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Establishment and characterization of a new human mesothelioma cell line (T-85) from malignant peritoneal mesothelioma with remarkable thrombocytosis.

A mesothelioma cell line, termed T-85, was established from a patient with malignant peritoneal mesothelioma and remarkable thrombocytosis (1.4 x 10(6)/mm3). Electron microscopically, two types of mesothelioma cells have been characterized; the major type of cells with dense-cored granules in the cytoplasm and the minor one with evenly dense granules. Immunologically, the cells showed staining for interleukin-6 (IL-6), cytokeratin, collagen type IV, vimentin, laminin, fibronectin and Factor VIII-related antigen. Quantitation by ELISA revealed a high concentration of IL-6 in T-85 cell culture supernatants. RT-polymerase chain reaction of T-85 cells showed two positive bands of cDNA at 628 and 251 base pairs indicating the constitutive expression of IL-6 and IL-6 receptor mRNA. Moreover, prominent pro-platelet process formation activity in T-85 cell culture supernatants indicated the presence of a thrombopoietic activity due mainly to IL-6 but not the c-Mpl ligand or erythropoietin. However, the fact that 15% of PPF activity remained in the supernatants treated with anti-IL-6 antibody indicated the presence of another thrombopoietic substance. T-85 is so far the first mesothelioma cell line derived from a case with remarkable thrombocytosis.

Base Sequence↗

Reactive thrombocytosis after caesarean section and vaginal delivery: implications for maternal thromboembolism and its prevention.

OBJECTIVE: To assess the duration and severity of reactive thrombocytosis after caesarean section and vaginal delivery. DESIGN: A prospective cohort study. SETTING: A large teaching hospital. METHODS: Women admitted for delivery at the Leicester Royal Infirmary were recruited into the study. The platelet count was measured before delivery and postnatally on days 3, 8, 12, 16, 20 and 24. Women who had antepartum haemorrhage, postpartum haemorrhage and those delivered by instrumental delivery were excluded from the study. Sixty-five were recruited, and 45 completed the study, 20 of whom were delivered by a normal vaginal delivery and 25 by caesarean section. A random effects model was used to compare platelet counts within and between the two groups to assess the severity and the timing of reactive thrombocytosis. RESULTS: There were no statistically significant differences in booking and pre-delivery platelet counts between the two groups (mean values 248.4 x 10(9)/L and 245 x 10(9)/L in the normal vaginal group and 269.4 x 10(9)/L and 251.6 x 10(9)/L in the caesarean section group, respectively). Postnatally, a rise in the platelet count was noted in the normal vaginal delivery group, reaching statistically significant peak values, compared with booking and pre-delivery at days 8 and 12 of the postnatal period (mean value 365.8 x 10(9)/L; P < 0.001 and 369.4 x 10(9)/L; P < 0.001 respectively). In the caesarean section group, the platelet count was raised to a statistically significant high value, compared with booking and pre-delivery at day 8 of the postnatal period. The platelet count peaked at days 12 and 16 of the postnatal period (mean value 522.5 x 10(9)/L; P < 0.0001 and 526.5 x 10(9)/L; P < 0.0001, respectively) and remained significantly higher than booking and predelivery values for 24 days after the caesarean section. There was a greater rise in the platelet count in the caesarean section group compared with the vaginal delivery group. The platelet counts in the caesarean section group were significantly higher than these in the normal vaginal delivery group from day 12 to day 24 of the postnatal period. CONCLUSION: A significant rise in platelet count occurred eight to twelve days after normal vaginal delivery and caesarean section. The increase in platelet count continued to rise for 16 days after caesarean section, and it stayed significantly higher for more than 24 days after the delivery.

Cesarean Section↗

A comparison of mice in rebound-thrombocytosis with platelet-hypertransfused mice for the assay of thrombopoietin.

