Relationship Between Mepacrine-Labelled Dense Body Number, Platelet Capacity to Accumulate ¹⁴C-5-HT and Platelet Density in the Bernard-Soulier and Hermansky-Pudlak Syndromes

 

PDF Download Buy Article Permissions and Reprints

Summary

We have used the mepacrine-labelling procedure to measure the dense body (serotonin storage organelle) content of the platelets of 2 hereditary disorders where abnormalities in dense body number were suspected. The platelets were incubated with mepacrine and examined by fluorescence microscopy. A mean number of 5.4 ± 0.8 (SD) dense bodies per platelet was calculated from the data obtained using platelets isolated from 40 normal human subjects. In contrast the platelets of 2 patients with the Bernard-Soulier syndrome contained an average of 14 and 17 labelled granules. This increase was associated with a much greater capacity of the platelets to accumulate ¹⁴C-5-HT. The opposite result was obtained using the platelets from 2 patients with the Hermansky-Pudlak syndrome which contained few granules labelled by mepacrine and took up less ¹⁴C-5-HT than normal human platelets. Centrifugation of the patients’ platelets on discontinuous sucrose gradients showed that the platelets of the 2 Bemard-Soulier patients were much denser than normal whereas a high proportion of low density platelets was observed in the Hermansky-Pudlak syndrome. These results further define the platelet abnormalities in the two syndromes and suggest that dense body number may be one of the factors governing platelet density.

