Platelet Sequestration During Hypothermia in Dogs Treated with Sulphinpyrazone and Ticlopidine - Reversibility Accelerated After Intra-Abdominal Rewarming

 

PDF Download Buy Article Permissions and Reprints

Summary

During body cooling, a progressive thrombocytopenia is observed, with platelet sequestration mainly in the liver. Platelets return progressively to the circulation during re warming. In this work the presence of platelet clumps is demonstrated by electron microscopy inside the hepatic sinusoids of dogs cooled to 20° C by immersion in iced water. Such clumps were not found either before cooling or after body rewarming. Similar platelet clumps in the hepatic microcirculation were found in two other groups of dogs cooled and rewarmed as before, but previously treated with the antiaggregants sulphinpyrazone or ticlopidine. Another group of dogs was cooled and rewarmed by intra-abdominal circulation of physiological saline respectively at 4° C and 40° C. In these animals a similar decrease of circulating platelets was observed. However, just after re warming was started, with the body temperature still at 22° C, sequestered platelets came back abruptly to circulation. We conclude that hepatic platelet sequestration induced by hypothermia appears mainly due to local haemodynamic conditions.

• References

• 1 Helmsworth GA, Stiles WJ, Elstun W. Changes in blood cellular elements in dogs during hypothermia. Surgery 1955; 38: 843-846
  PubMedGoogle Scholar
• 2 Willson JT, Miller WR, Eliot TS. Blood studies in the hypothermic dog. Surgery 1958; 43: 979-989
  PubMedGoogle Scholar
• 3 Villalobos TJ, Adelson E, Riley Jr PA, Crosby WH. A cause of the thrombocytopenia and leukopenia that occur in dogs during deep hypothermia. J Clin Invest 1958; 37: 1-7
  CrossrefPubMedGoogle Scholar
• 4 Wensel RH, Bigelow WG. The use of heparin to minimize thrombocytopenia and bleeding tendency during hypothermia. Surgery 1959; 45: 223-228
  PubMedGoogle Scholar
• 5 Biorck G, Johansson BW, Nilsson IM. Blood coagulation studies in hedgehogs, in an hibernating and a nonhibernating state, and in dogs hypothermic and normothermic. Acta Physiol Scand 1962; 56: 334-348
  CrossrefPubMedGoogle Scholar
• 6 Johansson BW, Nilsson IM. The effect of heparin and e-aminocaproic acid on the coagulation in hypothermic dogs. Acta Physiol Scand 1964; 60: 267-277
  CrossrefPubMedGoogle Scholar
• 7 Malmejac R, Dosne AM, Rieu M. Modifications thromboelasto-graphiques au cours de l‘hypothermie profonde provoquee chez le chien. Pathol Biol (Paris) 1966; 14: 429-432
  PubMedGoogle Scholar
• 8 Pina-Cabral JM. A coagulagao sanguinea do cao submetido a hipotermia profunda. In Trabalhos do Servigo de Fisiologia da Faculdade de Medicina do Porto - Homenagem ao Prof Dr. J. Afonso Guimarais 1970: 93
  PubMedGoogle Scholar
• 9 Pina-Cabral JM, Izolett Amaral, Macedo-Pinto M, Guerra e Paz LH. Hepatic and splenic platelet sequestration during deep hypothermia in the dog. Haemostasis 1973/74 2: 235-244
  PubMedGoogle Scholar
• 10 Paul J, Cornillon B, Baguet J, Dureau G, Belleville J. In vivo release of an heparin-like factor in dogs during profound hypothermia. J Thorac Cardiovasc Surg 1981; 82: 45-48
  PubMedGoogle Scholar
• 11 Austen DEG, Rhymes IL. A Laboratory Manual of Blood Coagulation Blackwell Scientific Publications. Oxford 1975; 101
  PubMedGoogle Scholar
