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Abstract Background Platelets and erythrocytes constitute over 95% of all hematopoietic stem cell output. However, the clonal dynamics of HSC contribution to these lineages remains largely unexplored. Results We use lentiviral genetic labeling of mouse hematopoietic stem cells to quantify output from all lineages, nucleate, and anucleate, simultaneously linking these with stem and progenitor cell transcriptomic phenotypes using single-cell RNA-sequencing. We observe dynamic shifts of clonal behaviors through time in same-animal peripheral blood and demonstrate that acute platelet depletion shifts the output of multipotent hematopoietic stem cells to the exclusive production of platelets. Additionally, we observe the emergence of new myeloid-biased clones, which support short- and long-term production of blood cells. Conclusions Our approach enables kinetic studies of multi-lineage output in the peripheral blood and transcriptional heterogeneity of individual hematopoietic stem cells. Our results give a unique insight into hematopoietic stem cell reactivation upon platelet depletion and of clonal dynamics in both steady state and under stress.

Platelets are key mediators of thrombus formation and inflammation during the acute phase of ischaemic stroke. Particularly, the platelet glycoprotein (GP) receptors GPIbα and GPVI have been shown to mediate platelet adhesion and activation in the ischaemic brain. GPIbα and GPVI blockade could reduce infarct volumes and improve functional outcome in mouse models of acute ischaemic stroke, without concomitantly increasing intracerebral haemorrhage. However, the functional role of platelets during long-term stroke recovery has not been elucidated so far.Thus, we here examined the impact of platelet depletion on post-stroke recovery after transient middle cerebral artery occlusion (tMCAO) in adult male mice. Platelet depleting antibodies or isotype control were applied from day 3–28 after tMCAO in mice matched for infarct size. Long-term functional recovery was assessed over the course of 28 days by behavioural testing encompassing motor and sensorimotorical functions, as well as anxiety-like or spontaneous behaviour. Whole brain flow cytometry and light sheet fluorescent microscopy were used to identify resident and infiltrated immune cell types, and to determine the effects of platelet depletion on the cerebral vascular architecture, respectively.We found that delayed platelet depletion does not improve long-term functional outcome in the tMCAO stroke model. Immune cell abundance, the extent of thrombosis and the organisation of the cerebral vasculature were also comparable between platelet-depleted and control mice. Our study demonstrates that, despite their critical role in the acute stroke setting, platelets appear to contribute only marginally to tissue reorganisation and functional recovery at later stroke stages.

ObjectiveTo explore the risk factors and predictive indexes of severe thrombocytopenia during concurrent radio-chemotherapy of nasopharyngeal carcinomas.MethodsRetrospective analysis was performed from the hospitalized patients with nasopharyngeal carcinoma from August 2014 to July 2017, and induction chemotherapy and concurrent radio-chemotherapy were completed. According to the lowest platelet count during concurrent chemotherapy, patients were divided into observation and control groups. General information and laboratory examinations were recorded and analyzed by univariate analysis, multivariate regression analysis, and ROC curve analysis.ResultsFactors, including age, PLT, IBIL, APTT at first visit, WBC, RBC, HGB, PLT, NEUT, APTT, IBIL, FFA, Crea, and urea before radio-chemotherapy, which are significant in univariate analysis into multivariate regression analysis, were taken. It turned out that RBC (OR = 10.060, 95% CI 2.679–37.777, p = 0.001), PLT (OR = 1.020, 95% CI 1.006–1.034, p = 0.005), and IBIL (OR = 0.710, 95% CI 0.561–0.898, p = 0.004) are independent predictors of severe TP in NPC. ROC analysis showed that the AUC of RBC, IBIL, PLT, and AGE is 0.746 (p < 0.001), 0.735 (p < 0.001), 0.702 (p = 0.001), and 0.734 (p < 0.001). New variables called joint predictors were calculated by a regression equation (Y = 2.309 * RBC - 0.343 * IBIL + 0.02 * PLT - 10.007), the AUC of which is 0.8700 (p < 0.001); best truncation value is >5.87 mmol/l.ConclusionsLower RBC, PLT, and higher IBIL before concurrent radio-chemotherapy are independent risk factors causing severe TP during concurrent radio-chemotherapy of NPC. The RBC, PLT, and IBIL before concurrent radio-chemotherapy and joint predictor have a good predictive value to evaluate the risk of severe TP during concurrent radio-chemotherapy of NPC.

The hemorrhagic syndrome of leptospirosis was studied in guinea pigs. The study correlates hematological, histopathological and immunohistochemical alterations in sixty animals inoculated by the intraperitoneal route with lml of the culture of virulent strain of Leptospira interrogans serovar copenhageni. Leptospirae antigens were detected by immunoperoxidase, chiefly in liver, kidney and heart muscle capillaries. Possible pathogenic mechanisms responsible for hemorrhagic syndrome are discussed with emphasis on toxic and anoxic attacks causing damage to endothelia, platelet depletion and alterations to hemostasia rates: prothrombin time [FT], partial thromboplastin time [PIT] and fibrinogen concentrations. Tide clinical-laboratoiy picture is compatible with the histopathological observation of disseminated intravascular coagulation [D1C] in most of the guinea pigs from day 4 of infection.Os autores estudam a síndrome hemorrágica da leptospirose em cobaios inoculados com amostra virulenta de Leptospira interrogans sorovar copenhageni. São abordados aspectos hematológicos, hístopatolôgicos e imuno- histoquímicos. Aumento do tempo de protrombina (PT) e do tempo parcial tromboplastina (PTT), bem como redução do número de plaquetas e do fibrinogênio acompanharam-se de congestão vascular, hemorragias e coagulação intravascular no fígado, rim, coração, músculo esquelético e pulmão. O antígetzo de Leptospira foi detectado principalmente em tecido hepático, renal e cardíaco. São discutidos possíveis mecanismos patogênicos responsáveis pela síndrome hemorrágica, com ênfase na agressão tóxico- anóxica do endotêlio vascular, que propiciaria a instalação de coagulação intravascular disseminada (CIVD) observada, sobretudo, nos cobaios dos grupos 4, 5 e 6.