Open Access Review Article

Thrombin Structural and Functional Determinants as Therapeutic Targets

Rita Marchi, Mercedes López

International Blood Research & Reviews, Page 1-22
DOI: 10.9734/IBRR/2016/27562

Thrombin is the final serine protease generated during blood coagulation. This enzyme possesses a complex and fascinating structure composed not only by an active site but also by two positively charged patches, called anion binding exosites o simply exosites 1 and 2, as well as several surface loops and a Na+ binding region. These complex structural determinants make of thrombin a highly versatile enzyme with multiple and opposed roles within haemostasis by cleaving different substrates, and interacting with diverse cofactors and inhibitors. However, it is well known that thrombin actions are not limited to haemostasis. Thrombin has also multiple functions or pleiotropic effects, interconnecting coagulation to other systems, including the immune and the nervous system. This review focus on thrombin as therapeutic target of direct thrombin inhibitors, and highlights the pharmacology of anticoagulants in clinical use; including unfractionated heparin, low-molecular-weight heparins as well as lepirudin, desirudin, bivalirudin, argatroban and dabigatran etexilate. Adverse effects, antidotes and monitoring of these anticoagulants are discussed in detail. Finally, we also review recent advances on the development of aptamers as thrombin inhibitors.

 

Open Access Review Article

Outpatient Management of Acute Leukemia: A Systematic Review and Meta Analysis

O. Elemam, S. Elmorsy, A. Shanqeeti, D. Abdelmoety

International Blood Research & Reviews, Page 1-24
DOI: 10.9734/IBRR/2016/29025

Background/Aim: Outpatient chemotherapy administration for solid tumors is a commonly accepted practice given its advantage of easy and safe drug administration, ability to value the patient’s wish to avoid hospitalization and decreased expenses compared to inpatient care. However, this practice is not commonly extended to patients with acute leukemia. The aim of this study was to compile the evidence about outpatient and early discharge of acute leukemia patients and its effects on the outcome.

Methods: A systematic review was done using MEDLINE, EMBASE and Cochrane Library databases. Both retrospective and prospective cohort studies as well as clinical trials for acute leukemia were included.

Results: Twenty one studies were included in this systematic review: Ten retrospective studies, 10 prospective studies and one non-randomized phase 2 trial. Most of the included studies reported that outpatient chemotherapy is feasible, safe, and resulted in decreased hospitalization days.

Conclusion: Studies reporting on outpatient and early discharge of acute leukemia are largely observational and highly heterogeneous. A trend towards a reduced incidence of septicemia was observed with early discharge. The effect of other clinical outcome measures was unclear. Reporting on social and economic impact is suboptimal.

 

Open Access Original Research Article

Preliminary Report on the Frequency of Pro12Ala Polymorphism of the Peroxisome Proliferator-Activated Receptor-gamma Gene in Egyptian β-Thalassemia Major Patients

Mohamed El-Dafrawy, Nahla A. M. Hamed, Omar Ghallab, Dalia Elneely, Marwa Khalifa

International Blood Research & Reviews, Page 1-7
DOI: 10.9734/IBRR/2016/28458

Osteoporosis represents an important cause of morbidity in adult thalassemic patients. Peroxisome proliferator-activated receptor-γ (PPAR γ) is a master transcriptional regulator involved in expression of probably hundreds of genes. Recent studies have suggested that PPAR-γ plays an important role in osteogenesis. Furthermore, PPARγ inhibition in mice, increased bone formation with no effect on bone resorption. Our aim was to investigate the frequency of Pro12Ala polymorphism (substitution of proline to alanine at codon 12 in exon B) of PPARγ gene in Egyptian β-thalassemia major (β-TM) patients and its influence on their bone mineral density (BMD). Blood samples from 30 β-TM patients and 10 healthy controls matched for age, sex and body weight were analyzed for PPARγ gene polymorphism using polymerase chain reaction-restriction fragment length polymorphism. BMD were measured in all patients and controls by a dual energy X-ray absorptiometry at the lumbar spine. Low BMD (Z score is -1 or lower) was present in all thalassemic cases. There was no statistically significant difference between BMD in thalassemic males (-3.43±-1.08) and females (-2.78±-0.81) (p=0.265). Pro12Ala polymorphism was present in 2 out of 30 (6.67%) β-TM patients with osteoporosis. One patient had heterozygous 12Ala polymorphism and the other had homozygous 12Ala polymorphism. Both had normal body mass index, lipid profile, ejection fraction and elevated serum ferritin. Only one male control (10%) has homozygous 12Ala polymorphism. This study suggests that Pro12Ala polymorphism is unrelated to BMD level in Egyptian thalassemic patients. Further studies on a larger population of patients are still needed to confirm this finding.

