Sequestration Pattern Research Articles

Study of platelet kinetics in immune thrombocytopenia to predict splenectomy response.

Despite the efficacy of splenectomy for chronic immune thrombocytopenia (ITP), its considerable failure rate and its possible related complications prove the need for further research into potential predictors of response. The platelet sequestration site determined by 111 In-labelled autologous platelet scintigraphy has been proposed to predict splenectomy outcome, but without standardisation in clinical practice. Here, we conducted a single-centre study by analysing a cohort of splenectomised patients with ITP in whom 111 In-scintigraphy was performed at La Paz University Hospital in Madrid to evaluate the predictive value of the platelet kinetic studies. We also studied other factors that could impact the splenectomy outcome, such as patient and platelet characteristics. A total of 51 patients were splenectomised, and 82.3% responded. The splenic sequestration pattern predicted a higher rate of complete response up to 12 months after splenectomy (p = 0.005), with 90% sensitivity and 77% specificity. Neither age, comorbidities, therapy lines nor previous response to them showed any association with response. Results from the platelet characteristics analysis revealed a significant loss of sialic acid in platelets from the non-responding patients compared with those who maintained a response (p = 0.0017). Our findings highlight the value of splenic sequestration as an independent predictor of splenectomy response.

The spatial patterns and driving mechanisms of blue carbon ‘loss’ and ‘gain’ in a typical mangrove ecosystem: A case study of Beihai, Guangxi Province of China

The role of mangroves in carbon sequestration is critical in mitigating climate change. For better identifying the carbon conservation hotspots of mangroves influenced by environmental factors, the spatial distribution and driving mechanisms of mangrove vegetation and soil carbon sequestration, as well as the future carbon dynamics of mangroves, required clarification. Firstly, we assessed the spatial pattern of vegetation biomass and soil depth-varied soil total organic carbon (TOC) in Xiaoguansha, Guangxi Province of China, and its relationships with duration of inundation (DTI) were explored. Additionally, the carbon storage capacity of adjacent mangrove tidal flats as potential carbon reservoirs was quantified. Thirdly, freshwater, and nutrient inputs, biotic factors of mangrove, and soil composition were selected as impact factors, and their mechanisms in carbon sequestration were elucidated by using Partial least squares path modeling (PLS-PM). Finally, medium values of environmental factors on mangrove carbon sequestration were revealed, based on which future loss and gain patterns of carbon sequestration under the combined effects were fully discussed. The results showed that: (1) The Above-ground biomass (AGB) and TOC densities were 32.89 Mg C/ha and 185.10 Mg C/ha in the study area, and both were enriched in the Interior areas. The carbon sequestration in the tidal flats was equivalented to >1/5 of total carbon sequestration of mangroves. (2) DTI was the most critical factor affecting the carbon sequestration pattern and was found to be positive correlated with AGB and TOC via changing soil contents (SC), whereas it exhibits a negative correlation with AGB and TOC through influencing canopy density (CD). CD and TP were identified as significant predictors. (3) Median analysis indicated that future carbon ‘gain’ area will move nearshore, whereas the carbon-rich intertidal area may undergo carbon loss. This study provided new insights and scientific understanding for management of mangrove blue carbon function.

