Mean platelet volume as an effective biomarker for predicting high-risk patients of hereditary thrombophilia: A retrospective study.

OBJECTIVE: Literature shows evidence of the use of mean platelet volume (MPV) as a biomarker in thromboembolic conditions. It is recommended that genetic testing be performed selectively for hereditary thrombophilia. It might be useful to determine the priority of patients for genetic testing of hereditary thrombophilia through appropriate methods. We aimed to investigate the predictive value of MPV for high-risk patients of hereditary thrombophilia. METHODS: The hematologic (MPV), biochemical (antithrombin III, protein S, protein C), molecular genetic test results (factor V Leiden [FVL], and prothrombin G20210A [PT]) obtained retrospectively from medical files of 263 patients categorized into high- versus low-risk for thrombophilia were statistically analyzed and the value of MPV in predicting high-risk patients was assessed by receiver operating characteristic (ROC) analysis. RESULTS: The frequencies of high- versus low-risk patients were 45.2% and 54.8%, respectively. Significantly more high-risk patients (n=81) compared to low-risk patients had FVL (n=66) and PT mutations (n=80 vs. 34) (p<0.001). The MPV values in high-risk patients (mean=11.1 fl, range=7.8-13.6) were significantly higher than those in the low-risk patients (mean=8.6 fl, range=6-10.9) (p<0.001). The ROC curve analysis for MPV revealed a statistically significant area under the curve of 0.961 (95% confidence interval=0.931-0.981) at a cut-off point of 10.1 fl with a sensitivity of 89.1% and a specificity of 91.7% (p<0.001). CONCLUSION: MPV might be used as an effective biomarker to screen and select patients for genetic thrombophilia testing. Large multicenter studies are needed for recommending the inclusion of MPV in future guidelines for hereditary thrombophilia.

Hematological and Inflammatory Parameters to Predict the Prognosis in COVID-19.

We aimed to evaluate the predictive ability of hematological and inflammatory parameters for mortality in COVID-19 patients. This was a retrospective study of hospitalized COVID-19 patients over 18 years old between March 2020 and May 2020. Patients were diagnosed to have COVID-19 based either on chest computed tomography findings or reverse transcriptase-polymerase chain reaction test. Age, gender, chronic medical conditions, and laboratory values including hemogram parameters (white blood cell, neutrophil, lymphocyte, and platelet counts), neutrophil to lymphocyte ratio, D-dimer, ferritin, fibrinogen, C-reactive protein, procalcitonin, prothrombin time, activated partial thromboplastin time and the international normalized ratio were recorded. Overall, we included 302 patients. Of these, 148 patients were male; the male to female ratio was 0.961. The mean age of the entire study cohort was 57.1 ± 17.6 years. The most common chronic medical condition was hypertension (38.1%). Half of the patients received low molecular weight heparin. During the study period, 25 patients (8.2%) died. White blood cell count and neutrophil count were significantly higher, whereas lymphocyte count was significantly lower in the deceased patients. The median neutrophil to lymphocyte ratio was 11.6 in the deceased patients, it was significantly higher than the surviving patients (p < 0.001). The values of C-reactive protein, procalcitonin, D-dimer, and ferritin were significantly higher among the deceased patients. Prothrombin time, activated partial thromboplastin time and the international normalized ratio were significantly longer in the deceased group compared with the surviving group. Logistic regression analysis showed age > 65 years, neutrophil to lymphocyte ratio, activated partial thromboplastin time, and hypertension as the independent predictors of mortality. The rate of abnormal inflammatory and hematologic-coagulation parameters increased with the COVID-19 severity. Age > 65 years, hypertension, activated partial thromboplastin time and neutrophil to lymphocyte ratio were the independent predictors of mortality.

Association of mast cells and bone marrow reticulin fibrosis in patients with bcr-abl negative chronic myeloproliferative neoplasms.

BACKGROUND: We aimed to investigate the association of bone marrow mast cell numbers (MCN) and the degree of reticulin fibrosis in patients with chronic myeloproliferative neoplasms (MPN). METHODS: This was a case-control study that recruited 47 patients who were diagnosed with bcr-abl negative MPN. Thirty patients with lymphoma served as controls. JAK2 mutation was studied and all subjects underwent bone marrow biopsy at the time of diagnosis. Mast and CD34+ cells were counted. Marrow reticulin fiber was graded. RESULTS: Thirty-four patients had essential thrombocythemia (ET), 8 patients had primary myelofibrosis (PMF) and 5 patients had polycythemia vera (PV). Fourteen MPN patients had JAK2, whereas the controls had not. MCN was higher in patients than controls (p = 0.001). There was no significant difference regarding CD34. Reticulin fibrosis was present in 57.4% of MPN patients, whereas there was any in controls. PMF patients had more CD34 + cells than PV and ET. PMF patients had more reticulin fibers compared with other subgroups (p < 0.001). MCN, but not CD34+ cell counts, was significantly higher in JAK2(+) patients than JAK2(-) patients. CONCLUSION: MCN and reticulin fibrosis were significantly increased in MPN patients. JAK2 positivity had significantly increased MCN compared to patients without JAK2. JAK2 was associated with increased reticulin fibrosis.

Decreased serum heat shock protein 60 levels in newly diagnosed immune thrombocytopenia patients.

