scholarly journals Platelet kinetics in patients with idiopathic thrombocytopenic purpura and moderate thrombocytopenia

Blood ◽  
1985 ◽  
Vol 65 (3) ◽  
pp. 584-588
Author(s):  
D Stoll ◽  
DB Cines ◽  
RH Aster ◽  
S Murphy
Keyword(s):  
Production Rate ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Normal Subjects ◽  
Normal Range ◽  
Thrombocytopenic Purpura ◽  
Platelet Production ◽  
Clinical Criteria ◽  
Platelet Counts ◽  
Cell Life ◽  
Multiple Hit

We studied ten normal subjects and 20 patients with stable, untreated idiopathic thrombocytopenic purpura (ITP) and platelet counts in the range of 35,000 to 110,000/microL. The diagnosis was made by clinical criteria. Platelet-associated IgG was increased in all nine of the nine patients studied. Autologous platelets were labeled with chromium 51 and reinfused for measurement of mean cell life and platelet production rate. Mean cell life was calculated by two methods, weighted mean and multiple hit, with excellent agreement between the two. As expected, mean cell life was significantly reduced in ITP patients as compared to the normal subjects (2.9 days v. 8.0 days, P less than .001). However, mean platelet production rates in ITP patients and normal subjects, 3.5 and 3.8 X 10(9) platelets/k/d respectively, were not significantly different. Platelet production rate was above and below the normal range (2 to 5.6 X 10(9) platelets/k/d) in two and four patients, respectively. We conclude that the rate of platelet production is not increased in most patients with ITP who have platelet counts greater than 35,000/microL. We did find that platelet size was increased in eight of the 12 patients in whom it was measured, including two of the patients with low platelet production.

scholarly journals Platelet kinetics in patients with idiopathic thrombocytopenic purpura and moderate thrombocytopenia

Blood ◽  
1985 ◽  
Vol 65 (3) ◽  
pp. 584-588 ◽  
Author(s):  
D Stoll ◽  
DB Cines ◽  
RH Aster ◽  
S Murphy
Keyword(s):  
Production Rate ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Normal Subjects ◽  
Normal Range ◽  
Thrombocytopenic Purpura ◽  
Platelet Production ◽  
Clinical Criteria ◽  
Platelet Counts ◽  
Cell Life ◽  
Multiple Hit

Abstract We studied ten normal subjects and 20 patients with stable, untreated idiopathic thrombocytopenic purpura (ITP) and platelet counts in the range of 35,000 to 110,000/microL. The diagnosis was made by clinical criteria. Platelet-associated IgG was increased in all nine of the nine patients studied. Autologous platelets were labeled with chromium 51 and reinfused for measurement of mean cell life and platelet production rate. Mean cell life was calculated by two methods, weighted mean and multiple hit, with excellent agreement between the two. As expected, mean cell life was significantly reduced in ITP patients as compared to the normal subjects (2.9 days v. 8.0 days, P less than .001). However, mean platelet production rates in ITP patients and normal subjects, 3.5 and 3.8 X 10(9) platelets/k/d respectively, were not significantly different. Platelet production rate was above and below the normal range (2 to 5.6 X 10(9) platelets/k/d) in two and four patients, respectively. We conclude that the rate of platelet production is not increased in most patients with ITP who have platelet counts greater than 35,000/microL. We did find that platelet size was increased in eight of the 12 patients in whom it was measured, including two of the patients with low platelet production.

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.

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

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.

scholarly journals The relation of thrombokinetics to bone marrow megakaryocytes in idiopathic thrombocytopenic purpura (ITP)

Blood ◽  
1975 ◽  
Vol 45 (4) ◽  
pp. 551-562 ◽  
Author(s):  
I Branehog ◽  
J Kutti ◽  
B Ridell ◽  
B Swolin ◽  
A Weinfeld
Keyword(s):  
Bone Marrow ◽  
Production Rate ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Inverse Relationship ◽  
Turnover Rate ◽  
Thrombocytopenic Purpura ◽  
Platelet Production ◽  
Platelet Size ◽  
Maturation Stages ◽  
The Mean

In 23 patients with untreated idiopathic thrombocytopenic purpura (TP), the relation of thrombokinetics to quantitative determinations of megakaryocytes in bone marrow sections was studied. The megakaryocytes were classified into maturation stages, and platelet sizes were determined. Megarkaryocyte number and volume per microliter of bone marrow were significantly higher in ITP as compared to controls. The megakaryocyte number and volume were inversely related to the peripheral platelet count. Platelet production rate was significantly increased in ITP and related to the megakaryocyte number and volume. The megakaryocytes were shifted towards more immature forms in ITP, suggesting an increased turnover rate of the expanded recognizable metakaryocyte compartment. Platelet size was significantly increased in ITP, and the mean platelet diameter was 1.6 times normal. There was a significant relationship between platelet size and platelet production rate, as well as an inverse relationship between platelet size and platelet mean life-span (MLS). There was also a significant correlation between platelet size and the proportion of young megakaryocytes.

scholarly journals The relation of thrombokinetics to bone marrow megakaryocytes in idiopathic thrombocytopenic purpura (ITP)