Predictive Value of Platelet Sequestration Studies in Splenectomy Response

Background: Splenectomy is an effective therapy for chronic immune thrombocytopenia (ITP), with high rates of long-term responses reported (about 60-80%). Because the possible related complications its indication has been limited, proving the need for further research into potential predictive factors of response. The platelet clearance determined by 111In-labelled autologous platelet scintigraphy has been proposed as an independent predictor of splenectomy outcome, with heterogenous recorded results.This study aimed to evaluate the effect of splenic platelet sequestration in predicting splenectomy response, as well as to identify other possible factors that could justify treatment failure. Methods: We retrospectively analyzed a cohort of refractory and relapsed ITP patients who underwent 111In-labelled platelet scintigraphy in one center in Madrid (La Paz University Hospital), between 2005 and 2021. The sequestration patterns were categorized based on the splenic:liver ratio (S:L), and dichotomized as splenic if purely splenic (S:L > 2) or predominantly splenic (S:L 1.4 < 2); and non-splenic if mixed (S:L 0.8 < 1.4) or hepatic (S:L < 0.8). The response to splenectomy was assessed in terms of blood platelet count at 3, 6 and 12 months post-splenectomy, according to ITP Spanish Group 2020 guidelines. Biological platelet characteristics were subsequently examined to investigate their role in splenectomy failure. Platelet activation markers (such as activation of fibrinogen receptor determined through PAC1-binding, TRAP-induced P-selectin and CD63 exposure) and active caspase-3, -7, -8 or -9 were evaluated. Platelet surface sialic acid exposure was studied by determining the binding of Ricinus Communis Agglutinin (RCA) labelled with fluorescein (FITC). Samples were analyzed by flow cytometry. Results were expressed as the ratio between each patient's values and the mean from healthy control group. Patients were separated into responders and non-responders for the analysis, applying univariate tests and multivariate regression models. Results: Platelet scintigraphy was performed in 80 patients, 51 of them underwent splenectomy. Median previous lines of treatment were 3.5 (2-6). Complications occurred in 10% of splenectomized patients, with only one non-hemorrhagic fatality event in the cohort (not related to splenectomy). Among the 51 patients with splenectomy performed, 86.2% did respond. When analyzed by sequestration pattern, complete response (CR) was observed in 75% of those with a splenic pattern. By univariate analysis, only splenic sequestration correlated with higher sustained response rate at 12 months (Table 1). The same parameter retained statistical significance through a multivariate logistic regression model (Odds ratio=37.65; p=0.005). No association was observed in terms of response with the other analyzed factors, including age, comorbidity, previous lines of treatment and previous response. Seven responders patients with splenic clearance relapsed within 3 months. Their platelet characteristics were compared to those from 16 responders controls. There were no significant differences between groups in the variables studied, except for increased binding of RCA to platelets of patients who relapsed (median, percentile 25/75= 2.05, 1.74/4.03), in contrast to those who maintained response (1.05, 0.71/1.37) (Figure 1). These findings suggest an increased desialylation pattern in platelets from the patients who relapsed. Conclusions: Our data confirm the predictive value of 111In-labelled platelet studies prior to splenectomy, with splenic sequestration emerging as an independent predictor of long-term response. Enhanced desialylation in platelets surface provides a potential explanation for splenectomy failure in those patients with a splenic clearance. The clinical relevance of these results is due to enabling a better selection of suitable candidates for splenectomy, to increase its efficacy and safety. Keywords: Chronic Immune Thrombocytopenia (ITP), splenectomy, autologous 111In-labelled platelet, splenic sequestration. Study supported by ISCIII-Fondos FEDER (PI19/00772) and PDSA. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Indium-labelled autologous platelet sequestration studies predict response to splenectomy in immune thrombocytopenia: an Australian experience.

Splenectomy is an effective intervention in primary immune thrombocytopenia (ITP). Attempts to define pre-clinical predictors of platelet response to splenectomy are inconsistent. Based on international studies defining the likelihood of platelet response using platelet sequestration, patients with relapsed/refractory ITP being considered for splenectomy at a regional Australian hospital were assessed with 111 indium-labelled autologous platelet sequestration (ILAPS) studies. To audit the use of ILAPS in an Australian setting and define its role in predicting response to splenectomy. A retrospective review of all patients referred for an ILAPS study at a regional hospital was performed. Results for each patient were expressed as an 'R' value (spleen/ liver uptake ratio) to quantify the platelet sequestration pattern and outcome post-splenectomy, based on platelet counts. A total of 45 patients was identified: 13 underwent splenectomy and 32 were medically managed. Patients with favourable ILAPS scans (pure or predominant splenic sequestration) demonstrated a superior response post-splenectomy (100% overall response rate (ORR); 83.5% complete remission (CR)) compared with those with unfavourable ILAPS scans (mixed or pure hepatic sequestration) (71.4% ORR; 57.1% CR) over 12 months. The use of ILAPS in the Australian setting is feasible and this experience confirms larger international studies demonstrating its utility as a predictor of response to splenectomy in ITP. An unfavourable ILAPS scan could be considered a negative predictor of response prompting consideration for other emerging ITP treatments such as thrombopoietin-receptor agonists or B-cell depleting therapy such as Rituximab.

