Clinical Hemorheology and Microcirculation - Volume 68, issue 2-3

Authors: Coates, Thomas D. | Chalacheva, Patjanaporn | Zeltzer, Lonnie | Khoo, Michael C.K.

Article Type: Research Article

Abstract: Sickle cell disease (SCD) is a genetic disorder of hemoglobin producing hemoglobin-S (HbS) and resulting in recurrent severe episodes of pain, organ damage and premature death due to vaso- occlusion. Deoxy HbS polymerizes, causing red cells to become rigid and lodge in the microvasculature if they do not escape into larger vessels before this transformation occurs. The mechanism that triggers this transition from steady state to vaso-occlusive crisis (VOC) is not known. Patients state that cold, emotional stress, and pain itself can trigger these events. In spite of the connection between these symptoms and the autonomic nervous system (ANS), and …the fact that the ANS regulates regional microvascular blood flow, the role of the ANS in sickle pathophysiology has not been significantly investigated. We will briefly review the mechanism of SCD vaso-occlusion, the dysautonomia associated with SCD and sickle trait, and the role that the ANS may play in the genesis of sickle vaso-occlusive crisis. Show more

DOI: 10.3233/CH-189011

Citation: Clinical Hemorheology and Microcirculation, vol. 68, no. 2-3, pp. 251-262, 2018

Authors: Conran, Nicola | Belcher, John D.

Article Type: Research Article

Abstract: The primary β-globin gene mutation that causes sickle cell disease (SCD) has significant pathophysiological consequences that result in hemolytic events and the induction of the inflammatory processes that ultimately lead to vaso-occlusion. In addition to their role in the initiation of the acute painful vaso-occlusive episodes that are characteristic of SCD, inflammatory processes are also key components of many of the complications of the disease including autosplenectomy, acute chest syndrome, pulmonary hypertension, leg ulcers, nephropathy and stroke. We, herein, discuss the events that trigger inflammation in the disease, as well as the mechanisms, inflammatory molecules and cells that propagate these …inflammatory processes. Given the central role that inflammation plays in SCD pathophysiology, many of the therapeutic approaches currently under pre-clinical and clinical development for the treatment of SCD endeavor to counter aspects or specific molecules of these inflammatory processes and it is possible that, in the future, we will see anti-inflammatory drugs being used either together with, or in place of, hydroxyurea in those SCD patients for whom hematopoietic stem cell transplants and evolving gene therapies are not a viable option. Show more

Keywords: Cytokine, endothelium, hemolysis, hydroxyurea, vaso-occlusion

DOI: 10.3233/CH-189012

Citation: Clinical Hemorheology and Microcirculation, vol. 68, no. 2-3, pp. 263-299, 2018

Authors: Faes, Camille | Sparkenbaugh, Erica M. | Pawlinski, Rafal

Article Type: Research Article

Abstract: Chronic activation of coagulation is one of the features of sickle cell disease (SCD). Increased tissue factor expression, phosphatidylserine exposure, thrombin generation and fibrinolysis, as well as decreased levels of natural anticoagulants have been reported in SCD patients and in the mouse models of SCD. Consistent with this, patients with SCD are prone to develop thrombotic complications. In addition, the altered morphology of sickle red blood cells (RBC) may also alter the properties and dynamics of clot formation in SCD patients. Clinical data and results from animal models have revealed complex interactions between coagulation, chronic hemolysis, and inflammation suggesting that …activation of coagulation may contribute to the pathophysiology of SCD. Show more

Keywords: Sickle cell anaemia, procoagulant state, haemolysis, clot, microparticles

DOI: 10.3233/CH-189013

Citation: Clinical Hemorheology and Microcirculation, vol. 68, no. 2-3, pp. 301-318, 2018

Authors: Romana, Marc | Connes, Philippe | Key, Nigel S.

Article Type: Research Article

Abstract: Several pathophysiological pathways in sickle cell disease (SCD), the most prevalent hemoglobinopathy worldwide, result in activation of circulating blood cells and the release of submicron vesicles, so-called microparticles (MPs). MPs are candidate biomarkers in vascular disease that exhibit functional biological properties. Compared to healthy individuals, higher level of plasma MPs, mostly derived from platelets and red blood cells (RBC), has been repeatedly observed in SCD patients in their steady-state condition. In contrast, conflicting results have been obtained on the impact of SCD complications and hydroxyurea treatment on circulating MP concentrations, largely due to non-standardized pre- and analytical procedures. Several factors …responsible for the increased release of MPs by RBC have been identified in SCD such as sickling/unsickling, oxidative stress and abnormal activity of RBC acid sphingomyelinase. Besides their well-known pro-coagulant effect, sickle RBC-derived MPs produced ex vivo can induce ROS production by endothelial cells and promote a pro-inflammatory and pro-adhesive phenotype that may lead to renal occlusion in SCD mice. However, the functional properties of circulating MPs in human sickle cell disease remain to be studied and fully characterized. Show more

Keywords: Sickle cell disease, microparticles, physiopathology

DOI: 10.3233/CH-189014

Citation: Clinical Hemorheology and Microcirculation, vol. 68, no. 2-3, pp. 319-329, 2018