Clonal Thrombocytosis Research Articles

Differential diagnosis of thrombocytosis (lecture for practitioners)

Thrombocytosis (an increase in the level of platelets in the peripheral blood above 450×109/l) has different causes and mechanisms of formation: it can be familial, primary (clonal), secondary (reactive). The ability to interpret peripheral blood parameters, knowledge of the main differential diagnostic criteria for diseases accompanied by thrombocytosis, allow the doctor to conduct the necessary examination to determine the cause of an increase in the platelet count in the blood. Clarification of the nature of thrombocytosis is very important, since clonal thrombocytosis is more often accompanied by the development of thrombotic complications and requires more active therapeutic intervention, specific therapy. Timely diagnosis helps to prevent the development of thrombosis, improves the prognosis, quality of life and survival of patients.

Platelet Indices as a Tool for Differentiation between Clonal Thrombocytosis and Reactive Thrombocytosis

Objective: To determine the efficacy of platelet indices as a tool for differentiation between clonal thrombocytosis and reactive thrombocytosis. Study Design: Cross sectional study. Place and Duration of Study: Department of Pathology, Combined Military Hospital, Lahore Pakistan, from Nov 2019 to Oct 2020. Methodology: Fifty-six subjects were included in Reactive thrombocytosis group and 56 in Clonal thrombocytosis group. Fresh blood in EDTA anticoagulant was analyzed to determine complete blood counts and platelet parameters (Platelet distribution width, mean platelet volume, Platelet large cell ratio, Plateletcrit) using the automated hematological analyzer Sysmex KX-21. Results: Mean age of the patients was 45.76 years with a range of 17-75 years. Assessing the cause of reactive thrombocytosi revealed that 20(35.7%) was infection and 16(28.5%) was iron deficiency anemia. In clonal thrombocytosis group 21(37.5%) were diagnosed with Chronic myeloid leukemia, 13(23.2%) with Essential thrombocythemia and 14(25%) with Polycythemia rubera vera. Platelet indices were compared in clonal thrombocytosis group and the reactive thrombocytosis group. Mean platelet volume, Platelet large cell ratio and Plateletcrit were significantly higher in the clonal thrombocytosis group (p=0.001). Difference in Platelet distribution width was not found to be statistically significant in the two groups (p=0.07) Conclusion: Platelet indices were higher in the clonal thrombocytosis group. Along with platelet count, they can serve as an efficient and cost-effective method in differentiating between clonal and reactive thrombocytosis.

Platelet Indices in Differentiating Reactive Versus Clonal Thrombocytosis

Aim: To evaluate the platelet indices in differentiating reactive and clonal thrombocytosis. Study Design: Observational study Place and Duration of Study: Department of Pathology, Saveetha Medical College, Chennai, and the duration of study is one year. Methods: This is an observational study conducted at our college for a one-year duration. A total of 100 patients with thrombocytosis of platelet count over 4.5 lakhs/mm3 will be included in the study. The study sample consists of cases with thrombocytosis of over 4.5 lakhs. The utility of platelet indices Mean Platelet Volume (MPV) and Platelet Distribution Width (PDW) for the differential diagnosis of thrombocytosis were analysed and assessed. Results: Out of the total 100 cases, 94 were reactive thrombocytosis, and 6 were confirmed to be clonal in origin. Infectious and reactive aetiology was significantly more compared to clonal thrombocytosis. Patients with reactive thrombocytosis showed a lower mean platelet volume and platelet distribution width compared to primary thrombocytosis. In reactive thrombocytosis, MPV ranged from 8.0 - 9.0 fl with mean MPV of 10.6 fl and PDW ranged from 8.4 – 10.1 % with mean PDW of 10.26 %. In clonal thrombocytosis, MPV ranged from 8.2 –1 1.1 fl with mean MPV of 9.5 fl and PDW range was 8.9 – 11.2 % with mean PDW of 10∙1%. Conclusions: The findings of our study favour a reactive cause in thrombocytosis when MPV and PDW are in the lower range and clonal causes had a high MPV and PDW in comparison to reactive causes.

