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Marked thrombocytosis following relapse of acute myeloblastic leukemia associated with development of translocation (2;14) (p13;q32).

Thrombocytosis is a rare finding in acute myeloblastic leukemia (AML). Here, we describe a patient with AML who relapsed with marked thrombocytosis. The patient was initially diagnosed as having AML (M4) with a low platelet count. The patient was started on combination chemotherapy including high-dose etoposide and achieved complete remission. However, the patient relapsed six months later with an extremely high platelet count (72.5 x 10(4)/microl). Cytogenetic analysis at relapse revealed the development of t(2;14)(p13;q32). Despite the repeated combination chemotherapy, the patient died with progressive disease. This case suggests that the additional chromosomal aberration t(2;14)(p13;q32) may be related to abnormal thrombocytosis in AML.

Adult↗

Marked thrombocytosis in a child with advanced myelodysplastic syndrome.

Myelodysplastic syndromes (MDS) are clonal disorders characterized by ineffective hematopoiesis with rare occurrence in childhood. Conversely to adult affected patients, refractory anemia with ringed sideroblasts and the 5q-syndrome, which are associated with thrombocytosis are virtually absent in the pediatric age group. We describe the case of an 1-year-old boy with advanced MDS, specifically refractory anemia with excess of blasts who presented with leukocytopenia and anemia but marked thrombocytosis at diagnosis. Thrombocytosis resolved without therapy. This case illustrates the relationship between MDS and myeloproliferative disorders.

Anemia, Refractory, with Excess of Blasts↗

Elevated serum thrombopoietin and interleukin-6 concentrations in thrombocytosis associated with inflammatory bowel disease.

Reactive thrombocytosis is a typical feature in inflammatory bowel disease (IBD). The question arose as to whether the normal negative feedback regulation of the concentration of thrombopoietin (TPO) in blood was altered in IBD patients. We measured serum immunoreactive TPO in 30 patients with active IBD, 29 patients with inactive IBD, and 56 healthy controls. The results were related to platelet and leukocyte counts and to the serum concentration of interleukin 6 (IL-6). Patients with active IBD exhibited significantly increased TPO levels (medians 112 pg/ml vs. 90 pg/ml in controls, p < 0.05) in association with thrombocytosis (428 platelets/nl blood vs. 241 platelets/nl blood in controls), leukocytosis, and increased IL-6 levels (12.9 pg/ml vs. 2.5 pg/nl in controls). In patients with inactive IBD, only platelets (322/nl) and leukocytes were above normal. Although the observation of increased TPO and IL-6 levels provides an explanation for the occurrence of thrombocytosis in IBD, the pathogenetic mechanisms underlying the elevated TPO level still need to be identified.

Adolescent↗

Thrombocytosis in intensive care.

We conducted a retrospective study of platelet count in 226 patients admitted for critical care over a 5-month period, to explore the incidence of thrombocytosis and its relation to admission category, duration of ICU stay and outcome. Our findings indicate that thrombocytosis is not rare in ICU patients. At least one platelet count greater than 450x10(9) litre(-1) was found in 21.7% of patients and was associated with lower ICU mortality (P=0.003), lower hospital mortality (P=0.006), but longer duration of ICU stay (P<0.0001). Thrombocytosis may serve as an independent predictor of favourable outcome in ICU patients.

Adult↗

Reactive thrombocytosis and stroke following cardiopulmonary bypass surgery: case report on three patients.

Reactive thrombocytosis following cardiopulmonary bypass surgery is generally considered to be a benign condition which is transient and does not require specific therapy. We describe three patients who developed stroke in association with reactive thrombocytosis in the late recovery period following cardiopulmonary bypass surgery. No evidence of embolic or cerebrovascular disease was detected in any patient. Analysis of a larger group of patients is required in order to determine whether reactive thrombocytosis may contribute to the pathogenesis of stroke in some patients following cardiopulmonary bypass surgery.

Blood Coagulation Tests↗

The effect of thrombocytosis on serum potassium and phosphorus concentrations.

