Every year, thousands of older Americans require emergency treatment to stop bleeding caused by taking warfarin, a frequently prescribed blood-thinning pill. My own mother received this drug in her later years, and her doctors encountered significant challenges getting the dose right. The problem is too much warfarin causes potentially serious bleeding, while too little leaves those who need the drug vulnerable to developing life-threatening clots in their legs or heart. The difference between too little and too much is distressingly small. But what if before writing a prescription, doctors could test for known genetic markers to help them gauge the amount of warfarin that a person should take?
Such tests have been available to doctors and patients for a few years, but they have not been widely used. The recent results of a national clinical trial offer some of the most convincing evidence that it’s time for that to change. In this study of 1,650 older adults undergoing elective hip or knee surgery, patients whose genetic makeup was used to help determine their dose of warfarin were less likely to suffer adverse events, including major bleeding. This trial marks an encouraging success story for the emerging field of pharmacogenomics, the study of how the variations in our genes affect our responses to medicines.
Tags: blood, blood thinner, blood-thinning drugs, clinical trial, coagulation, CYP2C9, CYP4F2, drug safety, drugs, FDA, Genetic InFormatics Trial (GIFT) of Warfarin Therapy to Prevent Deep Venous Thrombosis, geriatrics, GIFT, hematology, hip replacement, knee replacement, medicine, NIH All Of Us Research Program, pharmacogenomics, precision medicine, prescription drugs, randomized clinical trial, vitamin K, VKORC1, warfarin, warfarin dosing, warfarin sensitivity
There are new reports of an outbreak of Ebola virus disease in the Democratic Republic of Congo. This news comes just two years after international control efforts eventually contained an Ebola outbreak in West Africa, though before control was achieved, more than 11,000 people died—the largest known Ebola outbreak in human history . While considerable progress continues to be made in understanding the infection and preparing for new outbreaks, many questions remain about why some people die from Ebola and others survive.
Now, some answers are beginning to emerge thanks to a new detailed analysis of the immune responses of a unique Ebola survivor, a 34-year-old American health-care worker who was critically ill and cared for at the NIH Special Clinical Studies Unit in 2015 . The NIH-led team used the patient’s blood samples, which were drawn every day, to measure the number of viral particles and monitor how his immune system reacted over the course of his Ebola infection, from early symptoms through multiple organ failures and, ultimately, his recovery.
The researchers identified unexpectedly large shifts in immune responses that preceded observable improvements in the patient’s symptoms. The researchers say that, through further study and close monitoring of such shifts, health care workers may be able to develop more effective ways to care for Ebola patients.
Tags: adaptive immune system, Africa, blood, Congo, critical care, Ebola, Ebola epidemic, Ebola treatment, Ebola Virus Disease, global health, hemorrhagic fever, immunity, immunology, infectious disease, innate immunity, NIH Clinical Center, organ failure, pandemic, Sierra Leone, virology, West Africa
Bone marrow transplants offer a way to cure leukemia, sickle cell disease, and a variety of other life-threatening blood disorders.There are two major problems, however: One is many patients don’t have a well-matched donor to provide the marrow needed to reconstitute their blood with healthy cells. Another is even with a well-matched donor, rejection or graft versus host disease can occur, and lifelong immunosuppression may be needed.
A much more powerful option would be to develop a means for every patient to serve as their own bone marrow donor. To address this challenge, researchers have been trying to develop reliable, lab-based methods for making the vital, blood-producing component of bone marrow: hematopoietic stem cells (HSCs).
Two new studies by NIH-funded research teams bring us closer to achieving this feat. In the first study, researchers developed a biochemical “recipe” to produce HSC-like cells from human induced pluripotent stem cells (iPSCs), which were derived from mature skin cells. In the second, researchers employed another approach to convert mature mouse endothelial cells, which line the inside of blood vessels, directly into self-renewing HSCs. When these HSCs were transplanted into mice, they fully reconstituted the animals’ blood systems with healthy red and white blood cells.
Tags: adult stem cell therapy, adult stem cells, B cells, blood, blood cells, blood disorders, blood stem cells, bone marrow transplant, bone marrow transplantation, cell reprogramming, endothelial cells, graft versus host disease, hematopoietic stem cells, HSC, HSCs, immune system, immunosuppression, induced Pluripotent Stem cells, iPS cells, iPSCs, leukemia, red blood cells, regenerative medicine, sickle cell disease, stem cells, T cells, transcription factors, white blood cells
Scientists first described the sickle-shaped red blood cells that give sickle cell disease its name more than a century ago. By the 1950s, the precise molecular and genetic underpinnings of this painful and debilitating condition had become clear, making sickle cell the first “molecular disease” ever characterized. The cause is a single letter “typo” in the gene encoding oxygen-carrying hemoglobin. Red blood cells containing the defective hemoglobin become stiff, deformed, and prone to clumping. Individuals carrying one copy of the sickle mutation have sickle trait, and are generally fine. Those with two copies have sickle cell disease and face major medical challenges. Yet, despite all this progress in scientific understanding, nearly 70 years later, we still have no safe and reliable means for a cure.
Recent advances in CRISPR/Cas9 gene-editing tools, which the blog has highlighted in the past, have renewed hope that it might be possible to cure sickle cell disease by correcting DNA typos in just the right set of cells. Now, in a study published in Science Translational Medicine, an NIH-funded research team has taken an encouraging step toward this goal . For the first time, the scientists showed that it’s possible to correct the hemoglobin mutation in blood-forming human stem cells, taken directly from donors, at a frequency that might be sufficient to help patients. In addition, their gene-edited human stem cells persisted for 16 weeks when transplanted into mice, suggesting that the treatment might also be long lasting or possibly even curative.
Tags: anemia, blood, bone marrow stem cells, Cas9, CRISPR, CRISPR/Cas9, DNA editing, gene editing, genetic blood diseases, genetic engineering, genomics, hemaglobin, hematology, hematopoietic stem cells, human stem cells, immune deficiency, molecular disease, red blood cells, RNA, sickle cell anemia, sickle cell disease, sickle cell triat, sickle mutation, translational medicine