The risk of variceal bleeding in cirrhotics is associated with increasing liver dysfunction, larger varices, endoscopic red signs, and higher portal pressure. However, why bleeding occurs unpredictably and infrequently in individual patients is unknown.

Bacterial infections occur in 35–66% of cirrhotics presenting with gastrointestinal bleeding.¹ We proposed a possible pathophysiological basis linking infection and variceal bleeding via endotoxin induced endothelin release and subsequent portal pressure rise, combined with impaired platelet aggregation due to endotoxin induced nitric oxide and prostacyclin.² Infected cirrhotics demonstrate a heparin effect using heparinase I modified thromboelastography (TEG) and have anti-Xa activity.^3,4 Now we show similar findings in two cirrhotics during the course of acute variceal bleeding.

Patient 1 was male, 66 years old (Child-Pugh grade C), and patient 2 was female, 42 years old (Child-Pugh grade B), both with alcoholic cirrhosis. Both received endoscopic banding, intravenous terlipressin, and cefotaxime prophylactically as currently recommended.¹ Baseline bacterial screens were negative with no subsequent infections. Blood samples after informed consent were taken at baseline (before any therapy) and subsequently over seven days. Heparinase I modified and standard TEG (Haemoscope Corp., Skokie, Illinois, USA) were performed simultaneously using only calcium activated citrated blood from the same sample 90 minutes after venepuncture⁵: a heparin effect was defined as an improvement in r time, k time, and α angle occurring together. Anti-Xa was assessed by chromogenic (Sigma Diagnostics, Poole, Dorset, UK) and clotting assays (Diagnostic Reagents, Thame, Oxford, UK).

A heparin effect was detected between one hour (patient 2) and six hours (patient 1) after the initial bleeding episode and persisted for 6–7 days, not fully corrected by fresh frozen plasma and/or red blood cells (fig 1) given during the first 24 hours. In patient 1, anti-Xa activity was positive during the same time span in which there was a heparin effect.

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Figure 1

 Comparison of standard and heparinase I modified thromboelastography with respect to r time in two patients with variceal bleeding.

Evaluated TEG parameters were “r time” (time for the clot to start forming), “k time” (time between the TEG trace reaching 2 mm and 20 mm), and “α angle” (the slope drawn from the r to the k value). These worsened over time: in patient 1, r time 11 minutes (four hours after the bleeding episode) to 18.8 minutes (six hours later); k time from 2.7 minutes to 7.3 minutes; and α angle from 53.8° to 28.7°. In patient 2, r time increased from 11.2 minutes (one hour after the first haematemesis) to 33.8 minutes (two hours later); k time from 3.1 minutes to 10.7 minutes; and α angle from 50.8° to 17.8°. These values slowly returned to baseline concomitantly with disappearance of the heparin effect after 6–7 days.

Routine coagulation parameters (prothrombin time, activated partial thromboplastin time) did not show any correlation with worsening TEG parameters or the heparin effect.

The presence of endogenous heparinoids in cirrhotic patients with acute variceal bleeding is clearly demonstrated. There was no evidence of infection but the antibiotic prophylaxis possibly prevented or treated infection. Neither patient experienced early rebleeding. The heparin effect was documented shortly after the beginning of the haemorrhage and disappeared over five days, over the same time course of antibiotic therapy. This was also seen by Montalto and colleagues.³ The absence of a demonstrable heparin effect at the beginning of bleeding and appearance thereafter could suggest that bleeding is a cause of its occurrence, and not the other way round. However, citrated blood may mask an initial less severe heparin effect and this needs to be evaluated compared with native blood. The heparin effect could influence continued variceal bleeding or early rebleeding. It is possible that the heparin effect might be worse in the absence of antibiotics. This phenomenon deserves wider study, particularly as bacterial infection has been linked to failure to control variceal bleeding and early rebleeding, in a randomised study of prophylactic antibiotics.⁶