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Incidental splanchnic vein thrombosis: preliminary registry data
Comment
Nicoletta Riva and colleagues have gone to some geographical lengths to establish an international registry on incidentally detected splanchnic vein thrombosis,1 an underestimated disorder that branches into various specialties such as radiology, gastroenterology, hepatology, oncology, surgery, and haematology, and that is often managed according to the clinical judgment of different specialists given the poor knowledge of its natural history. Against such a blank background, this registry is timely and welcome since other registries or population-based studies dealing with similar occlusions that were diagnosed clinically describe a natural history that diverges from that of incidentally detected splanchnic vein thrombosis in terms of management, recurrence, and mortality.2 In this first registry on the topic, the prevalence of incidentally detected splanchnic vein thrombosis among patients with splanchnic vein thrombosis was 30% (177 of 597 patients), which compares favourably with the 28% prevalence of non-cirrhotic incidentally detected splanchnic vein thrombosis detected in a cohort of 121 patients with splanchnic vein thrombosis.3 Notably the reported figure of 35% (62 of 177) of incidentally detected splanchnic vein thromboses being detected in patients with solid cancer is greater than the 0·3% reported by others.4 With the large number of participants, the authors were able to identify factors that were associated with or predictive of bleeding and recurrent venous thromboembolism. Baseline thrombocytopenia (platelet count ≤100 × 10⁹ per L) was detected in 66 (46%) of 177 patients with incidentally detected splanchnic vein thrombosis and was associated with increased risk of bleeding and with patients not being given anticoagulation therapy. Furthermore, liver cirrhosis was also associated with an increased risk of bleeding, raising the question of how commonly thrombocytopenia and liver cirrhosis were combined and eventually associated with the subclinical disseminated intravascular coagulation of liver cirrhosis in determining this outcome. By viewing thrombocytopenia and disseminated intravascular coagulation from an oncological perspective, they might represent features and predictors of thrombosis, an issue that this registry should be able to address in the future. Given these observations, it is
worth considering whether measurement of D-dimers could have predictive value in these settings. The potential variability of thrombocytopenia (and thrombocytosis) over time should be taken into account to define the exact platelet level at the incident event or re-event. This figure would be the most relevant in view of the transient or persistent nature of the risk factors, and the same applies to thrombocytosis. As the registry accrues new entrants, by this reasoning, incidentally detected splanchnic vein thrombosis with liver cirrhosis should be separated from other patients, especially those with cancer, given the different pathogenesis and eventual natural histories. Another notable concept is that, given the presence of established risk factors, 150 (85%) occlusions in the patients with incidentally detected splanchnic vein thrombosis group were deemed to be provoked and would require a finite period of anticoagulation, unless the persistence of the thrombotic risk factors dictated otherwise. But without an acute presentation in incidentally detected splanchnic vein thrombosis, how should treatment proceed? Therapeutic anticoagulation starting at diagnosis for a finite period followed by prolonged thromboprophylaxis? Or prolonged thromboprophylaxis from diagnosis? The data from the registry are heterogeneous: treatment for incidentally detected splanchnic vein thrombosis in the registry ranged from parenteral anticoagulation for a median of 6 months to oral vitamin K antagonists for a median of 24 months. Furthermore, splanchnic vein thrombosis recurred in 17 patients with liver cirrhosis, solid cancer, or both (six during treatment with low-molecular-weight heparin at various dosages and 11 off-treatment): since it is difficult to assign which recurrence occurred in which group (liver cirrhosis vs cancer) it can only be inferred that thromboprophylaxis with low-molecular-weight heparin might be helpful but also inadequate unless the relevant data are disclosed. Thinking further on anticoagulation, and given the presence of a large number of patients with liver cirrhosis, another specific question that arises is whether asymptomatic portal vein thrombosis should be anticoagulated. Anticoagulation might prevent thrombosis progression and prevent patients
www.thelancet.com/haematology Published online May 11, 2016 http://dx.doi.org/10.1016/S2352-3026(16)30042-4
Medical Images, Universal Images Group/SPL
Incidental splanchnic vein thrombosis: preliminary registry data
Lancet Haematol 2016 Published Online May 11, 2016 http://dx.doi.org/10.1016/ S2352-3026(16)30042-4 See Online/Articles http://dx.doi.org/10.1016/ S2352-3026(16)30020-5
1
Comment
