Etiologies and sequelae of extreme thrombocytosis in a large pediatric hospital

Extreme thrombocytosis (ET, platelet count >1000 × 103/ul) is an uncommon clinical finding 1. Primary ET is associated with myeloproliferative disorders, such as essential thrombocythemia 2. Secondary ET is more common and occurs in reaction to infection, inflammation, or iron deficiency. Bleeding and thrombotic complications more frequently arise in primary ET cases 1, but have been reported with secondary ET in adults 3. Etiologies and complications associated with ET in children are less well-defined, as prior pediatric studies have been relatively small or restricted to specialized patient populations 4,5. We aimed to characterize ET in a large, single-center pediatric cohort.

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A Large Proportion of Patients With a Diagnosis of Essential Thrombocythemia Do Not Have a Clonal Disorder and May Be at Lower Risk of Thrombotic Complications

Blood ◽

10.1182/blood.v93.2.417 ◽

1999 ◽

Vol 93 (2) ◽

pp. 417-424 ◽

Cited By ~ 150

Author(s):

Claire N. Harrison ◽

Rosemary E. Gale ◽

Samuel J. Machin ◽

David C. Linch

Keyword(s):

Bone Marrow ◽

Platelet Count ◽

Essential Thrombocythemia ◽

Lower Risk ◽

Study Group ◽

Reactive Thrombocytosis ◽

Age Related ◽

Hemorrhagic Complications ◽

Thrombotic Complications

Abstract Essential thrombocythemia (ET) is traditionally considered to be a clonal disorder. No specific karyotypic abnormalities have been described, but the demonstration of clonality using X-chromosome inactivation patterns (XCIPs) has been used to differentiate ET from a non-clonal reactive thrombocytosis. However, these assays may be difficult to interpret, and contradictory results have been reported. We have studied 46 females with a diagnosis of ET according to the Polycythemia Vera Study Group (PVSG) criteria. XCIP results in 23 patients (50%) were uninterpretable due to either constitutive or possible acquired age-related skewing. Monoclonal myelopoiesis could be definitively shown in only 10 patients. Thirteen patients had polyclonal myelopoiesis, and in 8, it was possible to exclude clonal restriction to the megakaryocytic lineage. Furthermore, there was no evidence of clonal progenitors in purified CD34+CD33− and CD34+CD33+ subpopulations from bone marrow of 2 of these 13 patients. There was no difference between patients with monoclonal and polyclonal myelopoiesis with respect to age or platelet count at diagnosis, duration of follow-up, incidence of hepatosplenomegaly, or hemorrhagic complications. However, polyclonal patients were less likely to have experienced thrombotic events (P = .039). These results suggest that ET is a heterogeneous disorder, and the clinical significance of clonality status warrants investigation in a larger study.

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A Large Proportion of Patients With a Diagnosis of Essential Thrombocythemia Do Not Have a Clonal Disorder and May Be at Lower Risk of Thrombotic Complications

Blood ◽

10.1182/blood.v93.2.417.402a33_417_424 ◽

1999 ◽

Vol 93 (2) ◽

pp. 417-424 ◽

Cited By ~ 8

Author(s):

Claire N. Harrison ◽

Rosemary E. Gale ◽

Samuel J. Machin ◽

David C. Linch

Keyword(s):

Bone Marrow ◽

Platelet Count ◽

Essential Thrombocythemia ◽

Lower Risk ◽

Study Group ◽

Reactive Thrombocytosis ◽

Age Related ◽

Hemorrhagic Complications ◽

Thrombotic Complications

Essential thrombocythemia (ET) is traditionally considered to be a clonal disorder. No specific karyotypic abnormalities have been described, but the demonstration of clonality using X-chromosome inactivation patterns (XCIPs) has been used to differentiate ET from a non-clonal reactive thrombocytosis. However, these assays may be difficult to interpret, and contradictory results have been reported. We have studied 46 females with a diagnosis of ET according to the Polycythemia Vera Study Group (PVSG) criteria. XCIP results in 23 patients (50%) were uninterpretable due to either constitutive or possible acquired age-related skewing. Monoclonal myelopoiesis could be definitively shown in only 10 patients. Thirteen patients had polyclonal myelopoiesis, and in 8, it was possible to exclude clonal restriction to the megakaryocytic lineage. Furthermore, there was no evidence of clonal progenitors in purified CD34+CD33− and CD34+CD33+ subpopulations from bone marrow of 2 of these 13 patients. There was no difference between patients with monoclonal and polyclonal myelopoiesis with respect to age or platelet count at diagnosis, duration of follow-up, incidence of hepatosplenomegaly, or hemorrhagic complications. However, polyclonal patients were less likely to have experienced thrombotic events (P = .039). These results suggest that ET is a heterogeneous disorder, and the clinical significance of clonality status warrants investigation in a larger study.

