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.
	MYH9-associated disorders	Epstein's syndrome	epistaxis Gastrointestinal bleeding Hypertension (due to kidney disease) Deafness NO cataract	-	-	-	No leukocyte inclusion bodies	-	giant platelets on PBS
		Fechtner syndrome	Same as Alport syndrome: sensorineural deafness ocular abnormalities such as cataract nephritis				characteristic leukocyte inclusion bodies + impaired liver function and hypercholesterolemia in some cases	-
		May–Hegglin Anomaly					characteristic leukocyte inclusion bodies +	-
		Sebastian Syndrome	same hematologic changes as those in the Fechtner syndrome but without the manifestations of Alport syndrome.				characteristic leukocyte inclusion bodies +	-
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	Early symptoms: Muscle weakness Muscle pain Recurrent headaches Loss of appetite Vomiting Seizures Abdominal pain fatigue Difficulty breathing Eye Vision abnormalities Ear Hearing loss Extremeties Myoclonus Neurologic Stroke-like episodes beginning before age 40 hemiparesis Altered consciousness Ataxia Seizures Dementia			-	lactic acidosis	-
		Omenn syndrome
		TAR syndrome	Absent radius
		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