxicities (infection in all but one case). Infections and nausea/vomiting were somewhat more common in the L10M arm (occurring in 68% and 53% of patients respectively) than the DAT/MTX/L-asp arm (56% and 33%). The DAT/MTX/L-asp consolidation regimen was associated with some reduction in nonfatal toxicities, but no significant improvement in DFS, overall survival or non-relapse mortality when compared to the standard L10M regimen.

Adult↗

PubMed2001

Radioimmunotherapy: potential as a therapeutic strategy in non-Hodgkin's lymphoma.

Lymphomas are the fifth most common malignancy in the United States and are increasing in incidence. Despite being among the most responsive malignancies to radiation and chemotherapy, the majority of patients relapse or have progressive disease. Monoclonal antibodies (MAbs) directed at cell-specific surface antigens have been useful in the diagnosis of lymphomas and, more recently, the therapeutic mouse-human chimeric MAb rituximab has demonstrated effectiveness in B cell lymphomas. Conjugating MAbs to radionuclides is a strategy for improving the efficacy of MAb lymphoma therapy by delivering radiation in close proximity to the tumour (radioimmunotherapy or RIT). In addition, the low dose rate of the delivered radiation may exert a greater antitumour activity than an equivalent dose of conventional external beam radiation. The antigenic targets for MAb therapy have included CD20, CD22, HLA-DR, and B cell idiotype. Radionuclides that have been used include iodine-131, yttrium-90, and copper-67; there are relative merits and disadvantages to each source of radiation. Clinical studies to date have focused on relapsed and refractory patients with both indolent and aggressive lymphomas, although more recent studies have included previously untreated patients with indolent lymphoma. Radioimmunoconjugate has been delivered as either single or multiple doses. Response rates have varied widely, dependent on the patient population and the response criteria. Of note, complete responses can be achieved in this typically refractory patient group. Toxicities have generally consisted of mild infusion-related nausea, fever, chills, and asthenia. Neutropenia and thrombocytopenia are the dose-limiting toxicities and have prompted the incorporation of autologous stem cell support as a means of achieving dose escalation. To date, RIT has been delivered to highly selected patients in relatively few centres with requisite equipment and specialised personnel. In addition to these requirements, cost is likely to be a barrier to widespread use. The combination of RIT with chemotherapy at conventional or high dose, or with biological agents is a fertile area for investigation. The potential of RIT in the treatment for lymphomas will be defined only by well designed comparative prospective clinical studies.

Animals↗

PubMed2000

Cocoa inhibits platelet activation and function.

BACKGROUND: Epidemiologic studies have shown inverse associations between dietary polyphenols and mortality from coronary heart disease. However, the basis for this protective association is uncertain. Food polyphenols reportedly have antioxidant properties and decrease platelet function in vitro. OBJECTIVE: This study sought to evaluate whether consumption of a polyphenol-rich cocoa beverage modulates human platelet activation and primary hemostasis. DESIGN: Peripheral blood was obtained from 30 healthy subjects before and 2 and 6 h after ingestion of a cocoa beverage (n = 10), a caffeine-containing control beverage (n = 10), or water (n = 10). Platelet activation was measured in terms of expression of activation-dependent platelet antigens and platelet microparticle formation by using fluorescent-labeled monoclonal antibodies and flow cytometry. Primary platelet-related hemostasis was measured with a platelet function analyzer. RESULTS: Ex vivo epinephrine- or ADP-stimulated expression of the fibrinogen-binding conformation of glycoprotein IIb-IIIa was lower 2 and 6 h after consumption of cocoa than before consumption. Cocoa consumption also decreased ADP-stimulated P-selectin expression. In contrast, epinephrine-induced platelet glycoprotein IIb-IIIa expression increased after consumption of the caffeine-containing beverage but not after water consumption. Platelet microparticle formation decreased 2 and 6 h after cocoa consumption but increased after caffeine and water consumption. Primary hemostasis in response to epinephrine in vitro was inhibited 6 h after cocoa consumption. The caffeine-containing beverage inhibited ADP-induced primary hemostasis 2 and 6 h after consumption. CONCLUSIONS: Cocoa consumption suppressed ADP- or epinephrine-stimulated platelet activation and platelet microparticle formation. Cocoa consumption had an aspirin-like effect on primary hemostasis.

Adenosine Diphosphate↗

PubMed2000

Cocoa and wine polyphenols modulate platelet activation and function.

