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Studies on hypo-and hypercoagulability II. Coagulation and fibrin analyses in severe infectious and toxic conditions

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Summary

Plasma phospholipids were elevated in patients with severe infections with renal complications (except for pyelonephritis) without shock in comparison with normals and with patients with severe infectionswithout renal complications. In contrast, in patients with toxic conditions with and without shock, total phospholipids were decreased. The percentages of phosphatidyl-ethanolamine and of lecithin were increased and those of lysolecithin decreased in all patient groups.

By incubation of citrate plasma, partial thromboplastin or thromboplastin and Ca++ fibrins were produced, washed out, homogenized and phospholipids were estimated. In the patient groups with infections with renal complications and with peritoneal toxic conditions total phospholipids in the fibrins produced with partial thromboplastin reagent were significantly increased both in comparison to normals and to the corresponding amounts of reagent. Phospholipids in thromboplastinproduced fibrins were significantly elevated only in the patients with infections with renal complications.

The results suport the view that plasma phospholipids-and herewith lipoproteins-are not simply trapped by the fibrin network, but play a role in the coagulation process, particularly under pathological conditions:

  1. 1)

    In the patient groups with the most severe conditions the amount of total phospholipids in the PTT*-produced fibrins was significantly augmented in comparison to normals and the corresponding amount of reagent.

  2. 2)

    Total phospholipids in the PTT-produced fibrins were independent of the amount of phospholipids in the plasma.

  3. 3)

    They were also independent of fibrinogen or any of the coagulation factors.

  4. 4)

    There were significant differences in the complexing of phospholipids between PTT-and thromboplastin-produced fibrins within the same groups.

Routine coagulation parameters (fibrinogen, one-stage prothrombin time, partial thromboplastin time, platelets, thrombelastography, factors II, V, VII, VIII, IX, X) varied greatly. PT* and factor II and VII were significantly decreased in patients with toxic conditions. Fibrinogen was augmented, but the platelet count decreased in patients with infections with renal complications. Of all parameters tested, the increases of percentages of phosphatidylethanolamine in plasma and of total phospholipids in PTT-produced fibrins were most closely connected with clinical signs of hypercoagulability (i.e. of intravascular coagulation without excessive consumption of clotting factors leading to bleeding).

Zusammenfassung

Plasmaphospholipide waren bei Patienten mit schweren Infekten mit renalen Komplikationen (mit Ausnahme der Pyelonephritis) ohne Schock signifikant im Vergleich mit unkomplizierten Infekten und mit Normalen vermehrt. Im Gegensatz dazu waren sie bei infektiös-toxischen Zustandsbildern deutlich erniedrigt. Die Prozentwerte von Phosphatidyläthanolamin und von Lecithin waren bei allen Patientengruppen signifikant vermehrt, während die von Lysolecithin vermindert waren.

Durch inkubation von Zitratplasma, partiellem Thromboplastin oder Thromboplastin und Ca++ wurden Fibrine erzeugt, ausgewaschen, homogenisiert und die Phospholipide im Homogenat bestimmt. In allen Patientengruppen mit Ausnahme der unkomplizierten schweren Infekte waren die in den Fibrinen gefundenen Phospholipide beträchtlich im Vergleich mit Normalen und mit der entsprechenden Menge Reagens vermehrt. Phospholipide in mit Thromboplastin erzeugten Fibrinen waren nur bei schweren Infekten mit renalen Komplikationen erhöht.

Die Ergebnisse unterstützen die Ansicht, daß die Plasmaphospholipide — und damit Lipoproteine — sich nicht einfach im Fibrinnetzwerk verfangen sondern eine eigenständige Rolle im Gerinnungsprozeß, besonders unter pathologischen Bedingungen spielen, und zwar aus folgenden Gründen.

  1. 1.

    In den Patientengruppen mit den schwersten Zustandsbildern waren die Gesamtphospholipide in den mit PTT-Reagens produzierten Fibrinen signifikant im Vergleich zu Normalen und zur entsprechenden Menge Reagens vermehrt.

  2. 2.

    Die Gesamtphospholipide in den PTT-produzierten Fibrinen waren unabhängig von den Gesamtphospholipiden.

  3. 3.

    Sie waren auch unabhängig von Fibrinogen oder einem anderen der geprüften Gerinnungsfaktoren im Plasma.

  4. 4.

    In der Bindung der Phospholipide bestanden signifikante Unterschiede zwischen PTT-und Thromboplastin-produzierten Fibrinen innerhalb der gleichen Gruppen.

