Differential alterations of CXCR3, CXCR5 and CX3CR1 in patients with immune thrombocytopenia.

As a versatile element for maintaining homeostasis, the chemokine system has been reported to be implicated in the pathogenesis of immune thrombocytopenia (ITP). However, research pertaining to chemokine receptors and related ligands in adult ITP is still limited. The states of several typical chemokine receptors and cognate ligands in the circulation were comparatively assessed through various methodologies. Multiple variable analyses of correlation matrixes were conducted to characterize the correlation signatures of various chemokine receptors or candidate ligands with platelet counts. Our data illustrated a significant decrease in relative CXCR3 expression and elevated plasma levels of CXCL4, 9-11, 13, and CCL3 chemokines in ITP patients with varied platelet counts. Flow cytometry assays revealed eminently diminished CXCR3 levels on T and B lymphocytes and increased CXCR5 on cytotoxic T cell (Tc) subsets in ITP patients with certain platelet counts. Meanwhile, circulating CX3CR1 levels were markedly higher on T cells with a concomitant increase in plasma CX3CL1 level in ITP patients, highlighting the importance of aberrant alterations of the CX3CR1-CX3CL1 axis in ITP pathogenesis. Spearman's correlation analyses revealed a strong positive association of peripheral CXCL4 mRNA level, and negative correlations of plasma CXCL4 concentration and certain chemokine receptors with platelet counts, which might serve as a potential biomarker of platelet destruction in ITP development. Overall, these results indicate that the differential expression patterns and distinct activation states of peripheral chemokine network, and the subsequent expansion of circulating CXCR5+ Tc cells and CX3CR1+ T cells, may be a hallmark during ITP progression, which ultimately contributes to thrombocytopenia in ITP patients.

Binge-reading on immune thrombocytopenia: Everything you ever wanted to know.

Immune thrombocytopenia (ITP) is a complex clinical and pathophysiological autoimmune disorder and in the past decade, thousands of papers have been published on this topic. To shed light on the global scientific output, Ou et al. performed a comprehensive bibliometric analysis of the ITP literature to clarify the major hotspots and future research directions. Commentary on: Ou et al. A bibliometric analysis of primary immune thrombocytopenia from 2011 to 2021. Br J Haematol 2023;201:954-970.

Thrombocytopenia in the intensive care unit.

Thrombocytopenia is a common laboratory finding in critically ill patients admitted to the intensive care unit. Potential etiologies of thrombocytopenia are myriad, ranging from acute disease processes and concomitant conditions to exposures and drugs. The mechanism of decreased platelet counts can also be varied: laboratory measurement may be spurious, platelet production may be decreased, or platelet destruction or sequestration may be increased. In addition to evaluation for the cause of thrombocytopenia, the clinician must also guard against spontaneous bleeding due to thrombocytopenia, prophylax against bleeding resulting from an invasive procedure performed in the setting of thrombocytopenia, and treat active bleeding related to thrombocytopenia.

Platelet transfusion refractoriness due to HLA alloimmunization: Evolving paradigms in mechanisms and management.

Platelet transfusion refractoriness due to HLA alloimmunization presents a significant medical problem, particularly among multiply transfused patients with hematologic malignancies and those undergoing hematopoietic stem cell transplants. HLA compatible platelet transfusions also impose significant financial burden on these patients. Recently, several novel mechanisms have been described in the development of HLA alloimmunization and platelet transfusion refractoriness. We review the history of platelet transfusions and mechanisms of HLA-sensitization and transfusion refractoriness. We also summarize advances in the diagnosis and treatment of platelet transfusion refractoriness due to HLA alloimmunization.

Primary Immune Thrombocytopenia: Novel Insights into Pathophysiology and Disease Management.

