Application of a diagnostic algorithm for inherited thrombocytopenias to 46 consecutive patients.
OBJECTIVE
The Italian Gruppo di Studio delle Piastrine recently developed a diagnostic algorithm to assist clinicians in the diagnosis of inherited thrombocytopenias. This algorithm is based on the simplest possible diagnostic investigations and can also be used in centers that are not highly specialized. The aim of the present study was to validate this diagnostic algorithm by applying it to a case series of genetic thrombocytopenias.


METHODS
The diagnostic algorithm was applied retrospectively to 46 consecutive patients observed during the last five years at a single institution. Twenty-eight were affected by defined illnesses or their variants, while 18 had a disorder that did not fit the criteria for any known genetic thrombocytopenia. The study was based on the evaluation of clinical records and laboratory tests.


RESULTS
The diagnostic algorithm recognized: 4 homozygous and 4 heterozygous Bernard-Soulier syndromes, 11 MYH9-related diseases, one von WillebrandOs disease type 2B, one gray platelet syndrome and one X-linked thrombocytopenia with thalassemia. Moreover, it identified 4 patients with the clinical and laboratory features of heterozygous Bernard-Soulier syndrome not caused by mutations in the coding region of the GPIbalpha, GPIbbeta, GPIX or GPV genes, and two patients with the clinical phenotype of MYH9-related disease but without MYH9 mutations. Since the diagnostic flow chart did not allow prompt recognition of two subjects with MYH9-related disease, we introduced a small change to the previously proposed flow chart to obviate this defect.


CONCLUSIONS
The diagnostic algorithm correctly diagnosed 26 of 28 patients with known disorders or phenotypic variants of known disorders. By a simple modification of the investigation sequence, its sensitivity reached 100%. The algorithm also identified 18 patients with new, as yet uncharacterized forms of genetic thrombocytopenia.
Noris
Patrizia
P
Department of Internal Medicine, IRCCS Policlinico San Matteo-University of Pavia, Italy.
Pecci
Alessandro
A
Di Bari
Filomena
F
Di Stazio
Maria Teresa
MT
Di Pumpo
Michele
M
Ceresa
Iride F
IF
Arezzi
Nicoletta
N
Ambaglio
Chiara
C
Savoia
Anna
A
Balduini
Carlo L
CL
D000465:Algorithms; D001606:Bernard-Soulier Syndrome / Q000175:diagnosis / Q000235:genetics; D001791:Blood Platelet Disorders / Q000175:diagnosis / Q000235:genetics; D001792:Blood Platelets / Q000648:ultrastructure; D048429:Cell Size; D050172:Genes, X-Linked; D005838:Genotype; D005914:Globins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008403:Mass Screening; D020409:Molecular Motor Proteins / Q000235:genetics; D018995:Myosin Heavy Chains / Q000235:genetics; D010974:Platelet Aggregation; D010976:Platelet Count; D010980:Platelet Membrane Glycoproteins / Q000032:analysis / Q000235:genetics; D012189:Retrospective Studies; D013921:Thrombocytopenia / Q000175:diagnosis* / Q000235:genetics; D014842:von Willebrand Diseases / Q000175:diagnosis / Q000235:genetics
C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D010980:Platelet Membrane Glycoproteins; D005914:Globins; D018995:Myosin Heavy Chains