• 12 Behnke O. Further studies on microtubules. A marginal bundle in human and rat thrombocytes. J Ultrastruct Res 1965; 13: 469-477
  CrossrefPubMedGoogle Scholar
• 13 Behnke O. Incomplete microtubules observed in mammalian blood platelets during microtubule polimerization. J Cell Biol 1967; 34: 697-701
  CrossrefPubMedGoogle Scholar
• 14 Pina-Cabral JM, Magalhaes MM, Andrade JJ. “In vivo” ultrastruc-tural changes induced in blood platelets by cold. Abstracts III Congr Int Soc Thrombos Haemost, Washington 1972: 234
  PubMedGoogle Scholar
• 15 White JG. Platelet microtubules and microfilaments: Effects of cytochalasin B on structure and function. In Platelet Aggregation Caen J. ed Masson et Cie, Paris: 1971: 15-52
• 16 White JG, Krumwiede M. Influence of cytochalasin B on the shape change induced in platelets by cold. Blood 1973; 41: 823-832
  PubMedGoogle Scholar
• 17 Peerschke EI, Zucker MB. Fibrinogen receptor exposure and aggregation of human blood platelets produced by ADP and chilling. Blood 1981; 57: 663-670
  PubMedGoogle Scholar
• 18 Smith JB, Ingerman CM, Kocsis JJ, Silver MJ. Formation of prostaglandins during the aggregation of human blood platelets. J Clin Invest 1973; 52: 965-969
  CrossrefPubMedGoogle Scholar
• 19 Clemmons RM, Bliss EL, Dorsey-Lee MR, Seachord CL, Meyers KM. Platelet function, size and yield in whole blood and in platelet-rich plasma prepared using differing centrifugation force and time in domestic and food-producing animals. Thromb Haemostas 1983; 50: 838-843
  PubMedGoogle Scholar
• 20 Samuelsson B. The role of prostaglandin endoperoxides and thromboxanes in human platelets. In Prostaglandins in Haematology. Silver M J, Smith J B, Kocsis J J eds Spectrum, New York 1977; 235-246
  PubMedGoogle Scholar
• 21 Rajtar G, Cerletti C, Livio M, De Gaetano G. Sulphinpyrazone prevents “in vivo” the inhibitory effect of aspirin on rat platelet cyclo-oxygenase activity. Biochem Pharmacol 1981; 30: 2773-2776
  CrossrefPubMedGoogle Scholar
• 22 Badenhorst PN, Deckmyn H, Vermyien J. The effect of sulphinpyrazone on whole blood thromboxane and prostacyclin generation in man. Thromb Res 1982; 28: 59-66
  CrossrefPubMedGoogle Scholar
• 23 Ashida S, Abiko Y. Mode of action of ticlopidine in inhibition of platelet aggregation in the rat. Thromb Haemostas 1979; 41: 436-449
  PubMedGoogle Scholar
• 24 Johnson M, Heywood JB. Possible mode of action of ticlopidine: a novel inhibitor of platelet aggregation. 7th Int Congr Thrombos Haemost, London 1979. Thromb Haemostas 1979; 42: 367 Abstr
  PubMedGoogle Scholar
• 25 Lips JPM, 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
• 26 Kamm B, Bruno J, Molony B, Hass W, Day HJ. Ticlopidine aspirine stroke study - rationale and design. 10th Int Congr Thrombos Haemost, San Diego 1985. Thromb Haemostas 1985; 54: 8 Abstr
  PubMedGoogle Scholar
• 27 Packham MA. Platelet function inhibitors. Thromb Haemostas 1983; 50: 610-619
  PubMedGoogle Scholar
• 28 Hladovec J, Koleilat Z, Prerovsky I. The effect of venous occlusion on the sequestration of blood platelets. Thrombos Diathes Haemorrh 1972; 28: 383-392
  PubMedGoogle Scholar
• 29 Frojmovie MM, Milton JG. Human platelet size, shape, and related functions in health and disease. Physiol Rev 1982; 62: 185-261
  CrossrefPubMedGoogle Scholar
• 30 Cohen I. The contractile system of blood platelets and its function. In Meth Achiev exp Pathol, Vol 9 Karger, Basel: 1979: 40-86