Anti-glycoprotein antibodies and sequestration pattern of indium-labeled platelets in immune thrombocytopenia

AbstractAntiglycoprotein (anti-GP) antibodies play an important role in the pathophysiology of immune thrombocytopenia (ITP). The sequestration pattern of platelets in the spleen and liver can be studied with 111In-labeled autologous platelet scans. No studies have investigated the role of anti-GP antibodies in sequestration patterns in ITP patients. In this study, we examined the association between antibodies and (1) platelet sequestration site and (2) clearance rate of platelets. All ITP patients receiving an 111In-labeled autologous platelet study between 2014 and 2018 were included. Antibodies were measured using the direct MAIPA method to determine the presence and titer of anti-GPIIb/IIIa, anti-GPIb/IX, and anti-GPV antibodies. Multivariate regression models were used to study the association between anti-GP antibodies, sequestration site, and clearance rate. Seventy-four patients were included, with a mean age of 36 years. Forty-seven percent of the patients showed a predominantly splenic sequestration pattern, 29% mixed, and 25% a hepatic pattern. In 53% of the patients, anti-GP antibodies were detected. Regression models showed a significant association between splenic sequestration and GPV autoantibodies. Furthermore, in patients where antibodies were present, the clearance rate was higher in patients with a splenic sequestration. Anti-GPV antibodies are associated with a splenic sequestration pattern in ITP patients. These associations provide insight into the possible pathophysiological mechanisms of ITP, which may lead to better detection and treatment of this partly idiopathic and prevalent disease.

Kinetic Behaviors of Methane Hydrate Formation with Bubble Seeping at Conditions of “Haima” Cold Seep

Marine methane sequestration pattern and potential play significant roles in climate change mitigation. It is essential to study the fate of methane bubbles migrating from the seafloor, given the w...

Sequestration Pattern in ITP Liver/Spleen Scan Correlates with the Presence of Anti-Glycoprotein V Antibodies in ITP Patients

