Liver International ISSN 1478-3223
REVIEW ARTICLE
Big spleens and hypersplenism: fix it or forget it? Thomas D. Boyer and Shahid Habib Liver Research Institute and Department of Medicine, University of Arizona College of Medicine, Tucson, AZ, USA
Keywords hypersplenism – splenectomy – splenomegaly Abbreviations HCV, hepatitis C virus; PSE, partial splenic embolization; PVT, portal vein thrombosis; RFA, radiofrequency ablation; TIPS, transjugular intrahepatic portosystemic shunt; WBCs, white blood cell counts. Correspondence Thomas D. Boyer, MD, Department of Medicine, AHSC 245035, Tucson, AZ 85724, USA Tel: +520 626 7174 Fax: +520 626 2919 e-mail: [email protected] Received 30 May 2014 Accepted 9 October 2014 DOI:10.1111/liv.12702 Liver Int. 2015; 35: 1492–1498
Abstract Hypersplenism is a common manifestation of portal hypertension in the cirrhotic. More than half of cirrhotics will have low platelet counts, but neutropenia is much less common. Despite being common in the cirrhotic population, the presence of hypersplenism is of little clinical consequence. The presence of hypersplenism suggests more advanced liver disease and an increase in risk of complications, but there is no data showing that correcting the hypersplenism improves patient survival. In most series, the most common indications for treating the hypersplenism is to increase platelet and white blood cell counts to allow for use of drugs that suppress the bone marrow such as interferon alpha and chemotherapeutic agents. There are several approaches used to treat hypersplenism. Portosystemic shunts are of questionable benefit. Splenectomy, either open or laparoscopically, is the most effective but is associated with a significant risk of portal vein thrombosis. Partial splenic artery embolization and radiofrequency ablation are effective methods for treating hypersplenism, but counts tend to fall back to baseline long-term. Pharmacological agents are also effective in increasing platelet counts. Development of direct acting antivirals against hepatitis C will eliminate the most common indication for treatment. We lack controlled trials designed to determine if treating the hypersplenism has benefits other than raising the platelet and white blood cell counts. In the absence of such studies, hypersplenism in most patients should be considered a laboratory abnormality and not treated, in other words forget it.
Hypersplenism is seen when the spleen sequesters formed elements of the blood leading to a fall in red blood cells, white blood cells (WBCs), platelets or any combination thereof. The spleen is usually enlarged but the severity of the hypersplenism is not directly related to the size of the spleen or severity of portal hypertension. Hypersplenism is a consequence of portal hypertension, but relieving the portal hypertension does not resolve the hypersplenism (see below). Hypersplenism can be seen in a variety of conditions including infectious diseases such as malaria, infiltrative diseases and liver disease. This discussion is only about hypersplenism in patients with liver disease. Splenomegaly and hypersplenism are common in patients with cirrhosis. The two are however not directly related as patients with normal sized spleens may have hypersplenism and those with large spleens may not. For example, in one report, 24% of patients with cirrhosis had splenomegaly, whereas 64% had thrombocytopenia (1). This difference reflects the fact that factors other than an enlarged spleen contribute to the cytopenias seen in patients with cirrhosis. Factors that contribute to the thrombocytopenia seen in cirrhotics include pres-
1492
ence of antiplatelet antibodies, toxic effects of alcohol, bone marrow suppressive effects of hepatitis C virus (HCV) and decreased thrombopoietin production (2– 6). In patients with HCV infection causes of leukopenia in addition to hypersplenism include direct effects of the virus on the bone marrow and immunological phenomena (7). Lastly, causes of anaemia in patients with cirrhosis are numerous and include nutritional deficiencies, abnormalities in the RBC’s cell membrane and GI tract bleeding as well as hypersplenism (2). Given the complexities of anaemia in the patient with cirrhosis, most reports focus on thrombocytopenia and leukopenia as manifestations of hypersplenism. The prevalence of leukopenia (