Rebound-thrombocytosis and platelet hypertransfusions were compared as methods of preparing assay animals for the measurement of thrombopoietin (TSF). In immunothrombocythaemic mice, the amount of 35S incorporation into the platelet mass after injections of a standard dose of TSF was related to the length of time after rabbit anti-mouse platelet serum (RAMPS) injection. After 2 platelet transfusions, however, there was no decrease in 35S incorporation values of mice with time after injections of control or TSF-containing substances. When platelet counts were made 3 days after the last platelet transfusion, the counts decreased with the number of transfusions. Mice in rebound-thrombocytosis were responsive to TSF as evidenced by higher platelet counts (P less than 0.05) and increased 35S incorporation into platelets (P less than 0.005), whereas mice made thrombocytotic by platelet transfusions were not. Assuming that increased platelet counts induced by the different techniques affect assay mice only by inhibiting blood cell production by haematopoietic cells, these data are consistent with the hypothesis that sensitivity to TSF depends upon the proliferative state of the megakaryocytic precursor population.

Animals↗

Intermittent melphalan in the treatment of essential thrombocytosis with haemorrhage or thrombosis.

178 episodes of essential thrombocytosis with symptoms of haemorrhage or thrombosis, were treated in 15 patients with melphalan (5 mg/m2 orally during 4 d). An average reduction in the platelet count of 77% was achieved by oral melphalan in 14 responding patients. 1 patient appeared to be refractory to oral therapy, but a decrease of the thrombocyte count was achieved after intravenous administration of melphalan. All responding patients experienced a relief of the thrombocytosis-associated clinical symptoms. Reduction of the thrombocyte count persisted for 3-4 wk.

Adolescent↗

Familial thrombocytosis in infancy presenting with a leukaemoid reaction.

Familial thrombocytosis (FT) is a hereditary disorder probably involving the regulation of megakaryopoiesis. This report is the first documented case of FT in infancy. The clinical course was complicated by a leukaemoid reaction which lasted for several months, in combination with failure to thrive and hepatosplenomegaly. At the age of 5 years the patient, with the exception of thrombocytosis, is healthy and without medication.

Humans↗

Acute infantile thrombocytosis and vitamin K deficiency associated with intracranial haemorrhage.

A 5-week-old breast-fed girl presented unconscious and convulsing with heavily blood-stained CSF under increased pressure. This was associated with oozing from venepuncture sites, a grossly prolonged prothrombin time, and a raised platelet count. The prothrombin time became normal 18 hours after she had been given parenteral vitamin K and a transfusion of fresh plasma and red cells, but the thrombocytosis persisted. A moderate communicating hydrocephalus also remained and was treated, and one year later health and development appeared normal. The thrombocytosis resolved after a few weeks and has not recurred.

Acute Disease↗

Secondary thrombocytosis.

To estimate the incidence and causes of secondary thrombocytosis in children, a 12 month study of all patients attending a children's hospital and discovered to have a platelet count over two times the upper normal limit (> 800 x 10(9)/l) was undertaken. Data so obtained were analysed both separately and together with those from two previous studies to gain as broad a perspective as possible. Of 7916 children who had platelet counts during the study period, 36 (0.5%) produced a value > 800 x 10(9)/l; there were 19 boys and 17 girls. There was a preponderance of young infants (median age 13 months). Twenty seven of the 36 had some sort of associated infection, bacterial in 18 and viral in nine. The other nine were either recovering from anti-neoplastic chemotherapy (n = 6), were post-operative (n = 2), or simply iron deficient (n = 1). Combining these patients with those described in previous studies allowed a review of 139 unselected children with very high platelet counts. Fifty three (38%) had infections, 29 (20%) had traumatic or surgical tissue damage, 16 (11%) had malignant disease undergoing chemotherapy or surgery, and 13 (9%) had connective tissue or autoimmune disorders. Secondary thrombocytosis is not rare and is most frequently seen in very young infants after infection. It can arise in a wide variety of other circumstances including rebound from myelosuppression, iron lack, or as part of an acute phase response. It is clinically unimportant in terms of morbidity and requires no treatment other than that for the primary condition.

Adolescent↗

Thrombocytosis in rheumatoid arthritis. Recurrent arterial thromboembolism and death.