Introduction Immune thrombocytopenia (ITP) is characterized by low platelet counts due to high clearance and low production. Better insight in the pathophysiology of ITP is needed to personalize management regimes, especially in patients with persisting and chronic ITP. In the Haga Teaching Hospital, we reproduced and validated the ITP liver/spleen scan from St Bartholomew's Hospital in London. With this scan the in vivo sequestration patterns of platelets in either spleen, liver or a combination of both (mixed sequestration) can be assessed, by using Indium-111 labelled autologous platelets . The ITP liver/spleen scan may provide better insights in autoantibody-mediated platelet destruction in ITP patients. Autoantibodies directed against glycoprotein (GP) IIb/IIIa, Ib/IX and V namely are found in a majority of ITP patients and can be detected using specific assays, like platelet immunofluorescence test (PIFT) and Monoclonal Antibody Immobilization of Platelet Antigen (MAIPA). To the best of our knowledge no studies have investigated the possible association between sequestration patterns and glycoproteins. In this study we investigated associations between the sequestration patterns from the ITP liver/spleen scan and the presence of different anti-GP platelet antibodies.Methods All ITP patients receiving an ITP liver/spleen scan between 2014 and 2016 in the Haga Teaching Hospital, a large tertiary referral centre in the Netherlands, are collected from our electronic patient files. We retrospectively collected demographic and clinical characteristics, including duration of ITP, previous management of ITP (corticosteroids, rituximab, thrombopoietin receptor agonists (TPO-RA)), antibody assays (PIFT, direct and indirect MAIPA) and the results from the ITP liver/spleen scan. MAIPA is used as a continuous variable. To investigate the association between anti-GP antibodies and the sequestration pattern from the ITP liver/spleen scan we used linear regression models for the continuous variables and logistic regression models for the binary data. Observational data and scatter plots aid in the interpretation of the possible associations. Both univariate and multivariate regression models including age and sex will be performed.Results 55 ITP patients with a median age of 41 years (IQR 29-57) and 67% females underwent an liver/spleen scan in the study period. The median age of the cohort at diagnosis of ITP was 32 (IQR 22-54) years. Treatment history consisted of corticosteroid therapy in 96% of cases, 44% IVIG, 48% TPO-RA and 21% rituximab. 10% of patients received only 1 treatment line, 23% received 2 lines, 33% received 3 lines, 21% 4 lines, 10% 5 lines and 1 patient received 7 lines (2%). Clinical significant bleedings (WHO bleeding grade ≥2) were reported by 53%, and 8% of the patients received a transfusion in the past. Sequestration pattern of the ITP liver/spleen was in 51% of cases a splenic pattern vs. 49% a mixed/hepatic pattern. A significantly higher prevalence of a splenic pattern was present in patients under 30 years at diagnosis while patients older than 30 years showed a more mixed/hepatic pattern. Anti-glycoprotein antibodies were found in 54% of the patients. Interestingly, linear regression models showed no association between either anti-GPIIb/IIIa or anti-GPIb/IX antibody detection and sequestration pattern. However a significant association was observed between the presence of anti-GPV antibodies and sequestration pattern. A higher anti-GPV antibody level and/or affinity was associated with a higher level of splenic sequestration.Conclusions This study has shown that the presence of anti-GPV antibodies is associated with a splenic sequestration pattern in the ITP liver/spleen scan in patients suffering from persistent and chronic ITP. GPV is usually found as a complex with GPIb/IX in several other bleeding disorders. Surprisingly no association was found in our data between a splenic sequestration pattern and the presence of anti-GPIIb/IIIa and especially anti-GPIb/IX. Further studies are needed to clarify the possible role of anti-GPV antibodies in thrombocyte clearance by the spleen in ITP patients. DisclosuresAmini:AMGEN: Research Funding. Schutgens:Baxalta/Shire: Research Funding; Novo Nordisk: Research Funding; Bayer: Research Funding; CSL Behring: Research Funding; Pfizer: Research Funding; Uniqure BV: Research Funding. Schipperus:AMGEN: Research Funding; Novartis: Research Funding.

Autologous platelet scintigraphy and clinical outcome of splenectomy in immune thrombocytopenia: A systematic review and meta-analysis.

Autologous platelet sequestration pattern is associated with post-splenectomy platelet response in patients with immune thrombocytopenia (ITP). However, published results are contradictory, and have not been systematically reviewed. Our aim is to systematically review and meta-analyse the association between sequestration pattern and post-splenectomy platelet response. Articles were selected from MEDLINE when they a) included ITP patients, b) performed scintigraphy, and c) included post-splenectomy platelet response. The 23 included studies (published between 1969-2018) represented 2966 ITP-patients. Response to splenectomy occurred most frequently in patients with a splenic pattern (87.1 % in splenic versus 47.1 % in mixed and 25.5 % in hepatic patterns). A pooled analysis of 8 studies showed an odds ratio of 14.21 (95 % CI: 3.65-55.37) for platelet response in the splenic versus the hepatic group. Our findings indicate that a splenic sequestration pattern is associated with better response after splenectomy. Platelet sequestration patterns may be useful in the clinical decision-making regarding splenectomy.

Genomic and transcriptomic comparisons of closely related malaria parasites differing in virulence and sequestration pattern.