There is speculation that dietary polyphenols can provide cardioprotective effects due to direct antioxidant or antithrombotic mechanisms. We report in vitro and postingestion ex vivo effects of cocoa procyanidins, a procyanidin-rich cocoa beverage and dealcoholized red wine (DRW) on human platelet activation. In a series of in vitro studies, cocoa procyanidin trimers, pentamers or DRW (3 and 10 micromol/L) were incubated with citrated peripheral whole blood in the presence and absence of platelet agonists. Platelet activation was detected using fluorescent-labeled monoclonal antibodies recognizing the fibrinogen binding conformation of GPIIb-IIIa (referred to herein as PAC-1 binding) and the activation-dependent platelet epitope CD62P (P-selectin). The percentage of CD42a-positive platelets coexpressing PAC-1 binding and/or CD62P was determined by multiparameter flow cytometry. Procyanidin trimers, pentamers and DRW added to whole blood in vitro increased PAC-1 binding and P-selectin expression. In contrast, procyanidin trimers, pentamers and DRW inhibited the platelet activation in response to epinephrine. The effects on platelet activation of cocoa beverage and DRW consumption were also studied in healthy subjects. Citrated blood was obtained before and 2 and 6 h after the ingestion of a cocoa beverage, a caffeine-containing beverage, DRW or water. Platelet activation was measured by flow cytometry. The consumption of DRW did not affect the expression of activation-dependent platelet antigens, either unstimulated or after ex vivo activation with epinephrine. However, the consumption of DRW increased PAC-1 binding in response to 100 micromol/L ADP ex vivo. Cocoa consumption reduced platelet response to agonists ex vivo. The ingestion of water had no effect on platelet activation, whereas a caffeine-containing beverage augmented the response of platelets to epinephrine. In summary, select cocoa procyanidins and DRW added to whole blood in vitro increased expression of platelet activation markers in unstimulated platelets but suppressed the platelet activation response to epinephrine. In contrast, cocoa consumption suppressed unstimulated and stimulated platelet activation in whole blood. This suppressive effect observed on platelet reactivity may explain in part the reported cardioprotective effects of dietary polyphenols.

Adult↗

PubMed1999

Improved survival with plasma exchange in patients with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome.

PURPOSE: Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome are uncommon disorders that are generally fatal if left untreated. Plasma exchange therapy is associated with high response rates and improved short-term survival, but most previous studies have been limited by small numbers of patients or short duration of follow-up. METHODS: We performed a retrospective cohort analysis in 126 consecutive patients with thrombotic thrombocytopenic purpura/hemolytic uremic syndrome, most of whom were treated principally with plasma exchange at the Sacramento Medical Foundation Blood (Center and the University of California Davis Medical Center between 1978 and 1998. We measured the effect of therapeutic plasma exchange on 30-day mortality, response rate, and overall survival, and determined which factors were associated with 30-day mortality and relapse. RESULTS: The overall 30-day mortality was 10% of the 122 patients who received plasma exchange as their principal treatment (a median of 9 exchanges and a mean cumulative infused volume of 43 +/- 77 L fresh frozen plasma); 56% were complete responders and 21% were partial responders. The relapse rate was 13%. The estimated 2-year survival was about 60%; among patients without serious underlying comorbid conditions, the estimated 2-year survival was about 80%. Each unit increase in clinical severity score (on a 0 to 8 scale) was associated with a 2.2-fold (95% confidence interval [CI]: 1.3 to 3.9) increase in the odds of 30-day mortality. Patients who were febrile at presentation were substantially less likely to suffer a relapse (odds ratio = 0.2; 95% CI: 0.03 to 0.9). CONCLUSION: Plasma exchange therapy produced high response and survival rates in this large cohort of patients with thrombotic thrombocytopenic purpura/hemolytic uremic syndrome. The Clinical Severity Score may be useful in predicting 30-day mortality, whereas fever at onset was associated with a lesser risk of relapse. Prospective studies should stratify patients according to these prognostic factors.

Adult↗

PubMed1999

Platelet-erythrocyte adhesion in sickle cell disease.

BACKGROUND: The abnormal adherence of sickle red blood cells (sRBC) to other cell types likely contributes to vaso-occlusion. Increased numbers of platelet-erythrocyte aggregates (PEA) and platelet activation have been described in sickle cell disease. The present study was undertaken to determine the contribution, if any, of the extracellular matrix protein thrombospondin to the adhesion of sRBC and platelets. METHODS: Platelet activation and PEA were measured using fluorescent-labeled monoclonal antibodies and flow cytometry. Platelet red-cell adhesion was measured by a gravity sedimentation assay. Erythrocyte-bound thrombospondin (TSP) was determined by enzyme-linked immunoabsorbant assay (ELISA). RESULTS: Our studies demonstrate significant platelet activation and adhesion of sRBC to platelets in sickle cell disease. Thrombospondin was detected on sRBC. There was variable inhibition of sRBC-platelet adhesion by antibodies to CD36 (thrombospondin receptor) and antibodies to thrombospondin. CONCLUSIONS: Thrombospondin on sRBC may mediate, at least in part, sRBC-platelet adhesion in sickle cell disease. The study of heterotypic cell-cell interactions is important in understanding the pathogenesis of vaso-occlusion in sickle cell disease.