A patient with rheumatoid arthritis complicated by excessive thrombocytosis and recurrent thromboembolic events is presented. The platelet count correlated well with disease activity and thrombosis occurred when thrombocytosis was marked. The patient died from massive thrombosis of the aorta despite treatment with anticoagulants, corticosteroids, and azathioprine.

Adult↗

Thrombocytosis associated with enzyme replacement therapy in Gaucher disease.

We describe a patient with an intact spleen and moderately severe symptoms of Gaucher disease in whom, after initiation of (low-dose) enzyme replacement therapy (ERT), thrombocytosis (720 x 10(9)/l) was documented. Checking the International Gaucher Registry database revealed that this patient is the only nonsplenectomized patient of more than 1,000 treated patients to experience ERT-induced thrombocytosis. Platelet counts dropped immediately after the discontinuation of ERT.

Adult↗

Effects of interleukin-1 and tumor necrosis factor on megakaryocytopoiesis: mechanism of reactive thrombocytosis.

We studied the effects of interleukin-1 (IL-1) and tumor necrosis factor (TNF) on mouse megakaryocytopoiesis to evaluate the role of these cytokines in reactive thrombocytosis associated with inflammation. Injections of IL-1 or TNF to mice induced a significant increase in the megakaryocyte progenitor cell (CFU-Meg) count in the spleen. When IL-1 and TNF were injected simultaneously, the splenic CFU-Meg count was remarkably increased compared with mice injected with either IL-1 (p < 0.003) or TNF (p < 0.001) alone. On the other hand, neither IL-1 nor TNF showed any megakaryocyte-potentiating or -stimulating effects in vitro. In the sera obtained 4 h after administration of IL-1, TNF or both, high megakaryocyte potentiating activities were found. Furthermore, an extremely high level of IL-6 was detected in the serum after administration of both IL-1 and TNF. These results strongly suggest that IL-1 and TNF stimulate megakaryocytopoiesis indirectly via other cytokine(s) induced from accessory cells, and that increased levels of IL-1 and TNF play important roles in the development of reactive thrombocytosis caused by inflammation.

Animals↗

Thrombocytosis in quiescent chronic granulocytic leukaemia after vincristine and 6-mercaptopurine therapy.

In an attempt to retard the appearance of blastic transformation 11 patients recently diagnosed with chronic granulocytic leukaemia were given courses of vincristine and 6-mercaptopurine after stabilization of the disease by busulfan. In 4 of the patients a marked thrombocytosis developed shortly after the administration of such courses. When we compared the clinical and biological features at the moment of diagnosis, the patients in whom thrombocytosis developed after vincristine and 6-mercaptopurine courses showed higher platelet counts and a smaller spleen size than the other ones, although no statistical significance was reached. A possible thrombocytopoietic effect of vincristine is discussed.

Adolescent↗

Myocardial infarction complicating postsplenectomy thrombocytosis, with early left ventricular mural thrombus formation and cerebral embolism--a case report.

Thrombocytosis is a rare cause of ischemic cardiovascular and cerebrovascular events in patients with intrinsically normal coronary and cerebral vasculature. This report details the occurrence of inferior wall myocardial infarction (MI) consequent upon postsplenectomy thrombocytosis in a thirty-four-year-old man with angiographically normal coronary arteries. The MI was complicated by early left ventricular mural thrombus formation and embolic cerebral infarction. Combined anticoagulant and antiplatelet therapy was required to prevent the recurrence of ischemic events.

Adult↗

Thrombocytosis in pediatric HIV infection.

Thrombocytopenia has been extensively reported in association with HIV infection. Twenty-four children (6%) from a cohort of 400 children with platelet counts >500,000/mm(3) were reviewed. All had symptomatic disease and 10 (42%) patients died. In 4 children the platelet count exceeded 700,000/mm(3) and in 1 patient the platelet count was 1.5 million/mm(3). There were no thrombotic complications, and no specific therapy was required for the thrombocytosis. Thus HIV-1 infection, a chronic viral infection, is another etiologic agent for thrombocytosis and is associated with severe disease.

Child, Preschool↗

Thrombocytosis in children with Hemophilus influenzae meningitis.

