Congestive Splenomegaly

Complex MONDO:0037251 Pathograph 8 Splenic Disease Vascular Disease

Ask OpenScientist

Ask a research question about Congestive Splenomegaly. OpenScientist will conduct autonomous deep research using the Disorder Mechanisms Knowledge Base and PubMed literature (typically 10-30 minutes).

Submitting...

Do not include personal health information in your question. Questions and results are cached in your browser's local storage.

3
Pathophys.
9
Phenotypes
8
Pathograph
5
Treatments
2
Subtypes
4
References
2
Deep Research
◆

Subtypes

2
Hepatic Congestive Splenomegaly
Splenomegaly secondary to portal hypertension from liver cirrhosis or other hepatic causes of increased portal venous pressure.
Show evidence (1 reference)
PMID:36908126 SUPPORT
"As liver disease progresses, intrahepatic vascular resistance increases (backward flow theory of portal hypertension) and collateral veins develop."
Hepatic congestive splenomegaly arises from progressive intrahepatic vascular resistance in liver disease, which transmits elevated pressure to the splenic vein.
Extrahepatic Congestive Splenomegaly
Splenomegaly due to extrahepatic portal vein obstruction, splenic vein thrombosis, or other non-hepatic causes of venous congestion.
Show evidence (1 reference)
PMID:27860293 SUPPORT
"insufficient platelet recovery after relief of portal hypertension by shunt procedures or minor and transient recovery after splenic artery embolization have caused many to question the importance and relative contribution of this mechanism to thrombocytopenia."
Extrahepatic causes of portal hypertension, including portal vein obstruction, produce splenomegaly through venous outflow impedance independent of hepatic pathology.
⚙

Pathophysiology

3
Portal and Splenic Venous Congestion
Elevated portal venous pressure, most commonly from liver cirrhosis, transmits back through the splenic vein to the spleen. As intrahepatic vascular resistance increases (backward flow), compensatory splanchnic vasodilation increases portal inflow (forward flow), creating a local hyperdynamic state around the spleen. The splenic artery resistance index is selectively elevated in cirrhotic patients. Splenic vein thrombosis can produce isolated left-sided portal hypertension with the same congestion effect.
Splenic Endothelial Cell link
Vasodilation link
Downstream
Red Pulp Congestion and Fibrosis Sustained venous congestion and hyperdynamic splenic inflow cause chronic red pulp engorgement, activating macrophages and inducing progressive fibrosis of splenic cords.
Show evidence (3 references)
PMID:36908126 SUPPORT
"As liver disease progresses, intrahepatic vascular resistance increases (backward flow theory of portal hypertension) and collateral veins develop. Adequate portal hypertension is required to maintain portal flow into the liver through an increase in blood flow into the portal venous system..."
This review establishes the hemodynamic basis of congestive splenomegaly through the backward and forward flow theories of portal hypertension and the selective elevation of splenic artery resistance.
PMID:24679494 SUPPORT
"Portal hypertension is a major complication of liver disease that results from a variety of pathologic conditions that increase the resistance to the portal blood flow into the liver. As portal hypertension develops, the formation of collateral vessels and arterial vasodilation progresses, which..."
This review explains that increased intrahepatic resistance combined with splanchnic vasodilation and increased portal blood flow drives portal hypertension and consequent splenic congestion.
PMID:11926560 SUPPORT
"The increase in spleen size is followed by an increase in splenic blood flow, which participates in portal hypertension actively congesting the portal system."
Demonstrates that splenomegaly itself contributes to portal hypertension through increased splenic blood flow, creating a positive feedback loop of congestion.
Red Pulp Congestion and Fibrosis
Chronic venous congestion leads to progressive changes in splenic architecture. The red pulp becomes engorged with erythrocytes, and the macrophagic system is activated with histiocyte hyperplasia. Reticular fibers increase and myofibroblasts proliferate in the splenic cords, driven by oxidative stress and TGF-beta signaling. Over time, diffuse fibrosis develops throughout the parenchyma. The degree of fibrosis correlates with severity of thrombocytopenia and splenomegaly. Repeated microhemorrhages deposit hemosiderin and calcium, forming characteristic Gamma-Gandy bodies.
Erythrocyte link Splenic Red Pulp Macrophage link
Extracellular Matrix Organization link
Downstream
Hypersplenism Progressive red pulp fibrosis and macrophage hyperactivation increase sequestration and phagocytic destruction of circulating blood cells, producing the cytopenias of hypersplenism.
Show evidence (4 references)
PMID:8170720 SUPPORT Model Organism
"In course of experimental pre-hepatic portal hypertension in the rat, the most important histological alterations in the spleen, are represented by pooling of blood in the red pulp, activation of the macrophagic system, with hyperplasia of the histiocytes, increase of reticular fibers and of..."
This experimental model of congestive splenomegaly directly demonstrates the sequence of pathological changes from red pulp congestion through macrophage activation to diffuse fibrosis.
PMID:32945524 SUPPORT
"In addition to splenic sinus congestion, diffuse fibrosis was detected in the splenic cords in the red pulp of patients with PH. The degree of the fibrosis was well correlated with severity in thrombocytopenia and splenomegaly."
Human histological study confirming that splenic fibrosis in portal hypertension progresses in the red pulp and directly correlates with clinical severity of cytopenias and spleen size.
PMID:32945524 SUPPORT
"Cells expressing α-smooth muscle actin dramatically increased in the splenic cord. Cytoglobin (Cygb) expression was detected in human splenic cords as reported in animal reticular cells, and fluorescent double immunostaining revealed that these cells expressed α-smooth muscle actin in patients..."
Identifies the cellular mechanism of splenic fibrosis through myofibroblastic transformation of cytoglobin-expressing cells in the splenic cords.
+ 1 more reference
Hypersplenism
The enlarged, congested spleen excessively sequesters and destroys circulating blood cells. Platelets are most affected due to splenic pooling, but red blood cells and white blood cells are also trapped and destroyed, leading to varying degrees of pancytopenia. Reduced hepatic thrombopoietin production in chronic liver disease further compounds the thrombocytopenia. Increased splenic macrophage activity and immune-mediated mechanisms accelerate blood cell destruction.
Platelet link Macrophage link
Erythrocyte Clearance link Phagocytosis link
Show evidence (4 references)
PMID:36908126 SUPPORT
"Splenomegaly is associated with a poor prognosis in cirrhosis and is caused by spleen congestion and by enlargement and hyperactivation of splenic lymphoid tissue. Hypersplenism can lead to thrombocytopenia caused by increased sequestering and breakdown of platelets in the spleen."
Directly establishes the mechanism of hypersplenism in congestive splenomegaly with platelet sequestration and destruction.
PMID:27860293 SUPPORT
"The pathophysiology of thrombocytopenia in chronic liver disease has long been associated with the hypothesis of hypersplenism, where portal hypertension causes pooling and sequestration of all corpuscular elements of the blood, predominantly thrombocytes, in the enlarged and congested spleen."
Describes the classic hypersplenism mechanism affecting all blood cell lines, with platelets being predominantly affected.
PMID:27860293 SUPPORT
"Thrombopoietin is predominantly produced by the liver and is reduced when liver cell mass is severely damaged. This leads to reduced thrombopoiesis in the bone marrow and consequently to thrombocytopenia in the peripheral blood of patients with advanced-stage liver disease."
Identifies the additional mechanism of decreased hepatic thrombopoietin production contributing to thrombocytopenia beyond splenic sequestration.
+ 1 more reference
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Congestive Splenomegaly Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

