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Rapidly relapsing squamous cell carcinoma of the renal pelvis associated with paraneoplastic syndromes of leukocytosis, thrombocytosis and hypercalcemia.

A case history is reported here in which leukocytosis, thrombocytosis and hypercalcemia associated with rapidly relapsing squamous cell carcinoma (SCC) of the renal pelvis were observed. In a 58-year-old man, SCC of the renal pelvis was documented during nephrolithotomy, and right nephrectomy was performed. Local relapse of the tumor occurred rapidly in 2 months' time and hypercalcemia, leukocytosis and thrombocytosis worsened in accordance with tumor volume. Cranial computerized tomography (CT), thorax CT and bone scintigraphy were negative for metastasis. The serum parathyroid hormone level was 28 pg/ml (normal 9- 55 pg/ml). To disclose leukocytosis and thrombocytosis, peripheral smear and bone marrow aspiration were performed and no pathologic finding regarding any hematologic disorder was found; the samples were also BCR-ABL negative and Philadelphia chromosome negative. Production of several factors by tumor cells may be responsible for this paraneoplastic syndrome. The association of SCC of the renal pelvis with this triple paraneoplastic syndrome is an extremely rare occurrence.

Carcinoma, Squamous Cell↗

Initial (latent) polycythemia vera with thrombocytosis mimicking essential thrombocythemia.

Patients have previously been described who showed clinical signs and symptoms suggesting essential thrombocythemia (ET), but later transformed to polycythemia vera (PV). From a series of 344 patients with a sustained borderline to moderate erythrocytosis, 44 failed to conform initially with the diagnostic criteria of the WHO for PV, because of their low hemoglobin level. Twenty-three patients of this group presented with a thrombocytosis exceeding 600 x 10(9)/l and therefore suggested ET, but later developed full-blown PV. For comparison we investigated also 164 patients with manifest PV, 90 patients with ET and 22 patients with reactive thrombocytosis (Th). The histopathology of initial PV was evaluated by stepwise discriminant analysis of 17 standardized features. Quantity and left shifting of erythro- and granulopoiesis, giant forms and naked nuclei of megakaryocytes, cellularity and reticulin fibers proved to exert a significant relevance concerning differentiation from true ET and Th. In conclusion, initial PV with thrombocytosis is characterized by a special pattern of BM histopathology. Therefore, so-called masked PV in patients with ET or simultaneous PVR-1 gene expression and endogeneous erythroid colony growth in ET patients are probably in keeping with initial PV mimicking ET.

Discriminant Analysis↗

Carotid artery thrombus associated with severe iron-deficiency anemia and thrombocytosis.

BACKGROUND: Thrombus within the carotid artery usually occurs in vessels with severe atherosclerotic disease and may embolize to cause transient ischemic attacks and cerebral infarctions. The risk factors for carotid artery thrombus formation in the absence of atherosclerosis are not well characterized. A case series is presented that suggests an association of carotid artery thrombus with severe iron-deficiency anemia and thrombocytosis. CASE DESCRIPTIONS: We describe three women with severe iron-deficiency anemia and thrombocytosis secondary to menorrhagia who developed carotid artery thrombi. Thrombi were detected radiographically. The patients were treated with anticoagulation and antiplatelet therapy. In two patients, follow-up neuroimaging 10 to 14 days later demonstrated resolution of the thrombus and no identifiable vascular disease. CONCLUSIONS: Severe iron-deficiency anemia with thrombocytosis may be a risk factor for carotid artery thrombus formation. Medical management with anticoagulation and antiplatelet therapy is a reasonable approach for these patients while the thrombus resolves.

Adult↗

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.

Adult↗

Role of thrombocytosis in diagnosis of giant cell arteritis and differentiation of arteritic from non-arteritic anterior ischemic optic neuropathy.

