Health Dictionary

Overview

Myelodysplastic syndrome must be differentiated from other diseases that cause anemia, neutropenia, and thrombocytopenia, such as: aplastic anemia, fanconi anemia, pure red cell aplasia, Shwachman-Diamond syndrome, paroxysmal nocturnal hemoglobinuria, parovirus B19 infection, and vitamin B12 defeciency

Differentiating Myelodysplastic Syndrome from other Diseases

ABBREVIATIONS

EPO: Erythropoietin, FISH: Fluorescence in situ hybridization, Hb: Hemoglobin, LAD: Leukocyte alkaline dehydrgenase, LAP: Leukocyte alkaline phosphatase, LDH: Lactate dehydrogenase, LFTs: Liver function tests, NL: Normal, PCR: Polymerase chain reaction, Plt: Platelet, PUD: Peptic ulcer disease, RFTs: Renal function tests, WBCs: White blood cells.

Disease		Clinical manifestations		Diagnosis										Other features
		Symptoms	Signs	CBC & Peripheral smear								Bone marrow biopsy	Other investigations
				WBCs						Hb	Plt
				WBC	Blasts	Left shift	Baso- phils	Eosino- phils	Mono- cytes	Hb	Plt
Myelodysplastic syndromes (MDS)^[1]^[2]		Constitutional Anemia related Bleeding Infection	Pallor Petechiae Organomegaly	↓	Variable	–	↓	↓	↓	↓	↓	Hypercellular/ normocellular bone marrow with dysplastic changes	Cytogenetic analysis Flow cytometry Macro-ovalocytes Basophilic stippling Howell-Jolly body	Leukemia transformation Acquired pseudo-Pelger-Huët anomaly
Chronic myeloid leukemia (CML)^[3]^[4]		Asymptomatic Constitutional Hyperviscosity and/or anemia related Bleeding Infection	Splenomegaly (46–76%) Purpura Anemia related Priapism	↑	<2%	+	↑	↑	↑	↓	NL	Hypercellurarity with ↑ granuloscytosis and ↓ erythrocytosis Fibrosis	FISH for t(9;22)(q34;q11.2) Reverse transcriptase quantitative PCR (RQ-PCR) for BCR-ABL	Granulocytic dysplasia is minimal/absent May present with blast crisis Absolute leukocytosis (median of 100,000/µL) Classic myelocyte bulge thrombocytopenia indicates advanced stage
Polycythemia vera (PV)^[5]^[6]^[7]^[8]		Constitutional Thromboembolism and bleeding Pruritus after a warm bath PUD related	Facial ruddiness Related to underlying cause Splenomegaly Renal bruit	NL or ↑	None	–	↑ or ↓	NL or ↑	NL	↑↑	NL	Hypercellularity for age with tri-lineage growth Myelofibrosis (in up to 20% of patients)	Radioisotope studies Serum EPO levels LFTs RFTs Imaging studies ↓ Serum ferritin ↓ Folate levels ↑↑ B12 levels	May transform into myelofibrosis or leukemia
Primary myelofibrosis (PMF)^[9]^[10]^[11]^[12]		Constitutional Anemia related Bleeding Infection Abdominal Pain	Hepatosplenomegaly Petechiae & ecchymoses Abdominal distension Lymphadenopathy	↓	Erythroblasts	–	Absent	NL	NL	↓	↓	Variable with fibrosis or hypercellularity	JAK2 mutation CALR mutation MPL mutation ↑ LAP ↑ LAD ↑ Uric acid ↑ B12 levels	Bone marrow aspiration shows a dry tap Variable with leukocytosis or leukopenia
Disease		Symptoms	Sign	WBC	Blasts	Left shift	Baso- phils	Eosino- phils	Mono- cytes	Hb	Plt	Bone marrow biopsy	Other investigations	Other features
Essential thrombocythemia (ET)^[13]^[14]^[15]		Headache Dizziness Visual disturbances Priapism Acute chest pain	Splenomegaly Skin bruises	NL or ↑	None	–	↓ or absent	NL	NL	↓	↑↑	Normal/Hypercellular	JAK2 mutation CALR mutation MPL mutation	Thrombosis Hemorrhage Pregnancy loss
Myelodysplastic /myeloproliferative neoplasms (MDS/MPN)	Chronic myelomonocytic leukemia (CMML)^[16] ^[17]^[18]	Constitutional Anemia related Bleeding Infections Bone pain Leukemia Cutis	Organomegaly Bruising	↑	< 20%		NL	↑	↑↑	↓	↓	Myelodysplastic and myeloproliferative feature	Cytogenetic analysis Flow cytometry ↑ LDH	Overlapping of both, MDS and MPN Absolute monocytosis > 1 × 10⁹/L (defining feature) MD-CMML:WBC ≤ 13 × 10⁹/L (FAB) MP-CMML:WBC > 13 × 10⁹/L (FAB)
