Hypersplenism: Comprehensive Overview
Definition and Classification
Hypersplenism is a syndrome characterized by splenomegaly, peripheral cytopenias (affecting one or more cell lines), and compensatory bone marrow hyperplasia, most commonly occurring as a secondary manifestation of portal hypertension in cirrhotic patients. 1
Types of Hypersplenism
- Primary hypersplenism: Intrinsic splenic disorders without identifiable underlying cause 1
- Secondary hypersplenism: Results from underlying conditions, most commonly:
- Occult hypersplenism: Subclinical form with minimal manifestations 1
Pathophysiology
The mechanisms underlying hypersplenism are multifactorial and include 2, 3, 1:
- Portal hypertension with intra-splenic sequestration: Increased splenic blood flow and pooling leads to mechanical trapping of blood cells 2
- Enhanced phagocytosis: Hyperactive mononuclear phagocyte system in the enlarged spleen causes premature destruction of blood cells 1, 5
- Autoimmune mechanisms: Anti-platelet antibodies contribute to accelerated cell destruction 2
- Reduced thrombopoietin levels: Decreased hepatic synthesis in cirrhosis exacerbates thrombocytopenia 2
- Myeloid toxicity: Direct bone marrow suppression in advanced liver disease 2
Correlation with Portal Hypertension
- Among patients with clinically significant portal hypertension, 78% develop platelet counts below 100,000/mcL 3
- Moderate inverse correlation exists between hepatic venous pressure gradient and platelet counts (Spearman r = -0.44) 3
Clinical Manifestations
Symptoms
Most patients with hypersplenism are asymptomatic at presentation, with cytopenias discovered incidentally on routine laboratory testing. 4
When symptomatic, patients may experience 4:
- Post-prandial abdominal pain or right upper quadrant discomfort 4
- Fatigue and weight loss 4
- Episodes of fever and chills (particularly with complications) 4
- Symptoms related to the underlying etiology (cirrhosis, portal hypertension) 3
Signs
Physical examination findings include 4:
- Splenomegaly: Most frequent finding; palpable spleen on examination 4
- Hepatomegaly: Common in cirrhotic patients 4
- Signs of portal hypertension:
- Signs of chronic liver disease (in cirrhotic patients):
Key Clinical Distinction
- Splenomegaly provides strong evidence against immune thrombocytopenic purpura (ITP), as less than 3% of ITP patients have splenomegaly 3
Complications
The most frequent complications of hypersplenism in the context of portal hypertension include 4:
- Gastrointestinal bleeding: Most common complication, related to esophageal varices and portal hypertensive gastropathy 4, 2
- Recurrent thrombosis: Particularly in the splanchnic circulation 4
- Biliary complications: Portal cholangiopathy from compression of bile ducts by cavernomatous collaterals 4, 2
- Increased bleeding risk during procedures: Though platelet count alone does not predict bleeding in cirrhosis 2, 3
Investigations
Laboratory Tests
Initial evaluation should include complete blood count demonstrating cytopenias, with thrombocytopenia being the most common manifestation. 3, 5
- Complete blood count: Shows anemia, leukopenia, and/or thrombocytopenia 3, 1
- Liver function tests: Assess for underlying cirrhosis 3
- Bone marrow biopsy: Shows compensatory hyperplasia (not routinely required) 4, 1
Specialized Coagulation Testing
- Rotational thromboelastometry: Superior to routine coagulation tests for predicting bleeding risk during high-risk procedures, including liver transplantation 2
- Avoid relying solely on platelet count to determine bleeding risk in cirrhotic patients 2
Imaging Studies
Hepatic ultrasound with Doppler should be performed to assess for cirrhosis, portal hypertension, and portal vein patency. 2
- Ultrasound with Doppler: First-line imaging to confirm splenomegaly and assess portal vein flow 2, 3
- Computed tomography (CT) scan: Evaluates splenic size, portal vein thrombosis, and cavernomatous transformation 4, 2, 3
- Elastography: Distinguishes cirrhosis from isolated portal vein obstruction 2
- Angiography: May be needed in cases of splenic vein thrombosis 2
Evaluation for Underlying Etiology
In patients with extrahepatic portal vein obstruction, evaluate for 4, 2:
- Prothrombotic disorders:
- Local factors:
Treatment
General Principles
Treatment should prioritize addressing the underlying cause of hypersplenism, with interventions for cytopenias reserved for specific clinical scenarios requiring improved blood counts. 2, 1
