pDC as a modulator of platelet production

SummaryThe effect of total and partial splenectomy on the number and production of circulating platelets was studied in mice. Five days after total and partial splenectomy the number of the peripheral blood platelets increased by 87% and 60%, respectively and the incorporation of 75selenium methionine (75Se-Met) into platelets was enhanced indicating that the thrombocytosis was due to increased platelet production. The results obtained by the two operative procedures were compared.Since previous work from our laboratory has shown that a factor produced by splenic lymphocytes affects the platelet number in mice, it is suggested that the differences in the number of circulating platelets observed in animals after total and partial splenectomy may reflect a difference in the number of spleen lymphocytes removed.

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The thrombopoietin receptor: revisiting the master regulator of platelet production

Platelets ◽

10.1080/09537104.2021.1925102 ◽

2021 ◽

pp. 1-9

Author(s):

Ian S. Hitchcock ◽

Maximillian Hafer ◽

Veena Sangkhae ◽

Julie A. Tucker

Keyword(s):

Master Regulator ◽

Platelet Production ◽

Thrombopoietin Receptor

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Association between Platelet-Associated Immunoglobulin G Levels and Response to Corticosteroid Therapy in Patients with Newly Diagnosed Immune Thrombocytopenia

Acta Haematologica ◽

10.1159/000511698 ◽

2020 ◽

pp. 1-6

Author(s):

Masuho Saburi ◽

Masao Ogata ◽

Yasuhiro Soga ◽

Takako Satou ◽

Kazuhito Itani ◽

...

Keyword(s):

Corticosteroid Therapy ◽

Immunoglobulin G ◽

Immune Thrombocytopenia ◽

High Dose ◽

First Line ◽

Laboratory Findings ◽

Platelet Production ◽

First Line Therapy ◽

Line Therapy ◽

Immature Platelet Fraction

Objective: Platelet-associated immunoglobulin G (PA-IgG) refers to IgG attached to the surface of platelets, while the immature platelet fraction (IPF) reflects the state of platelet production in bone marrow. Since PA-IgG and IPF are increased in patients with immune thrombocytopenia (ITP), reflecting amounts of platelet antibodies and compensatory platelet production, respectively, we hypothesized that these laboratory findings may provide useful markers for predicting treatment response in patients with ITP. We therefore retrospectively investigated associations between levels of these markers at diagnosis and response to first-line therapy in patients with ITP. Methods: Forty-three patients diagnosed with ITP at Oita Kouseiren Tsurumi Hospital between May 2010 and November 2018 were included. Patients were divided into 2 groups based on response to corticosteroid as first-line therapy. Laboratory findings were compared between responders and nonresponders. Results: Median PA-IgG was 285 ng/107 cells (range, 45.5–18,200 ng/107 cells), and median IPF was 15.5% (range, 5.4–62.1%). Median levels were higher than the respective upper limits of normal range (PA-IgG, 0–46 ng/107 cells; IPF, 1.1–9.5%). First-line therapy was performed using standard-dose prednisolone (0.5–1.0 mg/kg/day) in 32 patients and high-dose dexamethasone (40 mg/day, 4 days) or methylprednisolone (125–1,000 mg/day, 3–4 days) in 11 patients. Twenty-four patients (55.8%) responded to first-line therapy. In univariate analysis, type of corticosteroid (p = 0.17) tended to differ between groups but did not differ significantly, and no difference in IPF level was apparent between responders (15.35%; range, 5.4–41.5%) and nonresponders (16.7%; range, 6.3–62.1%; p = 0.15). PA-IgG was significantly higher among nonresponders (430 ng/107 cells; range, 101–18,200 ng/107 cells) than among responders (254.5 ng/107 cells; range, 45.5–470 ng/107 cells; p = 0.004). Multivariate analysis revealed PA-IgG was independently associated with response to first-line therapy (odds ratio, 1.000; 95% confidence interval, 1.000–1.010; p = 0.029). Conclusion: Our data suggested that PA-IgG at diagnosis could offer a useful predictor of response to first-line corticosteroid therapy for ITP.

