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Dear Sir,

Re: Protein C deficiency presenting as portal hypertension due to portal vein thrombosis. (Shirazi et al, CME Journal Gastroenterology, Hepatology & Nutrition, 1999 ; 2: 23-24.).

Editor: We were interested to read this case report which highlighted the importance of investigating for thrombophilic diseases in patients presenting with portal vein thrombosis (PVT) and some dilemmas in management of this condition. However, on the evidence presented a secure diagnosis of primary protein C deficiency in the case presented remains questionable and we feel that it is important to clarify some potential misconceptions that may arise when interpreting coagulation profiles in patients with PVT. We have investigated a large series of patients with extrahepatic portal hypertension due to PVT and found that deficiencies in the natural anticoagulant proteins C, S and antithrombin are very common, with combined or multiple deficiencies occurring in some patients.¹ A similar finding has been reported in children with this disorder.² In both case series, it was rare to find any evidence of familial deficiencies of these proteins by family screening which, combined with the frequent finding of multiple deficiencies, suggests that these deficiencies are non-hereditary and, presumably, secondary. We and others have also reported deficiency of coagulation factors (with elevation of the prothrombin time) occurring in PVT in the presence of otherwise normal liver function.³ The mechanisms of these abnormalities have not been elucidated but do not appear to involve a typical consumption coagulopathy, and are at least partly dependent upon shunting of blood from the liver. Thus, whilst it remains important to screen for thrombotic disorders in patients with PVT we feel that reduced levels of natural anticoagulant proteins alone cannot be taken as definitive evidence of primary deficiency states unless accompanied by corroborative family studies or/and a previous or family history of recurrent thrombotic events. Although the case history presented did include a history of thromboembolism in an elderly relative, it would be interesting to know whether any other family members were available for screening.

A further point of contention concerns the role of warfarin in PVT; the authors appear to have used warfarin for an unspecified period in the case report and later suggest that a ‘good response’ to warfarin can be expected. However, although anticoagulation was recently suggested to be beneficial in acute PVT⁴ there remains very little evidence to support the use of warfarin in ‘mature’ PVT, where varices have developed, despite a theoretical potential benefit. In our own experience it is exceptional to find evidence of recurrence or extension of thrombosis in patients with PVT who have not been anticoagulated and most of these patients can be managed sufficiently by eradication of varices (although emergency portosystemic shunting is occasionally done to control severe haemorrhage at presentation). Furthermore, a retrospective review of the role of warfarin in PVT did not suggest any significant benefit⁵ and further follow-up of large numbers of cases will be required before any definitive conclusions can be drawn from the potential role of anticoagulation.

Finally in the case report it would have been interesting to know what the exact levels of protein S and antithrombin were, whether other thrombotic conditions were sought (APC resistance or factor V Leiden mutation, prothrombin gene G20210A mutation, lupus anticoagulant, paroxysmal nocturnal haemoglobinuria), and whether there was a history of abdominal surgery or any other abdominal inflammatory disease that may have predisposed to portal thrombosis.

References:

1. Fisher NC, Elias E, Roper J. Wilde M Natural Anticoagulant Protein Deficiency in Portal Vein Thrombosis A Secondary Phenomenon? Gut 1998; 42 suppl. 1: A26.

2. Dubuisson C, Boyer-Neumann C, Wolf M, Meyer D, Bemard 0. Protein C, protein S and antithrombin 111 in children with portal vein obstruction. Journal of Hepatology 1997; 27: 132-135.

3. Robson SC, Kahn D, Kruskal L, Bird AR, Kirsch RE. Disordered hemostasis in extrahepatic portal hypertension. Hepatology 1993; 18: 853-857.

4. Ramage L, Sheen CL, Richards W, Milne A, Green 1. Clinical features, diagnosis and outcome of acute portal vein thrombosis. Gut 1999; 44 (suppl. 1): A57.

5. Condat B, Pessione R, Erlinger S, Valla D. Portal vein thrombosis. Outcome in 94 adult patients. Hepatology 1997; 26 suppl: 204A.