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The registry of patients treated with Thromboreductin (anagrelide) in the Czech Republic contains data concerning patients that have been treated using this drug since 2004. As of June 2009, the total number of patients was 549. The current analysis focused mainly on evaluation of anagrelide dosage needed to achieve a complete response in high-risk patients: reduction in platelet count to below 400 x 10(9)/l, which was also considered as reaching the therapeutic goal. The outcomes of the registry confirm that although anagrelide (Thromboreductin) is a very effective platelet-reducing agent, the administration of which is related to a low incidence of adverse effects and complications, the therapeutic goal is not achieved in all cases and or despite a quick treatment response, the therapeutic goal is achieved more slowly.

An 81-year-old woman was scheduled for gastrectomy due to advanced gastric cancer. Preoperative serum potassium concentration was 6.5 mEq x l(-1), and the operation was postponed. Renal function was normal and hematopathy was denied after bone marrow biopsy. But thrombocyte was 130.5 x 10(4) x mm(-3). Plasma potassium concentration was within normal ranges, and she was diagnosed as pseudohyperkalemia caused by thrombocytosis. Difference between serum and plasma potassium concentrations was more than 1 mEq x l(-1) throughout the surgery. We should take a blood plasma sample in patients with hyperkalemia combined with thrombosis, when renal function was within normal ranges and hemolysis was denied.

The purpose of this study was to review the incidence of extreme thrombocytosis (ExT) (platelet count 1,000,000/microL or greater) in trauma patients and to examine the role of antiplatelet agents in its treatment. The Los Angeles County Medical Center trauma registry was used to obtain injury demographics, medications, and daily platelet counts for injured patients 16 years of age or older admitted between July 2005 and February 2008. Of 6,985 total trauma patients admitted during the study period, 95 developed ExT (1.4%). Average age was 29 years (range, 16-63 years), 89 per cent were male, 44 per cent had penetrating trauma, and mean Injury Severity Score was 24 (range, 1-57). Of the 95 patients with ExT, 41 were treated with aspirin (43%) and 54 were not (57%). The two groups did not differ with regard to basic demographics, injury patterns, vitals on admission, or splenectomy rate (34 vs 20%, P = 0.13). After adjusting for maximum platelet counts and duration of ExT, there was no difference between the treated and untreated groups in terms of mortality, complications, and intensive care unit or hospital lengths of stay. The incidence of ExT is approximately 1.4 per cent in trauma patients. Antiplatelet therapy does not affect ExT patient outcome. Further prospective studies are warranted.

Aortic thrombus is rare in patients with essential thrombocytosis (ET), so the optimal treatment remains undefined. A 45-year-old man with history of ET, under chronic treatment with aspirin, presented to the emergency department complaining of acute onset in both the legs and abdominal pain. Physical examination revealed that both dorsalis pedis pulses were not palpable with cold and pale feet. His abdomen was soft and nondistended. The platelet count was 436 x 10(9)/L. The thoraco-abdominal computerized tomographic scanning revealed normal aortic diameter with supraceliac and infrarenal nonoccluding thrombus and infarction areas in spleen and left kidney. At the emergency department he presented with recurrent symptoms, losing bilateral posterior tibial pulses. A decision was made to perform a thoracoretroperitoneal incision. A longitudinal sequential aortotomy was performed in the distal thoracic and infrarenal aorta, and the thrombus was easily removed. Following this, he underwent bilateral crural thrombectomy and local intra-arterial thrombolytic therapy. The postoperative course was uneventful. The left toes were amputated because of necrosis. He was discharged and put on antiaggregants, anticoagulants and hydroxyurea. Aortic thrombus in patients with ET is unusual, but potentially lethal. There is complete relief from symptoms in recurrent cases following surgery. An appropriate medical treatment after intervention must be supported.

Hereditary thrombocythemia is a rare autosomal dominant disorder caused by mutations in either the thrombopoietin gene (TPO) or its receptor c-MPL. TPO mutations described so far lead to thrombopoietin overproduction through increased translation of m-RNA. Unilateral transverse reduction limb defects are usually sporadic and generally thought to be caused by vascular disruptions. Reports of inherited unilateral limb defects are extremely rare. In the present study, we describe a family with segregation of G185T TPO mutation in the 5' UTR region in 4 subjects with thrombocythemia. Three of these patients also present congenital transverse limb defects. Association of these events gives a strong hint of the in vivo involvement of thrombopoietin in vasculogenesis, confirming the role of TPO in human development of the hemangioblast, the embryonic progenitor of the hematopoietic and endothelial lineages. This is the first report showing that vascular disruptions could be secondary to specific gene derangements.

