Mean Platelet Survival Research Articles

Development and validation of a Python 3 based software to calculate mean platelet survival time by multiple-hit method.

Platelet kinetic parameters predict the efficiency of splenectomy in patients with immune thrombocytopenia. The multiple hit model is recommended to calculate the mean platelet survival time. This method involves complex formulae and iterative calculations that need specialized software, but currently available programs present some drawbacks. A new optimized solution is proposed. A Python 3 based computer program was developed in order to perform the multiple-hit model calculations. Validation was done by comparing its results to two additional programs, one using the Microsoft Excel solver add-in and the other fitting the curve by brute force. There was no difference in the results obtained by the three programs. The brute force program however took much longer times to achieve the results. The new program proved to be a fast, robust solution to determine the multiple-hit parameters needed to assess platelet kinetics.

Mean platelet volume, thrombocytosis, and survival in non-small cell lung cancer patients treated with first-line pembrolizumab alone or with chemotherapy.

Patients treated with immune checkpoint inhibitors (ICIs) may not response to treatment and are at risk for immune-related adverse events (irAEs). Platelet function has been linked to both oncogenesis and immune evasion. We studied the association between the change in mean platelet volume (MPV), platelet count, survival, and the risk of developing irAEs in patients with metastatic non-small cell lung cancer (NSCLC) who have received first-line ICI. In this retrospective study, delta (∆) MPV was defined as the difference between cycle 2 and baseline MPV. Patient data were collected via chart review, and Cox proportional hazard and Kaplan-Meier method were used to assess the risk and estimate median overall survival. We identified 188 patients treated with first-line pembrolizumab, with or without concurrent chemotherapy. There were80 (42.6%) patients received pembrolizumab monotherapy, and 108 (57.4%) received pembrolizumab in combination with platinum-based chemotherapy. Patients whose MPV (∆MPV ≤ 0) decreased had hazard ratio (HR) = 0.64 (95% CI 0.43-0.94) for death with p = 0.023. Patients with ∆MPV ≤ -0.2 fL (median), there was a 58% increase in the risk of developing irAE (HR = 1.58, 95% CI 1.04-2.40, p = 0.031). Thrombocytosis at baseline and cycle 2 was associated with shorter OS with p = 0.014 and 0.039, respectively. Change in MPV after 1 cycle of pembrolizumab-based treatment was significantly associated with overall survival as well as the occurrence of irAEs in patients with metastatic NSCLC in the first-line setting. In addition, thrombocytosis was associated with poor survival.

EP1.01-90 The Prognostic Role of Mean Platelet Volume in Patients with Advanced Non-Small Cell Lung Cancer

Previous studies suggest the potential correlation between increased mean platelet volume (MPV) and survival in non-small cell lung cancer (NSCLC), but results are often contradictory. We herein aimed to further evaluate the prognostic value of MPV in patients with advanced-stage NSCLC in the real-world setting of a tertiary referral oncology center. Demographic, clinicopathological and laboratory data (including complete blood count parameters) of 30 patients with stage IIIB or IV NSCLC were retrieved from the Lung Cancer registry of the Oncology Clinic of Sotiria Athens General Hospital and analyzed. All the above variables (including MPV) were correlated to each other, as well as with overall survival (OS) and progression-free survival (PFS). Mean patients’ age was 68,5 (SD=7,5) years. The majority of patients were male (76.7%), had positive smoking history (90%), squamous cell carcinoma (53.3%), and stage IV disease (76.7%). No statistically significant correlations between survival and sex, age, smoking history or tumor histology (squamous cell carcinoma versus adenocarcinoma), or between MPV and histology were noted. Worse performance status (p=0.004) and higher white blood cell count (p=0.01) were correlated with reduced OS, while increased MPV was strongly correlated both with OS and PFS (p<0.0001 in both cases). Increased MPV may correlate with improved survival of patients with NSCLC, thus potentially representing a marker of favorable prognosis. Our study findings warrant confirmation in larger prospective series

