Thromb Haemost 1976; 36(01): 115-126
DOI: 10.1055/s-0038-1648015
Original Article
Schattauer GmbH

Bleeding in Uremic Patients after Carbenicillin[*]

K Andrassy**
1  Medizinische Universitätsklinik (Ludolf-Krehl-Klinik), D 6900 Heidelberg (Germany)
,
E Weischedel
1  Medizinische Universitätsklinik (Ludolf-Krehl-Klinik), D 6900 Heidelberg (Germany)
,
E Ritz
1  Medizinische Universitätsklinik (Ludolf-Krehl-Klinik), D 6900 Heidelberg (Germany)
,
T Andrassy
1  Medizinische Universitätsklinik (Ludolf-Krehl-Klinik), D 6900 Heidelberg (Germany)
› Author Affiliations
Further Information

Publication History

Received 06 November 1975

Accepted 28 April 1976

Publication Date:
03 July 2018 (online)

Summary

Hemorrhagic diathesis was observed in patients with renal insufficiency after carbenicillin at serum levels > 300 μg/ml. Normal coagulation factors (F. I, II, V, VII, VIII, X), normal PTT, normal platelet counts, negative ethanol gelation test (fibrin monomers) were found as well as a prolongation of thromboplastin time (Quick), thrombin time, reptilase time and thrombin coagulase time. Platelet function was disturbed. In addition, the plasmatic system was involved: inhibition of fibrinogen-fibrin conversion (Belitser assay) and enhanced antithrombin III activity; in vivo the latter was ascribed to a heparin-like activity. In vitro, abnormal fibrinogen-fibrin conversion and a modified electrophoretic mobility of antithrombin III was seen: however an enhanced antithrombin III activity in vitro was not found with carbenicillin and various penicillin derivatives.

This study demonstrates that carbenicillin, in addition to its known effect on platelet function, also disturbs the plasmatic coagulation system. This additional effect of carbenicillin is clinically important since protamin chloride effectively blocks bleeding without interfering with antibacterial activity.

Both penicillin and penicillin derivatives have been shown to interfere with hemostasis and to cause clinically manifest hemorrhagic diathesis (Fleming and Fish 1947, Lurie et al. 1970a, b, McClure et al. 1970, Yudis et al. 1972, Demos 1971, Waisbren et al. 1971). Carbenicillin interferes with ADP-, collagen- or thrombin-induced platelet aggregation and with the release reaction both in vivo (McClure et al. 1970, Cazenave et al. 1973) and in vitro (McClure et al. 1970, Cazenave et al. 1973). In addition Lurie and colleagues (1970b) concluded that an inhibition of the conversion of fibrinogen to fibrin is involved although no experimental details were given. Later Brown and colleagues (1974) concluded that carbenicillin at usual dose levels “only affects the platelet component of hemostasis and has little effect on fibrin formation or other phases of coagulation in patients with normal renal function”.

* The results were presented in part at the National Conference on Thrombosis and Hemostasis in Dallas, 1974, and at the VI. Congress Int. Society of Nephrology, Florence (Italy), 1975.


** Reprint requests to Prof. K. Andrassy, Ludolf-Krehl-Klinik, Bergheimer Straße 58, 6900 Heidelberg, Germany.