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by peripheral thrombocyte destruction. In some autoimmune disorders, heat-shock proteins (HSP) are suggested to be an important antigenic factor. In this study, we demonstrated the serum free levels of HSP60, HSP70, anti-HSP60, and anti-HSP70 in ITP patients and healthy controls. Twenty-eight newly diagnosed ITP patients, 35 ITP patients in chronic phase, and 25 healthy controls were enrolled to this study. Serum levels of HSP60, HSP70, anti-HSP60, and anti-HSP70 were determined by the ELISA method. Serum HSP60 levels of newly diagnosed ITP patients were significantly decreased when compared with both chronic phase ITP patients and healthy controls. HSP60 levels of ITP patients (both newly diagnosed and chronic phase) with thrombocyte counts more than 30 × 10(9)/L were significantly increased compared with ITP patients with thrombocyte counts less than 30 × 10(9)/L and there was a positive correlation between thrombocyte counts and serum free HSP60 levels in ITP patients. This is the first study demonstrating the extracellular HSP levels in adult ITP patients. HSPs are shown to have a place in the pathogenesis of many autoimmune disorders. Low level of HSP60 may lead to lack of anti-inflammatory response due to less Treg activation, hence, could be a counterpart in the pathogenesis of ITP. Further studies are needed to understand the role of HSPs in the pathogenesis of ITP and whether they can be used for diagnosis, prognosis, and treatment of ITP.

The association between gene polymorphisms and leukocytosis with thrombotic complications in patients with essential thrombocythemia and polycythemia vera.

OBJECTIVE: Vascular events are a common complication in patients with polycythemia vera (PV) and essential thrombocythemia (ET). This study aimed to analyze the association between PAI-1 4G/5G and ACE I/D gene polymorphisms, and leukocytosis with thrombosis in patients with PV and ET. MATERIAL AND METHODS: In total, 64 patients with ET and PV were evaluated. Arterial or venous thrombosis, such as cerebral transient ischemic attack, ischemic stroke, myocardial infarction, peripheral arterial thrombosis, deep venous thrombosis, and pulmonary embolism, were defined as a vascular event. DNA samples were screened for mutations via reverse hybridization strip assay. RESULTS: In terms of PAI-1 gene polymorphism, the frequency of the 4G and 5G allele was 48.5% and 51.5%, respectively. The ACE allele frequency was 51.2% and 48.8% for D and I, respectively. There wasn't an association between occurrence of vascular events and the frequency of any allele. In terms of occurrence of vascular events, there weren't any significance differences between the patients that were carrying the ACE D/D homozygous allele to ACE I/D and those that carried the I/I allele (P = 0.93). There wasn't a significant difference in occurrence of vascular events between the PAI-1 5G/5G homozygote allele carriers, and the 4G/5G and 4G/4G allele carriers (P = 0.97). Vascular events were significantly more common in the patients with leukocytosis (leukocyte count >10 × 109 L-1) than in those without leukocytosis (leukocyte count ≤10 × 109 L-1) (P = 0.00). Age >60 years was also a significant risk factor for occurrence of vascular events(P = 0.008). CONCLUSION: PAI-1 and ACE gene polymorphisms were not considered new risk factors for thrombosis in PV and ET patients. On the other hand, leukocytosis at diagnosis was associated with the occurrence of vascular events in the patients with ET and PV.

Effect of heat shock protein-90 (HSP90) and vascular endothelial growth factor (VEGF) on survival in acute lymphoblastic leukemia: an immunohistochemical study.

BACKGROUND: The significance of vascular endothelial growth factor (VEGF) and heat shock protein-90 (HSP90) has received only limited attention especially in acute lymphoblastic leukemia (ALL). In this study, we assessed expressions of HSP90 and VEGF in bone marrow samples of patients with ALL and effect of these expression quantities on the mean overall survival. PATIENTS AND METHODS: Using immunohistochemical methods, we assessed expression of HSP90 and VEGF in 22 cases of ALL. RESULTS: Expression of HSP90 was detected in 19/22 (86.4%) and 3/22 (13.6%) of patients with ALL, for strongly positive and moderate-weakly positive, respectively. Negative HSP90 expression was not detected in patients with ALL. Expression of HSP90 in patients with ALL and in control group were statistically significant (P<0.001), however, did not reflect the mean overall survival (P=0.910). Mean OS was evaluated 992±181 and 724.8±88.2 days for moderate-weak and high HSP90 expression, respectively. VEGF expressions were not significantly different between ALL and control groups (P<0.087). We did not find any relationship between HSP90 and VEGF expressions in bone marrow specimens of patients with ALL. CONCLUSION: This study demonstrated that HSP90 expression grades in patients with ALL were significantly higher than that in controls and presence of strong HSP90 expression was associated with worse overall survival. VEGF expression in patients with ALL was not different from that in control samples. Determination HSP90 with immunohistochemical method in bone marrow can provide information about prognosis.

Are cup-like blasts specific to AML patients with FLT3 ITD and a normal karyotype? An ALL case report and review of the literature.

Cup-like morphology is defined as cup-like nuclear invagination spanning ≥25% of the nuclear diameter in >10% of blasts. Studies have shown that FLT3 ITD and normal cytology are strongly associated with cup-like morphology in acute myeloid leukemia (AML) patients. Herein we describe a patient with cup-like blasts that was diagnosed and treated for common acute lymphoblastic leukemia (ALL). In contrast to the literature, the presented case was Philadelphia chromosome positive and FLT3 ITD negative.