PS1491 PLATELET KINETICS IN PATIENTS WITH CHRONIC IMMUNE THROMBOCYTOPENIA TREATED WITH THROMBOPOIETIN RECEPTOR AGONISTS

Background:Chronic immune thrombocytopenia (ITP) is characterised by antibody‐mediated platelet destruction, shortened platelet survival (PS) and impaired platelets production. Platelet kinetic study (PKS) assesses in vivo the mean PS, platelet production and the platelet sequestration site. Thrombopoietin receptor agonists (TPO‐RA) increase platelets counts (PC) in majority of chronic ITP patients. Moreover, some patients could retain stabile response after TPO‐RA discontinuation, which is attributed to the immunomodulatory effects of the drugs. Addressing this issue only a few studies have been done assessing the effect of TPO‐RA on PKS parameters.Aims:To evaluate the effects of TPO‐RA on PKS parameters.Methods:Ten patients with chronic ITP, median age 55.3 years (range 12–72), gender (f: n = 7, m: n = 3), splenectomised 6/10, were treated with TPO‐RA (eltrombopag, n = 7, romiplostim, n = 3). Response was assessed according to the criteria of the International Working Group (IWG) on ITP. Autologous 111Induim‐oxinate‐labeled PKS were performed in all patients before and 5 months after TPO‐RA therapy initiation.Results:A good treatment response was achieved in 8/10 of patients (eltrombopag, n = 6, romiplostim, n = 2). Two refractory patients were treated with TPO‐RA and low dose prednisolone. Baseline median parameters were as follows: PC 6.5x109/L (range 1–17), PS 0.5 days (range 0.1–1.6, normal: 7–10), platelet production ratio 0.65 (range 0.01–3.2, normal 1 ± 0.2), platelet turnover 30875 Plt/μL/day (range 1731–103500). The post−treatment PKS showed significantly higher median PC of 62.5x109/L (range 5–501) (p = 0.013) and median platelet production ratio of 1.8 (range 0.5–37.9) (p = 0.05). However, median PS of 0.7 days (range 0.1–2.9) (p = 0.09), as well as platelet turnover of 58471.5 Plt/μL/day (range 2800–462236) (p = 0.086) and platelet destruction site remained unaltered. It is of note that two refractory patients (N08 and N010 in table) increased their platelet production (platelet production ratio and platelet turnover), while their PS remained reduced. It is of note that there was no clear correlation between PC and PS. Nevertheless, PC correlated only with platelet turnover prior (p = 0.006) and after TPO‐RA therapy (p = 0.029).Summary/Conclusion:Our prospective study in which PKS was performed initially and during TPO‐RA therapy suggests that TPO‐RA could increase PC by augmented production. Further studies on larger cohorts are needed to confirm this idea.image

Glycoprotein V is a relevant immune target in patients with immune thrombocytopenia.

Platelet autoantibody-induced platelet clearance represents a major pathomechanism in immune thrombocytopenia (ITP). There is growing evidence for clinical differences between anti-glycoprotein IIb/IIIa and anti-glycoprotein Ib/IX mediated ITP. Glycoprotein V is a well characterized target antigen in Varicella-associated and drug-induced thrombocytopenia. We conducted a systematic study assessing the prevalence and functional capacity of autoantibodies against glycoprotein V. A total of 1140 patients were included. In one-third of patients, platelet-bound autoantibodies against glycoproteins Ib/IX, IIb/IIIa, or V were detected in a monoclonal antibody immobilization of platelet antigen assay; platelet-bound autoantiglycoprotein V was present in the majority of samples (222 out of 343, 64.7%). Investigation of patient sera revealed the presence of free autoantibodies against glycoprotein V in 13.5% of these patients by an indirect monoclonal antibody immobilization of platelet antigen assay, but in 39.6% by surface plasmon resonance technology. These antibodies showed significantly lower avidity (association/dissociation ratio 0.32±0.13 vs. 0.73±0.14; P<0.001). High- and low-avidity antibodies induced comparable amounts of platelet uptake in a phagocytosis assay using CD14+ positively-selected human macrophages [mean phagocytic index, 6.81 (range, 4.75-9.86) vs. 6.01 (range, 5.00-6.98); P=0.954]. In a NOD/SCID mouse model, IgG prepared from both types of anti-glycoprotein V autoantibodies eliminated human platelets with no detectable difference between the groups from the murine circulation [mean platelet survival at 300 minutes, 40% (range, 27-55) vs. 35% (16-46); P=0.025]. Our data establish glycoprotein V as a relevant immune target in immune thrombocytopenia. We would suggest that further studies including glycoprotein V will be required before ITP treatment can be tailored according to platelet autoantibody specificity.

