Novel fondaparinux protocol for anticoagulation therapy in adults with renal failure and suspected heparin-induced thrombocytopenia: a retrospective review of institutional protocol

Plain Language Summary New Fondaparinux Protocol to Reduce the Risk of Blood Thickening and Blood Clots Formation in Adults with Kidney Disease and Heparin-induced Thrombocytopenia (drop in platelets after the use of heparin): A Test Study. Fondaparinux is a drug used to treat patients suffering from thrombosis (clot in blood) and prevent vessels occlusions. When patients have kidney disease, the ideal treatment for thrombosis would be heparin; and, in case of Heparin Induced Thrombocytopenia (HIT), an unexpected drop in platelets after the use of heparin, the ideal treatment would be argatroban or bivalirudin. Fondaparinux can be used for HIT. However, studies recommend against its use in kidney disease as it might accumulate and cause bleeding. We were put in a challenging situation where we had patients with life-threatening thrombosis, kidney disease, HIT and unavailability of both argatroban and bivalirudin. Our only option was fondaparinux. We had to devise a safe and efficient protocol. The starting dose was the one used had the patient had a normal kidney function. Then, anti-Factor Xa activity was regularly measured with the target level 0.6-1.3units/ml 4 h after a dose. The dose was individualized, changed based on the Factor Xa activity result, the risk of bleeding or thrombosis, the overall kidney function and the need for dialysis. Our protocol was tested on 10 patients. All our patients could reach the target and safe Factor Xa activity. We had 2 exceptions. The first had a clotting event despite having therapeutic Factor Xa activity and the second was a very sick cancer patient who was bleeding despite skipping many doses of fondaparinux. We consider that these 2 cases developed complications due to their medical conditions rather than the use of fondaparinux. We concluded that fondaparinux can be safely used in patients with kidney disease, granted that Factor Xa activity is measured, the risk of bleeding is weighed to the risk of thrombosis and the dose is individualized. However, our sample size is small and further studies with a larger number of patients are needed to draw a conclusion

The hypertensive potential of estrogen: An untold story

Cardiovascular disease (CVD) is the major cause of morbidity and mortality worldwide. The implication of estrogen in this disease has been extensively studied. While the vast majority of published research argue for a cardioprotective role of estrogen in vascular inflammation such as in atherosclerosis, the role of estrogen in hypertension remains far from being resolved. The vasorelaxant effect of estrogen has already been well-established. However, emerging evidence supports a vasoconstrictive potential of this hormone. It has been proposed that the microenvironment dictates the effect of estrogen-induced type 1 nitric oxide synthase-1 (nNOS) on vasotone. Indeed, depending on nNOS product, nitric oxide or superoxide, estrogen can induce vasodilation or vasoconstriction, respectively. In this review, we discuss the evidence supporting the vasorelaxant effects of estrogen, and the molecular players involved. Furthermore, we shed light on recent reports revealing a vasoconstrictive role of estrogen, and speculate on the underlying signaling pathways. In addition, we identify certain factors that can account for the discrepant estrogenic effects. This review emphasizes a yin-yang role of estrogen in regulating blood pressure. 2019This publication was made possible by an MPP Fund (#320133) from the American University of Beirut-Faculty of Medicine to Ali Eid and The National Center for Scientific Research (CNRS) to Manal Fardoun.Scopu

MicroRNAs as Potential Pharmaco-targets in Ischemia-Reperfusion Injury Compounded by Diabetes.

Ischemia-Reperfusion (I/R) injury is the tissue damage that results from re-oxygenation of ischemic tissues. There are many players that contribute to I/R injury. One of these factors is the family of microRNAs (miRNAs), which are currently being heavily studied. This review aims to critically summarize the latest papers that attributed roles of certain miRNAs in I/R injury, particularly in diabetic conditions and dissect their potential as novel pharmacologic targets in the treatment and management of diabetes. PubMed was searched for publications containing microRNA and I/R, in the absence or presence of diabetes. All papers that provided sufficient evidence linking miRNA with I/R, especially in the context of diabetes, were selected. Several miRNAs are found to be either pro-apoptotic, as in the case of miR-34a, miR-144, miR-155, and miR-200, or anti-apoptotic, as in the case of miR-210, miR-21, and miR-146a. Here, we further dissect the evidence that shows diverse cell-context dependent effects of these miRNAs, particularly in cardiomyocytes, endothelial, or leukocytes. We also provide insight into cases where the possibility of having two miRNAs working together to intensify a given response is noted. This review arrives at the conclusion that the utilization of miRNAs as translational agents or pharmaco-targets in treating I/R injury in diabetic patients is promising and becoming increasingly clearer

The hypertensive potential of estrogen: An untold story

Cardiovascular disease (CVD) is the major cause of morbidity and mortality worldwide. The implication of estrogen in this disease has been extensively studied. While the vast majority of published research argue for a cardioprotective role of estrogen in vascular inflammation such as in atherosclerosis, the role of estrogen in hypertension remains far from being resolved. The vasorelaxant effect of estrogen has already been well-established. However, emerging evidence supports a vasoconstrictive potential of this hormone. It has been proposed that the microenvironment dictates the effect of estrogen-induced type 1 nitric oxide synthase-1 (nNOS) on vasotone. Indeed, depending on nNOS product, nitric oxide or superoxide, estrogen can induce vasodilation or vasoconstriction, respectively. In this review, we discuss the evidence supporting the vasorelaxant effects of estrogen, and the molecular players involved. Furthermore, we shed light on recent reports revealing a vasoconstrictive role of estrogen, and speculate on the underlying signaling pathways. In addition, we identify certain factors that can account for the discrepant estrogenic effects. This review emphasizes a yin-yang role of estrogen in regulating blood pressure. 2019This publication was made possible by an MPP Fund (#320133) from the American University of Beirut-Faculty of Medicine to Ali Eid and The National Center for Scientific Research (CNRS) to Manal Fardoun.Scopu