Eltrombopag Reverse Blood Deficiency

In the human body, Bone Marrow produces megakaryocytes, very large cells (10 - 15 times larger than red blood cells 1) aggregate to form platelets (thrombocyte) assist in blood clotting (coagulation), whenever hemorrhage (bleeding) occurs.2 "The mineral calcium, vitamin K, and a protein called fibrinogen help the platelets form a clot." The combination of fibrinogen and platelets form web-mess traps the blood cells by forming a clot or scab. A sufficient amount of calcium and vitamin K nutrients is necessary, otherwise may take longer duration of time to form a clot or bleeding to death may occur. Vitamin supplements sometimes are taken. 3 Normal platelet count 140,000 - 440,000 per microliter. A low platelet count (below 150,000/ml 11) attributed to many diseases, referred to as thrombocytopenia. 4 This prevents people from receiving necessary treatments. 9 Consequence of chemotherapy and secondary hepatitis C infection, approximately 5 - 10 percent of patients develop thrombocytopenia. 10

Symptoms associated to low platelet count include bruising, nosebleeds, red or purple discoloration on the forearms, and/or bleeding gums. 6 Also, blood may appear in the stool or urine. During menstrual periods bleeding may be heavy. 4 These symptoms occur when platelet count falls below 50,000 and worse below 10,000 - 20,000 platelets per microliter. 4 Also, Bone Marrow produces fewer numbers of platelets when patients undergo chemotherapy and/or radiation treatment. Patients may have to receive donated platelets or transfusion. The process to donate platelets may take up to two hours. The procedure involves a collection instrument where platelets are removed from one arm and the balance of the blood is returned to the donor in the other arm. Donation of platelets is not limited by blood types, compared to red blood cell. 5

GlaxoSmithKline developed a new drug eltrombopag (marketed as Promacta in the U.S. and Revolade in Europe by GlaxoSmithKline 8) stimulates the production of blood platelets in the bone marrow. Especially effective for hepatitis C virus patients (Estimated 4.0 million Americans are infected and 170 million World-Wide carry the hepatitis C virus, commonly transmitted by injected drug use. 8 Also, hepatitis C linked to cirrhosis of the liver. 12 ) treated with antiviral medication previously lowered platelet counts further, and attributed in some cases to bleeding in the brain. A phase two trail investigated the safety and effectiveness of eltrombopag in a small population, including 74 hepatitis C patients with thrombocytopenia. 7. The Study conducted at Duke University Medical Center and other medical centers around the world. 8 Patients grouped into four groups and each group received a specific oral dose from 30 - 75 milligrams of eltrombopag daily for four weeks. The results of the trial presented on Monday, October 30, 2006, at the annual meeting of the American Association for the Society of Liver Disease, in Boston. Duke University liver specialists John McHutchison, MD, professor of medicine and the primary investigator for the clinical trial said: "Eltrombopag increases platelet levels to the point where patients with thrombocytopenia can then be effectively treated with the antiviral therapies. If the promising results we've seen so far in these early clinical trials are borne out in future larger scale registration trials, we will be able to potentially treat more patients for whom there are currently no options." 7. Also, Dr. Mchutchison commented eltrombopag effectively increases platelet counts for patients undergoing cancer chemotherapy and broad use for many other diseases. 9 During the trial study, some patients experianced side effects: Dry Mouth, headache, nausea and diarrhea. Dr. McHutchison not concerned regarding these side effects. Subsequently, Professor Mchutchison and other investigators plan to further investigate the effectiveness of Eltrombopag during future Phase three larger clinical trials, before the drug approved by the Food and Drug Administration for distribution. 7

Besides cirrhosis of the liver, eltromobopag can treat other liver diseases attributed to low platelet count. Also, the drug significantly reduces risk of bleeding for patients undergoing surgery or other invasive procedures. 7

Published in the November 29, 2007, issue of the New England Journal of Medicine, validate short - term studies eltrombopag increase platelet count. Experts advice the short term results should be considered cautiously; Long terms studies are necessary to valid the proficiency use of eltrombopag. 9

During a European Haematology Association Congress meeting in Vienna, results of international Phase Three Study showed Revolade increased platelet counts patients administered 50 - 70 mg once daily. 10

References:

1) Megakaryocyte - http://en.wikipedia.org/wiki/Megakaryocyte

2.) platelet - http://www.britannica.com/eb/article-9060348/platelet

3.) Blood - http://www.fi.edu/learn/heart/blood/platelet.html

4.) Thromboctopenia (ITP, TTP) - http://www.merck.com/mmhe/sec14/ch173/ch173d.html

5.) Platelet Donations - http://www.childrenshospitalla.org/body.cfm?id=451

6.) Thrombocytopenia - http://en.wikipedia.org/wiki/Thrombocytopenia

7.) New Drug Helps Hepatitis C Patients Start Antriviral Therapy - http://www.sciencedaily.com/releases/2006/10/061030183252.htm

8.) Hepatitis C Information Central - http://www.hepatitis-central.com/mt/archives/2007/11/index.html

9.) Drug May Help Reverse Clotting Deficiency - http://www.medicinenet.com/script/main/art.asp?articlekey=85526

10.) Phase III data looks promising for GSK's Eltrombopag - http://www.natap.org/2007/HCV/061107_01.htm

11.) Eltrombopag significantly improved platelet count and allowed initiation of antiviral therapy in majority of hepatitis C patients - http://www.gsk.com/ControllerServlet?appId=4&pageId=402&newsid=922

12.) Drug May Help Reverse Clotting Deficiency - http://www.nlm.nih.gov/medlineplus/news/fullstory_58186.html