Can Biomarkers of Coagulation, Platelet Activation, and Inflammation Predict Venous Thromboembolism in Patients with Haematological Malignancies?

BACKGROUND: The incidence of venous thromboembolism (VTE) in haematological malignancies varies according to the type and grade of the disease and clinical variables, and there is a need to develop a tool to predict the occurrence of VTE in cancer patients at diagnosis to tailor prophylactic anticoagulation use during treatment. OBJECTIVE: To study the incidence of VTE in haematological malignancies and clarify whether vascular and inflammatory biomarkers could be used as predictors of VTE in those patients. METHODS: This was a prospective observational cohort study. Hypercoagulability and inflammatory biomarkers were assayed in a group of 171 patients with haematological malignancies at diagnosis. These markers included (1) coagulation and fibrinolysis activation markers (D-dimer, fibrinogen, antithrombin, plasminogen activator inhibitor 1), (2) endothelial and platelet activation markers (von Willebrand factor and soluble P-selectin), and (3) inflammatory markers (tumour necrosis factor αand interleukin 6). The end point was mortality or symptomatic VTE. RESULTS/CONCLUSION: The incidence of symptomatic VTE was 7%. None of the tested biomarkers showed statistical significance as predictors for the occurrence of VTE in haematological malignancies. However, there were statistically significant associations between the occurrence of VTE and central venous access device insertion, the prothrombin time, and the erythrocyte sedimentation rate. An ESR above 106.5 mm/h is associated with increased VTE occurrence.

CYP21A2 genetic profile in 14 Egyptian children with suspected congenital adrenal hyperplasia: a diagnostic challenge.

CYP21A2 genotyping remains an important element in the diagnosis and management of congenital adrenal hyperplasia, and establishing accurate genotype-phenotype correlations has facillitated adequate genetic counseling and prenatal management for at-risk families. Despite extensive efforts to establish a clear genotype-phenotype correlation, some discordance remains. Establishing a diagnosis of congenital adrenal hyperplasia on the basis of biochemical and clinical data is occasionally challenging, and the identification of CYP21A2 mutations may help confirm the diagnosis. We review the diagnostic challenges despite an extensive genetic evaluation for 14 patients with a suspected clinical and biochemical diagnosis of congenital adrenal hyperplasia. Other diagnostic entities should be considered in the absence of convincing genetic data.

Can biomarkers of coagulation, platelet activation, and inflammation predict mortality in patients with hematological malignancies?

BACKGROUND: Patients with cancer commonly demonstrate laboratory evidence for hypercoagulability. Coagulation and inflammation play a role in the pathophysiology of hematological malignancies and the correlation between hypercoagulability and inflammation with tumor outcomes and the patient's prognosis are well studied. OBJECTIVE: To identify an association between hemostasis activation, fibrinolysis and inflammation with mortality in patients with hematological malignancies to determine their prognostic significance. METHODS: This study is a prospective observational cohort study; Hypercoagulability and inflammatory biomarkers including:(1) Coagulation and fibrinolysis activation Markers (D-dimer, Fibrinogen, Antithrombin, plasminogen activator inhibitor 1 [PAI-1]);(2) Endothelium and platelet activation Markers (von Willebrand Factor [vWF], soluble P-selectin); and (3) Inflammation Markers (Tumor necrosis factor alpha [TNF-α], Interleukin-6 [IL-6]) were assayed on a group of 171 patients with hematological malignancies at time of diagnosis. They have been followed up for an average period of 416.8 days with an endpoint of mortality. RESULTS: Sixty patients died during follow up. There were statistically significant associations between Plasma cell dyscrasias mortality and ECOG performance status (P value:<0.005), Hemoglobin level (P value: 0.04), serum Albumin level (P value: 0.001), vWF (P value: 0.006) and IL-6 (P value 0.015), and between lymphoproliferative disorders mortality and presence of B symptoms (P value: 0.02), ECOG performance status (P value:<0.02), serum Albumin level (P value: 0.038), Antithrombin (P value: 0.004). CONCLUSION: Some biomarkers of coagulation and inflammation showed statistically significant associations with plasma cell dyscrasias mortality (vWF and IL-6) and lymphoproliferative disorders mortality (Antithrombin) and potentially could be used as prognostic markers.

Reported Benefits of Insulin Therapy for Better Glycemic Control in Type 2 Diabetic Patients-Is This Applicable in Saudi Patients?

