Effects of Urinary Extracts from Patients with Idiopathic Thrombocytopenic Purpura or Aplastic Anemia on Rodent Platelet Production and Megakaryocytopoiesis

Pathobiology ◽  
1987 ◽  
Vol 55 (5) ◽  
pp. 257-264
Author(s):  
Shin-ichiro Kuriya ◽  
T. Kamamoto ◽  
Martin J. Murphy, Jr.
Keyword(s):  
Aplastic Anemia ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Thrombocytopenic Purpura ◽  
Platelet Production

Aplastic Anemia and Idiopathic Thrombocytopenic Purpura with Antibody to Platelet Glycoprotein llb/llla Following Resection of Malignant Thymoma

1993 ◽  
Vol 90 (1) ◽  
pp. 42-45 ◽  
Author(s):  
Hikaru Kobayashi ◽  
Kiyoshi Kitano ◽  
Fumihiro Ishida ◽  
Hiroshi Saito ◽  
Hideharu Miyabayashi ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Platelet Glycoprotein ◽  
Thrombocytopenic Purpura ◽  
Malignant Thymoma

scholarly journals Studies on Thrombopoiesis

Blood ◽  
1957 ◽  
Vol 12 (6) ◽  
pp. 520-528 ◽  
Author(s):  
G. IZAK ◽  
D. NELKEN ◽  
MISS A. HERZOG
Keyword(s):  
Idiopathic Thrombocytopenic Purpura ◽  
Culture Media ◽  
Tissue Cultures ◽  
Continuous Observation ◽  
Healthy Individuals ◽  
Chronic Idiopathic Thrombocytopenic Purpura ◽  
Thrombocytopenic Purpura ◽  
Platelet Production ◽  
Bone Marrow Cultures ◽  
Marrow Cultures

Abstract Thrombocytopoiesis was studied by direct, continuous observation in tissue cultures of bone marrows taken from three patients with chronic idiopathic thrombocytopenic purpura and from normals following the addition of a potent anti-platelet serum to the culture media. The process of platelet production was similar in these two conditions and followed the pattern observed in bone marrow cultures of healthy individuals. The breakdown of megakaryocytes of patients with idiopathic thrombocytopenic purpura and those treated with anti-platelet serum was greatly accelerated. No morphologic evidence of injury to the megakaryocytes was present. The platelets produced showed degenerative changes, they were agglutinated and underwent phagocytosis by the myeloid elements and reticulum cells were present in the cultures.

Multiple Cycles of Recombinant Human Thrombopoietin Therapy in a Patient with Chronic Refractory Idiopathic Thrombocytopenic Purpura.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3933-3933
Author(s):  
Yongqiang Zhao ◽  
Baolai Hua ◽  
Nong Zou ◽  
Shujie Wang ◽  
Tienan Zhu
Keyword(s):  
Platelet Count ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Immunosuppressive Agents ◽  
Plasma Concentrations ◽  
Thrombocytopenic Purpura ◽  
Platelet Production ◽  
Platelet Counts ◽  
Multiple Cycles ◽  
Recombinant Human Thrombopoietin ◽  
Refractory Itp