Open Access Original Research Article

Comparative Effect of Chilli Pepper (Capsicum frutescens) Extract and Capsaicin on Some Haematological Parameters and Serum Electrolytes in Albino Wistar Rats

J. N. Nwangwa, A. L. Udefa, S. C. Anyaibe, A. S. Iragunima, N. C. Eze

International Blood Research & Reviews, Page 1-8
DOI: 10.9734/IBRR/2016/29195

Aim: Capsaicin is the active ingredient in chilli pepper, and is responsible for the pungency of chilli pepper. This study compared the effect of ethanolic extract of chilli pepper fruit and capsaicin on haematological parameters and serum electrolytes in female albino Wistar rats on the background that they are widely consumed in foods.

Methodology: Fifteen female Wistar rats (140 – 200 g b.w) fed with rat feed and water ad libitum were divided into three groups (n = 5) thus: control, chilli pepper and capsaicin groups. The three groups were treated with daily oral administration of 0.2 mL normal saline, chilli pepper extract (5 mg/100 g b.w) and capsaicin (3 mg/100 g b.w) respectively, for 30 days. Blood samples were collected from each animal via cardiac puncture for assessment of haematological parameters and serum concentration of electrolytes.

Results: Red blood cell (RBC) count, haemoglobin (Hb) concentration and packed cell volume (PCV) in both treated groups were significantly (p<0.01) reduced compared with control. PCV was significantly (p<0.05) reduced in capsaicin group compared with the chilli pepper group. Platelet count and platelet large cell ratio (P-LCR) were significantly reduced (p<0.01) in capsaicin group compared with the control. Serum Na+, Cl-, and urea concentrations showed no significant (p>0.05) difference among groups, but creatinine level decreased significantly (p<0.05) in the treated groups compared with the control. Serum HCO3- increased while K+ decreased significantly (p<0.05) in capsaicin treated group compared with the control. Furthermore, serum Kincreased (p<0.05) in chilli pepper group, compared with the control.

Conclusion: Capsaicin and chilli pepper did not cause serious electrolyte imbalance, but reduced red cell indices. Additionally, capsaicin altered platelet parameters. Therefore, we suggest that capsaicin might be detrimental to individuals with bleeding and/or blood coagulation disorders.

Open Access Original Research Article

Sickle Cell Carrier Frequency and the Need for Genetic/ Pre-marital Counseling among Students of a Nigerian University

Ugwu Ngozi Immaculata, Udeh Jude Nnanna

International Blood Research & Reviews, Page 1-4
DOI: 10.9734/IBRR/2016/29431

Aims: To determine the sickle cell carrier frequency among undergraduate students of a Nigerian University with a view to evaluate the need to institute genetic and premarital counseling program.

Methodology: This was a retrospective study and record of haemoglobin electrophoresis results of students screened between May 2010 and April 2011 was obtained from Ebonyi State University Medical Center. Data was analyzed using Epi info software, version 3.5.4.

Results: Three thousand, two hundred and eighty three results were obtained comprising 1749 (53.3%) males. The age of the students ranged from 16 – 47 years with mean age of 22 ±5 years. Among the population studied, haemoglobin AA was 74.47%, AS 25.19%, SS 0.18%, AC 0.06%, SC 0.10%.

Conclusion: Sickle cell carrier frequency was found to be high among the study population. There is need to institute genetic and pre-marital counseling program among the students in order to help them take informed decision concerning their marriage so as to prevent procreation of children affected with sickle cell disease.