Splenomegaly: Difference between revisions

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{{Infobox_Disease |
__NOTOC__
  Name          = {{PAGENAME}} |
  Image          = Abdomen splenomegaly.jpg|
  Caption        = Massively enlarged spleen, the result of extramedullary hematopoiesis,  is outlined above. This patient's left upper quadrant appears more full than the corresponding area  on the right. <br>  Image courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, California|
  DiseasesDB    = 12375 |
  ICD10          = {{ICD10|Q|89|0|q|80}}, {{ICD10|R|16|1|r|10}} |
  ICD9          = {{ICD9|759.0}}, {{ICD9|789.2}} |
  ICDO          = |
  OMIM          = |
  MedlinePlus    = 003276 |
  eMedicineSubj  = |
  eMedicineTopic =  |
  eMedicine_mult = |
  MeshID        = D013163 |
}}
{{Splenomegaly}}
{{CMG}}; {{AOEIC}} Gichoya Judy Wawira [mailto:judywawira@gmail.com], Moi University School of Medicine


==Differential diagnosis of causes by organ system or pathogenesis==
'''For the patient information page for this topic, click [[Splenomegaly (patient information)|here]]'''
'''Splenomegaly grouped on the basis of the pathogenic mechanism'''
{| class="wikitable"
|-
! Increased function
! Abnormal blood flow
! Infitration
|-
| '''''Removal of defective RBCs'''''
[[Spherocytosis]]<br />
[[Thalassemia]]<br />
[[Hemoglobinopathies]]<br />
Nutritional [[anemia]]s<br />
early [[sickle cell anemia]]<br />
'''''Immune hyperplasia'''''<br />
''Response to infection (viral,bacterial,fungal,parasitic'')<br />[[Mononucleosis]], [[AIDS]], [[viral hepatitis]]<br />subacute [[bacterial endocarditis]], bacterial [[septicemia]]<br /> splenic [[abscess]], [[typhoid fever]]<br />[[brucellosis]],[[ leptospirosis]], [[tuberculosis]]<br />[[histoplasmosis]]<br />[[malaria]], [[leishmaniasis]], [[trypanosomiasis]]<br />[[ehrlichiosis]]<br />''Disordered immunoregulation''<br />[[Rheumatoid arthritis]]<br />[[SLE]]<br />[[Serum sickness]]<br />[[Autoimmune hemolytic anemia]]<br />[[Idiopathic thrombocytopenic purpura|Immune thrombocytopenia]]<br />[[sarcoidosis]]<br />drug reactions<br />'''''Extramedullary hematopoiesis'''''<br />[[Myelofibrosis]]<br />Marrow infiltration by [[tumors]], [[leukemias]]<br />marrow damage by [[radiation]], [[toxins]]
|'''''Organ Failure'''''<br />
[[Cirrhosis]]<br />[[congestive heart failure]]<br />'''''Vascular'''''<br />[[hepatic vein obstruction]]<br />[[Portal vein thrombosis|portal vein obstruction]]<br />[[Budd-Chiari syndrome]]<br />[[splenic vein obstruction]]<br />'''''Infections'''''<br /><br />hepatic [[schistosomiasis]]<br />hepatic [[echinococcosis]]
|'''''Metabolic diseases'''''<br />[[Gauchers disease]]<br />[[Niemann-Pick disease]]<br />[[Hurler syndrome]] and other [[Mucopolysaccharidoses]]<br />[[Amyloidosis]]<br />[[Tangier disease]]<br />'''''Benign and malignant infiltrations'''''<br />[[Leukemias]](acute,chronic,lymphoid and myeloid)<br />lymphomas([[Hodgkins]] and [[Non-Hodgkin lymphoma|non-hodgkins]])<br />[[myeloproliferative]] disorders<br />[[metastatic]] tumors(commonly [[melanoma]])<br />[[histiocytosis X]]<br />[[Hemangioma]],[[lymphangioma]]<br />splenic [[cysts]]<br />[[hamartomas]]<br />[[eosinophilic granuloma]]


|}
{{CMG}}; {{AE}} {{SSH}}, Gichoya Judy Wawira [mailto:judywawira@gmail.com],
<br />
The causes of massive splenomegaly (>1000gms) are much fewer and include:<br /><br />[[Thalassemia]]<br />[[Kala-Azar]] ([[Leishmaniasis]])<br />[[Portal hypertension]] of Bilharziasis<br />[[Chronic myelogenous leukemia]]<br />[[lymphomas]]<br />[[hairy cell leukemia]]<br />[[myelofibrosis]]<br />[[polycythemia vera]]<br />[[Gauchers disease]]<br />[[chronic lymphocytic leukemia]]<br />[[sarcoidosis]]<br />[[autoimmune hemolytic anemia]]<br />[[Malaria]]


==Clinical presentation==
{{SK}} Spleen enlargement; enlarged spleen; spleen swelling


[[Symptoms]] may include [[abdominal pain]], early satiety due to splenic encroachment, or the symptoms of [[anemia]] due to accompanying cytopenia.
==Overview==


[[Medical sign|Sign]]s of splenomegaly may include a palpable left upper quadrant [[abdominal mass]] or splenic rub. It can be detected on [[physical examination]] by using [[Castell's sign]] or [[Traube's space]], but an [[ultrasound]] can be used to confirm diagnosis.<ref name="pmid8411607">{{cite journal |author=Grover SA, Barkun AN, Sackett DL |title=The rational clinical examination. Does this patient have splenomegaly? |journal=JAMA |volume=270 |issue=18 |pages=2218-21 |year=1993 |pmid=8411607 |doi=}} [http://gateway.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=8411607.ui Ovid full text]</ref>
==Pathophysiology==


==Causes==
The causes of splenomegaly vary widely and range from increased splenic function (such as [[hemoglobinopathies]]), splenic congestion due to abnormal blood flow (such as venous obstruction), and splenic infiltration (such as storage disorders and [[malignancies]]).


<gallery>
===Causes by Pathogenesis===
Image:
{| class="wikitable"
 
|-
Splenomegaly-001.jpg
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Mechanism
 
! colspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" + |Pathogenesis
Image:
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Example
 
|-
Splenomegaly-002.jpg
! rowspan="5" align="center" style="background:#4479BA; color: #FFFFFF;" + |Increased function
 
! colspan="2" |Removal of defective RBCs
Image:
|<div style="-moz-column-count:2; column-count:2;">
 
*[[Spherocytosis]]
Splenomegaly-101.jpg
*[[Thalassemia]]
 
