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Thromb Haemost 1984; 51(03): 303-306
DOI: 10.1055/s-0038-1661088
Original Article
Schattauer GmbH Stuttgart

A Double-Blind Trial of Ticlopidine in Sickle Cell Disease

M J Semple
The Department of Haematology, St. Thomas’ Hospital, London, U.K.
,
S F Al-Hasani
The Department of Haematology, St. Thomas’ Hospital, London, U.K.
,
P Kioy
The Department of Haematology, St. Thomas’ Hospital, London, U.K.
,
G F Savidge
The Department of Haematology, St. Thomas’ Hospital, London, U.K.
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Publikationsverlauf

Received 20. Juli 1983

Accepted 29. Dezember 1983

Publikationsdatum:
19. Juli 2018 (online)

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Summary

Baseline studies of 111indium oxine labelled platelet life-span, platelet α-granule release products, β-thromboglobulin (βTG) and platelet factor 4 (PF4), and factor VIII related activities were performed on 9 asymptomatic patients with sickle cell disease, who were subsequently randomised in a prospective double-blind trial of ticlopidine (250 mg. b. d.) or placebo for one month and the investigations repeated. Control studies indicated that 5 of the 9 patients had shortened platelet survivals: mean βTG (50.8 ng/ ml) and PF4 (19.5 ng/ml), factor VIII: C (283.4 i. u./dl) and factor VIIIR: AG (168.7 u/dl) levels were raised. Ticlopidine treatment did not significantly improve platelet life-span or factor VIII levels, though it was associated with reduced values of βTG and PF4. One patient taking ticlopidine developed an infarctive sickle crisis. Although ticlopidine blocked platelet activation, this alone did not improve platelet survival or prevent sickle crisis: in view of evidence of platelet activation in sickle cell disease, however, a longer trial of prophylactic antiplatelet drugs might be warranted.

Keywords

Sickle cell disease - Platelet survival - Ticlopidine - β-thromboglobulin - Platelet factor 4
 

