Defective Platelet Aggregation and Increased Platelet Turnover in Patients with Myelofibrosis and Other Myeloproliferative Diseases

Cunietti, E; Gandini, R; Mascaro, G.; Ferrari, María Rosa; Pappalepore, V; Scapellato, Luisa

doi:10.1111/j.1600-0609.1981.tb01671.x

Cited by 17 publications

(4 citation statements)

References 17 publications

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“…In CMPD patients, bleeding and arterial (mostly microvascular) or venous thrombosis are common complications (1)(2)(3)(4)(5)(6)(7)(8) where mechanisms are still unclear. Qualitative functional platelet abnormalities frequently observed in CMPD patients (1,(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) have been correlated with these complications (8,13,19). Such abnormalities encompass decreased platelet aggregation (PA) to adenosine diphosphate (ADP), collagen and particularly epinephrine (14,15,18) and acquired storage pool disease (16) as well as platelet hyperfunction indicated by enhanced PA (4,13), increased levels of plasma P-throm-boglobulin (PTG) (15,17) and shortened platelet survival time (1 5).…”

Section: Introductionmentioning

confidence: 99%

“…Qualitative functional platelet abnormalities frequently observed in CMPD patients (1,(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) have been correlated with these complications (8,13,19). Such abnormalities encompass decreased platelet aggregation (PA) to adenosine diphosphate (ADP), collagen and particularly epinephrine (14,15,18) and acquired storage pool disease (16) as well as platelet hyperfunction indicated by enhanced PA (4,13), increased levels of plasma P-throm-boglobulin (PTG) (15,17) and shortened platelet survival time (1 5). In addition, molecular and morphological abnormalities including a decrease in a adrenergic and PGD, receptor sites (21,22), number of a granules and dense bodies or in the concentration of glycoprotein I (1) were reported.…”

Section: Introductionmentioning

confidence: 99%

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

Zahavi¹,

Zahavi²,

Firsteter³

et al. 1991

European J of Haematology

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Platelet aggregation (PA) induced by ADP, collagen and epinephrine, plasma levels of β‐thromboglobulin (βTG) 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<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 βTG level and serum TXB2 generation (both corrected to a normal platelet concentration) were 2.9‐7.1 times higher (p < 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.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Zahavi¹,

Zahavi²,

Firsteter³

et al. 1991

European J of Haematology

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“…Fibrinopeptides are derived from fibrinogen in the presence of activated neutrophils. β‐thromboglobulin and platelet factor 4 are platelet‐derived CXC subfamily cytokines with regulatory roles in neutrophil activation and chemotaxis (Brandt et al , 2000) and are elevated in the inflammatory states associated with high neutrophil mobilisation (Cunietti et al , 1981; Rueda et al , 1991). CML patients have altered glycoprotein IV expression on the platelets and increased serum β‐thromboglobulin and platelet factor 4 levels as compared with normal controls (Liu et al , 1997).…”

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confidence: 99%

Serum profiling reveals distinctive proteomic markers in chronic myeloid leukaemia patients