*[[Hemoglobinopathy]]
</gallery>
*[[Anemia]]
*[[Sickle cell anemia]]</div>
|-
! rowspan="3" |Immune hyperplasia
!Response to infection (viral, bacterial, fungal, parasitic)
|<div style="-moz-column-count:2; column-count:2;">
*[[Mononucleosis]]
*[[AIDS]]
*[[Viral hepatitis]]
*[[Endocarditis|Subacute bacterial endocarditis]]
*[[Sepsis|Bacterial septicemia]]
*[[Splenic abscess]]
*[[Typhoid fever]]
*[[Leptospirosis]]
*[[Tuberculosis]]
*[[Histoplasmosis]]
*[[Malaria]]
*[[leishmaniasis]]
*[[Trypanosomiasis]]
*[[Ehrlichiosis]]</div>
|-
!Disordered immunoregulation
|<div style="-moz-column-count:2; column-count:2;">
*[[Rheumatoid arthritis]]
*[[SLE]]
*[[Serum sickness]]
*[[Autoimmune hemolytic anemia]]
*[[Idiopathic thrombocytopenic purpura|Immune thrombocytopenia]]
*[[Sarcoidosis]]</div>
|-
!Drug reactions
|
*[[Cidofovir]]
*[[Filgrastim]]
|-
! colspan="2" |Extramedullary hematopoiesis
|<div style="-moz-column-count:2; column-count:2;">
*[[Myelofibrosis]]
*[[Tumors]]
*[[Marrow infiltration by tumors, leukemias|Lukemias]]
*[[marrow damage by radiation, toxins|Marrow damage by radiation]]
*[[marrow damage by radiation, toxins|toxins]]</div>
|-
! rowspan="3" align="center" style="background:#4479BA; color: #FFFFFF;" + |Abnormal blood flow
! colspan="2" |Organ Failure
|
*[[Cirrhosis]]
*[[Congestive heart failure]]
|-
! colspan="2" |Vascular
|<div style="-moz-column-count:2; column-count:2;">
*[[Hepatic vein obstruction]]
*[[Portal vein thrombosis|Portal vein obstruction]]
*[[Budd-Chiari syndrome]]
*Splenic vein obstruction</div>
|-
! colspan="2" |Infections
|
*Hepatic [[schistosomiasis]]
*Hepatic [[echinococcosis]]
|-
! rowspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" + |Infiltration
! colspan="2" |Metabolic diseases
|<div style="-moz-column-count:2; column-count:2;">
*[[Gauchers disease]]
*[[Niemann-Pick disease]]
*[[Hurler syndrome]]
*[[Mucopolysaccharidoses]]
*[[Amyloidosis]]
*[[Tangier disease]]</div>
|-
! colspan="2" |Benign and malignant infiltrations
|<div style="-moz-column-count:2; column-count:2;">
*[[Leukemias]] ([[acute]], [[chronic]], [[lymphoid]] and [[myeloid]])
*[[Lymphomas]] ([[Hodgkins]] and [[Non-Hodgkin lymphoma|non-hodgkins]])
*[[Myeloproliferative]] disorders
*[[Metastatic]] tumors (commonly [[melanoma]])
*[[Histiocytosis X]]
*[[Hemangioma]]
*[[Lymphangioma]]
*[[Splenic cyst]]
*[[Hamartomas]]
*[[Eosinophilic granuloma]]</div>
|}
==Differentiating Splenomegaly from Other Diseases==
{|
! rowspan="4" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Category
! colspan="2" rowspan="4" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Disease
! rowspan="4" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Etiology
! colspan="12" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Clinical manifestations
! colspan="10" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Para−clinical findings
! rowspan="4" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Gold standard
! rowspan="4" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Associated findings
|-
! rowspan="3" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Demography
! rowspan="3" style="background: #4479BA; color: #FFFFFF; text-align: center;" |History
! colspan="5" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Symptoms
! colspan="5" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Signs
! colspan="9" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Lab Findings
! rowspan="3" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Imaging
|-
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Fever
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Fatigue
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Weight
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Abdominal pain
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Bleeding
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |BP
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |JVP
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Jaundice
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Ascites
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Other
! colspan="3" style="background: #4479BA; color: #FFFFFF; text-align: center;" |CBC
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Iron
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |LFT
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |PT/PTT
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |BUN/Cr
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |UA
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Histopathology
|-
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |WBC
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Hb
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Plt
|-
! rowspan="3" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Congestive
! colspan="2" align="center" style="background:#DCDCDC;" |[[Cirrhosis]]<ref name="pmid22710653">{{cite journal |vauthors=Wu Z, Zhou J, Pankaj P, Peng B |title=Laparoscopic and open splenectomy for splenomegaly secondary to liver cirrhosis: an evaluation of immunity |journal=Surg Endosc |volume=26 |issue=12 |pages=3557–64 |date=December 2012 |pmid=22710653 |doi=10.1007/s00464-012-2366-5 |url=}}</ref>
| align="left" style="background:#F5F5F5;" |
* [[Infection]]
* [[Alcohol]]
* [[Autoimmunity|Autoimmune]]
| align="center" style="background:#F5F5F5;" |Any age, more common in elderly
| align="left" style="background:#F5F5F5;" |
* [[Hepatitis]]
* [[Alcoholism|Alcohol use]]
* [[Non-alcoholic fatty liver disease|NAFLD]]
| align="center" style="background:#F5F5F5;" |–
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |↑↓
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |
* [[Spider angioma|Spider angiomata]]
* [[Palmar erythema]]
* [[Muscle weakness|Weakness]]
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |
* Dark [[urine]]
| align="left" style="background:#F5F5F5;" |
* [[Pancytopenia]]
* Regenerating nodules of [[Hepatocyte|hepatocytes]]
* [[Fibrosis]]
* Deposition of [[connective tissue]] between these nodules
| align="left" style="background:#F5F5F5;" |
* Small and nodular [[liver]] on [[ultrasound]]
* [[Fibrosis]] on [[liver]] scan
| align="center" style="background:#F5F5F5;" |[[Liver biopsy]]
| align="left" style="background:#F5F5F5;" |
* [[Hepatic encephalopathy]]
* [[Gynecomastia]]
* [[Hypogonadism]]
* [[Esophageal varices]]
* [[Caput medusae|Caput medusa]]
* [[Dupuytrens contracture|Dupuytren's contracture]]
|-
! colspan="2" align="center" style="background:#DCDCDC;" |[[Congestive heart failure|Heart failure]]<ref name="pmid26489162">{{cite journal |vauthors=Gedela M, Khan M, Jonsson O |title=Heart Failure |journal=S D Med |volume=68 |issue=9 |pages=403–5, 407–9 |date=September 2015 |pmid=26489162 |doi= |url=}}</ref>
| align="left" style="background:#F5F5F5;" |
* [[Coronary heart disease|Coronary artery disease]]
* [[Hypertension|HTN]]
| align="center" style="background:#F5F5F5;" |Elderly
| align="left" style="background:#F5F5F5;" |
* [[Smoking]]
* Sedentary lifestyle
* [[Sleep apnea|Obstructive sleep apnea]]
| align="center" style="background:#F5F5F5;" |–
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |↑↓
| align="center" style="background:#F5F5F5;" |–
| align="center" style="background:#F5F5F5;" |–
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |±
| align="center" style="background:#F5F5F5;" | +
| align="left" style="background:#F5F5F5;" |
* [[Dyspnea]]
* [[Muscle weakness|Weakness]]
* [[Chest pain]]
* [[Heart murmur]]
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |NA
| align="left" style="background:#F5F5F5;" |
* Normal or low [[ejection fraction]] on [[echocardiography]]
* [[Cardiomegaly]] on [[Chest X-ray|chest x-ray]]
| align="center" style="background:#F5F5F5;" |[[Echocardiography]]
| align="left" style="background:#F5F5F5;" |
* [[Pulmonary edema]]
* [[Hyponatremia]]
* Elevated [[Brain natriuretic peptide|BNP]]
|-
! colspan="2" align="center" style="background:#DCDCDC;" |[[Thrombosis]] of [[portal]], [[Liver|hepatic]], or [[Splenic vein|splenic veins]]<ref name="pmid22481689">{{cite journal |vauthors=Ferri PM, Ferreira AR, Fagundes ED, Liu SM, Roquete ML, Penna FJ |title=Portal vein thrombosis in children and adolescents: 20 years experience of a pediatric hepatology reference center |journal=Arq Gastroenterol |volume=49 |issue=1 |pages=69–76 |date=2012 |pmid=22481689 |doi= |url=}}</ref>
| align="left" style="background:#F5F5F5;" |
* [[Thrombosis]]
| align="center" style="background:#F5F5F5;" |Any age
| align="left" style="background:#F5F5F5;" |
* [[Inflammation]]
* [[Infection]]
* [[Cirrhosis]]
* [[Cancer]]
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |±
| align="center" style="background:#F5F5F5;" | +
| align="left" style="background:#F5F5F5;" |
* [[Muscle weakness|Weakness]]
*[[Hematemesis]]
*[[Melena]]
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="left" style="background:#F5F5F5;" |
* Dark [[urine]]
| align="center" style="background:#F5F5F5;" |NA
| align="left" style="background:#F5F5F5;" |
* Reduced or absent [[blood flow]] on [[Medical ultrasonography|doppler ultrasonography]]
| align="center" style="background:#F5F5F5;" |[[Medical ultrasonography|Doppler ultrasonography]]
| align="left" style="background:#F5F5F5;" |
* [[Portal hypertension]]
* [[Esophageal varices]]
|-
! rowspan="10" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Malignancy
! colspan="2" align="center" style="background:#DCDCDC;" |[[Lymphoma]]<ref name="pmid25131182">{{cite journal |vauthors=Ishibashi N, Maebayashi T, Aizawa T, Sakaguchi M, Abe O, Saito T, Tanaka Y |title=Myelosuppression toxicity of palliative splenic irradiation in myelofibrosis and malignant lymphoma |journal=Hematology |volume=20 |issue=4 |pages=203–7 |date=May 2015 |pmid=25131182 |doi=10.1179/1607845414Y.0000000192 |url=}}</ref>
| align="left" style="background:#F5F5F5;" |
* Unknown
* [[Mutation]]
* [[Infection]]
| align="center" style="background:#F5F5F5;" |Any age, most common malignant splenic tumor
| align="left" style="background:#F5F5F5;" |
* [[Epstein Barr virus]]
* Positive family history
* [[Smoking]]
* [[Human Immunodeficiency Virus (HIV)|HIV]]
* [[Autoimmunity|Autoimmune diseases]]
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |–
| align="left" style="background:#F5F5F5;" |
* [[Lymphadenopathy]]
* [[Itch|Itching]]
* [[Sleep hyperhidrosis|Night sweats]]
* [[Anorexia]]
* [[Dyspnea]]
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |High [[ferritin]]
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |Nl
| align="left" style="background:#F5F5F5;" |
* Different [[Histopathology|histopathological]] features based on types and stages
* [[Reed-Sternberg cell]]
* Malignant cells
| align="left" style="background:#F5F5F5;" |
* Peritoneal [[Primary central nervous system lymphoma|lymphomatosis]] on [[Computed tomography|CT scan]]
| align="center" style="background:#F5F5F5;" |[[Lymph node biopsy]]
| align="left" style="background:#F5F5F5;" |
* [[Immune disorder|Primary immune disorder]]
* Post-[[Organ transplant|transplant]]
|-
! colspan="2" align="center" style="background:#DCDCDC;" |[[Leukemia]]<ref name="pmid26614896">{{cite journal |vauthors=Quest GR, Johnston JB |title=Clinical features and diagnosis of hairy cell leukemia |journal=Best Pract Res Clin Haematol |volume=28 |issue=4 |pages=180–92 |date=December 2015 |pmid=26614896 |doi=10.1016/j.beha.2015.10.017 |url=}}</ref>
| align="left" style="background:#F5F5F5;" |
* Unknown
* [[Mutation]]
* [[Bone marrow]]<nowiki/>infiltration
* Ineffective [[hematopoiesis]]
* [[Immunity (medical)|Immune]] mediated
| align="center" style="background:#F5F5F5;" |Elderly, male>female
| align="left" style="background:#F5F5F5;" |
* History of [[Hematological|hematological disorder]]
* History of [[chemotherapy]] and[[ionizing radiation]]
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |±
| align="center" style="background:#F5F5F5;" | +
| align="left" style="background:#F5F5F5;" |
* [[Pallor]]
* [[Chloroma|Leukemia cutis]]
* [[Bruising]]
* [[Petechia|Petechiae]]
* [[Ecchymosis]]
* [[Fatigue]]
* Bone [[tenderness]]
* [[Satiety|Early satiety]]
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |High [[ferritin]]
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |Nl
| align="left" style="background:#F5F5F5;" |
* Leukemic blasts
* Leukoerythroblastic features
* Giant [[Platelet|platelets]]
| align="center" style="background:#F5F5F5;" |NA
| align="center" style="background:#F5F5F5;" |[[Bone marrow examination]] + clinical manifestation
| align="left" style="background:#F5F5F5;" |
* [[Infection|Infections]] of variable severity
* [[Nerve palsy|Cranial nerve palsy]]
|-
