Navigation Links
UTHealth, Swedish researchers uncover mystery in blood clotting disorder

HOUSTON (Aug. 27, 2013) Fifteen years ago, a hematologist came to Dianna Milewicz, M.D., Ph.D., with a puzzle: Multiple generations of an East Texas family suffered from a moderately severe bleeding disorder, but it wasn't hemophilia.

"No surgeon would do elective surgery because they bled too much after surgery," said Milewicz, professor and director of the Division of Medical Genetics at The University of Texas Health Science Center at Houston (UTHealth). "So we collected DNA and plasma from the family and were able to determine that a genetic variant in the Factor V gene was causing production of an abnormal form of the Factor V protein, which we called FV-Short. Factor V is a protein known to be important for the blood to clot."

But her team at the UTHealth Medical School couldn't pinpoint exactly how the variation was causing the clotting problem until they collaborated with Bjrn Dahlbӓck, M.D., Ph.D., from Lund University, Malm, Sweden.

"Dr. Dahlbӓck is a world expert on Factor V and he was very excited about the research," said Milewicz, who holds the President George H.W. Bush Chair in Cardiovascular Research. She is also on the faculty of The University of Texas Graduate School of Biomedical Sciences and director of the John Ritter Research Program in Aortic and Vascular Diseases at UTHealth.

"I was indeed very excited when hearing about the puzzling results because the knowledge at the time on the role of FV in coagulation could not explain the bleeding disorder. It has been a great privilege to work with Dr. Milewicz and her colleagues to decode the unexpected and intriguing mechanisms on how FV-Short caused the bleeding disorder," said Dahlbck who holds the chair as professor of Blood Coagulation Research at Lund University, Malm, Sweden.

The results were published in today's online issue of the Journal of Clinical Investigation. Milewicz and Dahlbck are senior co-authors.

Genes make proteins that do everything from giving cells shape and structure to helping carry out biological processes. To make the proteins, genes go through a process called alternative splicing that creates coded portions, called exons. The researchers discovered that a mutation in exon 13 of the coagulation FV gene caused a short form of the protein due to changes in the splicing of the exons. That FV-Short protein was unexpectedly found to form a complex in blood with tissue factor pathway inhibitor (TFPI), a protein that inhibits coagulation of the blood. An overabundance of the combined FV-Short/TFPI in the bloodstream keeps the blood from clotting in the affected family members. Other researchers have been looking at ways to inhibit TFPI, which could lead to a treatment for this family's clotting disorder.

What Milewicz called traditional genetics and "old-fashioned biochemistry" by lead co-author Lisa Vincent, Ph.D., led to the discovery of the FV-short protein in the blood of affected family members.

Dahlbӓck's work determined how the FV-Short was causing the problems with clotting the blood. Milewicz said studying this family with a rare blood disorder has provided further insight into how the blood clots.

"We knew there was something wrong with these patients' FV, but proving it required discovering unique properties of FV in coagulation," Vincent said. "After many trials and tribulations, our true success is finally being able to provide an answer to the family about their medical issues."


Contact: Deborah Lake
University of Texas Health Science Center at Houston

Related medicine news :

1. UTHealth, French researchers discover gene defect for new syndrome
2. Lifestyle changes could prevent 400 cardiac events and 200 deaths in Swedish PCI patients
3. Complementary and alternative medicine studied in Swedish surgical care
4. Feinstein Institute Scientist Wins Crafoord Award from Royal Swedish Academy of Sciences for Arthritis Research
5. Surgery is superior to radiotherapy in men with localized PCa, says prize-winning Swedish study
6. Swedish study suggests reduced risk of dementia
7. Extreme Birth Weights Tied to Autism in Swedish Study
8. NIH awards $20 million over 5 years to train next generation of global health researchers
9. Researchers develop a new cell and animal model of inflammatory breast cancer
10. Researchers uncover a viable way for colorectal cancer patients to overcome drug resistance
11. Researchers Find Gene Mutations That May Be a Key to Autism
Post Your Comments:
(Date:11/27/2015)... ... November 27, 2015 , ... Avid collector, Andrew Hawley ... Michigan boxing style concert posters. This is one of Joplin's most famous and beautiful ... at the University of Michigan in Ann Arbor. The According to Hawley, "It is ...
(Date:11/26/2015)... ... November 26, 2015 , ... Patients at ... Michigan, have come together on Thanksgiving Day to share the things that they ... on the Serenity Point YouTube channel, patients displayed what they wrote on index ...
(Date:11/26/2015)... ... November 26, 2015 , ... ... eReferral system for diagnostic imaging in the Waterloo region. Using the Ocean Platform, ... Medicine tests directly from their electronic medical record (EMR) without the need for ...
(Date:11/26/2015)... ... November 26, 2015 , ... The Catalent ... and the need to integrate dose form selection in early phase drug development. ... membership organization supporting and bringing together the UK’s emerging life sciences companies, corporate ...
(Date:11/26/2015)... , ... November 26, 2015 , ... PRMA Plastic Surgery ... 19, 2015, our surgeons performed their 6,000th free flap breast reconstruction surgery! , “What ... up every day excited to rebuild lives and it’s an honor to have served ...
Breaking Medicine News(10 mins):
(Date:11/26/2015)... November 26, 2015 ... the "Radioimmunoassay Market by Type (Reagents ... Industry, Academics, Clinical Diagnostic Labs), Application (Research, ... to 2020" report to their offering. ... the addition of the "Radioimmunoassay Market ...
(Date:11/25/2015)... Nov. 25, 2015  Amgen (NASDAQ: AMGN ) ... (BLA) with the United States ... a biosimilar candidate to Humira ® (adalimumab). Amgen ... submitted to the FDA and represents Amgen,s first BLA ... E. Harper , M.D., executive vice president of Research ...
(Date:11/25/2015)... , Nov. 25, 2015 On Tuesday, ... federal bellwether trial against Wright Medical Technology, Inc. ... their Conserve metal-on-metal hip implant device, awarded $11 ... a two week trial and three days of ... hip device was defectively designed and unreasonably dangerous, ...
Breaking Medicine Technology: