T2HemoStat detection of novel clot behavior could direct therapeutic choices for stroke and heart attack victims
T2 Biosystems, a company developing direct detection products enabling superior diagnostics, announced that scientists from the University of Pennsylvania and T2 Biosystems have published a paper in Blood describing novel clot structure biology detected while testing T2 Bio's T2HemoStat™. T2HemoStat is an innovative diagnostic tool for assessing blood clotting, platelet function, fibrinolytic activity and hematocrit measurements from a fingerstick blood sample in about 15 minutes. T2HemoStat uniquely detects millions of data points during a blood coagulation cascade. Researchers at the University of Pennsylvania, utilizing T2HemoStat, detected a signature of a novel clot structure, never before described in scientific literature. This clot structure involves a conformational change in red blood cell structure, termed polyhedrocytes. The presence of these structures could make stroke and heart attack victims less responsive to medications.
Blood clots are made up of fibrin, platelets and erythrocytes. Before now, little was known about the internal structure of contracted clots or the role that erythrocytes play in the contraction process. T2HemoStat is the first diagnostic method to enable the detection of this unique clot structure where erythrocytes are closely packed as polyhedra (polyhedrocytes) to form a seemingly impermeable barrier. This barrier means that these clot structures may be less susceptible to certain medications, called fibrinolytics, used to break up blood clots in the treatment of heart attacks and strokes.
"Physicians treating the millions of patients at risk for thrombosis and bleeding, including after surgery or trauma, are in need of a more convenient method to provide up to the minute results of key hemostatic parameters," commented co-author Douglas B. Cines, MD, Professor of Pathology and Laboratory Medicine and Director of the Special Coagulation Laboratory, Perelman School of Medicine at the University of Pennsylvania.
"Polyhedrocytes are likely to be central to preventing bleeding and promoting blood flow after damage to blood vessels has begun to heal. However, when the process goes awry, in the case of clotting diseases, these tightly packed erythrocytes present a challenge to clot-busting thrombolytic agents, as they are more resistant to fibrinolysis," said co-author John W. Weisel, Ph.D., Professor of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania.
"This landmark publication demonstrates that T2HemoStat can be an important tool to identify biomarkers for companion diagnostics or new drug development, in this case, specifically targeted at highly contracted clots containing polyhedrocytes," added Tom Lowery, Ph.D., Chief Scientific Officer, T2 Biosystems and co-author in the study. "Furthermore, this new finding enabled by T2HemoStat demonstrates the power and versatility of our T2MR® technology both in the research setting and as it can relate to meaningful clinical advances."
The paper, entitled "Clot contraction: compression of erythrocytes into tightly packed polyhedra and redistribution of platelets and fibrin", was authored by Douglas B. Cines, Tatiana Lebedeva, Chandrasekaran Nagaswami, Vincent Hayes, Walter Massefski, Rustem I. Litvinov, Lubica Rauova, Thomas J. Lowery and John W. Weisel. After identification of samples and sample conditions that form this novel clot with T2MR, the group used scanning electron and optical microscopy to determine that contracted clots consist of a meshwork of fibrin and platelet aggregates on the exterior of the clot with a closely-packed, tessellated array of compressed polyhedral erythrocytes (polyhedrocytes) on the interior.
This phenomenon was observable both in vivo and in vitro in humans and mice, and is likely caused by the force that the fibrin and platelets place upon the erythrocytes, as centrifugation of erythrocytes in the absence of these components also generated the polyhedral structure. These results demonstrate how contracted clots form an impermeable barrier important for hemostasis and wound healing and help explain how fibrinolysis is greatly slowed as clots contract.