PURPOSE: To investigate the role of thrombocytosis in the diagnosis of giant cell arteritis (GCA), and differentiation of arteritic (A-AION) from non-arteritic (NA-AION) anterior ischemic optic neuropathy; and comparison of the sensitivity and specificity of platelet count to that of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and some other hematologic variables in the diagnosis of GCA. METHODS: This retrospective study is based on 121 temporal artery biopsy confirmed GCA patients and 287 patients with NA-AION seen in our clinic. For inclusion in this study, all GCA patients, at their initial visit, prior to the initiation of corticosteroid therapy, must have had ESR (Westergren), platelet count and complete blood count, and temporal artery biopsy. From 1985 onwards CRP estimation was done. For inclusion in this study, all NA-AION patients at the initial visit must have undergone evaluation similar to that described above for GCA, except for temporal artery biopsy. Wilcoxon rank-sum test and the two-sample t-test were used to compare hematologic variables between GCA patients with and without visual loss, between those with and without systemic symptoms, and also between GCA and NA-AION patients. Pearson correlation coefficient was computed to measure the association of platelet counts and the other hematologic variables with ESR. Receiver operating characteristic (ROC) curves were constructed for ESR, CRP, platelet count, combinations of ESR and platelet count, and CRP and platelet count, hemoglobin, hematocrit, and white blood cell (WBC) count and the area under the curve (AUC) were compared. RESULTS: Comparison of ESR, CRP, and hematologic variables of GCA patients and of A-AION with the NA-AION group, showed significantly (p <0.0001) higher median levels of ESR, CRP, platelet count, and WBC count and lower levels of hemoglobin and hematocrit in the GCA patients and A-AION than in NA-AION. Comparing AUC of the ROC curve between ESR and platelet count, ESR was a better predictor of GCA compared to platelet count (AUC of 0.946 vs. 0.834). There was a slight improvement in prediction of GCA using the combination of ESR and platelet count (AUC=0.953). The other hematologic variables had an AUC that was smaller than platelet count (0.854 for hemoglobin; 0.841 for hematocrit), with WBC being the least predictive of GCA (AUC=0.666). The AUC of the ROC curve for CRP was 0.978. There was no improvement in prediction of GCA using platelet count in combination with CRP (AUC=0.976). CONCLUSIONS: Patients with GCA had significantly (p <0.0001) higher values of platelet count, ESR, CRP and WBC but lower values for hemoglobin and hematocrit compared to the NA-AION group. Predictive ability of an elevated platelet count did not surpass elevated ESR or CRP as a diagnostic marker for GCA. Thrombocytosis may complement ESR. Hemoglobin, hematocrit and WBC were much less predictive of GCA. Elevated CRP had a greater predictive ability for GCA compared to ESR or the other hematologic parameters; thrombocytosis in combination with CRP did not yield an improvement in prediction of GCA.

Aged↗

A case of pseudo-Bartter's syndrome associated with hypergastrinemia, thrombocytosis and increased serum thyroxine-binding globulin.

A housewife, 40 years of age, was admitted with dysesthesia of the extremities, muscle weakness, and attacks of adynamia and thirst. She had been taking a laxative for more than 20 years. On physical examination, blood pressure was 94/56 mmHg. Laboratory tests revealed thrombocytosis, low serum K and marked increases in both plasma renin activity and serum aldosterone. Serum TBG was increased. Serum gastrin was also markedly increased and could not be enhanced by exogenous secretin. Both angiotensin 11 loading test and noradrenalin loading test failed to increase blood pressure. Ammonium chloride loading to examine the disturbance of urinary acidification was abnormal in the short term test and borderline in the long term test. Following a diagnosis of pseudo-Bartter's syndrome induced by long term intake of laxative and repeated diarrhea, the administration of laxative was interrupted and potassium, indomethacin and spironolactone were administered. However, serum K remained low. Hypergastrinemia, thrombocytosis and a high serum TBG level also persisted, the causes of which remain unknown. This is the first reported case of pseudo-Bartter's syndrome associated with hypergastrinemia, thrombocytosis and increased serum TBG.

Adult↗

Determinants of magnitude of pseudohyperkalemia in thrombocytosis.

The release of potassium from platelets is a well-known cause of pseudohyperkalemia in thrombocytosis. In predicting the magnitude of pseudohyperkalemia associated with thrombocytosis, previous investigations considered only the amount of potassium released from platelets during blood clotting, although the increment in serum potassium during blood clotting depends on the quantity of potassium released from platelets as well as the volume of distribution of the released potassium, which is inversely proportionate to the hematocrit. The present study proposes a new mathematical formula to predict the magnitude of increase in serum potassium during blood clotting, and accuracy of this formula has been tested in a patient with thrombocytosis.

