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:

Category	Condition		Mechanism	Mechanism			Inherited	Acquried	Clinical manifestations										Para−clinical findings										Gold standard	Associated findings
									Age range	History	Symptoms				Signs
																			Lab Findings									Imaging
											Severity	Fever	Rash	Bleeding	BP	Splenomegaly	Jaundice	Other	CBC			PBS	Bone marrow exam	PT	PTT	BT	UA
				Decreased platelet production	Platelet destruction in blood	Platelet destruction in spleen													Plt	HB	WBC
Hematology	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		+
Category	Condition		Mechanism	Decreased platelet production	Platelet destruction in blood	Platelet destruction in spleen	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
Rheumatologic/autoimmune disorders	Immune thrombocytopenia		Antibody-mediated platelet destruction		+
	Systemic lupus erythematosus (SLE)				+
	Antiphospholipid syndrome (APS)		Autoantibody-mediated syndrome		+
	Felty's syndrome		Splenomegaly			+
Infection-induced	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	+	+	+
		Other viruses such as rubella, mumps, varicella, parvovirus, hepatitis C, & Epstein-Barr virus		+
	Intracellular parasites	Malaria
		Babesiosis
Category	Condition		Mechanism	Decreased platelet production	Platelet destruction in blood	Platelet destruction in spleen	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
Medication/toxicity	Drug-induced immune thrombocytopenia	Antibiotics Sulfonamides Ampicillin Piperacillin Vancomycin Rifampin Older antiepileptic agents carbamazepine Phenytoin Quinine	Occurrence of drug-dependent, platelet-reactive antibodies	+	+
	Heparin-induced thrombocytopenia				+
	Cytotoxic chemotherapy			+
	Radiation therapy		Predictable, dose-dependent myelosuppression	+
	OTC agents	Quinine-containing beverages
GI	Chronic liver disease			+
	Portal hypertension
Category	Condition		Mechanism	Decreased platelet production	Platelet destruction in blood	Platelet destruction in spleen	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
Vascular	Giant capillary hemangioma		Platelet destruction		+
	Aortic aneurysm		Platelet destruction		+
	Cardiopulmonary bypass		Platelet destruction		+
Other	Alcohol			+
	Post-transfusion purpura		Immune mediated platelet destruction		+
	Gestational thrombocytopenia
	HELLP syndrome