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
											Fever	Rash	Bleeding	BP	Splenomegaly	Jaundice	Other	CBC			PBS	Bone marrow exam	PT	PTT	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)			+		-	+											↓		Fragmented RBCs		Nl	Nl				Hemolysis Microvascular thrombosis
		Hemolytic uremic syndrome (HUS)			+		-	+															Nl	Nl				Hemolysis Microvascular thrombosis
		DIC		+			-	+															↑↑	↑				Hemolysis Microangiopathy
	Congenital platelet disorders	MYH-9 related disorders					+	-													Large platelets
		Bernard-Soulier syndrome	Absence of Gp Ib-IX-V				+	-
		Gray platelet syndrome					+	-
		Wiskott-Aldrich syndrome	Mutation in GATA-1				+	-
		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	Fever	Rash	Bleeding	BP	Splenomegaly	Jaundice	Other signs	Plt	HB	WBC	PBS	Bone marrow exam	PT	PTT	UA	Imaging	Gold standard	Associated findings
Rheumatologic/autoimmune disorders	ITP		Immune-mediated platelet destruction Inhibition of platelet release from the megakaryocyte	+	+	-	-	+	Any	-	-	Ecchymoses and petechia	+ Mucocutaneous	Nl	-	-	-	↓↓↓	Nl	Nl	Nl	Large platelets, otherwise normal	Nl	Nl	Nl	NA	Diagnosis of exclusion	Spontaneous remission
	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	An ITP-like condition called primary HIV-associated thrombocytopenia	+	+	+
		Other viruses such as rubella, mumps, varicella, parvovirus, hepatitis C, & Epstein-Barr virus		+
	Parasitic infections	Malaria
		Babesiosis
Category	Condition		Mechanism	Decreased platelet production	Platelet destruction in blood	Platelet destruction in spleen	Inherited	Acquried	Age range	History	Fever	Rash	Bleeding	BP	Splenomegaly	Jaundice	Other signs	Plt	HB	WBC	PBS	Bone marrow exam	PT	PTT	UA	Imaging	Gold standard	Associated findings
Medication/toxicity	Antibiotics/ Antiepileptic	Quinine Sulfonamides Carbamazepine Phenytoin	Occurrence of drug-dependent, platelet-reactive antibodies	+	+
	Heparin-induced thrombocytopenia		Anti-heparin/PF4 antibody		+																						ELISA	Early or delayed-onset
	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	Fever	Rash	Bleeding	BP	Splenomegaly	Jaundice	Other signs	Plt	HB	WBC	PBS	Bone marrow exam	PT	PTT	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