	Atypical chronic myeloid leukemia (aCML), BCR-ABL1-^[19]^[20]	Asymptomatic Constitutional Hyperviscosity and/or anemia related Bleeding Infection	Splenomegaly (46–76%) Purpura Anemia related Priapism	↑	<20%	+	<2% of WBCs	N/A	N/A	↓	↓	Granulocytic hyperplasia with prominent dysplasia	Cytogenetic analysis Flow cytometry	Granulocytic dysplasia is prominent Absence of BCR-ABL or PDGFRA, PDGFRB, or FGFR1 rearrangements WBC > 13 × 10⁹/L
	Juvenile myelomonocytic leukemia (JMML)^[21]^[22]	Infections Anemia related	Hepatosplenomegaly Lymphadenopathy Rash	↑	↑	N/A	N/A	N/A	↑	↓	↓	Hypercelluar with ↑ myeloid cells in stages of maturation	Cytogenetic analysis Flow cytometry ↓ Serum Iron ↑ B12 levels	Polyclonal hypergammaglobulinemia
	MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T)^[23]^[24]^[25]	Constitutional Anemia related Thrombosis	Variable	NL or ↑	NL	–	NL	N/A	N/A	↓	↑	Hypercellularity with dyserythropoiesis and increased megakaryocytes	Cytogenetic analysis Flow cytometry ↑ Serum Iron	Large atypical megakaryocytes Ringed sideroblasts SF3B1 mutation
Disease		Symptoms	Sign	WBC	Blasts	Left shift	Baso- phils	Eosino- phils	Mono- cytes	Hb	Plt	Bone marrow biopsy	Other investigations	Other features
Chronic neutrophilic leukemia (CNL)^[26]^[27]^[28]		Asymptomatic Constitutional symptoms Bleeding Infection	Splenomegaly Heptomegaly Purpura Anemia related	↑	Minimal	+	NL	NL	NL	↓	↓	Uniforme and intense hypercellularity with minimal to none fibrosis Neutrophil toxic granulations and Dohle bodies	FISH Imaging for hepatosplenomegaly ↑ LDH ↑ B12 levels	Associationed with polycythemia vera and plasma cell disorders Leukocytosis with chronic neutrophilia
Chronic eosinophilic leukemia, not otherwise specified (NOS)^[29]^[30]^[31]^[32]		Constitutional Rash Rhinitis Gastritis Thromboembolism related	Hypertension Eczema, mucosal ulcers, erythema Angioedema Ataxia Anemia Lymphadenopathy Hepatosplenomegaly	↑	Present	+	↑	↑↑	↑	↓	↓	Hypercelluar with ↑ eosinophilic precursors, ↑ eosinophils, and atypical mononuclear cells	FISH Cytogenetic analysis of purified eosinophils and X-chromosome inactivation analysis ↑ B12 levels ↑ LDH	Heart failure Lung fibrosis Encephalopathy Erythema annulare centrifugam
MPN, unclassifiable		Similar to other myeloproliferative neoplasms	Similar to other myeloproliferative neoplasms	↑	Variable	±	↑ or ↓	↑ or ↓	↑ or ↓	↓	↑	↑ megakaryocyte proliferation with variable hypercellularity in granulocytic or erythrocytic cell lines	May resemble other myeloproliferative neoplasms	Similar to other myeloprolifeartive neoplasms but do not fulfil the criteria to be classified to a specific type
Mastocytosis^[33]^[34]^[35]^[36]		Constitutional Pruritus & Flushing Urticaria & Blisters Hypotension & PUD Bleeding Bronchoconstriction	Mastocytosis exanthema Blistering Swelling Lymphadenopathy Bleeding Fibrosis	↑	None	–	NL	↑	NL	↓	↓ or ↑	Multifocal dense infiltrates of mast cells with atypical morphology in >25 %	Cytogenetic analysis for c-KIT receptor mutations Serum tryptase levels 24-hour urine test for N-methyl histamine and 11-beta-prostaglandine ↑ Alkaline phosphatase ↑ LDH	Skin most commonly involved Susceptibility to anaphylaxix Osteoporosis
Myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1, or with PCM1–JAK2^[37]^[38]^[39]^[40]		Asymptomatic Constitutional Rash Cough & breathlessness Peripheral neuropathy/ encephalopathy	Fever Lymphadenopathy	↑	NL	–	NL	↑	↑	NL	↓	Myeloid expansion with eosinophilia	FISH shows t(8;13) and t(8;22)	May present or evolve into acute myeloid or lymphoblastic leukemia Leukocytosis (30 – 59 × 10⁹/L
Disease		Symptoms	Sign	WBC	Blasts	Left shift	Baso- phils	Eosino- phils	Mono- cytes	Hb	Plt	Bone marrow biopsy	Other investigations	Other features
B-lymphoblastic leukemia/lymphoma^[41]^[42]		Constitutional Anemia related Bleeding Infection Bone pain	Pallor Petechiae Organomegaly Lymphadenopathy	NL or ↑	>25%	N/A	↑ or ↓	↑ or ↓	↑ or ↓	↓	↓	Hypercellular with blast infilterationwith or without myelodysplasia	Cytogenetic analysis Flow cytometry FISH Auer bodies	May present as extramedullary disease (Myeloid sarcoma)
Acute myeloid leukemia (AML) and related neoplasms^[43]^[44]		Constitutional Anemia related Bleeding Bone pain Joint pain Infections	Infection related Pallor Leukemia cutis Bruising & petechiae Lymphadenopathy Hepatosplenomegaly	NL or ↑	↑	N/A	↑ or ↓	↑ or ↓	↑ or ↓	↓	↓	Increased immaturemyeloid cells with dysplasia	Cytogenetic analysis Flow cytometry FISH ↑ Potassium ↑ Uric acid ↑ Phosphorus ↓ Calcium ↑ LDH	Common in Down syndrome
Blastic plasmacytoid dendritic cell neoplasm^[45]^[46]^[47]^[48]		Cutaneous symptoms (brown/purple nodular lesions) on face, scalp, lower limb & trunk	Brown/violaceous bruise like lesions Lymphadenopathy Splenomegaly	NL	↑		NL	NL	NL	↓	↓	Malignant cells	Immunohistochemistry or flow cytometry for CD4 & CD56 Neutropenia	TdT expression positive May develop chronic myelomonocytic leukemia (CMML)
Disease		Symptoms	Sign	WBC	Blasts	Left shift	Baso- phils	Eosino- phils	Mono- cytes	Hb	Plt	Bone marrow biopsy	Other investigations	Other features
T-lymphoblastic leukemia/ lymphoma	T-lymphoblastic leukemia/ lymphoma^[49]^[50]^[51]	Constitutional Anemia Related Bleeding Superior vena cava syndrome	Lymphadenopathy Mediastinal mass Pleural effusions Tracheal obstruction Pericardial effusions	↑	>25% blasts (Leukemia) <25% blasts (Lymphoma)	±	↑ or ↓	↑ or ↓	↑ or ↓	↓	↓	Hypercelluarity with increased T cells precursors	Cytogenetic analysis Flow cytometry FISH ↑ LDH Positive for TdT	May involve brain, skin, and testes.
	Provisional entity: Natural killer (NK) cell lymphoblastic leukemia/lymph^[52]	Constitutional Anemia Related Bleeding Superior vena cava syndrome	Lymphadenopathy Mediastinal mass Pleural effusions Tracheal obstruction Pericardial effusions	↑	↑	±	↑ or ↓	↑ or ↓	↑ or ↓	↓	↓	N/A	Cytogenetic analysis FISH Flow cytometry ↑ LDH	Similar to T-cell lymphoblastic leukemia but may have more aggressive clinical course. Diagnosis is usually based on presence of CD56 expression, and T-cell-associated markers such as CD2 and CD7. B-cell markers are absent.
	Provisional entity: Early T-cell precursor lymphoblastic leukemia^[53]^[54]	Constitutional Anemia Related Bleeding Superior vena cava syndrome	Lymphadenopathy Mediastinal mass Pleural effusions Tracheal obstruction Pericardial effusions	↑	↑	±	↑ or ↓	↑ or ↓	↑ or ↓	↓	↓	Hypercelluarity with increased T cells precursors	Cytogenetic analysis FISH Flow cytometry ↑ LDH	Similar to T-cell lymphoblastic leukemia but is more aggressive clinically and cell are characterized by cytometry as CD1a⁻, CD8⁻, CD5⁻ (dim), and positivity for 1 or more stem cell or myeloid antigens. Gene expression indicates more immature cells as compared to other subtypes of T-cell neoplasms.

