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Vaso-occlusion by sickle cells: evidence for selective trapping of dense red cells.

Abstract

We have characterized the type of red cells from sickle cell patients that were trapped in the course of sickle-cell vaso-occlusion. In addition, the perfusion conditions (arterial perfusion pressure [Pa] and oxygen tension [PO2]) leading to experimentally induced vaso-occlusion in the artificially perfused, innervated mesocecum microvascular preparation were determined. Microvascular obstruction was induced by decrease in Pa; the lower the Pa, the greater the peripheral resistance as well as the extent of obstruction. The cells involved in the obstruction were recovered by vasodilation (secondary to denervation) and increase in Pa. Densitometric analysis of density gradient-separated infused and trapped cells was supplemented with morphological analysis to ascertain the involvement of density classes as well as morphological types seen in oxy and deoxy sickle blood. The trapping phenomenon was sensitive to PO2. Percentage of densest gradient classes, ie, fraction 3 (F3; mainly dense unsicklable SS discocytes [USDs]) and fraction 4 (F4; irreversibly sickled cells [ISCs] and the densest discocytes), showed a significant increase in trapping when perfusion was switched from oxy to deoxy perfusate. Morphological analysis revealed that unsicklable SS discocytes are more effectively trapped when deoxygenated. The deoxygenation of infused cells did not further change the percentage of ISCs trapped, suggesting that ISCs are equally capable of sequestration in the oxy and the deoxy states. The venous effluent showed a selective and significant depletion of dense cells (F4) and ISC counts at all Pa. We conclude that the progressive obstruction of the microcirculation by sickle cells involves selective sequestration of the densest classes of cells and that this mechanism might explain their partial disappearance during painful sickle cell crisis.

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  • Authors

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    Source

    Blood 68:5 1986 Nov pg 1162-6

    MeSH

    Anemia, Sickle Cell
    Arterial Occlusive Diseases
    Centrifugation, Density Gradient
    Erythrocytes, Abnormal
    Humans
    In Vitro Techniques
    Microcirculation
    Models, Biological
    Oxygen

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    3768533

    Citation

    Kaul, D K., et al. "Vaso-occlusion By Sickle Cells: Evidence for Selective Trapping of Dense Red Cells." Blood, vol. 68, no. 5, 1986, pp. 1162-6.
    Kaul DK, Fabry ME, Nagel RL. Vaso-occlusion by sickle cells: evidence for selective trapping of dense red cells. Blood. 1986;68(5):1162-6.
    Kaul, D. K., Fabry, M. E., & Nagel, R. L. (1986). Vaso-occlusion by sickle cells: evidence for selective trapping of dense red cells. Blood, 68(5), pp. 1162-6.
    Kaul DK, Fabry ME, Nagel RL. Vaso-occlusion By Sickle Cells: Evidence for Selective Trapping of Dense Red Cells. Blood. 1986;68(5):1162-6. PubMed PMID: 3768533.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Vaso-occlusion by sickle cells: evidence for selective trapping of dense red cells. AU - Kaul,D K, AU - Fabry,M E, AU - Nagel,R L, PY - 1986/11/1/pubmed PY - 1986/11/1/medline PY - 1986/11/1/entrez SP - 1162 EP - 6 JF - Blood JO - Blood VL - 68 IS - 5 N2 - We have characterized the type of red cells from sickle cell patients that were trapped in the course of sickle-cell vaso-occlusion. In addition, the perfusion conditions (arterial perfusion pressure [Pa] and oxygen tension [PO2]) leading to experimentally induced vaso-occlusion in the artificially perfused, innervated mesocecum microvascular preparation were determined. Microvascular obstruction was induced by decrease in Pa; the lower the Pa, the greater the peripheral resistance as well as the extent of obstruction. The cells involved in the obstruction were recovered by vasodilation (secondary to denervation) and increase in Pa. Densitometric analysis of density gradient-separated infused and trapped cells was supplemented with morphological analysis to ascertain the involvement of density classes as well as morphological types seen in oxy and deoxy sickle blood. The trapping phenomenon was sensitive to PO2. Percentage of densest gradient classes, ie, fraction 3 (F3; mainly dense unsicklable SS discocytes [USDs]) and fraction 4 (F4; irreversibly sickled cells [ISCs] and the densest discocytes), showed a significant increase in trapping when perfusion was switched from oxy to deoxy perfusate. Morphological analysis revealed that unsicklable SS discocytes are more effectively trapped when deoxygenated. The deoxygenation of infused cells did not further change the percentage of ISCs trapped, suggesting that ISCs are equally capable of sequestration in the oxy and the deoxy states. The venous effluent showed a selective and significant depletion of dense cells (F4) and ISC counts at all Pa. We conclude that the progressive obstruction of the microcirculation by sickle cells involves selective sequestration of the densest classes of cells and that this mechanism might explain their partial disappearance during painful sickle cell crisis. SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/3768533/Vaso_occlusion_by_sickle_cells:_evidence_for_selective_trapping_of_dense_red_cells_ L2 - http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=3768533 DB - PRIME DP - Unbound Medicine ER -