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Fibrinolytic Activity in Patients with Essential Thrombocythemia.

Blood ◽

10.1182/blood.v110.11.3223.3223 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3223-3223

Author(s):

Bozena Sokolowska ◽

Aleksandra Nowaczynska ◽

Katarzyna Wejksza ◽

Adam Walter-Croneck ◽

Martyna Kandefer-Szerszen ◽

...

Keyword(s):

Platelet Count ◽

Platelet Aggregation ◽

Essential Thrombocythemia ◽

Fibrinolytic Activity ◽

Small Sample ◽

Control Group ◽

Minor Trauma ◽

Bleeding Tendency ◽

Thrombotic Complications ◽

Platelet Defects

Abstract Essential thrombocythemia (ET) is characterized by bleeding tendency, thrombotic complications and qualitative platelet defects. All those abnormalities are likely to contribute to the excessive mortality rate of this disease. Among many specific morphological, biochemical and metabolic platelet defects, a complete loss of platelet responsiveness to epinephrine is the most frequent in these patients. Since an abnormal platelet fibrinolytic activity was suggested to contribute to bleeding tendency, our initial goal was to see if platelet fibrinolysis activity is impaired in patients with ET. 22 patients were enrolled into the study (17 females, 5 males age 57.2±13.0.). This group included: 6 untreated patients, 9 treated with anagrelide, 4 with hydroxyurea, and 3 treated with a combination of both drugs. 8 thrombotic complications and 2 clinically significant bleeding episodes occurred. The control group consisted of 6 females age 33.3±9.9. Platelet count was 777±333 x109/L and 257±70 x109/L p<0.001, for the ET and the control group, respectively. Platelet activation was studied using flow cytometry to detect CD62P expression on the platelet surface. There was no difference between the control and the ET group. Platelet aggregation was measured using adenosine diphosphate and epinephrine as agonists. While 90% individuals from control group responded to epinephrine, in 45% of patients, a lack of epinephrine-induced platelet aggregation was detected. In this 45% of patients a statistically significantly lower expression of CD62P on CD61 positive cells was observed (mean value 1.90% versus 3.82%). Further, urokinase-type plasminogen activator (uPA) concentration was evaluated in plasma and in platelet lysates. Concentration of uPA was statistically significantly higher in patient plasma as compared to the control group (0.049±0.030 versus 0.029±0.015 ng/ml, p<0.05). Mean uPA concentration measured in platelet lysates was similar in both groups (ET 0.114±0.060ng/109 platelets, control group 0.110±0.042 ng/109 platelets). However, in platelets lysates from three patients, an extremely high uPA concentration was detected (more than 0.194 ng/109 platelets). One of these patients had an episode of hypermenorrhea and the second presented a thigh hematoma after a minor trauma. In both of those patients platelet count was above 600 x 109/L. In addition, in one patient very low uPA activity in platelet lysates was observed (0.030 ng/109 platelets). In this patient’s medical history, two episodes of DVT occurred. To evaluate platelet fibrinolytic activity, uPA activity was assessed by means of casein zymography. Zymograms have show that similar fibrinolytic activity was present both in patients and the control group and the activity of fibrinolytic enzymes was inhibited by AEBSF, an inhibitor of serine proteases. From the data gathered we concluded that uPA concentration is significantly higher in ET patient plasma as compared to the control group. However, platelet fibrinolytic activity, measured as uPA activity and uPA concentration in platelets lysates obtained from ET patients is not impaired as was initially presumed. Because of the small sample size, we could not precisely assess the clinical importance of extremely high or extremely low uPA activity in platelets lysates. All these data need further evaluation in a larger group of patients.

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Elevated Circulating Platelet-Derived Microparticles in Ph1 Negative Chronic Myeloproliferative Disorders.