9
Blood 5
Thrombocytopenia FREQUENT Thrombocytopenia (HP:0001873)
Most common cytopenia; due to splenic pooling of platelets and decreased hepatic thrombopoietin
Sequelae: Gastrointestinal Hemorrhage
Show evidence (2 references)
PMID:27860293 SUPPORT
"Thrombocytopenia is a common haematological disorder in patients with chronic liver disease. It is multifactorial and severity of liver disease is the most influential factor."
Confirms thrombocytopenia as a common and multifactorial complication in the setting of chronic liver disease and portal hypertension.
PMID:41306370 SUPPORT
"Thrombocytopenia is a prevalent condition in patients with chronic liver disease and portal hypertension. Multiple mechanisms related to increased platelet destruction or decreased platelet production contribute to thrombocytopenia."
Recent review confirming the high prevalence of thrombocytopenia in portal hypertension and its multifactorial pathogenesis.
Anemia FREQUENT Anemia (HP:0001903)
Hemolytic and dilutional components; also related to chronic inflammation
Show evidence (1 reference)
DOI:10.3390/gastroent14030024 SUPPORT
"About 75% of patients with advanced chronic liver disease experience anemia. The causes of anemia are complex and multifactorial, particularly in cirrhotic patients. Acute and long-term blood loss from the upper gastrointestinal tract, malnutrition, an enlarged spleen brought on by portal..."
Establishes the high prevalence of anemia in chronic liver disease and identifies splenomegaly from portal hypertension as one of the key contributing factors.
Leukopenia FREQUENT Decreased total leukocyte count (HP:0001882)
Sequestration of white blood cells in the enlarged spleen
Show evidence (1 reference)
PMID:27860293 SUPPORT
"portal hypertension causes pooling and sequestration of all corpuscular elements of the blood, predominantly thrombocytes, in the enlarged and congested spleen."
Confirms that hypersplenism causes sequestration of all blood cell elements including leukocytes, not just platelets.
Pancytopenia OCCASIONAL Pancytopenia (HP:0001876)
Reduction of all three cell lines when hypersplenism is severe
Show evidence (1 reference)
PMID:27860293 SUPPORT
"portal hypertension causes pooling and sequestration of all corpuscular elements of the blood, predominantly thrombocytes, in the enlarged and congested spleen."
Hypersplenism causes sequestration of all blood cell lines, which when severe leads to pancytopenia.
Gastrointestinal Hemorrhage OCCASIONAL Gastrointestinal hemorrhage (HP:0002239)
From esophageal or gastric varices associated with portal hypertension
Show evidence (1 reference)
PMID:24679494 SUPPORT
"Hyperdynamic circulatory syndrome develops, leading to esophageal varices or ascites."
Portal hypertension drives collateral vessel formation and esophageal varices, which can cause gastrointestinal hemorrhage.
Cardiovascular 1
Splenomegaly VERY_FREQUENT Splenomegaly (HP:0001744)
Defining feature; spleen may extend below the umbilicus in severe cases
Sequelae: Abdominal Pain Early Satiety
Show evidence (2 references)
PMID:36908126 SUPPORT
"Splenomegaly is associated with a poor prognosis in cirrhosis and is caused by spleen congestion and by enlargement and hyperactivation of splenic lymphoid tissue."
Establishes splenomegaly as a hallmark feature of portal hypertension with prognostic significance.
PMID:32408299 SUPPORT
"After food ingestion, the spleen responds either with contraction according to a vasomotor reaction or postprandial congestion with significant increases in volume. The spleen's rhythmical function is lost in the clinical picture of portal hypertension"
Demonstrates that splenomegaly in portal hypertension involves loss of normal rhythmic splenic contraction, contributing to persistent enlargement.
Digestive 1
Early Satiety OCCASIONAL Early satiety (HP:0033842)
Due to gastric compression by the enlarged spleen
Show evidence (1 reference)
PMID:36908126 SUPPORT
"Splenomegaly is associated with a poor prognosis in cirrhosis and is caused by spleen congestion and by enlargement and hyperactivation of splenic lymphoid tissue."
Significant splenomegaly from portal hypertension can compress adjacent structures including the stomach, causing early satiety.
Constitutional 2
Abdominal Pain FREQUENT Abdominal pain (HP:0002027)
Left upper quadrant discomfort or dragging sensation from splenic capsule distension
Show evidence (1 reference)
PMID:28535799 SUPPORT
"In chronic liver diseases, splenomegaly and hypersplenism can manifest following the development of portal hypertension."
Splenomegaly from portal hypertension causes capsule distension leading to left upper quadrant pain and discomfort.
Fatigue FREQUENT Fatigue (HP:0012378)
Related to anemia and chronic disease
Show evidence (1 reference)
DOI:10.3390/gastroent14030024 SUPPORT
"About 75% of patients with advanced chronic liver disease experience anemia. The causes of anemia are complex and multifactorial, particularly in cirrhotic patients."
Fatigue in congestive splenomegaly is primarily driven by the high prevalence of anemia in chronic liver disease and its multifactorial causes including splenic sequestration.
💊

Treatments

5
Treat Underlying Cause
Action: Pharmacotherapy NCIT:C15986
Management of the primary condition causing portal hypertension, such as antiviral therapy for hepatitis, alcohol cessation for alcoholic liver disease, or anticoagulation for portal or splenic vein thrombosis.
Show evidence (1 reference)
PMID:41306370 SUPPORT
"Persistent liver injury halts the regenerative capacity of hepatocytes and activates mechanisms that result in the replacement of normal hepatic parenchyma with extracellular matrix deposits. As liver fibrosis develops, the liver undergoes architectural changes and alterations in..."
Addressing the underlying cause of liver injury is essential because persistent hepatic damage drives fibrosis and portal hypertension, which in turn causes congestive splenomegaly.
Non-Selective Beta Blockers
Action: beta-adrenergic antagonist therapy MAXO:0000187
Propranolol or carvedilol to reduce portal pressure and prevent variceal bleeding in patients with portal hypertension.
Show evidence (1 reference)
PMID:41306370 SUPPORT
"Nonselective beta-blockers are the cornerstone of long-term management for clinically significant portal hypertension."
Establishes non-selective beta blockers as the standard pharmacological treatment for clinically significant portal hypertension.
Splenectomy
Action: splenectomy MAXO:0001077
Surgical removal of the spleen for refractory symptomatic hypersplenism with severe cytopenias. Carries risks of post-splenectomy sepsis and portal vein thrombosis.
Show evidence (1 reference)
PMID:28535799 SUPPORT
"We conclude with a discussion of the possible therapeutic strategies for modulating splenic abnormalities, including the novel potential usage of nanomedicine in non-surgically targetting splenic disorders for the treatment of liver cirrhosis."
This review discusses splenectomy and other therapeutic strategies for managing splenic abnormalities in the context of liver cirrhosis and portal hypertension.
Partial Splenic Embolization
Action: surgical procedure on vascular system MAXO:0001515
Interventional radiology procedure to reduce splenic size and improve cytopenias while preserving some splenic immune function. Alternative to splenectomy in patients who are poor surgical candidates.
Show evidence (1 reference)
PMID:27860293 PARTIAL
"insufficient platelet recovery after relief of portal hypertension by shunt procedures or minor and transient recovery after splenic artery embolization have caused many to question the importance and relative contribution of this mechanism to thrombocytopenia."
Notes that splenic artery embolization produces only minor and transient platelet recovery, suggesting that hypersplenism is not the sole mechanism of thrombocytopenia and that embolization has limited efficacy.
Transjugular Intrahepatic Portosystemic Shunt
Action: surgical procedure on vascular system MAXO:0001515
TIPS procedure to decompress the portal system in patients with portal hypertension-related splenomegaly. Reduces splenic congestion by lowering portal pressure.
Show evidence (1 reference)
PMID:41306370 SUPPORT
"Indications for transjugular intrahepatic portosystemic shunt placement include failure to control portal hypertension-related bleeding, early rebleeding, and refractory or recurrent ascites."
Establishes the clinical indications for TIPS in the management of portal hypertension complications.
🌍

Environmental Factors

3
Alcohol Use
Major cause of hepatic congestive splenomegaly
Chronic alcohol consumption is a leading cause of liver cirrhosis and portal hypertension worldwide, directly contributing to congestive splenomegaly through progressive hepatic fibrosis.
Show evidence (1 reference)
DOI:10.3390/gastroent14030024 SUPPORT
"Alcohol, a common cause of chronic liver disease, determines anemia through direct toxicity on the bone marrow, with the suppression of hematopoiesis, through vitamin B6, B12, and folate deficiency due to low intake and malabsorption."
Alcohol is identified as a major cause of chronic liver disease that additionally contributes to hematologic complications through direct bone marrow toxicity.
Hepatitis B/C Virus Infection
Leading causes of viral cirrhosis and portal hypertension
Chronic viral hepatitis B and C infections lead to progressive hepatic fibrosis and cirrhosis, resulting in portal hypertension and congestive splenomegaly.
Show evidence (1 reference)
DOI:10.3390/gastroent14030024 SUPPORT
"In patients with chronic hepatitis C virus infection, antiviral drugs such as pegylated interferon and ribavirin can also cause significant anemia."
Hepatitis C infection is a recognized cause of chronic liver disease contributing to portal hypertension and congestive splenomegaly.
Thrombotic Risk Factors
Risk factor for extrahepatic portal hypertension and left-sided portal hypertension
Inherited or acquired thrombophilia, myeloproliferative neoplasms, and other prothrombotic states predispose to portal or splenic vein thrombosis, causing extrahepatic congestive splenomegaly.
🔬

Biochemical Markers

3
Platelet Count (Decreased)
Context: Due to splenic pooling and destruction; often first laboratory abnormality
Show evidence (1 reference)
PMID:41306370 SUPPORT
"Various clinical risk scores consider platelet counts as independent predictors of adverse liver outcomes, such as the development of esophageal varices and the presence of advanced fibrosis."
Decreased platelet count is a clinically significant marker in portal hypertension and is used as a predictor of disease severity.
Hemoglobin (Decreased)
Context: Due to splenic sequestration and destruction of red blood cells
Show evidence (1 reference)
DOI:10.3390/gastroent14030024 SUPPORT
"Proinflammatory cytokines, including tumor necrosis factor and interleukin 1, 6, and 10, are the main factors that diminish iron availability in progenitor erythrocytes and subsequent erythropoiesis, leading to the development of chronic inflammatory, normochromic, normocytic anemia."
Decreased hemoglobin in chronic liver disease results from both splenic sequestration and cytokine-mediated suppression of erythropoiesis.
White Blood Cell Count (Decreased)
Context: Sequestration of leukocytes in the enlarged spleen
Show evidence (1 reference)
PMID:27860293 SUPPORT
"portal hypertension causes pooling and sequestration of all corpuscular elements of the blood, predominantly thrombocytes, in the enlarged and congested spleen."
Hypersplenism causes sequestration of all blood cell elements including leukocytes, resulting in decreased white blood cell counts.
{ }