! colspan="2" align="center" style="background:#DCDCDC;" |[[Polycythemia vera|Polycythemia Vera]]<ref name="pmid23281576">{{cite journal |vauthors=Chou YS, Gau JP, Yu YB, Pai JT, Hsiao LT, Liu JH, Hong YC, Liu CY, Yang CF, Chen PM, Chiou TJ, Tzeng CH |title=Leukocytosis in polycythemia vera and splenomegaly in essential thrombocythemia are independent risk factors for hemorrhage |journal=Eur. J. Haematol. |volume=90 |issue=3 |pages=228–36 |date=March 2013 |pmid=23281576 |doi=10.1111/ejh.12064 |url=}}</ref>
| align="left" style="background:#F5F5F5;" |
* Autonomous [[erythrocyte]]<nowiki/>production
* [[JAK2]]<nowiki/>mutation
| align="center" style="background:#F5F5F5;" |Mean age >60 years old
| align="left" style="background:#F5F5F5;" |
* Positive family history
| align="center" style="background:#F5F5F5;" |–
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |–
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |–
| align="center" style="background:#F5F5F5;" |–
| align="left" style="background:#F5F5F5;" |
* [[Erythromelalgia]]
* [[Chest pain]]
* [[Stroke]]-like symptoms
* [[Itch|Pruritus]]
* [[Dizziness]]
* [[Visual system|Visual disturbance]]
* Facial [[Hypervolemia|plethora]]
* Painful [[erythema]]
* [[Lymphadenopathy]]
| align="center" style="background:#F5F5F5;" |Nl to ↑
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |Nl to ↑
| align="center" style="background:#F5F5F5;" |High [[ferritin]]
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="left" style="background:#F5F5F5;" |
* Elevated normochromic, normocytic [[Red blood cell|RBCs]]
* [[Thrombocytosis]]
* Rarely immature cells
* Leukoerythroblastic picture
| align="center" style="background:#F5F5F5;" |NA
| align="center" style="background:#F5F5F5;" |WHO criteria for [[Polycythemia vera|PV]]
| align="left" style="background:#F5F5F5;" |
* [[Stroke]]
* [[Venous thrombosis]]
* [[Myelofibrosis]]
* [[Acute leukemia]]
|-
! colspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Disease
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Etiology
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Demography
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |History
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Fever
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Fatigue
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Weight loss
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Abdominal pain
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Bleeding
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |BP
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |JVP
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Jaundice
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Ascites
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Other
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |WBC
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Hb
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Plt
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Iron
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |LFT
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |PT/PTT
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |BUN/Cr
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |UA
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Histopathology
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Imaging
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Gold standard
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Associated findings
|-
! colspan="2" align="center" style="background:#DCDCDC;" |[[Multiple myeloma]]<ref name="pmid3400674">{{cite journal |vauthors=Grieco A, Manna R, Mancini R, Gambassi G |title=Massive hepatomegaly following splenectomy for myeloid metaplasia |journal=Am. J. Med. |volume=84 |issue=4 |pages=797 |date=April 1988 |pmid=3400674 |doi= |url=}}</ref>
| align="left" style="background:#F5F5F5;" |
* Unknown
* [[Mutation]]
* [[Infection]]
| align="center" style="background:#F5F5F5;" |Any age, more common in adults
| align="left" style="background:#F5F5F5;" |
* Exposure to chemicals
* [[Radiation therapy|Radiation]]
* Pre-existent [[Hematology|blood disorders]]
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |–
| align="left" style="background:#F5F5F5;" |
* [[Lymphadenopathy]]
* [[Itch|Itching]]
* [[Sleep hyperhidrosis|Night sweats]]
* [[Anorexia]]
* [[Dyspnea]]
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |High [[ferritin]]
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="left" style="background:#F5F5F5;" |
* [[Hemoglobinuria]]
| align="left" style="background:#F5F5F5;" |
* Blast cells
| align="center" style="background:#F5F5F5;" |
| align="center" style="background:#F5F5F5;" |[[Bone marrow examination]]
| align="left" style="background:#F5F5F5;" |
* [[Tumor lysis syndrome]]
* [[Infection]]
* [[CNS]] involvement
* [[Disseminated intravascular coagulation|DIC]]
|-
! colspan="2" align="center" style="background:#DCDCDC;" |[[Essential thrombocytosis|Essential thrombocythemia]]<ref name="pmid25611051">{{cite journal |vauthors=Tefferi A, Barbui T |title=Polycythemia vera and essential thrombocythemia: 2015 update on diagnosis, risk-stratification and management |journal=Am. J. Hematol. |volume=90 |issue=2 |pages=162–73 |date=February 2015 |pmid=25611051 |doi=10.1002/ajh.23895 |url=}}</ref>
| align="left" style="background:#F5F5F5;" |
* Acquired mutation of ''[[Janus kinase|JAK2]], CALR,'' or ''MPL''
| align="center" style="background:#F5F5F5;" |Mean age >60 years old, female > male
| align="left" style="background:#F5F5F5;" |
* Vascular occlusive events and [[Bleeding|hemorrhages]]
| align="center" style="background:#F5F5F5;" |±
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |–
| align="center" style="background:#F5F5F5;" |–
| align="left" style="background:#F5F5F5;" |
* [[Flushing]]
* [[Erythromelalgia]]
* [[Transient ischemic attack|Transient ischemic attacks]]
* [[Priapism]]
* [[Blurred vision|Decreased visual acuity]]
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑↑
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="left" style="background:#F5F5F5;" |
* Increased cellularity
* [[Hyperplasia]] and clustering of [[Megakaryocyte|megakaryocytes]]
* [[Bone marrow]] [[Reticular fiber|reticulin]] may be increased with no [[collagen]] [[fibrosis]]
| align="left" style="background:#F5F5F5;" |
* [[Splenomegaly]] on abdominal CT
* [[VTE]] on spiral chest CT
* [[Deep vein thrombosis|DVT]] on [[ultrasound]]
| align="center" style="background:#F5F5F5;" |[[Bone marrow examination|Bone marrow biopsy]]
| align="left" style="background:#F5F5F5;" |
* [[Thrombosis]]
|-
! colspan="2" align="center" style="background:#DCDCDC;" |[[Myelofibrosis|Primary myelofibrosis]]<ref name="pmid23514013">{{cite journal |vauthors=Cervantes F, Martinez-Trillos A |title=Myelofibrosis: an update on current pharmacotherapy and future directions |journal=Expert Opin Pharmacother |volume=14 |issue=7 |pages=873–84 |date=May 2013 |pmid=23514013 |doi=10.1517/14656566.2013.783019 |url=}}</ref>
| align="left" style="background:#F5F5F5;" |
* [[Bone marrow]] fibrosis
* [[Mutation]] in ''[[Janus kinase|JAK2]], CALR'', or ''MPL''
| align="center" style="background:#F5F5F5;" |Mean age >60 years old, male> female
| align="left" style="background:#F5F5F5;" |
* Other [[Myeloproliferative neoplasm|myeloproliferative]]<nowiki/>disorders
* [[Radioactive contamination|Radiation exposure]]
* [[Chemical substance|Chemicals]] exposure
| align="center" style="background:#F5F5F5;" |–
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |–
| align="left" style="background:#F5F5F5;" |
* [[Pallor]]
* [[Bruising]]
* [[Nodules|Skin nodules]]
* [[Nodules|Insert paragraph]]
* [[Fatigue]]
* [[Abdominal pain]]
* [[Nodules|Early satiety]]
* [[Dyspnea]]
* [[Lymphadenopathy]]
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↑/↓
| align="center" style="background:#F5F5F5;" |Low [[iron]]
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |Nl
| align="left" style="background:#F5F5F5;" |
* [[Urine|Dark urine]]
| align="left" style="background:#F5F5F5;" |
* Proliferation and [[atypia]] of [[megakaryocytes]]
* Reticulin or [[Collagen|collagen fibrosis]]
* Hypercellular [[bone marrow]]
| align="left" style="background:#F5F5F5;" |
* Diffuse bone [[sclerosis]] on [[CT angiography|CT]]
| align="center" style="background:#F5F5F5;" |[[Bone marrow examination|Bone marrow biopsy]]
| align="left" style="background:#F5F5F5;" |
* [[Thrombosis]]
* Variable risk for development of [[acute leukemia]]
|-
! colspan="2" align="center" style="background:#DCDCDC;" |[[Splenic tumor|Primary splenic tumors]]<ref name="pmid21810495">{{cite journal |vauthors=Adachi K, Ui M, Nojima H, Takada Y, Enatsu K |title=Isolated splenic peliosis presenting with giant splenomegaly and severe coagulopathy |journal=Am. J. Surg. |volume=202 |issue=2 |pages=e17–9 |date=August 2011 |pmid=21810495 |doi=10.1016/j.amjsurg.2010.10.002 |url=}}</ref>
| align="left" style="background:#F5F5F5;" |
* [[Lymphatic system|Lymphoid]] neoplasms
* [[Vascular]] neoplasms
| align="center" style="background:#F5F5F5;" |Very rare
| align="left" style="background:#F5F5F5;" |
* Positive family history
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |–
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |–
| align="center" style="background:#F5F5F5;" |–
| align="left" style="background:#F5F5F5;" |
* [[Lymphadenopathy]]
* [[Dyspnea]]
* Shoulder pain
* [[Constipation]]
* [[Cachexia]]
* [[Pleural effusion]]
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |Low [[iron]], low [[ferritin]]
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="left" style="background:#F5F5F5;" |
* [[Urine|Dark urine]]
| align="left" style="background:#F5F5F5;" |
* Different histopathologic features depends on the type of tumor
| align="left" style="background:#F5F5F5;" |
* Heterogeneous mass in the [[spleen]] on [[ultrasound]]
* Lymphomatous [[Nodule (medicine)|nodules]] and masses on [[Computed tomography|CT scan]]
| align="center" style="background:#F5F5F5;" |[[Biopsy]]
| align="left" style="background:#F5F5F5;" |
* [[Metastasis]] to [[liver]]
* Poor prognosis
|-
! colspan="2" align="center" style="background:#DCDCDC;" |[[Metastasis|Metastatic solid tumors]]<ref name="pmid24172780">{{cite journal |vauthors=Huprikar NA, Kurtz MT, Mount CA |title=Massive splenomegaly and lymphopenia: a unique case of obstructive shock |journal=BMJ Case Rep |volume=2013 |issue= |pages= |date=October 2013 |pmid=24172780 |pmc=3822246 |doi=10.1136/bcr-2013-201643 |url=}}</ref>
| align="left" style="background:#F5F5F5;" |
* [[Bone marrow]]<nowiki/>infiltration
* Ineffective [[hematopoiesis]]
* [[Immunity (medical)|Immune]] mediated
| align="center" style="background:#F5F5F5;" |Any age, more in adults
| align="left" style="background:#F5F5F5;" |
* Exposure to chemicals
* [[Radiation therapy|Radiation]]
* Pre-existent [[Hematology|blood disorders]]
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |±
| align="center" style="background:#F5F5F5;" |±
| align="left" style="background:#F5F5F5;" |
* [[Petechia|Petechiae]]
* [[Muscle weakness|Weakness]]
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |Low [[iron]], high [[ferritin]]
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="left" style="background:#F5F5F5;" |
* [[Urine|Dark urine]]
| align="left" style="background:#F5F5F5;" |
* Blast cells
| align="center" style="background:#F5F5F5;" |
| align="center" style="background:#F5F5F5;" |[[Biopsy]]
| align="left" style="background:#F5F5F5;" |
* [[Tumor lysis syndrome]]
* [[Infection]]
* [[CNS]] involvement
* [[Disseminated intravascular coagulation|DIC]]
|-
! colspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Disease
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Etiology
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Demography
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |History
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Fever
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Fatigue
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Weight
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Abdominal pain
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Bleeding
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |BP
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |JVP
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Jaundice
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Ascites
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Other
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |WBC
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Hb
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Plt
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Iron
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |LFT
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |PT/PTT
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |BUN/Cr
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |UA
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Histopathology
