Kinetics and in Vivo Redistribution of ¹¹¹Indium-Labelled Human Platelets after Intravenous Protamine Sulphate

Summary

The pathogenesis of thrombocytopenia induced by intravenous protamine sulphate was studied in six patients who underwent cardiopulmonary bypass surgery, and in three normal volunteers. Autologous platelets were labelled with ¹¹¹Indium-oxine. Platelet lifespan was determined. In vivo ¹¹¹In-platelet localization, organ redistribution and sites of destruction were quantitated with a scintillation camera and a computer-assisted imaging system. Protamine induced a transient thrombocytopenia, maximal 5-10 min after injection, and 30-40 min in duration. The thrombocytopenia was accompanied by a transient accumulation of platelets in the liver. The splenic platelet pool remained unaltered and no platelets accumulated in the lungs. Platelet survival, measured in two volunteers, was slightly longer than normal and fitted a linear function best. There was a severe transient neutropenia during the period of thrombocytopenia. We conclude that protamineinduced thrombocytopenia is caused by hepatic accumulation of "activated" platelets or platelet aggregates, the process is reversible, and in the two normal volunteers studied, platelet survival was not affected.

Key words

Platelet kinetics - ¹¹¹Indium-oxine labelled human platelets - Protamine sulphate - Thrombocytopenia, protamine induced - Neutropenia, protamine induced

• References

• 1 Gröttum KA. Platelet surface charge and aggregation: Effects of polyelectrolytes. Thromb Diath Haemorrh 1969; 21: 450-462
• 2 Eika C. On the mechanism of platelet aggregation induced by heparin, protamine and polybrene. Scand J Haematol 1972; 9: 248-257
• 3 Perkins HA, Harkins G, Gerbode F, Rolfs MR, Acra DJ. Comparison of effects of protamine and polybrene, with special emphasis on the factor VIII (antihemophilic globulin) deficiency induced. J Clin Invest 1961; 40: 1421-1430
• 4 Woods JE, Kirklin JW, Owen CA, Thompson JH, Taswell HF. Effects of bypass surgery on coagulation-sensitive clotting factors. Mayo Clin Proc 1967; 42: 724-735
• 5 Rådegran K, Bergentz S-E, Lewis DH, Ljungqvist U, Olsson P. Pulmonary effects of protamine induced platelet aggregation. Intravascular obstruction or vasoconstriction? Scand J Clin Lab Invest 1971; 28: 423-427
• 6 Jacques LB. A study of the toxicity of the protamine, salmine. Brit J Pharmacol 1949; 4: 135-144
• 7 Goldman BS, Joison J, Austen WG. Cardiovascular effects of protamine sulfate. Ann Thorac Surg 1969; 7: 459-471
• 8 Rådegran K, McAslan C. Circulatory and ventilatory effects of induced platelet aggregation and their inhibition by acetylsalicylic acid. Acta Anaesthesiol Scand 1972; 16: 76-84
• 9 Thakur ML, Welch MJ, Joist JH, Coleman RE. ¹¹¹Indium-labeled platelets: studies on preparation and evaluation of in vitro and in vivo functions. Thromb Res 1976; 9: 345-357
• 10 Heyns AduP, Lötter MG, Badenhorst PN, Van Reenen OR, Pieters H, Minnaar PC, Retief FP. Kinetics, distribution and sites of destruction of ¹¹¹Indium-labelled human platelets. Br J Haematol 1980; 44: 269-280
• 11 Lötter MG, Badenhorst PN, Heyns AduP, Van Reenen OR, Pieters H, Minnaar PC. Kinetics, distribution and sites of destruction of canine blood platelets with In-111 oxine. J Nucl Med 1980; 21: 36-40
• 12 ICSH panel on Diagnostic Application of radioisotopes in Hematology Recommended methods for radioisotope platelet survival studies. Blood 1977; 50: 1137-1144
• 13 Heyns AduP, Badenhorst PN, Pieters H, et al. Preparation of a viable population of Indium-111-labelled human blood platelets. Thromb Haemostas 1980; 42: 1473-1482
• 14 Murphy EA, Francis ME. The estimation of blood platelet survival. II The multiple hit model. Thromb Diath Haemorrh 1971; 25: 53-80
• 15 Swank RL. Platelet aggregation: its role and cause in surgical shock. J Trauma 1968; 8: 872-879
• 16 Jenkins CSP, Packham MA, Kinlough-Rathbone RL, Mustard JF. Interactions of polylysine with platelets. Blood 1971; 37: 395-412
• 17 Bennett Jr IL. Comparison of leucocyte changes produced by pyrogens and by anaphylaxis in the guinea pig. Proc Soc Exp Biol Med 1951; 77: 772-775
• 18 Bierman HR, Kelly KH, Petrakis NL, Cordes F, Foster M, Lose EA. Effect of intravenous histamine administration on level of white blood count in peripheral blood. Blood 1951; 6: 926-935