with portal vein thrombosis from developing the complications of portal hypertension. Formerly deemed a contraindication to liver transplantation,5 current opinion is that extensive portal vein thrombosis makes liver transplant more difficult: thrombosis prolongs surgical time, increases transfusion requirements, and is associated with a higher risk of renal insufficiency and eventual re-thrombosis.6 Therefore anticoagulation might provide some benefit in this setting. The incidence of major bleeding events was low in incidentally detected splanchnic vein thrombosis, and half of these events occurred while patients were on anticoagulation. However, minor bleeding events, according to site, could still affect quality of life and add to the clinical burden of the managing physicians. There is no right or wrong way to present data from a new registry; Riva and colleagues elected to compare incidentally detected splanchnic vein thrombosis with clinically suspected splanchnic vein thrombosis to highlight the clinical, laboratory, management, and prognostic differences between the two groups. As new participants accrue, mounting data should allow the comparison of specific subgroups of patients within the large incidentally detected splanchnic vein thrombosis
2
population and ultimately provide specific guidance in terms of management and outcomes, for the benefit of clinicians and patients alike. *Paul R J Ames, Maurizio Margaglione Haemostasis & Thrombosis Centre, Queen’s Medical Centre, Nottingham University Hospitals, Nottingham, UK (PRJA); Immune Response and Vascular Disease Unit, Nova University Lisbon, Lisbon, Portugal (PRJA); Dipartimento di Medicina Clinica e Sperimentale, Universita’ di Foggia, Foggia, Italy (MM) [email protected] We declare no competing interests. 1
2
3
4
5 6
Riva N, Ageno W, Schulman S, et al, for the International Registry on Splanchnic Vein Thrombosis (IRSVT) study group. Clinical history and antithrombotic treatment of incidentally detected splanchnic vein thrombosis: a multicentre, international prospective registry. Lancet Haematol 2016; published online May 11. http://dx.doi. org/10.1016/S2352-3026(16)30020-5. Søgaard KK, Darvalics B, Horváth-Puhó E, Sørensen HT. Survival after splanchnic vein thrombosis: a 20-year nationwide cohort study. Thromb Res 2016; 141: 1–7. Amitrano L, Guardascione MA, Scaglione M, et al. Prognostic factors in noncirrhotic patients with splanchnic vein thromboses. Am J Gastroenterol 2007; 102: 2464–70. Di Nisio M, Ferrante N, De Tursi M, et al. Incidental venous thromboembolism in ambulatory cancer patients receiving chemotherapy. Thromb Haemost 2010; 104: 1049–54. Manzanet G, Sanjuán F, Orbis P, et al. Liver transplantation in patients with portal vein thrombosis. Liver Transplant 2001; 7: 125–31. Llado L, Fabregat J, Castellote J, et al. Management of portal vein thrombosis in liver transplantation: influence on morbidity and mortality. Clin Transplant 2007; 21: 716–21.
www.thelancet.com/haematology Published online May 11, 2016 http://dx.doi.org/10.1016/S2352-3026(16)30042-4
Nicoletta Riva and colleagues have gone to some geographical lengths to establish an international registry on incidentally detected splanchnic vein thrombosis,1 an underestimated disorder that branches into various specialties such as radiology, gastroenterology, hepatology, oncology, surgery, and haematology, and that is often managed according to the clinical judgment of different specialists given the poor knowledge of its natural history. Against such a blank background, this registry is timely and welcome since other registries or population-based studies dealing with similar occlusions that were diagnosed clinically describe a natural history that diverges from that of incidentally detected splanchnic vein thrombosis in terms of management, recurrence, and mortality.2 In this first registry on the topic, the prevalence of incidentally detected splanchnic vein thrombosis among patients with splanchnic vein thrombosis was 30% (177 of 597 patients), which compares favourably with the 28% prevalence of non-cirrhotic incidentally detected splanchnic vein thrombosis detected in a cohort of 121 patients with splanchnic vein thrombosis.3 Notably the reported figure of 35% (62 of 177) of incidentally detected splanchnic vein thromboses being detected in patients with solid cancer is greater than the 0·3% reported by others.4 With the large number of participants, the authors were able to identify factors that were associated with or predictive of bleeding and recurrent venous thromboembolism. Baseline thrombocytopenia (platelet count ≤100 × 10⁹ per L) was detected in 66 (46%) of 177 patients with incidentally detected splanchnic vein thrombosis and was associated with increased risk of bleeding and with patients not being given anticoagulation therapy. Furthermore, liver cirrhosis was also associated with an increased risk of bleeding, raising the question of how commonly thrombocytopenia and liver cirrhosis were combined and eventually associated with the subclinical disseminated intravascular coagulation of liver cirrhosis in determining this outcome. By viewing thrombocytopenia and disseminated intravascular coagulation from an oncological perspective, they might represent features and predictors of thrombosis, an issue that this registry should be able to address in the future. Given these observations, it is