Anti-Glycoprotein V Autoantibodies in Patients with Immune Thrombocytopenia: Regularly Detectable and Functionally Relevant

Immune thrombocytopenia (ITP) results from autoimmunization against platelet antigens. Autoantibodies (aabs) are considered to represent a major mechanism of thrombocytopenia in ITP by inducing platelet clearance from the circulation. Several lines of evidence demonstrate that aabs against glycoproteins (GP) IIb/IIIa and Ib/IX are predominant in ITP patients. Both disease severity and treatment response rates to specific therapeutics have been associated with aabs patterns. GP V is a well characterized immune target in Varicella-associated and drug-induced thrombocytopenia, but has never been studied systematically in ITP.In this study, patients with a suspected diagnosis of primary ITP were included once they met pre-defined clinical inclusion criteria. The presence of GP IIb/IIIa-, GP Ib/IX, and GP V-specific aabs was investigated by monoclonal antibody immobilization of platelet antigens (MAIPA) assay, both on patients' autologous platelets (direct MAIPA) and in serum (indirect MAIPA). In addition, serum IgG fractions were prepared from all patients with a positive direct MAIPA. IgG fractions were tested by surface plasmon resonance (SPR) technology for the presence of anti-GP V aabs. Complete data sets were obtained from 1,140 qualified patients. Platelet-bound aabs were detected in 343/1,140 patients (30.1%). Of these, 222 (64.7%) had platelet-bound anti-GP V aabs, either alone (10/222), or together with other specificities (211/222). Free anti-GP V aabs were detected in 30/222 patients by indirect MAIPA, but in 88/222 by SPR. The avidity of aabs detected by both methods (n=29; R700/R350=0.73±0.14) was significantly higher than the avidity for aabs detected by SPR only (n=59; R700/R350=0.32±0.13, p < 0.001).In order to study the potential biological relevance of anti-GP V, a phagocytosis assay using CD14+ positively-selected macrophages from spleen specimens from splenectomized ITP patients was performed. Anti-GPV aabs induced a modest amount of platelet uptake above the normal human serum-incubated control. No difference was observed between high avidity and low avidity anti-GP V. The effect of anti-GPV on platelet clearance was further studied in a NOD/SCID mouse model. Freshly isolated human platelets were injected into the lateral mouse tail vein; after 30 min, IgG fractions isolated from human sera containing anti-GPV antibodies or control sera from healthy donors were injected into the other lateral tail vein, and the survival of human platelets in the mouse circulation was analyzed by taking murine blood 60, 120, 300 min and 24h after baseline. High avidity and low avidity anti-GP V aabs (n=3 per group) eliminated human platelets with no detectable difference between the groups (mean platelet survival at t=300 min: 40% [range 27-55] versus 35% [range, 16-46]). A comparable, dose-dependent platelet clearance was also obtained with monoclonal antibody SW16 against GP V.In summary, we have demonstrated that anti-GP V autoantibodies are regularly detectable in ITP patients; and that they are able to induce phagocytosis and platelet clearance. Our findings have implications for both, further development of laboratory testing, and guidance for clinical decision making. First, comparison between MAIPA and SPR reveals that free aabs may be more frequent than reported, since aabs appear to escape detection by standard laboratory methods because of low avidity. Better test methods are required. Second, predicting disease severity and/or tailoring ITP therapy can possibly not be restricted to the postulated difference between anti-GP IIb/IIIa and anti-GP Ib/IX. Prospective studies are required to understand the impact of different GP-specific platelet aabs on the clinical course of ITP including, anti-GP V. DisclosuresRummel:Celgene: Honoraria; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Honoraria; Mundipharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Symbio: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Eisai: Honoraria. Bakchoul:Aspen Germany gGmbH, CLS Behring, Stago gGmbH: Honoraria; German Research Society (DFG): Research Funding; Robert Bosch gGmbH: Research Funding.

Case-control study of plasma mean platelet component concentration and survival analysis for dogs with immune-mediated hemolytic anemia.

