Extreme thrombocytosis in patients with underlying malignancy; Management, complications and outcomes.

Abstract

Abstract Thrombocytosis is a commonly seen haematological abnormality. However, extreme thrombocytosis (EXT, defined as a platelet count of >1000 x 109/L) is a rare entity. It can be categorised as either primary (clonal) or secondary (reactive). There are little data on the incidence and management of secondary EXT in patients with underlying (non-myeloproliferative) malignancy. We retrospectively investigated the incidence, management and complications of EXT in patients at the Royal Marsden Hospital with underlying malignant diagnoses over a 12-year period. We identified 198 patients as having EXT during the study period; the majority (113, 57%) were female and the median age at diagnosis of malignancy was 55 years (range 1-86). Median follow-up was 55 months (range 0-177). The median highest platelet count reported in this patient population was 1112 x 109/L (range 1001 – 2593). The majority of patients had non-haematological malignancies (153, 77%). Of these, the most common diagnoses were lung cancer and mesothelioma (39, 25%) although a further 41 malignancies were seen. Myeloproliferative Neoplasm (MPN) screening for JAK2, CALR, MPL and BCR-ABL abnormalities was only done in 11 patients (5.5%); none were positive. The majority of patients in this cohort (70%) had complete resolution of thrombocytosis, but 56 (28%) had persistently elevated platelet counts. Antiplatelet therapy was documented in 32 patients (16%), although it was a pre-existing medication in 11 patients (34.5%). Indications for commencing antiplatelets included a new thrombotic event (CVA or MI) in six patients (18%), and for thrombocytosis itself in 11 patients (34.5%). In the remaining patients (13%) the reason for antiplatelet therapy was not documented. Therapeutic anticoagulation was commenced in 36 patients (18%). In the majority of cases, the indication for anticoagulation was thrombosis (35, 97.3%). Only one patient (2.7%) was started on therapeutic anticoagulation due solely to thrombocytosis. In this patient population, 42 patients (21%) had a diagnosed thrombotic event, of which the majority (35, 83%) were venous. Pulmonary embolism (PE) was the most common event, seen in 13 patients (31%). Twenty-five patients (59.5%) had thrombocytosis at the time of thrombosis. In terms of management of thrombosis, six of the patients with arterial thrombosis were treated with antiplatelet therapy. As outlined above, the majority of patients who had a venous thrombotic event were managed with therapeutic anticoagulation. The rate of thrombotic events in this study is higher than in the published literature, which generally quotes a rate of thrombosis in cancer patients as 4-6% (Khamis et al 2025, Bleeker et al 2011). Within this patient population a paediatric subgroup was analysed; 44 patients with EXT under the age of 18 were identified, with a median platelet count of 1147x109/L (range 1001 – 1781). None of the paediatric population received aspirin or anticoagulation as thromboprophylaxis, and 4 patients (9%) had thrombotic complications. Almost two thirds of patients had died at the time of data collection (128, 64.5%). The most common cause of death was progressive malignancy (84, 66%). Infection was the cause of death in 7 patients (5.5%), and 35 patients (27%) were lost to follow up and cause of death was unknown. Only 2 patients (1.5%) had a documented thrombotic cause of death (both CVA). The median overall survival from identification of thrombocytosis in this cohort of patients was 26 months (range 0 – 117). This study analysed a large cohort of patients with non-MPN malignancy who developed EXT. MPN screening is rarely undertaken in these patients despite persistence of the elevated platelet count in many cases. EXT may contribute to the risk of thrombotic complications in patients with malignancy. Given the high rate of thrombotic complications in this cohort, we suggest that patients with EXT in the setting of malignancy should be referred to the specialist Haematology team for consideration of further investigation including screening for MPN, especially if the thrombocytosis is persistent. This data would also support a change in practice to consider thromboprophylaxis in patients with underlying malignancy and EXT. This real-world data has shown that thrombotic complications occurred in a higher proportion of these patients than expected, and therefore further studies are required to identify the optimal management of these patients.