worth considering whether measurement of D-dimers could have predictive value in these settings. The potential variability of thrombocytopenia (and thrombocytosis) over time should be taken into account to define the exact platelet level at the incident event or re-event. This figure would be the most relevant in view of the transient or persistent nature of the risk factors, and the same applies to thrombocytosis. As the registry accrues new entrants, by this reasoning, incidentally detected splanchnic vein thrombosis with liver cirrhosis should be separated from other patients, especially those with cancer, given the different pathogenesis and eventual natural histories. Another notable concept is that, given the presence of established risk factors, 150 (85%) occlusions in the patients with incidentally detected splanchnic vein thrombosis group were deemed to be provoked and would require a finite period of anticoagulation, unless the persistence of the thrombotic risk factors dictated otherwise. But without an acute presentation in incidentally detected splanchnic vein thrombosis, how should treatment proceed? Therapeutic anticoagulation starting at diagnosis for a finite period followed by prolonged thromboprophylaxis? Or prolonged thromboprophylaxis from diagnosis? The data from the registry are heterogeneous: treatment for incidentally detected splanchnic vein thrombosis in the registry ranged from parenteral anticoagulation for a median of 6 months to oral vitamin K antagonists for a median of 24 months. Furthermore, splanchnic vein thrombosis recurred in 17 patients with liver cirrhosis, solid cancer, or both (six during treatment with low-molecular-weight heparin at various dosages and 11 off-treatment): since it is difficult to assign which recurrence occurred in which group (liver cirrhosis vs cancer) it can only be inferred that thromboprophylaxis with low-molecular-weight heparin might be helpful but also inadequate unless the relevant data are disclosed. Thinking further on anticoagulation, and given the presence of a large number of patients with liver cirrhosis, another specific question that arises is whether asymptomatic portal vein thrombosis should be anticoagulated. Anticoagulation might prevent thrombosis progression and prevent patients
www.thelancet.com/haematology Published online May 11, 2016 http://dx.doi.org/10.1016/S2352-3026(16)30042-4
Medical Images, Universal Images Group/SPL
Incidental splanchnic vein thrombosis: preliminary registry data
Lancet Haematol 2016 Published Online May 11, 2016 http://dx.doi.org/10.1016/ S2352-3026(16)30042-4 See Online/Articles http://dx.doi.org/10.1016/ S2352-3026(16)30020-5
1
Comment
with portal vein thrombosis from developing the complications of portal hypertension. Formerly deemed a contraindication to liver transplantation,5 current opinion is that extensive portal vein thrombosis makes liver transplant more difficult: thrombosis prolongs surgical time, increases transfusion requirements, and is associated with a higher risk of renal insufficiency and eventual re-thrombosis.6 Therefore anticoagulation might provide some benefit in this setting. The incidence of major bleeding events was low in incidentally detected splanchnic vein thrombosis, and half of these events occurred while patients were on anticoagulation. However, minor bleeding events, according to site, could still affect quality of life and add to the clinical burden of the managing physicians. There is no right or wrong way to present data from a new registry; Riva and colleagues elected to compare incidentally detected splanchnic vein thrombosis with clinically suspected splanchnic vein thrombosis to highlight the clinical, laboratory, management, and prognostic differences between the two groups. As new participants accrue, mounting data should allow the comparison of specific subgroups of patients within the large incidentally detected splanchnic vein thrombosis
2
population and ultimately provide specific guidance in terms of management and outcomes, for the benefit of clinicians and patients alike. *Paul R J Ames, Maurizio Margaglione Haemostasis & Thrombosis Centre, Queen’s Medical Centre, Nottingham University Hospitals, Nottingham, UK (PRJA); Immune Response and Vascular Disease Unit, Nova University Lisbon, Lisbon, Portugal (PRJA); Dipartimento di Medicina Clinica e Sperimentale, Universita’ di Foggia, Foggia, Italy (MM) [email protected] We declare no competing interests. 1
2
3
4
5 6
Riva N, Ageno W, Schulman S, et al, for the International Registry on Splanchnic Vein Thrombosis (IRSVT) study group. Clinical history and antithrombotic treatment of incidentally detected splanchnic vein thrombosis: a multicentre, international prospective registry. Lancet Haematol 2016; published online May 11. http://dx.doi. org/10.1016/S2352-3026(16)30020-5. Søgaard KK, Darvalics B, Horváth-Puhó E, Sørensen HT. Survival after splanchnic vein thrombosis: a 20-year nationwide cohort study. Thromb Res 2016; 141: 1–7. Amitrano L, Guardascione MA, Scaglione M, et al. Prognostic factors in noncirrhotic patients with splanchnic vein thromboses. Am J Gastroenterol 2007; 102: 2464–70. Di Nisio M, Ferrante N, De Tursi M, et al. Incidental venous thromboembolism in ambulatory cancer patients receiving chemotherapy. Thromb Haemost 2010; 104: 1049–54. Manzanet G, Sanjuán F, Orbis P, et al. Liver transplantation in patients with portal vein thrombosis. Liver Transplant 2001; 7: 125–31. Llado L, Fabregat J, Castellote J, et al. Management of portal vein thrombosis in liver transplantation: influence on morbidity and mortality. Clin Transplant 2007; 21: 716–21.
www.thelancet.com/haematology Published online May 11, 2016 http://dx.doi.org/10.1016/S2352-3026(16)30042-4