Thrombocytopenia 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], Farbod Zahedi Tajrishi, M.D. [2]

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
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[1]
  • Unknown
  • Mutation
+ ± + Elderly Exposure to + Petechiae, purpura, diffuse erythematous rash + Nl + + Nl Nl Nl Bone marrow examination + clinical manifestation
Aplastic anemia[2] + ± ± Biphasic (the young and the elderly) + Nl Nl Bone marrow examination +

laboratory findings

Acute leukemia[3][4] + + ± ± AML in adults
  • Exposure to chemicals
  • Radiation
  • Pre-existent blood disorders
± Petechiae + Nl ±
  • Blast cells
Bone marrow examination
Paroxysmal nocturnal hemoglobinuria (PNH)[5]
  • Mutations
+ + + Any age

(usually younger adults)

Nl ↓/Nl ↓/Nl
  • Hypocellular marrow in certain stages of the disease
Nl Nl Flow cytometry
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 Gold standard Associated findings
Thrombotic microangiopathy (TMA) Thrombotic thrombocytopenic purpura (TTP)[6]
  • Deficiency of, or antibodies to, the metalloprotease ADAMTS13  
+ ± + Any age
  • Neurologic manifestations
  • Fatigue due to anemia
+ Petechiae Not common Nl or ↑ + Nl

or ↑

  • Fragmented RBCs
NA Nl Nl Laboratory findings
Hemolytic uremic syndrome (HUS)[7] + ± + Children
  • Exposure to contaminated water or milk
  • Consuming undercooked ground beef
+ Petechiae + Nl

or ↑

  • Fragmented RBCs
NA Nl Nl Laboratory findings
DIC[8][9]
  • Overstimulation of the coagulation system
+ + + Any age + + + + ↓↓ ↑↑ Clinical manifestation + laboratory findings
Nutrient deficiencies Folate, vitamin B12, copper deficiencies[10][11]
  • Decreased platelet production
+ + Any age
  • Malnutrition
  • Alcohol use
Nl Nl Nl Nl Nl Laboratory findings
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 Gold standard Associated findings
Congenital platelet disorders[12][13][14] MYH9-related disorders[15] + + Any age, very rare
  • Positive family history
+ Nl Nl
  • Döhle body-like inclusions in peripheral blood neutrophils
NA Nl Nl Nl Genetic study
Bernard-Soulier syndrome[16]
  • Absence of Gp Ib-IX-V  
+ + Children, rare
  • Positive family history
+ Nl Nl Nl Nl Nl Nl Flow cytometry
Gray platelet syndrome[17] + + Rare
  • Positive family history
+

Mucocutaneous

Nl + Nl Nl Nl Nl Nl Genetic study
Wiskott-Aldrich syndrome[18] + + Rare
  • Positive family history
+ Nl Bloody diarrhea Nl Nl Nl Nl Nl Genetic study
Thrombocytopenia with absent radius (TAR) syndrome[19] + + Children
  • Positive family history
+ + Nl Nl Nl or ↑ Nl Nl Nl Evidence of absent radius

+

Laboratory findings

  • Cow's milk allergy
  • Various other anomalies
Fechtner syndrome[20]
  • Mutation of chromosome 22q11-13
+ + Children
  • Positive family history

petechia

+ Mucocutaneous Nl
  • Hearing loss
  • Eye abnormalities
Nl Nl or ↑ NA Nl Nl Clinical manifestation + genetic study
Von Willebrand disease[21]
  • VWF deficiency/dysfunction
+ + Rarely More common with O blood type
  • Positive family history
+ Nl/ ↓ Nl/↓ Nl NA Nl Nl or ↑ Laboratory findings
  • Lifelong bleeding disorder
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 Gold standard Associated findings
Rheumatologic/autoimmune disorders ITP[22] + + + Any age

petechia

+ Mucocutaneous Nl ↓↓↓ Nl Nl Nl Nl Nl Nl Diagnosis of exclusion
  • Spontaneous remission  
Systemic lupus erythematosus[23] + + Young women, more prevalent in Africans and Asians + Malar rash, generalized maculopapular rash, discoid rash +

Hemoptysis

Nl or ↑ + + Clinical manifestation + serology
Antiphospholipid syndrome[24]
  • Autoantibody-mediated syndrome
+ + + Middle aged women, more in African American and Hispanic population Nl Nl Nl Clinical manifestation + repeated positive tests of aPL
Felty's syndrome[25] + + ± + Rare, young women Nl +
  • Lymphadenopathy
Nl Nl Nl Nl Clinical manifestation
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 Gold standard Associated findings
Infection-induced Bacterial infections Sepsis[26] + + + Any + ± Nl to ↓ ± ↓/↑ Nl ↑↑ NA +

