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PubMed1996

Megakaryocyte-related interleukins in reactive thrombocytosis versus autonomous thrombocythemia.

The primary thrombocytosis (thrombocythemia) associated with myeloproliferative disorders is believed to be due to autonomous platelet production. Secondary or reactive thrombocytosis can be observed in a number of clinical circumstances, and may be related to persistent overproduction of some thrombocytopoietic factors acting on megakaryocytes. Several cytokines, including IL-6, IL-1 and IL-4 have been shown to act alone or in concert, to affect various cellular stages of megakaryocytopoiesis in humans. The aim of this study is to assess the serum concentrations of these cytokines in myeloproliferative disorders (MPD) with thrombocythemia and in rheumatoid arthritis (RA) with marked reactive thrombocytosis. Twenty-two patients (14 men, 8 women) with MPD and thrombocythemia (platelet counts > 500 x 10(9)/1; range 507-996 x 10(9)/1), 33 RA patients (28 women, 5 men) with marked thrombocytosis (platelet counts > 500 x 10(9)/1; range 500-745 x 10(9)/ 1), 27 RA patients (24 women, 3 men) with normal platelet counts (range 168-399 x 10(9)/1) and 15 healthy volunteers (8 women, 7 men) with normal platelet counts (range 161-385 x 10(9)/1) enrolled in the study. Serum IL-1 alpha, IL-1 beta, IL-4 and IL-6 concentrations were measured in these four groups. Of the 22 patients with MPD, 10 had chronic myelogenous leukemia, 5 had polycythemia vera, 6 had essential thrombocytosis and 1 had osteomyelofibrosis. Serum interleukin concentrations in patients with MPD and thrombocythemia were either suppressed or similar to those of normal subjects, whereas IL-6, IL-1 beta and IL-4 levels were increased in RA patients with reactive thrombocytosis. We conclude that thrombocythemia associated with MPD is an autonomous phenomenon, and is not regulated by cytokines which affect megakaryocytopoiesis.

Adolescent↗
PubMed1999

Patients with thrombocytosis have normal or slightly elevated thrombopoietin levels.

BACKGROUND AND OBJECTIVE: The distinction between clonal and reactive thrombocytoses is a frequent problem and implies different therapeutic options. As thrombopoietin (TPO) is the main regulator of megakaryocytopoiesis and thrombopoiesis, we measured TPO levels in patients with thrombocytosis in an attempt to understand the regulation and potential utility of distinguishing thrombocytoses. DESIGN AND METHODS: Serum TPO levels, platelet counts, mean platelet volume, hemoglobin, erythrocyte sedimentation rate and age were evaluated in 25 patients with clonal thrombocytosis (15 with essential thrombocythemia, 6 with polycythemia vera and 4 with chronic myeloid leukemia) and in 50 patients with reactive thrombocytosis distributed in three groups: 1) patients in post-surgical states; 2) patients with solid tumors; and 3) patients with inflammatory diseases. RESULTS: TPO levels were slightly increased in patients with clonal (135+/-50 pg/mL) and reactive (147+/-58 pg/mL) thrombocytosis compared with controls (121+/-58 pg/mL). Analyzing the different groups, patients with essential thrombocythemia had the lowest TPO levels (120+/-28 pg/mL) and patients with solid tumors the highest levels (162+/-59 pg/mL). Patients with clonal thrombocytosis were older, had higher platelet counts, mean platelet volume and hemoglobin, and lower erythrocyte sedimentation rate than patients with reactive thrombocytosis. INTERPRETATION AND CONCLUSIONS: Minor differences were observed in TPO levels between patients with primary and secondary thrombocytoses. Erythrocyte sedimentation rate, but not TPO levels, may be a useful tool for discriminating both types of thrombocytoses.

Adolescent↗
PubMedDate not supplied

Preoperative thrombocytosis is an independent prognostic factor in stage III and IV endometrial cancer.