Blood ◽

10.1182/blood.v114.22.1906.1906 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1906-1906

Author(s):

Véronique Tintillier-Colin ◽

Nathalie Cambier ◽

Emmanuelle Bourgeois-Petit ◽

Christian Rose ◽

Gérard Forzy ◽

...

Keyword(s):

Platelet Count ◽

Flow Cytometric Analysis ◽

Myeloproliferative Disorders ◽

Control Group ◽

Plasma Membrane Vesicles ◽

Chronic Myeloproliferative Disorders ◽

Testing Procedures ◽

Increased Risk ◽

Significant Difference ◽

Thrombotic Complications

Abstract Abstract 1906 Poster Board I-929 Microparticles (MP) are plasma membrane vesicles bearing potent procoagulant proteins and released into the circulation by various blood and endothelial cells during cellular activation and apoptosis. Their concentration has been shown markedly increased in vascular and thromboembolic diseases and in several types of cancer. Essential Thrombocythemia (ET), Polycythemia Vera (PV) and Primary Myelofibrosis (PM) are Bcr-Abl-negative chronic myeloproliferative disorders (MPD) with common biological and clinical features, especially thrombocytosis and more or less effective megakaryocytic proliferation. ET, PV and PMF are also characterized by an increased risk of thrombotic complications. Given the involvement of megacaryocytopoiesis in this group of diseases, we chose to focus on circulating platelet-derived microparticles (PMP) whose count can be established by flow cytometry. Our goals were to look for an increased release of PMP in MPD and if so, try to establish a correlation between thrombotic events recorded retrospectively and PMP level. Patients and methods: Plasma samples were collected from 85 patients with MPD (40 ET, 28 PV, 17 PMF) at any time of the disease course except blastic phase and 31 healthy age-paired controls ; the quantity of PMP (positive for the platelet marker CD41 and the microparticle marker AnnexinV) was measured by flow cytometric analysis using the FC500 cytometer from Beckmann-Coulter™. Pre-analytic and testing procedures complied with the recommendations of the ISTH Standardization Subcommittee and besides, our laboratory participates in a multicenter program to standardize the enumeration of cellular microparticles. Results: The number of PMP is significantly higher in ET, PV and MFP patients (median: 4862 MPP/mL, 3289 MPP/mL and 6114 MPP/mL respectively) than in controls (median 1310 MPP/mL) [p=0.000018, p=0.0013, p=0.0009]. Neither in MPD patients nor in control group PMP correlates with platelet count and appears thus as an independent parameter. ROC method allows to fix a cut-off at 3121 MPP/mL to discriminate MPD from controls. This value has a sensibility of 75 % and a specificity of 94%. Interestingly, the total number of PMP is not different between untreated patients (mean=7246 MPP/mL) and those who received myelosuppressive therapy (mean=6320 MPP/mL). Regarding thrombotic events, we failed to demonstrate any significant difference between patients with previous thrombosis and those without; however, the small size of the series and the retrospective assessment are possible bias. Conclusion: Patients with Phi negative MPDs have a high number of circulating PMP, irrelevant to platelet count or treatment by Hydroxy-urea or aspirin. A role for microparticles in the development of these diseases and in the occurrence of thrombotic complications can be hypothesized but requires further studies -;preferably prospective- on larger cohorts of patients. Disclosures: Charpentier: Schering-Plough: Research Funding.

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Correlation of Thrombosis With Increased Platelet Turnover in Thrombocytosis

Blood ◽

10.1182/blood.v91.4.1288 ◽

1998 ◽

Vol 91 (4) ◽

pp. 1288-1294 ◽

Cited By ~ 73

Author(s):

Henry M. Rinder ◽

Judith E. Schuster ◽

Christine S. Rinder ◽

Chao Wang ◽

Helen J. Schweidler ◽

...

