Plasma Hemoglobin and Hemoglobin Fractions in Sickle Cell Crisis

Naumann, Hans N.; Diggs, L. W.; Barreras, Luis; Williams, Beverly J.

doi:10.1093/ajcp/56.2.137

Cited by 66 publications

(58 citation statements)

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“…Therefore, the presence of these circulating vesicles might explain previous reports of elevated plasma hemoglobin during sickle crisis. 23,24 Indeed, we have observed that 50% Ϯ 32% of PFP hemoglobin can be removed by ultracentrifugation and is, therefore, most likely MP associated (A.S.S. and R.P.H., unpublished data, February 10, 2003).…”

Section: Discussionmentioning

confidence: 96%

Sickle blood contains tissue factor–positive microparticles derived from endothelial cells and monocytes

Shet

Aras

Gupta

et al. 2003

Blood

484

457

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Blood microparticles (MPs) in sickle cell disease (SCD) are reportedly derived only from erythrocytes and platelets. Yet in SCD, endothelial cells and monocytes are activated and abnormally express tissue factor (TF). Thus, sickle blood might contain TF-positive MPs derived from these cells. With the use of flow cytometry to enumerate and characterize MPs, we found total MPs to be elevated in crisis (P ‫؍‬ .0001) and steady state (P ‫؍‬ .02) in subjects with sickle cell disease versus control subjects. These MPs were derived from erythrocytes, platelets, monocytes, and endothelial cells. Erythrocytederived MPs were elevated in sickle crisis (P ‫؍‬ .0001) and steady state (P ‫؍‬ .02) versus control subjects, as were monocytederived MPs (P ‫؍‬ .0004 and P ‫؍‬ .009, respectively). Endothelial and plateletderived MPs were elevated in sickle crisis versus control subjects. Total TF-positive MPs were elevated in sickle crisis versus steady state (P ‫؍‬ .004) and control subjects (P < .0001) and were derived from both monocytes and endothelial cells. Sickle MPs shortened plasma-clotting time compared with control MPs, and a TF antibody partially inhibited this procoagulant activity. Markers of coagulation were elevated in patients with sickle cell disease versus control subjects and correlated with total MPs and TF-positive MPs (P < .01 for both). These data support the concept that SCD is an inflammatory state with monocyte and endothelial activation and abnormal TF activity.

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Section: Discussionmentioning

confidence: 96%

Sickle blood contains tissue factor–positive microparticles derived from endothelial cells and monocytes

Shet

Aras

Gupta

et al. 2003

Blood

484

457

View full text Add to dashboard Cite

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“…For example, in patients with sickle cell disease, the levels of plasma oxyheme range from 2 to 20 µM, with mean levels of 4 µM (18). During vasoocclusive crisis, levels can rise to 20-40 µM (27). Intravascular hemolysis in patients with paroxysmal nocturnal hemoglobinuria produces abdominal pain, gastric and esophageal dystonia, and erectile dysfunction, with levels of plasma Hb ranging from 30 to 120 µM (in heme concentration) and up to 600 µM during paroxysms of hemolysis (28).…”

Section: Figurementioning

confidence: 99%

Hemolysis-associated endothelial dysfunction mediated by accelerated NO inactivation by decompartmentalized oxyhemoglobin

Minneci¹

2005

Journal of Clinical Investigation

286

240

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During intravascular hemolysis in human disease, vasomotor tone and organ perfusion may be impaired by the increased reactivity of cell-free plasma hemoglobin (Hb) with NO. We experimentally produced acute intravascular hemolysis in a canine model in order to test the hypothesis that low levels of decompartmentalized or cell-free plasma Hb will severely reduce NO bioavailability and produce vasomotor instability. Importantly, in this model the total intravascular Hb level is unchanged; only the compartmentalization of Hb within the erythrocyte membrane is disrupted. Using a full-factorial design, we demonstrate that free waterinduced intravascular hemolysis produces dose-dependent systemic vasoconstriction and impairs renal function. We find that these physiologic changes are secondary to the stoichiometric oxidation of endogenous NO by cell-free plasma oxyhemoglobin. In this model, 80 ppm of inhaled NO gas oxidized 85-90% of plasma oxyhemoglobin to methemoglobin, thereby inhibiting endogenous NO scavenging by cell-free Hb. As a result, the vasoconstriction caused by acute hemolysis was attenuated and the responsiveness to systemically infused NO donors was restored. These observations confirm that the acute toxicity of intravascular hemolysis occurs secondarily to the accelerated dioxygenation reaction of plasma oxyhemoglobin with endothelium-derived NO to form bioinactive nitrate. These biochemical and physiological studies demonstrate a major role for the intact erythrocyte in NO homeostasis and provide mechanistic support for the existence of a human syndrome of hemolysis-associated NO dysregulation, which may contribute to the vasculopathy of hereditary, acquired, and iatrogenic hemolytic states. Introduction NO is continuously synthesized from endothelium and regulates homeostatic vascular functions such as vasodilation, inhibition of platelet activation and thrombosis, inhibition of endothelial adhesion molecule and endothelin-1 expression, and modulation of intimal and smooth muscle proliferation (1-5). A paradox and controversy in vascular biology surrounds the near diffusion-limited dioxygenation reaction of NO with oxyhemoglobin that oxidizes NO to nitrate, an inactive metabolite (Reaction 1).

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“…Under normal conditions, plasma cell-free hemoglobin represents approximately 10% of the hemoglobin from red blood cell turnover 18 (average concentration 0.2 μM, range <0.06-0.7). 19 Intravascular hemolysis that exceeds the ability of haptoglobin and haptoglobin-related protein-ApoL1 complexes to bind cell-free hemoglobin results in hemoglobinuria 20 and, based on animal models, cell-free hemoglobin-mediated damage to the proximal tubule may be a mechanism of kidney damage. 21 Cell-free hemoglobin rapidly converts to the less stable methemoglobin followed by release of heme 22 and free heme may also elicit damage to the kidney.…”

Section: Introductionmentioning

confidence: 99%

“…19 Markers of hemolysis have been associated with kidney disease in some [26][27][28][29][30] but not all [31][32][33] SCD cohorts. Hemoglobinuria, determined by urine dipstick analysis, has been observed in 15-42% of adults with SCD, [34][35][36] and is associated with elevated markers of hemolysis and risk of CKD progression.…”

Section: Introductionmentioning

confidence: 99%