Frequency of JAK2V617F and CALR somatic mutations in Egyptian patients with thrombocytosis

Background Thrombocytosis has a multitude of potential etiologies: spurious, reactive, and clonal. Clonal thrombocytosis carries a greater risk of thrombosis than reactive causes. Therefore, careful distinction between the causes of thrombocytosis is important and challenging as it carries implications for evaluation, prognosis, and treatment strategies. Aim of the work To determine the frequency of JAK2V617F and calreticulin (CALR) somatic mutations in patients with thrombocytsis and their relation with clinical and hematological phenotype. Patients and methods A total of 50 BCR-ABL-negative patients with persistent thrombocytosis were tested for both JAK2V617F mutation by real-time polymerase-chain reaction (RT-PCR) and CALR exon-9 mutation by high-resolution melting PCR. Results JAK2V615F mutation was detected in 17 (34%), whereas CALR exon-9 mutation was detected in 10 (20%) out of the 50 studied patients with thrombocytosis. One patient with essential thrombocythemia was heterozygous for both mutations. The incidence of JAK2V615F mutation was significantly higher in males (P=0.007), with higher mean age (P=0.001), higher incidence of thrombosis (0.034), and leukocytosis (0.035) compared with CALR and dual-negative mutations. Meanwhile, anemia (P=0.001), platelets (P=0.009), and lactate dehydrogenase (P=0.009) were significantly higher in CALR-mutated patients. Conclusion Both JAK2 and CALR somatic mutations were detected in 52% of patients with thrombocytosis. CALR-mutated cases show clinical and hematological phenotype different from JAKV617F-positive ones and might be considered as a distinct disease entity with more indolent course.

The Frequency and Importance of Hematological Parameters in Reactive and Clonal Thrombocytosis

Objectives: To evaluate the frequency of reactive and clonal thrombocytosis based on age, sex, clinical findings, and severity of thrombocytosis. We also highlight the determination of hematological parameters for the diagnosis of these disorders required the management of thrombocytosis to reduce the morbidity and mortality rate.
 Methods: This descriptive experimental study was conducted in the Diagnostic and Research laboratory, Peoples University of Medical and Health Sciences, Nawabshah and department of Pathology, from July 2017 to June 2018. Total 325 patients including 260 patients with reactive thrombocytosis and 65 patients with clonal thrombocytosis, their age ranged between 12 and 45 years and 35 to 68 years were selected. The male to female ratio were 1.5:1 and 2.5:1 while clinical history and clinical examination were noted. The blood samples were taken from all these patients for the analysis of hematological parameters by a hematological analyzer (Nihon Corden) and an iron profile performed for assessment of iron status to confirm the diagnosis of iron deficiency anemia. The examinations of peripheral blood smears and bone marrow smears in the case of clonal thrombocytosis seen in chronic myeloid leukemia essential for the diagnosis.
 Results: The mean ages and male to female ratio among 325 patients with reactive and clonal thrombocytosis were 28.5 + 16.5, 51.5 +16.5 and 1.5:1, 2.5:1 ratio were found in this study. The mild to moderate thrombocytosis were found in reactive thrombocytosis while moderate to severe thrombocytosis was detected in patients with chronic myeloid leukemia.
 Conclusions: The frequency of thrombocytosis was higher in clonal thrombocytosis than the reactive type.

Is It Possible to Predict Clonal Thrombocytosis in Triple-Negative Patients with Isolated Thrombocytosis Based Only on Clinical or Blood Findings?