BACKGROUND: To identify prognostic factors in stage III and IV endometrial cancer with special attention to pretreatment platelet count. MATERIALS AND METHODS: 59 patients with FIGO stage III or IV disease operated on between 1983 and 1993 were analyzed. Patients with preoperative thrombocytosis were compared with those without thrombocytosis. Prognostic factors were analyzed with a Cox proportional hazard model. RESULTS: With the exception of age, there were no significant differences between patients with or without thrombocytosis. At multivariate analysis, five-year disease-free survival was influenced significantly by FIGO stage (stage III vs stage IV; p = 0.009), thrombocytosis (p = 0.02) and cervical involvement (p = 0.024). Similarly, overall five-year survival was significantly influenced by stage (p < 0.001), cervical involvement (p = 0.005) and thrombocytosis (p = 0.01). Age, histology, grade, myometrial invasion, lymph-vascular space involvement or spread to adnexae were not significantly associated with survival. CONCLUSION: Thrombocytosis is an independent prognostic factor in stage III and IV endometrial cancer.

Adult↗
PubMedDate not supplied

[Refractory anaemia with ringed sideroblasts (RARS) associated with marked thrombocytosis: a provisional entity in the WHO classification of haematological malignancies].

The WHO classification describes a group of myelodysplastic/myeloproliferative diseases, including a provisional entity, refractory anaemia with ringed sideroblasts (RARS) associated with marked thrombocytosis, underlining that is a provisional entity without consensus of belonging to myelodysplastic rather than to myeloproliferative syndromes. The authors report two cases with features of refractory anaemia with excess of ringed sideroblasts and marked thrombocytosis. In the first case, RARS is concomitant with thrombocytosis and fits the WHO criteria for this temporary entity. The second case is a typical RARS, who developed a thrombocytosis after several years and emphasizes that a link, at least progressive, exists between RARS and myeloproliferative disorders. The authors summed up the various situations related to secondary or primary acquired sideroblastic anaemia, likewise to primitive and reactive thrombocytosis. The cases of RARS + marked thrombocytosis reported in the literature are few in number and do not allow to settle between a particular form of myelodysplastic syndrome and a myeloproliferative disorder, a fully justified reason to classify these patients in a temporary group. To date, there is no codified therapy for this disorders.

Aged↗
PubMed1985

Blood coagulation and platelet profiles in persistent post-splenectomy thrombocytosis. The relationship to thromboembolism.

To clarify the possible role of persistent thrombocytosis after splenectomy being a predisposing factor causing development of thromboembolism, blood coagulation profiles and platelet functions were studied in 34 cases being 1-18 years post-splenectomy from non-malignant diseases. Persistent thrombocytosis was observed in 16 with significant negative correlation between hemoglobin level and platelet count indicated the role of anemia on persistent post-splenectomy thrombocytosis. Blood coagulation profiles showed accelerated thrombin formation or hypercoagulability as measured by thrombin generation test especially in cases with thrombocytosis, together with decreased fibrinolytic activity and high fibrinogen, but in presence of high antithrombin III activity. Concerning the platelet, the aggregation to ristocetin was defective, the improved aggregation to ADP and adrenaline was achieved only in whom with intact spleen giving defective platelet aggregation. The finding indicated the role of spleen contributing to abnormal platelet aggregation. Another interesting observation was the decreased platelet 5-hydroxytryptamine content in splenectomized cases. The overall changes on blood coagulation and platelets post-splenectomy including those with persistent thrombocytosis did not thoroughly shift to hypercoagulable state, since a high antithrombin III activity and some platelet defect remained. These present findings, therefore, unlikely predisposed to the occurrence of thromboembolism even in those with persistent thrombocytosis.

Adolescent↗
PubMed1997

Platelet distribution width for differential diagnosis of thrombocytosis.