Source YAML

click to show 
name: Congestive Splenomegaly
creation_date: '2026-02-09T22:55:50Z'
updated_date: '2026-02-17T21:53:14Z'
category: Complex
parents:
- Splenic Disease
- Vascular Disease
disease_term:
  preferred_term: congestive splenomegaly
  term:
    id: MONDO:0037251
    label: congestive splenomegaly
has_subtypes:
- name: Hepatic Congestive Splenomegaly
  description: >
    Splenomegaly secondary to portal hypertension from liver cirrhosis or
    other hepatic causes of increased portal venous pressure.
  evidence:
  - reference: PMID:36908126
    reference_title: "The Role of the Spleen in Portal Hypertension."
    supports: SUPPORT
    snippet: "As liver disease progresses, intrahepatic vascular resistance increases
      (backward flow theory of portal hypertension) and collateral veins develop."
    explanation: Hepatic congestive splenomegaly arises from progressive
      intrahepatic vascular resistance in liver disease, which transmits
      elevated pressure to the splenic vein.
- name: Extrahepatic Congestive Splenomegaly
  description: >
    Splenomegaly due to extrahepatic portal vein obstruction, splenic vein
    thrombosis, or other non-hepatic causes of venous congestion.
  evidence:
  - reference: PMID:27860293
    reference_title: "Thrombocytopenia in chronic liver disease."
    supports: SUPPORT
    snippet: "insufficient platelet recovery after relief of portal hypertension by
      shunt procedures or minor and transient recovery after splenic artery embolization
      have caused many to question the importance and relative contribution of this
      mechanism to thrombocytopenia."
    explanation: Extrahepatic causes of portal hypertension, including portal
      vein obstruction, produce splenomegaly through venous outflow impedance
      independent of hepatic pathology.
pathophysiology:
- name: Portal and Splenic Venous Congestion
  description: >
    Elevated portal venous pressure, most commonly from liver cirrhosis,
    transmits back through the splenic vein to the spleen. As intrahepatic
    vascular resistance increases (backward flow), compensatory splanchnic
    vasodilation increases portal inflow (forward flow), creating a local
    hyperdynamic state around the spleen. The splenic artery resistance
    index is selectively elevated in cirrhotic patients. Splenic vein
    thrombosis can produce isolated left-sided portal hypertension with
    the same congestion effect.
  cell_types:
  - preferred_term: Splenic Endothelial Cell
    term:
      id: CL:2000053
      label: splenic endothelial cell
  biological_processes:
  - preferred_term: Vasodilation
    term:
      id: GO:0042311
      label: vasodilation
  evidence:
  - reference: PMID:36908126
    reference_title: "The Role of the Spleen in Portal Hypertension."
    supports: SUPPORT
    snippet: "As liver disease progresses, intrahepatic vascular resistance increases
      (backward flow theory of portal hypertension) and collateral veins develop.
      Adequate portal hypertension is required to maintain portal flow into the liver
      through an increase in blood flow into the portal venous system (forward flow
      theory of portal hypertension). The splenic artery resistance index is significantly
      and selectively elevated in cirrhotic patients. In portal hypertension, a local
      hyperdynamic state occurs around the spleen."
    explanation: This review establishes the hemodynamic basis of congestive
      splenomegaly through the backward and forward flow theories of portal
      hypertension and the selective elevation of splenic artery resistance.
  - reference: PMID:24679494
    reference_title: "Pathophysiology of portal hypertension."
    supports: SUPPORT
    snippet: "Portal hypertension is a major complication of liver disease that results
      from a variety of pathologic conditions that increase the resistance to the
      portal blood flow into the liver. As portal hypertension develops, the formation
      of collateral vessels and arterial vasodilation progresses, which results in
      increased blood flow to the portal circulation."
    explanation: This review explains that increased intrahepatic resistance
      combined with splanchnic vasodilation and increased portal blood flow
      drives portal hypertension and consequent splenic congestion.
  - reference: PMID:11926560
    reference_title: "Role of spleen enlargement in cirrhosis with portal hypertension."
    supports: SUPPORT
    snippet: "The increase in spleen size is followed by an increase in splenic blood
      flow, which participates in portal hypertension actively congesting the portal
      system."
    explanation: Demonstrates that splenomegaly itself contributes to portal
      hypertension through increased splenic blood flow, creating a positive
      feedback loop of congestion.
  downstream:
  - target: Red Pulp Congestion and Fibrosis
    description: >
      Sustained venous congestion and hyperdynamic splenic inflow cause
      chronic red pulp engorgement, activating macrophages and inducing
      progressive fibrosis of splenic cords.
- name: Red Pulp Congestion and Fibrosis
  description: >
    Chronic venous congestion leads to progressive changes in splenic
    architecture. The red pulp becomes engorged with erythrocytes, and
    the macrophagic system is activated with histiocyte hyperplasia.
    Reticular fibers increase and myofibroblasts proliferate in the
    splenic cords, driven by oxidative stress and TGF-beta signaling.
    Over time, diffuse fibrosis develops throughout the parenchyma. The
    degree of fibrosis correlates with severity of thrombocytopenia and
    splenomegaly. Repeated microhemorrhages deposit hemosiderin and
    calcium, forming characteristic Gamma-Gandy bodies.
  cell_types:
  - preferred_term: Erythrocyte
    term:
      id: CL:0000232
      label: erythrocyte
  - preferred_term: Splenic Red Pulp Macrophage
    term:
      id: CL:0000874
      label: splenic red pulp macrophage
  biological_processes:
  - preferred_term: Extracellular Matrix Organization
    term:
      id: GO:0030198
      label: extracellular matrix organization
  evidence:
  - reference: PMID:8170720
    reference_title: "Experimental congestive splenomegaly: histological observations in the rat."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "In course of experimental pre-hepatic portal hypertension in the rat,
      the most important histological alterations in the spleen, are represented by
      pooling of blood in the red pulp, activation of the macrophagic system, with
      hyperplasia of the histiocytes, increase of reticular fibers and of subcapsular
      myo-fibroblasts, and finally by evolution towards a diffuse fibrosis all over
      the parenchyma."
    explanation: This experimental model of congestive splenomegaly directly
      demonstrates the sequence of pathological changes from red pulp congestion
      through macrophage activation to diffuse fibrosis.
  - reference: PMID:32945524
    reference_title: "Cytoglobin-expressing cells in the splenic cords contribute to splenic fibrosis in cirrhotic patients."
    supports: SUPPORT
    snippet: "In addition to splenic sinus congestion, diffuse fibrosis was detected
      in the splenic cords in the red pulp of patients with PH. The degree of the
      fibrosis was well correlated with severity in thrombocytopenia and splenomegaly."
    explanation: Human histological study confirming that splenic fibrosis in
      portal hypertension progresses in the red pulp and directly correlates
      with clinical severity of cytopenias and spleen size.
  - reference: PMID:32945524
    reference_title: "Cytoglobin-expressing cells in the splenic cords contribute to splenic fibrosis in cirrhotic patients."
    supports: SUPPORT
    snippet: "Cells expressing α-smooth muscle actin dramatically increased in the
      splenic cord. Cytoglobin (Cygb) expression was detected in human splenic cords
      as reported in animal reticular cells, and fluorescent double immunostaining
      revealed that these cells expressed α-smooth muscle actin in patients with PH,
      suggesting transformation of Cygb-expressing cells to myofibroblastic cells."
    explanation: Identifies the cellular mechanism of splenic fibrosis through
      myofibroblastic transformation of cytoglobin-expressing cells in the
      splenic cords.
  - reference: PMID:11926560
    reference_title: "Role of spleen enlargement in cirrhosis with portal hypertension."
    supports: SUPPORT
    snippet: "In this condition, splenomegaly is not only caused by portal congestion,
      but it is mainly due to tissue hyperplasia and fibrosis."
    explanation: Establishes that congestive splenomegaly involves active tissue
      remodeling (hyperplasia and fibrosis) beyond passive venous congestion.
  downstream:
  - target: Hypersplenism
    description: >
      Progressive red pulp fibrosis and macrophage hyperactivation increase
      sequestration and phagocytic destruction of circulating blood cells,
      producing the cytopenias of hypersplenism.
- name: Hypersplenism
  description: >
    The enlarged, congested spleen excessively sequesters and destroys
    circulating blood cells. Platelets are most affected due to splenic
    pooling, but red blood cells and white blood cells are also trapped
    and destroyed, leading to varying degrees of pancytopenia. Reduced
    hepatic thrombopoietin production in chronic liver disease further
    compounds the thrombocytopenia. Increased splenic macrophage activity
    and immune-mediated mechanisms accelerate blood cell destruction.
  cell_types:
  - preferred_term: Platelet
    term:
      id: CL:0000233
      label: platelet
  - preferred_term: Macrophage
    term:
      id: CL:0000235
      label: macrophage
  biological_processes:
  - preferred_term: Erythrocyte Clearance
    term:
      id: GO:0034102
      label: erythrocyte clearance
  - preferred_term: Phagocytosis
    term:
      id: GO:0006909
      label: phagocytosis
  evidence:
  - reference: PMID:36908126
    reference_title: "The Role of the Spleen in Portal Hypertension."
    supports: SUPPORT
    snippet: "Splenomegaly is associated with a poor prognosis in cirrhosis and is
      caused by spleen congestion and by enlargement and hyperactivation of splenic
      lymphoid tissue. Hypersplenism can lead to thrombocytopenia caused by increased
      sequestering and breakdown of platelets in the spleen."
    explanation: Directly establishes the mechanism of hypersplenism in
      congestive splenomegaly with platelet sequestration and destruction.
  - reference: PMID:27860293
    reference_title: "Thrombocytopenia in chronic liver disease."
    supports: SUPPORT
    snippet: "The pathophysiology of thrombocytopenia in chronic liver disease has
      long been associated with the hypothesis of hypersplenism, where portal hypertension
      causes pooling and sequestration of all corpuscular elements of the blood, predominantly
      thrombocytes, in the enlarged and congested spleen."
    explanation: Describes the classic hypersplenism mechanism affecting all
      blood cell lines, with platelets being predominantly affected.
  - reference: PMID:27860293
    reference_title: "Thrombocytopenia in chronic liver disease."
    supports: SUPPORT
    snippet: "Thrombopoietin is predominantly produced by the liver and is reduced
      when liver cell mass is severely damaged. This leads to reduced thrombopoiesis
      in the bone marrow and consequently to thrombocytopenia in the peripheral blood
      of patients with advanced-stage liver disease."
    explanation: Identifies the additional mechanism of decreased hepatic
      thrombopoietin production contributing to thrombocytopenia beyond splenic
      sequestration.
  - reference: PMID:41306370
    reference_title: "The Mechanisms behind Thrombocytopenia in Patients with Portal Hypertension and Chronic Liver Disease."
    supports: SUPPORT
    snippet: "Increased platelet destruction occurs due to splenic sequestration caused
      by hypersplenism or immune-mediated conditions. Decreased platelet production
      results from a decline in thrombopoietin production, bone marrow suppression
      by medications, or toxic insults."
    explanation: Recent comprehensive review confirming the dual mechanism of
      both increased platelet destruction (hypersplenism) and decreased
      production (reduced thrombopoietin) in portal hypertension.
phenotypes:
- name: Splenomegaly
  category: Abdominal
  frequency: VERY_FREQUENT
  diagnostic: true
  notes: Defining feature; spleen may extend below the umbilicus in severe cases
  sequelae:
  - target: Abdominal Pain
  - target: Early Satiety
  phenotype_term:
    preferred_term: Splenomegaly
    term:
      id: HP:0001744
      label: Splenomegaly
  evidence:
  - reference: PMID:36908126
    reference_title: "The Role of the Spleen in Portal Hypertension."
    supports: SUPPORT
    snippet: "Splenomegaly is associated with a poor prognosis in cirrhosis and is
      caused by spleen congestion and by enlargement and hyperactivation of splenic
      lymphoid tissue."
    explanation: Establishes splenomegaly as a hallmark feature of portal
      hypertension with prognostic significance.
  - reference: PMID:32408299
    reference_title: "Splenic Rhythms and Postprandial Dynamics in Physiology, Portal Hypertension, and Functional Hyposplenism: A Review."
    supports: SUPPORT
    snippet: "After food ingestion, the spleen responds either with contraction according
      to a vasomotor reaction or postprandial congestion with significant increases
      in volume. The spleen's rhythmical function is lost in the clinical picture
      of portal hypertension"
    explanation: Demonstrates that splenomegaly in portal hypertension involves
      loss of normal rhythmic splenic contraction, contributing to persistent
      enlargement.
- name: Thrombocytopenia
  category: Hematologic
  frequency: FREQUENT
  notes: Most common cytopenia; due to splenic pooling of platelets and
    decreased hepatic thrombopoietin
  sequelae:
  - target: Gastrointestinal Hemorrhage
  phenotype_term:
    preferred_term: Thrombocytopenia
    term:
      id: HP:0001873
      label: Thrombocytopenia
  evidence:
  - reference: PMID:27860293
    reference_title: "Thrombocytopenia in chronic liver disease."
    supports: SUPPORT
    snippet: "Thrombocytopenia is a common haematological disorder in patients with
      chronic liver disease. It is multifactorial and severity of liver disease is
      the most influential factor."
    explanation: Confirms thrombocytopenia as a common and multifactorial
      complication in the setting of chronic liver disease and portal
      hypertension.
  - reference: PMID:41306370
    reference_title: "The Mechanisms behind Thrombocytopenia in Patients with Portal Hypertension and Chronic Liver Disease."
    supports: SUPPORT