  • References

  • 1 Richardson SG N, Matthews KB, Stuart J, Geddes AM, Wilcox RM. Serial changes in coagulation and viscosity during sickle cell crisis. Br J Haematol 1979; 41: 95-103
    CrossrefPubMedGoogle Scholar
  • 2 Leslie J, Langler D, Serjeant GR, Serjeant BE, Desai P, Gordon YB. Coagulation changes during the steady state in homozygous sicklecell disease in Jamaica. Br J Haematol 1975; 30: 159-166
    CrossrefPubMedGoogle Scholar
  • 3 Leichtman DA, Brewer GJ. Elevated plasma levels of fibrinopeptide A during sickle cell anaemia pain crisis - evidence for intravascular coagulation. Am J Hematol 1978; 5: 183-190
    CrossrefPubMedGoogle Scholar
  • 4 Alkjaersig N, Fletcher A, Joist H, Chaplin Jr H. Hemostasis alterations accompanying sickle cell pain crises. J Lab Clin Med 1976; 88: 440-449
    PubMedGoogle Scholar
  • 5 Ittyerah R, Alkjaersig N, Fletcher A, Chaplin H. Coagulation factor XIII concentration in sickle cell disease. J Lab Clin Med 1976; 99: 546-554
    PubMedGoogle Scholar
  • 6 Murphy RC, Shapiro S. The pathology of sickle cell disease. Ann Intern Med 1945; 23: 376-397
    CrossrefPubMedGoogle Scholar
  • 7 Mann JR, Deeble TJ, Breeze GR, Stuart J. Ancrod in sickle cell crisis. Lancet 1972; 1: 934-937
    PubMedGoogle Scholar
  • 8 Salvaggio JE, Arnold CA, Banov CH. Long-term anticoagulation in sickle-cell disease. N Engl J Med 1963; 269: 182-186
    CrossrefPubMedGoogle Scholar
  • 9 Chaplin Jr H, Alkjaersig N, Fletcher AP, Michael JM, Joist JH. Aspirin-dipyridamole prophylaxis of sickle cell disease pain crises. Thromb Haemostas 1980; 43: 218-221
    PubMedGoogle Scholar
  • 10 de Gramont A, Canuel C, Krulik M, Bauters F, Degos L, Marty M, Najean Y. Toxicite hématologique de la ticlopidine. Nouv Rev Fr Hematol 1982; 24: 35-37
    PubMedGoogle Scholar
  • 11 Chomienne C, Baumelou E, Rio B, Peuchavy C, Stanek L, Samama M, Zittoun R. Deux observations d’une granulocytose aiguë au cours d’un traitement anti-agrégant par la ticlopidine. Rev Med Ther 1983; 24: 589-590
    PubMedGoogle Scholar
  • 12 Hawker RJ, Hawker LM, Wilkinson AR. Indium (111In)-labelled human platelets: optimal method. Clin Sci 1980; 58: 243-248
    CrossrefPubMedGoogle Scholar
  • 13 Panel on diagnostic application of radioisotopes in Haematology. Recommended methods for radioisotope platelet survival studies. Blood 1977; 50: 1137-1144
    PubMedGoogle Scholar
  • 14 Bolton AE, Ludlam CA, Moore S, Pepper DS, Cash JD. Three approaches to the radioimmunoassay of human β-thromboglobulin. Br J Haematol 1976; 33: 233-238
    CrossrefPubMedGoogle Scholar
  • 15 Ludlam CA, Cash JD. Studies on the liberation of β-thromboglobulin from human platelets in vivo. Br J Haematol 1976; 33: 239-247
    CrossrefPubMedGoogle Scholar
  • 16 Hardisty RM, Macpherson JC. A one-stage factor VIII (anti- haemophilic globulin) assay and its use on venous and capillary plasma. Thrombos Diathes Haemorrh 1962; 7: 215-229
    PubMedGoogle Scholar
  • 17 Laurell C-B. Quantitative estimation of proteins by electrophoresis in agarose gel containing antibodies. Anal Biochem 1966; 15: 45-52
    CrossrefPubMedGoogle Scholar
  • 18 Haut MJ, Cowan DH, Harris JW. Platelet function and survival in sickle cell disease. J Lab Clin Med 1973; 82: 44-53
    PubMedGoogle Scholar
  • 19 Heyns Adu P, Lötter MG, Badenhorst PN, ven Reenen OR, Pieters H, Minnaar PC, Retief FP. Kinetics, distribution and sites of destruction of 111Indiumlabelled human platelets. Br J Haematol 1980; 44: 269-280
    CrossrefPubMedGoogle Scholar
  • 20 Kenny MW, George AJ, Stuart J. Platelet hyperactivity in sickle-cell disease: a consequence of hyposplenism. J Clin Pathol 1980; 33: 622-625
    CrossrefPubMedGoogle Scholar
  • 21 Pearson HA, Spencer RP, Cornelius EA. Functional asplenia in sickle cell anaemia. N Engl J Med 1969; 281: 923-926
    CrossrefPubMedGoogle Scholar
  • 22 duP HeynsA, Lötter MG, Badenhorst PN, van Reenen O, Pieters H, Minnaar PC. Kinetics and fate of 111Indium-oxine labelled blood platelets in asplenic subjects. Thromb Haemostas 1980; 44: 100-104
    PubMedGoogle Scholar
  • 23 Morgan AG, Sergeant GR. Renal function in patients over 40 with homozygous sickle-cell disease. Br Med J 1981; 282: 1181-1183
    CrossrefPubMedGoogle Scholar
  • 24 Kurihara Y, Nakayama H, Nakagawa S. Plasma β-thromboglobulin and platelet factor 4 in renal insufficiency. Thromb Res 1980; 18: 557-560
    CrossrefPubMedGoogle Scholar
  • 25 Kaplan KL, Owen J. Plasma levels of β-thromboglobulin and platelet factor 4 as indices of platelet activation in vivo. Blood 1981; 57: 199-202
    PubMedGoogle Scholar
  • 26 Lips JP M, Sixma JJ, Schiphorst ME. The effect of ticlopidine administration to humans on the binding of adenosine diphosphate to blood platelets. Thromb Res 1980; 17: 19-27
    CrossrefPubMedGoogle Scholar
  • 27 Ashida S, Abiko Y. Effect of ticlopidine and acetyl salicylic acid on generation of prostaglandin I2-like substance in rat arterial tissue. Thromb Res 1978; 13: 901-908
    CrossrefPubMedGoogle Scholar
  • 28 Stuart MJ, Sills RH. Deficiency of plasma prostacyclin or PGI2 . Regenerating ability in sickle cell anaemia Br J Haematol 1981; 48: 545-550
    CrossrefPubMedGoogle Scholar
  • 29 Kenny MW, Meakin M, Worthington DJ, Stuart J. Erythrocyte deformability in sickle-cell crisis. Br J Haematol 1981; 49: 103-109
    CrossrefPubMedGoogle Scholar
  • 30 Hebbel RP, Boogaerts MA B, Eaton JW, Steinberg MH. Erythrocyte adherence to endothelium in sickle-cell anaemia. N Eng J Med 1980; 302: 992-995
    CrossrefPubMedGoogle Scholar