Thrombocytosis differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sadaf Sharfaei M.D.[2]

Thrombocytosis Differential Diagnosis

Differentiating the diseases that can cause thrombocytosis :

Category	Condition		Etiology	Mechanism			Inherited	Acquried	Clinical manifestations									Para−clinical findings								Gold standard	Associated findings
									Demography	History	Symptoms			Signs
																		Lab Findings							Imaging
											Fever	Appearance	Bleeding	BP	Splenomegaly	Jaundice	Other	CBC			PBS	Bone marrow exam	PT	PTT
				Increased megakaryocyte proliferation	Accelerated platelet release	Reduced platelet turnover												Plt	HB	WBC
Autonomous thrombocytosis	Hematologic malignancies	Essential thrombocythemia	Acquired mutation of JAK2, CALR, or MPL	+	-	-	-	+	Mean age >60 years old, female > male	Vascular occlusive events and hemorrhages	±	Flushing	+	Nl	+	-	Erythromelalgia Transient ischemic attacks Priapism Decreased visual acuity	↑↑	↑	↑	Large platelets Megakaryocyte fragments Platelet aggregates	Increased cellularity Hyperplasia and clustering of megakaryocytes Bone marrow reticulin may be increased with no collagen fibrosis	Nl	Nl	Splenomegaly on abdominal CT VTE on spiral chest CT DVT on ultrasound	Bone marrow biopsy	Thrombo-hemorrhagic complications
		Polycythemia vera	Acquired mutation of JAK2	+	-	-	-	+	Mean age >60 years old	Family history of polycythemia vera Ashkenazi Jewish descent	-	Facial plethora	±	Nl	+	-	Erythromelalgia Pruritus Tinnitus Blurred vision Lymphadenopathy	↑	↑↑	↑	Panmyelosis including prominent erythroid, granulocyte, and megakaryocyte proliferation	Panmyelosis including prominent erythroid, granulocyte, and megakaryocyte proliferation Pleomorphic, mature megakaryocytes	↑	↑		Bone marrow biopsy	Thrombo-hemorrhagic complications
		Primary myelofibrosis	Bone marrow fibrosis Mutation in JAK2, CALR, or MPL	+	-	-	-	+	Mean age >60 years old, male> female	Other myeloproliferative disorders Radiation exposure Chemicals exposure	-	Pallor Bruising Skin nodules	+	Nl	+	+	Fatigue Abdominal pain Early satiety Dyspnea Lymphadenopathy	↑/↓	↓	↓	Decreased number of erythroid, granulocyte, and megakaryocyte proliferation	Proliferation and atypia of megakaryocytes Reticulin or collagen fibrosis Hypercellular bone marrow	↑	↑	Diffuse bone sclerosis on CT	Bone marrow biopsy	Thrombo-hemorrhagic complications Variable risk for development of acute leukemia
		Chronic myeloid leukemia	Translocation (9;22), the Philadelphia chromosome BCR-ABL1 oncogene	+	-	-	-	+	Mean age >50 years old, male> female	History of exposure to: Ionizing radiation Formaldehyde Benzene	+	Pallor Bruises Petechiae Ulcers Vesicles	+	Nl	+	-	Fatigue Abdominal pain Early satiety Dyspnea Lymphadenopathy	↑	↓	↑	Immature leukocytes Leukemic blasts Leukoerythroblastic features Giant platelets Blast crisis	↑ Proportion of metamyelocytes and other white blood cells at various stages of maturation	↑	↑	Enlarged lymph nodes and splenomegaly on CT scan	Bone marrow biopsy	Increase of immature myeloid cells
		Acute myeloid leukemia	Unknown	+	-	-	-	+	Median age of 63 years old	History of hematological disorder History of chemotherapy and ionizing radiation	+	Pallor Leukemia cutis Bruising Petechiae Ecchymosis	+	Nl	+	+	Fatigue Bone tenderness Early satiety	↑/↓	↓	↑/↓	Leukemic blasts Leukoerythroblastic features Giant platelets	"Dry tap" on aspiration Leukemic cells	↑	↑	NA	Bone marrow examination + clinical manifestation	Infections of variable severity Cranial nerve palsy
		Myelodysplastic syndromes	Unknown Mutation	+	-	-	-/+	+	Elderly	Exposure to Chemotherapy Radiation therapy Tobacco smoke	+/-	Petechiae, purpura, diffuse erythematous rash	+	Nl	+	+	Shortness of breath Fatigue	↑/↓	↓	↓	Large platelets Ovalomacrocytosis Basophilic stippling Howell-Jolly body Pelger-Huet anomaly Ring sideroblasts	Impaired myeloid maturation Dyserythropoiesis Dysgranulopoiesis Dysmegakaryocytopoiesis Hypercellular bone marrow Fibrosis	Nl	Nl	NA	Bone marrow examination + clinical manifestation	Thrombosis at unusual sites Thrombosis in younger patients Might transformed to acute leukemia