Keyword(s):

Platelet Count ◽

Treatment Response ◽

Myeloproliferative Disorders ◽

Healthy Controls ◽

Thrombotic Risk ◽

Platelet Counts ◽

Normal Platelet ◽

Reticulated Platelets ◽

Thrombotic Complications ◽

Deep Vein

Abstract There are no readily applicable methods to routinely assess thrombosis risk and treatment response in thrombocytosis. Reticulated platelets (RP) define the most recently released platelets in the circulation, and the RP% has been shown to estimate platelet turnover in thrombocytopenic states. We examined whether increased RP values were associated with thrombotic complications in thrombocytosis. Platelet count, RP%, and absolute RP count were measured at presentation in 83 patients with chronic or transient thrombocytosis, 46 patients with deep vein (DVT) or arterial (ART) thrombosis and normal platelet counts, and 83 healthy controls with normal platelet counts. Chronic thrombocytosis patients presenting with thrombosis (n = 14) had significantly higher RP% (14.7% ± 10.1%, mean ± SD) than asymptomatic chronic thrombocytosis patients (n = 23, RP% = 3.4% ± 1.8%), healthy controls (3.4% ± 1.3%), DVT patients (n = 21, 3.8% ± 2.1%), or ART patients (n = 25, 4.5% ± 4.1%, P < .05 for all comparisons). Chronic thrombocytosis patients with thrombosis also had significantly higher absolute RP counts than asymptomatic chronic thrombocytosis patients (98 ± 64 × 109/L [range, 54 to 249 × 109/L] v 30 ± 13 × 109/L [range, 11 to 51 × 109/L]; P = .0004), whereas healthy controls, DVT, and ART patients had similarly low absolute RP counts (6 ± 6 × 109/L, 9 ± 7 × 109/L, and 11 ± 7 × 109/L, respectively; P > .49). The RP% and absolute RP counts remained significantly higher in chronic thrombocytosis patients with thrombosis when patients were further subdivided into primary myeloproliferative disorders versus secondary thrombocytosis. Similarly elevated RP percentages and absolute counts were also noted in transient thrombocytosis patients with thrombosis (n = 6, 11.5% ± 4.4% and 90 ± 46 × 109/L, respectively) when compared with asymptomatic transient thrombocytosis patients (n = 40, 4.5% ± 2.7% and 35 ± 16 × 109/L, respectively) and to all control groups (P < .05 for all comparisons). In addition, 7 of 8 thrombocytosis patients who were studied before developing symptoms of thrombosis had elevated absolute RP counts compared with only 1 of 63 thrombocytosis patients who remained asymptomatic. Follow-up studies in seven chronic thrombocytosis patients showed that successful aspirin treatment of symptomatic recurrent thrombosis significantly reduced the RP% from 17.1% ± 10.9% before therapy to 4.8% ± 2.0% after therapy; absolute RP counts decreased from 102 ± 67 × 109/L to 26 ± 10 × 109/L (P < .01 for both). We conclude that thrombosis in the setting of an elevated platelet count is associated with increased platelet turnover, which is reversed by aspirin therapy. Measurement of reticulated platelets to assess platelet turnover may be useful in evaluating both treatment response and thrombotic risk in thrombocytosis.

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Therapeutic Thrombocytapheresis: A Review of 132 Patients

The International Journal of Artificial Organs ◽

10.1177/039139889301605s40 ◽

1993 ◽

Vol 16 (5_suppl) ◽

pp. 183-184 ◽

Cited By ~ 20

Author(s):

R. Adami

Keyword(s):

Platelet Count ◽

Comparative Study ◽

Essential Thrombocythemia ◽

Myeloproliferative Disorders ◽

Bleeding Complications ◽

Hemorrhagic Complications

Therapeutic thrombocytapheresis has been used is an attempt to obtain a rapid cytoreduction in thrombocythemic patients, in order to prevent or reduce thrombosis or bleeding complications. Long-term cytoreduction has to be performed with chemotherapy. We have treated with thrombocytapheresis 132 patients with increased platelet count (76 with thrombosis and/or bleeding) due to splenectomy, essential thrombocythemia and other myeloproliferative disorders: a comparative study has been perfomed to find a platelet count that could be helpful in preventing thrombotic and hemorrhagic complications and the role of diagnosis in predicting patient's risk.

