Thrombocytopenia differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-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.

Thrombocytopenia Differential Diagnosis

Differentiating the diseases that can cause thrombocytopenia:

Condition		Mechanism	Mechanism			Inherited	Acquried	Clinical manifestations										Para−clinical findings										Gold standard	Associated findings
								Age range	History	Symptoms				Signs
																		Lab Findings									Imaging
										Fever	Rash	Bleeding	BP	Splenomegaly	Jaundice	Other	CBC			PBS	Bone marrow exam	PT	PTT	BT	UA
			Platelet destruction in bloodstream	Platelet destruction in spleen/liver	Plt												HB	WBC
Bone marrow disorders	Myelodysplastic syndromes		+
	Aplastic anemia		+
	Acute leukemia		+
	Paroxysmal nocturnal hemoglobinuria (PNH)		+
Thrombotic microangiopathy (TMA)	Thrombotic thrombocytopenic purpura (TTP)			+
	Hemolytic uremic syndrome (HUS)			+
	DIC		+
Congenital platelet disorders	MYH-9 related disorders
	Bernard-Soulier syndrome
	Gray platelet syndrome
	Wiskott-Aldrich syndrome
	Thrombocytopenia with absent radius (TAR) syndrome
	Alport syndrome
	Von Willebrand disease
Nutrient deficiencies	Folate, vitamin B12, copper		+
Condition		Mechanism	Decreased platelet production	Platelet destruction in bloodstream	Platelet destruction in spleen/liver	Inherited	Acquried	Age range	History	Severity	Fever	Rash	Bleeding	BP	Splenomegaly	Jaundice	Other signs	Plt	HB	WBC	PBS	Bone marrow exam	PT	PTT	BT	UA	Imaging	Gold standard	Associated findings
Immune thrombocytopenia		Antibody-mediated platelet destruction		+
Systemic lupus erythematosus (SLE)				+
Antiphospholipid syndrome (APS)		Autoantibody-mediated syndrome		+
Felty's syndrome		Splenomegaly			+
Bacterial infections	Sepsis	Direct bone marrow suppression	+	+																			↑	↑
	Helicobacter pylori	Immune thrombocytopenia		+
	Tick-borne infection			+
Viral infections	HIV	Direct toxicity to megakaryocytes An ITP-like condition called primary HIV-associated thrombocytopenia (PHAT) Secondary opportunistic infections	+	+	+													↓↓	↓	↓		Confirm the diagnosis						Bone marrow examination and culture
	Other viruses such as rubella, mumps, varicella, parvovirus, hepatitis C, & Epstein-Barr virus	Immune mediated	+																										Might resolve spontaneously
Intracellular parasites	Malaria
	Babesiosis
Condition		Mechanism	Decreased platelet production	Platelet destruction in bloodstream	Platelet destruction in spleen/liver	Inherited	Acquried	Age range	History	Severity	Fever	Rash	Bleeding	BP	Splenomegaly	Jaundice	Other signs	Plt	HB	WBC	PBS	Bone marrow exam	PT	PTT	BT	UA	Imaging	Gold standard	Associated findings
Antibiotics/ Antiepileptics	Quinine Sulfonamides Carbamazepine Phenytoin	Occurrence of drug-dependent, platelet-reactive antibodies	+	+																								Resolution after discontinue
Heparin-induced thrombocytopenia				+						Not			-					↓											Increased risk of thrombosis
Cytotoxic chemotherapy			+
Radiation therapy		Predictable, dose-dependent myelosuppression	+
OTC agents	Quinine-containing beverages
Chronic liver disease			+
Portal hypertension
Condition		Mechanism	Decreased platelet production	Platelet destruction in bloodstream	Platelet destruction in spleen/liver	Inherited	Acquried	Age range	History	Severity	Fever	Rash	Bleeding	BP	Splenomegaly	Jaundice	Other signs	Plt	HB	WBC	PBS	Bone marrow exam	PT	PTT	BT	UA	Imaging	Gold standard	Associated findings
Giant capillary hemangioma		Platelet destruction		+
Aortic aneurysm		Platelet destruction		+
Cardiopulmonary bypass		Platelet destruction		+
Alcohol			+
Post-transfusion purpura		Immune mediated platelet destruction		+
Gestational thrombocytopenia
HELLP syndrome