Sequential occurrence of thrombotic thrombocytopenic purpura, essential thrombocythemia, and idiopathic thrombocytopenic purpura in a 42-year-old African-American woman: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Thrombotic thrombocytopenic purpura and idiopathic thrombocytopenic purpura are two well recognized syndromes that are characterized by low platelet counts. In contrast, essential thrombocythemia is a myeloproliferative disease characterized by abnormally high platelet numbers.</p> <p>The coexistence of thrombotic thrombocytopenic purpura and idiopathic thrombocytopenic purpura in a single patient has been reported in the literature on a few occasions. However, having essential thrombocythemia complicating the picture has never been reported before.</p> <p>Case presentation</p> <p>We present a case where thrombotic thrombocytopenic purpura, essential thrombocythemia, and idiopathic thrombocytopenic purpura were diagnosed in a 42-year-old African-American woman in the space of a few years; we are reporting this case with the aim of drawing attention to this undocumented occurrence, which remains under investigation.</p> <p>Conclusions</p> <p>As the three conditions have different natural histories and require different treatment modalities, it is important to recognize that these diseases may be seen sequentially. This case emphasizes the importance of reviewing peripheral blood smears for evaluation of thrombocytopenia and bone marrow aspirations for diagnosis of thrombocythemia in order to reach an accurate diagnosis and tailor therapy accordingly. Moreover, this case demonstrates the variability and complexity of platelet disorders. This occurrence of three different types of platelet disorders in one patient remains a pure observation on our part; regardless, this does raise the possibility of a common underlying, as yet undiscovered, pathophysiology that could explain the phenomenon.</p

Stretching Reduces Skin Thickness and Improves Subcutaneous Tissue Mobility in a Murine Model of Systemic Sclerosis

Objective: Although physical therapy can help preserve mobility in patients with systemic sclerosis (SSc), stretching has not been used systematically as a treatment to prevent or reverse the disease process. We previously showed in rodent models that stretching promotes the resolution of connective tissue inflammation and reduces new collagen formation after injury. Here, we tested the hypothesis that stretching would impact scleroderma development using a mouse sclerodermatous graft-versus-host disease (sclGvHD) model. Methods: The model consists in the adoptive transfer (allogeneic) of splenocytes from B10.D2 mice (graft) into Rag2−/− BALB/c hosts (sclGvHD), resulting in skin inflammation followed by fibrosis over 4 weeks. SclGvHD mice and controls were randomized to stretching in vivo for 10 min daily versus no stretching. Results: Weekly ultrasound measurements of skin thickness and subcutaneous tissue mobility in the back (relative tissue displacement during passive trunk motion) successfully captured the different phases of the sclGvHD model. Stretching reduced skin thickness and increased subcutaneous tissue mobility compared to no stretching at week 3. Stretching also reduced the expression of CCL2 and ADAM8 in the skin at week 4, which are two genes known to be upregulated in both murine sclGvHD and the inflammatory subset of human SSc. However, there was no evidence that stretching attenuated inflammation at week 2. Conclusion: Daily stretching for 10 min can improve skin thickness and mobility in the absence of any other treatment in the sclGvHD murine model. These pre-clinical results suggest that a systematic investigation of stretching as a therapeutic modality is warranted in patients with SSc

Physiological role of vascular endothelial growth factors as homeostatic regulators

The vascular endothelial growth factor (VEGF) family of proteins are key regulators of physiological systems. Originally linked with endothelial function, they have since become understood to be principal regulators of multiple tissues, both through their actions on vascular cells, but also through direct actions on other tissue types, including epithelial cells, neurons, and the immune system. The complexity of the five members of the gene family in terms of their different splice isoforms, differential translation, and specific localizations have enabled tissues to use these potent signaling molecules to control how they function to maintain their environment. This homeostatic function of VEGFs has been less intensely studied than their involvement in disease processes, development, and reproduction, but they still play a substantial and significant role in healthy control of blood volume and pressure, interstitial volume and drainage, renal and lung function, immunity, and signal processing in the peripheral and central nervous system. The widespread expression of VEGFs in healthy adult tissues, and the disturbances seen when VEGF signaling is inhibited support this view of the proteins as endogenous regulators of normal physiological function. This review summarizes the evidence and recent breakthroughs in understanding of the physiology that is regulated by VEGF, with emphasis on the role they play in maintaining homeostasis. © 2017 American Physiological Society. Compr Physiol 8:955-979, 2018