A rare case of cerebral venous thrombosis associated with thrombocythemia is reported. A 47-year-old man presented with headache, papilledema, and diplopia. Complete blood count showed an increased number of platelets. MR images and venography showed the thrombosis from the superior sagittal sinus (SSS) to the bilateral transverse sinuses (TS). The patient was treated with thrombolysis, continuous heparin infusion, and oral warfarin. On day 2, angiography demonstrated partial recanalization of the SSS and the left TS. Since CSF pressure was 30 cmH2O at day 11, a spinal drainage catheter was installed. Nevertheless, the patient presented with left hemiparesis, seizure, and loss of consciousness on day 12. Angiography revealed thrombosis from the SSS to the left TS and the right sigmoid sinus. Mechanical thrombolysis with a balloon was performed, and partial recanalization was obtained. In order to control the intracranial pressure, barbiturate coma therapy was performed for 1 week. On day 19 aspirin therapy was initiated become of continuous thrombocythemia. On day 25, the patient recovered completely. This case suggests that thrombocythemia may be able to cause refractory cerebral venous thrombosis.

We report a case of acute scrotal hematoma associated with idiopathic thrombocytosis. A 75-year-old man visited our hospital for the treatment of a left scrotal mass that had been increasing in size; the mass had developed after the puncture of left testicular hydrocele. The patient was diagnosed with acute scrotal hematoma on the basis of ultrasonography findings. The patient underwent an emergency operation for the removal of the hematoma. On 2 days after the surgery we noticed an increase in the size of the hematoma. The patient had a 4-year clinical history of idiopathic thrombocytosis for which he had not received any treatment. Although the platelet count was slightly high at the time of the operation, complete hemostasis did not occur because of the existence of platelet dysfunction. The second hematoma was treated conservatively. To our knowledge, this is the first case report on the acute scrotal hematoma associated with idiopathic thrombocytosis.

A patient with acute promyelocytic leukemia(APL)treated with all-trans retinoic acid(ATRA)and chemotherapy for remission induction developed marked thrombocytosis after bone marrow recovery. Thrombocytosis also occurred after post remission chemotherapies, although the degree of thrombocytosis gradually decreased. During thrombocytosis, plasma levels of interleukin-6(IL-6)were elevated while those of thrombopoietin(TPO)were not elevated. However, the plasma level of TPO was markedly elevated at the nadir after post remission chemotherapy. These findings suggest that in APL patients, thrombocytosis after treatment with ATRA and or chemotherapy may be caused by increased plasma levels of both of IL-6 and TPO.

Background: In up to 20% of patients with renal cell cancer (RCC) an inflammatory response consisting of low-grade fever, weight loss and an elevated ESR and CRP may occur with modest granulocytosis and thrombocytosis. Clinical and experimental data suggest a pathogenic role for tumour-derived cytokine production, especially interleukin-6., Case Report: A 79-year-old female with RCC presented with low-grade fever, weight loss and overt granulocytosis and thrombocytosis. Radiological examination revealed a right-sided renal tumour. During nephrectomy a gradient between the IL-6 levels in the renal artery and vein was demonstrated, providing direct evidence for in vivo production of IL-6 by the tumour affected kidney, which was confirmed by the demonstration of IL -6 in the tumour cells by immunohistochemical staining and in the supernatant of the homogenised tumour. Cytogenetic examination revealed complex abnormalities including a gain of chromosome 7. In addition we demonstrated production of IL-1alpha, IL-1beta, IL-8 and ICAM-1 in the tumour with systemic elevated levels of IL-6 and IL-8 with secondary increased serum G-CSF and TPO levels., Conclusion: We have provided direct evidence for the production of pro-inflammatory cytokines by renal cancer cells in a patient with RCC and a profound inflammatory response, with a central role of IL-6, probably due to a gain of chromosome 7. The extreme granulocytosis and thrombocytosis may have resulted from the secondary systemic production of G-CSF and TPO.

A 77-year-old man was admitted to our hospital with abdominal pain and ascites. He had an occupational history of working with asbestos. Abdominal CT showed multiple nodular lesions with enhancement by contrast medium in the cavity. Platelet counts, CRP and serum IL-6 level were increased. Biopsied materials obtained by laparoscopy showed oval cells with rich cytoplasm growing in an epithelial pattern. To clarify the characteristics of the cells, immunohistochemistry was performed. Calretinin and CK5/6 were positive, and CEA, S-100 protein, c-kit and CD34 were negative, result in confirmation of a diagnosis of malignant mesothelioma. Because IL-6, IL-6 receptor and VEGF were expressed markedly, the patient received chemotherapy for IL-6 suppression. During the treatment, thrombocytosis imploved satisfactorily.