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Imaging
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Gold standard
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Associated findings
|-
! rowspan="9" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Infection
! rowspan="3" align="center" style="background:#DCDCDC;" |[[Virus|Viral]]
! align="center" style="background:#DCDCDC;" |[[Hepatitis]]<ref name="pmid23904062">{{cite journal |vauthors=Kumar KJ, Kumar HC, Manjunath VG, Anitha C, Mamatha S |title=Hepatitis A in children- clinical course, complications and laboratory profile |journal=Indian J Pediatr |volume=81 |issue=1 |pages=15–9 |date=January 2014 |pmid=23904062 |doi=10.1007/s12098-013-1114-8 |url=}}</ref>
| align="left" style="background:#F5F5F5;" |
* [[Infection]]
* [[Autoimmunity|Autoimmune]]
| align="center" style="background:#F5F5F5;" |
* Any age
| align="left" style="background:#F5F5F5;" |
* High risk behaviors
* Close contact
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="left" style="background:#F5F5F5;" |
* [[Lymphadenopathy]]
* [[Muscle weakness]]
* [[Joint swelling]]
* [[Focal neurologic signs]]
* Depends on etiology
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="left" style="background:#F5F5F5;" |
* [[Urine|Dark urine]]
* [[Hematuria]]
| align="left" style="background:#F5F5F5;" |
* [[Pancytopenia]]
| align="center" style="background:#F5F5F5;" |NA
| align="center" style="background:#F5F5F5;" |Clinical manifestation + lab tests
| align="left" style="background:#F5F5F5;" |
* Depends on etiology
* [[Encephalomyelitis]]
|-
! align="center" style="background:#DCDCDC;" |[[Mononucleosis|Infectious mononucleosis]]<ref name="pmid21191775">{{cite journal |vauthors=Gao LW, Xie ZD, Liu YY, Wang Y, Shen KL |title=Epidemiologic and clinical characteristics of infectious mononucleosis associated with Epstein-Barr virus infection in children in Beijing, China |journal=World J Pediatr |volume=7 |issue=1 |pages=45–9 |date=February 2011 |pmid=21191775 |doi=10.1007/s12519-011-0244-1 |url=}}</ref>
| align="left" style="background:#F5F5F5;" |
* [[Epstein Barr virus|EBV]]
| align="center" style="background:#F5F5F5;" |
* More common in children and young adults
| align="left" style="background:#F5F5F5;" |
* Close contact
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |–
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |–
| align="left" style="background:#F5F5F5;" |
* [[Pharyngitis|Sore throat]]
* Enlarged [[Tonsil|tonsils]]
* [[Lymphadenopathy]]
* [[Headache]]
* [[Maculopapular rash]] on the arms or trunk
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |NA
| align="center" style="background:#F5F5F5;" |NA
| align="center" style="background:#F5F5F5;" |Clinical manifestation + [[heterophile antibody test]]
| align="left" style="background:#F5F5F5;" |
* [[Splenic rupture]]
* [[Lymphocytosis]]
* [[Seizure|Seizures]]
|-
! align="center" style="background:#DCDCDC;" |[[Cytomegalovirus]]<ref name="pmid25308607">{{cite journal |vauthors=Smiechura M, Strużycka M, Konopka W |title=Congenital and acquired cytomegalovirus infection and hearing evaluation in children |journal=Otolaryngol Pol |volume=68 |issue=6 |pages=303–7 |date=2014 |pmid=25308607 |doi=10.1016/j.otpol.2014.04.003 |url=}}</ref>
| align="left" style="background:#F5F5F5;" |
* [[Cytomegalovirus infection|CMV]]
| align="center" style="background:#F5F5F5;" |
* More common in:
** Immunocompromised patients
** During pregnancy
| align="left" style="background:#F5F5F5;" |
* Close contact
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |–
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |–
| align="left" style="background:#F5F5F5;" |
* Exudative [[pharyngitis]]
* Symmetrical cervical [[Lymphadenopathy|adenopathy]]
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |NA
| align="center" style="background:#F5F5F5;" |NA
| align="center" style="background:#F5F5F5;" |[[Enzyme linked immunosorbent assay (ELISA)|ELISA]]
| align="center" style="background:#F5F5F5;" |
|-
! rowspan="3" align="center" style="background:#DCDCDC;" |[[Bacteria|Bacterial]]
! align="center" style="background:#DCDCDC;" |[[Salmonella]]<ref name="pmid26068006">{{cite journal |vauthors=Rosche KL, Aljasham AT, Kipfer JN, Piatkowski BT, Konjufca V |title=Infection with Salmonella enterica Serovar Typhimurium Leads to Increased Proportions of F4/80+ Red Pulp Macrophages and Decreased Proportions of B and T Lymphocytes in the Spleen |journal=PLoS ONE |volume=10 |issue=6 |pages=e0130092 |date=2015 |pmid=26068006 |pmc=4466801 |doi=10.1371/journal.pone.0130092 |url=}}</ref>
| align="left" style="background:#F5F5F5;" |
* [[Salmonella]]
| align="center" style="background:#F5F5F5;" |
* Any age
| align="center" style="background:#F5F5F5;" |
* Eating contaminated meat, eggs, or milk
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |–
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |–
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |–
| align="center" style="background:#F5F5F5;" |–
| align="center" style="background:#F5F5F5;" |
* Diarrhea
* Abdominal cramps
* Vomiting
* Dehydration
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |
* [[Oliguria]]
| align="center" style="background:#F5F5F5;" |NA
| align="center" style="background:#F5F5F5;" |NA
| align="center" style="background:#F5F5F5;" |Stool test
| align="center" style="background:#F5F5F5;" |
* Typhoid fever
* Reactive arthritis
* Irritable bowel syndrome
|-
! align="center" style="background:#DCDCDC;" |[[Brucella]]<ref name="pmid24983999">{{cite journal |vauthors=Roset MS, Ibañez AE, de Souza Filho JA, Spera JM, Minatel L, Oliveira SC, Giambartolomei GH, Cassataro J, Briones G |title=Brucella cyclic β-1,2-glucan plays a critical role in the induction of splenomegaly in mice |journal=PLoS ONE |volume=9 |issue=7 |pages=e101279 |date=2014 |pmid=24983999 |pmc=4077732 |doi=10.1371/journal.pone.0101279 |url=}}</ref>
| align="center" style="background:#F5F5F5;" |
* Brucella
| align="center" style="background:#F5F5F5;" |
* Any age
| align="center" style="background:#F5F5F5;" |
* Ingesting contaminated food such as unpasteurized milk products
* Direct contact with an infected animal
* Inhalation of aerosols
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |–
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |–
| align="center" style="background:#F5F5F5;" |
* Headache
* Vomiting
* Diarrhea
* Constipation
* Arthralgia
* Night sweats
* Anorexia
* Foul-smelling perspiration
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |
* [[Oliguria]]
| align="center" style="background:#F5F5F5;" |NA
| align="center" style="background:#F5F5F5;" |NA
| align="center" style="background:#F5F5F5;" |Blood culture
| align="center" style="background:#F5F5F5;" |
* Arthritis
* Epididymo-orchitis
* Spondylitis
* Neurobrucellosis
* Liver abscess formation
* Endocarditis
|-
! align="center" style="background:#DCDCDC;" |[[Tuberculosis]]<ref name="pmid27051579">{{cite journal |vauthors=Chandni R, Chandni R, Chandni R |title=Extra pulmonary tuberculosis presenting as fever with massive splenomegaly and pancytopenia |journal=IDCases |volume=4 |issue= |pages=20–2 |date=2016 |pmid=27051579 |pmc=4802818 |doi=10.1016/j.idcr.2016.02.005 |url=}}</ref>
| align="center" style="background:#F5F5F5;" |
* Mycobacterium tuberculosis
| align="center" style="background:#F5F5F5;" |
* Any age
* More common in developing countries and among immunocompromised patients
| align="center" style="background:#F5F5F5;" |
* Close contact
* HIV
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |–
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |–
| align="center" style="background:#F5F5F5;" |
* Chronic cough with blood-containing sputum
* Night sweats
* Anorexia
* Chest pain
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |
* [[Oliguria]]
| align="center" style="background:#F5F5F5;" |
* Acid-fast bacillus
| align="center" style="background:#F5F5F5;" |
* Cavity on chest x ray
| align="center" style="background:#F5F5F5;" |Identifying M. tuberculosis in a clinical sample
| align="center" style="background:#F5F5F5;" |
* Tuberculous meningitis
* Urogenital tuberculosis
* Pott disease
* Miliary tuberculosis
|-
! rowspan="2" align="center" style="background:#DCDCDC;" |[[Parasitism|Parasitic]]
! align="center" style="background:#DCDCDC;" |[[Malaria]]<ref name="pmid26612502">{{cite journal |vauthors=Sumbele IU, Bopda OS, Kimbi HK, Ning TR, Nkuo-Akenji T |title=Influence of Plasmodium gametocyte carriage on the prevalence of fever, splenomegaly and cardiovascular parameters in children less than 15 years in the Mount Cameroon area: cross sectional study |journal=BMC Infect. Dis. |volume=15 |issue= |pages=547 |date=November 2015 |pmid=26612502 |pmc=4661959 |doi=10.1186/s12879-015-1290-4 |url=}}</ref>
| align="center" style="background:#F5F5F5;" |
* Plasmodium
| align="center" style="background:#F5F5F5;" |
* Worldwide
* More common in tropical and subtropical regions
| align="center" style="background:#F5F5F5;" |
* Bitten by Anopheles mosquito
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |–
| align="center" style="background:#F5F5F5;" |
* Flu-like symptoms
* [[Headache]]
* [[Shivering]]
* [[Joint]] pain
* [[Vomiting]]
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |
* [[Hemoglobinuria]]
| align="center" style="background:#F5F5F5;" |
| align="center" style="background:#F5F5F5;" |NA
| align="center" style="background:#F5F5F5;" |
| align="center" style="background:#F5F5F5;" |
|-
! align="center" style="background:#DCDCDC;" |[[Visceral leishmaniasis|Kala-azar]]<ref name="pmid24850963">{{cite journal |vauthors=Sayyahfar S, Ansari S, Mohebali M, Behnam B |title=Visceral leishmaniasis without fever in an 11-month-old infant: a rare clinical feature of Kala-azar |journal=Korean J. Parasitol. |volume=52 |issue=2 |pages=189–91 |date=April 2014 |pmid=24850963 |pmc=4028457 |doi=10.3347/kjp.2014.52.2.189 |url=}}</ref>
| align="center" style="background:#F5F5F5;" |
* [[Leishmaniasis|Leishmania]]
| align="center" style="background:#F5F5F5;" |
* Any age
| align="center" style="background:#F5F5F5;" |
* Bitten by sandflies
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |
* Asymptomatic
* Tender [[spleen]]
* [[Hepatomegaly]]
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |
* [[Hemoglobinuria]]
| align="center" style="background:#F5F5F5;" |
* Visualization of the characteristic amastigote in smears or tissue
| align="center" style="background:#F5F5F5;" |NA
| align="center" style="background:#F5F5F5;" |Culture
| align="center" style="background:#F5F5F5;" |
* Could be fatal
|-
! colspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Disease
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Etiology
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Demography
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |History
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Fever
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Fatigue
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Weight
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Abdominal pain
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Bleeding
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |BP
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |JVP
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Jaundice
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Ascites
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Other
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |WBC
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Hb
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Plt
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Iron
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |LFT
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |PT/PTT
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |BUN/Cr
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |UA
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Histopathology
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Imaging
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Gold standard
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Associated findings
|-
! rowspan="4" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Inflammation
! colspan="2" align="center" style="background:#DCDCDC;" |[[Sarcoidosis]]<ref name="pmid25473783">{{cite journal |vauthors=Modaresi Esfeh J, Culver D, Plesec T, John B |title=Clinical presentation and protocol for management of hepatic sarcoidosis |journal=Expert Rev Gastroenterol Hepatol |volume=9 |issue=3 |pages=349–58 |date=March 2015 |pmid=25473783 |doi=10.1586/17474124.2015.958468 |url=}}</ref>
| align="left" style="background:#F5F5F5;" |
* [[Immunity (medical)|Immune]] mediated
* Unknown
| align="center" style="background:#F5F5F5;" |
* [[Autoimmune disease]]
