Efficacy and Safety of Recombinant Thrombomodulin for the Prophylaxis of Veno-Occlusive Complication in Allogeneiccit Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis.

BACKGROUND: Hepatic veno-occlusive disease (VOD), also termed as sinusoidal obstruction syndrome (SOS), is a lethal complication after hematopoietic stem cell transplantation (HSCT). Various factors put patients undergoing allogeneic HSCT at an increased risk for VOD. Thrombomodulin (TM) is an important factor which has a wide range of effects, including anticoagulant, anti-inflammatory, angiogenic, and protective effect, on endothelial cells. It plays a role in preventing excessive coagulation and thrombosis by binding with thrombin and inhibiting the coagulation cascade. There are a limited number of options for the prevention of this fatal complication. Recombinant thrombomodulin (rTM), an endothelial anticoagulant co-factor, as prophylactic therapy might be able to prevent veno-occlusive complications after stem cell transplantation. METHODS: A literature search was performed on PubMed, Embase, and Web of Science. We used the following Mesh terms and Emtree terms, "Hepatic Veno-Occlusive Diseases" OR "Sinusoidal Obstruction" OR "Stem Cell Transplantations " AND "Thrombomodulin" from the inception of data up to April 1, 2021. The PICO (Patient/Population, Intervention, Comparison and Outcomes) framework was used for the literature search. RESULTS: For the VOD incidence after HSCTstem cell transplantation, the result was in favor of rTM with a risk ratio (RR) of 0.53 (I2 = 0%, 95% confidence interval [CI] = 0.32-0.89). The incidence of transplant-associated thrombotic microangiopathy (TA-TMA) after HSCT was reduced in rTM group. The RR for incidence of TA-TMA was 0.48 (I2 = 62%, 95% CI = 0.20-1.17) favoring rTM. The RR for incidence of graft-versus-host disease (GvHD) was also lower in rTM group, 0.48 (I2 = 64%, 95% CI = 0.32-0.72). CONCLUSION: In our meta-analysis, we evaluate the efficacy and safety of rTM in the prevention of SOS after HSCT. According to our results, rTM use led to a significant reduction in SOS episodes, TA-TMA, and GvHD after HSCT.

Werner syndrome associated with acroosteolysis.

Werner syndrome (WS) is an autosomal recessive syndrome characterized by genomic instability that affects multiple body systems. The characteristic features of the disease include growth retardation, short stature, alopecia, scleroderma, atrophic skin with ulcerations, infertility, cataracts, premature arteriolosclerosis, diabetes, osteoporosis, and increased risk of malignancies. Werner syndrome protein (WRN) protein deficiency in this disease causes changes in gene expression, similar to those observed in normal aging. As the median age of death in WS is the fourth or fifth decade of life, early diagnosis leads to a better screening opportunity for malignancies. Herein, we present a 28-year-old woman who presented with growth arrest, dyspigmentation, and acroosteolysis and was later diagnosed with Werner syndrome.