JAK2, MPL, and CALR mutations define clonal thrombocytosis in about 90% of patients with sustained isolated thrombocytosis. In the remainder of patients (triple-negative patients) diagnosing clonal thrombocytosis is especially difficult due to the different underlying conditions and possible inconclusive bone marrow biopsy results. The ability to predict patients with sustained isolated thrombocytosis with a potential clonal origin has a prognostic value and warrants further examination. The aim of our study was to define a non-invasive clinical or blood parameter that could help predict clonal thrombocytosis in triple-negative patients. We studied 237 JAK2 V617-negative patients who were diagnosed with isolated thrombocytosis and referred to the haematology service. Sixteen routine clinical and blood parameters were included in the logistic regression model which was used to predict the type of thrombocytosis (reactive/clonal). Platelet count and lactate dehydrogenase (LDH) were the only statistically significant predictors of clonal thrombocytosis. The platelet count threshold for the most accurate prediction of clonal or reactive thrombocytosis was 449 × 109/L. Other tested clinical and blood parameters were not statistically significant predictors of clonal thrombocytosis. The level of LDH was significantly higher in CALR-positive patients compared to CALR-negative patients. We did not identify any new clinical or blood parameters that could distinguish clonal from reactive thrombocytosis. When diagnosing clonal thrombocytosis triple-negative patients are most likely to be misdiagnosed. Treatment in patients with suspected triple negative clonal thrombocytosis should not be delayed if cardiovascular risk factors or pregnancy coexist, even in the absence of firm diagnostic criteria. In those cases the approach “better treat more than less” should be followed.

Analytical study of reactive thrombocytosis prevalence in microcytic hypochromic anemia

In routine hematology blood samples, every now and then when reporting peripheral smears, we come across cases of microcytic hypochromic anemia with increased platelet count more often in iron deficiency anemia. We have to differentiate is it the cases are just reactive thrombocytosis or else we are neglecting any platelet disorders. Iron deficiency is the commonest cause of secondary thrombocytosis. To know the prevalence of reactive thrombocytosis in microcytic hypochromic anemia cases. To analyze the range of hemoglobin levels and MCV values in which reactive thrombocytosis is more consistent. : The study includes 500 blood samples of patients of all the age groups and both the gender with microcytic hypochromic anemia. The samples were scrutinized for the corresponding thrombocytosis by using a hematology analyzer and confirmed by peripheral smear examination. Serum iron studies were done in confirmed samples of microcytic hypochromic anemia with valid thrombocytosis. Out of 500 cases of microcytic hypochromic anemia analysed 115 cases had associated thrombocytosis. out of which 17(14.78%) cases were males and 98 (85.22%) cases of females showed thrombocytosis. The majority of cases showed mild thrombocytosis which is frequently seen in cases with MCV 60-70 fl and moderate degree of anemia with hemoglobin level 7-9.9g/dl. The utmost prevalent cause of reactive thrombocytosis in microcytic hypochromic anemia is iron deficiency. It is rational to distinguish between reactive and clonal thrombocytosis. However, the distinction cannot be always made with certainty, and the diagnosis often depends on watching the platelet count over a while. By identifying the etiology of increased platelet count and type of anemia treatment will be ease.

English

BACKGROUND We wanted to evaluate the role of platelet indices in differentiating reactive and clonal thrombocytosis. METHODS This is a cross sectional observational study conducted for two years among 150 patients with platelet counts of 5 lac and above. Thrombocytosis and utility of platelet indices like Mean Platelet Volume (MPV), Platelet Distribution Width (PDW) for the differential diagnosis of thrombocytosis were done. RESULTS Out of total 150 cases, 144 (96 %) had reactive thrombocytosis, and 6 (4 %) had clonal thrombocytosis. Infectious aetiology is seen in 64 (42.6 %), tissue injury 35 (23 %), rebound thrombocytosis 22 (14.6 %), anaemia 13 (8.6 %), multiple causes 8 (5.3 %), clonal aetiology 6 (4 %), and inflammatory 2 (1.3 %). Patients with reactive thrombocytosis showed a lower mean platelet volume and platelet distribution width compared to primary thrombocytosis. In reactive thrombocytosis MPV range, 6.0 - 8.0 fl with mean MPV 6.5 fl and PDW ranges from 14.0 - 16.2 % with mean PDW 15.3 %. In clonal thrombocytosis MPV range, 6.9 - 8.5 fl with mean MPV 7.9 fl and PDW range was 15.9 - 17.2 % with mean PDW 16.4 %. CONCLUSIONS On analysing the platelet counts and indices, patients with high counts, low MPV and PDW suggested reactive aetiology and patients with high counts and high MPV and PDW suggested clonal aetiology. KEYWORDS Thrombocytosis, Mean Platelet Volume, Platelet Distribution Width