Management of Underlying Portal Hypertension
Vasoactive drugs (terlipressin, somatostatin, or octreotide) represent the primary approach for managing portal hypertension-related hypersplenism. 2
- Endoscopic variceal ligation (EVL): High efficacy for esophageal variceal bleeding, often combined with vasoactive drugs 2, 6
- Anticoagulation: Consider in extrahepatic portal vein obstruction to prevent thrombotic extension or recurrence, though evidence for benefit/risk ratio requires further evaluation 4, 2
Management of Cytopenias
Pre-Procedure Management
Avoid routine prophylactic platelet transfusions or fresh frozen plasma before nonsurgical procedures, as baseline bleeding risk is low and independent of preprocedure prophylaxis. 2
- Thrombopoietin receptor agonists (avatrombopag, lusutrombopag): Should be considered before high-risk procedures or in the presence of bleeding, as they are superior to no treatment in avoiding platelet transfusion and rescue therapy 2, 3
- Platelet transfusion: Can work synergistically with local hemostatic means in patients requiring high-risk procedures or with active bleeding 2
- Do not rely solely on platelet count to determine bleeding risk or need for transfusion 2
Interventional Procedures
Partial Splenic Embolization (PSE)
Partial splenic embolization is the preferred first-line interventional option for resistant hypersplenism, effectively reducing splenic volume and portal pressure while preserving some immune function. 2, 3
- Effectively increases circulating blood cell counts and improves liver synthetic function 7
- Mean infarcted area typically 66% of splenic volume 8
- Combination of EVL and PSE: Extends variceal eradication and reduces mortality in patients with large esophageal varices, hypersplenism, and thrombocytopenia 2
- Combined PSE and balloon-occluded retrograde transvenous obliteration (BRTO): Significantly reduces esophageal variceal aggravation (9% vs 45% at 3 years) 2
Complications of PSE
Common side effects include 8:
Severe complications (particularly in Child-Pugh class B/C patients) 8:
- Acute-on-chronic liver failure 8
- Bacterial peritonitis and splenic abscess requiring drainage 8
- PSE should be avoided in decompensated cirrhosis (Child-Pugh C) 8
Transjugular Intrahepatic Portosystemic Shunt (TIPS)
TIPS can treat portal hypertension-related hypersplenism but carries risk of shunt dysfunction and hepatic encephalopathy. 2
- MELD score >11 predicts poor outcomes with portosystemic shunt procedures; select patients carefully 2
- Rifaximin prophylaxis from 2 weeks before through 6 months post-TIPS significantly reduces post-TIPS hepatic encephalopathy 2
- Consider concomitant PSE when performing BRTO to mitigate increased portal hypertension 2
Surgical Options
- Splenectomy (open or laparoscopic): Most effective for abolishing hypersplenism but associated with significant risk of portal vein thrombosis and post-splenectomy sepsis 7, 9, 5
- Surgical shunt procedures: Effective in preventing bleeding but have not shown survival advantage 2
- Portacaval shunts have variable effects; hypersplenism rarely improves after surgery 7
Liver Transplantation
After liver transplantation, portal pressure decreases rapidly, thrombopoietin levels increase from day 1, and platelet counts usually normalize within 2 weeks. 2
- Subclinical hypersplenism may persist in patients with pre-transplant splenomegaly 2
- Hypersplenism usually improves following liver transplantation 5
Treatment Algorithm for Resistant Hypersplenism
- Identify and treat underlying cause (portal hypertension, cirrhosis, hematological disorders)
- For resistant hypersplenism:
- First option: Partial splenic embolization (if Child-Pugh A or early B)
- Second option: TIPS (if MELD ≤11 and no contraindications)
- Third option: Surgical shunt (rarely indicated)
Special Considerations
- Child-Pugh C cirrhosis: Avoid PSE and other invasive interventions due to high risk of life-threatening complications 4, 8
- Patients awaiting liver transplantation: Focus on managing complications of portal hypertension rather than hypersplenism itself 4
- Most patients with hypersplenism should be considered to have a laboratory abnormality that does not require treatment unless specific indications exist (need for bone marrow suppressive drugs, high-risk procedures, or active bleeding) 9