Aetiology and clinical significance of thrombocytosis: analysis of 732 patients with an elevated platelet count

Grießhammer, Martin; Bangerter, Markus; Sauer, Theodor C.; Wennauer, Roman; Bergmann, Lars; Heimpel, Hermann

doi:10.1046/j.1365-2796.1999.00452.x

Cited by 238 publications

(195 citation statements)

References 23 publications

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“…A recent study investigating etiology and clinical significance of thrombocytosis found a higher incidence of venous and arterial thrombosis in patients with primary thrombocytosis as compared to patients with secondary thrombocytosis (12.4% vs. 1.6%). The authors conclude that postsplenectomy thrombocytosis is not associated with an increased risk for hemostatic complications [20]. Thus thrombocytosis by itself does not seem an indication to initiate anti-coagulation or antiplatelet or plateletlowering therapy unless it is being used as secondary prophylaxis.…”

Section: Discussionmentioning

confidence: 95%

Thromboembolic complications after splenectomy for hematologic diseases

Mohren

Markmann²,

Dworschak³

et al. 2004

American J Hematol

101

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Thromboembolic complications following splenectomy for hematologic diseases occur in up to 10% of patients and may range from portal vein thrombosis (PVT) to pulmonary embolism (PE) and deep vein thrombosis (DVT). Up to now there exist no recommendations for the duration and intensity of prophylactic anticoagulation, which usually follows local institutional protocols. We report on three consecutive patients with severe portal vein thrombosis and/or pulmonary embolism—one with fatal outcome—7 to 35 days after splenectomy for autoimmune hemolytic anemia, immunothrombocytopenia, and indolent lymphoma, respectively. Incidence and pathophysiology of thromboembolic events (TE) in this patient group as well as prophylactic anticoagulation will be discussed, including a review of the current literature on this topic. Am. J. Hematol. 76:143–147, 2004. © 2004 Wiley‐Liss, Inc.

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Section: Discussionmentioning

confidence: 95%

Thromboembolic complications after splenectomy for hematologic diseases

Mohren

Markmann²,

Dworschak³

et al. 2004

American J Hematol

101

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“…Thus, under some circumstances, regulation of hepatic production may also be a mechanism for controlling TPO levels. Thrombocytosis in humans is observed in hospitalized patients with infection, cancer, and chronic inflammation (21,22), and this is frequently associated with increased circulating TPO (23). The liver mediates many of the protein changes recognized during the acutephase response, and pathways present in the liver that produce reactive changes in TPO may provide a mechanistic explanation for these clinical observations.…”

Section: Discussionmentioning

confidence: 99%

Deficiency of 5-hydroxyisourate hydrolase causes hepatomegaly and hepatocellular carcinoma in mice

Stevenson

Hyland²,

Zhang³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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With the notable exception of humans, uric acid is degraded to (S)-allantoin in a biochemical pathway catalyzed by urate oxidase, 5-hydroxyisourate (HIU) hydrolase, and 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline decarboxylase in most vertebrate species. A point mutation in the gene encoding mouse HIU hydrolase, Urah, that perturbed uric acid metabolism within the liver was discovered during a mutagenesis screen in mice. The predicted substitution of cysteine for tyrosine in a conserved helical region of the mutantencoded HIU hydrolase resulted in undetectable protein expression. Mice homozygous for this mutation developed elevated platelet counts secondary to excess thrombopoietin production and hepatomegaly. The majority of homozygous mutant mice also developed hepatocellular carcinoma, and tumor development was accelerated by exposure to radiation. The development of hepatomegaly and liver tumors in mice lacking Urah suggests that uric acid metabolites may be toxic and that urate oxidase activity without HIU hydrolase function may affect liver growth and transformation. The absence of HIU hydrolase in humans predicts slowed metabolism of HIU after clinical administration of exogenous urate oxidase in conditions of uric acid-related pathology. The data suggest that prolonged urate oxidase therapy should be combined with careful assessment of toxicity associated with extrahepatic production of uric acid metabolites.N-ethyl-N-nitrosourea mutagenesis | uric acid | 5-hydroxyisourate hydrolase | hepatocellular carcinoma | thrombopoietin U ric acid is the product of purine metabolism. In most mammals, uric acid, or urate, the form that predominates in vivo, is further metabolized to (S)-allantoin (1, 2). In humans and some higher primates, the urate oxidase gene is dysfunctional because of the introduction of premature stop codons during recent evolution (3). A nonfunctional urate oxidase enzyme causes a relative excess of uric acid in humans compared with most other vertebrate species. Because uric acid is relatively insoluble, humans are susceptible to diseases resulting from precipitation of uric acid such as gout and kidney stones as well as urate nephropathy associated with the tumor lysis syndrome. Chronic hyperuricemia in humans has also been linked to the development of cardiovascular disease and hypertension (4, 5).It is unclear why humans have evolved this block in uric acid metabolism during evolution, but suggested theoretical advantages of increased levels of circulating uric acid include its role as a potent antioxidant offering protection from cancer and aging (6) and its potential function in maintenance of adequate blood pressure during periods of low salt intake (7).The components of the full metabolic pathway that converts urate to allantoin in lower mammals have only recently been identified (1). Although it was originally thought that urate oxidase was the sole enzymatic component of this pathway, recent studies have established that conversion of uric acid to allantoin occurs by sequential ch...

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“…Although TPO production does not appear to be altered in the liver in response to alterations in platelet counts, it is less certain whether altered production of the hormone is responsible for the thrombocytosis seen in in¯ammatory conditions. It is clear that platelet counts rise in response to in¯ammation (Griesshammer et al, 1999), and with the development of reliable immunoassays of TPO, 50 ± 500% increases in blood TPO concentrations have been found in thrombocytotic post-surgical patients and in individuals with Crohn's disease and other in¯ammatory conditions (Cerutti et al, 1997;Uppenkamp et al, 1998;. Thus, the regulation of TPO production and levels may be rather complex.…”

Section: The Regulation Of Thrombopoietin Levelsmentioning

confidence: 99%