* More common in young African American women
| align="left" style="background:#F5F5F5;" |
* Positive family history
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |–
| align="center" style="background:#F5F5F5;" |–
| align="left" style="background:#F5F5F5;" |
* Bilateral [[Hilar lymphadenopathy|hilar adenopathy]]
* [[Blurred vision|Blurry vision]]
* [[Dyspnea|Shortness of breath]]
* [[Cough]]
* [[Erythema nodosum]]
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |NA
| align="left" style="background:#F5F5F5;" |
* Bilateral [[Hilar lymphadenopathy|hilar adenopathy]] on [[Chest X-ray|chest x-ray]]
| align="center" style="background:#F5F5F5;" |Diagnosis of exclusion
| align="left" style="background:#F5F5F5;" |
* [[Interstitial lung disease]]
* Systemic [[Inflammation|inflammatory]]<nowiki/>disease
|-
! colspan="2" align="center" style="background:#DCDCDC;" |[[Serum sickness]]<ref name="pmid26677148">{{cite journal |vauthors=Chiong FJ, Loewenthal M, Boyle M, Attia J |title=Serum sickness-like reaction after influenza vaccination |journal=BMJ Case Rep |volume=2015 |issue= |pages= |date=December 2015 |pmid=26677148 |pmc=4691861 |doi=10.1136/bcr-2015-211917 |url=}}</ref>
| align="left" style="background:#F5F5F5;" |
* Immune complex [[hypersensitivity]] (type III) to certain medications
| align="center" style="background:#F5F5F5;" |
* Any age
| align="left" style="background:#F5F5F5;" |
* Consumption of certain medications
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |–
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |–
| align="center" style="background:#F5F5F5;" |–
| align="left" style="background:#F5F5F5;" |
* [[Rash|Rashes]]
* [[Itch|Itching]]
* Facial [[Edema|swelling]]
* [[Arthralgia]]
* [[Lymphadenopathy]]
* [[Dyspnea]]
| align="center" style="background:#F5F5F5;" |↓ or ↑
Eosinophilia
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |↑
| align="left" style="background:#F5F5F5;" |
* [[Proteinuria]]
* [[Hematuria]]
| align="left" style="background:#F5F5F5;" |
* [[Plasma cell|Plasma cells]] on peripheral blood smear
* Numerous histological changes including [[inflammation]] of arterial wall or [[fibrosis]]
| align="center" style="background:#F5F5F5;" |NA
| align="center" style="background:#F5F5F5;" |Clinical manifestation + recent medication consumption
| align="left" style="background:#F5F5F5;" |
* [[Glomerular disease|Glomerulonephritis]]
* [[Shock]]
|-
! colspan="2" align="center" style="background:#DCDCDC;" |[[Systemic lupus erythematosus]]<ref name="pmid24461385">{{cite journal |vauthors=Yu C, Gershwin ME, Chang C |title=Diagnostic criteria for systemic lupus erythematosus: a critical review |journal=J. Autoimmun. |volume=48-49 |issue= |pages=10–3 |date=2014 |pmid=24461385 |doi=10.1016/j.jaut.2014.01.004 |url=}}</ref>
| align="left" style="background:#F5F5F5;" |
* Immune mediated [[Bone marrow suppression|bone marrow failure]]
| align="center" style="background:#F5F5F5;" |
* More common in young females
| align="left" style="background:#F5F5F5;" |
* Positive family history
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |Nl to ↓
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="left" style="background:#F5F5F5;" |
* [[Rash|Skin rash]]
* [[Oral ulcer|Mouth ulcers]]
* [[Chest pain]]
* [[Lymphadenopathy]]
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="left" style="background:#F5F5F5;" |
* [[Hemoglobinuria]]
* [[Proteinuria]]
| align="left" style="background:#F5F5F5;" |
* Hypocellular [[bone marrow]]
| align="center" style="background:#F5F5F5;" |
| align="center" style="background:#F5F5F5;" |Clinical findings + laboratory studies
| align="left" style="background:#F5F5F5;" |
* Multi organ damage
|-
! colspan="2" align="center" style="background:#DCDCDC;" |[[Felty's syndrome|Felty syndrome]]<ref name="pmid24472276">{{cite journal |vauthors=Huang T, Liu M, Xu G |title=Felty's syndrome with hyperthyroidism: a case report and literature review |journal=Int J Rheum Dis |volume=17 |issue=1 |pages=122–4 |date=January 2014 |pmid=24472276 |doi=10.1111/1756-185X.12117 |url=}}</ref>
| align="left" style="background:#F5F5F5;" |
* Immune mediated [[Bone marrow suppression|bone marrow failure]]
| align="center" style="background:#F5F5F5;" |
* Rare [[autoimmune disease]]
* More common in females 50-70 years old
| align="left" style="background:#F5F5F5;" |
* History of [[rheumatoid arthritis]]
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |Nl to ↓
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="left" style="background:#F5F5F5;" |
* [[Pallor]]
* [[Hyperpigmentation|Skin hyperpigmentation]]
* Painful, stiff, and swollen [[Joint|joints]]
* [[Keratoconjunctivitis sicca]]
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="left" style="background:#F5F5F5;" |
* Hypocellular [[bone marrow]]
| align="center" style="background:#F5F5F5;" |
| align="center" style="background:#F5F5F5;" |Clinical findings + laboratory studies
| align="left" style="background:#F5F5F5;" |
* [[Rheumatoid arthritis]]
* [[Infection|Infections]]
|-
! rowspan="4" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Infiltrative
! colspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Disease
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Etiology
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Demography
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |History
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Fever
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Fatigue
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Weight
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Abdominal pain
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Bleeding
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |BP
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |JVP
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Jaundice
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Ascites
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Other
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |WBC
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Hb
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Plt
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Iron
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |LFT
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |PT/PTT
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |BUN/Cr
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |UA
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Histopathology
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Imaging
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Gold standard
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Associated findings
|-
! colspan="2" align="center" style="background:#DCDCDC;" |[[Gaucher's disease|Gaucher disease]]<ref name="pmid23510067">{{cite journal |vauthors=Ayto R, Hughes DA |title=Gaucher disease and myeloma |journal=Crit Rev Oncog |volume=18 |issue=3 |pages=247–68 |date=2013 |pmid=23510067 |doi= |url=}}</ref>
| align="left" style="background:#F5F5F5;" |
* Accumulatio<nowiki/>n of [[glucocerebroside]]
| align="center" style="background:#F5F5F5;" |
* [[Autosomal recessive]] hereditary deficiency of the enzyme [[glucocerebrosidase]]
* More in Ashkenazi Jews
| align="left" style="background:#F5F5F5;" |
* Positive family history
| align="center" style="background:#F5F5F5;" | -
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |Nl to ↓
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="left" style="background:#F5F5F5;" |
* Painful [[bone]] lesions
* [[Lymphadenopathy]]
* Yellowish-brown [[Human skin color|skin pigmentation]]
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="left" style="background:#F5F5F5;" |
* [[Proteinuria]]
* [[Hematuria]]
| align="left" style="background:#F5F5F5;" |
* Hypocellular [[bone marrow]]
| align="center" style="background:#F5F5F5;" |NA
| align="center" style="background:#F5F5F5;" |[[Enzyme]] testing
| align="left" style="background:#F5F5F5;" |
* The most common of the [[Lysosomal storage disease|lysosomal storage diseases]]
* Severe neurological complications
* [[Infection|Infections]]
* [[Osteoporosis]]
|-
! colspan="2" align="center" style="background:#DCDCDC;" |[[Niemann-Pick disease]]<ref name="pmid23622394">{{cite journal |vauthors=Vanier MT |title=Niemann-Pick diseases |journal=Handb Clin Neurol |volume=113 |issue= |pages=1717–21 |date=2013 |pmid=23622394 |doi=10.1016/B978-0-444-59565-2.00041-1 |url=}}</ref>
| align="left" style="background:#F5F5F5;" |
* Mutations in the ''[[Sphingomyelin phosphodiesterase 1|SMPD1]]'' gene
* Deficiency in the activity of the lysosomal enzyme acid [[sphingomyelinase]]
* Accumulation of [[sphingomyelin]]
| align="center" style="background:#F5F5F5;" |
* [[Autosomal recessive]] [[lysosomal storage disease]]
* More common in Ashkenazi Jews
| align="left" style="background:#F5F5F5;" |
* Positive family history
| align="center" style="background:#F5F5F5;" | -
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |Nl to ↓
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="left" style="background:#F5F5F5;" |
* [[Ataxia|Unsteady gait]]
* Slurred [[speech]]
* [[Dysphagia]]
* [[Dystonia]]
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="left" style="background:#F5F5F5;" |
* [[Proteinuria]]
* [[Hematuria]]
| align="left" style="background:#F5F5F5;" |
* Hypocellular [[bone marrow]]
| align="center" style="background:#F5F5F5;" |NA
| align="center" style="background:#F5F5F5;" |[[Genetic testing]]
| align="left" style="background:#F5F5F5;" |
* [[CNS]] involvement
* [[Supranuclear ocular palsy|Supranuclear gaze palsy]]
* [[Dementia]]
* [[Seizure]]
* Gelastic [[cataplexy]]
* Pulmonary [[Infection|infections]]
* [[Splenic rupture]]
* [[Coronary arteries|Coronary artery]] or [[valvular heart disease]]
|-
! colspan="2" align="center" style="background:#DCDCDC;" |[[Langerhans cell histiocytosis]]<ref name="pmid25281259">{{cite journal |vauthors=DiCaprio MR, Roberts TT |title=Diagnosis and management of langerhans cell histiocytosis |journal=J Am Acad Orthop Surg |volume=22 |issue=10 |pages=643–52 |date=October 2014 |pmid=25281259 |doi=10.5435/JAAOS-22-10-643 |url=}}</ref>
| align="center" style="background:#F5F5F5;" |
* Clonal proliferation of Langerhans cells
| align="center" style="background:#F5F5F5;" |
* Any age
* More common in children between 5-10 years old
* Boys>girls
| align="center" style="background:#F5F5F5;" | -
| align="center" style="background:#F5F5F5;" | -
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | -
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | -
| align="center" style="background:#F5F5F5;" |
* Painful bone swelling
* Scaly erythematous lesions
* [[Lymphadenopathy]]
* [[Cough]]
* [[Dyspnea]]
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |
* [[Proteinuria]]
* [[Hematuria]]
| align="center" style="background:#F5F5F5;" |
* Birbeck [[granules]] on electron microscopy
| align="center" style="background:#F5F5F5;" |
* Osteolytic lesions on imaging
* Lung nodules on imaging
| align="center" style="background:#F5F5F5;" |Tissue biopsy
| align="center" style="background:#F5F5F5;" |
* [[Diabetes insipidus]]
|-
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Category
! colspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Disease
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Etiology
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Demography
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |History
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Fever
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Fatigue
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Weight
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Abdominal pain
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Bleeding
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |BP
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |JVP
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Jaundice
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Ascites
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Other
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |WBC
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Hb
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Plt
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Iron
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |LFT
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |PT/PTT
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |BUN/Cr
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |UA
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Histopathology
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Imaging
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Gold standard
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Associated findings
|}
==Diagnosis==


