International collaboration as a tool for diagnosis of patients with inherited thrombocytopenia in the setting of a developing country.
BACKGROUND
Inherited thrombocytopenias (ITs) are heterogeneous genetic disorders that frequently represent a diagnostic challenge. The requirement of highly specialized tests for diagnosis represents a particular problem in resource-limited settings. To overcome this difficulty, we applied a diagnostic algorithm and developed a collaboration program with a specialized international center in order to increase the diagnostic yield in a cohort of patients in Argentina.


METHODS
Based on the algorithm, initial evaluation included collection of clinical data, platelet size, blood smear examination and platelet aggregation tests. Confirmatory tests were performed according to diagnostic suspicion, which included platelet glycoprotein expression, immunofluorescence for myosin-9 in granulocytes and platelet thrombospondin-1 and molecular screening of candidate genes.


RESULTS
Thirty-one patients from 14 pedigrees were included; their median age was 32 (4-72) years and platelet count 72 (4-147)×10(9) L(-1). Autosomal dominant inheritance was found in nine (64%) pedigrees; 10 (71%) had large platelets and nine (29%) patients presented with syndromic forms. A definitive diagnosis was made in 10 of 14 pedigrees and comprised MYH9-related disease in four, while classic and monoallelic Bernard-Soulier syndrome, gray platelet syndrome, X-linked thrombocytopenia, thrombocytopenia 2 (ANKRD26 mutation) and familial platelet disorder with predisposition to acute myelogenous leukemia were diagnosed in one pedigree each.


CONCLUSIONS
Adoption of an established diagnostic algorithm and collaboration with an expert referral center proved useful for diagnosis of IT patients in the setting of a developing country. This initiative may serve as a model to develop international networks with the goal of improving diagnosis and care of patients with these rare diseases.
Department of Hematology Research, Instituto de Investigaciones Médicas Alfredo Lanari, University of Buenos Aires, CONICET, Buenos Aires, Argentina.
A C
AC
Glembotsky
R F
RF
Marta
A
A
Pecci
D
D
De Rocco
C
C
Gnan
Y R
YR
Espasandin
N P
NP
Goette
F
F
Negro
P
P
Noris
A
A
Savoia
C L
CL
Balduini
F C
FC
Molinas
P G
PG
Heller
D000293:Adolescent; D000328:Adult; D000368:Aged; D000465:Algorithms; D001118:Argentina; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003299:Cooperative Behavior; D004252:DNA Mutational Analysis; D003906:Developing Countries; D005240:Feasibility Studies; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D006297:Health Services Accessibility; D006403:Hematologic Tests / Q000379:methods; D040941:Heredity; D006801:Humans; D007391:International Cooperation; D007558:Italy; D008297:Male; D008875:Middle Aged; D020409:Molecular Motor Proteins / Q000097:blood; D018995:Myosin Heavy Chains / Q000097:blood; D010375:Pedigree; D010641:Phenotype; D010976:Platelet Count; D010979:Platelet Function Tests; D011237:Predictive Value of Tests; D011379:Prognosis; D012017:Referral and Consultation; D013921:Thrombocytopenia / Q000097:blood / Q000151:congenital / Q000175:diagnosis*; D019700:Thrombospondin 1 / Q000097:blood; D055815:Young Adult
D015415:Biomarkers; C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D019700:Thrombospondin 1; D018995:Myosin Heavy Chains