Fernando MoraesI; Helena NaderI; Carlos P DietrichI; Ênio BuffoloI
DOI: 10.1590/S0102-76381996000300010
ABSTRACT
In order to quantify seric levels of heparin, its attenuation as a time function and its residual value after neutralization with protamine sulfate, blood samples were collected, at pre-set intervals, from 27 patients undergoing myocardial revascularization surgery under extracorporeal circulation. After heparinization (400 Ul/Kg), blood samples were collected at 5, 10, 30 and 60 minutes and subsequently every 30 minutes depending upon the extracorporeal circulation lenght. At each hour after heparinization, a new heparin dose (200 Ul/Kg) was administered. The samples were kept at 4ºC prior to the heparin extract process, which was performed by physical/chemical method. The dosages showed that 5 minutes after heparinization the patients show maximal blood concentration of heparin and after 60 minutes it is aproximately 68% of the concentration at 5 minutes. At 90 minutes time, that is, after re-heparinization, the concentration of heparin is 96% of the one showed on the fifth minute and after the protamine sulfate neutralization (1.5:1), a residual value corresponding to 4% of the one initially observed is still found. It was observed that older patients have a tendency to keep longer seric heparin level, and heparin concentration at a given time could be estimated by the Equation Heparin - Concentration = 104.7 + (-12.85 x minutes (In) + 0.25 x age).RESUMO
Com o objetivo de quantificar o nível sérico de heparina, sua atenuação em função do tempo e o valor residual após a neutralização com sulfato de protamina, foram coletadas amostras de sangue em tempos pré-estabelecidos em 27 pacientes submetidos a revascularização do miocárdio com circulação extracorpórea. Após a heparinização (400 Ul/kg) as amostras de sangue foram coletadas nos tempos de 5, 10,30 e 60 minutos e subseqüentemente a cada 30 minutos, dependendo do tempo da circulação extracorpórea. A cada hora, após a heparinização, administrava-se nova dose de heparina (200 Ul/kg). As amostras eram armazenadas à temperatura de 4ºC antes do processo de extração da heparina que foi realizado por métodos físico-químicos. As dosagens mostraram que 5 minutos após a heparinização os pacientes apresentaram concentração sangüínea máxima de heparina e, ao tempo de 60 minutos, a sua concentração é de aproximadamente 68% da encontrada aos 5 minutos. Ao tempo de 90 minutos, ou seja, após a reheparinização a concentração de heparina é 96% da evidenciada aos cinco minutos e, após a neutralização com sulfato de protamina (1,5:1), ainda se encontra um valor residual de heparina que corresponde a 4% do observado inicialmente. Observou-se que os pacientes mais idosos têm uma tendência a manter um nível sérico mais prolongado e através da equação (Cone. de heparina = 104,7 + (- 12,85 x minutos (In)) + 0,25 x idade) podemos estimar a concentração de heparina em determinado tempo.REFERENCES
1. Bull B S, Korpan R A, Huse W M, Briggs B D - Heparin therapy during extracorporeal circulation: I. Problems inherent in existing heparin protocols. J Thorac Cardiovasc Surg 1975; 69: 674-84. [MedLine]
2. Abildgaard U - Highly purified antithrombin III with heparin cofator activity prepared by disc electrophoresis. Scand J Clin Lab 1968; 21: 89-91.
3. Hattersley P G - Activated coagulation time of whole blood. JAMA 1966; 196: 436-40. [MedLine]
4. Olsson P, Lagergren H, Stig E K - The elimination from plasma of intravenous heparin: an experimental study on dogs and humans. Acta Med Scand 1963; 173: 619-30. [MedLine]
5. Horkay F, Martin P, Rajah M, Walker D - Response to heparinization in adults and childern undergoing cardiac operations. Ann Thorac Surg 1922; 53: 822-6.
6. Dietrich C P & Dietrich S M C - Electrophoretic behavior of acidic mucopolysaccharides in diamine buffers. An Biochem 1976; 70: 645-7.
7. Dietrich C P, McDuffie N M, Sampaio L O - Identification of acidic mucopolysaccharides by agarose gel electrophoresis. J Chromatogr 1977; 130: 299-304. [MedLine]
8. Dietrich C P, Tersariol I L S, Silva R G, Bianchini P, Nader H B - Dependence of the C-6 sulfate of the glucosamine moiety and 1-4 glycosydic linkage of heparin disaccharides for production of hemorrhage: reversal of the antihemostatic activity of heparin and their fragments by adenosin triphosphate and myosin. Semin Thromb Hemost 1991; 17: 65-73. [MedLine]
9. Cassaro C M F & Dietrich C P - The distribution of sulfated mucopolysaccharides in invertebrates. J Biol Chem 1977; 252: 2254-61. [MedLine]
10. Jaques L B, Ballieux R E, Dietrich C P, Kavanagh L W - A microeletrophoresis method for heparin. Can J Physiol Pharmacol 1968; 46: 351-60.
11. Bounameaux H, Marbet G A, Lammle B, Eichlisberger R, Duckert F - Monitoring of heparin treatment: comparison of thrombin time, activated partial thromboplastin time, and plasma heparin concentration, and analysis of the behaviour of antithrombin III. Am J Clin Pathol 1980; 74: 68-73. [MedLine]
12. Garcia H V, Buffolo E, Nader H B, Dietrich C P - ATP reduces blood loss produced by heparin in cardiopulmonary bypass operations. Ann Thorac Surg 1994; 57: 956-9. [MedLine]
13. Jaberi M, Bel W R, Benson D W - Control of heparin therapy in open-heart surgery. J Cardiovasc Surg 1974; 67: 133-41.
14. Kaul T K, Crow M J, Rajah S M, Deverall P B, Watson D A - Heparin administration during extracorporeal circulation: heparin rebound and postoperative bleeding. J Thorac Cardiovasc Surg 1979; 78:95-102. [MedLine]
15. Effeney D J, Goldstone J, Chin U, Krupski W C, Ellis R J - Intraoperative anticoagulation in cardiovascular surgery. Surgery 1981; 90: 1068-74. [MedLine]
16. Estes J W & Poulin P F - Pharmacokinetics of heparin. Thrombos Diathes Haemorrh (Stuttgard) 1974; 33: 26-37.
17. Bârzu T, Molho P, Tobelem G, Petitou M, Caen J P - Binding of heparin and low molecular weight heparin fragments to human vascular endothelial cells in culture. Nouv Rev Fr Hematol 1984; 26: 243-7. [MedLine]
18. Swart C A M, Nijmeyer B, Roelofs J M M, Sixma J J - Kinetics of intravenously administered heparin in normal humans. Blood 1962; 60: 1251 -8.
19. Boldt J, Zickmann B, Herold C, Scholz S, Dapper F, Hempelmann G - Heparin management during cardiac surgery with respect to various blood-conservation techniques. Surgery 1992; 111: 260-5. [MedLine]
20. Nader H B, Dietrich C P, Strauss A H, Takahashi H K - Características físico-químicas da heparina relacionadas com a açâo anticoagulante e anti-hemostática. Rev Bras Biol 1979; 39: 793-816. [MedLine]