Differentiating myelodysplastic syndrome from other causes of macrocytic anemia

Disease	Genetics	Clinical manifestation					Lab findings
		History	Symptoms	Signs	Hemolysis	Intrinsic/Extrinsic	Hb concentration	MCV	RDW	Reticulocytosis	Haptoglobin levels	Hepcidin	Iron studies					Specific finding on blood smear
		History	Symptoms	Signs	Hemolysis	Intrinsic/Extrinsic	Hb concentration	MCV	RDW	Reticulocytosis	Haptoglobin levels	Hepcidin	Serum iron	Serum Tfr level	Transferrin or TIBC	Ferritin	Transferrin saturation	Specific finding on blood smear
Folate deficiency^[55]	Impaired DNA synthesis	Alcohol consumption History of using drugs like methotrexate, trimethoprim, and phenytoin Low socioeconomic groups with poor nutrition Older people Pregnant and lactating women	No neurological symptoms vs B12 deficiency Odynophagia Angular stomatitis	Glossitis Signs of heart failure Anencephaly and spina bifida	−	−	Anisochromic	Macrocytic	↑	↓	Nl	Nl	↑	↑	↓	↑	↑	RBC macrocytosis Hypersegmented neutrophils Pancytopenia in severe cases
Vitamin B12 deficiency^[56]	Impaired DNA synthesis	Pernicious anemia Crohn’s disease Gastrectomy Veganism Diphyllobothrium latum infection	Psychosis Insomnia Depression Cognitive slowing Restless leg syndrome	Neurological deficit Myelopathy Memory loss with reduced attention span Nystagmus Positive romberg sign Positive Lhermitte’s sign	−	−	Anisochromic	Macrocytic	↑	↓	Nl	Nl	↑	↑	↓	↑	↑	Senile neutrophil Anisocytosis Ovalocytes
Orotic aciduria^[57]	Autosomal recessive Deficiency of enzyme UMPS	Episodic vomiting Rhabdomyolysis	Coma Gastrointestinal manifestation	Neurological manifestation	−	−	Anisochromic	Macrocytic	↑	↓	Nl	Nl	↑	↑	↓	↑	↑	NA
Fanconi anemia^[58]	Autosomal recessive X-linked recessive	History of anemia at age 16	Hypopigmentation Cafe-au-lait patches Radial ray anomaly	Significant for bilateral short thumbs	−	−	Anisochromic	Macrocytic	↑	↓	Nl	Nl	↑	↑	↓	↑	↑	Nl appearing WBC, RBC and Platelets But the number is greatly reduced
Disease	Genetics	History	Symptoms	Signs	Hemolysis	Intrinsic/Extrinsic	Hb concentration	MCV	RDW	Reticulocytosis	Haptoglobin levels	Hepcidin	Serum iron	Serum Tfr level	IBC	Ferritin	Transferrin saturation	Specific finding on blood smear
Diamond-Blackfan anemia^[59]	Mutations in: RPL5 RPL11 RPL35A RPS7 RPS10 RPS17 RPS19 RPS24 RPS26	Associated with myelodysplastic syndrome Increased risk of AML	Pale skin Sleepiness Heart murmurs	Triphalangeal thumbs Short stature Microcephaly Hypertelorism Ptosis Micrognathia	−	−	Anisochromic	Macrocytic	Nl	↓	Nl	Nl	↑	↑	↓	↑	↑	NA
Liver disease^[60]	−	Hepatitis Binge drinking Gall bladder disease	Jaundice Abdominal pain Itchy skin	Ascites Right upper quadrant pain Hepatomegaly Swelling in the legs Ankle swelling	−	−	Anisochromic	Macrocytic	↑	↑	Nl	Nl	↑	↑	↓	↑	↑	Round macrocytes Target macrocytes
Alcoholism^[61]	−	History of increased alcohol intake Folic acid deficiency	Memory impairment Nausea Sweating	Truncal obesity Asterixis Encephalopathy Spider angiomas Hematemesis Gynecomastia	−	−	Anisochromic	Macrocytic	↑	↑	Nl	Nl	↑	↑	↓	↑	↑	Oval macrocytes Hypersegmented neutrophils
Disease	Genetics	History	Symptoms	Signs	Hemolysis	Intrinsic/Extrinsic	Hb concentration	MCV	RDW	Reticulocytosis	Haptoglobin levels	Hepcidin	Serum iron	Serum Tfr level	IBC	Ferritin	Transferrin saturation	Specific finding on blood smear