Differential diagnosis of thrombocytosis is not always obvious. The routine clinical chemistry laboratory classically provides only limited help in distinguishing between reactive thrombocytosis (RT) and autonomous thrombocytosis, where platelet production escapes normal regulatory processes, and which is seen in myeloproliferative diseases (MPD) such as essential thrombocythemia and polycythemia vera. We explored the clinical use of platelet distribution width (PDW) in the differential diagnosis of thrombocytosis. During a 3-month period, 250 patients presenting with a platelet count > 500 x 10(9)/L were studied; 174 were classified as having RT, 42 had a diagnosis of MPD, and 34 patients were excluded because they had a hemopathy different from MPD, and either did or did not present a known etiologic factor for RT. First, we determined that in the RT group the value of PDW was closely linked to both mean platelet volume (MPV) and platelet count (PLT) (PDW = 79.5-0.005 PLT -3.5 MPV; r = 0.848, R2 = 0.720). Therefore a new parameter, PDWresidual was defined (PDWresidual = PDWobserved -PDWexpected). Second, the discrimination between reactive and autonomous thrombocytosis obtained with PDWresidual was compared with that obtained with either PDW, MPV, or PLT. PDWresidual provided much more powerful than each of the other parameters used separately: 76% of MPD patients had a PDWresidual above the 95th percentile value of the RT population and none of the MPD patients had a PDWresidual below the 50th percentile. Thus, the combined interpretation of PLT, MPV, and PDW through the use of a PDWresidual appears highly useful in the differential diagnosis of thrombocytosis. Also, through simple modeling, more information can be drawn from parameters such as PDW that hitherto were mostly discarded as being without clinical interest.

Blood Platelets↗
PubMed1998

P-selectin as a circulating molecular marker in rheumatoid arthritis with thrombocytosis.

OBJECTIVE: To compare plasma concentrations of soluble P-selectin (sP-selectin) in patients with rheumatoid arthritis (RA) and thrombocytosis with those with RA with normal platelet counts and healthy controls, and to explore the relationship between clinical and serological measures of disease activity. METHODS: Nineteen patients with RA with marked thrombocytosis, 20 with normal platelet counts, and 24 controls were enrolled. Ritchie articular index and morning stiffness were recorded as clinical markers of disease activity. Blood samples were collected for platelet count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and plasma sP-selectin determinations. Correlations between sP-selectin and clinical and serological markers of disease activity were noted. RESULTS: Patients with RA and thrombocytosis compared to patients with normal platelet counts showed evidence of more active disease when ESR, CRP, morning stiffness, and Ritchie articular index were considered. The thrombocyte count in patients with RA with marked thrombocytosis revealed a positive correlation with CRP and Ritchie articular score. Plasma sP-selectin levels were found to be significantly higher in patients with RA compared to controls. sP-selectin levels were significantly higher in patients with RA with thrombocytosis compared to those with normal platelet counts, and positive correlations were observed between plasma sP-selectin levels and Ritchie index, morning stiffness, and thrombocyte counts in those patients. CONCLUSION: Elevated plasma sP-selectin levels in RA could indicate the presence of a continuous underlying inflammatory stimulus. In addition, the augmented increase in patients with RA and thrombocytosis and its correlation with clinical activity may imply the cytokine-adhesion molecule interaction mediates the chronic inflammation of RA.

Adult↗
PubMed1998

[The prognostic value of thrombocytosis in patients with primary lung cancer].

The prognostic information provided by platelet counts was studied in 1115 patients with primary lung cancer and in 550 control patients with benign lung disorders. Patient records were retrospectively reviewed regarding histological tumour type, TNM stage, thromboembolic episodes and survival. The prevalence of thrombocytosis (platelet count > 400 x 10(9)/l) in patients with lung cancer was 32.1% vs. 6.4% in controls (p < 0.0001). Platelet counts increased with TNM stage (p < 0.0001). Patients with thrombocytosis had a shorter survival than patients with normal platelet count (p < 0.0001). Thrombocytosis was a predictor of short survival also when adjusted for tumour type, sex, age, and TNM stage (p < 0.001). The platelet count and the frequency of thrombocytosis declined after tumour resection (p < 0.0001). Thrombocytosis was not associated with thromboembolism. In conclusion, thrombocytosis is a clinically significant prognostic indicator regarding survival in patients with primary lung cancer.