Humans↗

Isolated spleen agenesis: a rare cause of thrombocytosis mimicking essential thrombocythemia.

Thrombocytosis is a common feature of myeloproliferative disorders but may also result from various conditions including chronic iron deficiency, hemorrhage, chronic inflammation and splenectomy. We report two cases of secondary thrombocytosis caused by isolated and congenital asplenia, mimicking essential thrombocythemia. These two adult cases of spleen agenesis were unexpected. We conclude that in thrombocytosis without clinical evidence of splenomegaly, attentive screening of blood in search of Howell-Jolly bodies and abdominal ultrasonography should always be performed not only to detect mild spleen enlargement but also to make sure of the presence of this organ.

Diagnosis, Differential↗

Pseudohyperkalemia secondary to postsplenectomy thrombocytosis.

Hyperkalemia is a regularly encountered electrolyte abnormality. Less commonly recognized is pseudohyperkalemia. In vitro clotting results in the release of potassium from the formed elements of blood; this falsely elevates the serum potassium concentration. Usually attributed to thrombocytosis, leukocytosis, or hemolysis it is rarely reported in the postsplenectomy trauma patient. A 49-year-old man underwent splenectomy for a grade IV splenic injury. He developed an elevated serum potassium on postoperative day 16. His renal function remained normal, and an active search for causes of hyperkalemia failed to delineate a source for his elevated potassium. Pseudohyperkalemia was proposed as an etiology and confirmed by analyzing simultaneous serum (5.9 mEq/L) and plasma potassium levels (3.9 mEq/L). The serum potassium showed a concomitant rise with the evolution of the patient's postsplenectomy thrombocytosis. This is a case report of our patient and a literature review of this rarely reported and underestimated cause of a potentially serious electrolyte abnormality. We found through our patient that pseudohyperkalemia does occur in the postsplenectomy population and that this should be included in the differential diagnosis of any patient with an elevated serum potassium level and thrombocytosis.

Humans↗

Reactive thrombocytosis in children with upper urinary tract infections.

UNLABELLED: The relationship between reactive thrombocytosis and the level of urinary tract infections was studied in 48 children. Platelets were counted before, during and after treatment. Reactive thrombocytosis was noticed in 74% of children with upper and in 14% with lower urinary tract infections. A significant rise in the platelet count presented in another five children (15%) with upper urinary tract infections. CONCLUSION: Reactive thrombocytosis was found almost exclusively in the renal parenchymal infections, usually during the recovery phase.

Adolescent↗

[Blood coagulation changes in patients with post-splenectomy persistent thrombocytosis].

To clarify the possible role of persistent thrombocytosis after splenectomy as being a predisposing factor causing thromboembolism. Blood coagulation profiles were studied in 35 patients (20 M and 15 F, mean age 42 +/- 17.5) suffering from thrombocytosis (> 500,000/dl) who underwent splenectomy for non-malignant and non-traumatic diseases. Seventy healthy subjects acted as a control group. Tests were performed 6 months after the operation and for both groups (patients and controls) blood samples were collected for: platelets, fibrinogen, PT, APTT, AT III, plasminogen, F1 + 2, t-PA and DNA analysis for F V, F II and MTHFR. After one year all subjects were controlled for thrombocytosis, genomic abnormalities and venous thrombosis. All the analyses were performed according to the Statistical Package for Social Science. The significance of the differences in means was evaluated by non-parametric tests, differences with a P value < 0.05 being considered significant. Increased plasma levels of fibrinogen, D-dimer, F1 + 2 and PAI-1 were found in the patients compared with the control group. TPA was significantly lower in the patients than in the controls. At the one year follow-up, two patients with genetic polymorphism had suffered deep venous thrombosis. Our findings indicate that splenectomy contributes to abnormal platelet aggregation and endothelial cell activation with hypercoagulability.

Adult↗

[Successful treatment of primary myelofibrosis with thrombocytosis during pregnancy with alfa-interferon].

