Thrombocytopenia differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-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.

Differential Diagnosis

Category Disease History and symptoms Physical exam Laboratory findings Pathology Other specifics
WBC changes RBC/hemoglobinchanges other findings
Cardiovascular endocarditis[1] Skin

Oral Cavity

Eyes

Ear Nose and Throat

Cardiovascular

Lungs

Abdomen

Neurologic

-

Pathological Criteria

  • Microorganisms demonstrated by culture or histological examination of a vegetation, a vegetation that has embolized, or an intracardiac abscess specimen
OR
  • Pathological lesions; vegetation or intracardiac abscess confirmed by histological examination showing active endocarditis
Diagnostic criteria:[2]

Criteria for Rejecting the Diagnosis

  • Firm alternate diagnosis to infective endocarditis
  • Resolution of infective endocarditis syndrome in under 4 days on antibiotics
  • Does not meet the criteria below:

Criteria for Definitive Endocarditis

The Duke Clinical Criteria for definitive infective endocarditis require either:

  • Two major criteria
OR
  • One major and three minor criteria
OR
  • Five minor criteria

Major Criteria

1. Positive Blood Culture for Infective Endocarditis

A. Typical microorganism consistent with infective endocarditis from 2 separate blood cultures, as noted below:
Viridans streptococci, Streptococcus bovis, or
HACEK group, or
☑ Community-acquired Staphylococcus aureus or enterococci, in the absence of a primary focus
OR
B. Microorganisms consistent with infective endocarditis from persistently positive blood cultures defined as:
☑ 2 positive cultures of blood samples drawn >12 hours apart, or
☑ All of 3 or a majority of 4 separate cultures of blood (with first and last sample drawn 1 hour apart)

2. Evidence of endocardial involvement

Positive echocardiogram for infective endocarditis defined as:
☑ Oscillating intracardiac mass on valve or supporting structures, in the path of regurgitant jets, or
☑ On implanted material in the absence of an alternative anatomic explanation, or
☑ Abscess, or
☑ New partial dehiscence of prosthetic valve
OR
☑ New valvular regurgitation (worsening or changing of preexisting murmur not sufficient)

Minor criteria:

☑ Predisposition: predisposing heart condition or intravenous drug use
Fever: temperature > 38.0° C (100.4° F)
☑ Vascular phenomena: major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, and Janeway lesions
☑ Immunologic phenomena: glomerulonephritis, Osler's nodes, Roth spots, and rheumatoid factor
☑ Microbiological evidence: positive blood culture but does not meet a major criterion as noted above (see footnote) or serological evidence of active infection with organism consistent with infectious endocarditis
☑ Echocardiographic findings: consistent with infectious endocarditis but do not meet a major criterion as noted above
Footnote: It should be noted that the criteria exclude single positive cultures for coagulase-negative staphylococci, diphtheroids, and organisms that do not commonly cause endocarditis.
pulmonary embolism[3]
Chemical/poisoning Strontium-89
zinc
Dermatologic Cholesterol embolism General:

Organ-dependent:

Lower extremities

Kidney

Gastroinstestinal

Central nervous system

↑/- ↓/-
-
Griscelli syndrome - - -
Ear Nose Throat Alport syndrome[4][5][6][7][8][9][10][11]
Renal Auditory Ocular
  • Hematuria
  • Proteinuria
  • Hypertension
  • Reduced Creatinine Clearance
  • Early Tinnitus
  • Vertigo
  • High-Frequency Progressive Bilateral Hearing Loss
  • Refractory Error
  • Posterior Polymorphous Dystrophy
  • Arcus
  • Glaucoma
  • Vogt’s White Limbal Girdle
  • Band Keratopathy
  • Lenticonus
  • Spherophakia
  • Cataracts
  • Lens Coloboma
  • Anterior Lenticonus
  • Flecked Retinopathy of the Macula or Periphery

Vital signs

Eyes

Fundoscopy shows:

  • Cataracts
  • Subcapsular posterior lens opacities
  • Lenticonus
  • Retinal flecks (dot-and-fleck retinopathy)
  • Posterior polymorphous corneal dystrophy/corneal epithelial erosions

Ears

Extremities

Miscellaneous

- -

Urinalysis

Electrolytes and Metabolic

- Diagnostic criteria:[12]
Mandatory Criterion Persistent Hematuria
Optional Criteria Presence of at Least 1 of 4:
  • Positive Family History of Alport's Syndrome
  • Characteristic Clinical Features
  • Characteristic Pathology Findings
  • Genetic Testing

The equivocal or non-characteristic finding of any of the above prompts further work-up until the diagnosis is made or rejected.