Thrombocytosis is a cause of falsely elevated serum potassium concentrations, and phosphorus concentrations may be similarly distorted. Because plasma concentrations are not affected, the difference between the serum and plasma concentrations detects spurious elevations. The authors, in this study, sought to determine the degree of correlation between thrombocytosis and false elevations in serum potassium and phosphorus concentrations. Ninety-one general, medical/surgical patients with elevated platelet counts were identified by laboratory reports. Subjects were stratified into blocks by platelet count. Samples were obtained simultaneously for serum and plasma potassium and phosphorus concentrations and complete blood counts. The serum minus plasma concentrations for potassium (Kdiff) and phosphorus (Pdiff) were calculated and analyzed against each other and the platelet count by linear regression. A control group of 20 subjects with normal platelet counts was used to verify laboratory results with literature values. The Kdiff and Pdiff values in the control group very closely approximated literature values of 0.4 mmol/L and 0.08 mmol/L, respectively. Platelet count was a moderate predictor of Kdiff, r2 = 0.55 (p = 0.00001). Kdiff exceeded the upper limit of control at a platelet count of approximately 600 x 10(9)/L. Platelet count also correlated with Pdiff, r2 = 0.31 (p = 0.00001). Additionally, Kdiff correlated with Pdiff, r2 = 0.39 (p = 0.00001). Thrombocytosis is associated with false elevations in measured serum potassium and phosphorus concentrations. Additionally, the magnitude of elevations in potassium and phosphorus concentrations appear to be related.

Adult↗

Thrombocytosis after major lower extremity trauma: mechanism and possible role in free flap failure.

Microvascular thrombosis and free flap failure are complications of free tissue transfer for coverage of lower extremity soft-tissue and bony defects despite appropriate vessel selection and adherence to meticulous technique. Increased rates of flap failure have been associated with reconstruction performed between 3 days and 6 weeks after injury, as well as in patients with thrombocytosis. We have found that serum platelet levels rise significantly after lower extremity injury. It is our theory that a circulating mediator or cytokine is released in response to injury, inducing the thrombocytosis. Twenty-one patients with Gustilo grade IIIb and IIIc injuries were studied prospectively. Serum was collected throughout the postinjury period. Platelet count, leukocyte count, hemoglobin concentration, and hematocrit were determined. Samples were also subjected to a platelet aggregation study as well as enzyme-linked immunosorbent assay for interleukin-3, interleukin-6, interleukin-11, and granulocyte macrophage-colony-stimulating factor. Megakaryocyte growth and development factor enzyme-linked immunosorbent assay and a myleoproliferative leukemia virus-transfected cell line assay for thrombopoietin were performed. Bone marrow was studied with flow cytometric analysis. Mean initial platelet count was 196,000 per cubic millimeter. There was an initial 26% decline to 140,000 per cubic millimeter, followed by an increase to 361% of baseline on day 16. No significant variations in serum leukocyte count or hemoglobin concentration were seen. Spontaneous and induced platelet aggregation responses were normal. Interleukin-6 was detected at elevated levels. However, interleukin-3, interleukin-11, granulocyte macrophage-colony-stimulating factor, and thrombopoietin were not measurable. Marked megakaryocytosis was seen on bone marrow analysis. Interleukin-6 may, therefore, play a role in the mechanism of thrombocytosis. We suggest that because patients with complex bony injuries of the leg experience platelet elevations that peak approximately 2 weeks after injury, microvascular free flap reconstructions should be considered high risk during this time period.

Adult↗

Extreme thrombocytosis as a sign of coeliac disease in the elderly: case report.