Adult↗
PubMed2000

Macrocytic anemia and thrombocytosis associated with thymoma: a case report.

Thymomas are often associated with autoimmune disorders. We report on a 45-year-old female patient with thymoma and hypogammaglobulinemia (Good's syndrome) who developed symptomatic macrocytic anemia (Hb 4.4 g/dl, MCV 112 fl) and thrombocytosis (Plt 442 G/l). Besides hypogammaglobulinemia (IgG 589 mg/dl), an inverted ratio of CD4(+)/CD8(+) cells was seen. The bone marrow biopsy showed a slightly hypercellular bone marrow with normal granulopoiesis, normal megakaryopoiesis and a mild dyserythropoiesis without any ring-sideroblasts. The in-vitro stem cell culture from the bone marrow revealed an atypical growth of macroclusters, reduced BFU-E and CFU-GEMM colony growth, whereas the CFU-GM colony growth was within the normal range. The chromosomal analysis showed a normal karyotype. The plasma vitamin B(12) and folate levels were within normal ranges, and we could not detect any autoantibodies. These findings excluded the differential diagnoses pure red cell aplasia (PRCA) and pernicious anemia. After resection of the thymoma of mixed cell type, the macrocytic anemia and thrombocytosis disappeared. The clinical course was complicated by a cerebral palsy and a life-threatening fungal septicemia after surgery. In the third year after thymectomy, hyporegenerative macrocytic anemia and thrombocytosis reappeared and an immunosuppressive treatment with prednisolone (1 mg/kg BW) was started. After initiation of the prednisolone therapy, reticulocyte counts increased and macrocytic anemia as well as thrombocytosis disappeared. The normalization of these laboratory parameters during glucocorticoid therapy suggests that in rare cases the constellation of macrocytic anemia, thrombocytosis and hypogammaglobulinemia may be due to an underlying immunologic mechanism.

Agammaglobulinemia↗
PubMed1992

Poor prognosis associated with thrombocytosis in patients with cervical cancer.

The medical records of 113 patients treated with radiation therapy for invasive cervical cancer between 1975 and 1985 were retrospectively reviewed. Patients with thrombocytosis (platelet count greater than 400,000/microliters) were compared with those with normal platelet counts. Thrombocytosis was present at the initiation of therapy in 20 (17.7%) of the 113 patients. The 5-year cumulative survival rate for the 93 patients with normal platelet counts was 65%, whereas it was 25% for the 20 with thrombocytosis (P less than 0.0001, log-rank test). Using Cox's proportional hazards model, thrombocytosis continued to correlate strongly with poor survival even when adjusted for histologic type, patient age, and disease stage (P less than 0.001). Thrombocytosis is an independent indicator of poor prognosis in patients with cervical cancer.

Female↗
PubMed1994

Thrombocytosis as a prognostic factor in women with cervical cancer.

BACKGROUND: Thrombocytosis (a platelet count > 400 x 10(9)/l) is found frequently in association with malignant disease and recently has been suggested to be a poor prognostic indicator in patients with cervical cancer. The authors decided to see if these findings could be verified. METHODS: The pretreatment platelet counts of 643 women treated for cervical cancer between 1983 and 1992 were reviewed and correlated to each patient's age, stage of disease, histologic type, node status (when available), and outcome. Differences between groups were analyzed using the chi 2 test, and survival was compared using the log rank test on Kaplan-Meier life tables. RESULTS: The 5-year survival rate for patients with thrombocytosis was 57.1%, which was significantly worse than the 76.5% for those with normal platelet counts (P < 0.01). When adjusted for stage of disease, however, thrombocytosis failed to have a significant effect on patient survival. There was also no relation between thrombocytosis and the incidence of positive lymph nodes. CONCLUSION: Thrombocytosis was not found to be an independent prognostic factor in patients with carcinoma of the cervix in this series of 643 patients.