Background: Patients with advanced malignancies for whom standard therapy is ineffective may participate in phase 1 trials. To gain a better understanding of the clinical features that could influence benefit versus risk, the authors of this report assessed prognostic factors and survival for patients who were referred to a phase 1 clinic focused primarily on targeted agents., Methods: The medical records of 200 sequential patients who presented to the Phase 1 Clinic at The University of Texas M. D. Anderson Cancer Center were reviewed, and their characteristics and survival were analyzed., Results: The median patient age was 58 years (range, 12-85 years), and 57% of patients were men. The median number of prior therapies was 4. Of 200 patients, 182 were treated on at least 1 phase 1 clinical trial. The median follow-up of surviving patients was 21 months, and the median overall survival was 9 months (95% confidence interval [CI], 7.4-10.8). In univariate analysis, the factors that predicted shorter survival were primary tumor in the gastrointestinal tract; a history of thrombosis, liver metastases, and elevated levels of serum lactate dehydrogenase; platelet count; carbohydrate antigen 9 (Ca19-9) and Ca-125 levels; aspartate aminotransferase levels, and alkaline phosphatase levels (P < .05 for each). In multivariate analysis, independent factors that predicted shorter survival were a history of thromboembolism (hazard ratio [HR], 2.38; 95% CI, 1.29-4.39; P = .005), platelets >or=440 x 10(9)/L (HR, 1.72; 95% CI, 1.12-2.65; P = .014), and the presence of liver metastases (HR, 1.51; 95% CI, 1.09-2.09; P = .013)., Conclusions: Patients who were referred to phase 1 studies had a short median survival (9 months). Patients with thrombocytosis, liver metastases, and a history of thromboembolism had worse outcomes. A prognostic score is proposed., ((c) 2009 American Cancer Society.)

Anemia is common in congestive heart failure (CHF) and is associated with an increased mortality and morbidity. The most likely causes of anemia are chronic kidney disease (CKD) and excessive cytokine production, both of which can cause depression of erythropoietin (EPO) production and bone marrow activity. The cytokines also induce iron deficiency by both reducing gastrointestinal iron absorption and iron release from iron stores located in the macrophages and hepatocytes. Iron deficiency can cause thrombocytosis which might also contribute to cardiovascular complications in both CHF and CKD and is partially reversible with iron treatment. Thus attempts to control this anemia will have to consider both the use of erythropoiesis-stimulating agents (ESA), such as EPO, as well as oral and, probably more importantly, intravenous (IV) iron. The many studies on anemia in CHF patients treated with ESA and oral or IV iron, and even with IV iron without ESA have up to now shown a quite consistent positive effect on hospitalization, fatigue, shortness of breath, quality of life, exercise capacity, and beta-natriuretic peptide reduction, in the absence of increased cardiovascular damage related to the therapy. Adequately powered long-term placebo-controlled studies of ESA and/or IV iron are currently being carried out and their results are eagerly awaited., (Copyright 2009 S. Karger AG, Basel.)

Thrombocytosis is a common feature of chronic myeloproliferative disorders (MPD) and may be asymptomatic or associated with transient microvascular vaso-occlusive symptoms or large vessel arterial or venous thrombosis. Failure of either the hematocrit or the platelet count to correlate with thrombotic events is a peculiar conundrum of the MPDs. Asymptomatic thrombocytosis in young MPD patients with no cardiovascular risk factors does not require treatment. It is also undisputed that lowering the platelet count reduces the incidence of microvascular events in MPD patients. At the same time, no study to date has demonstrated that platelet count reduction prolongs survival in MPD patients. Agents such as hydroxyurea, busulfan, IFN-alpha and anagrelide, have been used to reduce an elevated platelet count and decrease thrombohemorrhagic events in at-risk patients with thrombocytosis associated with an MPD. When treatment is required, it makes sense to use drugs that are not myelotoxic or mutagenic. Based on the Primary Thrombocythaemia 1 study, hydroxyurea is the treatment of choice for thrombocytosis-associated transient ischemic attacks. However, hydroxyurea does not prevent venous thrombosis, is not more effective in preventing arterial thrombosis than anagrelide and its long-term safety is not established. Therefore, unless curative therapy is planned, one should use the least myelotoxic agent when platelet count reduction is required. In this regard, anagrelide can be considered a first-line drug. With regard to long-term safety of anagrelide, the EMEA has required close monitoring of the safety points identified in future Periodic Safety Update Reports and in a Post Authorisation Safety Study in the EU, which will focus especially on cardiovascular events and acute leukemia. In this article, we review anagrelide pharmacology, the physiology of thrombopoiesis, the differential diagnosis of thrombocytosis and the management of patients with an elevated platelet count.

