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		Etiology	Mechanism			Inherited	Acquried	Clinical manifestations									Para−clinical findings									Gold standard	Associated findings
									Demography	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	Unknown Mutation	+	-	-	-/+	+	Elderly	Exposure to Chemotherapy Radiation therapy Tobacco smoke	+	Petechiae, purpura, diffuse erythematous rash	+	Nl	+	+	Shortness of breath, fatigue	↓	↓	↓	Ovalomacrocytosis Basophilic stippling Howell-Jolly body Dysplastic neutrophils	Impaired myeloid maturation Dyserythropoiesis Dysgranulopoiesis Dysmegakaryocytopoiesis Hypercellular bone marrow Fibrosis	Nl	Nl	Nl	NA	Bone marrow examination + clinical manifestation	Might transformed to acute leukemia
		Aplastic anemia	Acquired: idiopathic secondary to radiation, drugs and chemicals, pregnancy, PNH and viral or autoimmune causes Inherited: Unknown	+	-	-	-/+	-/+	Biphasic (the young and the elderly)	Exposure to Chemicals Radiation History of Prior drug use Viral infection	-	-	+	Nl	-	-	Shortness of breath, fatigue, pallor	↓	↓	↓	large RBCs low platelets and granulocytes	Hypocellular bone marrow replacement of bone marrow by fat				NA	Bone marrow examination + laboratory findings	Inherited forms are associated with: Fanconi Anemia Dyskeratosis congenita Schwachman-Diamond syndrome Reticular dysgenesis Amegakaryocytic thrombocytopenia Familial aplastic anemias Preleukemia (monosomy 7, etc.) Nonhematologic syndrome
		Acute leukemia		+
		Paroxysmal nocturnal hemoglobinuria (PNH)	Deficiency of complement regulatory proteins Mutations	+			-	+	Any age (usually younger adults)								thrombosis smooth muscle dystonia	↓/-	↓	↓/-		Usually cellular marrow Erythroid hyperplasia dyserythropoiesis The marrow may also become hypocellular or even aplastic in certain stages of the disease	Nl	Nl	hemoglobinuria	NA	Peripheral blood flow cytometry	Chronic renal failure Pulmonary hypertension Aplastic anemia
	Thrombotic microangiopathy (TMA)	Thrombotic thrombocytopenic purpura (TTP)	Deficiency of, or antibodies to, the metalloprotease ADAMTS13		+		-/+	+	Any age		+								↓		Fragmented RBCs		Nl	Nl				Hemolysis Microvascular thrombosis
		Hemolytic uremic syndrome (HUS)	Escherichia coli O157:H7 Genetic defects		+		-/+	+	Children														Nl	Nl				Acute renal failure 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		Etiology	Decreased platelet production	Platelet destruction in blood	Platelet destruction in spleen	Inherited	Acquried	Demography	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 age	-	-	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		Etiology	Decreased platelet production	Platelet destruction in blood	Platelet destruction in spleen	Inherited	Acquried	Demography	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		Etiology	Decreased platelet production	Platelet destruction in blood	Platelet destruction in spleen	Inherited	Acquried	Demography	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 (Kasabach-Merritt syndrome)		Platelet destruction		+
	Aortic aneurysm		Platelet destruction		+
	Cardiopulmonary bypass		Platelet destruction	-	+	-	-	+
Other	Alcohol		Platelet production suppression	+	-	+	-	+	Any	History of alcohol use	-	-	-	Nl	+	+	Hepatomegaly	↓	↓	↓	Cytopenia, macrocytosis	Cytopenia, macrocytosis	↑	↑	Nl	NA	Clinical manifestation	Chronic liver disease
	Post-transfusion purpura		Platelet destruction by anti-platelet antibodies	-	+	-	-	+	Women	History of blood transfusion or pregnancy	-	Purpura, petechiae	+	↓	-	-	-	↓↓↓	↓	Nl	Nl	NA	Nl	Nl	Nl	NA	Positive circulating alloantibody to a common platelet antigen	Severe but rare reaction
	Gestational thrombocytopenia		Might be physiologic adaptation of pregnancy	-	-	-	-	+	Pregnant women	Positive history of mild thrombocytopenia	-	-	-	Nl	-	-	-	↓	Nl	Nl	Nl	NA	Nl	Nl	Nl	NA	Diagnosis of exclusion	Self-limited condition
	HELLP syndrome		Unknown	-	+	-	-	+	Pregnant > 25 years	History of preeclampsia	-	-	+	↑	-	+	Abdominal tenderness Ascites	↓	↓	Nl	Schistocytes	NA	Nl	Nl	Proteinuria	NA	Lab abnormalities	Elevated liver enzymes and bilirubin Multiorgan dysfunction