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Characterization of the Rate, Predictors, and Thrombotic Complications of Thrombocytosis in Iron Deficiency Anemia

Blood ◽

10.1182/blood-2019-122359 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 959-959 ◽

Cited By ~ 1

Author(s):

Andrew B Song ◽

David J. Kuter ◽

Hanny Al-Samkari

Keyword(s):

Platelet Count ◽

Iron Deficiency ◽

Multivariate Regression ◽

Research Funding ◽

Chart Review ◽

Deficiency Anemia ◽

Thrombotic Risk ◽

Reactive Thrombocytosis ◽

Thrombotic Complications ◽

Platelet Mass

Introduction: Iron deficiency anemia (IDA) is the most common cause of anemia worldwide and is frequently untreated or undertreated (Kesselbaum et al. 2014). The association of thrombocytosis with IDA is well-recognized, with recent work elucidating its underlying physiology (Xavier-Ferrucio et al. 2018). Thrombocytosis in IDA may predispose to thrombotic complications, as described in many case reports. Given that IDA is ubiquitous, even minor increases in thrombotic risk due to thrombocytosis have dramatic public health implications. Data describing the rate, predictors, and risk of thrombotic complications are limited. This study characterizes these features of thrombocytosis in IDA. Methods: We queried a large institutional patient data repository containing comprehensive chart data for over 5.8 million patients to identify patients with IDA with and without thrombocytosis and thrombotic events over a 40-year time period (1979 to 2019). Demographic information, hematological parameters, thrombosis history, and other medical history were collected at time of peak thrombocytosis, time of IDA diagnosis, and clinical baseline (before IDA diagnosis or after resolution). The fidelity of query data was assessed by performing detailed manual chart review of 700 total patients. Clinical diagnoses of IDA were verified by confirming ferritin values <30 ng/ml and consistent CBC parameters. Temporal association of thrombocytosis with IDA was confirmed and patients with other causes of thrombocytosis (including active malignancy, infection, inflammatory bowel disease, recent surgery/trauma, inflammatory arthritis, and myeloproliferative neoplasms) were excluded. Only arterial and venous thrombotic events occurring concurrently with IDA or IDA with thrombocytosis were included. Data were analyzed using t-tests, chi-square tests, Pearson correlations, and multivariate regression. Results: Our queries identified 36,327 IDA cases and 15,022 IDA with thrombocytosis cases. Query fidelity rates were 95% and 75%, respectively, yielding a true thrombocytosis rate of 32.6% in patients with IDA. After excluding cases with other causes of thrombocytosis, we calculated a 7.8% rate of thrombosis in patients with IDA and a 15.8% rate of thrombosis in patients with reactive thrombocytosis secondary to IDA (Table 1, Figure). The odds ratio for thrombosis in IDA with thrombocytosis vs IDA alone was 2.23 (2.09-2.38, p<0.0001). Both venous and arterial thrombotic events were more likely in patients with IDA and thrombocytosis (Table 1). Risk factors for thrombotic events were slightly more common in patients with IDA and thrombosis (OR 1.28, Table 1). Mean duration of IDA episode (from IDA diagnosis to normalization of hemoglobin and platelet count) was 2.03 years. Among patients with IDA and thrombocytosis, ferritin and hemoglobin (Hgb) were both moderately negatively correlated with platelet count (Plt) (Table 2). Platelet mass index (Plt x MPV) at time of IDA diagnosis and peak thrombocytosis was significantly higher than baseline. Platelet mass index and Hgb were strongly negatively correlated at peak thrombocytosis. Multivariate regression including age, sex, WBC count, Hgb, Plt, and MCV demonstrated a significant predictive relation between decreasing Hgb and increasing Plt at peak thrombocytosis. Conclusions: In this large retrospective analysis, we describe the rate and predictors of thrombocytosis in IDA in addition to rates of thrombosis in IDA patients with and without reactive thrombocytosis. Combining queries of a massive clinical database with manual chart review to ensure data validity, we found a 32.6% rate of thrombocytosis in IDA, negative correlations between both Hgb/ferritin and Plt, and a 2-fold increased thrombotic risk in patients with thrombocytosis reactive to IDA relative to IDA alone. We also found increased total body platelet mass in IDA patients with thrombocytosis, which may contribute to this increased thrombotic risk. Thrombosis rates overall were high, possibly due to database inclusion of more morbid inpatients in addition to outpatients. Given the global burden of untreated and undertreated IDA, our findings suggest that adequate IDA treatment may reduce thrombotic complications and associated morbidity and mortality. Acknowledgements: A. Song is the recipient of the American Society of Hematology HONORS Award (provides research support). Disclosures Kuter: Daiichi Sankyo: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Merck Sharp Dohme: Consultancy, Honoraria; Up-to-Date: Consultancy, Honoraria, Patents & Royalties: 3 Up-to-Date chapters; Caremark: Consultancy, Honoraria; Bristol Myers Squibb (BMS): Consultancy, Honoraria, Research Funding; Platelet Disorder Support Association: Consultancy, Honoraria; Alnylam: Consultancy, Honoraria, Research Funding; Zafgen: Consultancy, Honoraria; UCB: Consultancy, Honoraria; Genzyme: Consultancy, Honoraria; Kezar: Research Funding; Principia: Consultancy, Honoraria, Research Funding; Shire: Consultancy, Honoraria; Takeda (Bioverativ): Consultancy, Honoraria, Research Funding; Kyowa-Kirin: Consultancy, Honoraria; Momenta: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Argenx: Consultancy, Honoraria, Research Funding; Agios: Consultancy, Honoraria, Research Funding; Actelion (Syntimmune): Consultancy, Honoraria, Research Funding; Dova: Consultancy, Honoraria; Protalix: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Protalex: Consultancy, Honoraria, Research Funding; Shinogi: Consultancy, Honoraria; Rigel: Consultancy, Honoraria, Research Funding. Al-Samkari:Agios: Consultancy, Research Funding; Dova: Consultancy, Research Funding; Moderna: Consultancy.