Background: Malaria parasite species differ greatly in the harm they do to humans. While P. falciparum kills hundreds of thousands per year, P. vivax kills much less often and P. malariae is relatively benign. Strains of the rodent malaria parasite Plasmodium chabaudi show phenotypic variation in virulence during infections of laboratory mice. This make it an excellent species to study genes which may be responsible for this trait. By understanding the mechanisms which underlie differences in virulence we can learn how parasites adapt to their hosts and how we might prevent disease. Methods: Here we present a complete reference genome sequence for a more virulent P. chabaudi strain, PcCB, and perform a detailed comparison with the genome of the less virulent PcAS strain. Results: We found the greatest variation in the subtelomeric regions, in particular amongst the sequences of the pir gene family, which has been associated with virulence and establishment of chronic infection. Despite substantial variation at the sequence level, the repertoire of these genes has been largely maintained, highlighting the requirement for functional conservation as well as diversification in host-parasite interactions. However, a subset of pir genes, previously associated with increased virulence, were more highly expressed in PcCB, suggesting a role for this gene family in virulence differences between strains. We found that core genes involved in red blood cell invasion have been under positive selection and that the more virulent strain has a greater preference for reticulocytes, which has elsewhere been associated with increased virulence. Conclusions: These results provide the basis for a mechanistic understanding of the phenotypic differences between Plasmodium chabaudi strains, which might ultimately be translated into a better understanding of malaria parasites affecting humans.

Genomic and transcriptomic comparisons of closely related malaria parasites differing in virulence and sequestration pattern

Background: Malaria parasite species differ greatly in the harm they do to humans. While P. falciparum kills hundreds of thousands per year, P. vivax kills much less often and P. malariae is relatively benign. Strains of the rodent malaria parasite Plasmodium chabaudi show phenotypic variation in virulence during infections of laboratory mice. This make it an excellent species to study genes which may be responsible for this trait. By understanding the mechanisms which underlie differences in virulence we can learn how parasites adapt to their hosts and how we might prevent disease. Methods: Here we present a complete reference genome sequence for a more virulent P. chabaudi strain, PcCB, and perform a detailed comparison with the genome of the less virulent PcAS strain. Results: We found the greatest variation in the subtelomeric regions, in particular amongst the sequences of the pir gene family, which has been associated with virulence and establishment of chronic infection. Despite substantial variation at the sequence level, the repertoire of these genes has been largely maintained, highlighting the requirement for functional conservation as well as diversification in host-parasite interactions. However, a subset of pir genes, previously associated with increased virulence, were more highly expressed in PcCB, suggesting a role for this gene family in virulence differences between strains. We found that core genes involved in red blood cell invasion have been under positive selection and that the more virulent strain has a greater preference for reticulocytes, which has elsewhere been associated with increased virulence. Conclusions: These results provide the basis for a mechanistic understanding of the phenotypic differences between Plasmodium chabaudi strains, which might ultimately be translated into a better understanding of malaria parasites affecting humans.

Genomic and transcriptomic comparisons of closely related malaria parasites differing in virulence and sequestration pattern

Background: Malaria parasite species differ greatly in the harm they do to humans. While P. falciparum kills hundreds of thousands per year, P. vivax kills much less often and P. malariae is relatively benign. Strains of the rodent malaria parasite Plasmodium chabaudi show phenotypic variation in virulence during infections of laboratory mice. This make it an excellent species to study genes which may be responsible for this trait. By understanding the mechanisms which underlie differences in virulence we can learn how parasites adapt to their hosts and how we might prevent disease. Methods: Here we present a complete reference genome sequence for a more virulent P. chabaudi strain, PcCB, and perform a detailed comparison with the genome of the less virulent PcAS strain. Results: We found the greatest variation in the subtelomeric regions, in particular amongst the sequences of the pir gene family, which has been associated with virulence and establishment of chronic infection. However, despite substantial variation at the sequence level, the repertoire of these genes has been largely maintained, highlighting the requirement for functional conservation as well as diversification in host-parasite interactions. However, a subset of pir genes, previously associated with increased virulence, were more highly expressed in PcCB, suggesting a role for this gene family in virulence differences between strains. We found that core genes involved in red blood cell invasion have been under positive selection and that the more virulent strain has a greater preference for reticulocytes, which has elsewhere been associated with increased virulence. Conclusions: These results provide the basis for a mechanistic understanding of the phenotypic differences between Plasmodium chabaudi strains, which might ultimately be translated into a better understanding of malaria parasites affecting humans.