Increase in the number of blood platelets to over 1,000,000/mm3 in elderly patients is generally considered secondary to a myeloproliferative or neoplastic disease. To report the case of an elderly woman hospitalized for extreme thrombocytosis associated with severe anaemia, who was found to be suffering from coeliac disease. The patient, aged 83 years, was hospitalized presenting with fatigue. Laboratory tests showed microcytic hypochromic anaemia (haemoglobin 4 g/dl) and extreme thrombocytosis (platelet count 1,400,000/mm3). Physical examination was normal, with the exception of marked thinness. There was no evidence of macroscopic bleeding from the gastrointestinal or genitourinary tracts. She had never suffered from gastrointestinal problems and had no family history of gastroenterological diseases. Oesophagogastroduodenoscopy and histology of the gastric and duodenal mucosa evidenced atrophic gastritis and an adenomatous polyp. The duodenal mucosa showed total villous atrophy, suggesting the diagnosis of coeliac disease. Antiendomysial IgA and anti-transglutaminase IgA antibodies were also positive. Colonoscopy was negative. An ultrasound examination of the abdomen was normal, and the spleen was within the normal range. A peripheral blood smear showed no alterations in erythrocyte morphology typical of hyposplenism due to coeliac disease. The platelet count decreased rapidly after blood transfusions, when both serum iron and ferritin levels were still below normal limits. Furthermore, we observed a significant inverse correlation between the platelet count and haemoglobin concentration (r = -0.94, P < 0.003). Platelet count and red blood cell count normalized after 2 months of a gluten-free diet; the haemoglobin concentration was also normal at this time. After 1 year of following a gluten-free diet, the patient remained well and had no complaints. There were no gastrointestinal disturbances. All haematological parameters were within normal limits. Intestinal biopsies showed normal villi and crypts without inflammatory infiltration of the lamina propria. This case shows that the association of haematological signs--extreme thrombocytosis and severe anaemia--considered in an elderly patient to be typical of myeloproliferative disorders or neoplastic conditions can be due to coeliac disease; thus, coeliac disease must also be considered among the possible diagnoses.

Aged↗

Thrombocytosis and hyposplenism in an infant with fetal hydantoin syndrome.

An infant boy with fetal hydantoin syndrome was evaluated for the finding of thrombocytosis. Delayed splenic maturation was identified by a decreased splenic uptake of 99mTc sulfur colloid and by an increased number of pitted erythrocytes at 6 months of age. We speculate that the patient's thrombocytosis may be related to delayed maturation of splenic function and conclude that hyposplenism and secondary thrombocytosis may be associated with fetal hydantoin syndrome.

Abnormalities, Drug-Induced↗

Uncontrolled thrombocytosis in chronic myeloproliferative disorders.

A retrospective study was performed to examine the natural course of uncontrolled thrombocytosis associated with chronic myeloproliferative disorders. Thirty-eight patients with polycythaemia rubra vera (PV), myelofibrosis/myeloid metaplasia (MM), chronic myelogenous leukaemia (CML) or essential thrombocythaemia (ET) had platelet counts greater than 1000 X 10(9)/1 and were followed closely for a total of 246 patient years. Eleven of the patients experienced haemorrhagic episodes. Bleeding was twice as frequent in patients over 59 years old as in those younger and no bleeding occurred in those less than 51 years of age. There was no correlation between frequency of bleeding and extent of thrombocytosis. Bleeding events occurred concurrently with use of anti-inflammatory agents in 32% of episodes. The gastrointestinal tract was the most frequent site. Documented thrombotic events occurred in three patients, two of whom had PV with haematocrits greater than 53%. This study suggests that the thrombocytosis of myeloproliferative processes may pose a less serious threat than originally thought and that aggressive lowering of the platelet count may not be indicated in all cases.

Adult↗

The determination of spontaneous megakaryocyte colony formation is an unequivocal test for discrimination between essential thrombocythaemia and reactive thrombocytosis.

Spontaneous colony formation from bone marrow megakaryocyte progenitors (BMsCFU-Mk) was studied in 24 patients with essential thrombocythaemia (ET), 20 patients with reactive thrombocytosis (RT), 20 patients with polycthaemia rubra vera with thrombocytosis (PRVtr), 16 patients with chronic myeloid leukaemia with thrombocytosis (CMLtr) and 18 normal control subjects (C). The culture medium which was used in the methylcellulose assay in vitro contained 30% of plasma from a single patient with hereditary haemochromatosis. Remarkable BMsCFU-Mk growth was recorded in all patients with ET but in none with RT or in C. BMs-CFU-Mk were present in 11/20 patients with PRVtr and 7/16 patients with CMLtr. Spontaneous bone marrow erythroid progenitors (BMsBFU-E) were also determined in these patients. BMsBFU-E were found in 21/24 patients with ET and none in the patients with RT and C. All patients with PRVtr and one patient with CMLtr showed BMsBFU-E. We conclude that our implementation of the in vitro methylcellulose assay allows the BMsCFU-Mk to be used as an unequivocal test for discrimination between ET and RT which has not been shown in previously published studies. In addition, we present evidence that in 10 patients BMsCFU-Mk and/or BMsBFU-E growth in the test persisted after long-lasting haematological remission.

