Secondary polycythemia in acutely ill COVID-19 patients is associated with higher mortality but not markedly higher thrombotic risk.

Secondary polycythemia is commonly observed among patients with chronic pulmonary diseases. However, its significance in the context of Coronavirus disease 2019 (COVID-19) is unknown. We retrospectively evaluated a total of 5872 hospitalized COVID-19 patients with mostly severe and critical symptoms, and without prior or subsequently diagnosed myeloproliferative neoplasm. Patients were stratified based on admission hemoglobin into four subgroups: anemia (hemoglobin <120 g/L for females and 130 g/L for males), normal hemoglobin, mild (hemoglobin 160-165 g/L for females and 165-185 g/L for males) and severe polycythemia (hemoglobin >165 g/L for females and >185 g/L for males). Among 5872 patients, a total of 158 (2.7%) had mild and 25 (0.4%) severe polycythemia. Polycythemia was significantly associated with higher respiratory and functional impairment, reduced plasma volume, higher serum osmolarity and comorbidity burden specific to the degree of polycythemia. Patients presenting with mild (odds ratio (OR) = 1.63, p = .003) and severe polycythemia (OR = 4.98, p < .001) had increased risk of death in comparison to patients with normal hemoglobin, whereas no significant associations with venous thromboembolism, arterial thrombosis nor major bleeding were observed. Anemia was associated with higher risk of death (OR = 1.42, p < .001), venous thromboembolism (OR = 1.34, p < .006) and major bleeding (OR = 2.27, p < .001) in comparison to normal hemoglobin. Associations of polycythemia and anemia with mortality diminished, and anemia with venous thromboembolism and major bleeding persisted, after multivariate adjustments for age, sex, comorbidities, COVID-19 severity and functional status. Secondary polycythemia in hospitalized COVID-19 patients without prior of subsequently diagnosed myeloproliferative neoplasm is rare and is associated with high mortality, increasing with degree of polycythemia, but not markedly higher thrombotic risk.

Hypoosmolar and hyperosmolar COVID-19 patients are predisposed to dismal clinical outcomes.

We aimed to investigate the associations of hypo- and hyperosmolarity at hospital admission with clinical characteristics and outcomes in 5645 consecutive hospitalized COVID-19 patients treated at a tertiary-level institution. Serum osmolarity was calculated as 2x Na (mmol/L) + urea (mmol/L) + glucose (mmol/L), with normal range from 275 to 295 mOsm/L. Median serum osmolarity was 292.9 mOsm/L with 51.8% normoosmolar, 5.3% hypoosmolar and 42.9% hyperosmolar patients present at the time of hospital admission. Hypoosmolarity was driven by hyponatremia, and was associated with the presence of chronic liver disease, liver cirrhosis, active malignancy and epilepsy. Hyperosmolarity was driven by an increase in urea and glucose and was associated with the presence of chronic metabolic and cardiovascular comorbidities. Both hypo- and hyperosmolar patients presented with more severe COVID-19 symptoms, higher inflammatory status, and experienced higher mortality in comparison to normoosmolar patients. In multivariate analysis, hypoosmolarity (adjusted odds ratio (aOR)=1.39, p = 0.024) and hyperosmolarity (aOR = 1.9, p < 0.001) remained significantly associated with higher mortality independently of older age, male sex, higher Charlson Comorbidity Index and more severe COVID-19. Disruptions in serum osmolarity are frequent in COVID-19 patients, may be easy to detect and target therapeutically, and thus potentially moderate associateds poor prognosis.

High absolute basophil count is a powerful independent predictor of inferior overall survival in patients with primary myelofibrosis.

OBJECTIVES: To investigate the clinical and prognostic significance of absolute basophil count (ABC) in patients with primary myelofibrosis (PMF). METHODS: We retrospectively investigated 58 patients with PMF treated in our institution in the period from 2006 to 2017. ABC was obtained in addition to other hematological and clinical parameters. Patients were separated into high and low ABC groups using the Receiver operating characteristic curve analysis. RESULTS: ABC was higher in PMF patients than in healthy controls (P < 0.001). Patients with high ABC had higher white blood cells (P < 0.001), higher red cell distribution width (P = 0.035), higher lactate dehydrogenase (P < 0.001), more frequently had circulatory blasts (P < 0.001), constitutional symptoms (P = 0.030) and massive splenomegaly (P = 0.014). ABC was also positively correlated with absolute monocyte count (AMC) (P < 0.001) and other components of differential blood count. There was no difference in ABC regarding driver mutations or degree of bone marrow fibrosis. Univariately, high ABC was significantly associated with inferior overall survival (hazard ratio (HR) 4.79, P < 0.001). This effect remained statistically significant (HR 4.27, P = 0.009) in a multivariate Cox regression model adjusted for age, gender, Dynamic International Prognostic Scoring System (HR 2.6, P = 0.001) and AMC (HR 8.45, P = 0.002). DISCUSSION: High ABC reflects higher disease activity and stronger proliferative potential of disease. ABC and AMC independently predict survival and therefore seem to reflect different underlying pathophysiologic processes. Hence, both have a potential for improvement of current prognostic scores. CONCLUSION: Basophils represent a part of malignant clone in PMF and are associated with unfavorable disease features and poor prognosis which is independent of currently established prognostic scoring system and monocytosis.

