Deep Vein Thrombosis Research Paper

Pradaxa Deep Vein Thrombosis (DVT), also known as venous thromboembolism, is estimated to affect upwards of 900,000 Americans each year (http://www.cdc.gov/ncbddd/dvt/data.html). Treatments for DVT typically consists of two primary options; surgical implementation of a filter within the vena cava to catch blood clots that form and prevent them from moving to parts of the body where they may become dangerous; or through treatment with medication that act as anti-coagulants through thinning blood. Until recently, there has primarily only been one preferred choice by physicians, being Coumadin (Warfarin). However, Coumadin is far from perfect. With public health concerns continuing to grow as more people are affected by DVT each year, pharmaceutical

In it’s current state, no FDA antidote currently exists to reverse the thrombin inhibiting effects of the drug. This means that if severe bleeding does occur, there is no proven way to stop it and may potentially lead to death. While such cases are rare, an antidote to reduce such cases further is necessary. Idarucizumab, a drug currently undergoing phase two clinical trials, demonstrates the capability to completely reverse the effects of dabigatran in study conducted on a small group of human participants. “Idarucizumab is a monoclonal antibody fragment that acts by binding dabigatran with very high affinity” (Allen-Dicker http://blogs.nejm.org/now/index.php/idarucizumab-for-dabigatran-reversal-the-re-verse-ad-trial/2015/08/05/). This ability of Idarucizumab to bind to dabigatran so effectively is due to it’s chemical structure, consisting of four hydroxyl groups in a cyclic formation attached to a tertiary amine. These hydroxyl groups will work to reverse the effectiveness of hydrolysis of dabigatran by attaching to the structure itself and ‘stealing’ the water protons for itself. The current studies show that in patients undergoing urgent procedures, 92% were reported to have normal intraoperative hemostasis after receiving idarucizumab

Such a change may include the use of a stronger base, acting to be attack the water molecules at a much faster rate than the amides of dabigatran can undergo hydrolysis. In order provide a safe way of binding a stronger base to dabigatran to reverse its affects, amino acids already found within the human body may be of use. Amino acids such as proline, leucine, and alanine all contain amine, NH2, functional groups. If one of the amino acids provided was discovered to have binding capabilities, perhaps in a slightly altered form, to dabigatran, the strong basic capabilities of the amines would act to deprotonate water at a very fast rate. The aftereffects of such a reaction may be potentially hazourdous, as the byproduct would be NH3, but that still presents an interesting method of preventing