Antibodies, Monoclonal↗

PubMed1998

Platelet activation during dobutamine stress echocardiography.

BACKGROUND: Dobutamine stress echocardiography (DSE) is a common, useful test for the evaluation of coronary artery disease. Two of 650 patients who underwent DSE at our institution sustained nonfatal myocardial infarction either during DSE or shortly thereafter. Although DSE is associated with low morbidity rates, this rate is higher than our experience with exercise treadmill testing (ETT). METHODS: Six individuals who did not undergo DSE or ETT were enrolled to evaluate direct in vitro effects of dobutamine on platelets. Nine patients undergoing DSE and seven patients undergoing ETT were enrolled to evaluate in vivo platelet activation. We used flow cytometry and fluorescent-labeled monoclonal antibodies to activation-dependent platelet antigens to detect dobutamine-associated platelet activation both in vitro and in vivo. RESULTS: In vitro we found a synergistic increase in epinephrine-induced CD62 expression in the presence of dobutamine. The response to the combination of dobutamine and epinephrine was 151% to 565% of the expected response. In vivo there was a dose- and time-dependent rise in the percentage of platelets expressing CD62 in all nine subjects undergoing DSE. The median percentage of platelets expressing CD62 was 1.6% (range 0.1% to 6.8%), 6.5% (range 0.2% to 11.7%), 11.6% (range 5.9% to 19.1%), and 11.4% (range 7.2% to 25.0%) in the samples obtained at baseline, 20 microg/kg/min of dobutamine, 40 microg/kg/min of dobutamine, and during the recovery phase, respectively (repeated measures analysis of variance, p = 0.02). There was no increase in CD62 expression on platelets obtained from seven patients at peak ETT. The median percentage of CD62 at baseline ETT was 1.9% (range 0.2% to 7.3%) and at peak was 2.6% (range 0.4% to 7.0%) (p = 0.156, Wilcoxon signed rank test). CONCLUSION: We conclude that platelet activation occurs in vivo in patients undergoing DSE and that this may be caused by a synergistic effect of dobutamine with physiologic platelet agonists.

Adult↗

PubMed1998

Platelet activation in patients with sickle cell disease.

Vascular occlusion and vasculopathy underlie much of the morbidity in patients with sickle cell anaemia. Platelets may play a role in this vasculopathy. Samples from 43 patients with sickle cell disease (SCD) were examined for evidence of platelet activation using fluorescent-labelled monoclonal antibodies and flow cytometry. There was increased expression of activation-dependent antigens on the platelets from patients with SCD compared to those from both Caucasian and African-American controls. In addition, SCD patients had increased levels of platelet microparticles. Platelets are activated in patients with sickle cell disease. The contribution of platelet activation to sickle cell pathophysiology is under active investigation in our laboratories.

Adolescent↗

PubMed1997

Peripheral blood stem cell mobilization for hematopoietic support of radioimmunotherapy in patients with breast carcinoma.

BACKGROUND: In clinical trials of radiolabeled monoclonal antibodies targeting metastatic breast carcinoma, myelosuppression has been the initial dose-limiting toxicity. We previously have shown that mobilized peripheral blood stem cell transfusions ameliorate this toxicity of radioimmunotherapy (RIT). Because of the difficulty we experienced harvesting adequate numbers of precursor cells from some of these heavily pretreated patients, we have compared the mobilization results and clinical histories of the metastatic breast carcinoma patients referred for RIT with those of metastatic breast carcinoma patients referred for high dose chemotherapy (HDCT) with transplantation. METHODS: Mobilization of stem cells into the peripheral blood was accomplished using granulocyte-colony stimulating factor with or without chemotherapy. Granulocyte macrophage colony-forming assays (CFU-GM) and flow cytometric analysis for CD34 positive cells were used to evaluate the number of hematopoietic precursors mobilized and collected with each apheresis procedure. Clinical characteristics, including prior chemotherapy and external beam radiotherapy, tumor bulk, and performance status, were determined by chart review. RESULTS: Significantly fewer hematopoietic precursors (both CD34 positive cells and CFU-GM) were harvested per procedure from the six RIT patients compared with a group of six patients with metastatic breast carcinoma who had stem cells harvested prior to HDCT (P = 0.002). There was no significant difference between the groups with regard to age or prior radiotherapy. All the RIT patients had received more chemotherapy, had a less favorable performance status (1 vs. 0), and had measurable tumor, whereas all the HDCT patients had minimal residual disease. CONCLUSIONS: Patients enrolled in RIT studies had lower stem cell yields than metastatic breast carcinoma patients scheduled to receive HDCT with stem cell transplantation. Poor mobilization is unlikely to be due to the mobilizing regimen alone and may be related to the intensity of prior therapy and/or tumor bulk. Mobilizing adequate stem cells for multiple treatment cycles from patients on Phase I/II RIT trials may require new, more effective mobilizing regimens, but referral of patients earlier in their disease course, prior to chronic bone marrow damage and disease progression, is recommended strongly.

