Thrombogenesis in sickle cell disease

Tomer, Aaron; Harker, Laurence A.; Kasey, Suha; Eckman, James R.

doi:10.1067/mlc.2001.115450

Cited by 199 publications

(205 citation statements)

References 41 publications

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“…[82][83][84][85][86] Hemostatic abnormalities, including low protein C and protein S levels, and elevated plasma concentrations of TAT, F 1,2 , and D-dimer complexes have been found in sickle cell patients. 61,75,[87][88][89] In addition, chronic platelet activation was indicated by the elevated plasma levels of platelet factor 4 (PF4) and ␤-thromboglobulin (␤-TG) and the expression of P selectin and enhanced binding of annexin V to the SCD platelets. 89 These markers of platelet activation, thrombin generation, and enhanced fibrinolyisis were significantly elevated in asymptomatic subjects with SCD and further increased during episodes of pain.…”

Section: Similarity Of Thromboembolic Manifestations and Hemostatic Cmentioning

confidence: 99%

The hypercoagulable state in thalassemia

Eldor

Rachmilewitz

2002

Blood

436

376

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Thalassemia is a congenital hemolytic disorder caused by a partial or complete deficiency of ␣-or ␤-globin chain synthesis. Homozygous carriers of ␤-globin gene defects suffer from severe anemia and other serious complications from early childhood. The disease is treated by chronic blood transfusion. However, this can cause severe iron overload resulting in progressive organ failure. Some forms of ␣ thalassemia are also associated with a similar clinical picture. Despite the difficulties associated with treatment, standards of care for thalassemic patients have improved in recent years, resulting in almost doubling of the average life expectancy. As a consequence, additional previously undescribed, complications are now being recognized. In particular, profound hemostatic changes have been observed in patients with ␤-thalassemia major (␤-TM) and ␤-thalassemia intermedia (␤-TI) and also in patients with ␣ thalassemia (hemoglobin H disease). The presence of a higher than normal incidence of thromboembolic events, mainly in ␤-TI, and the existence of prothrombotic hemostatic anomalies in the majority of the patients, even from a very young age, have led to the recognition of the existence of a chronic hypercoagulable state in thalassemic patients. Despite the appearance of numerous publications on the frequent occurrence of thromboembolic complications in thalassemia, this complication has not been emphasized or comprehensively reviewed. This review summarizes the current literature and discusses possible mechanisms of the lifelong hypercoagulable state that exists in thalassemia. (Blood. 2002;99:36-43)

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Section: Similarity Of Thromboembolic Manifestations and Hemostatic Cmentioning

confidence: 99%

The hypercoagulable state in thalassemia

Eldor

Rachmilewitz

2002

Blood

436

376

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“…A biochemical coagulopathy is evident in patients with sickle cell anemia both during acute vasoocclusive events and during ''steady state'' between acute events [1,2]. This is accompanied by-and is presumably causally related to-risk for clinical thrombosis, evident in the form of ischemic stroke completion and pulmonary thrombosis.…”

Section: Introductionmentioning

confidence: 99%

Endothelial nitric oxide synthase and nitric oxide regulate endothelial tissue factor expression in vivo in the sickle transgenic mouse

et al. 2009

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Activation of the coagulation system is a characteristic feature of sickle cell anemia, which also includes clinical thrombosis. The sickle transgenic mouse abnormally expresses tissue factor (TF) on the pulmonary vein endothelium. Knowing that this aberrancy is stimulated by inflammation, we sought to determine whether nitric oxide (NO) contributes to regulation of endothelial TF expression in the sickle mouse model. We used the NY1DD sickle mouse, which exhibits a low-TF to high-TF phenotype switch on exposure to hypoxia/reoxygenation. Manipulations of NO biology, such as breathing NO or addition of arginine or L-NAME (N-nitro-L-arginine-methyl-ester) to the diet, caused significant modulations of TF expression. This was also seen in hBERK1 sickle mice, which have a different genetic background and already have high-TF even at ambient air. Study of NY1DD animals bred to overexpress endothelial nitric oxide synthase (eNOS; eNOSTg) or to have an eNOS knockout state (one eNOS 2/2 animal and several eNOS 1/2 animals) demonstrated that eNOS modulates endothelial TF expression in vivo by down-regulating it. Thus, the biodeficiency of NO characteristic of patients with sickle cell anemia may heighten risk for activation of the coagulation system. Am. J. Hematol. 85:41-45, 2010. V

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“…The fact that leukocytes are far larger, stiffer, and stickier than red cells, they are more effective in slowing microvascular blood flow, and ultimately, the initiation and propagation of vasoocclusion (Chiang and Frenette, 2005;Hebbel et al, 2009). The prothrombotic activity (Ataga and Orringer, 2003;Setty, 2001a, 2001b) and elevated levels of markers of platelet activation, such as plasma soluble P-selectin (CD62P) and CD40L (Inwald et al, 2000;Tomer et al, 2001a;Wun et al, 1997), that are manifested in steady state patients are thought to contribute significantly to vasoocclusive events.…”

Section: Pathophysiology Of Vasoocclusionmentioning

confidence: 99%

“…The effect fish oil supplementation, a source of EPA and DHA, was investigated in African-American HbSS patients (n 5 6) by Tomer et al (2001a). The patients were given menhaden fish oil (0.25 g/kg/day) containing 12% EPA and 18% DHA, or placebo (olive oil, 0.25 g/kg/day) for 1 year.…”

Section: Omega-3 Fatty Acid Supplementation Of Sickle Cell Patientsmentioning

confidence: 99%