OBJECTIVE To determine whether dogs with immune-mediated hemolytic anemia (IMHA) had a low plasma mean platelet component (MPC) concentration and whether MPC was associated with outcome. DESIGN Retrospective case-control study and survival analysis. ANIMALS 95 dogs with IMHA (cases) as well as 95 healthy dogs and 95 sick dogs without IMHA (controls) matched to cases by age, reproductive status, and breed. PROCEDURES Plasma MPC concentration at initial examination was compared among groups. For dogs with IMHA only, sex, age, serum urea and bilirubin concentrations, Hct, platelet count, and plasma fibrinogen, D-dimer, and MPC concentrations were evaluated for associations with survival to 42 days after initial examination. RESULTS Plasma MPC concentration was significantly lower in dogs with IMHA than in the other 2 dog groups. In dogs with IMHA, plasma MPC concentration was the only factor significantly associated with outcome. The optimal plasma MPC concentration cutoff value for predicting nonsurvival of dogs with IMHA was 19.1 g/dL; values ≤ 19.1 g/dL were associated with nonsurvival. Likewise, the survival curve for dogs with plasma MPC concentrations ≤ 19.1 g/dL differed significantly from that for dogs with values > 19.1 g/dL. The mean estimated risk of death for dogs with IMHA decreased by 16% for every unit increase in plasma MPC concentration. CONCLUSIONS AND CLINICAL RELEVANCE In dogs with IMHA, platelets appeared to have been activated to a greater degree, as determined by lower plasma MPC concentrations, than in healthy dogs or sick dogs without IMHA. Plasma MPC concentration at initial examination may be useful for predicting prognosis in dogs with IMHA.

HUMAN INTRAPLATELET 5-HYDROXYTRYPTAMINE IS CORRELATED WITH MEAN PLATELET SURVIVAL TIME

HUMAN INTRAPLATELET 5-HYDROXYTRYPTAMINE IS CORRELATED WITH MEAN PLATELET SURVIVAL TIME

A Comparative Study in Volunteers of Apheresis and Buffy Coat Derived Platelets

It is important that, at the time of transfusion, platelets prepared by different techniques are effective in vivo and meet acceptable criteria. A paired study was undertaken in 8 volunteer donors to compare apheresis platelets collected on the COBE Spectra with platelets derived from the buffy coat of whole blood donations after 5 days storage. In vivo recovery, survival and biodistribution were determined following indium-111 labelling of the platelets and autologous infusion into volunteers together with the in vitro evaluation of platelet function and biochemistry. The in vivo and in vitro characteristics of both types of platelet concentrate were not significantly different. Both products were equally viable after 5 d storage and both were of an acceptable quality as judged by currently used platelet products. Mean platelet survival (multiple hit) was 5.4 d for the apheresis platelets and 6.9 d for the buffy coat derived platelets and maximum recovery in circulation was 28.1% and 34.8%, respectively. There was a significantly higher platelet yield, as expected, from apheresis and a 1.5 log lower level of white cell contamination. This would be advantageous for patients in need of prolonged or recurrent transfusions as the number of donor exposures and the risk of alloimmunisation or viral transmission would be reduced.

Decreased platelet counts and decreased platelet serotonin in poststreptococcal nephritis.

Mean platelet survival time in patients with acute poststreptococcal glomerulonephritis (APSGN) is reduced to 50-60% of the control values, and glomerular deposits of platelet factor 4 are found in these patients. In order to investigate further systemic platelet changes of pathogenic, clinical or prognostic significance, we measured the platelet serotonin (5-HT) content and the blood platelet counts during the 1st week of the disease in 27 patients with APSGN. Platelet 5-HT was significantly reduced in patients with APSGN as compared with patients with impetigo without glomerular involvement (785 +/- 54 vs. 1,329 +/- 94 ng 5-HT/10(9) platelets; p < 0.001). Similarly, the mean blood platelet count was reduced to 247 +/- 16 x 10(3) as compared with 303 +/- 14 x 10(3) in the controls (p < 0.05). Thirteen (48%) of these patients had individual values of platelet 5-HT lower than the 95% confidence interval calculated in the control group. No significant correlation was observed between the concentration of 5-HT and either the severity of the disease judged by the amount of urinary protein excretion and the serum creatinine value or the presence of circulating immune complexes. Significant correction of the platelet 5-HT content (to 1,180 +/- 111 ng/10(9) platelets; p < 0.01) and of the platelet counts (to 309 +/- 21 x 10(3); p < 0.01) were observed in the longitudinal study at least 2 weeks later. Platelet activation, with secretion of granular content and increased consumption, may explain these findings. Additionally, the reduced mean age of the circulating platelets could contribute to their decreased 5-HT levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Platelet Consumption in Thrombocythemia Complicated by Erythromelalgia: Reversal by Aspirin

