Changes in Heme Levels During Acute Vaso-occlusive Crisis in Sickle Cell Anemia

Cardoso, Evilázio Cunha; Hounkpe, Bidossessi Wilfried; Chenou, Francine; Albuquerque, Cintia Cristina Mateus Xerez; Garcia, Nadja Pinto; Silva-Junior, Alexander Leonardo; Malheiro, Adriana; Cesar, Purim; Lima, Franciele de; Paula, Erich Vinícius De; Fraiji, Nelson Abrahim

doi:10.1016/j.hemonc.2021.08.002

Cited by 5 publications

(6 citation statements)

References 28 publications

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“…These interesting results have led to a clinical trial of hemopexin in adults with SCD 25 . Associated with these results, Cardoso et al reported that total extracellular heme levels, both plasma and serum, are correlated with the difference of hemoglobin between admission and convalescence and with SCD severity estimated by composite score 26 . Heme levels were neither associated with VOC severity or hemostasis activation.…”

Section: Discussionmentioning

confidence: 88%

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Lactate dehydrogenase and hemolysis index to predict vaso-occlusive crisis in sickle cell disease

Feugray,

Dumesnil,

Grall

et al. 2023

Sci Rep

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Sickle cell disease (SCD) is an inherited hemoglobinopathy disorder associated with chronic hemolysis. A major complication is vaso-occlusive crisis (VOC), associating frequent hospitalization, morbidity and mortality. The aim of this study was to investigate whether hemolysis biomarkers were able to predict VOC risk in adult patients with SCD requiring hospitalization within 1 year. This single-center prospective study included adult patients with SCD at steady state or during VOC. A total of 182 patients with SCD were included, 151 at steady state and 31 during VOC. Among the 151 patients at steady state 41 experienced VOC within 1 year (median: 3.0 months [2.0–6.5]). We observed an increase of lactate dehydrogenase (LDH) (p = 0.01) and hemolysis index (HI) (p = 0.0043) during VOC compared to steady state. Regarding patients with VOC requiring hospitalization, LDH (p = 0.0073) and HI (p = 0.04) were increased. In unadjusted logistic regression, LDH > median (> 260 U/L) (RR = 3.6 [1.29–10.88], p = 0.0098) and HI > median (> 8 UA/L) (RR = 3.13 [1.91–5.33]; p < 0.001) were associated with VOC. The association of LDH > 260 U/L and HI > 12 UA/L presented a sensitivity of 90%, and a specificity of 72.9% to predict VOC. The association of LDH and HI cut-off was able to predict VOC risk in SCD.

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Section: Discussionmentioning

confidence: 88%

“…Heme levels were neither associated with VOC severity or hemostasis activation. Moreover VOC is not characterized by significant increases in total extracellular heme levels 26 .…”

Section: Discussionmentioning

confidence: 97%

Lactate dehydrogenase and hemolysis index to predict vaso-occlusive crisis in sickle cell disease

Feugray,

Dumesnil,

Grall

et al. 2023

Sci Rep

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“…No data are available on differences between these porphyrins comparing plasma and serum. However, there are data for heme showing higher concentrations in serum, even though the levels of both matrices are correlating 18 . We assume that this applies also to CPs, as these molecules share the porphyrin structure.…”

Section: Discussionmentioning

confidence: 99%

Various effects of repeated rifampin dosing on coproporphyrin levels in humans

Kinzi,

Grube,

Brecht

et al. 2023

Clinical Translational Sci

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In recent years, the identification of endogenous substrates as biomarkers became an uprising topic. Particularly coproporphyrins (CPs), byproducts of heme biosynthesis, are intensely investigated as biomarkers for predicting interactions with the organic anion transporting polypeptide (OATP) 1B transporters. In the context of drug‐drug interactions, several preclinical and clinical studies assessed the effect of the OATP1B‐index inhibitor rifampin on CPI levels. However, rifampin is not only a “perpetrator” drug of transporters but is also known for its interaction with the nuclear receptor pregnane X receptor (PXR) leading to the efficient induction of PXR‐target genes. These include hemoproteins like cytochrome P450 enzymes but also the δ‐aminolevulinate synthase 1, which is the rate‐limiting enzyme in heme biosynthesis. In this study, we showed that quantification of CPs in clinical serum samples was possible after long‐term storage at ‐20 °C. We quantified CPI, CPIII, and heme levels in clinical serum samples (at selected time points) that originated from a trial investigating the interaction potential of repeated rifampin administration in 12 healthy participants. In samples collected at the assumed tmax of rifampin, higher CP levels were observed compared to baseline. Increased levels persisted even 14 hours after discontinuation of rifampin. No impact on heme serum levels was observed. We found a correlation between coproporphyrin isomers at baseline and at 14 hours after rifampin intake. In summary, we show that multiple doses of rifampin affect CP levels. However, besides inhibition of hepatic OATP function there is evidence for an interaction with CP levels beyond the transporter level.

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“…Coagulation activation is a hallmark of both COVID-19 20 and of conditions associated with high levels of extracellular heme, HPX consumption, and HO-1 induction. 21 –23 Whether the heme/HPX/HO-1 pathway is associated with coagulation activation in COVID-19 has not been explored.…”

Section: Introductionmentioning

confidence: 99%

Association of heme-oxygenase 1, hemopexin, and heme levels with markers of disease severity in COVID-19

Lima

Moraes

Barbosa

et al. 2023

Exp Biol Med (Maywood)

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Heme-oxygenase 1 (HO-1) is an enzyme with well-known anti-inflammatory and antioxidant properties, whose levels have been previously associated with disease severity in the context of sterile and infectious diseases. Moreover, the heme/HO-1 pathway has been associated with prothrombotic changes in other diseases. Accordingly, the potential of modulating HO-1 levels for the treatment of COVID-19 was extensively speculated during the COVID-19 pandemic, but very few actual data were generated. The aim of our study was to explore the association of HO-1, heme, and hemopexin (HPX) levels with COVID-19 severity and with markers of inflammation and coagulation activation. The study was conducted in 30 consecutive patients with COVID-19 admitted due to hypoxemia, and 30 healthy volunteers matched by sex, age, and geographic region. HO-1 and HPX levels were measured by enzyme immunoassay (ELISA) and heme levels were measured by a colorimetric method. A comprehensive panel of coagulation and fibrinolysis activation was also used. Patients with COVID-19 presented increased levels of HO-1 when compared to controls (5741 ± 2696 vs 1953 ± 612 pg/mL, respectively, P < 0.0001), as well as a trend toward increased levels of HPX (3.724 ± 0.880 vs 3.254 ± 1.022 mg/mL, respectively; P = 0.06). In addition, HO-1 and HPX levels reduced from admission to day + 4. HO-1 levels were associated with duration of intensive care unit stay and with several markers of coagulation activation. In conclusion, modulation of HO-1 could be associated with the prothrombotic state observed in COVID-19, and HO-1 could also represent a relevant biomarker for COVID-19. New independent studies are warranted to explore and expand these findings.

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Changes in Heme Levels During Acute Vaso-occlusive Crisis in Sickle Cell Anemia

Cited by 5 publications

References 28 publications

Lactate dehydrogenase and hemolysis index to predict vaso-occlusive crisis in sickle cell disease

Lactate dehydrogenase and hemolysis index to predict vaso-occlusive crisis in sickle cell disease

Various effects of repeated rifampin dosing on coproporphyrin levels in humans

Association of heme-oxygenase 1, hemopexin, and heme levels with markers of disease severity in COVID-19

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