Patients with reactive thrombocytosis are generally asymptomatic and platelet counts of up to 1,000,000/microL are seen in this disorder. However, in a small proportion of cases platelet counts may be in the range generally seen in Clonal Thrombocytosis (CT). In elderly patients or those with symptomatic atherosclerosis or thrombotic disease or immobility, thrombosis may occur even with reactive thrombocytosis. We report a case of a rare presentation of Reactive Thrombocytosis with digital gangrene in an elderly lady. She was evaluated for thrombocytosis and was given supportive treatment after which she clinically improved.

To elucidate the role of thrombocytosis, alone or in combination with standard (age, previous cardiovascular events) and novel (leukocytosis, JAK2(V617F) mutational status) risk factors, in the cardiovascular events of essential thrombocythemia (ET), we analyzed a cohort of 1063 patients. We found that a platelet count at diagnosis greater than 1000 x 10(9)/L was associated with significantly lower rate of thrombosis in multivariable analysis and, if combined with leukocytes less than 11 x 10(9)/L, pointed to a "low-risk" category with a rate of thrombosis of 1.59% of patients/year. On the contrary, the highest risk category (thrombosis rate, 2.95% of patients/year) was constituted of patients with leukocytosis, lower platelet count, and a JAK2(V617F) mutated genotype in most cases (77% vs 26% in the low-risk group), independently from standard risk factors. These data challenge the theory that elevated platelet count increases thrombosis risk in ET and suggest prospective clinical trials to support this hypothesis.

Background and Purpose: Reactive thrombocytosis (RT) is usually a benign process and is not associated with thrombotic or hemorrhagic events, Summary of Case: We report a case of a young man who suffers a stroke caused by RT, which was secondary to splenectomy, iron deficiency, and infection., Conclusions: : Although rarely documented, RT can be the cause of a major vascular event.

Essential thrombocytosis (ET) remains a rare cause of aortic thromboembolic disease. Management options vary based on the state of clinical presentation and range from observation and medical management to immediate operative intervention. We report a case of ET causing "trash foot" from an aortic thrombus. The patient was administered appropriate cytoreductive therapy and eventually underwent an aortic interposition graft. The various management strategies are discussed.

Relationship between thrombocytosis and poor prognosis has been reported in lung cancer. However, the majority of previous studies included many advanced stage and small cell lung cancer patients. Few studies focused on resectable non-small cell lung cancer patients. In the present study, therefore, consecutive 240 non-small cell lung cancer patients who received surgical resection were reviewed retrospectively, and investigated the survival impact of preoperative platelet count. In our results, the frequency of preoperative thrombocytosis was only 5.83% (14/240). The 5-year survival of patients with and without thrombocytosis was 28.87% and 63.73%, respectively. Both univariate and multivariate analyses indicated the independent prognostic impact of thrombocytosis. The present study is the first evaluation of prognostic effect of thrombocytosis in patients with resectable non-small cell lung cancer. Preoperative platelet count was a prognostic factor for resectable non-small cell lung cancer patients.

We present the case of a 13 year-old boy who had chronic sclerosing osteomyelitis of the right femur in whom S. aureus was confirmed as the etiologic agent. Typical picture was apparent after one year period in which there were two hospital admissions. Only soft tissue infection of the right thigh was misdiagnosed in the first admission in spite of gammagraphic evidence of bone recording at the distal right femur. In the second admission, formal bone infection with a special pattern was diagnosed as a chronic sclerosing osteomyelitis, since the following criteria were addressed: 1) clinical features of infection, 2) laboratory features for infection, 3) low-virulence bacteriae, 4) an unusually high organic and tissue reaction which involved thrombocytosis in this patient, 5) bone sclerosis and hypertrophic bone response, 6) a very slow production of pus, and 7) chronicity.

Aim: To test the possible neuroprotective effect of early high-dose erythropoietin-alpha (Epo-alpha) after out-of-hospital cardiac arrest (OHCA)., Methods: A matched control study. Following resuscitation with mild hypothermia after OHCA, participants received a first dose of Epo-alpha followed by four additional injections within 48 h (40,000 IU intravenously each injection). Plasma Epo-alpha levels were measured at different time points. Outcome and adverse events were assessed up to day 28 and were compared with those of matched-paired controls., Results: In all 18 participants received Epo-alpha and were compared with 40 matched controls. Pharmacokinetic variables were similar to those previously reported for healthy people or for persons treated with usual dosages of Epo. At day 28, survival rates among the Epo-treated group and the controls (55% versus 47.5%, p=0.17) and rates of full neurological recovery (55% versus 37.5%) did not differ significantly. Incidences of thrombocytosis in the Epo-treated group and controls were 15% and 5%, respectively; an arterial vascular thrombosis was observed in one case (5%) from the Epo-treated cohort., Conclusions: Among victims of OHCA treated with Epo-alpha and hypothermia, we observed a high survival rate, with no minor cerebral sequels but potential haematological side effects. Future studies of Epo should pay particular attention to these findings.