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Proplatelets and stress platelets

Blood ◽

10.1182/blood.v69.2.522.522 ◽

1987 ◽

Vol 69 (2) ◽

pp. 522-528 ◽

Cited By ~ 44

Author(s):

M Tong ◽

P Seth ◽

DG Penington

Keyword(s):

Bone Marrow ◽

Platelet Rich Plasma ◽

Early Period ◽

Platelet Volume ◽

Plasma Exposure ◽

Functional Characteristics ◽

Platelet Production ◽

Relationship Of ◽

The Relationship ◽

Platelet Formation

Abstract The process of platelet formation by the fragmentation of megakaryocyte pseudopodia, termed proplatelets, demonstrable in the marrow sinusoids is poorly understood. “Stress” platelets produced under conditions of stimulated platelet production differ from normal circulating platelets with respect to volume and a number of functional characteristics. To clarify the relationship of stress platelets to proplatelets, rats were injected with heterologous platelet antiserum. Nondiscoid platelet forms, some characteristically beaded in appearance, strongly resembling bone marrow proplatelets, can be recovered in the circulation of normal rats. During the early period of recovery from acute thrombocytopenia, there was a substantial increase in the proportion of these elongated platelets in the citrated platelet rich plasma. Exposure to EDTA rendered them spherical. Circulating proplatelets may contribute significantly to the prompt increase in platelet volume during recovery from acute thrombocytopenia at a time prior to significant increase in megakaryocyte size and ploidy.

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Flow cytometric analysis of megakaryocytes from patients with abnormal platelet counts

Blood ◽

10.1182/blood.v74.2.594.594 ◽

1989 ◽

Vol 74 (2) ◽

pp. 594-601 ◽

Cited By ~ 48

Author(s):

A Tomer ◽

P Friese ◽

R Conklin ◽

W Bales ◽

L Archer ◽

...

Keyword(s):

Cell Size ◽

Flow Cytometric Analysis ◽

Distribution Analysis ◽

Membrane Expression ◽

Platelet Destruction ◽

Platelet Production ◽

Flow Cytometric ◽

High Ploidy ◽

The Right ◽

Primary Thrombocytosis

Abstract Megakaryocytes (MKs) from 40 patients with quantitative platelet disorders and 19 normal volunteers were analyzed by flow cytometry for size, fine cell internal structure and granularity, membrane expression of the glycoprotein (GP) IIb/IIIa complex, and for ploidy distribution. Analysis was performed on unfractionated minimally manipulated marrows obtained from routine bone marrow aspirates. MKs were labeled with a fluorescent lineage-specific monoclonal antibody to the GPIIb/IIIa complex followed by DNA staining with propidium iodide. Eight hundred to 3,000 MKs were analyzed in each sample. The modal ploidy distribution in normals was 16N, comprising about half of the megakaryocytic population, with 22.6% of the cells less than or equal to 8N and 22.0% greater than or equal to 32N. Twelve thrombocytopenic patients with decreased marrow MKs on biopsy (mean platelet count [MPC] 44,600/microliters) showed an increase in low ploidy cells with 53.2% less than or equal to 8N (P less than .01); cell size was reduced in three patients when compared to normal cells of identical ploidy (P less than .05). Eight thrombocytopenic patients with enhanced platelet destruction (with normal or increased MKs on biopsy and shortened platelet survival; MPC 41,400/microliters) showed an increased proportion of high ploidy cells greater than or equal to 32N to 39.2% (P less than .01). Increased cell size and granularity were found in four of these patients (P less than .05). Six patients with thrombocytopenia secondary to multiple mechanisms affecting both platelet production and destruction (MPC 66,700/microliters) showed no shift in ploidy. Four patients with primary thrombocytosis (two with thrombocythemia and two with polycythemia vera; MPC 822,500/microliters) showed a marked shift toward high ploidy cells with 42.3% greater than or equal to 32N and 7.6% greater than or equal to 64N cells (P less than .01). The shift was accompanied by a marked increase in cell size and granularity in the patients with thrombocythemia. Ten patients with thrombocytosis secondary to chronic blood loss, malignant or inflammatory disorders (MPC 714,000/microliters), showed variable distributions with four patients exhibiting a shift in ploidy to the right similar to that found in the patients with increased platelet destruction. Based upon the present data, flow cytometric ploidy distribution may be diagnostically useful in thrombocytopenic patients by discriminating between disorders of platelet production and destruction.