Response to Erythropoiesis Stimulating Agents in Patients with WHO-Defined Myelodysplastic Syndrome/Myeloproliferative Neoplasm with Ring Sideroblasts and Thrombocytosis (MDS/MPN-RS-T)

Background: Myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) was formally included as a unique WHO-defined entity in the 2016, iteration of the classification of hematological neoplasms (under MDS/MPN overlap syndromes). Patients with MDS/MPN-RS-T have features of MDS-RS-single lineage dysplasia (SLD), persistent thrombocytosis (platelet count ≥450x109/L), with proliferation of large atypical megakaryocytes. Anemia, including red blood cell transfusion dependency (RBC-TD) is a major problem. While extensive studies have documented erythroid response rates (ERR) to erythropoiesis stimulating agents (ESA) in MDS and MDS-RS-SLD, the data in MDS/MPN-RS-T is less clear. We carried out this study to asses ERR in ESA treated patients with MDS/MPN-RS-T. Methods: After approval by the IRB, patients with 2016, WHO-defined MDS/MPN-RS-T were included in the study. The bone marrow (BM) morphology, cytogenetics and BM RS% were retrospectively reviewed. All study patients underwent next generation sequencing for 29 myeloid-relevant genes, obtained on BM mononuclear cells, at diagnosis, or at first referral, by previously described methods (Patnaik et al., BCJ 2016). Treatment details, including the type of ESA used, dose administered, side effects and reason for discontinuation were retrospectively abstracted. Erythroid responses were assessed using the 2006, international working group (IWG) MDS and the 2015, IWG MDS/MPN response criteria. Results: Forty seven patients with MDS/MPN-RS-T were identified, of which 37 (79%) patients received ESA treatment at any time point during their disease course; median age 73 years (range, 52-93), 46% male.The hemoglobin at diagnosis (HB) and baseline erythropoietin (EPO) levels were 9.1 gm/dL (range, 6.6-12.1) and 39 IU/L (range, 8-500), respectively. Ten (29%) patients were RBC-TD at baseline. None of the 37, ESA-treated patients were on concomitant cyto-reductive therapy for thrombocytosis. Twenty (54%) patients were treated with erythropoietin-a, 13 (35%) with darbepoetin, and 4 (11%) with both sequentially. Median doses were 40,000 IU weekly (range, 20,000-80,000) for erythropoietin-a and 200 mcg every 2 weeks (range, 100-500), for darbepoetin. Median treatment duration was 14 months (range, 1-173) and causes for discontinuation included; ESA failure/loss of response in 20 (54%), sustained HB rise in 1 (3%) and other causes, including adverse events in 4 (11%) patients. With regards to safety, the following events were considered potentially ESA related; treatment emergent hypertension in 2 (5%), venous thromboembolism, ischemic stroke and splenic infarction in 1 (3%) patient each, respectively. All patients with thrombotic/ischemic events had been on low dose aspirin prophylaxis. Erythroid responses by the IWG MDS and MDS/MPN response criteria were assessable in 35 (95%) patients: with 16 (46%) meeting criteria for an erythroid response, by both assessment systems. The median duration of ER was 20 months (range, 2-172). In comparison to ESA non-responders, those that responded were more likely to have baseline EPO levels ≤44 IU/L (ROC analysis; median, 28 vs 112 IU/L; p=0.0080), while there was a trend for inferior responses associated with RBC-TD (p=0.0857). Age, gender, baseline white blood cell and platelet counts, type of ESA used, BM RS %, JAK2V617F, SF3B1, DNMT3A, TET2 and ASXL1 mutational status did not impact ESA response (Table 1). On a univariate survival analysis (OS), survival was not significantly different between ESA responders vs non-responder (median OS, 76 vs 45 months; p=0.2929). After ESA failure, 7 (19%) patients received hypomethylating agents (HMA), while 5 (14%) received lenalidomide. There were no erythroid responses to HMA, while 1 of 3 (33%) assessable lenalidomide treated patients achieved a morphological complete response. Conclusion: Erythropoiesis stimulating agents are effective first line therapies for the management of anemia in patients with MDS/MPN-RS-T, with 46% achieving an erythroid response (median duration of response of 20 months). Low baseline endogenous EPO level (<44 IU/L) was the best predictor of response, with a trend towards an inferior response in the presence of RBC-TD. In the context of clonal thrombocytosis, potentially related thrombotic/ischemic events were documented in 8% of patients. Disclosures Al-Kali: Astex Pharmaceuticals, Inc.: Research Funding. Patnaik:Stem Line Pharmaceuticals.: Membership on an entity's Board of Directors or advisory committees.