==Treatment==
==Treatment==
If the splenomegaly underlies hypersplenism, a [[splenectomy]] is indicated and will correct the problem. After splenectomy, however, patients have an increased risk for infectious diseases.
If the splenomegaly underlies hypersplenism, a [[splenectomy]] is indicated and it will correct the problem. After [[splenectomy]], patients have an increased risk for infectious diseases. After [[splenectomy]], patients should be [[vaccine|vaccinated]] against ''[[Haemophilus influenzae]]'' and ''[[Streptococcus pneumoniae]]''. They should receive annual [[influenza vaccination]]. Long-term [[prophylaxis|prophylactic]] [[antibiotic]] should be given.
 
After splenectomy, patients should be [[vaccine|vaccinated]] against ''[[Haemophilus influenzae]]'' and ''[[Streptococcus pneumoniae]]''. They should receive annual [[influenza vaccination]]s. Long-term [[prophylaxis|prophylactic]] [[antibiotic]]s should be given.
 
==Related chapters==
* [[sign (medicine)]]
* [[Hepatosplenomegaly]]
 
==Resources==
* [http://www.patient.co.uk/ PatientPlus] [http://www.patient.co.uk/showdoc/40001069/ Splenomegaly and hypersplenism]
* {{MerckManual|11|141|b}} (Hypersplenism)