AIM: To compare the effect of different treatment regimens (oral hypoglycemic agents [OHGs], insulin therapy, and combination of both) on glycemic control and other cardiometabolic risk factors in type 2 diabetes mellitus (T2DM) patients in Saudi. SUBJECTS AND METHODS: Patients with T2DM, but no serious diabetic complications, were randomly recruited from the diabetes clinics at two large hospitals in Jeddah, Saudi Arabia, during June 2013 to July 2014. Only those without change in treatment modality for the last 18 months were included. Blood pressure and anthropometric measurements were measured. Treatment plan was recorded from the patients' files. Fasting blood sample was obtained to measure glucose, HbA1c, and lipid profile. RESULTS: A total of 197 patients were recruited; 41.1% were men and 58.9% were women. The mean (±SD) age was 58.5 ± 10.5 years. Most patients (60.7%) were on OHGs, 11.5% on insulin therapy, and 27.7% were using a combination of insulin and OHGs. The mean HbA1c was lower in patients using OHGs only, compared with means in those using insulin, or combined therapy in patients with disease duration of ≤10 years (P = 0.001) and also in those with a longer duration of the disease (P < 0.001). A lower mean diastolic and systolic blood pressure was found among patients on insulin alone (P < 0.01). No significant differences were found in lipid profiles among the groups. CONCLUSION: Insulin therapy, without adequate diabetes education, fails to control hyperglycemia adequately in Saudi T2DM patients. There is a challenge to find out reasons for poor control and the ways as to how to improve glycemic control in T2DM.

Association of E-selectin gene polymorphism and serum PAPP-A with carotid atherosclerosis in end-stage renal disease.

BACKGROUND: Atherosclerotic vascular disease represents a significant cause of morbidity and mortality in patients with end-stage renal disease (ESRD). The endothelium plays a crucial role in vascular inflammation. E-selectin is exclusively expressed on activated endothelial cells and is upregulated following an inflammatory response and oxidative stress, while serum pregnancy-associated plasma protein-A (PAPP-A) concentrations are related to the presence and stability of carotid atherosclerotic plaques. OBJECTIVE: The aim of this study was to investigate whether there is an association between SELE rs5355C>T gene polymorphism, serum PAPP-A level and the presence of carotid atherosclerosis in ESRD patients. SUBJECTS AND METHODS: Seventy subjects were recruited into this study; 40 ESRD patients [age (mean ± SD) 43.42 ± 13.94 years] and 30 age- and gender-matched healthy individuals assigned to the control group. Polymerase chain reaction-restriction fragment length polymorphism was performed for the analysis of SELE rs5355C>T gene polymorphism, while serum PAPP-A concentrations were measured using electro-chemiluminescence immunoassay. Routine laboratory tests were measured on an automated chemistry analyzer. Carotid ultrasonographic studies were performed by a bilateral high-resolution B-mode ultrasound. RESULTS: There was no significant relationship between the SELE rs5355C>T gene polymorphism and ESRD incidence. Serum PAPP-A levels were significantly higher in ESRD patients compared with controls [median (interquartile range) 5.8 (5.1-11.6) and 5.1 (4.1-6.7), respectively; p = 0.005]. Serum PAPP-A correlated positively with urea, creatinine, systolic and diastolic blood pressure (DBP). Serum PAPP-A showed a statistically significant increase in SELE rs5355TT versus CC in both patients and controls. There was no association on comparing right intima-media thickness (IMT), left IMT, right cross-sectional area (CSA) and left CSA with the CC, CT and TT genotypes of SELE rs5355C>T. No correlation between serum PAPP-A with each of the above-mentioned carotid doppler findings was observed. There was a statistically significant increase in DBP in TT genotype carriers when compared with CC genotype carriers (p = 0.009). Serum PAPP-A levels were higher in hypertensive ESRD patients when compared with normotensive ESRD patients. There was a statistically significant decrease in high-density lipoprotein cholesterol (HDL-C) in TT genotype carriers when compared with CT genotype carriers in the whole study group (p = 0.003). Serum PAPP-A correlated negatively with HDL-C. CONCLUSION: The lack of a direct association between SELE rs5355C>T gene polymorphism, serum PAPP-A level and IMT suggests that their hypothesized association with carotid atherosclerosis might reflect an indirect mechanism of SELE rs5355C>T gene polymorphism and serum PAPP-A with cardiovascular risk factors such as blood pressure and HDL-C rather than a direct effect on the vasculature.