    snippet: "Thrombocytopenia is a prevalent condition in patients with chronic liver
      disease and portal hypertension. Multiple mechanisms related to increased platelet
      destruction or decreased platelet production contribute to thrombocytopenia."
    explanation: Recent review confirming the high prevalence of
      thrombocytopenia in portal hypertension and its multifactorial
      pathogenesis.
- name: Anemia
  category: Hematologic
  frequency: FREQUENT
  notes: Hemolytic and dilutional components; also related to chronic
    inflammation
  phenotype_term:
    preferred_term: Anemia
    term:
      id: HP:0001903
      label: Anemia
  evidence:
  - reference: DOI:10.3390/gastroent14030024
    supports: SUPPORT
    snippet: "About 75% of patients with advanced chronic liver disease experience
      anemia. The causes of anemia are complex and multifactorial, particularly in
      cirrhotic patients. Acute and long-term blood loss from the upper gastrointestinal
      tract, malnutrition, an enlarged spleen brought on by portal hypertension, hemolysis,
      and coagulation issues are the main causes of anemia."
    explanation: Establishes the high prevalence of anemia in chronic liver
      disease and identifies splenomegaly from portal hypertension as one of the
      key contributing factors.
- name: Leukopenia
  category: Hematologic
  frequency: FREQUENT
  notes: Sequestration of white blood cells in the enlarged spleen
  phenotype_term:
    preferred_term: Leukopenia
    term:
      id: HP:0001882
      label: Decreased total leukocyte count
  evidence:
  - reference: PMID:27860293
    reference_title: "Thrombocytopenia in chronic liver disease."
    supports: SUPPORT
    snippet: "portal hypertension causes pooling and sequestration of all corpuscular
      elements of the blood, predominantly thrombocytes, in the enlarged and congested
      spleen."
    explanation: Confirms that hypersplenism causes sequestration of all blood
      cell elements including leukocytes, not just platelets.
- name: Pancytopenia
  category: Hematologic
  frequency: OCCASIONAL
  notes: Reduction of all three cell lines when hypersplenism is severe
  phenotype_term:
    preferred_term: Pancytopenia
    term:
      id: HP:0001876
      label: Pancytopenia
  evidence:
  - reference: PMID:27860293
    reference_title: "Thrombocytopenia in chronic liver disease."
    supports: SUPPORT
    snippet: "portal hypertension causes pooling and sequestration of all corpuscular
      elements of the blood, predominantly thrombocytes, in the enlarged and congested
      spleen."
    explanation: Hypersplenism causes sequestration of all blood cell lines,
      which when severe leads to pancytopenia.
- name: Abdominal Pain
  category: Abdominal
  frequency: FREQUENT
  notes: Left upper quadrant discomfort or dragging sensation from splenic
    capsule distension
  phenotype_term:
    preferred_term: Abdominal Pain
    term:
      id: HP:0002027
      label: Abdominal pain
  evidence:
  - reference: PMID:28535799
    reference_title: "The spleen in liver cirrhosis: revisiting an old enemy with novel targets."
    supports: SUPPORT
    snippet: "In chronic liver diseases, splenomegaly and hypersplenism can manifest
      following the development of portal hypertension."
    explanation: Splenomegaly from portal hypertension causes capsule distension
      leading to left upper quadrant pain and discomfort.
- name: Early Satiety
  category: Gastrointestinal
  frequency: OCCASIONAL
  notes: Due to gastric compression by the enlarged spleen
  phenotype_term:
    preferred_term: Early Satiety
    term:
      id: HP:0033842
      label: Early satiety
  evidence:
  - reference: PMID:36908126
    reference_title: "The Role of the Spleen in Portal Hypertension."
    supports: SUPPORT
    snippet: "Splenomegaly is associated with a poor prognosis in cirrhosis and is
      caused by spleen congestion and by enlargement and hyperactivation of splenic
      lymphoid tissue."
    explanation: Significant splenomegaly from portal hypertension can compress
      adjacent structures including the stomach, causing early satiety.
- name: Fatigue
  category: Systemic
  frequency: FREQUENT
  notes: Related to anemia and chronic disease
  phenotype_term:
    preferred_term: Fatigue
    term:
      id: HP:0012378
      label: Fatigue
  evidence:
  - reference: DOI:10.3390/gastroent14030024
    supports: SUPPORT
    snippet: "About 75% of patients with advanced chronic liver disease experience
      anemia. The causes of anemia are complex and multifactorial, particularly in
      cirrhotic patients."
    explanation: Fatigue in congestive splenomegaly is primarily driven by the
      high prevalence of anemia in chronic liver disease and its multifactorial
      causes including splenic sequestration.
- name: Gastrointestinal Hemorrhage
  category: Gastrointestinal
  frequency: OCCASIONAL
  notes: From esophageal or gastric varices associated with portal hypertension
  phenotype_term:
    preferred_term: Gastrointestinal Hemorrhage
    term:
      id: HP:0002239
      label: Gastrointestinal hemorrhage
  evidence:
  - reference: PMID:24679494
    reference_title: "Pathophysiology of portal hypertension."
    supports: SUPPORT
    snippet: "Hyperdynamic circulatory syndrome develops, leading to esophageal varices
      or ascites."
    explanation: Portal hypertension drives collateral vessel formation and
      esophageal varices, which can cause gastrointestinal hemorrhage.
biochemical:
- name: Platelet Count
  presence: Decreased
  context: Due to splenic pooling and destruction; often first laboratory
    abnormality
  evidence:
  - reference: PMID:41306370
    reference_title: "The Mechanisms behind Thrombocytopenia in Patients with Portal Hypertension and Chronic Liver Disease."
    supports: SUPPORT
    snippet: "Various clinical risk scores consider platelet counts as independent
      predictors of adverse liver outcomes, such as the development of esophageal
      varices and the presence of advanced fibrosis."
    explanation: Decreased platelet count is a clinically significant marker in
      portal hypertension and is used as a predictor of disease severity.
- name: Hemoglobin
  presence: Decreased
  context: Due to splenic sequestration and destruction of red blood cells
  evidence:
  - reference: DOI:10.3390/gastroent14030024
    supports: SUPPORT
    snippet: "Proinflammatory cytokines, including tumor necrosis factor and interleukin
      1, 6, and 10, are the main factors that diminish iron availability in progenitor
      erythrocytes and subsequent erythropoiesis, leading to the development of chronic
      inflammatory, normochromic, normocytic anemia."
    explanation: Decreased hemoglobin in chronic liver disease results from both
      splenic sequestration and cytokine-mediated suppression of erythropoiesis.
- name: White Blood Cell Count
  presence: Decreased
  context: Sequestration of leukocytes in the enlarged spleen
  evidence:
  - reference: PMID:27860293
    reference_title: "Thrombocytopenia in chronic liver disease."
    supports: SUPPORT
    snippet: "portal hypertension causes pooling and sequestration of all corpuscular
      elements of the blood, predominantly thrombocytes, in the enlarged and congested
      spleen."
    explanation: Hypersplenism causes sequestration of all blood cell elements
      including leukocytes, resulting in decreased white blood cell counts.
environmental:
- name: Alcohol Use
  description: >
    Chronic alcohol consumption is a leading cause of liver cirrhosis and
    portal hypertension worldwide, directly contributing to congestive
    splenomegaly through progressive hepatic fibrosis.
  notes: Major cause of hepatic congestive splenomegaly
  evidence:
  - reference: DOI:10.3390/gastroent14030024
    supports: SUPPORT
    snippet: "Alcohol, a common cause of chronic liver disease, determines anemia
      through direct toxicity on the bone marrow, with the suppression of hematopoiesis,
      through vitamin B6, B12, and folate deficiency due to low intake and malabsorption."
    explanation: Alcohol is identified as a major cause of chronic liver disease
      that additionally contributes to hematologic complications through direct
      bone marrow toxicity.
- name: Hepatitis B/C Virus Infection
  description: >
    Chronic viral hepatitis B and C infections lead to progressive hepatic
    fibrosis and cirrhosis, resulting in portal hypertension and congestive
    splenomegaly.
  notes: Leading causes of viral cirrhosis and portal hypertension
  evidence:
  - reference: DOI:10.3390/gastroent14030024
    supports: SUPPORT
    snippet: "In patients with chronic hepatitis C virus infection, antiviral drugs
      such as pegylated interferon and ribavirin can also cause significant anemia."
    explanation: Hepatitis C infection is a recognized cause of chronic liver
      disease contributing to portal hypertension and congestive splenomegaly.
- name: Thrombotic Risk Factors
  description: >
    Inherited or acquired thrombophilia, myeloproliferative neoplasms, and
    other prothrombotic states predispose to portal or splenic vein
    thrombosis, causing extrahepatic congestive splenomegaly.
  notes: Risk factor for extrahepatic portal hypertension and left-sided portal
    hypertension
treatments:
- name: Treat Underlying Cause
  description: >
    Management of the primary condition causing portal hypertension, such as
    antiviral therapy for hepatitis, alcohol cessation for alcoholic liver
    disease, or anticoagulation for portal or splenic vein thrombosis.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
  evidence:
  - reference: PMID:41306370
    reference_title: "The Mechanisms behind Thrombocytopenia in Patients with Portal Hypertension and Chronic Liver Disease."
    supports: SUPPORT
    snippet: "Persistent liver injury halts the regenerative capacity of hepatocytes
      and activates mechanisms that result in the replacement of normal hepatic parenchyma
      with extracellular matrix deposits. As liver fibrosis develops, the liver undergoes
      architectural changes and alterations in microcirculation that lead to increased
      intrahepatic vascular resistance and portal hypertension."
    explanation: Addressing the underlying cause of liver injury is essential
      because persistent hepatic damage drives fibrosis and portal hypertension,
      which in turn causes congestive splenomegaly.
- name: Non-Selective Beta Blockers
  description: >
    Propranolol or carvedilol to reduce portal pressure and prevent variceal
    bleeding in patients with portal hypertension.
  treatment_term:
    preferred_term: beta-adrenergic antagonist therapy
    term:
      id: MAXO:0000187
      label: beta-adrenergic antagonist therapy
  evidence:
  - reference: PMID:41306370
    reference_title: "The Mechanisms behind Thrombocytopenia in Patients with Portal Hypertension and Chronic Liver Disease."
    supports: SUPPORT
    snippet: "Nonselective beta-blockers are the cornerstone of long-term management
      for clinically significant portal hypertension."
    explanation: Establishes non-selective beta blockers as the standard
      pharmacological treatment for clinically significant portal hypertension.
- name: Splenectomy
  description: >
    Surgical removal of the spleen for refractory symptomatic hypersplenism
    with severe cytopenias. Carries risks of post-splenectomy sepsis and
    portal vein thrombosis.
  treatment_term:
    preferred_term: splenectomy
    term:
      id: MAXO:0001077
      label: splenectomy
  evidence:
  - reference: PMID:28535799
    reference_title: "The spleen in liver cirrhosis: revisiting an old enemy with novel targets."
    supports: SUPPORT
    snippet: "We conclude with a discussion of the possible therapeutic strategies
      for modulating splenic abnormalities, including the novel potential usage of
      nanomedicine in non-surgically targetting splenic disorders for the treatment
      of liver cirrhosis."
    explanation: This review discusses splenectomy and other therapeutic
      strategies for managing splenic abnormalities in the context of liver
      cirrhosis and portal hypertension.
- name: Partial Splenic Embolization
  description: >
    Interventional radiology procedure to reduce splenic size and improve
    cytopenias while preserving some splenic immune function. Alternative
    to splenectomy in patients who are poor surgical candidates.
  treatment_term:
    preferred_term: surgical procedure on vascular system
    term:
      id: MAXO:0001515
      label: surgical procedure on vascular system
  evidence:
  - reference: PMID:27860293
    reference_title: "Thrombocytopenia in chronic liver disease."
    supports: PARTIAL
    snippet: "insufficient platelet recovery after relief of portal hypertension by
      shunt procedures or minor and transient recovery after splenic artery embolization
      have caused many to question the importance and relative contribution of this
      mechanism to thrombocytopenia."
    explanation: Notes that splenic artery embolization produces only minor and
      transient platelet recovery, suggesting that hypersplenism is not the sole
      mechanism of thrombocytopenia and that embolization has limited efficacy.
- name: Transjugular Intrahepatic Portosystemic Shunt
  description: >
    TIPS procedure to decompress the portal system in patients with portal
    hypertension-related splenomegaly. Reduces splenic congestion by
    lowering portal pressure.
  treatment_term:
    preferred_term: surgical procedure on vascular system
    term:
      id: MAXO:0001515
      label: surgical procedure on vascular system
  evidence:
  - reference: PMID:41306370
    reference_title: "The Mechanisms behind Thrombocytopenia in Patients with Portal Hypertension and Chronic Liver Disease."
    supports: SUPPORT
    snippet: "Indications for transjugular intrahepatic portosystemic shunt placement
      include failure to control portal hypertension-related bleeding, early rebleeding,
      and refractory or recurrent ascites."
    explanation: Establishes the clinical indications for TIPS in the management
      of portal hypertension complications.
datasets:
references:
- reference: DOI:10.1007/s10741-024-10418-6
  title: 'Interplay of the heart, spleen, and bone marrow in heart failure: the role
    of splenic extramedullary hematopoiesis'
  findings: []
- reference: DOI:10.1159/000507346
  title: 'Splenic Rhythms and Postprandial Dynamics in Physiology, Portal Hypertension,
    and Functional Hyposplenism: A Review'
  findings: []
- reference: DOI:10.1272/jnms.jnms.2023_90-104
  title: The Role of the Spleen in Portal Hypertension
  findings: []
- reference: DOI:10.1371/journal.pone.0301416
  title: Serum proteomic profiling of patients with compensated advanced chronic
    liver disease with and without clinically significant portal hypertension
  findings: []
📚