==References==
==References==
{{reflist|2}}
{{Reflist|2}}
 
{{Phakomatoses and other congenital malformations not elsewhere classified}}
{{Symptoms and signs}}
 
[[de:Splenomegalie]]
[[fr:Splénomégalie]]
[[it:Splenomegalia]]
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[[pl:Splenomegalia]]
[[pt:Esplenomegália]]
[[ru:Спленомегалия]]
 
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[[Category:Medical signs]]
[[Category:Signs and symptoms]]
[[Category:Physical examination]]


[[Category:Hematology]]
[[Category:Hematology]]
[[Category:Gastroenterology]]
[[Category:Pediatrics]]
[[Category:Primary care]]
[[Category:Immunology]]

Latest revision as of 18:38, 3 February 2019


For the patient information page for this topic, click here

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sadaf Sharfaei M.D.[2], Gichoya Judy Wawira [3],

Synonyms and keywords: Spleen enlargement; enlarged spleen; spleen swelling

Overview

Pathophysiology

Causes

The causes of splenomegaly vary widely and range from increased splenic function (such as hemoglobinopathies), splenic congestion due to abnormal blood flow (such as venous obstruction), and splenic infiltration (such as storage disorders and malignancies).

Causes by Pathogenesis

Mechanism Pathogenesis Example
Increased function Removal of defective RBCs
Immune hyperplasia Response to infection (viral, bacterial, fungal, parasitic)
Disordered immunoregulation
Drug reactions
Extramedullary hematopoiesis
Abnormal blood flow Organ Failure
Vascular
Infections
Infiltration Metabolic diseases
Benign and malignant infiltrations