Abstract Thrombopoietin (TPO) is the key regulator of megakaryocytepoiesis and platelet production. TPO binds to its specific receptor, c-Mpl, on the surfaces of megakaryocytes, and may promote the proliferation, differentiation and maturation of megakaryocytes, and finally increase the circulating platelet count. The role of TPO in the pathogenesis of idiopathic thrombocytopenic purpura (ITP) is not certain. Plasma concentrations of TPO in ITP patients were similar to or little lower than that in healthy subjects. Therefore it is possible that supplemental TPO could significantly promote platelet production and increase platelet counts in ITP patients. Here, we report the result of multiple cycles of recombinant human thrombopoietin (rhTPO) therapy in a patient with refractory ITP. The patient, a 42-year-old woman, was admitted to our department on December 30, 2003. She had suffered from chronic ITP for more than 4 years. The patient had been treated with glucocorticosteroids, immunosuppressive agents and splenectomy. No sustained response could be achieved. The diagnosis of chronic refractory ITP was made. There were petechiae and gingival bleeding on admission. Liver and spleen were not palpable. Hemoglobin was 142g/L, white blood cell count 7.6×10 9/L, platelet count 15×10 9/L. Bone marrow aspiration revealed that erythroid and myeloid development were normal, megakaryocytes were increased in number and no dysplastic features. After an informed consent was obtained from the patient, rhTPO (Sunshine Pharmaceutical Corporation, China) was administrated subcutaneously at dosage of 1.0 μg/kg, daily for 14 days or until platelet count sustained more than 50×109/L. Anti-rhTPO antibodies were determined weekly by ELISA. Three cycles of rhTPO therapy was given with 6, 13 and 8 dosing for each cycle. The platelet counts before each cycle were all less than10×109/L and increased above 50×109/L on day 5, 11 and 8 of rhTPO administration, respectively. The peak platelet counts of 456, 130 and 82×109/L were reached on day 9, 15 and 13 for each cycle. Then platelet count decreased gradually. The durations of platelet count more than 50×109/L in 3 cycles were 13, 7 and 10 days respectively. No increase of WBC count and Hb level occurred. No liver and kidney function damage, abnormal coagulation functions or thrombosis developed during the treatment. rhTPO antibodies were not detectable. The result indicated that rhTPO could transiently increase peripheral platelet counts of the patient with chronic refractory ITP. It was uncertain why peak platelet counts declined and durations of platelet count more than 50×109/L shortened when multiple cycles of rhTPO were given.

Human thrombopoietin levels are high when thrombocytopenia is due to megakaryocyte deficiency and low when due to increased platelet destruction

Blood ◽  
1996 ◽  
Vol 87 (10) ◽  
pp. 4068-4071 ◽  
Author(s):  
RV Emmons ◽  
DM Reid ◽  
RL Cohen ◽  
G Meng ◽  
NS Young ◽  
...  
Keyword(s):  
Platelet Count ◽  
Detection Limit ◽  
Aplastic Anemia ◽  
Blood Levels ◽  
Platelet Destruction ◽  
Thrombocytopenic Purpura ◽  
Platelet Production ◽  
Normal Individuals ◽  
Per Se ◽  
Posttransfusion Purpura

Thrombopoietin (TPO), the ligand for c-mpl, stimulates proliferation of committed megakaryocytic progenitors and induces maturation of megakaryocytes. To better understand factors regulating TPO levels, we measured blood levels of TPO in patients with impaired platelet production due to aplastic anemia (AA) and with platelet destructive disorders, including idiopathic thrombocytopenic purpura (ITP), posttransfusion purpura (PTP), drug purpura (DP), and X-linked thrombocytopenia (XLTP). The TPO receptor capture enzyme immunoassay (EIA) used had a detection limit of integral of approximately-150 to 200 pg/mL. TPO was undetectable in 88 of 89 normal individuals. Eighteen of 19 patients with AA and a mean platelet count (MPC) of 18,000/microliters (2,000 to 61,000/microliters) had markedly elevated TPO levels (mean, 1,467 pg/mL; range, 597 to 3,834 pg/mL). Eight AA patients who responded to immunosuppressive therapy with their MPC increasing to 140,000/microliters (92,000 to 175,000/microliters) had substantial decreases in TPO (mean, 440 pg/mL; range, 193 to 771 pg/mL). Initial TPO levels did not differ significantly between responders and nonresponders. In contrast, all 21 patients with ITP and an MPC of 16,000/microliters (1,000 to 51,000 /microliters) had undetectable TPO levels, as did 6 patients with acute PTP or DP and 2 patients with XLTP. Megakaryocyte mass, reflected in the rate of platelet production, appears to be the major determinant of TPO levels in thrombocytopenic patients rather than circulating platelet levels per se. Measurement of serum TPO may be useful in differentiating thrombocytopenias due to peripheral destruction from those due to thrombopoietic failure.

scholarly journals Platelet production rate predicts the response to prednisone therapy in patients with idiopathic thrombocytopenic purpura

2008 ◽  
Vol 87 (12) ◽  
pp. 975-983 ◽  
Author(s):  
Ewout J. Houwerzijl ◽  
Henk Louwes ◽  
Wim J. Sluiter ◽  
Jan W. Smit ◽  
Edo Vellenga ◽  
...  
Keyword(s):  
Production Rate ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Thrombocytopenic Purpura ◽  
Platelet Production ◽  
Prednisone Therapy

scholarly journals Characterization of human megakaryocyte colony-stimulating factor in the urinary extracts from patients with aplastic anemia and idiopathic thrombocytopenic purpura