et al. 2008

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Chronic myeloid leukaemia (CML) is characterised by a reciprocal translocation t(9;22)(q34;q11) which leads to the production of the BCR-ABL1 protein tyrosine kinase (De Keersmaecker & Cools, 2006). In the chronic phase, the disease is maintained by BCR-ABL1 activity and responds well to treatment with tyrosine kinase inhibitor therapy (Giles et al, 2005). To improve the understanding of the biology of CML, we used surface enhanced laser desorption/ionization time of flight (SELDI-TOF) mass spectrometry to identify diseasespecific serum proteins.Serum samples were collected from 23 CML patients at presentation (CML-P), median age 46 years (range 21-85), male:female 1AE3:1, median spleen size 7 cm (range 5-23), mean white cell count 135 · 10 9 /l (range 35-665) and mean absolute neutrophil count 102 · 10 9 /l (range 25-235). Median duration of Gleevec therapy (n = 27) until haematological remission (World Health Organization criteria) was achieved was 20 months (range 6-51). Seven additional paired samples were available from patients at diagnosis and following the induction of HR. Subjects with neutrophilia due to nonmalignant causes (n = 24) (absolute neutrophil count >15 · 10 9 /l) were analysed as a control group and compared the results to age and sex matched normal donors (n = 34). Serum was stored in multiple aliquots at )80°C for single use. A Biomek 2000 liquid handling station was used to prepare arrays and bind samples in duplicate. Immobilised metal affinity chromatography arrays (Ciphergen, Guildford, UK) were used and scanned on a PCS 4000 (Ciphergen) time of flight mass spectrometer using 9000 and 20 000 Da focus masses (deflector: 1500 Da). Peaks were automatically detected using Ciphergen Express 3.0 (CE 3) software following manufacturer's instructions. Useful peaks for cluster analysis were selected with a signal:noise of ‡3, resolution between 300 and 400 and confirmed visually.Informative m/z peaks were enriched by pH fractionation of pooled sera (n = 8) using anion exchange chromatography (Q HyperD F, Ciphergen) or reverse phase chromatography and concentrated using either YM-30 or YM-50 filters (Millipore, Livingstone, UK) followed by one dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis. Coomasie-stained bands were excised and either passively eluted to confirm the correct m/z peak or subjected to in-gel trypsinization (Roche, UK) on NP-20 arrays (Delbosc et al, 2008). Peptides which could not be enriched for peptide mass fingerprinting were directly identified by fragmentation on the Micromass Q-TOF2 instrument. Unique peptide mass fingerprints were matched to in silico trypsin digested protein signatures using MASCOT (http://www.matrixscience.com). The most abundant peptide was fragmented to confirm protein identity (PCI 1000 tandem MS interface with a Q-TOF2; Micromass, Manchester, UK).Thirty-eight clusters of serum protein peaks from 2AE5 to 50 kDa were annotated in CML-P, normal and neutrophilia patients, CE 3.0 was used to perform univariate data analysis. Receive...

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“…Bleeding and thrombosis are common complications in patients with myeloproliferative disorders (MPD), sometimes occurring sequentially in the same patient during the course of the disease. Qualitative platelet abnormalities are frequently found in these patients and range from platelet hypofunction as demonstrated by defective in vitro platelet aggregation (1)(2)(3), acquired storage pool disease (4, 5 ) and/or platelet membrane defects (6,7), to abnormalities suggesting increased platelet reactivity by exhibiting enhanced platelet aggregation (8-lo), increased plasma B thromboglobulin levels (2,7,11) or shortened platelet survival (2).…”

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confidence: 99%

Platelet function in myeloproliferative disorders: Characterization and sequential studies show multiple platelet abnormalities, and change with time

Baker

Manoharan

1988

European J of Haematology

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Bleeding and thrombosis are well known major causes of morbidity and mortality in patients with myeloproliferative disorders (MPD) but the relationship between these clinical events and the commonly found platelet function abnormalities have not been established. In this study we performed simultaneous laboratory evaluations in 54 patients with MPD to investigate abnormalities in platelet aggregation and cyclooxygenase activity, the latter by using an in vitro aspirin inhibition test; the studies were repeated in 22 patients 1–27 months later. We have found platelet hyper‐ and hypofunction co‐existing in some patients (9/54), and change of platelet function during the course of the disease (7/22) with platelet hypofunction being the only constant abnormality over time. These results may explain the lack of correlation between the clinical events and the limited assessment of platelet function in the hitherto published studies, and also suggest the need for repeated evaluations to properly assess the relative risk for bleeding and thrombosis.

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Defective Platelet Aggregation and Increased Platelet Turnover in Patients with Myelofibrosis and Other Myeloproliferative Diseases

Cited by 17 publications

References 17 publications

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

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

Serum profiling reveals distinctive proteomic markers in chronic myeloid leukaemia patients

Platelet function in myeloproliferative disorders: Characterization and sequential studies show multiple platelet abnormalities, and change with time

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