Primary myelofibrosis is predominantly a disease of old age, poor prognosis and no curable treatment. Thrombocytosis was observed in only 12% of patients. To our knowledge, there is only one reported case of a young woman with primary myelofibrosis who had a term pregnancy [1]. We report on a 29-year-old woman with thrombocytosis and medical history of two miscarriages in the last 2 years, the iirst at 30 weeks of gestation and the second at 27 weeks. Multiple placental infarctions were observed. She was without symptoms but with moderate splenomegaly 4.5 cm below left costal margin). The platelet count was 651 x 10(9)/L, WBC 7.2 x 10(9)/L with normal differential formula, and haemoglobin level 12 g/dl. Bone marrow biopsy showed fibrotic phase of primary myelofibrosis, with hyperplasia of megacaryocytes, decreased numbers of erythroid and granulocytic cells, and increased amounts of reticulin fibres. Cyctogenetic examination of the bone marrow showed normal female caryotype. Increased numbers of progenitors CFU-Mk, CFU-GM and BFU-E were observed in peripheral blood, and decreased numbers in bone marrow cultures. As the patient wished to become pregnant, the treatment with interferon-a (Roferon A) was started at a dose of 3 MU s.c., three times per week. The platelet count rapidly decreased at a level of 260-370 x 10(9)/L. The pregnancy was diagnosed 5 months later. At the 24 week of pregnancy, platelet count raised to 690 x 10(9)/l and the dose of interferon-a was augmented, 3 MU every day, until delivery. Foetal growth and placental circulation were monitored by serial ultrasonography. At the end of 34 weeks of pregnancy, it was noted that placental flow became insufficient, and after foetal lung maturity was stimulated with dexamethasone, Cesarean section was performed. Male baby was born, weighting 2000 g, with respiratory distress syndrome. This complication was successfully treated, and the child is now one year old, with normal growth and development. The mother is still on therapy with interferon-a, 3 MU, three times a week, and the last blood count was as follows: haemoglobin 10.7 g/dl, WBC 6.1 x 10(9)/L and platelet comt 437 x 10(9)/L. In conclusion, according to the clinical results of interferon-d in thrombocytosis and experimental studies which showed the absence of placental transfer of interferon-d, this therapy could be recommended to women with primary myelofibrosis who wish to have a baby.

Adult↗

Thrombocytosis and anaemia in women with recurrent ovarian cancer prior to a second-line chemotherapy.

BACKGROUND: To investigate the incidence and the prognostic value of platelet count and serum haemoglobin (Hb) in patients with recurrent ovarian cancer prior to second-line chemotherapy. MATERIALS AND METHODS: Clinical records were reviewed for 31 patients with recurrent ovarian cancer. Survival analysis was evaluated by univariate (Kaplan-Meier product limit method and log-rank test) analysis. We analysed the results for the overall survival. Anaemia and thrombocytosis were defined as a serum Hb level < 12 g/dl and as platelet count > 300,000/microL, respectively. RESULTS: Thrombocytosis and tumour anaemia were present in 55% and 42% of the patients, respectively. Tumour anaemia was of no prognostic value with respect to overall survival in our series. In patients with thrombocytosis, the median survival rate was reduced (p = 0.05). CONCLUSION: Our data suggest that a platelet count > 300,000/microL appears to be an adverse prognostic parameter in patients with recurrent ovarian cancer prior to a second-line chemotherapy.

Adult↗

Serum thrombopoietin levels in patients with reactive thrombocytosis due to lung cancer and in patients with essential thrombocythemia.

In patients with thrombocytosis normal to increased serum thrombopoietin (TPO) levels have been reported. The aim of this study was to investigate the relationship between serum TPO concentration, platelet number and plasma levels of fibrinogen in patients with reactive thrombocytosis (RT) due to lung cancer and in patients with essential (primary) thrombocythemia (ET). A total of 70 newly diagnosed patients with RT or ET (platelet counts >600 G/l) were studied: 45 with RT due to lung cancer (25 with non-small cell lung cancer, NSCLC and 20 with small cell lung cancer, SCLC), and 25 with ET. Twenty normal volunteers were used as controls. TPO was measured by immunoassay technique (ELISA). Mean serum TPO values in patients with RT due to lung cancer were statistically significantly higher than those in patients with ET or in controls. The highest platelet count was seen in patients with ET, and mean plasma fibrinogen levels were the highest in RT patients. In NSCLC patients mean serum TPO concentrations were higher (not statistically significant) than in SCLC, and a statistically significant relationship between TPO serum concentration and fibrinogen level was observed. No correlations between platelet counts and TPO serum concentrations were found. Our results indicate increased serum TPO levels in patients with thrombocytosis in lung cancer which may be related to the activity of neoplasms. In addition, it is postulated that the relatively low TPO values in patients with ET may result from a dysregulation of the feedback loop involved in platelet production.