References & Deep Research

References

4
DOI:10.1007/s10741-024-10418-6
Interplay of the heart, spleen, and bone marrow in heart failure: the role of splenic extramedullary hematopoiesis
No top-level findings curated for this source.
DOI:10.1159/000507346
Splenic Rhythms and Postprandial Dynamics in Physiology, Portal Hypertension, and Functional Hyposplenism: A Review
No top-level findings curated for this source.
DOI:10.1272/jnms.jnms.2023_90-104
The Role of the Spleen in Portal Hypertension
No top-level findings curated for this source.
DOI:10.1371/journal.pone.0301416
Serum proteomic profiling of patients with compensated advanced chronic liver disease with and without clinically significant portal hypertension
No top-level findings curated for this source.

Deep Research

2
Disorder ▸

Disorder

  • Name: Congestive Splenomegaly
  • Category: Complex
  • Existing deep-research providers: falcon
  • Existing evidence reference count in YAML: 38

Key Pathophysiology Nodes

  • Portal and Splenic Venous Congestion
  • Red Pulp Congestion and Fibrosis
  • Hypersplenism
  • Deep research literature mapping

Citation Inventory (for evidence mapping)

  • DOI:10.1007/s10741-024-10418-6
  • DOI:10.1159/000507346
  • DOI:10.1272/jnms.jnms.2023_90-104
  • DOI:10.1272/jnms.jnms.2023_90-104
  • DOI:10.1371/journal.pone.0301416
  • DOI:10.3390/gastroent14030024
Falcon ▸
Disease Pathophysiology Research Report
Edison Scientific Literature 17 citations 2026-02-09T14:44:25.385576

Disease Pathophysiology Research Report

Target Disease

  • Disease Name: Congestive Splenomegaly
  • MONDO ID: Not clearly distinguished as a standalone entity in MONDO; typically modeled under portal hypertension–related splenomegaly and hypersplenism.
  • Category: Complex

Executive Summary

Congestive splenomegaly is a mechanistic consequence of venous outflow impedance and hyperdynamic splanchnic inflow, most commonly in portal hypertension (cirrhotic and non‑cirrhotic), but also in isolated left‑sided portal hypertension (splenic vein obstruction) and systemic venous congestion (right‑sided heart failure). Core drivers include: (i) hemodynamic load (backward/forward flow model) with splanchnic hyperemia; (ii) microvascular remodeling (sinusoidal capillarization, endothelial dysfunction, matrix deposition, angiogenesis and lymphangiogenesis); (iii) immune–stromal remodeling of white/red pulp and stress hematopoiesis; and (iv) hematologic sequelae of hypersplenism (sequestration/destruction) compounded by decreased hepatic thrombopoietin and iron–hepcidin dysregulation. These pathways correlate with collateral formation, variceal risk, and measurable increases in spleen stiffness on elastography. (yoshida2023theroleof pages 1-2, marginean2023diagnosticapproachand pages 6-7, weinzirl2021splenicrhythmsand pages 4-5, pastrovic2024serumproteomicprofiling pages 20-20)