Influence of sowing time and crop geometry on carbon sequestration pattern through high value medicinal plant Valeriana jatamansi underforest ecosystem

The current study was carried out in lava range (Kalimpong Block II) of forest of Darjeeling Himalayaduring the year 2010–14 under the aegis of Regional Research Station (Hill Zone), Uttar Banga Krishi Viswavidyalay with an altitude of 1550 m a.s.l.Main objectiveof this experiment was to increase the soil carbon pool with improved cultivation aspect of Valeriana jatamansi - A high value threatened medicinal plant of Darjeeling Himalaya. Significantly more sequestration of carbon registered with June transplanting at 12, 15, 18, 21 and 24 month stage with spacing of 30 × 45 cm.Assimilation of total underground part on fresh weight basis produced noteworthy response at 12 and 18 month stageof Juneplanting. Utmost underground carbon storage was recorded with 30 × 45 cm, and was at par with the spacing of 30 cm × 30 cm. Date of transplanting failed to produce any significant effect on carbon storage through rhizome biomass at all the stage of observation, except at 9, 21 and 24 month stage where July transplanting produced significantly more assimilation of carbon compared to June transplanting of seedlings. More underground carbon accumulation through rhizome production was recorded with maximum spacing, and was at par with 30 cm × 30 cm spacing at 12, 15, 18 and 21 month stage. More root carbon assimilation was recorded with June transplanting with 30 cm × 30 cm and 30 cm × 45 cm spacing. We can conclude that early planting (i.e. first week of June planting) along with wider spacing (30 cm × 45 cm) of Valeriana jatamansi gave more biomass yield, which help to more confiscation of atmospheric carbon. This has benefit with respect to soil fertility, increased income, increased carbon stock, reduced vulnerability, increased productivity and help to reduced impact of climate change on forest microhabitate.

Distribution of radiolabeled l-glutamate and d-aspartate from blood into peripheral tissues in naive rats: Significance for brain neuroprotection

Excess l-glutamate (glutamate) levels in brain interstitial and cerebrospinal fluids (ISF and CSF, respectively) are the hallmark of several neurodegenerative conditions such as stroke, traumatic brain injury or amyotrophic lateral sclerosis. Its removal could prevent the glutamate excitotoxicity that causes long-lasting neurological deficits. As in previous studies, we have established the role of blood glutamate levels in brain neuroprotection, we have now investigated the contribution of the peripheral organs to the homeostasis of glutamate in blood. We have administered naive rats with intravenous injections of either l-[1- 14C] Glutamic acid ( l-[1- 14C] Glu), l-[G- 3H] Glutamic acid ( l-[G- 3H] Glu) or d-[2,3- 3H] Aspartic acid ( d-[2,3- 3H] Asp), a non-metabolized analog of glutamate, and have followed their distribution into peripheral organs. We have observed that the decay of the radioactivity associated with l-[1- 14C] Glu and l-[G- 3H] Glu was faster than that associated with glutamate non-metabolized analog, d-[2,3- 3H] Asp. l-[1- 14C] Glu was subjected in blood to a rapid decarboxylation with the loss of 14CO 2. The three major sequestrating organs, serving as depots for the eliminated glutamate and/or its metabolites were skeletal muscle, liver and gut, contributing together 92% or 87% of total l-[U- 14C] Glu or d-[2,3- 3H] Asp radioactivity capture. l-[U- 14C] Glu and d-[2,3- 3H] Asp showed a different organ sequestration pattern. We conclude that glutamate is rapidly eliminated from the blood into peripheral tissues, mainly in non-metabolized form. The liver plays a central role in glutamate metabolism and serves as an origin for glutamate metabolites that redistribute into skeletal muscle and gut. The findings of this study suggest now that pharmacological manipulations that reduce the liver glutamate release rate or cause a boosting of the skeletal muscle glutamate pumping rate are likely to cause brain neuroprotection.

