Summary
The ascitic form of a chemically-induced pancreatic ductal adenocarcinoma in the Syrian
golden hamster was very bloody and indistinguishable from blood macroscopically. Unlike
blood, the bloody fluid remained unclotted at room temperature. To explore the possibility
of presence of anticoagulants, we mixed 40% cell-free fluid with 60% normal human
plasma and tested the clottability of the mixture with standard techniques. Plasma
containing the fluid showed markedly prolonged activated partial thromboplastin time
(APTT), thrombin time (TT) and recalcification time (RCT), and normal prothrombin
time (PT) and reptilase time (RT). Comparing the prolongation of APTT of samples containing
the fluid to those containing a commercial heparin, the fluid contained an anticoagulant
activity equivalent to 0.436 ± 0.03 unit heparin per ml (mean ± SEM, n = 14). In addition
to prolonging the APTT, TT and RCT, the fluid also inhibited the clotting and amidolytic
activities of thrombin. “Heparsorb” had nearly completely neutralized the anticoagulant
activity in fluid samples, while protamine sulfate was only partially effective. Incubation
of fluid with pronase or phospholi-pase did not affect its anticoagulant activity;
incubation with heparinase had only a minimal effect. Electrophoresis of an alkali
digested fluid on cellulose acetate revealed the presence of heparan sulfate. The
native ascitic fluid also contained other hemostatic components including platelets,
fibrinogen and antithrombin III, but their concentrations were much lower than in
blood. Apparently, heparan sulfate in the neoplastic effusion is largely responsible
for the bloody ascites tumor remaining unclotted.
Key words
Experimental pancreatic adenocarcinoma - Neoplastic effusion - Anticoagulant - Heparan
sulfate