Blood ◽  
1983 ◽  
Vol 61 (3) ◽  
pp. 556-560 ◽  
Author(s):  
M Kawakita ◽  
M Ogawa ◽  
E Goldwasser ◽  
T Miyake
Keyword(s):  
Aplastic Anemia ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Colony Formation ◽  
Specific Activity ◽  
Elution Profile ◽  
Colony Stimulating Factor ◽  
Thrombocytopenic Purpura ◽  
Phenol Treatment ◽  
Stimulating Factor

Abstract Using procedures that were effective in the purification of human urinary erythropoietin (Epo), we attempted initial purification of megakaryocyte colony-stimulating factors (CSF) in urinary extracts from patients with aplastic anemia (AA) and idiopathic thrombocytopenic purpura (ITP). Comparison of colony stimulation by purified human Epo and crude urinary extracts revealed: (1) that the pure Epo augments megakaryocyte colony formation in culture and (2) MEG-CSF activity is also present in materials other than Epo in the crude urinary extracts from the two types of patients. Similar to purification of Epo, ethanol precipitation and sulfopropyl-Sephadex chromatography provided twofold and threefold increases in the specific activity of MEG-CSF, respectively. In contrast to Epo, however, significant inactivation of MEG-CSF activity was seen with phenol treatment. The elution profile of MEG-CSF seen on hydroxylapatite chromatography of urinary extracts was different from that of Epo. These data provided a basis for initial steps for purification of MEG-CSF and support the notion that MEG-CSF is distinct from Epo.

Concentrations of Thrombopoietin in Bone Marrow in Normal Subjects and in Patients With Idiopathic Thrombocytopenic Purpura, Aplastic Anemia, and Essential Thrombocythemia Correlate With Its mRNA Expression of Bone Marrow Stromal Cells

Blood ◽  
1998 ◽  
Vol 92 (1) ◽  
pp. 46-52 ◽  
Author(s):  
Yasuo Hirayama ◽  
Sumio Sakamaki ◽  
Takuya Matsunaga ◽  
Takashi Kuga ◽  
Hiroyuki Kuroda ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Aplastic Anemia ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Essential Thrombocythemia ◽  
Stromal Cells ◽  
Detection System ◽  
Normal Subjects ◽  
Normal Range ◽  
Thrombocytopenic Purpura ◽  
Polymerase Chain

The function of bone marrow (BM) stromal thrombopoietin (TPO) in megakaryopoiesis remains unknown. In the present study we attempted to clarify the pathophysiological implications of stromal TPO in normal subjects (NS) and in patients with idiopathic thrombocytopenic purpura (ITP), aplastic anemia (AA), and essential thrombocythemia (ET) by measuring TPO concentrations in BM and peripheral blood (PB) and by estimating the levels of stromal TPO mRNA with TaqMan fluorescence-based post–reverse transcription-polymerase chain reaction product detection system. The results showed that TPO concentrations in PB were significantly elevated in patients with ITP (34.9 ± 11.7 pg/mL) and AA (364.1 ± 153.5 pg/mL) but within normal range in patients with ET (each 20.0 and 22.1; NS, 22.1 ± 8.2 pg/mL). In all subjects, the TPO concentrations in BM correlated well with the PB levels, and the former were consistently higher than the latter. The concentrations of TPO in BM also correlated with the levels of TPO mRNA in stromal cells. Furthermore, expression levels of TPO mRNA clearly correlated with megakaryocyte counts in NS and patients with ITP, indicating that stromal TPO actually enhances megakaryopoiesis. Thus, our results in the present study indicate that TPO from BM stromal cells is considered to play an essential role for megakaryopoiesis under various patho-physiological conditions.

