Thrombocytopenia differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Farbod Zahedi Tajrishi, M.D.

Overview

Thrombocytopenia has a broad range of potential causes. While a good history and physical examination can be helpful to diagnose some of these causes such as drug-induced thrombocytopenia, they usually don't suffice and further evaluation is often needed. There are also some useful points that may guide the physician to an appropriate diagnosis. For example, asymptomatic, isolated thrombocytopenia most probably suggests ITP, while thrombocytopenia in critically ill, hospitalized patients is usually suggestive of iatrogenic causes (eg. dilution), platelet consumption, bone marrow suppression from infection/sepsis, or even drug-induced thrombocytopenia. One should consider however, that a wide variety of other conditions such as autoimmune disorders, nutrient deficiencies, thrombotic microangiopathies could all as well cause thrombocytopenia.

Differential Diagnosis

Category	Disease	History and symptoms	Physical exam	Laboratory findings			Pathology	Other specifics
				WBC changes	RBC/hemoglobinchanges	other findings
Cardiovascular	endocarditis	Rigors Fevers Chills Anorexia Malaise Fatigue Weight loss Embolic symptoms	Skin Petechiae Splinter hemorrhages Osler's nodes Janeway lesions Oral Cavity Periodontal abnormalities Eyes Conjunctival hemorrhage Roth's spots in the retina Ear Nose and Throat Bobbing of the uvula may be present among patients with new onset aortic regurgitation. Cardiovascular Heart murmurs Wide pulse pressure Lungs Rales as a result of heart failure Abdomen Abdominal pain and reduced bowel sounds due to mesenteric embolization or ileus Splenomegaly Flank pain as a result of an embolus to the kidney. Neurologic Septic emboli may result in stroke and focal neurologic findings Seizures Intracranial hemorrhage	↑	-	↑ ESR ↑ RF, BUN and Cr may also be present	Pathological Criteria Microorganisms demonstrated by culture or histological examination of a vegetation, a vegetation that has embolized, or an intracardiac abscess specimen OR Pathological lesions; vegetation or intracardiac abscess confirmed by histological examination showing active endocarditis	Diagnostic criteria: Criteria for Rejecting the Diagnosis Firm alternate diagnosis to infective endocarditis Resolution of infective endocarditis syndrome in under 4 days on antibiotics Does not meet the criteria below: Criteria for Definitive Endocarditis The Duke Clinical Criteria for definitive infective endocarditis require either: Two major criteria OR One major and three minor criteria OR Five minor criteria Major Criteria 1. Positive Blood Culture for Infective Endocarditis A. Typical microorganism consistent with infective endocarditis from 2 separate blood cultures, as noted below: ☑ Viridans streptococci, Streptococcus bovis, or ☑ HACEK group, or ☑ Community-acquired Staphylococcus aureus or enterococci, in the absence of a primary focus OR B. Microorganisms consistent with infective endocarditis from persistently positive blood cultures defined as: ☑ 2 positive cultures of blood samples drawn >12 hours apart, or ☑ All of 3 or a majority of 4 separate cultures of blood (with first and last sample drawn 1 hour apart) 2. Evidence of endocardial involvement Positive echocardiogram for infective endocarditis defined as: ☑ Oscillating intracardiac mass on valve or supporting structures, in the path of regurgitant jets, or ☑ On implanted material in the absence of an alternative anatomic explanation, or ☑ Abscess, or ☑ New partial dehiscence of prosthetic valve OR ☑ New valvular regurgitation (worsening or changing of preexisting murmur not sufficient) Minor criteria: ☑ Predisposition: predisposing heart condition or intravenous drug use ☑ Fever: temperature > 38.0° C (100.4° F) ☑ Vascular phenomena: major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, and Janeway lesions ☑ Immunologic phenomena: glomerulonephritis, Osler's nodes, Roth spots, and rheumatoid factor ☑ Microbiological evidence: positive blood culture but does not meet a major criterion as noted above (see footnote) or serological evidence of active infection with organism consistent with infectious endocarditis ☑ Echocardiographic findings: consistent with infectious endocarditis but do not meet a major criterion as noted above Footnote: It should be noted that the criteria exclude single positive cultures for coagulase-negative staphylococci, diphtheroids, and organisms that do not commonly cause endocarditis.
	pulmonary embolism	Dyspnea Pleuritic chest pain Fainting Cough Substernal chest pain Hemoptysis Wheezing Cyanosis Fever				↑ D-dimer		positive findings on CT-angiogram
Chemical/poisoning	Strontium-89
	zinc
