Bone Marrow Effects of High Dose Folic Acid Therapy in Chronic Idiopathic Thrombocytopenic Purpura.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4016-4016
Author(s):  
Elizabeth Schulz ◽  
Rosangela Albuquerque Ribeiro Holanda ◽  
Francisco Dario Rocha Filho ◽  
Guilherme Alves de Lima Henn ◽  
Ricardo Alves Oliveira
Keyword(s):  
Bone Marrow ◽  
Folic Acid ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Peripheral Blood ◽  
High Dose ◽  
Chronic Idiopathic Thrombocytopenic Purpura ◽  
Thrombocytopenic Purpura ◽  
Bone Marrow Biopsies ◽  
Platelet Counts ◽  
Marrow Cellularity

Abstract Chronic idiopathic thrombocytopenic purpura (CITP) is an autoimmune disorder characterized by the production of autoantibodies against specific platelet antigens and characterized by low platelet counts in peripheral blood over a period of at least 6 months. Corticosteroids have been generally used as first line therapy with serious side effects. Previously, we described the beneficial effect of high dose folic acid (HDFA), 5 to 20 mg PO daily), in the therapy of this disease. Presently, we report the treatment of two patients with severe thrombocytopenia with HDFA. A 46 year old splenectomized woman (P1) and a 32 year old non-splenectomized man (P2), who were moderately refractory to prednisone and prednisolone, had a previous history of undifferentiated connective tissue disease characterized by one episode of arthritis (P2 with a positive rheumatoid factor and morning stiffness). Both patients had normal serum folic acid and vitamin B12, and no signs of megaloblastic or dysplastic alterations were evidenced in bone marrow aspirates. Ham test was negative and CD55/CD59 values for both patients were equal to normal controls. Bone marrow biopsies were also performed prior to the treatment with folic acid (FA) to evidence a global decrease in bone marrow cellularity (30% in case 1 and 20% in case 2). Concomitant infections or other diseases were excluded. Prednisone was tapered slowly, and high dose folic acid administration was initiated at this time. P1 achieved complete remission (CR) in 5 months with slowly tapering of folic acid during one year, remaining with normal platelet counts after one more year with no treatment. P2 achieved sustained partial remission (PR) with platelet counts ranging 63 x 109L to 113 x109/L. Interestingly, sequential bone marrow biopsies performed 2 years after the beginning of HDFA therapy revealed a marrow cellularity of 50% and 35% for P1 and P2, respectively. We demonstrated that the successful CR and PR to HDFA are associated with a significant increase in the overall bone marrow cellularity in both cases (20% in P1 and 15% in P2). Apoptotic features in idiopathic thrombocytopenic purpura (ITP) were characterized by Houwerzijl et al who demonstrated apoptosis and para-apoptosis as ultrastructural alterations in bone marrow megacaryocytes, supportive of ineffective thrombopoiesis as an underlying phenomenon in this study. Buemi et al demonstrated that addition of folic acid to the medium of vascular smooth muscle cells in culture inhibited the percentage of apoptotic and necrotic cells through a decrease in homocysteine concentration. The exact mechanism through which high dose folic acid is able to increase platelets measured in peripheral blood of patients with ITP and induce sustained CR and PR is so far unknown and remains to be explained. However, the present response to HDFA suggest a qualitative and especially quantitative role for this drug in protecting and upgrading the hematopoietic bone marrow and, consequently, restoring the platelet production in these 2 patients.

Acute kidney injury and nephrotic syndrome associated with eltrombopag therapy in chronic idiopathic thrombocytopenic purpura

2021 ◽  
Vol 14 (4) ◽  
pp. e241462
Author(s):  
Suchi Anindita Ghosh ◽  
Jean Patrick ◽  
Kyaw Zin Maw
Keyword(s):  
Acute Kidney Injury ◽  
Renal Failure ◽  
Nephrotic Syndrome ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Kidney Injury ◽  
High Dose ◽  
Chronic Idiopathic Thrombocytopenic Purpura ◽  
Thrombocytopenic Purpura ◽  
Antibody Screen ◽  
Auto Antibody

