الفهرس 
THROMBOCYTOSISOnly 14 pages are availabe for public view
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Abstract
T
hrombocytosis is defined as elevated platelet count above 450 × 109/L; this threshold was recommended by WHO (2016) and by BCSH (2010). In most literature, for thrombocytosis to be persistent, it should be sustained for at least 3 months.
The major causes of thrombocytosis can be divided into reactive and clonal thrombocytosis. Reactive causes include transient processes such as acute blood loss, acute infection or inflammation, extreme physical exertion, or other stress. Sustained forms of reactive thrombocytosis include iron deficiency, hemolytic anemia, asplenia, cancer, chronic inflammatory or infectious diseases, and rare drug reactions.
Clonal thrombocytosis is typically due to a chronic MPN particularly ET and pre-PMF. These clonal disorders are associated with adverse events related to the thrombocytosis, including thrombotic, vascular and bleeding complications.
Calreticulin (CALR) gene mutation is now a major criterion for establishing the diagnosis of classical myeloproliferative neoplasms (essential thrombocythemia, prefibrotic primary myelofibrosis and primary myelofibrosis). It is the second common gene mutation encountered in these disorders after JAK2 mutation as it accounts for about 25-30% of cases. Cases with CALR mutation show distinct clinical and laboratory features from JAK2 mutated cases, being younger in age, with lower hemoglobin level, higher platelet count and lower thrombotic risk.
The current study aimed at detecting CALR gene mutation in adult Egyptian patients with persistent thrombocytosis for ≥ 3 months. Furthermore, evaluating the clinical and epidemiological features together with laboratory data of the studied patients in correlation with their mutation status.
Fifty patients with persistent thrombocytosis (≥ 3 months) were divided into 2 subgroups according to the cause resulting in thrombocytosis (1ry or 2ry). The patients were evaluated for the presence of CALR mutation using HRM PCR.
All patients with reactive thrombocytosis didn’t reveal to harbor the CALR mutation except for one patient with metastatic cancer colon which is considered an uncommon finding as most of recurrent mutations in the CALR gene occurs in MPNs despite a small number of mutations reported in different solid tumors.
In clonal thrombocytosis, CALR mutations were observed in 30% of ET cases, while JAK2 mutation positive cases were about 53.3% and about 13.3% of cases were double negative for both mutations. One patient with ET was identified to harbor both JAK2 and CALR mutations adding an exception for the mutual exclusivity of both mutations.
As regard the impact of CALR mutation on the clinical phenotype of the patient, we noticed that the CALR mutation positive cases were younger, with lower TLC and hemoglobin level, higher platelets count and LDH level than JAK2 mutation positive cases. In addition, CALR mutated patients show reduced incidence for developing a major thrombotic event and tendency of megakaryocytes to form clusters on bone marrow examination.
In the current study, no significant differences regarding organomegaly and RBCs indices (MCV, MCH, MCHC and RDW) were observed between CALR mutated and JAK2 mutated groups.
In conclusion, detection of CALR mutation in cases of persistent thrombocytosis could help distinguishing 1ry and 2ry thrombocytosis and might uncover the presence of ongoing clonal disorder. This also could help in predicting the clinical phenotype and disease outcome. Eventually, detection of CALR mutation by HRM PCR could be used as screening test saving time and money, then the positive samples are to be validated and further identified by sequencing techniques.