Depends on the etiology

Clinical manifestation + culture
  • Associated with ↑ mortality
Helicobacter pylori[27]
  • Immune thrombocytopenia
+ + Any Nl Nl Nl NA Nl Nl Nl Clinical manifestation + culture
Tick-borne infection[28]
  • Immune thrombocytopenia
+ + Endemic area like China, Japan, and Korea
  • Being bitten by a tick
+ ± Nl to ↓ ± ± Nl NA Nl Nl PCR
Viral infections HIV[29]
  • Immune thrombocytopenia
+ + + + Any
  • High risk behaviors
  • Close contact
+ ± Nl to ↓ ± ± Isolation of HIV
Other viruses such as rubella, mumps, varicella, parvovirus, hepatitis C, & Epstein-Barr virus[30]
  • Immune thrombocytopenia
+ + Any
  • High risk behaviors
  • Close contact
+ Nl ± ± Nl Nl Clinical manifestation + lab tests
Parasitic infections Malaria[31]
  • Unknown
  • Immune thrombocytopenia
+ + Endemic area
  • Being bitten by a mosquito
+ ± Nl to ↓ ± ± Nl Nl Clinical manifestation + microscopic examination of blood smear
Babesiosis[32]
  • Unknown
  • Immune thrombocytopenia
+ + Rare + ± Nl to ↓ ± ± Nl Nl Clinical manifestation + microscopic examination of blood smear
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 Gold standard Associated findings
Medication/toxicity Antibiotics/

Antiepileptic[33]

  • Occurrence of drug-dependent, platelet-reactive antibodies
+ + + Any
  • Drug ingestion or injection
Nl ↓↓ Nl NA Nl Nl Nl Clinical manifestation + exclusion of the other causes NA
Heparin-induced thrombocytopenia[34]
  • Anti-heparin/PF4 antibody 
+ + Any
  • Heparin injection
  • Necrotic skin lesions
Nl Nl Nl NA Nl Nl Nl ELISA
Cytotoxic chemotherapy[35] + + Patients with malignancy
  • Drug ingestion or injection
  • Cancer
Nl
  • Megakaryocytic hypoplasia or aplasia
Hematuria Clinical manifestation + exclusion of the other causes
Radiation therapy[36] + + Patients with malignancy + Nl
  • Megakaryocytic hypoplasia or aplasia
Hematuria Clinical manifestation + exclusion of the other causes
GI Chronic liver disease[37] + + Any + + + Nl NA Nl Biopsy
Portal hypertension[38] + + Any + + + Nl NA Nl Clinical manifestation
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 Gold standard Associated findings
Vascular Giant capillary hemangioma (Kasabach-Merritt syndrome)[39][40] + + Infants Intralesional bleeding Nl Visceral hemangiomas ↓↓ ↓↓ Nl Normocytic normochromic erythrocytes and markedly reduced platelets Normal erythropoiesis, myelopoiesis, and megakaryocytic hyperplasia Hematuria Biopsy
  • Kaposiform hemangioendothelioma
  • Tufted angioma
Cardiopulmonary bypass[41] + + Elderly + Nl or ↑ Nl Normocytic normochromic erythrocytes and markedly reduced platelets NA Hematuria Clinical manifestation
Other Alcohol[42] + + + Any Nl + + Cytopenia, macrocytosis Cytopenia, macrocytosis Nl Clinical manifestation
Post-transfusion purpura[43][44] + + Women + ↓↓↓ Nl Nl NA Nl Nl Nl Positive circulating alloantibody to a common platelet antigen
  • Severe but rare reaction
Gestational thrombocytopenia[45]
  • Might be physiologic adaptation of pregnancy
+ Pregnant women
  • Positive history of mild thrombocytopenia
Nl Nl Nl Nl NA Nl Nl Nl Diagnosis of exclusion
  • Self-limited condition
HELLP syndrome[46][47]
  • Unknown
+ + Pregnant > 25 years + + Nl Schistocytes NA Nl Nl Proteinuria Lab abnormalities
Idiopathic cyclic thrombocytopenia[48] + + + Females with the median age of onset 35 years
  • Misdiagnosed as ITP with uniformly poor responses
Minor mucocutaneous bleeding Nl Nl Nl Reduced platelets and megakaryocytes Megakaryocytic hypoplasia or aplasia Nl Nl Nl Diagnosis of exclusion
Pseudothrombocytopenia[49] + Rare Collected sample in EDTA anticoagulant Nl Nl Nl Low platelet count and platelet clumps Low platelet count and platelet clumps Nl Nl Nl Repeat collecting sample in a heparin tube Nl
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 Gold standard Associated findings

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