Differentiating myelodysplastic syndrome from other causes of thrombocytopenia

Condition		Etiology	Mechanism			Inherited	Acquried	Clinical manifestations									Para−clinical findings						Gold standard	Associated findings
								Demography	History	Symptoms			Signs				Para−clinical findings
										Symptoms			Signs				Lab Findings
										Fever	Rash	Bleeding	BP	Splenomegaly	Jaundice	Other	CBC			PBS	Bone marrow exam	Other
			Decreased platelet production	Platelet destruction in blood	Platelet destruction in spleen					Fever	Rash	Bleeding	BP	Splenomegaly	Jaundice	Other	Plt	HB	WBC	PBS	Bone marrow exam	Other
Bone marrow disorders	Myelodysplastic syndromes^[62]	Unknown Mutation	+	−	−	±	+	Elderly	Exposure to Chemotherapy Radiation therapy Tobacco smoke	+	Petechiae, purpura, diffuse erythematous rash	+	Nl	+	+	Shortness of breath Fatigue Pallor	↓	↓	↓	Ovalomacrocytosis Basophilic stippling Howell-Jolly body Dysplastic neutrophils	Impaired myeloid maturation Dyserythropoiesis Dysgranulopoiesis Dysmegakaryocytopoiesis Hypercellular bone marrow Fibrosis	Nl	Bone marrow examination + clinical manifestation	Might transformed to acute leukemia
	Aplastic anemia^[63]	Unknown secondary to radiation, drugs and chemicals, pregnancy, PNH and viral or autoimmune causes	+	−	−	±	±	Biphasic (the young and the elderly)	Exposure to chemicals Radiation History of prior drug use Viral infection Positive family history of aplastic anemia	−	−	+	Nl	−	−	Shortness of breath Fatigue Pallor	↓	↓	↓	Large RBCs Low platelets and granulocytes	Hypocellular bone marrow replacement of bone marrow by fat	Elevated PT/PTT	Bone marrow examination + laboratory findings	Fanconi Anemia Dyskeratosis congenita Schwachman-Diamond syndrome Preleukemia
	Acute leukemia^[64]^[65]	Immune mediated Chromosomal abnormalities	+	+	−	±	±	AML in adults	Exposure to chemicals Radiation Pre-existent blood disorders	±	Petechiae	+	Nl	±	−	Weakness	↓	↓	↓	Pancytopenia	Blast cells	Hemoglobinuria Elevated PT/PTT	Bone marrow examination	Tumor lysis syndrome Infection CNS involvement DIC
	Paroxysmal nocturnal hemoglobinuria (PNH)^[66]	Deficiency of complement regulatory proteins Mutations	+	+	−	−	+	Any age (usually younger adults)	Sudden nocturnal hemoglobinuria with partial clearing during the day	−	−	−	Nl	−	−	Thrombosis Smooth muscle dystonia	↓/Nl	↓	↓/Nl	Pancytopenia	Cellular marrow Erythroid hyperplasia dyserythropoiesis Hypocellular marrow in certain stages of the disease	Hemoglobinuria	Flow cytometry	Chronic renal failure Pulmonary hypertension Aplastic anemia
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	UA	Gold standard	Associated findings
Thrombotic microangiopathy (TMA)	Thrombotic thrombocytopenic purpura (TTP)^[67]	Deficiency of, or antibodies to, the metalloprotease ADAMTS13	−	+	−	±	+	Any age	Neurologic manifestations Fatigue due to anemia	+	Petechiae	Not common	Nl or ↑	−	+	Neurologic findings Signs of renal impairment	↓	↓	Nl or ↑	Fragmented RBCs	NA	Hemoglobinuria	Laboratory findings	Hemolysis Microvascular thrombosis
	Hemolytic uremic syndrome (HUS)^[68]	Escherichia coli O157:H7 Genetic defects	−	+	−	±	+	Children	Exposure to contaminated water or milk Consuming undercooked ground beef	+	Petechiae	−	↓	−	+	Abdominal tenderness Diarrhea	↓	↓	Nl or ↑	Fragmented RBCs	NA	Hemoglobinuria	Laboratory findings	Acute renal failure Hemolysis Microvascular thrombosis
	DIC^[69]^[70]	Overstimulation of the coagulation system	+	+	−	−	+	Any age	History of trauma, sepsis, malignancy, vasculitis or exogenous toxins	+	+	+	↓	−	+	Neurologic findings Signs of renal impairment	↓	↓↓	↑	Schistocytes Helmet cells	Low platelets Low RBCs	Hemoglobinuria Elevated PT/PTT	Clinical manifestation + laboratory findings	Hemolysis Microangiopathy Multi-organ dysfunction
