Two-layered susceptibility vessel sign is associated with biochemically quantified thrombus red blood cell content.

BACKGROUND AND PURPOSE: Better characterization of the thrombus could be useful to determine acute ischaemic stroke (AIS) aetiology and predict response to thrombolysis and endovascular therapy (EVT). To test the hypothesis that susceptibility vessel sign (SVS) on baseline magnetic resonance imaging (MRI) is related to red blood cell (RBC) content of AIS thrombi, the total haemoglobin contents (HbCs) of AIS thrombi retrieved by EVT from patients with or without SVS or two-layered SVS (TLSVS) were compared. METHODS: Baseline MRI of 84 anterior AIS patients was reviewed by neuro-radiologists blinded to clinical and biochemical data. Thrombi from these patients were retrieved by EVT and analysed for HbC by quantitative enzyme-linked immunosorbent assay and measurement of haem concentration. RESULTS: Susceptibility vessel sign and TLSVS were respectively observed in 85.7% and 50.0% of cases. The median HbC content was 253 µg/mg thrombus (interquartile range 177-333) and the median haem content was 219 µg/mg thrombus (131-264). Thrombus HbC and haem content were highly correlated with thrombus RBC content determined by flow cytometry (r = 0.94). Thrombi from patients with TLSVS weighed more [31.1 (16.5-68.3) mg vs. 17.7 (11.7-33.3) mg; P = 0.005] and had a higher HbC content [278 (221-331) µg/mg vs. 196 (139-301) µg/mg; P = 0.010] compared to thrombi from patients without TLSVS. There was no difference in thrombus weight or HbC content according to SVS status. CONCLUSIONS: Our study shows that TLSVS is significantly associated with a higher thrombus weight and RBC content, as determined by quantitative assays.

Spontaneous bleeding in thrombocytopenia: Is it really spontaneous?

Spontaneous bleeding is a clinical hallmark of thrombocytopenia and can take multiple forms including petechiae, epistaxis, gum bleeding, or, in worst cases, intracranial hemorrhage. Those bleeding events are called " spontaneous " because they occur in the absence of overt trauma. Spontaneous bleeding manifestations have long been considered to be a direct consequence of low platelet counts. Nevertheless, although low platelet counts may lead to ultrastructural endothelial alterations, those alterations and the associated state of vascular fragility are unlikely sufficient to cause spontaneous rupture of the microvessel wall. Indeed, in addition to endothelial injury, factors capable of damaging the basement membrane are required to allow escape of red blood cells in the extravascular space. Therefore, despite their misleading name, spontaneous bleeding events in thrombocytopenia are most likely provoked and involve subclinical biological processes in which platelets normally intervene to ensure hemostasis. In this review, we discuss past and more recent studies on the possible triggers of spontaneous bleeding events in thrombocytopenia, with a particular focus on the role of inflammatory reactions.

How platelets safeguard vascular integrity.

The haemostatic role of platelets was established in the 1880s by Bizzozero who observed their ability to adhere and aggregate at sites of vascular injury. It was only some 80 years later that the function of platelets in maintaining the structural integrity of intact blood vessels was reported by Danielli. Danielli noted that platelets help preserve the barrier function of endothelium during organ perfusion. Subsequent studies have demonstrated further that platelets are continuously needed to support intact mature blood vessels. More recently, platelets were shown to safeguard developing vessels, lymphatics, as well as the microvasculature at sites of leukocyte infiltration, including inflamed organs and tumours. Interestingly, from a mechanistic point of view, the supporting role of platelets in these various vessels does not necessarily involve the well-understood process of platelet plug formation but, rather, may rely on secretion of the various platelet granules and their many active components. The present review focuses on these nonconventional aspects of platelet biology and function by presenting situations in which platelets intervene to maintain vascular integrity and discusses possible mechanisms of their actions. We propose that modulating these newly described platelet functions may help treat haemorrhage as well as treat cancer by increasing the efficacy of drug delivery to tumours.