Immune thrombocytopenia (ITP) is an autoimmune disorder defined by a significantly reduced number of platelets in blood circulation. Due to low levels of platelets, ITP is associated with frequent bruising and bleeding. Current evidence suggests that low platelet counts in ITP are the result of multiple factors, including impaired thrombopoiesis and variations in immune response leading to platelet destruction during pathological conditions. Patient outcomes as well as clinic presentation of the disease have largely been shown to be case-specific, hinting towards ITP rather being a group of clinical conditions sharing common symptoms. The most frequent characteristics include dysfunction in primary haemostasis and loss of immune tolerance towards platelet as well as megakaryocyte antigens. This heterogeneity in patient population and characteristics make it challenging for the clinicians to choose appropriate therapeutic regimen. Therefore, it is vital to understand the pathomechanisms behind the disease and to consider various factors including patient age, platelet count levels, co-morbidities and patient preferences before initiating therapy. This review summarizes recent developments in the pathophysiology of ITP and provides a comprehensive overview of current therapeutic strategies as well as potential future drugs for the management of ITP.

Immune thrombocytopenic purpura presenting as unprovoked gingival hemorrhage: a case report.

Immune thrombocytopenic purpura is an autoimmune disease characterized by auto-antibody induced platelet destruction and reduced platelet production, leading to low blood platelet count. In this case report, the clinical diagnose of a patient with immune thrombocytopenic purpura and spontaneous gingival hemorrhage by a dentist is presented. The patient did not have any systemic disease that would cause any spontaneous hemorrhage. The patient was referred to a hematologist urgently and her thrombocyte number was found to be 2000/µL. Other test results were in normal range and immune thrombocytopenic purpura diagnose was verified. Then hematological treatment was performed and patient's health improved without further problems. Hematologic diseases like immune thrombocytopenic purpura, in some cases may appear firstly in the oral cavity and dentists must be conscious of unexplained gingival hemorrhage. In addition, the dental treatment of immune thrombocytopenic purpura patients must be planned with a hematologist.

Extracorporeal ("ex vivo") connection of pig kidneys to humans. I. Clinical data and studies of platelet destruction.

The pioneering experiment by Welsh et al. (Immunological Lett 1991:29:167-170) connecting a pig kidney to the human circulation has been repeated in a modified manner. Two volunteer dialysis patients were pretreated by daily plasmapheresis on days -2,-1, and 0 to remove the naturally occurring anti-pig xenoantibodies. The anti-pig lymphocytotoxic liters were reduced from 1:8 to 1:2 in patient 1 and from 1:8 to 1:1 in patient 2. No steroids or immunosuppressive drugs were administrated before or during the experiments. A sterile pig kidney was extracorporeally ("ex vivo") connected to the patients a/v fistula using an arterial and a venous pump similar to a dialysis. The two experiments gave different results. In the first experiment the perfusion pressure was kept at 100 mmHg for the initial 25 min by reducing the pump speed until the minimum blood flow of 30 ml/min was reached. Thereafter, the pressure rose continuously and the experiment was terminated at 65 min at a perfusion pressure of 200 mmHg. The patient did not feel any discomfort during the perfusion. In the second experiment, a stable blood flow of 200 ml/min was reached at a pressure of 100 mmHg after a few minutes. The perfusion was terminated at 15 min when the patient developed chest and abdominal pain, hypotension, and electrocardiographic signs of myocardial ischemia. The patient recovered quickly. In the first experiment, small volumes of clear urine was produced until the pressure rose above 100 mmHg, which resulted in hematuria. In the second experiment clear urine (4 ml/min) was produced. (51)Chromium clearance values were after 15 min <1 ml/min for kidney 1 and 12 ml/min (8 ml/min/100 g) for kidney 2. A drastic reduction in platelet count (128 to 48 and 64 to 8 × 10(9)/1, respectively) during the passage through the kidney was found in blood samples collected simultaneously before and after the organ. No change in hemoglobin values and leucocyte counts were found. Light- and electron-microscopical analysis of the kidney tissues revealed for kidney 1 focal areas with obliteration of the glomerular and peritubular capillaries by platelets and PMN cells and severe damage of the endothelial cells comparable to a picture of a hyperacute rejection. In kidney 2, all vessels were patent but in the capillaries large amount of membrane fragments were detected by electron microscopy and a discrete damage of the endothelial cells were seen in some segments. No intact platelets were present in the vascular tree. These human experiments support the hypothesis that hyperacute rejection of pig to human xenografts is delayed in time by removal of the preformed anti-pig xenoantibodies. A new finding was a very rapid destruction of platelets occurring in the kidney of patient 2 who had very low liters of xenoantibodies. The humoral immune response is described in detail in an accompanying paper (Rydberg et al., this issue).