Acquired JAK-2 V617F Mutational Analysis in Pakistani Patients with Essential Thrombocythemia.

Essential thrombocythemia (ET) is a clonal hemopoietic stem cell myeloproliferative neoplasm characterized by persistent thrombocytosis along with megakaryocytic hyperplasia. In the last decade following the identification of an acquired JAK2 V617F mutation, there has been acceleration in our understanding of this disease. The rational of this study was to determine the mutational profile of JAK2 V617F in Pakistan patients with ET. In this retrospective cross sectional study, 21 patients with ET were enrolled from January 2011 to December 2014. Patients were diagnosed based on WHO criteria for essential thrombocythemia. Complete blood count was done on an automated hematology analyzer, while JAK2 V617F expression was evaluated by polymerase chain reaction. The mean age was 56.7±19.0 years (range 18-87) and the male to female ratio was 1:1.1. The frequency of JAK2 V617F positivity in our ET patients was found to be 61.9%. The mean hemoglobin was 11.7±2.4 g/dl with a total leukocyte count of 13.3±8.1x109/l and a platelet count of 1188±522x109/l. Positive correlations for JAK2 V617F mutation were established with high TLC count and raised LDH (P<0.05). No correlation of JAK2 V617F could be established with age and gender (P>0.05). JAK2 V617F mutation frequency in our ET patients was similar to those reported previously. Screening for the mutation in all suspected essential thrombocythemia cases could be beneficial in differentiating patients with reactive and clonal thrombocytosis.

Thrombocytosis: Diagnostic Evaluation, Thrombotic Risk Stratification, and Risk-Based Management Strategies

Thrombocytosis is a commonly encountered clinical scenario, with a large proportion of cases discovered incidentally. The differential diagnosis for thrombocytosis is broad and the diagnostic process can be challenging. Thrombocytosis can be spurious, attributed to a reactive process or due to clonal disorder. This distinction is important as it carries implications for evaluation, prognosis, and treatment. Clonal thrombocytosis associated with the myeloproliferative neoplasms, especially essential thrombocythemia and polycythemia vera, carries a unique prognostic profile, with a markedly increased risk of thrombosis. This risk is the driving factor behind treatment strategies in these disorders. Clinical trials utilizing targeted therapies in thrombocytosis are ongoing with new therapeutic targets waiting to be explored. This paper will outline the mechanisms underlying thrombocytosis, the diagnostic evaluation of thrombocytosis, complications of thrombocytosis with a special focus on thrombotic risk as well as treatment options for clonal processes leading to thrombocytosis, including essential thrombocythemia and polycythemia vera.