REVIEW ARTICLE
Big spleens and hypersplenism: fix it or forget it? Thomas D. Boyer and Shahid Habib Liver Research Institute and Department of Medicine, University of Arizona College of Medicine, Tucson, AZ, USA
Keywords hypersplenism – splenectomy – splenomegaly Abbreviations HCV, hepatitis C virus; PSE, partial splenic embolization; PVT, portal vein thrombosis; RFA, radiofrequency ablation; TIPS, transjugular intrahepatic portosystemic shunt; WBCs, white blood cell counts. Correspondence Thomas D. Boyer, MD, Department of Medicine, AHSC 245035, Tucson, AZ 85724, USA Tel: +520 626 7174 Fax: +520 626 2919 e-mail: [email protected] Received 30 May 2014 Accepted 9 October 2014 DOI:10.1111/liv.12702 Liver Int. 2015; 35: 1492–1498
Abstract Hypersplenism is a common manifestation of portal hypertension in the cirrhotic. More than half of cirrhotics will have low platelet counts, but neutropenia is much less common. Despite being common in the cirrhotic population, the presence of hypersplenism is of little clinical consequence. The presence of hypersplenism suggests more advanced liver disease and an increase in risk of complications, but there is no data showing that correcting the hypersplenism improves patient survival. In most series, the most common indications for treating the hypersplenism is to increase platelet and white blood cell counts to allow for use of drugs that suppress the bone marrow such as interferon alpha and chemotherapeutic agents. There are several approaches used to treat hypersplenism. Portosystemic shunts are of questionable benefit. Splenectomy, either open or laparoscopically, is the most effective but is associated with a significant risk of portal vein thrombosis. Partial splenic artery embolization and radiofrequency ablation are effective methods for treating hypersplenism, but counts tend to fall back to baseline long-term. Pharmacological agents are also effective in increasing platelet counts. Development of direct acting antivirals against hepatitis C will eliminate the most common indication for treatment. We lack controlled trials designed to determine if treating the hypersplenism has benefits other than raising the platelet and white blood cell counts. In the absence of such studies, hypersplenism in most patients should be considered a laboratory abnormality and not treated, in other words forget it.
Hypersplenism is seen when the spleen sequesters formed elements of the blood leading to a fall in red blood cells, white blood cells (WBCs), platelets or any combination thereof. The spleen is usually enlarged but the severity of the hypersplenism is not directly related to the size of the spleen or severity of portal hypertension. Hypersplenism is a consequence of portal hypertension, but relieving the portal hypertension does not resolve the hypersplenism (see below). Hypersplenism can be seen in a variety of conditions including infectious diseases such as malaria, infiltrative diseases and liver disease. This discussion is only about hypersplenism in patients with liver disease. Splenomegaly and hypersplenism are common in patients with cirrhosis. The two are however not directly related as patients with normal sized spleens may have hypersplenism and those with large spleens may not. For example, in one report, 24% of patients with cirrhosis had splenomegaly, whereas 64% had thrombocytopenia (1). This difference reflects the fact that factors other than an enlarged spleen contribute to the cytopenias seen in patients with cirrhosis. Factors that contribute to the thrombocytopenia seen in cirrhotics include pres-
1492
ence of antiplatelet antibodies, toxic effects of alcohol, bone marrow suppressive effects of hepatitis C virus (HCV) and decreased thrombopoietin production (2– 6). In patients with HCV infection causes of leukopenia in addition to hypersplenism include direct effects of the virus on the bone marrow and immunological phenomena (7). Lastly, causes of anaemia in patients with cirrhosis are numerous and include nutritional deficiencies, abnormalities in the RBC’s cell membrane and GI tract bleeding as well as hypersplenism (2). Given the complexities of anaemia in the patient with cirrhosis, most reports focus on thrombocytopenia and leukopenia as manifestations of hypersplenism. The prevalence of leukopenia (