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Microparticles (platelet, Endothelial, and Leucocyte) Are Elevated in Patients with Myeloproliferative Disorders.

Blood ◽

10.1182/blood.v110.11.1552.1552 ◽

2007 ◽

Vol 110 (11) ◽

pp. 1552-1552

Author(s):

Susan Lynch ◽

David Stirling ◽

Christopher A. Ludlam

Keyword(s):

Platelet Count ◽

Jak2 V617f ◽

Myeloproliferative Disorders ◽

Active Role ◽

Current Treatment ◽

Polycythaemia Vera ◽

Healthy Controls ◽

Thrombotic Risk ◽

Significant Difference ◽

Thrombotic Complications

Abstract Patients with myeloproliferative disorders (MPD) have an excess of thrombotic complications which is not fully corrected by normalisation of their elevated haematocrit or thrombocytosis. The mechanisms responsible for this are not completely understood but platelets, leucocytes and endothelial cells have all been implicated. Plasma microparticles are observed to be elevated in other diseases associated with thrombotic complications. We measured platelet (PMP), endothelial (EMP), red cell (RMP) and leucocyte (LMP) microparticles in patients with MPD compared to healthy controls. Microparticles, of less than 1μm were measured by flow cytometry on platelet poor plasma obtained from citrated peripheral blood samples. Subtypes were identified using fluorescent conjugated monoclonal antibodies; EMP CD31+CD42-, PMP CD31+42+, RMP Glycophorin A + and LMP CD45+ events. Absolute concentrations of microparticles per μl plasma were calculated using Trucount beads. Results are currently available for 27 MPD patients, 9 polycythaemia vera (PV), and 18 primary thrombocythaemia and 14 healthy controls. All patients except 1 PV were on current treatment with hydroxycarbamide and all but 3 were receiving aspirin. PMP and LMP were elevated in MPD patients compared to healthy controls, PMP 12432 (1653) v 2371 (278) per μl, mean (SEM) p<0.001, LMP 98.7 (14) v 62.6 (7.7) per μl, p=0.03. EMP were elevated in MPD patients at 202 (34) v 34 (14) per μl, p<0.001. There was no significant difference in RMP levels 646 (131) v 589 (241) per μl, p=0.84. There were no significant differences in MP numbers between the PT and PV patients or by Jak2 V617F mutation status. Platelet count (x109/l) was higher in the MPD patients, PT 503 (39) v PV 372 (43) v control 236 (12), all comparisons p<0.04. PMP/platelet count was calculated to adjust for this and the ratio remained elevated in the MPD patients, PV 28.5 (4.5) and PT 26.1 (3.7) v controls 9.9 (1.2), both p=<0.03. In conclusion, these results demonstrate that PMP, EMP and LMP are elevated in MPD despite standard treatment, with the PMP elevated disproportionately to the platelet count. This is further evidence for platelet activation, endothelial dysfunction and a role for leucocytes in the thrombotic risk of MPD and that the microparticles also play an active role in promoting the prothrombotic state.

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Increased Response to Arachidonic Acid and U-46619 and Resistance to Inhibitory Prostaglandins in Patients with Chronic Myeloproliferative Disorders

Thrombosis and Haemostasis ◽

10.1055/s-0038-1642568 ◽

1988 ◽

Vol 59 (01) ◽

pp. 073-076 ◽

Cited By ~ 9

Author(s):

Sergio Cortelazzo ◽

Monica Galli ◽

Donatella Castagna ◽

Piera Viero ◽

Giovanni de Gaetano ◽

...