The involvement of platelets in the pathogenesis of erythromelalgia, a frequent and characteristic microvascular thrombotic manifestation in patients with primary thrombocythemia and polycythemia rubra vera, was investigated by measuring the survival and turnover of 51Cr labeled autologous platelets in 10 patients with thrombocythemia complicated by erythromelalgia, in 10 asymptomatic thrombocythemia patients and in 6 subjects with reactive thrombocytosis. The mean platelet survival time of the erythromelalgia patients was 4.2 +/- 0.2 days, which is significantly decreased as compared with asymptomatic thrombocythemia patients (6.6 +/- 0.3 days, p < 0.001) and patients with reactive thrombocytosis (8.0 +/- 0.4 days, p < 0.001). The mean platelet survival time of asymptomatic thrombocythemia patients was significantly decreased (p < 0.01) as compared with reactive thrombocytosis patients. Treatment of erythromelalgia with aspirin increased the mean platelet survival time from 4.0 +/- 0.3 days to 6.9 +/- 0.4 days (p < 0.001) and was associated with an elevation of the platelet count of 216 +/- 30 x 10(9) platelets per liter (p < 0.001). Coumadin failed to improve platelet survival or symptoms caused by erythromelalgia. The increased platelet consumption in erythromelalgia is attributed to the formation of platelet thrombi in the arterial microvasculature. This conclusion is supported by the ability of aspirin to interrupt platelet consumption and clinical features of erythromelalgia.

Idiopathic Thrombocytopenic Purpura (ITP)

Sir.—I read with interest the article by Movassaghi et al entitled Antiplatelet Antibodies in Childhood Idiopathic Thrombocytopenic Purpura (Journal133:257-259, 1979). However, I cannot agree with their conclusion that platelet antibody usually disappears with recovery from thrombocytopenia in childhood ITP. We have already shown in three chronic and five acute cases of childhood ITP that have been in remission for up to six years that mean platelet survival is shorter with platelet opsonization in five cases (in whom it could be determined).1.2 The study has been extended to include 14 children with ITP (six chronic and eight acute) in remission, and again, severe reduction in platelet survival (mean, 4.0 days, which is shorter than in previous reports1.2) with platelet opsonization was shown in every case. The antiplatelet antibodies shown by the Handin and Stossel method3related to acute phase and remission of 49 childhood ITP cases, and

Experimental animal model of refractoriness to donor platelets: the effect of plasma removal and the extent of white cell reduction on allogeneic alloimmunization.

Platelet transfusion effectiveness may be limited in multiply transfused patients by the development of the refractory state. White cell (WBC)-reduction filters with variable efficiency (1-3 log10 reduction) are available and have been shown to be effective in reducing the incidence of platelet alloimmunization. However, the threshold number of WBCs below which alloimmunization would no longer occur is yet to be determined. A previously established animal model was used to examine the relative efficiency of second- and third-generation filters in reducing the frequency of refractoriness to allogeneic platelets. In this model, California Black rabbits are used as blood donors and New Zealand White rabbits as transfusion recipients. Eight weekly transfusions of either second-generation or third-generation WBC-reduced blood resulted in no difference between the two groups in mean platelet survival and rate of refractoriness to allogeneic platelets. To evaluate the possible incremental benefit of removing supernatant plasma to prevent platelet refractoriness, experiments were performed in which groups of animals were given transfusion(s) with red cell suspensions that had been WBC-reduced or both plasma-depleted and WBC-reduced. A significantly lower rate of allogeneic platelet refractoriness was seen in the rabbits that received WBC-reduced and plasma-depleted red cells than in those that received red cells that had been WBC-reduced only. These data provide evidence that the combined use of plasma depletion and WBC reduction can decrease still further the frequency of refractoriness produced by allogeneic blood transfusions.

Mechanism of thrombocytopenia in liver cirrhosis: kinetics of indium-111 tropolone labelled platelets.