A 77-year-old man was admitted with severe acute kidney injury and nephrotic syndrome. He was started on eltrombopag for chronic idiopathic thrombocytopenic purpura 6 weeks earlier. An ultrasound of the kidneys was normal and an auto-antibody screen was negative. The use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 5) between the patient’s development of acute renal failure and eltrombopag therapy. Literature review identified only one other case of nephrotic syndrome and acute kidney injury associated with eltrombopag therapy in which a kidney biopsy revealed focal segmental glomerulosclerosis. Due to the challenges faced during the prevailing SARS-CoV-2 pandemic and persistent low platelet counts a renal biopsy was not undertaken. On stopping eltrombopag, the patients renal function stabilised and he successfully went into remission following treatment with high dose corticosteroids and diuretics. This report of a serious case of reversible renal failure and nephrotic syndrome after treatment with eltrombopag may serve to inform clinicians about the possible severe renal adverse effects of eltrombopag before its commencement for future use.

Abnormalities In Platelet Arachidonic Acid Metabolism In Chronic Idiopathic Thrombocytopenic Purpura

1981 ◽  
Author(s):  
M J Stuart ◽  
J G Kelton ◽  
J B Allen
Keyword(s):  
Arachidonic Acid ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Inverse Correlation ◽  
Arachidonic Acid Metabolism ◽  
Thromboxane B2 ◽  
Bleeding Tendency ◽  
Chronic Idiopathic Thrombocytopenic Purpura ◽  
Thrombocytopenic Purpura ◽  
Platelet Counts ◽  
Platelet Thromboxane

Patients with chronic idiopathic thrombocytopenic purpura (CITP) have been described to have bleeding times (B.Ts) that were shorter than would be predicted by their platelet counts. This phenomenon was explained by the presence in CITP of a young platelet population with increased hemostatic competence (NEJM 287:155, ’72). In contradistinction, we have observed patients with CITP to have a bleeding tendency at platelet counts >75,000/cu mm. We therefore evaluated B.Ts and platelet arachidonic acid (AA) metabolism in 7 patients with CITP who demonstrated increased amounts of platelet associated IgG (PAIgG >3fg per platelet) and compared them to 20 healthy controls. 3/7 patients with CITP and platelet counts of >75,000/cu mm demonstrated marked prolongations in their B.Ts. (10’, 12’ and 14’, normal <7’). Marked abnormalities in the metabolism of AA through the cyclo-oxygenase (Thromboxane B2 and HHT) and lipoxygenase (HETE) pathways were also observed in patients with CITP. Platelets in CITP synthesized less amounts (p <0.005) of Thromboxane B2 (10.3 ± 3.1%) in comparison to controls (22.9 ± 1.8). Values for HHT were decreased (23.7 ± 4.9 vs 39.7 ± 1.9; p<0.005), while HETE production was increased (59.5 ± 7.8 vs 30.7 ± 1.8; p<0.001). No correlation was observed between PAIgG and platelet Thromboxane B2 formation. However, an inverse correlation (r=0.81, p<0.05 was observed between the B.T. and platelet Thromboxane B2 formation in patients with chronic ITP. We have demonstrated platelet dysfunction and impaired Thromboxane B2 formation in CITP. This association should be investigated in the individual patient, since the bleeding tendency in these patients is exacerbated by the superimposed impairment in platelet function.

Profiles of Th1, Th2, Th17 and Treg Cells in Patients with Chronic Idiopathic Thrombocytopenic Purpura.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3404-3404
Author(s):  
Rong-Fu Zhou ◽  
Jian Ou-yang ◽  
Da-Yu Chang ◽  
Jing-Yan Xu ◽  
Bing Chen ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Peripheral Blood ◽  
Th17 Cells ◽  
Treg Cells ◽  
Chronic Idiopathic Thrombocytopenic Purpura ◽  
Active Stage ◽  
Thrombocytopenic Purpura ◽  
Chronic Itp ◽  
Ifn Γ

