Effects of antiplatelet and anticoagulant medications on the vasoocclusive and thrombotic complications of sickle cell disease: A review of the literature

Charneski, Lisa; Congdon, Heather Brennan

doi:10.2146/ajhp090229

Cited by 31 publications

(24 citation statements)

References 15 publications

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“…The potential benefits of antiplatelet medications have long been discussed for SCD; earlier studies to investigate the effects of aspirin, dipyridamole and heparin, however, were inconclusive [36]–[39]. More recent ongoing trials of antiplatelet agents include those that have employed prasugrel, a P2Y(12) adenosine phosphate (ADP) receptor antagonist that inhibits platelet activation and aggregation, and eptifibatide, an α iib β 3 -integrin antagonist, that has also been used during acute pain episodes [40]–[43].…”

Section: Discussionmentioning

confidence: 99%

Endothelial Activation by Platelets from Sickle Cell Anemia Patients

et al. 2014

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Sickle cell anemia (SCA) is associated with a hypercoagulable state. Increased platelet activation is reported in SCA and SCA platelets may present augmented adhesion to the vascular endothelium, potentially contributing to the vaso-occlusive process. We sought to observe the effects of platelets (PLTs) from healthy control (CON) individuals and SCA individuals on endothelial activation, in vitro. Human umbilical vein endothelial cells (HUVEC) were cultured, in the presence, or not, of washed PLTs from CON or steady-state SCA individuals. Supernatants were reserved for cytokine quantification, and endothelial adhesion molecules (EAM) were analyzed by flow cytometry; gene expressions of ICAM1 and genes of the NF-κB pathway were analyzed by qPCR. SCA PLTs were found to be more inflammatory, displaying increased adhesive properties, an increased production of IL-1β and a tendency towards elevated expressions of P-selectin and activated αIIbβ3. Following culture in the presence of SCA PLTs, HUVEC presented significant augmentations in the expressions of the EAM, ICAM-1 and E-selectin, as well as increased IL-8 production and increased ICAM1 and NFKB1 (encodes p50 subunit of NF-κB) gene expressions. Interestingly, transwell inserts abolished the effects of SCA PLTs on EAM expression. Furthermore, an inhibitor of the NF-κB pathway, BAY 11-7082, also prevented the induction of EAM expression on the HUVEC surface by SCA PLTs. In conclusion, we find further evidence to indicate that platelets circulate in an activated state in sickle cell disease and are capable of stimulating endothelial cell activation. This effect appears to be mediated by direct contact, or even adhesion, between the platelets and endothelial cells and via NFκB-dependent signaling. As such, activated platelets in SCD may contribute to endothelial activation and, therefore, to the vaso-occlusive process. Results provide further evidence to support the use of anti-platelet approaches in association with other therapies for SCD.

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Section: Discussionmentioning

confidence: 99%

Endothelial Activation by Platelets from Sickle Cell Anemia Patients

et al. 2014

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“…Other antiplatelet agents such as aspirin/dipyridamole, clopidrogel and ticlopidine have not been studied in acute stroke, although they do have a role for secondary prevention [31,36]. In the specific case of adults with SCD, aspirin, aspirin combined with dipyridamole and ticlopidine have all been evaluated in small studies for the prevention or treatment of pain from SCD without increased bleeding [39], but these agents increase the risk of hemorrhagic stroke in the general population [40]. This may be of additional concern in adults with SCD given limited data that hemorrhagic stroke occurs even more frequently in those with a history of ischemic stroke as children [41].…”

Section: Treatment Of Ischemic Strokementioning

confidence: 99%

The epidemiology, evaluation and treatment of stroke in adults with sickle cell disease

Strouse

Lanzkron

Urrutia

2011

Expert Review of Hematology

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Stroke is a frequent and severe complication in adults with sickle cell disease. Ischemic stroke often causes physical and cognitive disability, while hemorrhagic stroke has a high mortality rate. As more children survive, the number of strokes in adults is increasing, yet stroke remains poorly understood. We review the epidemiology of ischemic and hemorrhagic stroke in adults with sickle cell disease and outline a practical approach to the evaluation of stroke including both sickle cell disease specific and general risk factors. We discuss the acute treatment and secondary prevention of stroke in this population based on the evidence in children with sickle cell disease and the general population, in addition to the limited studies in adults with sickle cell disease.

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“…The most common cause of stroke in SCD patients is large vessel narrowing with superimposed thrombosis, as demonstrated by histopathology studies [15,16]. Additionally, postmortem evaluations of patients with SCD often reveal old and new thrombi in the pulmonary vasculature [26], and thrombosis in sickle cell patients is also associated with avascular necrosis of large joints, leg ulcers, and certain pregnancy complications [15,16]. The hypercoaguable state associated with SCD is thought to be due to abnormalities in the cell membrane of RBCs.…”

Section: Discussionmentioning

confidence: 99%

“…The hypercoaguable state associated with SCD is thought to be due to abnormalities in the cell membrane of RBCs. Repeated cycles of sickling and unsickling can lead to exposure of phosphatidylserine, an anionic phospholipid generally restricted to the inner cell membrane of RBCs [15,16,27]. Studies have suggested that this abnormal phosphatidylserine exposure in a subset of RBCs can lead to in vivo activation of coagulation.…”

Section: Discussionmentioning

confidence: 99%

“…However, given the prevalence of vasoocclusive events in SCD, the risks associated with COS in this clinical setting are ambiguous. Given their red blood cells (RBCs) abnormalities, patients with SCD are at increased risk for thromboembolic disease [15,16]. Whether the supraphysiologic estradiol levels associated with COS increases this risk significantly is unknown.…”

Section: Introductionmentioning

confidence: 99%

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Oocyte cryopreservation in a patient with sickle cell disease prior to hematopoietic stem cell transplantation: first report

Dovey

Krishnamurti

Sanfilippo

et al. 2012

J Assist Reprod Genet

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Purpose To report the first occurrence of successful ovarian stimulation, oocyte retrieval and oocyte cryopreservation for fertility preservation in an adolescent with severe sickle cell disease scheduled to undergo a hematopoietic stem cell transplant Methods Case report Results A 19 year old female with severe sickle cell disease presented for fertility preservation counseling prior to hematopoietic stem cell transplantation. She ultimately underwent ovarian stimulation using a minimal stimulation GnRH antagonist protocol resulting in the successful banking of oocytes prior to transplant. The unique hazards associated with ovarian stimulation in patients with sickle cell disease, such as thrombosis and vaso-occlusive events, are discussed and the methods undertaken to minimize these risks are described. Conclusions Controlled ovarian hyperstimulation and oocyte banking for fertility preservation is feasible in young women with sickle cell disease requiring hematopoietic stem cell transplant and deserves further investigation. Given the elevated risk of thrombosis and predisposition to painful vaso-occlusive events, controlled ovarian hyperstimulation in patients with sickle cell disease is not straightforward and requires a multi-disciplinary team approach to adequately address and minimize the risks in this unique patient population.

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Effects of antiplatelet and anticoagulant medications on the vasoocclusive and thrombotic complications of sickle cell disease: A review of the literature

Abstract: Based on the existing data, sickle cell disease should not be used as an independent indication for treatment with an antiplatelet or anticoagulant medication.

Cited by 31 publications

References 15 publications

Endothelial Activation by Platelets from Sickle Cell Anemia Patients

Endothelial Activation by Platelets from Sickle Cell Anemia Patients

The epidemiology, evaluation and treatment of stroke in adults with sickle cell disease

Oocyte cryopreservation in a patient with sickle cell disease prior to hematopoietic stem cell transplantation: first report

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