A female patient with Down Syndrome (DS) had neonatal thrombocytosis with platelet counts exceeding 2,000 x 10(3)/microL and transient myeloproliferative disorder (TMD). Platelet counts remained elevated the first 2 months of life. A translocation located between chromosomes 17 and 11 was observed. We describe a patient with thrombocytosis and TMD showing an 11q13 translocation. The leukocytosis and thrombocytosis improved after an exchange transfusion., ((c) 2007 Wiley-Liss, Inc.)

Rapid oxygen consumption by markedly increased numbers of hypermetabolic leukocytes in leukaemic patients resulting in the apparent diagnosis of hypoxaemia on arterial blood gas analyses is termed leukocyte larceny. In the present report, a case of polycythaemia vera, extreme thrombocytosis, normal leukocyte counts and arterial hypoxaemia in the absence of clinical, radiological or physiological evidence of lung disease is described. This pseudohypoxaemia case was established by pulse oximetry, as well as by incubation of a blood specimen with potassium cyanide, and became less significant after the use of cytoreductive agents showed a proportionate increase in arterial oxygen tension as platelet counts decreased on serial arterial blood gas analyses. The present case report demonstrates spurious hypoxaemia due to extreme thrombocytosis and shows that, beside significant leukocytosis, even markedly elevated platelet counts can cause larceny of arterial blood oxygen.

Acquired sideroblastic anemia with unilineage dysplasia (WHO RARS) is a clonal stem cell disorder characterized by erythroid dysplasia, mitochondrial accumulation of mitochondrial ferritin, defective erythroid maturation and anemia. A fraction of these patients also show elevated platelet counts; since 2001 this has been defined as RARS with marked thrombocytosis (RARS-T). It has recently been described that around half of RARS-T patients, along with a small subset of other MDS and mixed myelodysplastic/ myeloproliferative disorders, carry the JAK2 mutation, and that MPL mutations are found in single patients. Clinically, RARS-T patients show features of both RARS, essential thrombocythmia (ET) and to some extent also myelofibrosis. However, the degree of anemia and overall survival is more similar to RARS than myeloproliferative disorders. The occurrence of JAK2 mutations and features of ET in RARS is too frequent to be the result of chance only, and it is possible that this link may provide a key to an increased understanding of the genetic abnormalities causing ring sideroblast formation.

Little is known about the management of coronary thrombosis in myeloproliferative disease. The occurrence of myocardial infarction in myeloproliferative disease is mostly attributed to coronary thrombosis due to hyperviscosity and thrombocytosis. We presented three cases of acute myocardial infarction associated with polycythemia vera in one patient (male, age 33 years) and essential thrombocytosis in two patients (male, ages 36 and 46 years). None of the patients had diabetes mellitus, hypertension, hyperlipidemia, or a positive family history. One patient with early presentation received thrombolytic therapy, and all the patients were treated with aspirin, beta-blocker, angiotensin 2 receptor blocker, statin, low-molecular-weight heparin, parenteral nitrate, and clopidogrel for acute coronary syndrome, and hydroxyurea for essential thrombocytosis. Control angiographies showed patent coronary arteries in all the cases.

The recognition and treatment of stroke in children is challenging as there are fundamental developmental differences in children compared to adults. A young boy presented with sudden weakness of right side of body followed by unconsciousness and convulsion that was not preceded by any history of fever or trauma. Neurological examination revealed upper motor neuron lesion in the right extremities. CT scan showed diffuse hypodense area in fronto-parietal regions. Complete blood count and iron profile evaluated iron deficiency anemia with thrombocytosis. Thrombosis resulting from thrombocytosis secondary to iron deficiency anemia was considered as etiological explanation of stroke in this young child.

A 57 year-old woman was admitted to our hospital because of large hepatocellular carcinoma (HCC). Laboratory data showed hypercholesterolemia, thrombocytosis and hypoglycemia. Based on several examinations and the clinical course, we diagnosed HCC with paraneoplastic syndrome. It is rare that 3 paraneoplastic phenomena occur in a patient with HCC. In particular, paraneoplastic thrombocytosis is very rare in paraneoplastic syndrome associated with HCC.