Left upper lobe pulmonary sequestration

A 64-year-old non-smoking woman with a left upper lobe mass underwent a wedge resection by video-thoracoscopic approach. Intraoperative frozen section examination was unable to rule out a neoplastic disease and a lobectomy was performed. Microscopic analysis showed a typical pulmonary sequestration pattern including arteries with elastic layers in a systemic fashion. Pulmonary sequestration is a development lung disease: upper lobe location is considered uncommon and much controversy exists concerning this form which may be underrated.

P.P.2 05 Muscleblind-like protein 1 nuclear sequestration and splicing pattern in myotonic dystrophy type 2

P.P.2 05 Muscleblind-like protein 1 nuclear sequestration and splicing pattern in myotonic dystrophy type 2

Pathophysiology of HIV related thrombocytopenia: an analysis of 41 patients.

To analyse the pathogenic mechanism of HIV related thrombocytopenia. Forty one patients with thrombocytopenia and HIV-1 infection were investigated over two years. Anticardiolipin antibodies were measured using an enzyme linked immunosorbent assay and antiplatelet antibodies were measured using an immunocapture technique. Tests for VDRL, C3 and C4, antinuclear antibodies and rheumatoid factor were also carried out in all patients and 80 control subjects (HIV-1 positive but non-thrombocytopenic). Indiumoxine labelled platelets were transfused in 13 patients. P24 antigen were also measured in 12 bone marrow aspirates. Antiplatelet antibodies and circulating immune complexes were found exclusively in the thrombocytopenic group; values for antiplatelet antibodies and circulating immune complexes were both higher in homosexual and bisexual patients. Three kinds of pattern were observed using 111 In-labelled platelets: splenic (n = 10); hepatic (n = 2); and destruction of bone marrow in just one case. The two most influential factors in the sequestration pattern were antiplatelet antibodies in the splenic uptake and circulating immune complexes in the hepatic and marrow sequestration. All patients, except three, had decreased platelet recovery. In those patients with a CD4 lymphocyte count of less than 200 x 10(6) cells/l the recovery was clearly greater (53%) than in patients who had more than 200 x 10(6) /l (28%). Finally, in seven of the 12 patients who were chosen for immunohistochemical study, p24 antigen was detected in the megakaryocytes, verifying that HIV-1 infects such cells. The pathogenic mechanism of HIV related thrombocytopenia is probably multifaceted. Antiplatelet antibodies and circulating immune complexes would cause peripheral destruction in the spleen, liver, and bone marrow, in that order; and, on the other hand, there would be an ineffective immune thrombopoiesis and direct infection of the megakaryocytes which could cause a change in the function and maturity of these cells.

Sequestration pattern of parasitized erythrocytes in cerebrum, mid-brain, and cerebellum of Plasmodium coatneyi-infected rhesus monkeys (Macaca mulatta).

Six rhesus monkeys (Macaca mulatta) infected with Plasmodium coatneyi were studied for parasitized red blood cell (PRBC) sequestration in microvessels of the brain. The degree of PRBC sequestration is different in the cerebral, mid-brain, and cerebellar microvessels, with sequestration occurring preferentially in the cerebellum. This pattern resembles that of PRBC sequestration in cerebral and cerebellar microvessels in human falciparum malaria. The morphologic appearance of sequestered cells under light and electron microscopy as well as the PRBC sequestration pattern bolsters the contention that the rhesus monkey infected with P. coatneyi is an appropriate primate model for the experimental study of human cerebral malaria.