A retrospective study of thrombocytosis in children with Hemophilus influenzae meningitis was performed. Forty-five percent of patients had a platelet count greater than 500 X 10(9)/l during hospitalization. The mean platelet count was 284 X 10(9)/l on admission, and gradually increased to 648 X 10(9)/l on day 11 of hospitalization. These results document that thrombocytosis is common among children with H. influenzae meningitis and suggest that it is probably a recovery phenomenon.

Child↗

Polyarteritis presenting with thrombocytosis and central retinal vein thrombosis.

We report a case of polyarteritis in a 54 year old woman who presented with marked thrombocytosis and acute blindness in one eye secondary to central retinal vein thrombosis. She also developed bilateral pulmonary infiltrates and renal failure. The diagnosis was confirmed by histological changes in the renal biopsy. Treatment with immunosuppressives, plasma exchange and antiplatelet drugs led to rapid clinical improvement and recovery of renal function and prevented further thromboembolic episodes. Plasma exchange and antiplatelet drugs should be considered in polyarteritis group of systemic vasculitis especially in the presence of thromboembolic complications or thrombocytosis.

Female↗

Safety and efficacy of picotamide, a dual anti-thromboxane agent, in patients with thrombocytosis and a previous thromboembolic event: a 1-year observational study.

Patients with chronic myeloproliferative disease are at increased risk of both thromboembolic and haemorrhagic complications. Cerebral thrombosis is a common cause of death in myeloproliferative disease patients. Picotamide is a new anti-platelet drug sharing a dual anti-thromboxane activity: inhibition of thromboxane A2 synthase and thromboxane A2 receptor antagonism. Picotamide inhibits in vitro and ex vivo platelet aggregation induced by different agonists. Interestingly, in vitro studies show that picotamide is able to increase prostacycline biosynthesis. In the clinical setting, picotamide treatment induces only a slight prolongation of bleeding time. The safety and efficacy of picotamide long-term treatment in 15 patients with essential thrombocytosis and a positive history of previous thromboembolic events was evaluated. After 12-month treatment with picotamide no patients suffered from thrombotic events and only one minor and transient bleeding episode was observed. This observational long-term trial shows that picotamide treatment in patients with thrombocytosis at high risk of thrombotic events is safe and well tolerated. Picotamide did not increase the risk of bleeding in these patients, while at the same time, no thrombotic events were observed during the 1-year treatment.

Adult↗

Agranulocytosis, plasmacytosis, and thrombocytosis followed by a leukemoid reaction due to acute acetaminophen toxicity.

OBJECTIVE: To describe a patient who developed hepatotoxicity, reactive plasmacytosis with thrombocytosis and life-threatening agranulocytosis, followed by a leukemoid reaction, apparently caused by acute acetaminophen toxicity. SETTING: University-affiliated hospital. CASE SUMMARY: A 19-year old white women who took an overdose of acetaminophen developed hepatotoxicity and reactive plasmacytosis with thrombocytosis and life-threatening agranulocytosis, followed by a leukemoid reaction. Symptoms, signs, and laboratory findings regressed with symptomatic therapy during the follow-up period. CONCLUSIONS: We believe that acute acetaminophen toxicity was responsible for these hematologic abnormalities. This profile of hematologic adverse effects associated with acetaminophen toxicity has not been reported previously.

Acetaminophen↗

Lessons to be learned: a case study approach: pseudohyperkalaemia due to thrombocytosis in a case of tubo-ovarian abscess.

The case described here is that of a 48-year-old lady who presented with abdominal pain and fever; at a later stage she was found to have hyperkalaemia of uncertain origin. Blood examination revealed there to be marked elevation of the platelets (thrombocytosis) on some occasions. It was then realised that there was correlation between the platelet levels and serum potassium values. During the clotting process the release of potassium from the increased number of platelets caused the serum potassium to be elevated on account of an in vitro effect. The important point is that the raised serum potassium levels were not due to an in vivo phenomenon and, therefore, the patient did not need treatment for this; however, the presence of thrombocytosis was itself a clue to the diagnosis--which was eventually recognised as being due to an infection. At operation a tubo-ovarian abscess was discovered to be the cause of the problem.

Abscess↗