• References

• 1 Bernard J, Soulier JP. 1948; Sur une nouvelle variété de dystrophie thrombocytaire hémorragipare cong�nitale. Sem. Hôp. Paris 24: 3217
  PubMedGoogle Scholar
• 2 Bithell TC, Parekh SJ, Strong RR. 1972; Platelet function studies in the Bemard-Soulier syndrome. Annals of the New York Academy of Science 201: 145
  CrossrefPubMedGoogle Scholar
• 3 Booyse F, Rafelson MF. 1969. Protein synthesis and platelet function. In JOHNSON SA, Guest MM. “Dynamics of thrombus formation and dissolution”. Ed Lippincott; Philadelphia: 1969. p 149
  Google Scholar
• 4 Caen J, Cousin C, Vainer H, Michel H. 1967; Enzymatic activities ADP-induced aggregation and survival in vivo as criteria of platelet viability during storage. Transfusion 7: 143
  CrossrefPubMedGoogle Scholar
• 5 Caen JP, Nurden AT, Jeanneau C, Michel H, Tobelem G, Levy-Toledano S, Sultan Y, Valensi F, Bernard J. 1976; Bemard-Soulier syndrome: a new platelet glycoprotein abnormality. Its relationship with platelet adhesion to subendothelium and with the factor VIII von Willebrand protein. Journal of Laboratory and Clinical Medicine 87: 586
  PubMedGoogle Scholar
• 6 Costa JL, Reese TS, Murphy DL. 1974; Serotonin storage in platelets: estimation of storage-packet size. Science 193: 537
  PubMedGoogle Scholar
• 7 Da Prada M, Pletscher A. 1975; Accumulation of basic drugs in 5-hydroxytryptamine organelles of blood platelets. European Journal of Pharmacology 32: 179
  CrossrefPubMedGoogle Scholar
• 8 Evensen SA, Solum NO, Grottum KA, Hovig T. 1974; Familial bleeding disorder with a moderate thrombocytopenia and giant blood platelets. Scandinavian Journal of Haematology 13: 203
  PubMedGoogle Scholar
• 9 Frojmovic MM, Milton JG, Caen JP, Tobelem G. 1978; Platelets from giant platelet syndrome (BSS) are discocytes and normal sized. Journal of Laboratory and Clinical Medicine 91: 109
  PubMedGoogle Scholar
• 10 Grottum KA, Solum NO. 1969; Congenital thrombocytopenia with giant platelets: a defect in the platelet membrane. British Journal of Haematology 16: 277
  CrossrefPubMedGoogle Scholar
• 11 Hardisty RM, Hutton RA. 1967; Bleeding tendency associated with a “new” abnormality of platelet behaviour. Lancet 1: 983
  PubMedGoogle Scholar
• 12 Hardisty RM, Mills DC B, KETSA-ARD K. 1972; The platelet defect associated with albinism. British Journal of Haematology 23: 679
  CrossrefPubMedGoogle Scholar
• 13 Hermansky F, Pudlak P. 1959; Albinism associated with hemorrhagic diathesis and unusual pigmented reticular cells in the bone marrow: report of two cases with histochemical studies. Blood 14: 162
  CrossrefPubMedGoogle Scholar
• 14 Karpatkin S. 1978; Heterogeneity of human platelets. VI. Correlation of platelet function with platelet volume. Blood 51: 307
  PubMedGoogle Scholar
• 15 Lorez HP, Da Prada A, Pletscher A. 1975; Flashing phenomenon in blood platelets stained with fluorescent basic drugs. Experientia 31: 593
  CrossrefPubMedGoogle Scholar
• 16 Lorez HP, Da Prada M, Rendu F, Pletscher A. 1977; Mepacrine a tool for investigating the 5-hydroxytryptamine organelles of blood platelets by fluorescence microscopy. Journal of Laboratory and Clinical Medicine 89: 200
  PubMedGoogle Scholar
• 17 Maldonado JE, Gilchrist GS, Brigden LP, Bowie EJ W. 1975; Ultrastructure of platelets in Bemard-Soulier syndrome. Mayo Clinic Proceedings 50: 402
  PubMedGoogle Scholar
• 18 Malmsten C, Kindahl H, Samuelsson B, Levy-Toledano S, Tobelem G, Caen JP. 1977; Thromboxane synthesis and the platelet release reaction in Bernard-Soulier syndrome, thrombasthenia Glanzmann and Hermansky-Pudlak syndrome. British Journal of Haematology 35: 511
  CrossrefPubMedGoogle Scholar
• 19 Nurden AT, Caen JP. 1978; Annotation: Membrane glycoproteins and human platelet function. British Journal of Haematology 38: 155
  CrossrefPubMedGoogle Scholar
• 20 Pareti FI, Day J, Mills DC B. 1974; Nucleotide and serotonin metabolism in platelets with defective secondary aggregation. Blood 44: 789
  PubMedGoogle Scholar
• 21 Picottt GB, Da Prada M, Pletscher A. 1976; Uptake and liberation of mepacrine in blood platelets. Naunyn-Schmiedeberg’s Archives of Pharmacology 292: 127
  PubMedGoogle Scholar
• 22 Rendu F, Caen JP. 1973; Effect of reserpine on¹⁴C-serotonin uptake by human platelet populations. Haemostasis 1: 161
  PubMedGoogle Scholar
• 23 Rendu F, Breton-Gorius J, Trugnan G, Castro-Malaspina H, Rieu JM, Bereziat G, Lebret M, Caen JP. 1979; Studies on a new variant of the Hermansky-Pudlak syndrome: qualitative, ultrastructural and functional abnormalities of the platelet dense bodies associated with a phospholipase A defect. American Journal of Hematology 4: 387
  PubMedGoogle Scholar
• 24 Schick PK, Yu BP. 1973; Methylene blue-induced serotonin release in human platelets. Journal of Laboratory and Clinical Medicine 82: 546
  PubMedGoogle Scholar
• 25 Walsh PN, Mills DC B, Pareti FI, Stewart GJ, Macfarlane DE, Johnson MM, Egan JJ. 1975; Hereditary giant platelet syndrome. Absence of collagen-induced coagulant activity and deficiency of Factor XI binding to platelets British Journal of Haematology 29: 639
  CrossrefPubMedGoogle Scholar
• 26 Weiss HJ, Tschopp TB, Baumgartner HR, Sussman IA, Johnson MJ, Egan JJ. 1974; a Decreased adhesion of giant (Bernard-Soulier) platelets to subendothelium. Further implications on the role of the von Willebrand factor in haemostasis American Journal of Medicine 57: 920
  CrossrefPubMedGoogle Scholar
• 27 Weiss HJ, Tschopp TB, Rogers J, Brand H. 1974; b Studies of platelet 5-hydroxytryptamine (serotonin) in storage pool disease and albinism. Journal of Clinical Investigation 54: 421
  CrossrefPubMedGoogle Scholar
• 28 White JG, Edson JR, Desnick SJ, Witkop CJ. 1971; Studies of platelets in a variant of the Hermansky-Pudlak syndrome. American Journal of Pathology 63: 319
  PubMedGoogle Scholar
• 29 Witkop CJ, Hill CW, Desnick S, Thies JK, Thorn ML, Jenkins M, White JG. 1973; Ophthalmologic, biochemical, platelet and ultrastructural defects in the various types of oculocutaneous albinism. Journal of Investigative Dermatology 60: 443
  CrossrefPubMedGoogle Scholar
• 30 Zeigler Z, Murphy S, Gardner FH. 1978; Microscopic platelet size and morphology in various hematologic disorders. Blood 51: 479
  PubMedGoogle Scholar