Abstract Objective: To explore the profiles of Th1,Th2, Th17 and Treg cells in patients with chronic idiopathic thrombocytopenic purpura. Methods: Samples of peripheral blood were collected from 30 chronic ITP patients ( 9 males and 21 females), aged 41, 21 being in active stage, and 9 in remission stage, and 9 healthy persons in control (3 males and 6 females), aged 36. Peripheral blood was cultured, and activated with PMA/ionomycin when Th1, Th2 and Th17 cells were detected. Flow cytometry was used to measure the intracellular cytokines interferon (IFN)-γ, interleukin (IL)-4 and interleukin (IL)-17 so as to identify the Th1 cells (CD3+ CD8− IFN-γ+ IL-4− cells), Th2 cells (CD3+ CD8− IFN-γ − IL-4+ cells) and IL-17 cells (CD3+ CD8− IL-17+ cells); Treg cells were identified to CD4+ CD25+ Foxp3+ cells and uncultured peripheral blood was used to measured the CD4+ CD25+ Foxp3+ cells by flow cytometry. The ratios of Th1/Th2 were calculated. Results: The Th1/Th2 ratio for patients in active stage was 15.04±9.67, significantly higher than those for patients in remission stage (7.17±5.38, P <0.05) and in control (8.47±3.78, P <0.05); the percentage of Treg cells of the patients in active stage was 0.89±0.58%, significantly decreased than those of patients in remission stage (6.41±1.86%, P <0.001) and in control (6.06±0.85%, P <0.001); the percentage of Th17 cells was 1.94±0.77% for patients in active stage, 2.16±0.52% for patients in remission stage and 1.82±0.58% for patients in control, respectively, and there was no statistic significance between them. Conclusion: Chronic ITP is a Th1 predominant disease; decreased number and function of Treg cells might be one of mechanisms that cause immune regulation dysfunction in chronic ITP; Th17 cells might not play a role in the development of chronic ITP.

Ultrastructural study shows morphologic features of apoptosis and para-apoptosis in megakaryocytes from patients with idiopathic thrombocytopenic purpura

Blood ◽  
2004 ◽  
Vol 103 (2) ◽  
pp. 500-506 ◽  
Author(s):  
Ewout J. Houwerzijl ◽  
Nel R. Blom ◽  
Johannes J. L. van der Want ◽  
Mariet T. Esselink ◽  
Jan J. Koornstra ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Bone Marrow Cells ◽  
Thrombocytopenic Purpura ◽  
Bone Marrow Biopsies ◽  
Cd34 Cells ◽  
Colony Forming Units ◽  
Circulating Antibodies ◽  
Marrow Cells

Abstract To investigate whether altered megakaryocyte morphology contributes to reduced platelet production in idiopathic thrombocytopenic purpura (ITP), ultrastructural analysis of megakaryocytes was performed in 11 ITP patients. Ultrastructural abnormalities compatible with (para-)apoptosis were present in 78% ± 14% of ITP megakaryocytes, which could be reversed by in vivo treatment with prednisone and intravenous immunoglobulin. Immunohistochemistry of bone marrow biopsies of ITP patients with extensive apoptosis showed an increased number of megakaryocytes with activated caspase-3 compared with normal (28% ± 4% versus 0%). No difference, however, was observed in the number of bone marrow megakaryocyte colony-forming units (ITP, 118 ± 93/105 bone marrow cells; versus controls, 128 ± 101/105 bone marrow cells; P = .7). To demonstrate that circulating antibodies might affect megakaryocytes, suspension cultures of CD34+ cells were performed with ITP or normal plasma. Morphology compatible with (para-)apoptosis could be induced in cultured megakaryocytes with ITP plasma (2 of 10 samples positive for antiplatelet autoantibodies). Finally, the plasma glycocalicin index, a parameter of platelet and megakaryocyte destruction, was increased in ITP (57 ± 70 versus 0.7 ± 0.2; P = .009) and correlated with the proportion of megakaryocytes showing (para-) apoptotic ultrastructure (P = .02; r = 0.7). In conclusion, most ITP megakaryocytes show ultrastructural features of (para-) apoptosis, probably due to action of factors present in ITP plasma.

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