Blood ◽  
1975 ◽  
Vol 45 (4) ◽  
pp. 551-562 ◽  
Author(s):  
I Branehog ◽  
J Kutti ◽  
B Ridell ◽  
B Swolin ◽  
A Weinfeld
Keyword(s):  
Bone Marrow ◽  
Production Rate ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Inverse Relationship ◽  
Turnover Rate ◽  
Thrombocytopenic Purpura ◽  
Platelet Production ◽  
Platelet Size ◽  
Maturation Stages ◽  
The Mean

Abstract In 23 patients with untreated idiopathic thrombocytopenic purpura (TP), the relation of thrombokinetics to quantitative determinations of megakaryocytes in bone marrow sections was studied. The megakaryocytes were classified into maturation stages, and platelet sizes were determined. Megarkaryocyte number and volume per microliter of bone marrow were significantly higher in ITP as compared to controls. The megakaryocyte number and volume were inversely related to the peripheral platelet count. Platelet production rate was significantly increased in ITP and related to the megakaryocyte number and volume. The megakaryocytes were shifted towards more immature forms in ITP, suggesting an increased turnover rate of the expanded recognizable metakaryocyte compartment. Platelet size was significantly increased in ITP, and the mean platelet diameter was 1.6 times normal. There was a significant relationship between platelet size and platelet production rate, as well as an inverse relationship between platelet size and platelet mean life-span (MLS). There was also a significant correlation between platelet size and the proportion of young megakaryocytes.

scholarly journals Quantification of platelet-bound IgG by 125I-Staphylococcal protein A in immune thrombocytopenic purpura and other thrombocytopenic disorders

Blood ◽  
1984 ◽  
Vol 63 (1) ◽  
pp. 154-161 ◽  
Author(s):  
GM Shaw ◽  
J Axelson ◽  
JG Maglott ◽  
AF LoBuglio
Keyword(s):  
Immune Thrombocytopenic Purpura ◽  
Protein A ◽  
Normal Subjects ◽  
Unknown Etiology ◽  
Staphylococcal Protein A ◽  
Thrombocytopenic Purpura ◽  
Clinical Criteria ◽  
Staphylococcal Protein ◽  
Wide Range ◽  
Immune Hemolytic Anemia

Abstract In this report we describe the use of an 125I-Staphylococcal protein A (SPA) assay to measure platelet-bound IgG in the evaluation of 62 thrombocytopenic patients. Platelets from 150 normal subjects were found to bind 146 +/- 112 molecules of SPA per platelet (mean +/- 2 SD). Nineteen of 20 patients with untreated immune thrombocytopenia had platelet IgG values above this range, with 15 of 20 having values above 1,000 molecules of SPA per platelet. Patients with immune thrombocytopenic purpura by clinical criteria, but who had failed conventional therapy (corticosteroids or splenectomy), had a wide range of platelet IgG levels: 4 of 20 had normal values, 6 of 20 had minimally elevated levels in the range seen with nonimmune thrombocytopenia, and 10 of 20 had much higher values. Fifteen patients with thrombocytopenia of apparent nonimmune origin and 7 others with chronic stable thrombocytopenia of unknown etiology were found to have platelet IgG levels within or only slightly above the normal range. Because of its simplicity, accuracy, and clinical correlation, the 125I- SPA assay provides an important new approach for studying platelet IgG in thrombocytopenic states. The data obtained with this technique are similar to those found in immune hemolytic anemia and suggest that the platelet-bound IgG so measured has pathophysiologic relevance in immune thrombocytopenic purpura.

scholarly journals Microscopic platelet size and morphology in various hematologic disorders

Blood ◽  
1978 ◽  
Vol 51 (3) ◽  
pp. 479-486
Author(s):  
Z Zeigler ◽  
S Murphy ◽  
FH Gardner
Keyword(s):  
Idiopathic Thrombocytopenic Purpura ◽  
Lupus Erythematosus ◽  
Thrombocytopenic Purpura ◽  
Hematologic Disorders ◽  
Platelet Counts ◽  
Normal Platelet ◽  
Large Size ◽  
Platelet Size ◽  
Microscopic Evaluation ◽  
Size And Morphology

Microscopic evaluation of apparent platelet size and morphology was examined in a variety of hematologic disorders. The time of preparation of the blood smear was important. An artifactual increase in platelet size was noted on blood films from 20 normal individuals that were prepared either immediately or 180 min after venipuncture. The clearest differentiation of patient categories was obtained with smears prepared 60 min after venipuncture using blood anticoagulated with K3EDTA. Under these conditions, normal size and morphology values were found in thrombocytopenic patients with aplasia or with increased splenic pooling. In contrast, large size values were a reliable finding in idiopathic thrombocytopenic purpura patients, whose platelet counts were less than 50,000/microleter. Large size values were also noted in patients with infiltrated bone marrows or myeloproliferative syndromes regardless of the platelet count. The last two groups usually showed abnormal platelet morphology with greater than 10% hypogranular platelets. Normal platelet size and morphology were observed in patients with iron-deficiency and megaloblastic anemias and in patients with idiopathic thrombocytopenic purpura and systemic lupus erythematosus who had normal platelet counts.

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