Aliment Pharmacol Ther 31, 366‐374 Summary Background  As current imaging techniques in cirrhosis allow detection of asymptomatic portal vein thrombosis during routine ultrasonography, more patients with cirrhosis are diagnosed with portal vein thrombosis. Although a consensus on noncirrhotic extra‐hepatic portal vein thrombosis has been published, no such consensus exists for portal vein thrombosis with cirrhosis. Aim  To perform a systematic review of nonmalignant portal vein thrombosis in cirrhosis in terms of prevalence, pathogenesis, diagnosis, clinical course and management. Methods  Studies were identified by a search strategy using MEDLINE and EMBASE. Results  Portal vein thrombosis is encountered in 10–25% of cirrhotics. In terms of pathophysiology, cirrhosis is no longer considered a hypocoagulable state; rather than a bleeding risk in cirrhosis, various clinical studies support a thrombotic potential. Clinical findings of portal vein thrombosis in cirrhosis vary from asymptomatic disease to a life‐threatening condition at first presentation. Optimal management of portal vein thrombosis in cirrhosis is currently not addressed in any consensus publication. Treatment strategies most often include the use of anticoagulation, while thrombectomy and transjugular intrahepatic portosystemic shunts are considered second‐line options. Conclusions  Portal vein thrombosis in cirrhosis has many unresolved issues, which are often the critical problems clinicians encounter in their everyday practice. We propose a possible research agenda to address these unresolved issues.

To cite this article: Gatt A, Riddell A, Calvaruso V, Tuddenham EG, Makris M, Burroughs AK. Enhanced thrombin generation in patients with cirrhosis-induced coagulopathy. J Thromb Haemost 2010; 8: 1994-2000 Summary. Background: Prothrombin time (PT) and the international normalized ratio (INR) are still routinely measured in patients with liver cirrhosis to ÔassessÕ their bleeding risk despite the lack of correlation with the two. Thrombin generation (TG) assays are global assays of coagulation that are showing promise in assessing bleeding and thrombosis risks. Aim: To study the relationship between the INR and TG profiles in cirrhosis-induced coagulopathy. Methods: Seventy-three patients with cirrhosis were studied. All TG parameters were compared with those from a normal control group. Contact activation was prevented using corn trypsin inhibitor. TG was also assayed in the presence of Protac Ò . The endogenous thrombin potential (ETP) ratio was derived by dividing the ETP with ProtacÒ by the ETP without ProtacÒ. Results: The INR (mean 1.7) did not correlate with the ETP and the velocity of TG (P > 0.05). There was no difference between the lag time and ETP of the two groups (P > 0.05). The velocity of TG was increased in cirrhosis (67.95 ± 34.8 vs. 45.05 ± 25.9 nM min )1 ; P = 0.016) especially in patients with INRs between 1.21 and 2.0. Both the ETP with Protac Ò and the ETP ratio were increased in cirrhosis (mean 1074 ± 461.4 vs. 818 ± 357.9 nM min, P = 0.004 and 0.80 ± 0.21 vs. 0.44 ± 0.15, P £ 0.0001, respectively). Conclusion: Despite a raised INR, TG parameters are consistent with a hypercoagulable profile in cirrhosis-related coagulopathy. This confirms that the PT or INR should not be used to assess bleeding risk in these patients, and other parameters, such as TG, need to be explored as clinical markers of coagulopathy.

Summary Thrombin is the central enzyme in the coagulation cascade. Estimation of an individual’s potential to generate thrombin may correlate more closely with a hyper‐ or hypo‐coagulable phenotype, compared to traditional coagulation tests. The possible correlation and recent technical advances in thrombin generation measurement has caused a significant interest in the method and the development of commercial assays. Several variations of the assay exist depending on the defect to be investigated. Fluorogenic thrombin generation assays have acceptable intra‐laboratory variation but a higher inter‐laboratory variation. Variation in preanalytical variables makes comparisons between studies difficult. Thrombin generation is highly variable between individuals and there are suggestions that this may allow individualized treatment based on global haemostatic response in patients with bleeding disorders or on anticoagulant therapy. In patients with thrombotic disorders it may be possible to identify those at higher risk of recurrent thrombosis. For both scenarios, however, data from large prospective studies are lacking or inconclusive and a good relationship between thrombin generation and phenotype remains to be established. Further standardization of the assay is needed before large multicentre studies can be conducted and until then thrombin generation in routine clinical practice is not yet a reality.

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