Nutrient deficiencies	Folate, vitamin B12, copper deficiencies^[71]^[72]	Decreased platelet production	+	−	−	−	+	Any age	Malnutrition Alcohol use	−	−	−	Nl	−	−	Fatigue Weakness	↓	↓	Nl	Low platelets Low RBCs	Low platelets Low RBCs	Nl	Laboratory findings	Megaloblastic anemia
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	UA	Gold standard	Associated findings
Congenital platelet disorders^[73]^[74]^[75]	MYH9-related disorders^[76]	Cytoskeletal defects in megakaryocytes Mutation	+	−	−	+	−	Any age, very rare	Positive family history	−	Petechiae	+	Nl	−	−	Hearing loss Renal impairment Cataract	↓	↓	Nl	Large platelets Döhle body-like inclusions in peripheral blood neutrophils	NA	Nl	Genetic study	Autosomal dominant
	Bernard-Soulier syndrome^[77]	Absence of Gp Ib-IX-V	+	−	−	+	−	Children, rare	Positive family history	−	−	+	Nl	−	−	−	↓	Nl	Nl	Large platelets	Large platelets	Nl	Flow cytometry	Autosomal recessive Increased bleeding time
	Gray platelet syndrome^[78]	Reduction or absence of alpha-granules in blood platelets	+	−	−	+	−	Rare	Positive family history	−	Petechiae	+ Mucocutaneous	Nl	+	−	Epistaxis	↓	Nl	Nl	Large platelets and lack of granulation	Myelofibrosis	Nl	Genetic study	Autosomal recessive
	Wiskott-Aldrich syndrome^[79]	Mutation in GATA-1	+	−	−	+	−	Rare	Positive family history	−	Eczema	+	Nl	−	−	Bloody diarrhea	↓	Nl	Nl	Small but low platelets	Small but low platelets	Nl	Genetic study	Recurrent infections autoimmune disorders Malignancy
	Thrombocytopenia with absent radius (TAR) syndrome^[80]	1q21.1 deletion and bone marrow failure	+	−	−	+	−	Children	Positive family history	−	+	+	Nl	−	−	Bilateral radial aplasia	↓	Nl	Nl or ↑	Normal size platelets	Normal or hypercellular bone marrow Decreased, absent, or immature megakaryocytes Small, basophilic, vacuolated megakaryocytes Erythroid hyperplasia	Nl	Evidence of absent radius + Laboratory findings	Cow’s milk allergy Various other anomalies
	Fechtner syndrome^[81]	Mutation of chromosome 22q11-13	+	−	−	+	−	Children	Positive family history	−	Ecchymoses and petechia	+ Mucocutaneous	Nl	−	−	Hearing loss Eye abnormalities	↓	Nl	Nl or ↑	Large platelets Granulocytic inclusions	NA	Microscopic hematuria Pyuria Red cell casts Cylindrical casts Proteinuria	Clinical manifestation + genetic study	Autosomal dominant variant of Alport syndrome Renal failure Hypoalbuminemia
	Von Willebrand disease^[82]	VWF deficiency/dysfunction	+	−	−	+	Rarely	More common with O blood type	Positive family history	−	−	+	−	−	−	−	Nl/ ↓	Nl/↓	Nl	Large platelets	NA	Hematuria	Laboratory findings	Lifelong bleeding disorder
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	UA	Gold standard	Associated findings
ITP^[83]		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	Diagnosis of exclusion	Spontaneous remission
Systemic lupus erythematosus^[84]		Immune-mediated platelet destruction	−	+	−	−	+	Young women, more prevalent in Africans and Asians	Medication use History of weight changes Other rheumatologic and autoimmune diseases Family history of rheumatologic diseases	+	Malar rash, generalized maculopapular rash, discoid rash	+ Hemoptysis	Nl or ↑	+	+	Mucosal ulcers Lymphadenopathy Crackles Chest tenderness Murmur Hepatomegaly Cognitive impairment	↓	↓	↓	Pancytopenia	Pancytopenia	Hematuria Pyuria Proteinuria Cellular casts Elevated PT/PTT	Clinical manifestation + serology	TTP Multiorgan dysfunction Infections Atherosclerosis Malignancies Poor prognosis with lupus nephritis
Antiphospholipid syndrome^[85]		Autoantibody-mediated syndrome	−	+	−	+	+	Middle aged women, more in African American and Hispanic population	Abortion Other rheumatologic and autoimmune diseases Family history of rheumatologic diseases	−	−	−	Nl	−	−	DVT	↓	Nl	↓	Reduced platelets and WBC	Reduced platelets and WBC	Hematuria Elevated PTT	Clinical manifestation + repeated positive tests of aPL	Recurrent thrombosis Stroke