Platelet Production Rate Predicts the Response to Prednisone Therapy in Patients with Idiopathic Thrombocytopenic Purpura.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1325-1325
Author(s):  
Ewout Houwerzijl ◽  
Henk Louwes ◽  
Wim Sluiter ◽  
Jan Smit ◽  
Edo Vellenga ◽  
...  
Keyword(s):  
Production Rate ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Therapeutic Strategy ◽  
Patient Characteristics ◽  
Platelet Destruction ◽  
Thrombocytopenic Purpura ◽  
Platelet Production ◽  
Prednisone Therapy ◽  
The Mean

Abstract The thrombocytopenia in ITP is predominantly caused by autoantibodies that recognize antigens on platelets and megakaryocytes resulting in accelerated platelet destruction and a decreased platelet production rate (PPR). ITP patients with a predominantly suppressed PPR might respond differently to therapy than patients with predominantly peripheral platelet destruction. Tests and/or patient characteristics that can make a distinction between a reduced platelet half life and a reduced PPR could therefore influence diagnostic and therapeutic strategy in ITP. Therefore, in the present study the predictive value of clinical and platelet kinetic parameter for treatment outcome in idiopathic thrombocytopenic purpura (ITP) was investigated. Seventy-five patients with severe ITP (platelets ≤20 × 109/L) were studied. Median age was 46 (range 16–89) years and 34 (45%) patients were males. Median platelet count was 8 (1–20) × 109/L. The mean platelet life was 1 (0.1–6.5) days, and the PPR 160 (2–4670) × 109/day (normal 223 (100–355) × 109/day, p = 0.7). PPR was decreased (<100 × 109/day), normal (100–355 × 109/day) and increased (>355 × 109/day) in 33%, 48%, and 19% of the patients, respectively. All patients started with prednisone at diagnosis (1 mg/kg/day). Initial complete and partial response (CR/PR) was 84% and a durable CR/PR (defined as CR/PR for ≥6 months without treatment) was attained in 44% of the patients. Apart from a higher proportion of patients with a decreased PPR in the group that responded to prednisone therapy (p=0.03), there were no significant differences regarding clinical and platelet kinetic parameters between responders and nonresponders. A durable CR/PR was noticed in 64% of the patients with a decreased PPR (median follow-up of 81 months (18–92)), compared to 34% of the patients with normal or increased PPR (median follow-up 141 (10–284) months (HR: 0.47 [95% CI (0.24–0.92)], p = 0.03). Splenectomy was performed in 32% of the patients with decreased PPR and in 62% of patients with normal or increased PPR (p = 0.03). In addition, patients with a decreased PPR showed significantly less splenic sequestration and a significantly longer mean platelet life than patients with a normal or increased PPR, which underscores that in these patients peripheral destruction of platelets contributes relatively less to thrombocytopenia than suppressed platelet production. Thirty-nine of 42 nonresponders to prednisone underwent splenectomy. Durable CR/PR postsplenectomy was reached in 74%. There were no significant differences with regard to patient characteristics between responders and nonresponders to splenectomy. In conclusion, ITP patients with suppressed PPR have a significant higher durable CR/PR rate to prednisone therapy and are less frequently exposed to splenectomy, than those with a normal or increased PPR.

Idiopathic thrombocytopenic purpura: Current concepts in pathophysiology and management

2008 ◽  
Vol 99 (01) ◽  
pp. 4-13 ◽  
Author(s):  
Maria Laura Evangelista ◽  
Elisa Stipa ◽  
Francesco Buccisano ◽  
Adriano Venditti ◽  
Sergio Amadori ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Immune Modulation ◽  
Cellular Mechanisms ◽  
Platelet Destruction ◽  
Thrombocytopenic Purpura ◽  
Platelet Production ◽  
Structural Resemblance ◽  
Thrombopoietin Receptor ◽  
Low Platelet Count

SummaryIdiopathic thrombocytopenic purpura (ITP) is characterized by a low platelet count, which is the result of both increased platelet destruction and insufficient platelet production. Although the development of autoantibodies against platelet glycoproteins remains central in the pathophysiology of ITP, several abnormalities involving the cellular mechanisms of immune modulation have been identified. Conventional treatments for ITP aim at reducing platelet destruction, either by immunosuppression or splenectomy. Two new thrombopoietic agents, AMG 531 and eltrombopag, have been used in clinical trials to stimulate platelet production in ITP patients not responsive to standard treatments. These new molecules bear no structural resemblance to thrombopoietin, but still bind and activate the thrombopoietin receptor. This review will focus on the pathophysiology and treatment of ITP in adults, highlighting recent advances in both fields.

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