	Condition		Etiology	Increased megakaryocyte proliferation	Accelerated platelet release	Reduced platelet turnover	Inherited	Acquried	Demography	History	Fever	Appearance	Bleeding	BP	Splenomegaly	Jaundice	Other signs	Plt	HB	WBC	PBS	Bone marrow exam	PT	PTT	Imaging	Gold standard	Associated findings
	Familial thrombocytosis		Mutation in TPO and MPL	+	-	-	+	-	Rare familial disease, middle age male and female	Family history of thrombocytosis	-	Normal	-	Nl	-	-	-	↑	Nl	Nl	Giant platelets Platelet conglomerates Bizarre forms Megakaryocytic fragments	Proliferation of megakaryocytes	Nl	Nl	NA	Genetic study	Polyclonal hematopoiesis Familial polycythemia vera Familial primary myelofibrosis
Reactive thrombocytosis	Anemia/ blood loss	Iron deficiency Blood loss Hemolysis	Unknown Proliferation of megakaryocytes	+	-	-	-	+	Any	History of bleeding or iron deficiency	-	Pallor	+	Nl to ↓	-	-	Depends on the etilogy	↑	↓	Nl	Microcytic anemia Megakaryocytic fragments	Proliferation of megakaryocytes	Nl	Nl	NA	Clinical manifestation	Required iron studies
	Infection	Chronic infections	Proliferation of megakaryocytes	+	+	-	-	+	Any	History of immunodeficiency	+	Pallor	±	Nl to ↓	-	±	Depends on the etilogy	↑	↓	↑	Microcytic anemia Megakaryocytic fragments	Proliferation of megakaryocytes	Nl	Nl	Depends on the etiology	Culture	Depends on the etilogy
		Tuberculosis	Proliferation of megakaryocytes	+	+	-	-	+	Any	History of close contact	+	Cachectic	-	Nl	-	-		↑	Nl	↑	Large platelets	Proliferation of megakaryocytes	Nl	Nl	Cavitation on chest imaging	Clinical manifestation+ culture
		Acute bacterial and viral infections	Proliferation of megakaryocytes	+	+	-	-	+	Any	History of close contact	+	Acutely ill	-	Nl	-	-	Depends on the etilogy	↑		↑	Large platelets	Proliferation of megakaryocytes	Nl	Nl	Depends on the etiology	Clinical manifestation+ culture	Depends on the etiology
	Inflammation	Vasculitides	Unknown	+	+	-	±	+	Any	Family history of rheumatologic isorders	+	Acutely ill	+	Nl	-	-	Arthritis	↑	Nl to ↓	↑	Microcytic anemia Megakaryocytic fragments	Proliferation of megakaryocytes	Nl to ↑	Nl to ↑	Depends on the type	Clinical manifestation+ culture	Depends on the type
		Acute pancreatitis	Proliferation of megakaryocytes	+	+	-	-	+	Any	Alcohol consumption Gallstone Hypertriglyceridemia Obesity	+	Acutely ill	-	Nl to ↓	-	+	Abdominal tenderness N/V Dyspnea	↑	Nl to ↓	↑	Large platelets	Proliferation of megakaryocytes	Nl to ↑	Nl to ↑	Diffusely enlarged and hypoechoic pancreas on abdominal ultrasound Focal or diffuse enlargement of the pancreas with heterogeneous enhancement on abdominal CT scan	Clinical manifestation	Rarely progress to severe inflammation and necrosis Organ failure
		Malignancy	Proliferation of megakaryocytes Accelerated platelet release	+	+	-	±	±	Any	Prior malignancy Exposure to chemicals Family history of malignancy	+	Cachectic	-	Nl to ↓	Depends on the type	-	Tenderness	↑	Nl to ↓	↑	Microcytic anemia Megakaryocytic fragments	Proliferation of megakaryocytes	Nl to ↑	Nl to ↑	Depends on the type	Biopsy	Potential effective predictor of overall survival Venous thromboembolism
	Condition		Etiology	Increased megakaryocyte proliferation	Accelerated platelet release	Reduced platelet turnover	Inherited	Acquried	Demography	History	Fever	Appearance	Bleeding	BP	Splenomegaly	Jaundice	Other signs	Plt	HB	WBC	PBS	Bone marrow exam	PT	PTT	Imaging	Gold standard	Associated findings
	Tissue damage	Thermal burns																↑
		Trauma																↑
		Myocardial infarction																↑
	Medication	Myelosuppressive agents																↑
		Vincristine																↑
		Epinephrine, glucocorticoids																↑
		Interleukin-1B																↑
		All-trans retinoic acid																↑
		Thrombopoietin																↑
	Other	Post-splenectomy or functional asplenia				+				Prior surgical removal of the spleen Sickle cell disease								↑			Howell-Jolly bodies Nucleated RBCs
		Allergic reactions																↑
		Exercise																↑
	Pseudothrombocytosis	Mixed cryoglobulinemia
		Cytoplasmic fragments
Category	Condition		Etiology	Increased megakaryocyte proliferation	Accelerated platelet release	Reduced platelet turnover	Inherited	Acquried	Demography	History	Fever	Appearance	Bleeding	BP	Splenomegaly	Jaundice	Other signs	Plt	HB	WBC	PBS	Bone marrow exam	PT	PTT	Imaging	Gold standard	Associated findings