Adult↗

Thrombocytosis in gynecologic malignancies.

Recent studies have addressed the prevalence and prognostic impact of thrombocytosis in various gynecologic and non-gynecologic malignancies. Thrombocytosis appears to be of prognostic value in certain patients with gynecologic malignancies. In this survey we review the published data and attempt to analyze the prognostic implications of thrombocytosis in patients with gynecologic malignancies.

Female↗

Thrombocytosis at an early stage of respiratory tract viral infection.

AIM: To determine whether thrombocytosis, a platelet count of more than 500 x 10(9)/l, occurs at an early stage of respiratory tract viral infection. METHODS: The medical records of 345 patients with respiratory syncytial virus (RSV), influenza, measles, adenovirus or human herpes virus 6 infections were retrospectively reviewed. RESULTS: The mean platelet count was significantly higher in RSV patients than in patients with other respiratory infections. Among the 29 patients with thrombocytosis, 24 (82.8%) had RSV infection. CONCLUSION: When thrombocytosis is positive at an early stage of respiratory tract infection, RSV should be taken into account as a causative agent.

Humans↗

Thrombosis and hemorrhage in thrombocytosis: evaluation of a large cohort of patients (357 cases).

We report clinical and laboratory findings in a large cohort of patients with thrombocytosis (357 cases). At the time of study, the patients showed a platelet number greater than 500 x 10(9)/L. The follow-up of patients ranged between 3 and 16 years. 123 patients were affected by polycythemia vera (PV), 97 by essential thrombocythemia (ET), 13 by chronic myeloid leukemia (CML) and 31 by myelofibrosis (MF). In 93 subjects, the thrombocytosis was reactive (ST). We found the highest incidence of thrombosis in PV patients, especially concerning the cerebro-vascular system; thrombosis, but in a lower percentage, was recognized in MF patients. Also, ET patients showed a number of thrombosis in peripheral arteries. Thrombosis of the coronary arteries were quite rare while 25% of MPD subjects showed peripheral vein thrombosis. We take into account that many patients showed thrombocytosis associated to one or more atherosclerotic risk factors. Hemorrhages were present especially in CML and in ET, but were not as frequent as thrombosis. The most common bleeding manifestations affected skin and mucosa. Hemorrhages after surgical procedures were also frequent. Gastro-intestinal bleeding was not strictly related to anti-aggregating therapy and occurred not only in PV but also in ET patients.

Adult↗

5-fluorouracil-induced thrombocytosis in mice is independent of the spleen and can be partially reproduced by repeated doses of cytosine arabinoside.

Experiments were done to characterize the pronounced and prolonged thrombocytosis that develops in mice during recovery from the marrow hypoplastic effects of a single injection of 5-fluorouracil (5-FU). Measurements were made of platelet and megakaryocyte numbers, size of mature megakaryocytes, marrow cellularity, hematocrit, and reticulocytes. Mice that had been splenectomized a month before receiving 5-FU displayed the same pattern of thrombocytosis as intact mice, so a role for the spleen in its genesis or persistence could not be identified. During recovery from two or three doses of cytosine arabinoside (Ara-C), given at intervals of 2 days, thrombocytosis and megakaryocytosis of similar magnitudes to those seen after 5-FU occurred. Bone marrow cellularity, hematocrits, and reticulocytes were identical after three doses of Ara-C or one dose of 5-FU. Megakaryocytes were initially macrocytic during recovery from the hypoplastic thrombocytopenia produced by 5-FU or Ara-C. These similarities to effects of repeated doses of Ara-C suggested that some of the effects of 5-FU were due to its prolonged action in vivo, which could cause sequential killing of proliferating cells. Abnormalities of megakaryocytes and platelets reversed promptly when normal or increased numbers of megakaryocytes and/or platelets were produced after Ara-C, but they persisted in mice that received 5-FU. This difference suggested that regulation of megakaryocyte progenitors was perturbed during recovery from 5-FU.

Animals↗