A review of immune thrombocytopenic purpura: focus on the novel thrombopoietin agonists

Mıkhael, Joseph

doi:10.2147/jbm.s6803

Cited by 6 publications

(2 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Platelet depletion occurs when autoantibodies targeting glycoproteins found on the surface of platelets opsonize the cells, resulting in destruction by macrophages. These antibodies can also bind to megakaryocytes and prevent complete maturation, which results in lowered levels of platelet production [11,12]. Several treatments are currently in use in the clinical setting that increase platelet counts, including steroid and immunosuppressive therapy.…”

Section: Discussionmentioning

confidence: 99%

Refractory immune thrombocytopenia successfully treated with high-dose vitamin D supplementation and hydroxychloroquine: two case reports

Bockow

Kaplan

2013

J Med Case Reports

View full text Add to dashboard Cite

IntroductionImmune thrombocytopenic purpura is thought to be characterized by an immune response against the host’s own platelets. If the thrombocytopenia is severe, patients are initially treated with high-dose steroids. Other more toxic second line treatments are considered if steroids fail. Here, we report the case of two patients in whom conventional treatment was unsuccessful but who responded to hydroxychloroquine and high-dose vitamin D replacement therapy. To the best of our knowledge, this is the first description of successful treatment for immune thrombocytopenia with high-dose vitamin D and hydroxychloroquine.Case presentationCase 1: We report the case of a 79-year-old Caucasian man who presented with high titer antinuclear antibodies, positive anti-SSA/Ro autoantibodies and clinically was felt to have an overlap of systemic lupus erythematosus and/or Sjögren’s syndrome with profound life-threatening thrombocytopenia. There was no evidence of underlying malignancy. The patient’s platelet count significantly increased with vitamin D and hydroxychloroquine treatment, but upon vitamin D discontinuation his platelet levels plummeted. Hydroxychloroquine therapy was maintained throughout treatment. With reinstitution of high-dose vitamin D therapy, platelet counts were restored to normal levels.Case 2: We also report the case of an 87-year-old Caucasian woman who presented with high titer antinuclear antibodies, positive anti-SSA/Ro autoantibodies and was felt to have an overlap of systemic lupus erythematosus and/or Sjögren’s syndrome with immune thrombocytopenia; she also had severely low levels of 25-hydroxy vitamin D (17ng/mL). There was no evidence of underlying malignancy. She responded to high-dose vitamin D replacement and hydroxychloroquine treatment, thereby alleviating the need for high-dose steroid treatment. She remains in remission while taking vitamin D, hydroxychloroquine and very low-dose prednisone. No untoward side effects were observed in either patient.ConclusionsIn our two case reports, we found an association between vitamin D deficiency and immune thrombocytopenia where platelet levels responded to vitamin D treatment and hydroxychloroquine but not to prednisone. We believe there may be synergism between vitamin D supplementation and hydroxychloroquine. The mechanism by which high-dose vitamin D results in increased platelet counts in immune thrombocytopenia patients is unknown. However, vitamin D has long been thought to play an immunomodulatory role, which may include a dampened immune response in patients with immune thrombocytopenia or other autoimmune diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

Refractory immune thrombocytopenia successfully treated with high-dose vitamin D supplementation and hydroxychloroquine: two case reports

Bockow

Kaplan

2013

J Med Case Reports

View full text Add to dashboard Cite

show abstract

“…Autoantibodies binding to the platelet membrane proteins leads to direct damage and promotes the removal of these platelets from circulation by phagocytosis in the liver and spleen [6]. Megakaryocyte depletion impairs the production of new platelets in the bone marrow and hence, cannot compensate for the depletion taking place in the circulatory system [6,7]. Based on this background, it is clear that these patients will tend to bleed even from minor injury.…”

Section: Discussionmentioning

confidence: 99%

Immune Thrombocytopenic Purpura and Intracranial Haemorrhage a Formidable Medical Challenge

Calderon¹

2020

OAJNN

View full text Add to dashboard Cite

show abstract

A Novel Role for Thrombopoietin in Regulating Osteoclast Development in Humans and Mice

Bethel

Barnes

Taylor

et al. 2015

Journal Cellular Physiology

View full text Add to dashboard Cite

Emerging data suggest that megakaryocytes (MKs) play a significant role in skeletal homeostasis. Indeed, osteosclerosis observed in several MK-related disorders may be a result of increased numbers of MKs. In support of this idea, we have previously demonstrated that MKs increase osteoblast (OB) proliferation by a direct cell-cell contact mechanism and that MKs also inhibit osteoclast (OC) formation. As MKs and OCs are derived from the same hematopoietic precursor, in these osteoclastogenesis studies we examined the role of the main MK growth factor, thrombopoietin (TPO) on OC formation and bone resorption. Here we show that TPO directly increases OC formation and differentiation in vitro. Specifically, we demonstrate the TPO receptor (c-mpl or CD110) is expressed on cells of the OC lineage, c-mpl is required for TPO to enhance OC formation in vitro, and TPO activates the MAPK, JAK/STAT, and NFκB signaling pathways, but does not activate the PI3K/AKT pathway. Further, we found TPO enhances OC resorption in CD14+CD110+ human OC progenitors derived from peripheral blood mononuclear cells (PBMCs), and further separating OC progenitors based on CD110 expression enriches for mature OC development. The regulation of OCs by TPO highlights a novel therapeutic target for bone loss diseases and may be important to consider in the numerous hematologic disorders associated with alterations in TPO/c-mpl signaling as well as in patients suffering from bone disorders.

show abstract

A review of immune thrombocytopenic purpura: focus on the novel thrombopoietin agonists

Cited by 6 publications

References 83 publications

Refractory immune thrombocytopenia successfully treated with high-dose vitamin D supplementation and hydroxychloroquine: two case reports

Refractory immune thrombocytopenia successfully treated with high-dose vitamin D supplementation and hydroxychloroquine: two case reports

Immune Thrombocytopenic Purpura and Intracranial Haemorrhage a Formidable Medical Challenge

A Novel Role for Thrombopoietin in Regulating Osteoclast Development in Humans and Mice

Contact Info

Product

Resources

About