Extreme Thrombocytosis: What Are the Etiologies?

Increase platelet count or thrombocytosis, defined as a platelet count greater than or equal to 350 x 10(9)/L, is a common hematologic aberration seen in complete blood cell count. Several etiologies are documented for thrombocytosis. Extreme thrombocytosis, defined as a platelet count greater than or equal to 1,000 x 10(9)/L, is rarely seen in general practice. There are limited data on the etiology of this abnormality. Here, a retrospective investigation for the etiology of severe thrombocytosis was performed. Of the 3 included reports, 535 cases with extreme thrombocytosis were investigated for their etiologies. The 2 defined etiologies are secondary thrombocytosis (66.6%) and clonal thrombocytosis. Of those cases with clonal thrombocytosis, 93.8% had myeloproliferative disorders, and 6.2% had essential thrombocytosis. Concerning bleeding and vaso-occlusive complications, all cases had these complications. In this study, 7.9% of the cases with secondary thrombocytosis experienced bleeding and vaso-occlusive complications, while 17.1% of the cases with clonal thrombocytosis did.

Plasma Levels of Thrombin-Activatable Fibrinolysis Inhibitor in Primary and Secondary Thrombocytosis

An elevated platelet count is a common finding in both hospitalized and ambulatory patients. Thrombosis and bleeding complications are more frequently observed in patients with clonal thrombocytosis than secondary thrombocytosis. The aim of this study was to investigate the behaviors of thrombin-activatable fibrinolysis inhibitor (TAFI) activity, the inhibitor of fibrinolysis, and also prothrombin time (PT), active partial thromboplastin time, and D-dimer and fibrinogen levels in 21 patients affected with clonal thrombocytemia as compared with 21 patients with reactive thrombocytosis and 21 healthy controls. In the clonal thrombocytemia group, plasma levels of TAFI activity were significantly higher than in both the reactive thrombocytosis and the control group. Plasma levels of leukocyte and platelet counts were significantly higher in the clonal thrombocytemia group than in the other two groups and also higher in the reactive thrombocytosis group than in the control group, which was also significant. Fibrinogen and D-dimer levels were higher in patients than in the control group but showed no significant difference between the clonal and secondary thrombocytosis groups. Plasma levels of PT and aPTT were higher in secondary thrombocytosis group than the clonal thrombocytosis group. The results of this study showed for the first time that TAFI activity is increased in patients with clonal thrombocytosis. These increased levels in clonal thrombocytosis can be considered a factor to explain the thrombotic tendency in myeloproliferative disorders.

The Plasma Levels of Prostanoids and Plasminogen Activator Inhibitor-1 in Primary and Secondary Thrombocytosis

An elevated platelet count is a common finding in both hospitalized and ambulatory patients. Thrombosis and bleeding complications are more frequently observed in patients with clonal thrombocytosis than secondary thrombocytosis. The aim of this study was to investigate the behaviors of plasminogen activator inhibitor type 1 (PAI-1), the inhibitor of fibrinolysis; and thromboxane A2 and 6-keto-PGF1 alpha, the products of endoperoxides, in 16 patients affected with clonal thrombocytemia as compared with 16 patients with reactive thrombocytosis and 15 normal controls. In the clonal thrombocytemia group, plasma levels of PAI-1 antigen and activity were significantly higher than both reactive thrombocytosis and control group. Plasma levels of 6-keto-PGF1alpha were significantly higher in the clonal thrombocytemia group than the other two groups and also higher in the reactive thrombocytosis group than the control group, which was also significant. This study confirms that arachidonate metabolism is frequently deranged in patients with thrombocytosis and hypofibrinolysis due to increased PAI-1 plasma levels as shown in the clonal thrombocytosis group. This may explain the thrombotic tendency in myeloproliferative disorders.