Felty’s syndrome^[86]		Autoantibody-mediated syndrome Splenomegaly	−	+	+	±	+	Rare, young women	Arthritis Family history of RA	−	Necrotizing skin lesions Rheumatoid nodule	−	Nl	+	−	Lymphadenopathy	↓	Nl	↓	Reduced platelets and WBC	Reduced platelets and WBC	Nl	Clinical manifestation	Rheumatoid arthritis Positive RF and anti-citrullinated peptide antibodies Episcleritis Pleuropericarditis
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	UA	Gold standard	Associated findings
Bacterial infections	Sepsis^[87]	Direct bone marrow suppression	+	+	−	−	+	Any	Bacterial infection	+	Petechiae Purpura Erythema Ulceration	±	Nl to ↓	−	±	Malaise Lymphadenopathy	↓/↑	Nl	↑↑	Reduced platelets	NA	Elevated PT/PTT	Clinical manifestation + culture	Associated with ↑ mortality
	Helicobacter pylori^[88]	Immune thrombocytopenia	−	+	−	−	+	Any	−	−	−	−	Nl	−	−	Epigastric tenderness Heartburn	↓	Nl	Nl	Reduced platelets	NA	Nl	Clinical manifestation + culture	GERD
	Tick-borne infection^[89]	Immune thrombocytopenia	−	+	−	−	+	Endemic area like China, Japan, and Korea	Being bitten by a tick	+	Petechiae Purpura Erythema Ulceration	±	Nl to ↓	±	±	Encephalitis Hemorrhagic fever	↓	Nl	↓	Reduced platelets	NA	Proteinuria	PCR	Elevated ALT and AST Multiple organ failure Lymphadenopathy
Viral infections	HIV^[90]	Immune thrombocytopenia	+	+	+	−	+	Any	High risk behaviors Close contact	+	Skin lesions	±	Nl to ↓	±	±	Lymphadenopathy Muscle weakness Joint swelling Focal neurological deficits	↓	↓	↓	Pancytopenia	Pancytopenia	Proteinuria Elevated PT/PTT	Isolation of HIV	Malignancy Severe immunodeficiency
Viral infections	Other viruses such as rubella, mumps, varicella, parvovirus, hepatitis C, & Epstein-Barr virus^[91]	Immune thrombocytopenia	+	−	−	−	+	Any	High risk behaviors Close contact	+	Petechiae Purpura	−	Nl	±	±	Lymphadenopathy Muscle weakness Joint swelling Focal neurological deficits Depends on etiology	↓	↓	↓	Pancytopenia	Pancytopenia	Hematuria	Clinical manifestation + lab tests	Depends on etiology Encephalomyelitis
Parasitic infections	Malaria^[92]	Unknown Immune thrombocytopenia	+	−	−	−	+	Endemic area	Being bitten by a mosquito	+	−	±	Nl to ↓	±	±	Headache Weakness Night sweats Joint pain Muscle pain	↓	↓	↓	Pancytopenia	Pancytopenia	Hematuria	Clinical manifestation + microscopic examination of blood smear	Life-threatening disease Multiple organ failure
Parasitic infections	Babesiosis^[93]	Unknown Immune thrombocytopenia	+	−	−	−	+	Rare	Being bitten by a tick Immunodeficiency	+	−	±	Nl to ↓	±	±	Fatigue Chills Sweats Headache	↓	↓	↓	Pancytopenia	Pancytopenia	Hematuria	Clinical manifestation + microscopic examination of blood smear	Severe hemolytic anemia DIC Multiple organ failure
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	UA	Gold standard	Associated findings
Antibiotics/ Antiepileptic^[94]	Quinine Sulfonamides Carbamazepine Phenytoin	Occurrence of drug-dependent, platelet-reactive antibodies	+	+	−	−	+	Any	Drug ingestion or injection	−	Ecchymoses Petechia	−	Nl	−	−	−	↓↓	↓	Nl	Reduced platelets	NA	Nl	Clinical manifestation + exclusion of the other causes	NA
Heparin-induced thrombocytopenia^[95]		Anti-heparin/PF4 antibody	−	+	−	−	+	Any	Heparin injection	−	Necrotic skin lesions	−	Nl	−	−	−	↓	Nl	Nl	Reduced platelets	NA	Nl	ELISA	Early or delayed-onset Thrombosis
Cytotoxic chemotherapy^[96]		Bone marrow suppression	+	−	−	−	+	Patients with malignancy	Drug ingestion or injection Cancer	−	Ecchymoses Petechia	−	Nl	−	−	−	↓	↓	↓	Reduced platelets	Megakaryocytic hypoplasia or aplasia	Hematuria Elevated PT/PTT	Clinical manifestation + exclusion of the other causes	Thrombosis
