Clinical and Hematological Features of 335 Patients of Chronic Myelogenous Leukemia Diagnosed at Single Centre in Northern Pakistan

There are no studies regarding analysis of clinical and haematological features of chronic myelogenous leukemia (CML) from Pakistan. This study analyzes the data of patients suffering from CML, reporting to a major referral Institute in Northern Pakistan in the past 6 years and 3 months. CML constitutes approximately 80% of all myeloproliferative disorders, with a peak incidence between 21-50 years of age, and a male:female ratio of 2:1. Anaemia and massive splenomegaly were the main clinical features found in 92% and 47% patients respectively. There was significant correlation between anaemia and WBC counts with degree of splenomegaly. Three percent of all CML patients presented as de novo accelerated phase, and another 3% presented as blast crises without any previous history of chronic phase. The ratio of myeloid and lymphoid blast crisis was 2:1. Median duration of chronic phase in patients on hydroxyurea treatment was 6 years. Thirty six percent of patients in chronic phase of CML belonged to intermediate and high risk according to Sokal and Hasford scoring systems. In contrast to the Caucasian populations where the peak incidence of the disease is in 6th to 7th decade, CML occurs in Pakistan in a much younger population, with a broad peak between 21-50 years of age. Patients present in fairly advanced disease because of poor access to health care facilities, due to non-affordability and lack of health insurance coverage.

Clinicopathological Features and Outcomes of T- and NK-Cell Lymphomas in European Russia

With the introduction of the revised World Health Organization Classification of Tumors of Hematopoietic and Lymphoid Tissues in 2001, many patients had to be re-evaluated for the correct diagnosis of T- and NK-cell lymphomas. Because some T-cell malignancies are associated with poor outcome, it is important to identify subsets of patients that may benefit from novel or more intensive therapies. The purpose of this study was to determine, for the first time, the relative frequencies, pathological features and outcomes of patients with T- and NK-cell lymphomas in a predominantly Russian Slavic population. We identified 291 patients with a diagnosis of T- and NK-cell malignancies treated at our Center between 2000-2008. In applying the revised WHO classification, we confirmed the diagnosis and had complete clinical follow up and pathological information on 264 cases that were included in the analysis. We found some differences in frequency of several subsets as compared with previously published reports, including younger age of onset and relatively higher incidence of T-LGL in our patients. We also confirm that intensive treatment regimens of advanced stage PTCL and ALK—ALCL led to considerable improvement in response rates, but not in the overall survival.

Safety and Efficacy of Argatroban in the Management of Heparin-Induced Thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is a life-threatening adverse reaction to heparin therapy that is characterized by thrombocytopenia and an increased risk of venous and arterial thrombosis. According to guidelines, in patients with strongly suspected or confirmed HIT all sources of heparin have to be discontinued and an alternative, nonheparin anticoagulant for HIT treatment must immediately be started. For both the prophylaxis of thrombembolic events in HIT and the treatment of HIT with thrombosis the direct thrombin inhibitor argatroban is approved in the United States. The objective of this review is to describe the mechanism of action and the pharmacokinetic profile of argatroban, to characterize argatroban regarding its safety and therapeutic efficacy and to discuss its place in therapy in HIT.

C1 Esterase Inhibitor (Human) for the Treatment of Acute Hereditary Angioedema

Hereditary angioedema (HAE) is a relatively rare disease characterized by acute episodes of swelling. These swellings can be disfiguring, painful and life-threatening. Since the symptoms occur in different areas and most patients experience a delay in their diagnosis, resulting in unnecessary suffering and dangerous situations. HAE can have a tremendous impact on the quality of life. The major genetic deficiency in this disorder is either an absent or nonfunctional C1INH which regulates the complement, fibrinolitic, kalikrein and plasmin pathways.

Pattern of AST and ALT changes in Relation to Hemolysis in sickle cell Disease

Background Elevated aminotransferase levels are commonly associated with compromised hepatic integrity from various insults. In sickle cell disease, aspartate transaminase (AST) is also released via intravascular hemolysis. This study was done to determine the pattern of changes in AST and alanine transaminase (ALT), in particular the AST:ALT ratio, and to relate these to the hemolytic state, which we consider to be more important than hepatic and cardiac dysfunction in some individuals with sickle cell disease. Methods Serum aminotransferase levels were measured in 330 subjects with sickle cell disease, as well as hemoglobin, reticulocytes, and lactate dehydrogenase. The AST:ALT ratio was designated as a hemolytic marker, and simple and multivariate regression analyses were carried out between this ratio and other hemolytic markers. Results Mean AST and ALT levels were 48.24 % 27.78 and 26.48 % 22.73 U/L, respectively. However, for 49 subjects without sickle cell disease, mean AST and ALT levels were the same, ie, 23.0 U/L. In the subjects with sickle cell disease, the increases in AST levels were far higher than for ALT, supporting its release via intravascular hemolysis. In 95.8% of the subjects with sickle cell disease, the AST:ALT ratio was > 1, but our results did not suggest overt malfunctioning of the liver and heart in the majority of subjects. Conclusion Regression analyses support the use of the AST:ALT ratio as a hemolytic marker, because it has an inverse association with the hemoglobin level. Whether in steady state or in crisis, provided hepatic and cardiac integrity has not been compromised, subjects with sickle cell disease would have higher AST levels due to the hemolytic nature of the condition. This is the first report highlighting the AST:ALT ratio in sickle cell disease.