Die Routinegerinnungsparameter zeigten große Schwankungen. PT und die Faktoren II und VII waren signifikant bei Patienten mit infektiös-toxischen Zustandsbildern vermehrt. In der Gruppe der Infektionen mit renalen Komplikationen war Fibrinogen vermehrt, jedoch die Thrombozyten vermindert.

Von allen geprüften Parametern waren die Vermehrung der Prozentwerte von Phosphatidyläthanolamin im Plasma und der Gesamtphospholipide in den PTT-produzierten Fibrinen am ausgeprägtesten mit klinischen Zeichen von Hyperkoagulabilität (intravasale Fibrinbildung ohne massiven, zu Blutungen führenden Verbrauch von Gerinnungsfaktoren) verbunden.

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Abbreviations

DIC:

disseminated intravascular coagulation

CCO:

consumption coagulopathy

PTT:

partial thromboplastin time in sec

PT:

results of one stage prothrombin test expressed in %

Plt:

Platelets

PL:

Phospholipid(s)

PLP:

Phospholipid phosphorus

LL:

Lysolecithin

SM:

Sphingomyelin

L:

Lecithin

C:

Cephalin (including PI, PS, PE)

LC:

Lysocephalin (including lysophosphatidylethanolamine, lysophosphatidylserine and lysophosphatidylinositol)

PI:

Phosphatidylinositol

PS:

Phosphatidylserine

PE:

Phosphatidylethanolamine

References

  1. Bartlett, G. R.: Phosphorus assay in column chromatography. J. biol. Chem.234, 446 (1959).

    Google Scholar 

  2. Beller, F.K.: Experimental animal models for the production of disseminated intravascular coagulation, In: Thrombosis and bleeding disorders, p. 514–524. Ed. N. U. Bang, F. K. Beller, E. Deutsch and E. M. Mammen, Georg Thieme Verlag, Stuttgart 1971.

    Google Scholar 

  3. Bergentz, S. E. and L. Leandoer: Disseminated intravascular coagulation in schock, Ann. Chir. et Gynaecol. Fenn.60, 175 (1971).

    Google Scholar 

  4. Brecher, G. and E. P. Cronkite: Morphology and enumeration of human blood platelets, J. applied Physiol.3, 365 (1950).

    Google Scholar 

  5. Breen, F. A. and J. L. Tullit: Ethanol gelation: A rapid screening test for intravascular coagulation, Annals Int. Med.69, 1197 (1968).

    Google Scholar 

  6. Clarkson, A. R., Mary K. MacDonald, V. Fuster, J. D. Cash and J. S. Robson: Glomerular coagulation in acute ischaemic renal failure. Quart. J. Med. New Series39, 695 (1970).

    Google Scholar 

  7. Clauss, A.: Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens, Acta haematol. (Basel)17, 237 (1957).

    Google Scholar 

  8. Corrigan, J., L. R. Walker and N. May: Changes in the blood coagulation system associated with septicemia. New Engl. J. Med.279, 851 (1968).

    Google Scholar 

  9. Das, P. C.: Investigation and preparation of fibrinogen coated tanned sheep red cells, J. clin. Path.23, 149 (1970).

    Google Scholar 

  10. Davison, A. M., D. Thomson, Mary K. MacDonald, J. K. Rae, W. S. Uttley and A. R. Clarkson: Identification of renal fibrin deposition. J. Clin. Path.26, 102 (1973).

    Google Scholar 

  11. Doizaki, W. M. and L. Zieve: Similarities between postheparin lipase and phospholipase. Proc. Soc. Exptl. Biol. Med.129, 382 (1968).

    Google Scholar 

  12. Fitzgerald, D. E., W. J. H. Butterfield, D. Smink and H. E. J. Kruisheer: Platelet adhesiveness: Postmyocardial infarction patients compared with controls, Atherosclerosis13, 217 (1971).

    Google Scholar 

  13. Folch, J., M. Lees and G. H. Sloane-Stanley: A simple method for the isolation and purification of total lipids from animal tissues, J. biol. Chem.226, 497 (1957).

    Google Scholar 

  14. Gralwick, H. R., S. Marcheri and H. Givelber: Intravascular coagulation in acute leukemia: Clinical and subclinical abnormalities. Blood40, 709 (1972).

    Google Scholar 

  15. Hampton, J. R. and J. R. A. Mitchell: Thrombosis, In: Human Blood Coagulation, Haemostasis and Thrombosis, p. 476–496. Ed. Rosemary Biggs, Oxford: Blackwell Sci. Public. 1972.