Dermatologic	Cholesterol embolism	General: fever, myalgia weight loss Organ-dependent: Lower extremities livedo reticularis Kidney symptoms of renal failure or nephrotic syndrome Gastroinstestinal reduced appetite nausea and vomiting nonspecific abdominal pain gastrointestinal hemorrhage Central nervous system stroke-like symptoms headache amaurosis fugax paraparesis cauda equina syndrome loss of control over the bladder, rectum and skin sensation around the anus mononeuropathy.		↑/-	↓/-	↑ BUN and Cr in case of renal failure ↑ CPK and troponin in case of myocardial infarction OB+ in case of mesenteric ischemia Peripheral eosinophilia Urinary eosinophilia in patients with cholesterol-renal disease Hypocomplementemia ↑ ESR	-
	Griscelli syndrome	characteristic hypopigmentation	-	-	-
Ear Nose Throat	Alport syndrome	Renal Auditory Ocular Hematuria Proteinuria Hypertension Reduced Creatinine Clearance Early Tinnitus Vertigo High-Frequency Progressive Bilateral Hearing Loss Refractory Error Posterior Polymorphous Dystrophy Arcus Glaucoma Vogt’s White Limbal Girdle Band Keratopathy Lenticonus Spherophakia Cataracts Lens Coloboma Anterior Lenticonus Flecked Retinopathy of the Macula or Periphery	Vital signs Systemic hypertension may be present Eyes Fundoscopy shows: Cataracts Subcapsular posterior lens opacities Lenticonus Retinal flecks (dot-and-fleck retinopathy) Posterior polymorphous corneal dystrophy/corneal epithelial erosions Ears Sensorineural hearing loss Extremities Peripheral edema Leiomyomatosis Miscellaneous Anasarca	-	-	Urinalysis Microscopic hematuria Pyuria Red cell casts Cylindrical casts Proteinuria Electrolytes and Metabolic ↑ BUN ↑ Cr Hypoalbuminemia	-	Diagnostic criteria: Mandatory Criterion Persistent Hematuria Optional Criteria Presence of at Least 1 of 4: Positive Family History of Alport's Syndrome Characteristic Clinical Features Characteristic Pathology Findings Genetic Testing The equivocal or non-characteristic finding of any of the above prompts further work-up until the diagnosis is made or rejected.
	Arias oculootoradial syndrome
	Epstein's syndrome	epistaxis Gastrointestinal bleeding Hypertension (due to kidney disease) Deafness	-	-	-	-	-	-
	Fechtner syndrome
Endocrine	Immunodysregulation polyendocrinopathy and enteropathy, X-linked
Gastroenterologic	Dibasic aminoaciduria type 2
	liver failure
	Niemann-Pick disease type b
	portal hypertension
Genetic	Aicardi-Goutieres syndrome
	Chediak-Higashi disease
	complement factor H deficiency
	Fanconi anaemia
	Fechtner syndrome
	holocarboxylase synthase deficiency
	iminodipeptiduria
	Jacobsen syndrome
	MELAS
	Omenn syndrome
	TAR syndrome
	X-linked hyperimmunoglobulin M syndrome
Hematologic	Acquired pure megakaryocytic aplasia
	aplastic anemia			+ / ↓	+ / ↓
	Bernard-Soulier syndrome
	congenital amegakaryocytic thrombocytopenia (CAMT)
	disseminated intravascular coagulation
	Epstein's syndrome
	familial histiocytic reticulosis
	Gasser syndrome
	GATA1-related cytopenia
	Glanzmann's thrombasthenia
	grey platelet syndrome
	hemolytic uremic syndrome
	histiocytosis X
	hypersplenism
	idiopathic thrombocytopenic purpura
	Jacobsen syndrome
	Kasabach-Merritt syndrome
	May-Hegglin anomaly
	Moschcowitz syndrome
	myelodysplastic syndrome
	myelofibrosis
	neonatal alloimmune thrombocytopenia
	pancytopenia
	Paris-Trousseau thrombocytopenia
	paroxysmal nocturnal hemoglobinuria
	post-transfusion purpura
	radial aplasia-thrombocytopenia syndrome
	Sebastian platelet syndrome
	Shwachman-Diamond syndrome
	thrombotic thrombocytopenic purpura
	Von Willebrand disease, platelet type
	Werlhof disease
	Wiskott-Aldrich syndrome
Iatrogenic	Cardiac bypass
	chemotherapy
	intra-aortic balloon pump placement
	massive blood transfusion
	radiation therapy
Infectious diseases	Congenital syphilis
	cytomegalovirus
	Dengue fever
	ehrlichiosis
	Epstein-Barr virus
	hantavirus
	hepatitis C
	HIV
	human granulocytic ehrlichiosis
	human monocytotropic ehrlichiosis
	lassa fever
	leptospirosis
	malaria
	measles
	mumps
	mycoplasma pneumonia
	Oklahoma tick fever
	parvovirus
	Q fever
	rubella
	sepsis
	tick-borne encephalitis
	toxic shock syndrome (staphylococcal)
	varicella
	visceral leishmaniasis
Nutritional/Metabolic	folate deficiency
	Gaucher disease
	holocarboxylase synthase deficiency
	iminodipeptiduria
	iron deficiency
	isovaleric acidaemia
	methylmalonic aciduria type 2
	platelet glycoprotein 4 deficiency
	platelet glycoprotein Ib deficiency
	prolidase deficiency
	propionyl-CoA carboxylase deficiency
	sea blue histiocytosis
	sitosterolemia
	vitamin B12 deficiency
Obstetric/Gynecologic	Eclampsia, pre-eclampsia
	HELLP syndrome
Oncologic	Acute lymphoblastic leukemia
	acute myeloid leukemia
	acute promyelocytic leukemia
	chronic lymphocytic leukaemia
	chronic myeloid leukaemia
	hairy cell leukaemia
	hepatosplenic T-cell lymphoma
	lymphoma
	myeloma
	Non-Hodgkins lymphoma
	paraneoplastic syndrome
Overdose/Toxicity	ethanol
	arsenic trioxide
Pulmonary	Acute respiratory distress syndrome
Renal/Electrolyte	hemolytic uremic syndrome
Rheumatology/Immunology/Allergy	Anticardiolipin syndrome
	antiphospholipid syndrome
	autoimmune lymphoproliferative syndrome type 1
	autoimmune lymphoproliferative syndrome type 2
	complement factor H deficiency
	Evans syndrome
	immunodysregulation polyendocrinopathy and enteropathy, X-linked
	macrophage-activation syndrome
	neonatal alloimmune thrombocytopenia
	systemic lupus erythematosus
Miscellaneous	Snakebites