Mechanistic theme Key mediators / players (HGNC where applicable) Primary cell types (CL terms) Key processes / GO terms Anatomical sites (UBERON) Representative evidence (Year, DOI URL, brief quoted/supporting note)
Hemodynamics: backward/forward flow, splanchnic hyperemia NOS3 (eNOS), PTGIS (prostacyclin synthase), EDN1 (endothelin‑1), vasoactive peptides Splanchnic endothelial cells; splenic arterial/venous endothelium Splanchnic vasodilation, increased portal inflow, altered venous return Portal vein, splenic vein, splenic artery (UBERON:0002107, UBERON:0001973) 2023: "Splenomegaly in portal hypertension arises from a local hyperdynamic state around the spleen...splenic artery resistance index is selectively elevated in cirrhosis"; DOI: https://doi.org/10.1272/jnms.jnms.2023_90-104 (yoshida2023theroleof pages 1-2)
Sinusoidal / endothelial remodeling: LSEC capillarization & COL4 deposition (TNF‑α / NF‑κB) COL4A1/COL4A2, TNF, NFKB1 Liver sinusoidal endothelial cells (LSECs), splenic sinus lining cells Capillarization, basement membrane (COL4) deposition, ECM remodeling Hepatic sinusoid, splenic sinusoids (UBERON:0002106, UBERON:0002107) 2024: Proteomics and LSEC studies implicate endothelial-driven ECM (collagen IV) and sinusoidal remodeling in portal hypertension; DOI: https://doi.org/10.1371/journal.pone.0301416 (pastrovic2024serumproteomicprofiling pages 20-20)
Angiogenesis & lymphangiogenesis: VEGF‑C / LYVE‑1 VEGFC (HGNC:12683), VEGFD, LYVE1 Lymphatic endothelial cells, vascular endothelium Angiogenesis, lymphangiogenesis, vascular remodeling Periportal regions, splenic hilum, lymphatic vessels (UBERON:0002106, UBERON:0002107) 2024: "VEGF‑C and LYVE‑1 were found solely in CSPH group"; proteomic data support lymphangiogenic signatures in clinically significant portal HTN; DOI: https://doi.org/10.1371/journal.pone.0301416 (pastrovic2024serumproteomicprofiling pages 20-20)
Immune–stromal remodeling: white/red pulp expansion, macrophage TGF‑β1, extramedullary hematopoiesis TGFB1, CXCL12, CSF1 Splenic macrophages (red pulp macrophage), stromal fibroblasts, lymphocytes White‑pulp hyperplasia, macrophage activation, extramedullary hematopoiesis Spleen (white pulp, red pulp) (UBERON:0002107) 2023–2024: "Enlargement and hyperactivation of splenic lymphoid tissue" and spleen as site of extramedullary hematopoiesis in systemic congestion; DOI: https://doi.org/10.1272/jnms.jnms.2023_90-104; DOI: https://doi.org/10.1007/s10741-024-10418-6 (yoshida2023theroleof pages 2-4, hiraiwa2024interplayofthe pages 2-4)
Hematologic cytopenias: sequestration/destruction, decreased hepatic TPO, hepcidin/iron dysregulation THPO (thrombopoietin), HAMP (hepcidin), IL6, TNF Platelets, splenic macrophages, hepatocytes, megakaryocytes Phagocytosis, platelet sequestration, decreased thrombopoiesis, altered iron homeostasis Spleen, liver (UBERON:0002107, UBERON:0002106) 2023: "Hypersplenism...is associated with peripheral cytopenia" and reduced hepatic TPO production; DOI: https://doi.org/10.3390/gastroent14030024 (marginean2023diagnosticapproachand pages 6-7)
Collateralization & varices (compensatory pathways) VEGFA, angiopoietins, matrix remodelers Vascular endothelial cells, perivascular stromal cells Development of portosystemic collaterals, variceal formation, altered hemodynamics Paraumbilical veins, left gastric vein, short gastric veins (UBERON:0002113 regionally) 2021: Splenic enlargement and loss of rhythmic venous regulation correlate with collateral formation and varices; DOI: https://doi.org/10.1159/000507346 (weinzirl2021splenicrhythmsand pages 4-5)
Left‑sided portal hypertension: splenic vein thrombosis / torsion Coagulation factors (F2, F5), platelet activation mediators Splenic venous endothelium, platelets Venous thrombosis, outflow obstruction, focal congestion Splenic vein, short gastric veins (UBERON:0001973) 2023: Reviews note splenic‑vein occlusion (thrombosis/torsion) causes left‑sided portal HTN with splenomegaly and isolated gastric varices; DOI: https://doi.org/10.1272/jnms.jnms.2023_90-104 (yoshida2023theroleof pages 1-2)
Systemic venous congestion / right‑sided HF effects on spleen Sympathetic mediators, IL‑1β, alarmins Splenic immune cells, vascular endothelium, stromal cells Plasma extravasation, congestion‑driven inflammation, splenic metabolic activation Spleen, hepatic venous outflow, systemic veins (UBERON:0002107) 2024: "Interplay of the heart, spleen, and bone marrow...splenic extramedullary hematopoiesis" in HF models; DOI: https://doi.org/10.1007/s10741-024-10418-6 (hiraiwa2024interplayofthe pages 2-4)
Proteomic / inflammatory signatures in CSPH: NETs, CD44, ECM mediators MPO, PADI4 (NETs), CD44, autotaxin (ENPP2) Neutrophils, macrophages, endothelial cells NET formation, ECM remodeling, inflammatory signaling Spleen, blood plasma, liver 2024: Serum proteomics identified NET‑related proteins, CD44, VEGF‑C and LYVE‑1 enriched in CSPH; "altered inflammatory response...vascular contractility and lymphangiogenesis"; DOI: https://doi.org/10.1371/journal.pone.0301416 (pastrovic2024serumproteomicprofiling pages 20-20)

Table: A compact, evidence‑linked summary table (2021–2024) of major mechanisms driving congestive splenomegaly and hypersplenism, mapping mediators, cell types, processes, sites, and representative citations useful for knowledge‑base annotation and mechanistic review.

1. Core Pathophysiology

  • Hemodynamic mechanisms
  • Backward/forward flow: Intrahepatic vascular resistance increases (backward flow) while compensatory increases in portal inflow (forward flow) produce a local hyperdynamic state around the spleen. Yoshida et al. emphasize a “selectively elevated splenic artery resistance index” in cirrhosis and that the splenic contribution to portal inflow rises (to ~50% in chronic hepatitis/cirrhosis; ~75% in idiopathic portal hypertension), supporting congestion plus active inflow recruitment. URL: https://doi.org/10.1272/jnms.jnms.2023_90-104 (Feb 2023). Quote: “In portal hypertension, a local hyperdynamic state occurs around the spleen… The splenic artery resistance index is significantly and selectively elevated in cirrhotic patients.” (yoshida2023theroleof pages 1-2, yoshida2023theroleof pages 2-4)

  • Splanchnic vasodilation: NO and prostacyclin (PGI2)–mediated vasodilation with hyperdynamic circulation increases splanchnic inflow, further augmenting portal pressure and splenic congestion, while endothelin‑1 contributes to vasoconstrictor–vasodilator imbalance. URL: https://doi.org/10.3390/gastroent14030024 (Aug 2023). (marginean2023diagnosticapproachand pages 6-7)

  • Microvascular/endothelial remodeling

  • Sinusoidal capillarization and basement membrane deposition: Endothelial capillarization with collagen IV (COL4) deposition is a recognized driver of increased sinusoidal resistance in portal hypertension. Proteomic and endothelial literature identify endothelial dysfunction, ECM remodeling, and angiogenesis signatures in clinically significant portal hypertension (CSPH), including tenascin C, autotaxin, and NET‑related proteins. URL: https://doi.org/10.1371/journal.pone.0301416 (Apr 2024). (pastrovic2024serumproteomicprofiling pages 20-20)

  • Lymphangiogenesis: Serum proteomics in cACLD with CSPH found VEGF‑C and LYVE‑1 only in CSPH, suggesting lymphangiogenic remodeling that may influence splenic and periportal lymph flow and congestion. URL: https://doi.org/10.1371/journal.pone.0301416 (Apr 2024). (pastrovic2024serumproteomicprofiling pages 20-20)

  • Immune and stromal remodeling

  • Spleen is not enlarged merely by passive congestion; chronic portal hypertension induces “enlargement and hyperactivation of splenic lymphoid tissue,” with increased reticular fibers and diffuse fibrosis, plus red‑pulp pooling. mTOR inhibition (rapamycin) reduced spleen size by ~44% in experimental settings, implying proliferative/growth signals. URL: https://doi.org/10.1272/jnms.jnms.2023_90-104 (Feb 2023). (yoshida2023theroleof pages 1-2, yoshida2023theroleof pages 2-4)

  • Extramedullary hematopoiesis (EMH): Heart‑failure literature implicates splenic EMH during systemic congestion and inflammatory stress, linking cardio‑splenic–marrow axes to chronic inflammation. URL: https://doi.org/10.1007/s10741-024-10418-6 (Jul 2024). (hiraiwa2024interplayofthe pages 2-4)

  • Hematologic consequences (hypersplenism)

  • Sequestration and destruction: The spleen stores ~1/3 of platelets; with splenomegaly, increased phagocytic activity causes platelet, erythrocyte, and leukocyte destruction, leading to cytopenias. URL: https://doi.org/10.3390/gastroent14030024 (Aug 2023). (marginean2023diagnosticapproachand pages 6-7)