    Google Scholar 

  16. Hardaway, R. M.: Shock and disseminated intravascular coagulation, Thrombos. Diathes. haemorrh.20, 121 (1966).

    Google Scholar 

  17. Hardaway, R. M.: Disseminated intravascular coagulation. In: Current Concepts of Coagulation and Haemostasis, p. 209–227. Ed. R. Losito and B. Longpre (F. K. Schattauer) Stuttgart 1971.

    Google Scholar 

  18. Hartert, H.: Blutgerinnungsstudien mit der Thromelastographie, einem neuen Verfahren. Klin. Wschr.37/38, 577 (1948).

    Google Scholar 

  19. Hawinger, J. S., S. Niewarowski, V. Gurewich and D. P. Thomas: Measurement of fibrinogen and fibrin degradation products in serum by staphylococcal clumping test. J. Lab. Clin. Med.93, 75 (1970).

    Google Scholar 

  20. Hedner, V. and I. M. Nilsson: Parallel determinations of FDP and fibrin monomers with various methods. Thrombos. Diathes. haemorrh.28, 268 (1972).

    Google Scholar 

  21. Hirano, K., K. Kamaura, H. Shibuto and M. Matamuto: Lipids of Sendai virus and changes in cellular phospholipid synthesis caused by infection. Japan. J. Microbiol.15, 383 (1971).

    Google Scholar 

  22. Horowitz, H. I., R. Des Prez and E. W. Hock: Effects of bacterial endotoxin on rabbit platelets. Enhancement of platelet factor 3 activity in vitro and in vivo, J. exp. Med.116, 619 (1962).

    Google Scholar 

  23. Horwitz, D. L., R. B. Moquin and C. M. Herman: Coagulation changes of septic shock in the sub-human primate and their relationship to hemodynamic changes, Annals. Surg.175, 417 (1972).

    Google Scholar 

  24. Kahn, M. J. P., M. Hans and R. H. Bourgain: The action on blood clotting of different lipoid fractions of beef brain (methods of fractionation and chromatographic isolation procedure of a phospholipid anticoagulant), Thrombos. Diathes. haemorrh.14, 445 (1965).

    Google Scholar 

  25. Kleinknecht, D., A. Kanfer and F. Josso: Intravascular coagulation and heparin therapy in acute renal failure: a reappraisal, Rev. Europ. études clin. et biol.17, 695 (1972).

    Google Scholar 

  26. Korsan-Bengtson, K., L. Wilhelmsen D. Elmefeldt and G. Tibblin: Blood coagulation and fibrinolysis in man after myocardial infarction compared with a representative population sample, Atherosclerosis16, 83 (1972).

    Google Scholar 

  27. Kunz, F.: The participation of phospholipids in the extrinsic pathway of the coagulation process. Thrombos. Diathes. haemorrh.27, 655 (1972).

    Google Scholar 

  28. Kunz, F.: The participation of phospholipids in the intrinsic pathway of the coagulation process. Klin. Wschr.50, 528 (1972).

    Google Scholar 

  29. Kunz, F. and D. Kosin: Plasma phospholipids in cirrhosis of liver and fatty liver. Clin. Chim. Acta27, 185 (1970).

    Google Scholar 

  30. Kunz, F. and W. Stumvoll: Plasmaphosphatidylethanolamine—a better indicator in the predictability of atherosclerotic complications? Atherosclerosis13, 43 (1971).

    Google Scholar 

  31. Kunz, F., E. Rumpl and F. Holzknecht: The role of phospholipids in haemophilia A. Klin. Wschr.50, 1058 (1972).

    Google Scholar 

  32. Kunz, F., H. Hörtnagl, G. Kroesen, E. Rumpl and F. Holzknecht: Studies on hyper-and hypocoagulability. Part I: Evidence for occurence of incomplete consumption coagulopathy. Blut28, 56 (1974).

    Google Scholar 

  33. Lasch, H. G.: Coagulation disturbances in shock, Postgrad. Med. J.45, 539 (1969).

    Google Scholar 

  34. Lasch, H. G., K. Huth, D. L. Heene, G. Müller-Berghaus, M. H. Hörder, H. Janzarik, C. Mittermayer and W. Sandritter: Die Klinik der Verbrauchskoagulopathie, Dtsch. Med. Wochenschr.96, 715 (1971).

    Google Scholar 

  35. Loew, D., R. Wiedemann and W. Remmele: Gerinnungsanalytische und pathologisch-anatomische Untersuchungen beim traumatischen Schock. Klin. Wschr.49, 1101 (1971).