Adult↗
PubMed1989

Thrombocytosis as a presenting feature of acute lymphoblastic leukemia in childhood.

To determine the incidence of thrombocytosis at presentation in acute lymphoblastic leukemia (ALL), medical records of all children diagnosed at the Children's Hospital of Pittsburgh from 1980 to 1987 were reviewed. Out of 217 such patients, 7 (3.2%) had platelet counts greater than 400,000/mm3. All of the seven were boys compared with a male:female ration of 1.4:1 in the entire ALL population. Other than sex, no characteristics were clearly associated with thrombocytosis, including white blood cell count, hemoglobin, lymphoblast morphology, and immunologic or chromosomal markers. Apart from ALL, no inflammatory or infectious process which might have caused a thrombocytosis, was detected in any of these patients. The period of induction therapy was notable for the preservation of platelet counts greater than 20,000/mm3 in all patients. However, of the seven children with thrombocytosis, two had major induction complications: one, a cavernous sinus thrombosis; and the other, gastrointestinal bleeding with duodenal perforation. We conclude that thrombocytosis at diagnosis can be seen in children, particularly boys, with ALL. Based on small numbers, this group of patients may be at risk for major events during induction therapy. Large numbers, longer follow-up, and platelet function studies on similar patients will be of interest.

Biopsy↗
PubMed1993

Marked thrombocytosis with chromosomal abnormalities in a patient with rheumatoid arthritis.

An 80 year-old Japanese woman with rheumatoid arthritis (RA), complicated with thrombocytosis is described. Mild to moderate thrombocytosis is commonly observed in patients with RA, but she had marked thrombocytosis of over 1000 x 10(3)/mm3 and monosomy 22 with marker chromosome. This case suggests that thrombocytosis unusual with disease activity of RA might occur, and that careful evaluation of the thrombocytosis is required.

Aged↗
PubMed1994

Significance of thrombocytosis in patients with epithelial ovarian cancer.

OBJECTIVES: Our objective was to determine the relevance of a preoperative platelet count in ovarian cancer. Special interest was directed to a possible prognostic significance of thrombocytosis in this disease. STUDY DESIGN: Charts of 130 patients with epithelial ovarian cancer were reviewed retrospectively. Survival analyses were performed with the Kaplan-Meier method. Differences in survival were examined according to Mantel and Breslow. Platelet counts were furthermore correlated to other clinical parameters. For this purpose the Spearman rank test and a stepwise logistic regression model were used. Data comparison was accomplished with the Mann-Whitney U test and the chi 2 test. RESULTS: Prevalence of thrombocytosis was 38%. No differences in survival between patients with or without thrombocytosis was found. Volume of ascites and hemoglobin concentrations were independently associated with thrombocytosis (p = 0.002 and p = 0.004, respectively). CONCLUSIONS: Thrombocytosis is not a useful prognostic factor in ovarian cancer. Elevated platelets are predominantly associated with the presence of ascites and marked anemia.

Adult↗
PubMed2001

Early elevation of serum thrombopoietin levels and subsequent thrombocytosis in healthy preterm infants.

To verify pathophysiological mechanisms underlying thrombocytosis in low-birth-weight (LBW) preterm babies, we evaluated kinetic changes in platelet counts and thrombopoietic cytokines including thrombopoietin (TPO), interleukin 6 (IL-6) and IL-11 in 24 uncomplicated preterm infants. Platelet counts in cord blood (CB) (265 +/- 64 x 10(9)/l) were similar to adult levels, increased by d 14 (473 +/- 140 x 10(9)/l), and then remained fairly constant. Thrombocytosis (> 500 x 10(9)/l) was observed in 9/24 (38%) subjects. Mean TPO level in CB was 5.11 +/- 1.51 fmol/ml, peaked at d 2 (7.64 +/- 3.28 fmol/ml), decreased at d 5 (3.93 +/- 1.67 fmol/ml), and thereafter kept fairly constant during the remaining neonatal period. Compared with term infants, mean TPO levels of preterm infants in CB and at d 2 were significantly higher (P < 0.01). There was an inverse correlation between platelet counts and TPO levels (r = 0.45, P < 0.001, n = 88). Preterm neonates with thrombocytosis had significantly higher TPO values in CB than those without thrombocytosis (P < 0.05). There was no significant relationship between platelet counts and IL-6. IL-11 was not detectable. These results suggest that an early elevation of serum TPO levels is related to the subsequent thrombocytosis in LBW preterm infants.