Anagrelide: an update on its mechanisms of action and therapeutic potential

Thrombocytosis is an increasingly recognized clinical problem due to the widespread availability of automated cell counters. While reactive thrombocytosis does not require any therapeutic intervention, clonal thrombocytosis may require therapy to prevent thrombohemorrhagic complications. The clinician has a number of therapeutic options available when confronted with a patient having clonal thrombocytosis. One of these agents is anagrelide (Agrylin®, Bristol–Myers Squibb). In this drug profile, a synopsis of the available data on this agent and its role in the control of thrombocytosis will be provided. The main side effects of the medication are discussed, as well as the potential future developments in the field.

Bone Marrow and Peripheral Blood C-kit Ligand Concentrations in Patients with Thrombocytosis and Thrombocytopenia

C-kit ligand (stem cell factor, SCF) is a hematopoietic growth factor with diverse effects. It has stimulatory effects on megakaryocytopoiesis acting in synergism with interleukin-3 (IL-3), thrombopoietin (TPO) and granulocyte-macrophage colony stimulating factor (GM-CSF). The relationship between SCF and megakaryocytopoiesis, especially the correlations between blood and bone marrow SCF levels have been not clearly established in the literature. We therefore, investigated peripheral and bone marrow SCF levels in patients with thrombocytosis and thrombocytopenia. Subjects were divided into three groups: those with (i) thrombocytopenia, (ii) thrombocytosis and (iii) healthy adults as controls. When the three groups were compared, the mean peripheral blood SCF level of the thrombocytosis group (2149±197) was significantly higher than the thrombocytopenia (1586±178) and normal control groups (1371±68; p<0.05) and the bone marrow SCF level was higher (2694±267) than the thrombocytopenia group (1700±182; p<0.05). In the correlation analysis, considering all the groups together the bone marrow and peripheral blood SCF concentrations were positively and significantly correlated (p<0.01; r=0.93). Correlations between platelet number and both bone marrow SCF concentration (p<0.01; r=0.51) and peripheral blood concentrations (p<0.01; r=0.40) were also shown. Our results indicate that SCF is operative in the pathological megakaryopoiesis of clonal origin and reactive thrombocytosis both in the local bone marrow microenvironment and the peripheral circulating blood. We feel that further studies on the platelet-SCF relationship and SCF levels in different disease states are required.

Increased erythropoietin levels in reactive thrombocytosis.

Erythropoietin, the major humoral regulator of red cell production, was reported to stimulate various levels of megakaryocytopoiesis. We investigated levels of thrombopoietin (TPO) and erythropoietin (EPO) in patients with reactive thrombocytosis (RT) and clonal thrombocytosis (CT). 17 patients with RT and 18 patients with CT and 15 healthy subjects were enrolled into the study. TPO levels were higher in both patient groups than the controls. EPO levels were significantly higher than these in reactive thrombocytosis and in controls (p < 0.05). We suggest that besides TPO, EPO may play an important role in the pathogenesis of RT.

Thrombocytosis and thrombocythemia

Thrombocytosis is caused by three major pathophysiological mechanisms: (1) reactive or secondary thrombocytosis; (2) familial thrombocytosis; and (3) clonal thrombocytosis, including essential thrombocythemia and related myeloproliferative disorders. Recent work has begun to elucidate the abnormal megakaryocytopoiesis of essential thrombocythemia, which is associated with paradoxically elevated plasma levels of thrombopoietin. The clonal nature of all cases of essential thrombocythemia has been challenged. Thrombotic complications are the major causes of morbidity and mortality in this disease. Indications for platelet cytoreduction and antiplatelet therapy, as well as complications of treatment, are being clarified.

Reactive and Clonal Thrombocytosis

Reactive and Clonal Thrombocytosis

Reactive and Clonal Thrombocytosis

Reactive and Clonal Thrombocytosis