Blood tests may predict early primary myelofibrosis in patients presenting with essential thrombocythemia

Abstract

According to World Health Organization (WHO)-defined criteria, patients presenting clinically as essential thrombocythemia (ET) may show early primary myelofibrosis (PMF) with accompanying thrombocythemia [1]. Previous clinicopathological studies revealed that laboratory parameters like gender-matched hemoglobin (Hb), white blood cell (WBC) count, and particularly lactate dehydrogenase (LDH) values are significantly different in PMF [2]. By strictly applying the WHO criteria, our investigation was aimed to study sensitivity and specificity of these features in an exploratory cohort of 536 patients and to validate the results on an independently recruited series of 321 strictly corresponding patients. The discriminatory power of these parameters (Hb, WBC, and LDH) was tested by plotting their receiver operating characteristic curves. The best performance was found for LDH (areas under the curve, AUC 5 0.7059). WBC and Hb had superimposable curves, with AUC of 0.6279 and 0.6257, respectively. A diagnostic algorithm was generated by applying these parameters in a stepwise fashion. Nearly half of the patients could be correctly allocated to WHOdefined ET or early PMF in both cohorts investigated. It is important to note that this result does not substitute bone marrow morphology with hematological parameters, however, in clinical practice may alert physicians to get more suspicious of early PMF in a patient presumably presenting with ET.Following current criteria established by the World Health Organization (WHO), patients presenting with a clinical picture of essential thrombocythemia (ET) can actually have an early primary myelofibrosis (PMF) [3]. Incidences may vary depending on the accuracy of applied diagnostic guidelines [4][5][6] and was recently reported in about 18% of cases of socalled ET [7]. Laboratory tests which are significantly different in early PMF as compared with histologically confirmed ET (WHO-ET) include decreased Hb, increased white blood cell (WBC) and lactate dehydrogenase (LDH) values. Although bone marrow biopsy represents the gold standard for differentiating WHO-ET from early PMF [8], in clinical practice it might be very useful to know whether one or more of these baseline laboratory parameters may help to differentiate these two entities. To tackle this issue, we evaluated sensitivity (SE) and specificity (SP) of blood cells counts and LDH for the diagnosis of early PMF versus WHO-ET in an exploratory cohort of 536 histologically diagnosed patients aimed to propose an algorithm for the practical clinical use of these tests. This algorithm was then applied to an independently recruited validation cohort of 321 patients presenting with similar diagnosis of early PMF versus WHO-ET. The starting point of this study was an international database of 1,071 patients with ET either confirmed by WHO criteria (891 cases) or revised to early PMF (180 cases) as detailed elsewhere [7]. From this database, 536 patients (50%) who had complete laboratory data measured at diagnosis were extracted and c...

Spleen enlargement is a risk factor for thrombosis in essential thrombocythemia: Evaluation on 1,297 patients

“…As a result, some cases of early-primary myelofibrosis (early-PMF) could have been included in the analysis. However, the strict distinction between ET and early-PMF is not of pivotal importance when looking for thrombotic risk factors, since the incidence of thrombosis has been reported to be comparable in these two clinical entities [23,24]. Moreover, the histological discrimination between ET and early-PMF is not always easy to assess and reproducible, particularly in peripheral Centers without a specific expertise on MPNs histology; therefore, exploring additional risk factors for thrombosis in these patients is of utmost relevance for everyday clinical management.…”

Mutations and long-term outcome of 217 young patients with essential thrombocythemia or early primary myelofibrosis

“…6,[25][26][27] However, little data are available on selected cohorts of young individuals with an ET/early-PMF diagnosis.…”

Protein C zymogen in severe sepsis: a double-blinded, placebo-controlled, randomized study

“…This study was extremely original and innovative since, in spite of the recent widening of the off-label indications in pediatric [20,21,27,28] and adult [19] patients, no randomized, placebo-controlled trial in critically ill pediatric or adult patients has ever investigated clinically relevant endpoints. Another unique feature of our trial is that it enrolled patients admitted to the ICU for a primary disorder other than sepsis (mostly cardiac pathology or acute lung failure).…”

“…No bleeding complications related to the study drug were reported, and most studies underlined normalization of inflammatory markers and of coagulation abnormalities. Notably, recent case reports suggest that the use of protein C zymogen is widespread in in other clinical settings such as adult solid tumors, oncohematology, and pediatric amputations [19,20,27].…”

“…At the clinical level, protein C zymogen has been administered to more than 340 patients with congenital protein C deficits without any bleeding or allergic complications, and with improvements in coagulation abnormalities [16]. Recent reports suggest that its use is expanding in other settings [19][20][21]. However, the absence of a randomized clinical trial (RCT) leaves clinicians uncertain as to whether protein C zymogen, an expensive drug, should be prescribed in adult patients with severe sepsis and septic shock to improve clinically relevant outcomes.…”