Sickle cells and sickle trait in thrombosis

Abstract

The blood cells form a beautiful and elegant system. For a century, hematologists have comfortably understood that each type of blood cell has its own independent function in immunity, hemostasis, or oxygen transport, but in this issue of Blood, Faes and colleagues show that nature is far more efficient than that. Faes and colleagues confirm the findings of others that venous fibrin clots entrap red cells. This phenomenon is especially prominent in clots involving sickle erythrocytes (see figure), consistent with the increased rate of venous thromboembolism observed in patients with sickle cell disease. They show that fibrin interacts with phosphatidylserine exposed on the senescent sickle red cell membrane. The entrapped sickle red cells make the attached fibrin more resistant to fibrinolysis by tissue plasminogen activator (tPA), exacerbating the prothrombotic effect. This is an unexpected way that sickle red cells modulate the clotting mechanism.

Sickle red cell entrapment in a blood clot. In this scanning electron micrograph, Faes and colleagues show entrapped sickled red cells in an experimentally induced, fatal inferior vena cava blood clot in a sickle cell mouse. The acellular material appears in other images to be a dense fibrin network. Original magnification ×5000. SS, sickle cell. See Figure 1B in the article by Faes et al that begins on page 2529.