    Google Scholar 

  36. McKay, D. G. and S. S. Shapiro: Alternations in the blood coagulation system induced by bacterial endotoxin. J. Exptl. Med.107, 353 (1958).

    Google Scholar 

  37. Müller-Berghaus, G.: Pathophysiology of disseminated intravascular coagulation, Thrombos. Diathes. haemorrh. Suppl.36, 45 (1969).

    Google Scholar 

  38. Quick, A. J.: The prothrombin in haemophilia and in obstructive jaundice, J. biol. Chem.109, 73 (1935).

    Google Scholar 

  39. Remmele, W. and D. Harms: Zur pathologischen Anatomie des Kreislaufschocks beim Menschen. I. Mikrothrombose der peripheren Blutgefäße. Klin. Wschr.46, 352 (1968).

    Google Scholar 

  40. Riedler, F. G., P. W. Straub and P. G. Frick: Thrombocytopenia in septicemia. Helv. Med. Acta36, fasc. 1, 23 (1971).

    Google Scholar 

  41. Robinson, D. S. and J. C. P. Poole: The similar effect of chylomicra and ethanolamine phosphatide on the generation of thrombin during coagulation. Quart. J. exp. Physiol.41, 36 (1956).

    Google Scholar 

  42. Rodman, N. F., E. M. Barrow and J. B. Graham: Diagnosis and control of the haemophiloid states with the partial thromboplastin time (PTT) test, Amer. J. clin. Path.29, 525 (1958).

    Google Scholar 

  43. Seaman, A. J.: The recognition of intravascular clotting, Arch. Int. Med.125, 1016 (1970).

    Google Scholar 

  44. Sandritter, W.: Zur pathologischen Anatomie des Schocks, Klin. Wschr.51, 1 (1973).

    Google Scholar 

  45. Siss, H. S., C. B. Moschos and R. Becker: On the nature of hypercoagulability. Amer. J. Med.33, 217 (1962).

    Google Scholar 

  46. Wardle, E. N. and G. Taylor: Fibrin breakdown products and fibrinolysis in renal disease. J. Clin. Path.21, 140 (1968).

    Google Scholar 

  47. Wessler, S. and W. E. Stehbens: Thrombosis, In: Thrombosis and bleeding disorders, p. 488–498. Ed. by N. U. Bang, F. K. Beller, E. Deutsch and E. M. Mammen. Georg Thieme Verlag, 1971.

  48. Yamakazi, H. T., T. Odakura, K. Takeuchi and T. Sano: Adhesive platelet count and blood coagulability in myocardial infarction and cerebral thrombosis, Thrombos. Diathes. haemorrh.24, 450 (1970).

    Google Scholar 

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Author notes

  1. Friedl Kunz,  Helmut Hörtnagl,  Dietmar Egg,  Rudolf Aschauer &  Fritz Holzknecht

    Present address: Department of Internal Medicine, University of Innsbruck, Austria

  2. Gunnar Kroesen

    Present address: Department of Anaesthesiology, University of Innsbruck, Austria

  3. Erik Rumpl

    Present address: Department of Neurology, University of Innsbruck, Austria

  4. Wilfried Schennach

    Present address: Chir. Univ.-Klinik, alle Anichstraße Nr. 35, A-6028, Innsbruck

Authors and Affiliations

  1. Department of Internal Medicine, University of Innsbruck, Austria

    Gunnar Kroesen,  Wilfried Schennach &  Erik Rumpl

  2. Department of Anaesthesiology, University of Innsbruck, Austria

    Friedl Kunz,  Helmut Hörtnagl,  Wilfried Schennach,  Dietmar Egg,  Erik Rumpl,  Rudolf Aschauer &  Fritz Holzknecht

  3. Department Surgery, University of Innsbruck, Austria

    Friedl Kunz,  Helmut Hörtnagl,  Gunnar Kroesen,  Wilfried Schennach,  Dietmar Egg,  Erik Rumpl,  Rudolf Aschauer &  Fritz Holzknecht

  4. Department of Neurology, University of Innsbruck, Austria

    Friedl Kunz,  Helmut Hörtnagl,  Gunnar Kroesen,  Wilfried Schennach,  Dietmar Egg,  Rudolf Aschauer &  Fritz Holzknecht

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  1. Friedl Kunz
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Supported by “Österreichischer Fonds zur Förderung der wissenschaftlichen Forschung”.

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Kunz, F., Hörtnagl, H., Kroesen, G. et al. Studies on hypo-and hypercoagulability II. Coagulation and fibrin analyses in severe infectious and toxic conditions. Blut 28, 360–369 (1974). https://doi.org/10.1007/BF01631523

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