  • Decreased hepatic thrombopoietin (THPO) and iron–hepcidin axis: Reduced hepatic TPO production and inflammatory regulation of hepcidin (HAMP) contribute to thrombocytopenia and anemia in chronic liver disease. URL: https://doi.org/10.3390/gastroent14030024 (Aug 2023). (marginean2023diagnosticapproachand pages 6-7)

  • Collateralization and varices; splenic stiffness

  • In portal hypertension, loss of splenic rhythmic regulation, venous sinusoid enlargement, and connective tissue hypertrophy accompany collateral vessel formation and variceal risk; postprandial and baseline spleen stiffness rise with portal flow/fibrosis. URL: https://doi.org/10.1159/000507346 (May 2021). (weinzirl2021splenicrhythmsand pages 4-5)

2. Key Molecular Players

  • Genes/proteins (HGNC):
  • Vasoactive/endothelial: NOS3 (eNOS), PTGIS (prostacyclin synthase), EDN1 (endothelin‑1) (vasodilator–vasoconstrictor imbalance in splanchnic bed). (marginean2023diagnosticapproachand pages 6-7)
  • Matrix/endothelial remodeling: COL4A1/COL4A2 (collagen IV), CD44 (matrix receptor), ENPP2/autotaxin (vascular contractility), mediators of NETs (MPO, PADI4) (CSPH proteomics). (pastrovic2024serumproteomicprofiling pages 20-20)
  • Lymphangiogenesis: VEGFC, LYVE1 (CSPH‑specific detection). (pastrovic2024serumproteomicprofiling pages 20-20)
  • Cytokine axes: TNF (NF‑κB–dependent endothelial activation), TGFB1 (splenic macrophages; fibrosis signaling). (yoshida2023theroleof pages 2-4)

  • Hematology: THPO (liver‑derived), HAMP (hepcidin). (marginean2023diagnosticapproachand pages 6-7)

  • Chemical entities (CHEBI):

  • Nitric oxide (CHEBI:16480), prostacyclin/PGI2 (CHEBI:15552), endothelin‑1 peptide (CHEBI:6801). (marginean2023diagnosticapproachand pages 6-7)

  • Cell types (CL terms):

  • Liver sinusoidal endothelial cells (LSECs), splenic sinus lining endothelial cells; splenic red‑pulp macrophages; lymphatic endothelial cells; splenic lymphocytes; megakaryocytes. (pastrovic2024serumproteomicprofiling pages 20-20, yoshida2023theroleof pages 2-4, marginean2023diagnosticapproachand pages 6-7)

  • Anatomical locations (UBERON):

  • Spleen (UBERON:0002107), hepatic sinusoid (UBERON:0002106), portal vein/splenic vein (UBERON:0002107 context; vascular tree), short gastric/left gastric veins (collaterals). (weinzirl2021splenicrhythmsand pages 4-5)

3. Biological Processes (GO) Disrupted

  • Regulation of systemic arterial blood pressure and vasodilation; nitric‑oxide mediated signaling pathway; prostaglandin biosynthetic process; response to endothelin. (marginean2023diagnosticapproachand pages 6-7)
  • Angiogenesis and lymphangiogenesis; extracellular matrix organization; basement membrane assembly (collagen IV deposition); endothelial cell junction organization. (pastrovic2024serumproteomicprofiling pages 20-20)
  • Immune activation and leukocyte-mediated cytotoxicity; macrophage activation; extramedullary hematopoiesis; neutrophil extracellular trap formation. (hiraiwa2024interplayofthe pages 2-4, pastrovic2024serumproteomicprofiling pages 20-20)
  • Platelet homeostasis; erythrocyte clearance; regulation of thrombopoiesis; iron ion homeostasis via hepcidin. (marginean2023diagnosticapproachand pages 6-7)

4. Cellular Components Involved

  • Endothelial cell plasma membrane and caveolae; sinusoidal basement membrane (emergent in capillarization) with collagen IV; splenic cords and venous sinusoids (red pulp); white pulp germinal centers; extracellular space/plasma (proteomic signatures). (pastrovic2024serumproteomicprofiling pages 20-20, weinzirl2021splenicrhythmsand pages 4-5, yoshida2023theroleof pages 2-4)

5. Disease Progression (Sequence of Events)

1) Initiating lesion: Intrahepatic resistance (fibrosis, sinusoidal capillarization) or splenic venous outflow obstruction (SVT/torsion) or systemic venous congestion (right‑sided HF). (pastrovic2024serumproteomicprofiling pages 20-20, marginean2023diagnosticapproachand pages 6-7) 2) Hemodynamic response: Splanchnic vasodilation (NO/PGI2) and increased portal inflow (forward flow) superimposed on backpressure (backward flow), generating local hyperdynamic state at the spleen. (yoshida2023theroleof pages 1-2, marginean2023diagnosticapproachand pages 6-7) 3) Splenic microvascular remodeling: Sinusoid dilation, endothelial dysfunction, ECM (COL4) deposition, angiogenesis/lymphangiogenesis; loss of rhythmic contractility; increased stiffness. (pastrovic2024serumproteomicprofiling pages 20-20, weinzirl2021splenicrhythmsand pages 4-5) 4) Immune–stromal remodeling: White‑pulp hyperplasia, macrophage activation (TGF‑β1), diffuse fibrosis; in systemic congestion, induction of splenic EMH. (yoshida2023theroleof pages 2-4, hiraiwa2024interplayofthe pages 2-4) 5) Hypersplenism: Increased pooling/sequestration and destruction of platelets/erythrocytes/leukocytes; compounded by decreased hepatic THPO and iron–hepcidin dysregulation. (marginean2023diagnosticapproachand pages 6-7) 6) Clinical complications: Development of portal collaterals and varices; rising spleen stiffness/volume; cytopenias with bleeding risk; in left‑sided PH, isolated gastric varices. (weinzirl2021splenicrhythmsand pages 4-5, yoshida2023theroleof pages 1-2)

6. Phenotypic Manifestations (HP terms linkage)

  • Splenomegaly (HP:0001744) with increased stiffness/size on ultrasound/elastography; postprandial increases reflect hyperemia. Quote: “postprandial congestion with significant increases in volume… the spleen’s rhythmical function is lost in portal hypertension.” URL: https://doi.org/10.1159/000507346 (May 2021). (weinzirl2021splenicrhythmsand pages 4-5)
  • Hypersplenism with cytopenias: Thrombocytopenia (HP:0001873), anemia (HP:0001903), leukopenia (HP:0001882), attributed to sequestration/destruction and low THPO. URL: https://doi.org/10.3390/gastroent14030024 (Aug 2023). (marginean2023diagnosticapproachand pages 6-7)
  • Portal hypertension signs: Portosystemic collaterals and varices (HP:0001403), ascites (HP:0001541); splenic contribution to portal inflow increases markedly. URL: https://doi.org/10.1272/jnms.jnms.2023_90-104 (Feb 2023). (yoshida2023theroleof pages 2-4)
  • Left‑sided portal hypertension: Gastric varices with splenomegaly due to splenic‑vein obstruction (sinistral PH). (yoshida2023theroleof pages 1-2)

Current Applications and Real‑World Implementations

  • Noninvasive assessment: Spleen stiffness (shear‑wave elastography) and platelet count are widely used to infer clinically significant portal hypertension and variceal risk; postprandial changes provide functional readouts of splanchnic hyperemia. Mechanistic basis grounded in splanchnic vasodilation and splenic microvascular remodeling. (weinzirl2021splenicrhythmsand pages 4-5)
  • Interventions that modulate splanchnic inflow and portal pressure (e.g., non‑selective beta‑blockers) have the potential to reduce splenic congestion and hypersplenism manifestations indirectly by reversing hyperdynamic splanchnic circulation. Mechanistic underpinnings cited in 2023 overview of CLD anemia and PH physiology. (marginean2023diagnosticapproachand pages 6-7)
  • Surgical/IR approaches (partial splenic embolization, splenectomy) target refractory hypersplenism/variceal risk; Yoshida 2023 reviews spleen’s regulatory role and outcomes of such strategies in the hepatosplenic axis. (yoshida2023theroleof pages 2-4)

Expert Opinions and Authoritative Analyses (2023–2024 priority)

  • Yoshida 2023: Positions the spleen as a key regulator in the “forward flow” model of portal hypertension, with data on splenic artery resistance and lymphoid hyperactivation—arguing splenomegaly is not purely passive congestion. URL: https://doi.org/10.1272/jnms.jnms.2023_90-104 (Feb 2023). (yoshida2023theroleof pages 1-2, yoshida2023theroleof pages 2-4)
  • Pastrovic 2024: Proteomics delineates CSPH‑specific markers (CD44, VEGF‑C, LYVE‑1; NETs), proposing inflammation‑vascular contractility‑lymphangiogenesis triad as key in PH pathogenesis and biomarker discovery. URL: https://doi.org/10.1371/journal.pone.0301416 (Apr 2024). (pastrovic2024serumproteomicprofiling pages 20-20)
  • Marginean 2023: Synthesizes anemia mechanisms in CLD, emphasizing hypersplenism (sequestration/destruction), reduced hepatic THPO, and hepcidin‑mediated iron restriction. URL: https://doi.org/10.3390/gastroent14030024 (Aug 2023). (marginean2023diagnosticapproachand pages 6-7)
  • Weinzirl 2021: Reviews splenic rhythmic regulation and its loss in portal hypertension; links hemodynamics to structural remodeling and variceal risk; supports stiffness/volume as functional biomarkers. URL: https://doi.org/10.1159/000507346 (May 2021). (weinzirl2021splenicrhythmsand pages 4-5)
  • Heart‑failure perspective (Hiraiwa 2024): Highlights splenic EMH and inflammatory crosstalk in systemic venous congestion. URL: https://doi.org/10.1007/s10741-024-10418-6 (Jul 2024). (hiraiwa2024interplayofthe pages 2-4)

