A 60-year-old man with cirrhosis is admitted to the hospital with concern for spontaneous bacterial peritonitis. His body mass index is 35 kg/m2. He is severely deconditioned and largely bed bound. His admission labs show thrombocytopenia (platelets 65,000/mcL) and an elevated international normalized ratio (INR) of 1.6. Should this patient be placed on venous thromboembolism (VTE) prophylaxis on admission?
Patients with chronic liver disease (CLD) have previously been considered “auto-anticoagulated” because of markers of increased bleeding risk, including a decreased platelet count and elevated INR, prothrombin time, and activated partial thromboplastin time. It is being increasingly recognized, however, that CLD often represents a hypercoagulable state despite these abnormalities.1
While cirrhotic patients produce less of several procoagulant substances (such as factors II, V, VII, X, XI, XII, XIII, and fibrinogen), they are also deficient in multiple anticoagulant factors (such as proteins C and S and antithrombin) and fibrinolytics (plasminogen). While the prothrombin time and activated partial thromboplastin time are sensitive to levels of procoagulant proteins in plasma, they do not measure response to the natural anticoagulants and therefore do not reflect an accurate picture of a cirrhotic patient’s risk of developing thrombosis. In addition, cirrhotic patients have many other risk factors for thrombosis, including poor functional status, frequent hospitalization, and elevated estrogen levels.
Overview of the data
VTE incidence among patients with CLD has varied across studies, ranging from 0.5% to 6.3%.2 A systemic review of VTE risk in cirrhotic patients concluded that they “have a significant risk of VTE, if not higher than noncirrhotic patients and this risk cannot be trivialized or ignored.”2
In a nationwide Danish case-control study, patients with cirrhosis had a 1.7 times increased risk of VTE, compared with the general population.3 Hypoalbuminemia appears to be one of the strongest associated risk factors for VTE in these patients, likely as a reflection of the degree of liver synthetic dysfunction (and therefore decreased synthesis of anticoagulant factors). One study showed that patients with an albumin of less than 1.9 g/dL had a VTE risk five times higher than patients with an albumin of 2.8 g/dL or higher.4
Given the increased risks of bleeding and thrombosis in patients with cirrhosis, how should VTE prophylaxis be managed in hospitalized patients? While current guidelines do not specifically address the use of pharmacologic prophylaxis in cirrhotic patients, the Padua Predictor Score, which is used to assess VTE risk in the general hospital population, has also been shown to be helpful in the subpopulation of patients with CLD (Table 1).
In one study, cirrhotic patients who were “high risk” by Padua Predictor score were over 12 times more likely to develop VTE than those who were “low risk.”5 Bleeding risk appears to be fairly low, and similar to those patients not receiving prophylactic anticoagulation. One retrospective case series of hospitalized cirrhotic patients receiving thromboprophylaxis showed a rate of GI bleeding of 2.5% (9 of 355 patients); the rate of major bleeding was less than 1%.6
Selection of anticoagulant for VTE prophylaxis should be similar to non-CLD patients. The choice of agent (low-molecular-weight heparin (LMWH) or unfractionated heparin) and dosing depends on factors including renal function and bodyweight. If anticoagulation is contraindicated (because of thrombocytopenia, for example), then mechanical prophylaxis should be considered.7