Pulsed and Tissue Doppler Echocardiographic Changes in Patients with Thalassemia Major

Background Doppler echocardiographic studies of left ventricle (LV) systolic and diastolic function in patients with β-Thalassemia Major (β-TM) had shown different patterns of systolic and diastolic dysfunction. Aim This cross-sectional study was designed to study the LV systolic and diastolic function in patients with β-TM using Pulsed Doppler (PD) and Tissue Doppler (TD) echocardiography. Methods All patients were evaluated clinically and by echocardiography, The study included patients with β-TM (n = 38, age 15.7 ± 8.9 years) compared with an age-matched control group (n = 38, age 15.9 ± 8.9 years). The pulse Doppler indices were normalized for age and heart rate. Results Compared with control patients, M-Mode showed that patients with β-TM have thicker LV septal wall index (0.659 ± 0.23 vs. 0.446 ± 0.219 cm, P ≤ 0.001), posterior wall index (0.659 ± 0.235 vs. 0.437 ± 0.214 cm, P ≤ 0.01), and larger LVEDD index is (3.99 ± 0.48 vs. 2.170 ± 0.57 mm. P = 0.035). Pulsed Doppler showed high LV trans-mitral E wave velocity (70.818 ± 10.139 vs. 57.532 ± 10.139, p = 0.027) and E/A ratio (1.54 vs. 1.23, P ≤ 0.01). The duration of Deceleration time (DT) and isovolumic relaxation time (IVRT) were significantly shorter in patients with β-TM (150.234 ± 20.0.23 vs. 167.123 ± 19.143 msec, P ≤ 0.01) and (60.647 ± 6.77 vs. 75.474 ± 5.83 msec, P ≤ 0.001), respectively. The ratio of transmitral E wave velocity to the tissue Doppler E wave at the basal septal mitral annulus E/Em– was significantly higher in β-TM group (14.024 ± 2.29 vs. 12.132 ± 1.82, P ≤ 0.01). The Tissue Doppler systolic velocity (Sm) and the early diastolic velocity (Em) were significantly lower in β-TM group compared to control (4.31 ± 1.2 cm/s vs. 6.95 ± 2.1, P ≤ 0.01 and 4.31 ± 2.7 cm/s vs. 5.82 ± 2.5, P ≤ 0.01) respectively. The tricuspid valve velocity was significantly higher than controls (2.993 ± 0.569 vs. 1.93 ± 0.471 m/sec, respectively, P ≤ 0.01). However, the LVEF% and fractional shortening were normal with no significant difference in both groups. Conclusion In this study, patients with β-thalassemia major compared with controls, have significantly thicker LV wall, and larger LV cavity and LV diastolic filling indices suggestive of restrictive pattern with a higher tricuspid valve velocity. These data showed that left ventricle diastolic indices are compromised initially in patients with β-thalassemia major.

Update on Rivaroxaban

Anticoagulants are recommended for the prevention and treatment of venous thromboembolism (VTE). The new anticoagulants which target specific factors in the coagulation cascade offer the advantage that they can be administered orally. These drugs seek to offer safe anticoagulation without the need for regular monitoring and frequent dose adjustment. Some of these newer drugs are in the advanced stages of clinical trials or have already completed them and thereby aim to provide more options in the management of thromboembolism. In the present review we discuss the currently available evidence supporting the use of these new anticoagulants, in particular rivaroxaban.

Platelet Gene Expression as a Biomarker Risk Stratification Tool in Acute Myocardial Infarction: A Pilot Investigation

Platelets play a major role in the pathophysiology of acute myocardial infarction (AMI). Recent evidence reveals megakaryocyte-derived platelet pre-mRNA is spliced to mRNA and then translated into functional proteins in response to external stimulation. An exon microarray analyzes pre-mRNA alternative splicing and is thus applicable for studying gene expression in the anucleate platelet. We hypothesized a subset of megakaryocyte/platelet genes exists that are significantly over or underexpressed in AMI compared with stable coronary artery disease (CAD), yielding a gene expression profile for further study. Microarray analysis employing platelet mRNA was used to generate gene expression data in the above two patient groups. Unsupervised hierarchical clustering has revealed an expression profile that includes 95 over- or under-expressed genes depicted in a heat map where separation of both sets takes place. This preliminary study reveals a platelet-based gene expression signature that differentiates between AMI and stable CAD, and further study may yield a prognostic tool for a future AMI event in atherosclerosis risk factor-based subsets of CAD patients.

Castleman's Disease: A Study of a Rare Lymphoproliferative Disorder in a University Hospital

Castleman's disease (CD) is a group of rare lymphoproliferative disorders sharing characteristic clinical and histological features, and usually accompanied by a marked systemic inflammatory response. Three histological patterns of lymph nodes were described: the hyaline-vascular, the plasma-cell and the mixed types. The former is more common (80%-90%) and tends to be localized. The plasma cell type is more aggressive and usually multicentric. It is interesting that the inflammatory manifestations seem to be related to a lymph node lesion, because the systemic symptoms and inflammatory activity can return to normal after surgical excision or successful medical treatment of the disease. We report here our 15-year experience with this rare disease in King Fahd Hospital of the University, Al-Khobar, Saudi Arabia, focusing on the clinical features, therapy, and patients'outcome.

Birth MCV and MCH are Quite Reliable Parameters for the Prediction of Alpha Thalassemia Trait

To assess some simple blood parameters at birth that can be used as a basis to suspect α-thalassemia minor (ATM), a prospective study involving 202 consecutive neonates with MCV of less than 95 fl or less were checked for Hb Barts by HPLC. The group was divided into two, one with an MCV of 90-95 (89 cases) and the other with an MCV below 90 (113 cases). For control, 104 consecutive neonates with an MCV ≥ 95 fl were similarly checked. It has been confirmed that an MCV that is below 90 fl, especially with and MCH of ≤30 pg is a strong indicator of the presence of ATM (109/113). On the other hand, MCV of 90 or more, especially with an MCH of 30 or more is a strong negative indicator for ATM (70/89). Firm diagnosis of ATM at birth can thus be secured in majority of neonates.