Thrombosis in thrombocythemic Ph- myeloproliferations is associated with higher platelet count prior to the event: results of analyses of prothrombotic risk factors from a registry of patients treated with anagrelide
Language English Country Great Britain, England Media print-electronic
Document type Journal Article
PubMed
25807961
DOI
10.1111/ejh.12554
Knihovny.cz E-resources
- Keywords
- JAK2, anagrelide, myeloproliferative disorders, platelets, thrombophilia, thrombosis,
- MeSH
- Aspirin administration & dosage MeSH
- Fusion Proteins, bcr-abl MeSH
- Quinazolines administration & dosage MeSH
- Philadelphia Chromosome * MeSH
- Janus Kinase 2 genetics MeSH
- Humans MeSH
- Mutation, Missense MeSH
- Platelet Count MeSH
- Prospective Studies MeSH
- Registries * MeSH
- Risk Factors MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Amino Acid Substitution MeSH
- Thrombocytosis * blood complications drug therapy genetics MeSH
- Thrombosis * blood drug therapy etiology genetics MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- anagrelide MeSH Browser
- Aspirin MeSH
- Fusion Proteins, bcr-abl MeSH
- BCR-ABL1 fusion protein, human MeSH Browser
- Quinazolines MeSH
- JAK2 protein, human MeSH Browser
- Janus Kinase 2 MeSH
Controversies still exist regarding definition of the thrombotic risks in Ph- (BCR/ABL1-) myeloproliferative disorders with thrombocythemia (MPD-T). Platelet counts at diagnosis are currently not taken as a risk factor of thrombosis. In our cohort of 1179 patients with MPD-T, prospectively registered for anagrelide treatment, we found that the median platelet count prior to the thrombotic event was significantly higher than at time points without any ensuing thrombosis (453 vs. 400 × 10(9)/L, P < 0.001), albeit higher platelet counts at diagnosis tended to be connected with fewer thrombotic events (in contrast to WBC counts at diagnosis). The JAK2(V617F) mutation predicted both arterial and venous events, while age >65 yr, hypertension, diabetes mellitus, smoking, elevated triglyceride and homocysteine levels predicted arterial events only. For venous events, the specific thrombophilic risk factors (factor V 'Leiden' and others), antiphospholipid antibodies, and elevated factor VIII levels played a major role. During anagrelide treatment (± aspirin), we documented a decrease in both venous (6.7-fold) and arterial events (1.8-fold), while bleeding (mostly minor events) increased twofold compared to history. Our results suggest that keeping platelet counts at low levels may be a meaningful therapeutic measure to prevent thrombosis, although their counts at diagnosis lack any prognostic value.
Department of Clinical Hematology Faculty Hospital Brno Masaryk University Brno Czech Republic
Department of Pathology Faculty Hospital Brno Masaryk University Brno Czech Republic
Institute of Biostatistics and Analyses Masaryk University Brno Czech Republic
Institute of Hematology and Blood Transfusion Prague Czech Republic
Internal Hematology Clinic Faculty Hospital Královské Vinohrady Prague Czech Republic
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