Abstract
JAK2, MPL, and CALR mutations define clonal thrombocytosis in about 90% of patients with sustained isolated thrombocytosis. In the remainder of patients (triple-negative patients) diagnosing clonal thrombocytosis is especially difficult due to the different underlying conditions and possible inconclusive bone marrow biopsy results. The ability to predict patients with sustained isolated thrombocytosis with a potential clonal origin has a prognostic value and warrants further examination. The aim of our study was to define a non-invasive clinical or blood parameter that could help predict clonal thrombocytosis in triple-negative patients. We studied 237 JAK2 V617-negative patients who were diagnosed with isolated thrombocytosis and referred to the haematology service. Sixteen routine clinical and blood parameters were included in the logistic regression model which was used to predict the type of thrombocytosis (reactive/clonal). Platelet count and lactate dehydrogenase (LDH) were the only statistically significant predictors of clonal thrombocytosis. The platelet count threshold for the most accurate prediction of clonal or reactive thrombocytosis was 449 × 109/L. Other tested clinical and blood parameters were not statistically significant predictors of clonal thrombocytosis. The level of LDH was significantly higher in CALR-positive patients compared to CALR-negative patients. We did not identify any new clinical or blood parameters that could distinguish clonal from reactive thrombocytosis. When diagnosing clonal thrombocytosis triple-negative patients are most likely to be misdiagnosed. Treatment in patients with suspected triple negative clonal thrombocytosis should not be delayed if cardiovascular risk factors or pregnancy coexist, even in the absence of firm diagnostic criteria. In those cases the approach “better treat more than less” should be followed.
Highlights
Thrombocytosis is a common abnormality and a frequent cause of referral to the haematologist
It is of prognostic significance to distinguish between clonal and reactive thrombocytosis as probably only clonal thrombocytosis is related to an increased risk of thrombo-haemorrhagic complications [3]
The following parameters were collected: sex, age at the date of the first examination, white blood count (WBC), neutrophil count, erythrocyte count, haemoglobin level, haematocrit level, mean corpuscular volume (MCV), platelet count, ferritin level, iron level, total iron binding capacity (TIBC), saturation of transferrin, C-reactive protein (CRP), lactate dehydrogenase (LDH), the presence of splenomegaly determined by clinical examination, the presence of MPL or calreticulin gene (CALR) mutations and bone marrow biopsy results
Summary
Thrombocytosis is a common abnormality and a frequent cause of referral to the haematologist. In patients with clonal thrombocytosis, the uncontrolled production of platelets is caused by the clonal disease of the haematopoietic stem cell, most commonly seen in essential thrombocythaemia (ET) [1]. Reactive thrombocytosis is most commonly caused by infections, inflammatory diseases, hyposplenism, recent surgery, haemorrhage, malignant disease or most frequently, by iron deficiency [2]. It is of prognostic significance to distinguish between clonal and reactive thrombocytosis as probably only clonal thrombocytosis is related to an increased risk of thrombo-haemorrhagic complications [3]. ET is one of the classical myeloproliferative neoplasms (MPNs) with an increased risk of thrombo-haemorrhagic complications that can occur in more than 20% of patients [4,5]. In a Swedish study performed on 1284 patients with ET, vascular complications were present in up to 35% of those patients [6]
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