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Platelet production estimation in thrombocytopenic patient: a non-invasive or invasive approach?

Nuclear Medicine Communications ◽

10.1097/00006231-200404000-00103 ◽

2004 ◽

Vol 25 (4) ◽

pp. 422 ◽

Cited By ~ 1

Author(s):

M. Todorovic-Tirnanic ◽

V. Obradovic ◽

N. Suvajdzic ◽

I. Elezovic ◽

M. Rolovic ◽

...

Keyword(s):

Invasive Approach ◽

Platelet Production ◽

Non Invasive ◽

Thrombocytopenic Patient

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Stimulating platelet production to raise platelet count in immune thrombocytopenic purpura: A novel approach

The Indian Journal of Pediatrics ◽

10.1007/s12098-009-0206-y ◽

2009 ◽

Vol 76 (10) ◽

pp. 1065-1066

Author(s):

Jagdish Chandra ◽

V. P. Choudhry

Keyword(s):

Platelet Count ◽

Immune Thrombocytopenic Purpura ◽

Thrombocytopenic Purpura ◽

Platelet Production ◽

Novel Approach

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Bacterial survival and distribution during buffy coat platelet production

Vox Sanguinis ◽

10.1111/vox.12427 ◽

2016 ◽

Vol 111 (4) ◽

pp. 333-340 ◽

Cited By ~ 11

Author(s):

M. Taha ◽

M. Kalab ◽

Q.-L. Yi ◽

E. Maurer ◽

C. Jenkins ◽

...

Keyword(s):

Buffy Coat ◽

Bacterial Survival ◽

Platelet Production

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Improving Human Induced Pluripotent Stem Cell-Derived Megakaryocyte Differentiation and Platelet Production

International Journal of Molecular Sciences ◽

10.3390/ijms22158224 ◽

2021 ◽

Vol 22 (15) ◽

pp. 8224

Author(s):

Linda Krisch ◽

Gabriele Brachtl ◽

Sarah Hochmann ◽

André Cronemberger Andrade ◽

Michaela Oeller ◽

...

Keyword(s):

Pluripotent Stem Cells ◽

Iterative Process ◽

Pluripotent Stem Cell ◽

Induced Pluripotent Stem Cell ◽

Mesoderm Induction ◽

Related Protein ◽

Media Composition ◽

Platelet Production ◽

Induced Pluripotent ◽

Related Proteins

Several protocols exist for generating megakaryocytes (MKs) and platelets from human induced pluripotent stem cells (hiPSCs) with limited efficiency. We observed previously that mesoderm induction improved endothelial and stromal differentiation. We, therefore, hypothesized that a protocol modification prior to hemogenic endothelial cell (HEC) differentiation will improve MK progenitor (MKP) production and increase platelet output. We further asked if basic media composition affects MK maturation. In an iterative process, we first compared two HEC induction protocols. We found significantly more HECs using the modified protocol including activin A and CHIR99021, resulting in significantly increased MKs. MKs released comparable platelet amounts irrespective of media conditions. In a final validation phase, we obtained five-fold more platelets per hiPSC with the modified protocol (235 ± 84) compared to standard conditions (51 ± 15; p < 0.0001). The regenerative potency of hiPSC-derived platelets was compared to adult donor-derived platelets by profiling angiogenesis-related protein expression. Nineteen of 24 angiogenesis-related proteins were expressed equally, lower or higher in hiPSC-derived compared to adult platelets. The hiPSC-platelet’s coagulation hyporeactivity compared to adult platelets was confirmed by thromboelastometry. Further stepwise improvement of hiPSC-platelet production will, thus, permit better identification of platelet-mediated regenerative mechanisms and facilitate manufacture of sufficient amounts of functional platelets for clinical application.

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