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Drug-induced thrombocytosis.

Thrombocytosis is generally defined as platelet counts greater than 400,000/mm3. Thrombocytosis can be either primary or secondary. Adrenalin was one of the first drugs noticed to cause platelet elevations, probably due to demargination of platelets in the pulmonary vasculature. Vinca alkaloids have the most convincing data to show that they can induce thrombocytosis through their thrombocyte-stimulating properties. Miconazole has been implicated in causing thrombocytosis and has a documented case validated by drug rechallenge. Iron, predictably, can cause a transient thrombocytosis. The beta-lactam antibiotic data are very difficult to interpret due to the possibility of an acute-phase reaction in an infected patient being the cause of the thrombocytosis.

Anti-Bacterial Agents↗

Neonatal thrombocytosis resulting from the maternal use of non-narcotic antischizophrenic drugs during pregnancy.

Neonatal thrombocytosis can result from maternal narcotic drug abuse. The case of a male infant is reported who was born to a woman with schizophrenia treated with non-narcotic psychotropic drugs during pregnancy; he developed severe prolonged thrombocytosis. The platelet count reached 1310 x 10(9)/l on day 15. This thrombocytosis persisted for three months. The patient was treated with dipyridamole. A bone marrow aspirate showed normal myeloid and erythroid precursors with an increased number of megakaryocytes. Plasma concentrations of interleukin 6 and thrombopoietin were suppressed. No obvious complications from the thrombocytosis occurred, and the platelet count fell to within the upper limit of normal after 3 months of age. This case indicates that thrombocytosis may occur in infants born to mothers treated with non-narcotic psychopharmaceutical drugs during pregnancy. The thrombocytosis in this case may have been induced by factors other than interleukin 6 or thrombopoietin.

Dipyridamole↗

Tumor anemia and thrombocytosis in patients with vulvar cancer.

The aim of our study was to determine the prevalence of tumor anemia and thrombocytosis in patients with vulvar cancer, and to evaluate the prognostic value or pretreatment hemoglobin (Hb) and platelet count regarding disease-free and overall survival of patients with vulvar cancer. We measured pretreatment Hb and platelet count in 62 patients with squamous cell vulvar cancer. The results were correlated to clinical data. Median Hb and platelet count in patients with vulvar cancer were 13.1 g/dl (range 8.3-16.2) and 268, 500/microl (range 88,000-778,000), respectively. Cut-off levels of 12 g/dl and 300,000/microl were selected for tumor anemia and tumor thrombocytosis, respectively according to published criteria. Tumor anemia and tumor thrombocytosis were present in 30.6 and 27.4% of patients with vulvar cancer, respectively. In a univariate analysis tumor stage and tumor thrombocytosis were significantly associated with a shortened disease-free (log-rank test, p < 0.001 and p = 0. 003, respectively) and overall survival (log-rank test, p < 0.001 and p < 0.001, respectively). Tumor anemia was not associated with a shortened disease-free, but with a shortened overall survival of patients with vulvar cancer (log-rank test, p = 0.1 and p = 0.002, respectively). A multivariate Cox regression model considering tumor stage, tumor anemia, and tumor thrombocytosis showed, however, that pretreatment Hb and platelet count did not confer additional prognostic information to that already obtained by the established prognosticator tumor stage on disease free (multivariate Cox regression model, p = 0.8, p = 0.2, and p = 0.003, respectively) and overall survival (multivariate Cox regression model, p = 0.4, p = 0. 5, and p = 0.04, respectively). Pretreatment tumor anemia and tumor thrombocytosis were associated with a poor prognosis, but were not an independent predictor of outcome in patients with vulvar cancer.

Adult↗

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↗

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↗

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↗

[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↗

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↗

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↗

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↗

[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↗

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↗

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↗

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↗

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↗

Thrombocytosis as a prognostic factor for survival in patients with metastatic renal cell carcinoma.

BACKGROUND: It has been suggested that thrombocytosis, as defined by a platelet count >400,000/microL, is a negative predictor for survival among patients with metastatic renal cell carcinoma. However, this has not been a uniform finding. METHODS: To address this issue, retrospective analysis of 700 previously untreated patients entering on institution review board-approved phase 1, 2, or 3 clinical trials in the United States and Europe was conducted between 1982 and 2002. RESULTS: Thrombocytosis was present at study entry in 25% of patients. Median baseline platelet count was 304,000/microL (range, 86-1,420,000/microL). Eighty-seven percent of patients died with a median survival of 13.0 months. Median follow-up for patients not known to have died was 2.4 years. On univariate analysis, patients with elevated platelet counts had significantly shorter survival than patients with normal platelet counts; median survivals of 8.4 and 14.6 months, respectively, P < .001. However, platelet count was associated with several clinical and biochemical factors, including gender, age, performance status, time from diagnosis to study entry, prior radiotherapy or nephrectomy, presence of liver metastasis, number of metastatic sites, amount of hemoglobin, white blood cell count, amount of lactate dehydrogenase, and amount of serum alkaline phosphatase. Several of these factors have previously been reported as prognostic indicators for survival, and, therefore, multivariable analyses were conducted to determine whether thrombocytosis is an independent predictor of survival. After adjusting for multiple factors, thrombocytosis continued to impact negatively on survival, P < .001. CONCLUSIONS: Thrombocytosis was found to be an independent prognostic factor for survival in patients with metastatic renal cell carcinoma.

Carcinoma, Renal Cell↗

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↗

Thrombocytosis in pediatric patients is associated with severe lower respiratory tract inflammation.

BACKGROUND: Secondary thrombocytosis is associated with a variety of clinical conditions. The aim of this study was to determine the incidence and to analyze the clinical significance and prognostic value of thrombocytosis in lower respiratory tract infection. METHODS: A total of 102 pediatric patients were hospitalized with lower respiratory tract infection during a period of 30 months. RESULTS: Forty nine (48%) of those patients had platelet counts >500 x 10(9)/L. The median age of the thrombocytotic patients was 31 months as opposed to 61 months for the non-thrombocytotic ones. The patients with thrombocytosis had more serious illness. This is indicated by three factors: more severe clinical condition on admission, presence of respiratory distress and longer hospitalization. Sedimentation rate >70 mm/h was observed in 44.4% patients of the thrombocytotic group compared to only 27.7% of the non-thrombocytotic ones. Almost all patients with pleural effusion were thrombocytotic. The children with very high platelet counts >650 x 10(9)/L presented with respiratory distress on admission and required longer hospitalization time. No other significant clinical or laboratory differences were demonstrated between these patients and the remainder of the thrombocytotic patients. CONCLUSIONS: Thrombocytosis is a common finding among patients with lower respiratory tract infection. Thrombocytotic patients have a more severe clinical condition. Importantly, thrombocytosis occurs almost exclusively in patients with pleural effusion. The platelet count may be a useful clinical marker associated with the severity of the lower respiratory tract infection.

Blood Platelets↗