Assessing serum albumin concentration, lymphocyte count and prognostic nutritional index might improve prognostication in patients with myelofibrosis.

BACKGROUND: Primary and secondary myelofibrosis (PMF and SMF) are malignant diseases of hematopoietic stem cell characterized by the neoplastic myeloproliferation and a strong inflammatory milieu. The prognostic nutritional index (PNI) integrates information on albumin and absolute lymphocyte count (ALC) and reflects the inflammatory, nutritional and immune status of a patient. The clinical and prognostic significance of albumin, ALC and PNI in patients with myelofibrosis has not been previously investigated. METHODS: We retrospectively analyzed a cohort of 83 myelofibrosis patients treated in our institution from 2006 to 2017. Albumin, ALC and PNI were assessed in addition to other disease specific markers. RESULTS: The PMF and SMF patients had significantly lower ALC and PNI but similar albumin compared to controls. Lower albumin was significantly associated with older age and parameters reflecting more aggressive disease biology (e.g. anemia, lower platelet levels, higher lactate dehydrogenase (LDH), circulatory blasts, transfusion dependency, blast phase disease), inflammation (higher C reactive protein (CRP), constitutional symptoms) and higher degree of bone marrow fibrosis. Lower ALC was significantly associated with lower white blood cells (WBC) and lower circulatory blasts. Low PNI was associated with lower albumin, lower ALC, anemia, lower WBCs, lower serum iron and lower transferrin saturation. There was no difference in albumin, ALC and PNI regarding the driver mutations. In multivariate analysis adjusted for age and gender, low albumin (hazard ratio [HR] = 4.61, P = 0.001), low ALC (HR = 3.54, P = 0.004) and Dynamic International Prognostic Scoring System (DIPSS) (HR = 2.45, P = 0.001) were able to predict inferior survival independently of each other. Accordingly, low PNI (HR = 4.32, P < 0.001) predicted poor survival independently of DIPSS (HR = 3.31, P < 0.001). CONCLUSION: Assessing albumin, ALC and PNI might improve prognostication in patients with myelofibrosis and could assist in recognition of patients under increased risk of death.

Increased mean platelet volume (MPV) is an independent predictor of inferior survival in patients with primary and secondary myelofibrosis.

Neoplastic megakaryopoiesis is a dominant feature of Philadelphia-chromosome-negative myeloproliferative neoplasms (Ph- MPNs), and elevated mean-platelet-volume (MPV) is a common finding in these diseases. The clinical and prognostic significances of MPV in patients with primary (PMF) and secondary myelofibrosis (SMF) have not been reported. We retrospectively analyzed 87 patients with myelofibrosis (66 with PMF, 21 with SMF) treated at our institution. MPV was recorded in addition to other hematological and clinical parameters. MPV was elevated in both PMF and SMF patients in comparison to controls, whereas there was no statistically significant difference between PMF and SMF. Elevated MPV was associated with lower platelets (P = 0.016), higher white blood cells (P = 0.015), higher percentage of circulatory blasts (P = 0.009), higher lactate dehydrogenase (P = 0.011), larger spleen size (P = 0.014) and higher Dynamic International Prognostic score category (P = 0.027), while there was no statistically significant association with driver mutations or degree of bone marrow fibrosis. Higher MPV was univariately associated with inferior overall survival in the whole cohort (HR = 3.82, P = 0.006), PMF (HR = 4.35, P = 0.007) and SMF patients (HR = 7.22, P = 0.034). These associations remained significant in multivariate analyses adjusted for DIPSS. Higher MPV is associated with more aggressive disease features and exhibits powerful independent prognostic properties in both PMF and SMF settings.

Elevated Neutrophil-to-Lymphocyte-ratio and Platelet-to-Lymphocyte Ratio in Myelofibrosis: Inflammatory Biomarkers or Representatives of Myeloproliferation Itself?

BACKGROUND/AIM: We aimed to investigate clinical associations of inflammatory biomarkers neutrophil-to-lymphocyte-ratio (NLR) and platelet-to-lymphocyte-ratio (PLR) in patients with myelofibrosis, myeloproliferative neoplasm with inflammatory background. PATIENTS AND METHODS: We retrospectively analyzed a cohort of 102 myelofibrosis patients. NLR and PLR were assessed in addition to other disease-specific parameters. RESULTS: NLR and PLR were significantly higher in myelofibrosis than in healthy controls. Higher NLR was significantly associated with Janus-kinase-2 (JAK2)-mutation, wild-type-Calreticulin (CALR), older age and parameters reflecting increased proliferative potential of disease (higher leukocytes, higher hemoglobin, larger spleen-size), whereas there was no significant association with C-reactive-protein (CRP). Higher PLR was significantly associated with absence of blast-phase-disease, absence of constitutional-symptoms, lower percentage-of-circulatory-blasts, smaller spleen-size and lower CRP. In the Cox-regression-model, higher-NLR (HR=2.76; p=0.004), lower-PLR (HR=1.99; p=0.042) and Dynamic-International-Prognostic-System (DIPSS) (HR=3.26; p<0.001) predicted inferior survival independently of each other. CONCLUSION: In the context of myelofibrosis, elevated NLR and PLR are more likely to represent myeloproliferation itself and not necessary the extent of inflammation.