Elevated levels of von Willebrand factor are associated with maintained normal primary haemostasis in thrombocytopenic patients with liver cirrhosis

Introduction:

Primary haemostasis is characterized by the von Willebrand factor mediated adhesion of platelets to subendothelial structures. In patients with liver cirrhosis thrombocytopenia, as well as increased vWF, is common, while the prevalence of concomitant thrombocytopathy is still discussed. In this study on cirrhotic patients we assessed the presence of thrombocytopathy in patients with normal thrombocytes and the influence of elevated von Willebrand factor on primary haemostasis in thrombocytopenic patients using the platelet function analyzer PFA-100.

Patients and Methods:

In 57 patients who were evaluated for liver transplantation due to end-stage liver disease the PFA-100 was performed using standard cartridges containing collagen-ADP (COL-ADP) or collagen-epinephrine (COL-Epi). Platelet count, haematocrit, vWF-activity and vWF-antigen were as well determined. In patients with thrombocytopenia (defined as a platelet count <150/nl) the influence of increased vWF on the PFA-100 was analysed. To detect thrombocytopathy the PFA-100 was performed in cirrhotic patients with a platelet count >150/nl and a haematocrit >27.0%. Patients taking antiplatelet drugs or NSAIDs were excluded.

Results:

The 57 patients (Child-Pugh A/B/C: n=13/26/18) had a mean (±SE) platelet count of 115/nl (±67), haematocrit of 33.8% (±6.4), vWF-antigen 393.8% (±209.2) and vWF-activity 314.1% (±174.6). Median closure times for COL-Epi were 176s (±61) and 159s (±73) with COL-ADP. Thrombocytopenic patients with normal PFA-100 after induction with COL-Epi had significant higher levels of vWF-antigen than patients with pathological PFA-100 (494.8±269.7% vs. 351.4±129.5%, p=0.039). In patients without thrombocytopenia pathological results for the PFA-100 were found in 5 of 11 (45.5%) for COL-Epi and in 3 of 11 (27.3%) for COL-ADP; in 3 of these 11 patients both test were pathologic.

Conclusion:

There is evidence for thrombocytopathy in patients with liver cirrhosis and normal platelet count. Furthermore, increased levels of vWF in patients with liver cirrhosis might compensate for a reduced platelet count to maintain normal primary haemostasis. Substitution of vWF might therefore be an interesting approach to improve primary haemostasis in thrombocytopenic patients with liver cirrhosis undergoing medical interventions.