Opposing Role, Depending on the Stage, of PU.1 during Erythroid Differentiation

PU.1 is a member of the Ezb transformation-specific sequence family of transcription factors and is expressed mainly in granulocytic, monocytic and B-lymphoid cells. The downregulation of PU.1 was reported to play a role in the pathogenesis of various hematological malignancies, including Acute Myeloid Leukemia (AML), multiple myeloma and Myelodysplastic Syndrome (MDS). 

PU.1 is also normally present in immature erythroid cells , and several reports have indicated that their downregulation is required for erythroid terminal differentiation. Constitutive upregulation of PU.1 is believed to be the main cause for a blockade in the differentiation process of Murine Erythroleukemia (MEL) cells. However, several findings  indicate a requirement for PU.1 expression for erythroid differentiation. Back et al.have reported an important study. They produced a line of PU.1 deficient mice carrying a green fluorescent protein reporter at this locus. They revealed that, PU.1 deficient fetal erythroid progenitors lose their self-renewal capacity and undergo proliferation arrest, premature differentiation and apoptosis. Read more>>>>>>>>>>>>

Sustained Responses following Treatment with Romiplostim in Immune Thrombocytopenia

Immune thrombocytopenia (ITP) is an organ-specific autoimmune disease leading to a low peripheral blood platelet count. The underlying pathophysiology is complex and involves platelet destruction caused by antibodies directed at platelet glycoproteins and a relative platelet underproduction by the bone marrow. Until recently, most treatments have targeted only platelet destruction by inducing immune suppression. 

Recently a new class of therapy, the thrombopoietin receptor agonists (TRA), has been developed which enhances platelet production by the marrow. TRAs, which include the peptibody romiplostim, and the oral small molecule eltrombopag, are regarded as palliative therapies which elevate the platelet count in refractory patients, who continue to bleed, to cover invasive procedures or to delay or be a bridge to transplant. The expectation is that the platelet count will fall to baseline once the drug is stopped. Romiplostim is a thrombopoietin peptide mimetic agent recently approved for the treatment of adults with chronic immune thrombocytopenia (ITP). Read more>>>>>>>>>>>>

Skin Signs of Graft Versus Host Disease

Graft-Versus-Host Disease (GVHD) is a common complication associated with high mortality that results from the immunologic insult of introducing immunologically competent cells into an immunoincompetent host, which allows these grafted cells to mount a destructive immune response against the recipient tissues. The main cause ofGVHD is allogenic Hematopoietic Cell Transplantation (HCT) although it can also be seen secondary to solid organ transplantation. 

The skin is one of the initial and main organs affected by GVHD in up to 94.2% of patients, and as such, recognizing these dermatologic manifestations represents an important tool for early diagnosis allowing prompt installation of treatment, although an early start to therapy is not always determinant of outcome. Historically, GVHD has been divided into acute GVHD (aGVHD) and chronic GVHD (cGVHD). Acute GVHD describes a distinctive syndrome of dermatitis, bilirubin elevation, and diarrea developing within 100 days of transplantation. Chronic GVHD describes a more diverse syndrome developing after day 100. However, this definition falls short, and in 2005 the National Institutes of Health classification included late-onset acute GVHD (after day 100) and an overlap syndrome with features of both acute and chronic GVHD. Read more>>>>>>>>>>>>>>

Intermittent Pneumatic Compression from a Surgical Perspective

In the surgical setting, venous thrombo-embolism (VTE) occurs in 14.5% patients when prophylaxis is not employed. The incidence is reduced to 4.2% with pharmacological prophylaxis, and further to 0.6% when mechanical prophylaxis modalities are combined with pharmacological methods. VTE prophylaxis is conceptually based on gradual risk assessment. One of the most clinically relevant and useful tools for this assessment is the Caprini Score.   

This consists of various medical and surgical conditions, and is primarily designed to screen for any given patient being admitted to a hospital ward. Patients are allocated the relevant risk points for each of the existing conditions. The risk is classified per 9th edition of American College of Chest Physicians(ACCP) guidelines into four categories: very low (0 points); low (1-2 points); moderate (3-4 points) and high (≥5 points). The subsequent management following VTE risk allocation is primarily dictated per the patients bleeding risk at the time of hospitalization. The definition of bleeding risk is rather vague, and is at the discretion of the attending physician. Read more>>>>>>>>>>>>>

Warfarin Therapy: New Challenges of an Old Drug

The anticoagulant drug warfarin is a vitamin K antagonist (VKA), coumarin derivative, formed by the racemic mixture of two optically active isomers known by Rectus (R) and Sinister (S) enantiomers in equal proportion, being the S-warfarin five times more potent. It is normally administered as the racemate and its effect is observed normally within two to seven days after initiation of therapy, according to the administered dose. Warfarin acts by interfering in the interconversion of cyclic 2,3 vitamin K epoxide. 

The vitamin K epoxide reductase is inhibited by therapeutic doses of warfarin inhibiting thus the synthesis of vitamin K-dependent factors, leading to inhibition of γ-carboxylation of clotting factors II, VII, IV and X, and the anticoagulant proteins C and S. Effects on prothrombin time are produced in 24 to 36 hours after the initial dose and reach the maximum plasmatic concentration in 36 to 48 hours, maintained for 48 hours or more after discontinuance of dosing. Read more>>>>>>>>>>>>>