Radiation therapy^[97]		Predictable, dose-dependent myelosuppression	+	−	−	−	+	Patients with malignancy	Radiation Cancer	−	Purpura Petechiae	+	Nl	−	−	−	↓	↓	↓	Reduced platelets	Megakaryocytic hypoplasia or aplasia	Hematuria Elevated PT/PTT	Clinical manifestation + exclusion of the other causes	Thrombosis
Chronic liver disease^[98]		Bone marrow suppression	+	−	−	−	+	Any	Cirrhosis Alcohol use	−	Purpura Petechiae	+	↓	+	+	−	↓	↓	Nl	Reduced platelets	NA	Hematuria Elevated PT/PTT	Biopsy	Portal vein thrombosis Hepatorenal syndrome Variceal hemorrhage Hepatic hydrothorax Spontaneous bacterial peritonitis
Portal hypertension^[99]		Bone marrow suppression	+	−	−	−	+	Any	Cirrhosis Alcohol use	−	Purpura Petechiae	+	↓	+	+	−	↓	↓	Nl	Reduced platelets	NA	Elevated PT/PTT	Clinical manifestation	Portal vein thrombosis Ascites
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	UA	Gold standard	Associated findings
Giant capillary hemangioma (Kasabach-Merritt syndrome)^[100]^[101]		Platelet destruction	−	+	−	+	−	Infants	Rare but serious infantile coagulopathy	−	Multiple purple hemangioma	Intralesional bleeding	Nl	−	−	Visceral hemangiomas	↓↓	↓↓	Nl	Normocytic normochromic erythrocytes and markedly reduced platelets	Normal erythropoiesis, myelopoiesis, and megakaryocytic hyperplasia	Hematuria Elevated PT/PTT	Biopsy	Kaposiform hemangioendothelioma Tufted angioma
Cardiopulmonary bypass^[102]		Platelet destruction	−	+	−	−	+	Elderly	Coronary artery disease	−	Purpura Petechiae	+	Nl or ↑	−	−	−	↓	↓	Nl	Normocytic normochromic erythrocytes and markedly reduced platelets	NA	Hematuria Elevated PT/PTT	Clinical manifestation	Coagulopathy Hypofibrinogenemia
Alcohol^[103]		Platelet production suppression	+	−	+	−	+	Any	History of alcohol use	−	−	−	Nl	+	+	Hepatomegaly	↓	↓	↓	Cytopenia, macrocytosis	Cytopenia, macrocytosis	Elevated PT/PTT	Clinical manifestation	Chronic liver disease
Post-transfusion purpura^[104]^[105]		Platelet destruction by anti-platelet antibodies	−	+	−	−	+	Women	History of blood transfusion or pregnancy	−	Purpura Petechiae	+	↓	−	−	−	↓↓↓	↓	Nl	Nl	NA	Nl	Positive circulating alloantibody to a common platelet antigen	Severe but rare reaction
Gestational thrombocytopenia^[106]		Might be physiologic adaptation of pregnancy	−	−	−	−	+	Pregnant women	Positive history of mild thrombocytopenia	−	−	−	Nl	−	−	−	↓	Nl	Nl	Nl	NA	Nl	Diagnosis of exclusion	Self-limited condition
HELLP syndrome^[107]^[108]		Unknown	−	+	−	−	+	Pregnant > 25 years	History of preeclampsia	−	−	+	↑	−	+	Abdominal tenderness Ascites	↓	↓	Nl	Schistocytes	NA	Proteinuria	Lab abnormalities	Elevated liver enzymes and bilirubin Multiorgan dysfunction
Idiopathic cyclic thrombocytopenia^[109]		Unknown Might be autoimmune platelet destruction	+	+	−	−	+	Females with the median age of onset 35 years	Misdiagnosed as ITP with uniformly poor responses	−	Purpura Petechiae	Minor mucocutaneous bleeding	Nl	−	−	−	↓	Nl	Nl	Reduced platelets and megakaryocytes	Megakaryocytic hypoplasia or aplasia	Nl	Diagnosis of exclusion	Rebound thrombocytosis Myeloproliferative diseases Myelodysplastic syndrome
Pseudothrombocytopenia^[110]		Platelet clumping due to EDTA	−	−	−	−	+	Rare	Collected sample in EDTA anticoagulant	−	−	−	Nl	−	−	−	↓	Nl	Nl	Low platelet count and platelet clumps	Low platelet count and platelet clumps	Nl	Repeat collecting sample in a heparin tube	Nl
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	UA	Gold standard	Associated findings

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Health Dictionary

Myelodysplastic syndrome differential diagnosis

Introduction

Overview

Differentiating Myelodysplastic Syndrome from other Diseases

Differentiating myelodysplastic syndrome from other causes of macrocytic anemia

Differentiating myelodysplastic syndrome from other causes of thrombocytopenia

References