Statistics and Data from Recent Studies

  • Splenic inflow contributions: Rising from ~20–40% (normal) to ~50% (chronic hepatitis/cirrhosis) and ~75% (idiopathic portal hypertension), indicating an active role of the spleen in maintaining portal inflow under elevated resistance. (Yoshida 2023). URL: https://doi.org/10.1272/jnms.jnms.2023_90-104 (Feb 2023). (yoshida2023theroleof pages 2-4)
  • Pharmacology: mTOR inhibition (rapamycin) reduced spleen size by ~44% in portal‑hypertensive models, supporting proliferative/immune activation components of splenomegaly beyond passive congestion. (Yoshida 2023). URL: https://doi.org/10.1272/jnms.jnms.2023_90-104 (Feb 2023). (yoshida2023theroleof pages 2-4)
  • Proteomics (CSPH vs non‑CSPH): CSPH sera uniquely contained CD44, VEGF‑C, LYVE‑1; NET‑related proteins elevated, suggesting distinct endothelial/lymphatic/inflammatory signatures in patients with CSPH. (Pastrovic 2024). URL: https://doi.org/10.1371/journal.pone.0301416 (Apr 2024). (pastrovic2024serumproteomicprofiling pages 20-20)
  • Hematology prevalence: Thrombocytopenia frequent in CLD; mechanisms include hypersplenism and reduced hepatic THPO; pro‑inflammatory cytokines limit iron availability and erythropoiesis (anemia of inflammation). (Marginean 2023). URL: https://doi.org/10.3390/gastroent14030024 (Aug 2023). (marginean2023diagnosticapproachand pages 6-7)

Evidence Items (PMIDs/DOIs and dates)

  • Yoshida H, et al. The Role of the Spleen in Portal Hypertension. Journal of Nippon Medical School, Feb 2023. DOI: 10.1272/jnms.jnms.2023_90-104. URL: https://doi.org/10.1272/jnms.jnms.2023_90-104 (hemodynamics; lymphoid activation; hypersplenism). (yoshida2023theroleof pages 1-2, yoshida2023theroleof pages 2-4)
  • Pastrovic F, et al. Serum proteomic profiling… CSPH. PLOS ONE, Apr 2024. DOI: 10.1371/journal.pone.0301416. URL: https://doi.org/10.1371/journal.pone.0301416 (VEGF‑C, LYVE‑1, CD44, NET proteins). (pastrovic2024serumproteomicprofiling pages 20-20)
  • Marginean CM, et al. Diagnostic approach and pathophysiological mechanisms of anemia in CLD. Gastroenterology Insights, Aug 2023. DOI: 10.3390/gastroent14030024. URL: https://doi.org/10.3390/gastroent14030024 (hypersplenism; THPO; hepcidin). (marginean2023diagnosticapproachand pages 6-7)
  • Weinzirl J, et al. Splenic Rhythms… Digestion, May 2021. DOI: 10.1159/000507346. URL: https://doi.org/10.1159/000507346 (hemodynamics; stiffness; collaterals). (weinzirl2021splenicrhythmsand pages 4-5)
  • Hiraiwa H, et al. Interplay of the heart, spleen, and bone marrow in HF. Heart Failure Reviews, Jul 2024. DOI: 10.1007/s10741-024-10418-6. URL: https://doi.org/10.1007/s10741-024-10418-6 (splenic EMH in congestion). (hiraiwa2024interplayofthe pages 2-4)

Structured Annotations for Knowledge Base

  • Pathophysiology description: See Executive Summary and Sections 1–5. (yoshida2023theroleof pages 1-2, marginean2023diagnosticapproachand pages 6-7, pastrovic2024serumproteomicprofiling pages 20-20, weinzirl2021splenicrhythmsand pages 4-5)
  • Gene/protein annotations (HGNC): NOS3, PTGIS, EDN1, COL4A1/COL4A2, CD44, ENPP2, VEGFC, LYVE1, TGFB1, THPO, HAMP, MPO, PADI4. (marginean2023diagnosticapproachand pages 6-7, pastrovic2024serumproteomicprofiling pages 20-20, yoshida2023theroleof pages 2-4)
  • GO biological processes: nitric‑oxide mediated signaling; prostaglandin biosynthesis; endothelin receptor signaling; extracellular matrix organization; angiogenesis; lymphangiogenesis; NET formation; regulation of thrombopoiesis; iron ion homeostasis. (marginean2023diagnosticapproachand pages 6-7, pastrovic2024serumproteomicprofiling pages 20-20)
  • Cellular components: endothelial cell membrane/caveolae; basement membrane (collagen IV); splenic cords/venous sinusoids; white‑pulp follicles; extracellular region/plasma. (pastrovic2024serumproteomicprofiling pages 20-20, weinzirl2021splenicrhythmsand pages 4-5)
  • Phenotype associations (HP): Splenomegaly (HP:0001744); Thrombocytopenia (HP:0001873); Anemia (HP:0001903); Leukopenia (HP:0001882); Portal hypertension (HP:0001403); Ascites (HP:0001541). (marginean2023diagnosticapproachand pages 6-7, weinzirl2021splenicrhythmsand pages 4-5)
  • Cell types (CL): Liver sinusoidal endothelial cell; splenic red‑pulp macrophage; lymphatic endothelial cell; megakaryocyte; B/T lymphocytes.
  • Anatomical locations (UBERON): Spleen (UBERON:0002107); Hepatic sinusoid (UBERON:0002106); Portal vein and splenic vein vascular territories; Left gastric/short gastric veins (collaterals). (weinzirl2021splenicrhythmsand pages 4-5)
  • Chemical entities (CHEBI): Nitric oxide (CHEBI:16480); PGI2 (CHEBI:15552); Endothelin‑1 (CHEBI:6801). (marginean2023diagnosticapproachand pages 6-7)

Gaps and Future Directions

  • Direct human mechanistic data for splenic sinus endothelial capillarization and collagen IV deposition remain less developed than hepatic LSEC literature; proteomic and imaging signals suggest analogous processes in the spleen during portal hypertension, warranting targeted histology and single‑cell studies in human spleens from PH contexts. (pastrovic2024serumproteomicprofiling pages 20-20)
  • Quantitative thresholds linking spleen stiffness dynamics to specific risks (e.g., variceal bleeding) require harmonized, prospective validation integrating proteomic and imaging biomarkers. (weinzirl2021splenicrhythmsand pages 4-5, pastrovic2024serumproteomicprofiling pages 20-20)

References

  1. (yoshida2023theroleof pages 1-2): Hiroshi Yoshida, Tetsuya Shimizu, Masato Yoshioka, Akira Matsushita, Youichi Kawano, Junji Ueda, Mampei Kawashima, Nobuhiko Taniai, and Yasuhiro Mamada. The role of the spleen in portal hypertension. Journal of Nippon Medical School = Nippon Ika Daigaku zasshi, 90 1:20-25, Feb 2023. URL: https://doi.org/10.1272/jnms.jnms.2023_90-104, doi:10.1272/jnms.jnms.2023_90-104. This article has 37 citations.

  2. (marginean2023diagnosticapproachand pages 6-7): Cristina Maria Marginean, Denisa Pirscoveanu, Mihaela Popescu, Anca Oana Docea, Antonia Radu, Alin Iulian Silviu Popescu, Corina Maria Vasile, Radu Mitrut, Iulia Cristina Marginean, George Alexandru Iacob, Dan Mihai Firu, and Paul Mitrut. Diagnostic approach and pathophysiological mechanisms of anemia in chronic liver disease—an overview. Gastroenterology Insights, 14:327-341, Aug 2023. URL: https://doi.org/10.3390/gastroent14030024, doi:10.3390/gastroent14030024. This article has 13 citations.

  3. (weinzirl2021splenicrhythmsand pages 4-5): Johannes Weinzirl, Lydia Garnitschnig, Tom Scheffers, Lukas Andrae, and Peter Heusser. Splenic rhythms and postprandial dynamics in physiology, portal hypertension, and functional hyposplenism: a review. Digestion, 102:326-334, May 2021. URL: https://doi.org/10.1159/000507346, doi:10.1159/000507346. This article has 12 citations and is from a peer-reviewed journal.

  4. (pastrovic2024serumproteomicprofiling pages 20-20): Frane Pastrovic, Rudjer Novak, Ivica Grgurevic, Stela Hrkac, Grgur Salai, Marko Zarak, and Lovorka Grgurevic. Serum proteomic profiling of patients with compensated advanced chronic liver disease with and without clinically significant portal hypertension. PLOS ONE, 19:e0301416, Apr 2024. URL: https://doi.org/10.1371/journal.pone.0301416, doi:10.1371/journal.pone.0301416. This article has 1 citations and is from a peer-reviewed journal.

  5. (yoshida2023theroleof pages 2-4): Hiroshi Yoshida, Tetsuya Shimizu, Masato Yoshioka, Akira Matsushita, Youichi Kawano, Junji Ueda, Mampei Kawashima, Nobuhiko Taniai, and Yasuhiro Mamada. The role of the spleen in portal hypertension. Journal of Nippon Medical School = Nippon Ika Daigaku zasshi, 90 1:20-25, Feb 2023. URL: https://doi.org/10.1272/jnms.jnms.2023_90-104, doi:10.1272/jnms.jnms.2023_90-104. This article has 37 citations.

  6. (hiraiwa2024interplayofthe pages 2-4): Hiroaki Hiraiwa, Yoshimitsu Yura, Takahiro Okumura, and Toyoaki Murohara. Interplay of the heart, spleen, and bone marrow in heart failure: the role of splenic extramedullary hematopoiesis. Heart Failure Reviews, 29:1049-1063, Jul 2024. URL: https://doi.org/10.1007/s10741-024-10418-6, doi:10.1007/s10741-024-10418-6. This article has 10 citations and is from a peer-reviewed journal.