Arias oculootoradial syndrome
Epstein's syndrome - - - - - -
Fechtner syndrome
Endocrine Immunodysregulation polyendocrinopathy and enteropathy, X-linked
Gastroenterologic Dibasic aminoaciduria type 2
liver failure
Niemann-Pick disease type b
portal hypertension
Genetic Aicardi-Goutieres syndrome
Chediak-Higashi disease
complement factor H deficiency
Fanconi anaemia
Fechtner syndrome
holocarboxylase synthase deficiency
iminodipeptiduria
Jacobsen syndrome
MELAS
Omenn syndrome
TAR syndrome
X-linked hyperimmunoglobulin M syndrome
Hematologic Acquired pure megakaryocytic aplasia
aplastic anemia + / ↓ + / ↓
Bernard-Soulier syndrome
congenital amegakaryocytic thrombocytopenia (CAMT)
disseminated intravascular coagulation
Epstein's syndrome
familial histiocytic reticulosis
Gasser syndrome
GATA1-related cytopenia
Glanzmann's thrombasthenia
grey platelet syndrome
hemolytic uremic syndrome
histiocytosis X
hypersplenism
idiopathic thrombocytopenic purpura
Jacobsen syndrome
Kasabach-Merritt syndrome
May-Hegglin anomaly
Moschcowitz syndrome
myelodysplastic syndrome
myelofibrosis
neonatal alloimmune thrombocytopenia
pancytopenia
Paris-Trousseau thrombocytopenia
paroxysmal nocturnal hemoglobinuria
post-transfusion purpura
radial aplasia-thrombocytopenia syndrome
Sebastian platelet syndrome
Shwachman-Diamond syndrome
thrombotic thrombocytopenic purpura
Von Willebrand disease, platelet type
Werlhof disease
Wiskott-Aldrich syndrome
Iatrogenic Cardiac bypass
chemotherapy
intra-aortic balloon pump placement
massive blood transfusion
radiation therapy
Infectious diseases Congenital syphilis
cytomegalovirus
Dengue fever
ehrlichiosis
Epstein-Barr virus
hantavirus
hepatitis C
HIV
human granulocytic ehrlichiosis
human monocytotropic ehrlichiosis
lassa fever
leptospirosis
malaria
measles
mumps
mycoplasma pneumonia
Oklahoma tick fever
parvovirus
Q fever
rubella
sepsis
tick-borne encephalitis
toxic shock syndrome (staphylococcal)
varicella
visceral leishmaniasis
Nutritional/Metabolic folate deficiency
Gaucher disease
holocarboxylase synthase deficiency
iminodipeptiduria
iron deficiency
isovaleric acidaemia
methylmalonic aciduria type 2
platelet glycoprotein 4 deficiency
platelet glycoprotein Ib deficiency
prolidase deficiency
propionyl-CoA carboxylase deficiency
sea blue histiocytosis
sitosterolemia
vitamin B12 deficiency
Obstetric/Gynecologic Eclampsiapre-eclampsia
HELLP syndrome
Oncologic Acute lymphoblastic leukemia
acute myeloid leukemia
acute promyelocytic leukemia
chronic lymphocytic leukaemia
chronic myeloid leukaemia
hairy cell leukaemia
hepatosplenic T-cell lymphoma
lymphoma
myeloma
Non-Hodgkins lymphoma
paraneoplastic syndrome
Overdose/Toxicity ethanol
arsenic trioxide
Pulmonary Acute respiratory distress syndrome
Renal/Electrolyte hemolytic uremic syndrome
Rheumatology/Immunology/Allergy Anticardiolipin syndrome
antiphospholipid syndrome
autoimmune lymphoproliferative syndrome type 1
autoimmune lymphoproliferative syndrome type 2
complement factor H deficiency
Evans syndrome
immunodysregulation polyendocrinopathy and enteropathy, X-linked
macrophage-activation syndrome
neonatal alloimmune thrombocytopenia
systemic lupus erythematosus
Miscellaneous Snakebites

References

  1. Infective endocarditis. Wikipedia (2015). https://en.wikipedia.org/wiki/Infective_endocarditis Accessed on September 24, 2015
  2. Durack D, Lukes A, Bright D (1994). "New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings. Duke Endocarditis Service". Am J Med. 96 (3): 200–9. PMID 8154507.
  3. Cohen AT, Dobromirski M, Gurwith MM (2014). "Managing pulmonary embolism from presentation to extended treatment". Thromb Res. 133 (2): 139–48. doi:10.1016/j.thromres.2013.09.040. PMID 24182642.
  4. Chugh KS, Sakhuja V, Agarwal A, Jha V, Joshi K, Datta BN; et al. (1993). "Hereditary nephritis (Alport's syndrome)--clinical profile and inheritance in 28 kindreds". Nephrol Dial Transplant. 8 (8): 690–5. PMID 8414153.
  5. McCarthy PA, Maino DM (2000). "Alport syndrome: a review". Clin Eye Vis Care. 12 (3–4): 139–150. PMID 11137428.
  6. Andreoli SP, Deaton M (1992). "Alport's syndrome". Ear Nose Throat J. 71 (10): 508–11. PMID 1425373.
  7. Kashtan CE, Michael AF (1993). "Alport syndrome: from bedside to genome to bedside". Am J Kidney Dis. 22 (5): 627–40. PMID 8238007.
  8. Flinter F (1993). "Molecular genetics of Alport's syndrome". Q J Med. 86 (5): 289–92. PMID 8327646.
  9. Andreoli SP, Deaton M (1992). "Alport's syndrome". Ear Nose Throat J. 71 (10): 508–11. PMID 1425373.
  10. Amari F, Segawa K, Ando F (1994). "Lens coloboma and Alport-like glomerulonephritis". Eur J Ophthalmol. 4 (3): 181–3. PMID 7819734.
  11. Govan JA (1983). "Ocular manifestations of Alport's syndrome: a hereditary disorder of basement membranes?". Br J Ophthalmol. 67 (8): 493–503. PMC 1040106. PMID 6871140.
  12. Savige J, Gregory M, Gross O, Kashtan C, Ding J, Flinter F (2013). "Expert guidelines for the management of Alport syndrome and thin basement membrane nephropathy". J Am Soc Nephrol. 24 (3): 364–75. doi:10.1681/ASN.2012020148. PMID 23349312.

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