Keyword(s):

Bone Marrow ◽

Arachidonic Acid ◽

Platelet Aggregation ◽

Myeloproliferative Disorders ◽

Bone Marrow Stem Cell ◽

Healthy Controls ◽

Aggregation Response ◽

Thrombotic Complications ◽

Cyclic Endoperoxide ◽

Marrow Stem Cell

SummaryIn patients with myeloproliferative disorders (MPD) a group of related diseases of the bone marrow stem cell and recurrent haemorrhagic and/or thrombotic complications, the production of aggregating prostaglandins (PGs) may be normal or slightly reduced, while PGI2 production is normal. However, MPD platelet sensitivity to antiaggregatory PGs is still unknown.We studied the potency of PGD2, PGI2 and PGEi as inhibitors of platelet aggregation induced by threshold aggregating concentrations of arachidonic acid and U-46619-analogue of the cyclic endoperoxide PGH2 in 20 patients with MPD in comparison with healthy controls, with the aim of evaluating the sensitivity of MPD platelets to antiaggregatory PGs. In these patients platelet prostanoid metabolism was normal. However, the functional response of platelets to aggregating and antiaggregating prostanoids was shifted towards potentially increased platelet aggregation response. These findings could have a clinical relevance in view of the haemostatic and thrombotic complications so frequent in MPD.

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Increased Thromboxane Biosynthesis in Essential Thrombocythemia

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649916 ◽

1995 ◽

Vol 74 (05) ◽

pp. 1225-1230 ◽

Cited By ~ 71

Author(s):

Bianca Rocca ◽

Giovanni Ciabattoni ◽

Raffaele Tartaglione ◽

Sergio Cortelazzo ◽

Tiziano Barbui ◽

...

Keyword(s):

Platelet Count ◽

Platelet Activation ◽

Essential Thrombocythemia ◽

Therapeutic Strategy ◽

Low Dose ◽

Thrombotic Risk ◽

Dose Aspirin ◽

Gender And Age ◽

Low Dose Aspirin

SummaryIn order to investigate the in vivo thromboxane (TX) biosynthesis in essential thromboeythemia (ET), we measured the urinary exeretion of the major enzymatic metabolites of TXB2, 11-dehydro-TXB2 and 2,3-dinor-TXB2 in 40 ET patients as well as in 26 gender- and age-matched controls. Urinary 11-dehydro-TXB2 was significantly higher (p <0.001) in thrombocythemic patients (4,063 ± 3,408 pg/mg creatinine; mean ± SD) than in controls (504 ± 267 pg/mg creatinine), with 34 patients (85%) having 11-dehydro-TXB2 >2 SD above the control mean. Patients with platelet number <1,000 × 109/1 (n = 25) had significantly higher (p <0.05) 11 -dehydro-TXB2 excretion than patients with higher platelet count (4,765 ± 3,870 pg/mg creatinine, n = 25, versus 2,279 ± 1,874 pg/mg creatinine, n = 15). Average excretion values of patients aging >55 was significantly higher than in the younger group (4,784 ± 3,948 pg/mg creatinine, n = 24, versus 2,405 ± 1,885 pg/mg creatinine, n = 16, p <0.05). Low-dose aspirin (50 mg/d for 7 days) largely suppressed 11-dehydro-TXB2 excretion in 7 thrombocythemic patients, thus suggesting that platelets were the main source of enhanced TXA2 biosynthesis. The platelet count-corrected 11-dehydro-TXB2 excretion was positively correlated with age (r = 0.325, n = 40, p <0.05) and inversely correlated with platelet count (r = -0.381, n = 40, p <0.05). In addition 11 out of 13 (85%) patients having increased count-corrected 11-dehydro-TXB2 excretion, belonged to the subgroup with age >55 and platelet count <1,000 × 1099/1. We conclude that in essential thrombocythemia: 1) enhanced 11-dehydro-TXB2 excretion largely reflects platelet activation in vivo;2) age as well as platelet count appear to influence the determinants of platelet activation in this setting, and can help in assessing the thrombotic risk and therapeutic strategy in individual patients.

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