Using indium-111 tropolone-labelled platelets, a study of platelet kinetics was performed on the basis of the relationship between platelet count, platelet survival time, platelet dynamics, platelet-associated immunoglobulin G (PA-IgG) and splenic volume in 31 patients with liver cirrhosis and a platelet count of less than 100 x 10(9)/l. The mean platelet count was 46.6 +/- 25.3 x 10(9)/l, and the mean platelet survival time was 6.50 +/- 1.33 days. The mean uptake into the spleen was 43.2% +/- 14.8% on the 1st day, and 53.7% +/- 14.3% on the 7th day. The mean PA-IgG level was 107.6 +/- 66.0 ng/10(7) platelets in five patients with chronic active hepatitis who were studied as controls, the mean platelet count was 197 +/- 30 x 10(9)/l, the mean platelet survival time 9.33 +/- 0.78 days, and the mean PA-IgG 21.2 +/- 2.9 ng/10(7) platelets. The former two parameters were significantly higher (P < 0.05), and the latter significantly lower (P < 0.05). In liver cirrhosis, the platelet count showed a positive correlation with the platelet survival time and a negative correlation with PA-IgG and the splenic volume. These results suggest that the increases in both the splenic platelet pool and platelet destruction in the spleen through immunological mechanisms may influence thrombocytopenia in liver cirrhosis.

Kinetic studies of the mechanism of thrombocytopenia in patients with human immunodeficiency virus infection.

Isolated thrombocytopenia accompanied by increased amounts of platelet-associated antibody is a common manifestation of human immunodeficiency virus (HIV) infection, and the thrombocytopenia often improves with zidovudine. It is not clear whether the mechanism of HIV-related thrombocytopenia primarily involves autoimmune destruction of platelets or reduced platelet production by megakaryocytes. We studied the survival of 111In-labeled autologous platelets and performed platelet imaging in 24 men with isolated HIV-related thrombocytopenia (16 who received no treatment and 8 who received zidovudine). We also studied 20 HIV-infected men with normal platelet counts (10 who received no treatment and 10 who received zidovudine) and studied 12 healthy seronegative men as controls. Mean (+/- SD) platelet survival was significantly decreased in both the untreated and the zidovudine-treated patients with HIV-related thrombocytopenia (to 92 +/- 33 and 129 +/- 44 hours, respectively; both P < 0.001), as compared with the normal controls (198 +/- 15 hours). Mean platelet survival was also significantly decreased in the HIV-infected patients with normal platelet counts (untreated, 162 +/- 23 hours, P < 0.01; zidovudine-treated, 166 +/- 35 hours, P < 0.05). Imaging studies, however, revealed no evidence of increased clearance of autologous platelets in the liver or spleen in any of these groups. Mean platelet production was significantly depressed in the untreated patients with thrombocytopenia (23,000 +/- 11,000 platelets per cubic millimeter per day, P < 0.001) as compared with the healthy controls (45,000 +/- 6,000 per cubic millimeter per day). Mean platelet production was significantly increased, however, in the men treated with zidovudine, both in those with thrombocytopenia (60,000 +/- 31,000 platelets per cubic millimeter per day, P < 0.01 vs. controls) and in those without thrombocytopenia (68,000 +/- 22,000 per cubic millimeter per day, P < 0.01). Although there was a moderate reduction in platelet survival in HIV-infected persons, these patients, regardless of platelet counts, also had decreased production of platelets, possibly due to viral infection of the megakaryocytes. Zidovudine appears to improve platelet production.

Platelet kinetics in asthmatic patients with and without aspirin intolerance.

A reduced platelet survival time has been described in asthmatic patients. There is also good evidence that platelets are involved in aspirin induced asthma. Since aspirin intolerant patients usually suffer from an active disease and often require anti-inflammatory treatment, it has been suggested that platelet survival time may be shorter in aspirin intolerant asthmatic subjects than in aspirin tolerant subjects. The objective of this study was to investigate this hypothesis. Thirteen asthmatic subjects (six aspirin tolerant and seven aspirin intolerant) in a stable clinical condition and ten healthy subjects were studied. Platelet kinetics and survival time were measured with indium-111 labelled autologous platelets. Mean (SD) platelet sequestration ratios in the spleen and liver were lower in asthmatic (2.3 (0.9) and 0.6 (0.2) respectively) than in healthy subjects (3.2 (0.7) and 1.1 (0.4) respectively). However, mean (SD) platelet survival time in asthmatic subjects (8 (2.7) days) did not differ from that in healthy subjects (7.6 (1.1) days). No differences were observed in platelet kinetics between aspirin tolerant and aspirin intolerant patients. These results suggest the existence of an active non-splenic pool of platelets in patients with asthma. However, they failed to show platelet kinetic differences among asthmatic subjects with and without aspirin intolerance and do not support previous studies suggesting an altered platelet survival in stable asthma.