Adult↗

Ringed sideroblasts with thrombocytosis: an uncommon mixed myelodysplastic/myeloproliferative disease of older adults.

Sideroblastic anaemia with ringed sideroblasts and marked thrombocytosis, hereupon referred to as ringed sideroblasts with thrombocytosis (RST), is a provisional entity in the 2001 World Health Organisation classification scheme. This retrospective study identified 16 patients with RST over a 7-year period. Proposed diagnostic criteria include a sustained platelet count > 500 x 10(9)/l, > or = 15% ringed sideroblasts, < 3% bone marrow blasts, and normal conventional cytogenetics. The median age was 76 years with eight males and eight females. With a median follow-up of 41 months, RST patients had a median overall survival of 71 months, comparable with refractory anaemia having ringed sideroblasts, but less favourable than essential thrombocythaemia. Thus far, no patients with RST are known to have died of disease-related causes. Patients with ringed sideroblasts and/or thrombocytosis need to be carefully evaluated for a variety of haematological diseases that may confer significantly different prognoses.

Adult↗

Cancer of gallbladder with severe thrombocytosis.

An autopsy case of severe thrombocytosis associated with cancer of gallbladder is described as the first case in the literature. A 78-year-old male patient was admitted to the hospital with abnormal hepatic functions on August 6, 1975. Laboratory examination revealed platelet count of 5,664,000/cu mm, anemia, leukocytosis and bilirubinemia. Jaundice was progressive and the patient died after a month. Severe thrombocytosis persisted throughout the course. Main autopsy findings were cancer of gallbladder with metastasis to the liver, fibrosis of spleen and purulent bronchopneumonia. A possible mechanism of unusually severe degree of thrombocytosis associated with the present case is discussed in light of the literature.

Adenocarcinoma↗

Megakaryocyte ploidy in thrombocytosis: improved microdensitometric measurements with a new image analysis system.

Megakaryocyte (MK) nuclear deoxyribonucleic acid (DNA) content was measured on a new image analysis system. Feulgen-stained bone marrow aspirate smears were analysed from 9 patients with thrombocytosis. Average optical density (OD) of stained nuclei was evaluated by pixel discrimination over 128 grey levels. Projected nuclear area was delineated manually. The product of these two parameters gave an index of nuclear DNA content. Neutrophils were used as 2N reference cells. Reproducibility of OD, nuclear area and their product was excellent for individual cells (CV less than 2.0% for MKs, less than 4.0% for neutrophils). The average CV for DNA content of 18 groups of 10 neutrophils was 5.5% (range 3.0-9.7%). A significant linear regression existed between MK nuclear area and DNA content (p much less than 0.001) for 627 MKs in essential thrombocythaemia (ET) and 346 MKs in reactive thrombocytosis (RT). Compared with RT, more 8N and 64N MKs were seen in ET (p less than 0.05). 128N MKs were unique to ET. Image analysis of MK ploidy may assist the clinical discrimination between primary and secondary thrombocytosis.

DNA↗

An abnormal pattern of multiple platelet function abnormalities and increased thromboxane generation in patients with primary thrombocytosis and thrombotic complications.