Differentiating Splenomegaly from Other Diseases

Category Disease Etiology Clinical manifestations Para−clinical findings Gold standard Associated findings
Demography History Symptoms Signs Lab Findings Imaging
Fever Fatigue Weight Abdominal pain Bleeding BP JVP Jaundice Ascites Other CBC Iron LFT PT/PTT BUN/Cr UA Histopathology
WBC Hb Plt
Congestive Cirrhosis[1] Any age, more common in elderly + ↑↓ + + Nl + + Nl Liver biopsy
Heart failure[2] Elderly + ↑↓ ± + Nl Nl NA Echocardiography
Thrombosis of portal, hepatic, or splenic veins[3] Any age + + + + Nl ± + Nl NA Doppler ultrasonography
Malignancy Lymphoma[4] Any age, most common malignant splenic tumor + + + + Nl Nl + High ferritin Nl Lymph node biopsy
Leukemia[5] Elderly, male>female + + + + Nl Nl ± + High ferritin Nl
  • Leukemic blasts
  • Leukoerythroblastic features
  • Giant platelets
NA Bone marrow examination + clinical manifestation
Polycythemia Vera[6] Mean age >60 years old
  • Positive family history
+ Nl + Nl Nl Nl to ↑ Nl to ↑ High ferritin Nl Nl Nl Nl
  • Elevated normochromic, normocytic RBCs
  • Thrombocytosis
  • Rarely immature cells
  • Leukoerythroblastic picture
NA WHO criteria for PV
Disease Etiology Demography History Fever Fatigue Weight loss Abdominal pain Bleeding BP JVP Jaundice Ascites Other WBC Hb Plt Iron LFT PT/PTT BUN/Cr UA Histopathology Imaging Gold standard Associated findings
Multiple myeloma[7] Any age, more common in adults + + + + Nl Nl + High ferritin Nl
  • Blast cells
Bone marrow examination
Essential thrombocythemia[8]
  • Acquired mutation of JAK2, CALR, or MPL
Mean age >60 years old, female > male ± + Nl + + Nl Nl ↑↑ Nl Nl Nl Nl Nl Bone marrow biopsy
Primary myelofibrosis[9] Mean age >60 years old, male> female + Nl + + Nl Nl + ↑/↓ Low iron Nl Nl Bone marrow biopsy
Primary splenic tumors[10] Very rare
  • Positive family history
+ + + Nl Nl Low iron, low ferritin
  • Different histopathologic features depends on the type of tumor
Biopsy
Metastatic solid tumors[11] Any age, more in adults + + + + Nl ± ± Low iron, high ferritin
  • Blast cells
Biopsy
Disease Etiology Demography History Fever Fatigue Weight Abdominal pain Bleeding BP JVP Jaundice Ascites Other WBC Hb Plt Iron LFT PT/PTT BUN/Cr UA Histopathology Imaging Gold standard Associated findings
Infection Viral Hepatitis[12]
  • Any age
  • High risk behaviors
  • Close contact
+ + + + Nl Nl + + Nl NA Clinical manifestation + lab tests
Infectious mononucleosis[13]
  • More common in children and young adults
  • Close contact
+ + Nl + Nl Nl + Nl Nl Nl Nl Nl NA NA Clinical manifestation + heterophile antibody test
Cytomegalovirus[14]
  • More common in:
    • Immunocompromised patients
    • During pregnancy
  • Close contact
+ + Nl + Nl Nl + Nl Nl Nl Nl Nl NA NA ELISA
Bacterial Salmonella[15]
  • Any age
  • Eating contaminated meat, eggs, or milk
+ Nl + Nl
  • Diarrhea
  • Abdominal cramps
  • Vomiting
  • Dehydration
Nl Nl Nl Nl NA NA Stool test
  • Typhoid fever
  • Reactive arthritis
  • Irritable bowel syndrome
Brucella[16]
  • Brucella
  • Any age
  • Ingesting contaminated food such as unpasteurized milk products
  • Direct contact with an infected animal
  • Inhalation of aerosols
+ + Nl + Nl +
  • Headache
  • Vomiting
  • Diarrhea
  • Constipation
  • Arthralgia
  • Night sweats
  • Anorexia
  • Foul-smelling perspiration
Nl Nl Nl Nl NA NA Blood culture
  • Arthritis
  • Epididymo-orchitis
  • Spondylitis
  • Neurobrucellosis
  • Liver abscess formation
  • Endocarditis
Tuberculosis[17]
  • Mycobacterium tuberculosis
  • Any age
  • More common in developing countries and among immunocompromised patients
  • Close contact
  • HIV
+ + + Nl +
  • Chronic cough with blood-containing sputum
  • Night sweats
  • Anorexia
  • Chest pain
Nl Nl
  • Acid-fast bacillus
  • Cavity on chest x ray
Identifying M. tuberculosis in a clinical sample
  • Tuberculous meningitis
  • Urogenital tuberculosis
  • Pott disease
  • Miliary tuberculosis
Parasitic Malaria[18]
  • Plasmodium
  • Worldwide
  • More common in tropical and subtropical regions
  • Bitten by Anopheles mosquito
+ + Nl + + Nl + Nl Nl NA
Kala-azar[19]
  • Any age
  • Bitten by sandflies
+ + + + Nl + + Nl
  • Visualization of the characteristic amastigote in smears or tissue
NA Culture
  • Could be fatal
Disease Etiology Demography History Fever Fatigue Weight Abdominal pain Bleeding BP JVP Jaundice Ascites Other WBC Hb Plt Iron LFT PT/PTT BUN/Cr UA Histopathology Imaging Gold standard Associated findings
Inflammation Sarcoidosis[20]
  • Positive family history
+ + + + Nl Nl Nl Nl Nl Nl Nl NA Diagnosis of exclusion
Serum sickness[21]
  • Any age
  • Consumption of certain medications
+ + Nl + Nl ↓ or ↑

Eosinophilia

Nl Nl Nl NA Clinical manifestation + recent medication consumption
Systemic lupus erythematosus[22]
  • More common in young females
  • Positive family history
+ + + + Nl to ↓ Nl + + Clinical findings + laboratory studies
  • Multi organ damage
Felty syndrome[23] + + + + Nl to ↓ Nl + + Nl Nl Nl Nl Nl Clinical findings + laboratory studies
Infiltrative Disease Etiology Demography History Fever Fatigue Weight Abdominal pain Bleeding BP JVP Jaundice Ascites Other WBC Hb Plt Iron LFT PT/PTT BUN/Cr UA Histopathology Imaging Gold standard Associated findings
Gaucher disease[24]
  • Positive family history
- + + + Nl to ↓ Nl + + Nl Nl NA Enzyme testing
Niemann-Pick disease[25]
  • Positive family history
- + + + Nl to ↓ Nl + + Nl NA Genetic testing
Langerhans cell histiocytosis[26]
  • Clonal proliferation of Langerhans cells
  • Any age
  • More common in children between 5-10 years old
  • Boys>girls
- - + + - Nl Nl + - Nl
  • Osteolytic lesions on imaging
  • Lung nodules on imaging
Tissue biopsy
Category Disease Etiology Demography History Fever Fatigue Weight Abdominal pain Bleeding BP JVP Jaundice Ascites Other WBC Hb Plt Iron LFT PT/PTT BUN/Cr UA Histopathology Imaging Gold standard Associated findings

Diagnosis

Treatment

If the splenomegaly underlies hypersplenism, a splenectomy is indicated and it will correct the problem. After splenectomy, patients have an increased risk for infectious diseases. After splenectomy, patients should be vaccinated against Haemophilus influenzae and Streptococcus pneumoniae. They should receive annual influenza vaccination. Long-term prophylactic antibiotic should be given.

References

  1. Wu Z, Zhou J, Pankaj P, Peng B (December 2012). "Laparoscopic and open splenectomy for splenomegaly secondary to liver cirrhosis: an evaluation of immunity". Surg Endosc. 26 (12): 3557–64. doi:10.1007/s00464-012-2366-5. PMID 22710653.
  2. Gedela M, Khan M, Jonsson O (September 2015). "Heart Failure". S D Med. 68 (9): 403–5, 407–9. PMID 26489162.
  3. Ferri PM, Ferreira AR, Fagundes ED, Liu SM, Roquete ML, Penna FJ (2012). "Portal vein thrombosis in children and adolescents: 20 years experience of a pediatric hepatology reference center". Arq Gastroenterol. 49 (1): 69–76. PMID 22481689.
  4. Ishibashi N, Maebayashi T, Aizawa T, Sakaguchi M, Abe O, Saito T, Tanaka Y (May 2015). "Myelosuppression toxicity of palliative splenic irradiation in myelofibrosis and malignant lymphoma". Hematology. 20 (4): 203–7. doi:10.1179/1607845414Y.0000000192. PMID 25131182.
  5. Quest GR, Johnston JB (December 2015). "Clinical features and diagnosis of hairy cell leukemia". Best Pract Res Clin Haematol. 28 (4): 180–92. doi:10.1016/j.beha.2015.10.017. PMID 26614896.
  6. Chou YS, Gau JP, Yu YB, Pai JT, Hsiao LT, Liu JH, Hong YC, Liu CY, Yang CF, Chen PM, Chiou TJ, Tzeng CH (March 2013). "Leukocytosis in polycythemia vera and splenomegaly in essential thrombocythemia are independent risk factors for hemorrhage". Eur. J. Haematol. 90 (3): 228–36. doi:10.1111/ejh.12064. PMID 23281576.
  7. Grieco A, Manna R, Mancini R, Gambassi G (April 1988). "Massive hepatomegaly following splenectomy for myeloid metaplasia". Am. J. Med. 84 (4): 797. PMID 3400674.
  8. Tefferi A, Barbui T (February 2015). "Polycythemia vera and essential thrombocythemia: 2015 update on diagnosis, risk-stratification and management". Am. J. Hematol. 90 (2): 162–73. doi:10.1002/ajh.23895. PMID 25611051.
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