Objective: Thrombocytosis (platelet count greater than 400,000/mm3) has been identified as a poor prognostic factor in many cancers. The objectives of the present study were to determine the incidence of thrombocytosis in advanced epithelial ovarian cancer and the cut off point level of platelet count in Thai patients determining thrombocytosis condition and association between survival time in both thrombocytosis condition (platelet count greater than 400,000/mm3 and 305,000/mm3)., Design: Descriptive study., Material and Method: One hundred and twenty epithelial ovarian cancer patients were included between January 2004 and December 2005. Their medical records were retrospectively reviewed and data was analyzed using chi2, Fisher's exact test, and Student t- test. The level of platelet counts determining thrombocytosis condition in Thai patients were record and analyzed by ROC curve. Survival was analyzed by the method of Kaplan and Meier., Results: When using the standard criteria of thrombocytosis (platelet counts greater than 400,000/mm3), the incidence was 35% (42/120 cases). Among advanced-stage patients, such incidence was 56.7% (42/74 cases). The criteria for diagnosis of thrombocytosis in the present study was platelet counts greater than 305,000/ mm3. When using such criteria, the overall incidence of thrombocytosis was 49.1% (59/120 cases) and was 72.97% (54/74 cases) in advanced stage. Patients with preoperative thrombocytosis were found to have higher CA - 125 level, greater prevalence of ascites, and worse prognosis., Conclusion: The incidence of thrombocytosis in Thai patients with advanced epithelial ovarian cancer was 56.7% and 72.9% when using platelet count level greater than 400,000/mm3 and 305,000/mm3 respectively, which was higher than that of the early stage. This implies that thrombocytosis is probably a marker of cancer aggressiveness.

Thrombocytosis, which is defined as a platelet count greater than 400 platelets/nl, has been found to be an independent predictor of shorter survival in various tumors. Release of growth factors from tumors has been proposed to increase platelet counts. Preoperative platelet counts and other clinical and hematological parameters were reviewed from the records of 153 patients diagnosed between 1999 and 2004 with histologically confirmed glioblastoma in order to evaluate the prognostic significance of preoperative thrombocytosis in these patients. The relationship between thrombocytosis and survival was initially analyzed in all patients regardless of further therapy. Univariate log-rank tests showed that the median survival time of 29 patients with preoperative thrombocytosis (19%) was significantly shorter (4 months; 95% confidence interval [95% CI], 3-6 months) compared to 124 patients with normal platelet counts (11 months; 95% CI, 8-13 months; p = 0.0006). Multivariate analysis (Cox proportional hazards model) confirmed preoperative platelet count, age, prothrombin time, and activated partial thromboplastin time to be prognostic factors of survival (all p < 0.05). In a subset of patients (only operated patients with radiation therapy with or without additional chemotherapy), survival was likewise significantly shorter when preoperative thrombocytosis was diagnosed (6 months; 95% CI, 4-12 months) compared to patients with normal platelet count (13 months; 95% CI, 11-15 months; p = 0.0359). In multivariate analysis, age, platelet count, preoperative prothrombin time, and degree of tumor resection retained significance as prognostic factors of survival (all p < 0.05). The results of our study demonstrate preoperative thrombocytosis to be a prognostic factor associated with shorter survival time in patients with glioblastoma.

An unusual histiocytic dermatitis associated with a lymphoplasmacytic and histiocytic panniculitis appears to represent a previously undescribed disease process. A 56-year-old woman presented with a 5 year history of a violaceous, maculo-papular rash primarily on her legs. It began approximately 8 months before therapy for thrombocytosis. The rash subsequently progressed to form confluent patches and plaques on her torso and arms. The clinical impression was of disseminated granuloma annulare, but multiple biopsies from different sites did not confirm this. Histologic examination revealed a diffuse proliferation of histiocytic cells in the dermis, without well-formed granulomas or necrobiosis. The cells had large, focally irregular nuclei with prominent nucleoli, and were associated with scattered, often bizarre multinucleate giant cells. Immunohistochemistry demonstrated the histiocytic cells to be positive for S100 and CD68 and negative for CD1a. Perivascular siderophages as well as a lymphoplasmacytic and histiocytic panniculitis accompanied the process. The striking cutaneous changes are of unknown etiology but appear to be previously undescribed.

Thrombocytosis is not a frequent event in myelodysplasia (MDS) and is observed mainly in 5q- syndrome and MDS/myeloproliferative (MPD) overlap syndromes. The pathogenetic mechanism of thrombocytosis in 5q- has not been fully elucidated to-date. Bortezomib is a proteasome inhibitor which seems to be effective in MDS. We present here the first case in the literature with MDS/MPD syndrome, sole 5q- anomaly and thrombocytosis in which bortezomib administration normalized platelet count, produced a major erythroid response, and reduced levels of interleukin-6 (IL-6) and TNF-alpha while increased levels of IL-4 in the bone marrow plasma. The study of such cases will reveal the exact role of bortezomib in the management of MDS/MPD.

