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”.