Prediction of the effect of immunoglobulin therapy in ITP.

The correlation between the response to high-dose immunoglobulin therapy (IVIg) and the sequestration pattern of Indium-labeled platelets (In-PLT) in the body was studied in 9 patients with chronic idiopathic thrombocytopenic purpura (ITP). Patients that has prominent platelet sequestration in the spleen responded to IVIg. In these patients, splenic sequestration decreased by 20-30% after IVIg without significant changes in hepatic sequestration. This finding suggests that the blocking of splenic Fc receptors with immunoglobulin minimized the destruction of sensitized platelets. However, patients who had almost equal platelet sequestration in the liver and spleen did not respond to IVIg. In these patients, hepatic sequestration decreased after IVIg, whereas splenic sequestration increased. Thus, it appears that estimating the platelet sequestration pattern using In-PLT is useful for predicting the effects of IVIg.

Kinetics and In Vivo Distribution of In-111-Labelled Platelets and Platelet Function in Familial Hypercholesterolaemia

The kinetics, in vivo distribution and sites of sequestration of autologous In-111-labelled platelets and other platelet function parameters were studied in ten patients with type IIa or IIb familial hypercholesterolaemia and thrombotic complications of atherosclerosis. The in vitro platelet aggregation response to ADP (P = 0.50) and collagen (P = 0.46); binding of fibrinogen to platelets (P = 0.61); and plasma beta-thromboglobulin levels (P = 0.42) of the patients and normal reference subjects did not differ significantly. The in vivo distribution of In-111-labelled platelets at equilibrium was within normal limits, and at the end of platelet life-span the sequestration pattern of labelled platelets in the reticuloendothelial system was also normal (spleen P = 0.31; liver P = 0.54). There was minimal evidence of in vivo platelet activation: only mean platelet lifespan (MPLS), 195 +/- 57 hours (difference between mean MPLS of patients and controls was 25 hours, with a 95% confidence interval from 23 to 31 hours; P = 0.02); mean platelet platelet turnover, 2298 +/- 824 platelets/microliter/hour (P = 0.005); plasma platelet factor 4 (P = 0.02); and the mean circulating platelet aggregate ratio, 0.8 +/- 0.1 (P = 0.02); differed significantly from normal. These results suggest that abnormalities of platelet function and kinetics observed in type II hyperlipoproteinaemia cannot be ascribed wholly to the hyperlipidaemia, but may be induced by the associated atherosclerosis.

Platelet-associated immunoglobulins IgG, IgM, IgA and complement C3c in chronic idiopathic autoimmune thrombocytopenia: relation to the sequestration pattern of 111indium labelled platelets.

Levels of platelet-associated immunoglobulins (PAIg) IgG, IgM, IgA and complement C3c were related to parameters of 111Indium-labelled platelet kinetics in 17 patients with chronic idiopathic autoimmune thrombocytopenia (cAITP). Elevated levels of PAIg/C3c were found in 14 patients (82%) (PAIgG n = 13, PAIgM n = 11, PAIgA n = 1, PAC3c n = 5). Only PAIgG correlated with platelet counts (RS = -0.71, p less than 0.01). Mean platelet life span (MLS) was shortened in all patients (median 12.0 h, range 0.3-45.6 h) and correlated with the platelet counts (RS = 0.49, p less than 0.05). MLS was correlated with PAIgG (RS = -0.52, p less than 0.05), but not with PAIgM, PAIgA, or PAC3c. The site of sequestration was splenic in 10 patients and splenic-hepatic in 7 patients. Although no significant correlation between either site of platelet sequestration and any of the investigated PAIg/C3c was demonstrable, platelets coated with higher PAIgG levels were more readily sequestrated in the spleen, while elevations of PAC3c were found in 4 out of 7 patients with hepatic involvement.