The objective of this study was to review the prevalence and prognostic impact of pretreatment thrombocytosis in patients with oral squamous cell carcinoma (OSCC). Medical records of 253 patients with OSCC were retrospectively reviewed. The relationship between the platelet count, TNM stage, histologic differentiation, recurrence rate, metastasis, and survival were analyzed. Pretreatment thrombocytosis was found in 61 (24.1%) of 253 patients and was associated with aggressive tumour growth (p=0.015), lymph node metastasis (p=0.009), and distant metastasis (p=0.001). Association with tumour recurrence fell just short of statistical significance (p=0.058). Patients with preoperative thrombocytosis had a poorer survival than those with normal platelet counts (p=0.004). Multivariate analysis using Cox's proportional hazards model indicated that thrombocytosis was an independent predictor of shorter survival (RR 2.48, 95% CI 1.30- 4.73, p=0.006).

Vascular manifestations are the main clinical complication of essential thrombocythemia (ET). They include arterial thrombosis (30-40% of patients), venous thrombosis (5%), and ischemia due to microcirculatory disorders. Their incidence is highest at disease onset and diminishes gradually thereafter. The pathophysiology of ET involves dysmegakaryocytopoiesis, leading to platelet, leukocyte and vascular endothelial cell activation. The recent discovery of the V617F mutation of the JAK2 tyrosine kinase in 50-60% of patients with ET defined a new subgroup resembling polycythemia vera. This review examines biological findings and their correlation with the risk of thrombosis. Until now, stratification of the vascular risk has relied on a clinical case-control study showing that thrombotic and vascular complications are more frequent in patients over 60 and those with a history of thrombosis. These criteria, along with a rapid increase in thrombocytosis (>1500 G/L) leading to an increase in the bleeding risk, define a high-vascular-risk subgroup of patients warranting cytoreductive therapy. Although many biological markers of dysmegakaryocytopoiesis and cellular hyperactivation have been linked to an increase in the thrombotic risk, none is available for large-scale prediction of an intermediate vascular risk. The role of the JAK2 V617F mutation itself is controversial. Whatever the ET subgroup, antiplatelet therapy is largely used, based on the results of the ECLAP prospective controlled trial that showed a statistically significant reduction in thrombotic complications in patients receiving aspirin for polycythemia vera, a very similar myeloproliferative disorder.

Essential thrombocytosis (ET) is an uncommon pediatric hematologic disorder that can result in thrombotic complications, including cerebral venous sinus thrombosis (CVST). Although CVST associated with ET is exceedingly rare, it can be devastating to the patient. We here report a pediatric case of CVST associated with ET. The patient was treated with hydroxyurea and warfarin, which was later replaced by low-dose aspirin. Platelet counts were well controlled after 16 months of follow-up, and no further thrombotic events occurred. Mucositis was the main adverse effect of treatment.

We report a case of prenatally diagnosed intracranial hemorrhage and hydrops in the fetus of a mother with a past history of surgical and medical treatment for gastric lymphoma and having high platelet counts thereafter. To the best of our knowledge, such a complication of maternal thrombocythemia has not been described in the literature. In our opinion, the possible pathophysiology of the disease is based on placental insufficiency due to infarctions and related fetal platelet dysfunction, leading to intracranial hemorrhage with subsequent hydrops fetalis. The trigger in this event appears to be trauma to the maternal abdomen. Certain measures for high-risk mothers such as avoidance of trauma to the abdomen and platelet-lowering medications like interferon-alpha may be useful for preventing such fetal complications., (Copyright 2007 S. Karger AG, Basel.)

Operating on patients with abnormal coagulation is a challenge frequently faced by surgeons. Achieving haemostasis perioperatively can involve bleeding points that would not ordinarily present a problem with intact clotting function. Here we present two women with localised wound bleeding following a gynaecological surgery in the presence of a clotting disorder. Haemostasis was successfully achieved with tropical use of tranexamic acid. These two cases illustrate a novel use for this antifibrinolytic agent. We suggest that there is a role for topical use of tranexamic acid in perioperative haemostasis in patients with clotting disorders.