Renal Trapping of ln-111 Troponolate Labeled Platelets in Thrombotic Thrombocytopenic Purpura

A patient with active thrombotic thrombocytopenic purpura underwent examination with In-111 troponolate labeled autologous platelets. A mean platelet survival of 1.2 days was found, comparable to formerly described studies using other methods. Furthermore, remarkable renal uptake of radioactivity consistent with abnormal platelet trapping was demonstrated. In the absence of any other signs of renal involvement, the conclusion was reached that the platelet scan is a sensitive and direct method for showing renal involvement in thrombotic thrombocytopenic purpura.

Platelet 5-Hydroxytryptamine Increases with Platelet Age in Dogs

Thrombocytopenia was induced in mongrel dogs by two mechanisms: immunologically, by intravenous injection of heterologous antiplatelet antibody, and non-immunologically, by circulating the blood through glass beads in anesthetized animals. The platelet content of 5-HT was monitored before and during the recovery of the blood platelet counts. This period is associated with the normalization of the mean platelet survival time and with a progressive increase in the mean age of the circulating platelet population. A continuous increment in platelet 5-HT closely followed the increase in platelet counts in both models of thrombocytopenia, and a strong correlation was found between the platelet age and 5-HT content. These findings support the concept that platelets accumulate 5-HT during their physiological aging process, contradicting the notion that a negative balance in 5-HT content results at the end of their physiological lifespan in circulation. These results are not in conflict with the concept that circulating platelets release and re-uptake 5-HT.

Platelet survival and turnover: important factors in predicting response to splenectomy in immune thrombocytopenic purpura.

Autologous indium-111 platelet sequestration and survival studies were performed on 59 immune thrombocytopenic purpura (ITP) patients, 21 of whom underwent splenectomy shortly thereafter. Sequestration patterns were primarily splenic in 46 patients, primarily hepatic in 6 patients, and both splenic and hepatic in 8 patients. The mean platelet survival ranged from 15 to 211 hr (normal, 180-220 hr), and mean platelet turnover (a measure of platelet production rate) varied from 99 platelets/microliters/hr to 7,585 platelets/microliters/hr (normal 1,200-1,600 platelets/microliters/hr). Among splenectomy patients, 13 had an excellent response, and 8 had a fair or poor response. Neither the pattern of platelet sequestration nor the quantity of platelet-associated IgG was useful in predicting response to splenectomy. There was, however, a striking correlation between platelet studies showing short survival/high turnover and subsequent excellent response to splenectomy. Conversely, patients with only moderately decreased survival and low turnover had an unpredictable response to splenectomy. This investigation demonstrates that ITP patients are a heterogeneous population and include a significant subset whose thrombocytopenia results primarily from decreased turnover. Platelet kinetic studies appear useful in predicting beneficial response to splenectomy.

Viability of platelets following storage in the irradiated state. A pair-controlled study.

Gamma irradiation of blood products is a standard practice recommended for the prevention of posttransfusion graft-versus-host disease in susceptible hosts. We studied the effects of irradiation on stored platelet concentrates and evaluated whether platelets could be stored for 5 days in the irradiated state without adverse effects on their viability. Using a pair-controlled design in which each of six normal subjects acted as his or her own control, we compared in vitro storage characteristics and in vivo kinetics of platelet concentrates exposed to 30 Gy and stored for 5 days with those of platelet concentrates simply stored for 5 days without irradiation. Irradiation had no significant effects on in vitro storage characteristics (platelet count, mean platelet volume, pH, and white cell count) or on in vivo kinetics, including initial recovery and mean platelet survival. Using the multiple-hit model, initial recovery was 49.6 +/- 10.8 percent, and mean platelet survival was 5.6 +/- 1.05 days for irradiated concentrates, compared with 51.3 +/- 13.0 percent and 5.9 +/- 0.50 days, respectively, for the unirradiated control concentrates. We conclude that irradiation of platelet concentrates with up to 30 Gy has no effect on their in vivo recovery or survival, and that irradiation administered before storage of platelet concentrates does not interfere with their clinical efficacy.