Skip to main content
PMC home page
Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 1988 Oct;47(10):849–854. doi: 10.1136/ard.47.10.849

Immune mediated mechanism for thrombosis: antiphospholipid antibody binding to platelet membranes.

M A Khamashta 1, E N Harris 1, A E Gharavi 1, G Derue 1, A Gil 1, J J Vázquez 1, G R Hughes 1
PMCID: PMC1003615  PMID: 3196084

Abstract

Because thrombocytopenia occurs frequently in patients with anticardiolipin (aCL) antibodies and thrombosis, some investigators have proposed that aCL antibodies may play a direct part in thrombosis by binding and activating platelets. To test this proposal experiments were performed to determine whether aCL antibodies can bind platelets. Preincubation of aCL positive sera with freeze-thawed platelets caused significant inhibition of aCL activity in four serum samples tested. Antibodies with cardiolipin binding activity were subsequently eluted from these platelets. Total phospholipids extracted from platelets inhibited aCL activity, and the specific phospholipids bound were shown to be phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol. It is concluded that aCL antibodies can bind phospholipids in platelet membranes but pertubation of the membrane must first occur.

Full text

PDF
851

Images in this article

851Image
on p.851

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alving C. R. Antibodies to liposomes, phospholipids and phosphate esters. Chem Phys Lipids. 1986 Jun-Jul;40(2-4):303–314. doi: 10.1016/0009-3084(86)90075-7. [DOI] [PubMed] [Google Scholar]
  2. BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
  3. Cohen P., Derksen A. Comparison of phospholipid and fatty acid composition of human erythrocytes and platelets. Br J Haematol. 1969 Oct;17(4):359–371. doi: 10.1111/j.1365-2141.1969.tb01382.x. [DOI] [PubMed] [Google Scholar]
  4. Gharavi A. E., Harris E. N., Asherson R. A., Hughes G. R. Anticardiolipin antibodies: isotype distribution and phospholipid specificity. Ann Rheum Dis. 1987 Jan;46(1):1–6. doi: 10.1136/ard.46.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Harris E. N., Asherson R. A., Gharavi A. E., Morgan S. H., Derue G., Hughes G. R. Thrombocytopenia in SLE and related autoimmune disorders: association with anticardiolipin antibody. Br J Haematol. 1985 Feb;59(2):227–230. doi: 10.1111/j.1365-2141.1985.tb02988.x. [DOI] [PubMed] [Google Scholar]
  6. Harris E. N., Chan J. K., Asherson R. A., Aber V. R., Gharavi A. E., Hughes G. R. Thrombosis, recurrent fetal loss, and thrombocytopenia. Predictive value of the anticardiolipin antibody test. Arch Intern Med. 1986 Nov;146(11):2153–2156. [PubMed] [Google Scholar]
  7. Harris E. N., Gharavi A. E., Hughes G. R. Anti-phospholipid antibodies. Clin Rheum Dis. 1985 Dec;11(3):591–609. [PubMed] [Google Scholar]
  8. Harris E. N., Gharavi A. E., Loizou S., Derue G., Chan J. K., Patel B. M., Mackworth-Young C. G., Bunn C. C., Hughes G. R. Crossreactivity of antiphospholipid antibodies. J Clin Lab Immunol. 1985 Jan;16(1):1–6. [PubMed] [Google Scholar]
  9. Harris E. N., Gharavi A. E., Tincani A., Chan J. K., Englert H., Mantelli P., Allegro F., Ballestrieri G., Hughes G. R. Affinity purified anti-cardiolipin and anti-DNA antibodies. J Clin Lab Immunol. 1985 Aug;17(4):155–162. [PubMed] [Google Scholar]
  10. Harris E. N. Syndrome of the black swan. Br J Rheumatol. 1987 Oct;26(5):324–326. doi: 10.1093/rheumatology/26.5.324. [DOI] [PubMed] [Google Scholar]
  11. Howard M. A., Firkin B. G. Investigations of the lupus-like inhibitor by-passing activity of platelets. Thromb Haemost. 1983 Dec 30;50(4):775–779. [PubMed] [Google Scholar]
  12. Hughes G. R., Harris N. N., Gharavi A. E. The anticardiolipin syndrome. J Rheumatol. 1986 Jun;13(3):486–489. [PubMed] [Google Scholar]
  13. Hughes G. R. Thrombosis, abortion, cerebral disease, and the lupus anticoagulant. Br Med J (Clin Res Ed) 1983 Oct 15;287(6399):1088–1089. doi: 10.1136/bmj.287.6399.1088. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lockshin M. D. Anticardiolipin antibody. Arthritis Rheum. 1987 Apr;30(4):471–472. doi: 10.1002/art.1780300420. [DOI] [PubMed] [Google Scholar]
  15. Lockshin M. D., Druzin M. L., Goei S., Qamar T., Magid M. S., Jovanovic L., Ferenc M. Antibody to cardiolipin as a predictor of fetal distress or death in pregnant patients with systemic lupus erythematosus. N Engl J Med. 1985 Jul 18;313(3):152–156. doi: 10.1056/NEJM198507183130304. [DOI] [PubMed] [Google Scholar]
  16. Marcus A. J., Ullman H. L., Safier L. B. Lipid composition of subcellular particles of human blood platelets. J Lipid Res. 1969 Jan;10(1):108–114. [PubMed] [Google Scholar]
  17. Rauch J., Tannenbaum M., Tannenbaum H., Ramelson H., Cullis P. R., Tilcock C. P., Hope M. J., Janoff A. S. Human hybridoma lupus anticoagulants distinguish between lamellar and hexagonal phase lipid systems. J Biol Chem. 1986 Jul 25;261(21):9672–9677. [PubMed] [Google Scholar]
  18. Schick P. K., Kurica K. B., Chacko G. K. Location of phosphatidylethanolamine and phosphatidylserine in the human platelet plasma membrane. J Clin Invest. 1976 May;57(5):1221–1226. doi: 10.1172/JCI108390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Tan E. M., Cohen A. S., Fries J. F., Masi A. T., McShane D. J., Rothfield N. F., Schaller J. G., Talal N., Winchester R. J. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982 Nov;25(11):1271–1277. doi: 10.1002/art.1780251101. [DOI] [PubMed] [Google Scholar]
  20. Thiagarajan P., Shapiro S. S., De Marco L. Monoclonal immunoglobulin M lambda coagulation inhibitor with phospholipid specificity. Mechanism of a lupus anticoagulant. J Clin Invest. 1980 Sep;66(3):397–405. doi: 10.1172/JCI109869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Triplett D. A., Brandt J. T., Kaczor D., Schaeffer J. Laboratory diagnosis of lupus inhibitors: a comparison of the tissue thromboplastin inhibition procedure with a new platelet neutralization procedure. Am J Clin Pathol. 1983 Jun;79(6):678–682. doi: 10.1093/ajcp/79.6.678. [DOI] [PubMed] [Google Scholar]
  22. Vermylen J., Blockmans D., Spitz B., Deckmyn H. Thrombosis and immune disorders. Clin Haematol. 1986 May;15(2):393–412. [PubMed] [Google Scholar]

Articles from Annals of the Rheumatic Diseases are provided here courtesy of BMJ Publishing Group

RESOURCES