Biomarkers↗
PubMed1986

Essential thrombocytosis with the Philadelphia chromosome (Ph').

Essential thrombocytosis is a myeloproliferative disease not known to have consistent cytogenetic abnormalities. A 46-year-old black woman with essential thrombocytosis and a Philadelphia chromosome is reported. Iron deficiency and tuberculosis were present but when effectively treated did not result in resolution of thrombocytosis. Megakaryocytic hyperplasia of bone marrow, abnormal platelet function studies and a compatible clinical state suggested the diagnosis of essential thrombocytosis. The diagnostic criteria for other myeloproliferative diseases were not met. The Philadelphia chromosome was consistently obtained from bone marrow preparations. We conclude that the Philadelphia chromosome may be found in essential thrombocytosis as well as other, previously reported, myeloproliferative diseases.

Bone Marrow↗
PubMed1990

Thrombocytosis after pneumonia with empyema and other bacterial infections in children.

Thrombocytosis is seen in association with many conditions, including infectious diseases. We studied thrombocytosis after severe bacterial infections, particularly pneumonia with empyema in children. A systematic survey of the phenomenon was conducted. Twenty-seven children admitted for pneumonia with empyema were studied. Thrombocytosis (platelet counts greater than 500 x 10(3)/microliters) was present in 92.5%. Platelet counts reached their maximum at 15.1 +/- 3.7 days (range, 7 to 25) and declined to normal after 3 weeks of illness. Compared with a healthy control group, significant thrombocytosis, but of lower incidence, was also noted in children with lobar pneumonia without pleural effusion, bacterial meningitis and osteomyelitis. Platelet functions were examined in seven of the children but no abnormalities were observed. Bone marrow aspiration of three children with pneumonia and empyema showed megakaryocytic hyperplasia. We found no correlation between thrombocytosis, neutrophilia, fever, the clinical course, complications, prognosis or treatment. Neither thromboembolic nor hemorrhagic phenomena were observed.

Bacterial Infections↗
PubMed1991

Elevated serum interleukin-6 levels in patients with reactive thrombocytosis.

Interleukin-6 (IL-6) is known to promote megakaryocytopoiesis in vitro and raise platelet counts in vivo. To determine if there is a relationship between circulating IL-6 and thrombocytosis in man, we measured bioactive IL-6 in the serum of 13 patients with myeloproliferative disorders and 143 patients with reactive thrombocytosis having platelet counts greater than or equal to 600 x 10(9)/l. IL-6 activity was assayed using the IL-6-responsive B9 cell line. Seventy-one controls with normal platelet counts had a mean IL-6 level of 2.19 U/ml +/- 1.08 (SD). None of the 13 patients with myeloproliferative disorders had elevated IL-6 levels (1.56 U/ml +/- 1.2). In contrast, serum IL-6 levels of 143 patients (158 samples) with reactive thrombocytosis were significantly greater than controls (38.3 U/ml +/- 94.6; P less than 0.001), with 83% of the samples showing elevated serum IL-6. No significant correlation was observed between serum IL-6 levels and platelet counts in the reactive thrombocytosis group. We conclude that elevated IL-6 is associated with reactive thrombocytosis, and hypothesize that the increased platelet count in many cases is causally related to elevated IL-6.

Humans↗