Adult↗

PubMed1997

Thrombopoietin is synergistic with other hematopoietic growth factors and physiologic platelet agonists for platelet activation in vitro.

Thrombopoietin (TPO) is the primary physiologic regulator of platelet production. The effect of TPO on platelet function, both alone and in combination with other hematopoietic growth factors, adenosine diphosphate (ADP), and epinephrine, was investigated using fluorescent-labeled antibodies to the activation-dependent antigen CD62 (P-selectin) and flow cytometry. TPO stimulated CD62 expression on normal human platelets, and this expression was completely inhibited by the soluble extracellular domain of the TPO receptor, MPL. The growth factors granulocyte colony-stimulating factor (G-CSF) and erythropoietin (EPO), but not interleukin-3 (IL-3) or stem-cell factor (SCF), also stimulated platelet activation. The combination of EPO, SCF, ADP, and epinephrine with TPO were synergistic for platelet CD62 expression. These data further support a role for TPO in modulating platelet function.

Adenosine Diphosphate↗

PubMed1997

Platelet activation and platelet-erythrocyte aggregates in patients with sickle cell anemia.

Vascular occlusion and vasculopathy underlie much of the morbidity in patients with sickle cell anemia. Platelets may play a role in this vasculopathy. Samples from 12 adults patients with sickle cell anemia were examined for evidence of platelet activation and formation of platelet-erythrocyte aggregates (PEA) using fluorescent-labeled monoclonal antibodies and flow cytometry. We noted an increased expression of activation-dependent antigens on the platelets from patients with sickle cell anemia compared with those from both white and black control subjects. In addition, patients with sickle cell anemia had increased levels of platelet microparticles and PEA. Platelets are activated in patients with sickle cell anemia and they adhere to sickle erythrocytes. The significance of this activation and adherence are the subject of further investigation.

Adolescent↗

PubMed1997

Vasopressin and platelets: a concise review.

Arginine vasopressin (AVP or vasopressin) is a neurophypophyseal peptide hormone with both vasopressor and antidiuretic properties. This review will briefly discuss the chemistry and physiology of AVP, with the main focus being on AVP and the hemostatic system. Recent data on the effects of AVP, and its analogues, on platelet function will be highlighted. AVP-induced platelet activation could explain, in part, the benefit seen with AVP infusions in gastrointestinal bleeding. These data also suggest that AVP may have a role in physiologic hemostasis and platelet activation.

Journal Article↗

PubMed1996

Physiologic concentrations of arginine vasopressin activate human platelets in vitro.

Arginine vasopressin (AVP) is a neurohypophyseal peptide hormone with protean effects. Previous reports had shown that AVP stimulates platelets, but only at concentrations 3-6 logs higher than the normal plasma concentrations in humans. In this study we tested the hypothesis that AVP, at physiologic concentrations, stimulated the expression of an activation-dependent platelet antigen. Platelets obtained from normal volunteers were incubated with increasing concentrations of AVP and the expression of the activation-dependent platelet antigen P-selectin (CD62) was determined by monoclonal antibodies and flow cytometry. There was a concentration-dependent increase in CD62 expression with increasing AVP concentration; at 1 pm AVP, 24.5% (1.3-88.5%) [median (range)] of platelets expressed CD62. The selective vasopressin V1 receptor antagonist d(CH2)(5)-Tyr(me)AVP (TM-AVP) completely abolished AVP-stimulated CD62 expression. We conclude that AVP can activate platelets at concentrations found in normal humans, at least in vitro, and that this response is mediated by the platelet V1 receptor. AVP may be a physiologic platelet agonist.

Adult↗