Platelet aggregation (PA) induced by ADP, collagen and epinephrine, plasma levels of beta-thromboglobulin (beta TG) and thromboxane B2 (TXB2) and serum TXB2 generation were studied in 11 patients with primary thrombocytosis (7 with essential thrombocythaemia and 4 with polycythaemia vera) and compared with 16 healthy subjects. 5 patients suffered from peripheral vascular ischaemia and another 3 had venous thrombosis, but none had bleeding complications. The patients showed an abnormal pattern of platelet function and of thromboxane generation distinct from the healthy subjects in three aspects. a) Shape change was 5-26 times greater, the lag-time of collagen PA was 2.3-2.9 times longer and the extent of epinephrine PA was nil or very low. ADP- or collagen-induced PA was also reduced (p less than 0.02). b) Plasma TXB2 generation (corrected to a normal platelet concentration) stimulated by the three PA inducers was within the range of the healthy subjects in spite of the reduced extent of PA. c) Plasma beta TG level and serum TXB2 generation (both corrected to a normal platelet concentration) were 2.9-7.1 times higher (p less than 0.001) indicating enhanced in vivo platelet activation and possibly increased thrombin generation. These abnormalities were not detected in another 4 patients with secondary thrombocytosis. The abnormal pattern of platelet function and thromboxane generation can be a useful laboratory method in the evaluation of patients with primary thrombocytosis. It might also explain the thrombotic complications which occurred in 8 of the patients in a manner such that increased or normal TXB2 generation overcomes the reduced extent of PA. In this respect, the pronounced serum TXB2 synthesis might be a marker of intravascular thrombosis.

Female↗

Therapeutic plateletpheresis in a case of symptomatic thrombocytosis in chronic myeloid leukemia.

Extreme thrombocytosis is a frequent feature in myeloproliferative disorders which can predispose a person to thrombotic complications. As opposed to other myeloproliferative disorders, symptomatic thrombocytosis is rare in chronic myeloid leukemia. We describe a second case report of chronic myeloid leukemia (Ph chromosome positive) in a patient in chronic phase on hydroxyurea who presented with sudden onset digital cyanosis of the left hand, giddiness, headache and malaise due to extreme thrombocytosis. A 67% global reduction in the platelet count from 1553 x 10(9)/L to 513 x 10(9)/L after two therapeutic plateletpheresis procedures was seen. There was simultaneous improvement in all symptoms except cyanosis on the tip of the middle finger that progressed to dry gangrene. Dramatic reduction in the platelet count and ablation of symptoms by therapeutic plateletpheresis is an effective therapy and should begin as soon as possible.

Cyanosis↗

Factitious hyperkalemia in dogs with thrombocytosis. The effect of platelets on serum potassium concentration.

To determine the effect of platelet count on the accurate assessment of serum electrolyte concentrations, simultaneous platelet counts and electrolyte determinations were performed on serum and plasma from 40 dogs. Dogs were grouped according to platelet count as follows: thrombocytopenic (less than 150,000/microliters), normal (150,000 to 600,000/microliters), or thrombocytotic (greater than 600,000/microliters). Serum potassium concentration was significantly higher than plasma potassium concentration in normal dogs (mean difference, 0.63 +/- 0.17 mEq/l) and in dogs with thrombocytosis (mean difference, 1.55 +/- 0.73 mEq/l). This difference in potassium concentration between serum and plasma was positively correlated with platelet count (r2 = 0.86). In the blood of dogs with thrombocytosis, the serum-plasma potassium difference was further increased when the time period between blood collection and separation of serum or plasma from cells was lengthened. Differences between serum and plasma concentrations of sodium or chloride were not seen in any platelet group. These results suggest that a portion of the measured serum potassium concentration is released from platelets during the clotting process. In fact, profound elevations in serum potassium concentrations can occur factitiously in dogs with thrombocytosis. Therefore, the actual concentration of potassium in blood is determined more accurately by measuring the plasma concentration rather than the serum concentration of this electrolyte.

Animals↗

Reactive thrombocytosis in pulmonary tuberculosis.

The incidence of reactive thrombocytosis in active pulmonary tuberculosis was studied in 122 patients. Thrombocytosis was common, platelet counts often exceeding 1 X 10(12)/1. A significant inverse correlation was noted between the mean platelet volume and the platelet count (r = -0.54, p less than 0.0001). Interval estimation suggested that this relation was non-linear. Further studies were done in a small group of six patients. Platelet survival was considerably shortened, the platelets aggregated excessively in vitro, serum concentrations of thrombopoiesis stimulating activity were raised, and serotonin uptake and release were within normal limits. The degree of thrombocytosis correlated significantly with the degree of inflammation measured by the erythrocyte sedimentation rate (r = 0.40, p less than 0.003) and serum C-reactive protein concentration (r = 0.35, p less than 0.008).

Arachidonic Acids↗