Purpose: Thrombotic risk is increased in patients with cancer and further potentiated by chemotherapy. We assessed whether early hemostatic alterations could represent a risk factor for thrombosis in patients undergoing chemotherapy for lung cancer., Patients and Methods: Forty-nine patients receiving chemotherapy for unresectable, locally advanced, or metastatic lung cancer were included. Blood cell count, prothrombin time, partial thromboplastin time, fibrinogen, antithrombin, D-dimers, protein C, protein S, homocysteine, folates, vitamin B12, and activated protein-C resistance were measured at day 0, +7, +15, and +21 of the first chemotherapy cycle. Factor V Leiden and FII G20210A mutations were assessed. Follow-up of patients was prospectively performed for thrombosis during all chemotherapy treatment. Factor V Leiden and FII G20210A frequency were the same as in controls., Results: Average basal levels of prothrombin time, partial thromboplastin time, antithrombin, protein C, protein S, folates, vitamin B12, and activated protein-C resistance were normal and remained stable during chemotherapy. Homocysteine, D-dimers, and fibrinogen basal levels were high but remained constant after chemotherapy. An average reduction in platelet count was recorded at day +14 in all patients after a striking increase (5.2-fold) at day +21 in the group of patients treated with gemcitabine (P < 0.001). Four thrombotic events were recorded. In all cases, thrombosis occurred within 10 days of the second or the following chemotherapy cycle with gemcitabine and cisplatin. One patient had Factor V Leiden heterozygous disease., Conclusion: Our findings exclude alterations of coagulation inhibitors or activation of disseminated intravascular coagulopathy/fibrinolysis as factors that induce chemotherapy-related thrombosis in lung cancer. The temporal relationship between thrombocytosis at the time of chemotherapy administration and the clinical onset of thrombotic events suggests that thrombocytosis plays a role in triggering thrombotic complications.

Patients with atrial fibrillation taking either indirect anticoagulant acenocumarol or most often prescribed antiaggregant aspirin were followed for 1 year. The results have shown that therapy with acenocumarol lowers content of D-dimer, prevents formation and promotes lysis of left auricular thrombi and lowers risk of development of ischemic stroke in patients with atrial fibrillation and high risk of thromboembolism. Therapy with aspirin in a dose providing maximal suppression of platelet function, does not lower D-dimer levels, does not promote lysis of left auricular thrombi and is inferior to acenocumarol in prevention of ischemic stroke.

We present a 75-year-old Japanese man with essential thrombocytosis presenting nephrotic syndrome. Proteinuria developed soon after the patient was given a diagnosis of essential thrombocytosis and, 4 years later, it increased to a nephrotic range. Renal biopsy revealed one third of the obtained glomeruli totally sclerotic and the other glomeruli showed a marked thickening of the glomerular basement membrane and mild mesangial proliferation. Remarkable widening of the subendothelial space was evident on electron microscopy. Increased expression of platelet derived growth factor receptor beta was detected in the mesangium and interstitium by immunohistochemistry. Abnormal platelet activation in myeloproliferative disease has been shown to contribute in glomerulosclerosis by releasing various growth factors and cytokines including PDGF. Considering his clinical course and the pathological findings, the probable risk factor for developing severe endothelial damage and glomerulosclerosis is due to the persistence of high platelet count and platelet abnormality.

An 89-year-old woman with essential thrombocythemia and chronic respiratory failure was admitted for treatment of hemoptysis. She stopped taking aspirin and was given tranexamic acid. Though her hemoptysis improved, respiratory failure suddenly worsened. As a result of various examinations and laboratory findings, acute exacerbation of chronic pulmonary thromboembolism was diagnosed. Though there was the risk of recurrence of hemoptysis, she started taking aspirin again. Her respiratory failure improved but hemoptysis did not reappear. Thrombosis and hemorrhage are common complications of essential thrombocythemia, however, pulmonary thromboembolism is a rare complication. There is a possibility that the exacerbation of this case was caused by tranexamic acid as well as rest and cessation of aspirin. If a patient with essential thrombocythemia bleeds, we should be careful when using tranexamic acid.

The aim of the study was to determine the incidence and etiology of thrombocytosis in an adult Turkish population. The medical records of 2000 patients were reviewed retrospectively to determine (i) the etiology of elevated platelet counts, (ii) additional laboratory parameters (i.e., complete blood counts), and (iii) the presence of thromboembolic complications. Within 5 years, 174 678 platelet counts had been performed for 124,340 patients. Of the 124,340 patients, 2000 (1.6%; mean age, 55.2 +/- 17.4 years; range 16-94 years; male-to-female ratio, 3.6:1 [1570:430]) had one or more platelet counts of 500 x 10(3)/mm3 or higher during the study period. Secondary thrombocytosis was the most frequent cause of an elevated platelet count and occurred in 1934 cases (96.7%). Infection was the most common cause of secondary thrombocytosis, occurring in 1001 patients (50.1%). Compared with secondary thrombocytosis, primary thrombocytosis was significantly associated with a higher rate of thromboembolic complications. It is concluded that a high platelet count may have both diagnostic and therapeutic implications. Secondary thrombocytosis is a common finding and mostly secondary to infection. Primary thrombocytosis has a higher risk for thromboembolic events than does secondary thrombocytosis.