Analysis of 12,517 inhabitants of a Sardinian geographic isolate reveals that predispositions to thrombocytopenia and thrombocytosis are inherited traits

Abstract

Background: Thrombocytopenia is a common finding in several diseases but almost nothing is known about the prevalence of thrombocytopenia in the general population. We examined the prevalence of thrombocytopenia and determinants of platelet count in a healthy population with a wide age range.

Design and methods: We performed a cross-sectional study on 12,517 inhabitants of ten villages (80% of residents) in a secluded area of Sardinia (Ogliastra). Participants underwent a complete blood count evaluation and a structured questionnaire, used to collect epidemiological data.

Results: We observed a platelet count lower than 150 × 10⁹/L in 3.2% (2.8%-3.6%) of females and 4.8% (4.3%-5.4%) of males, with a value of 3.9% (3.6%-4.3%) in the entire population. Thrombocytopenia was mild (platelet count: 100 × 10⁹/L-150 × 10⁹/L), asymptomatic and not associated with other cytopenias or overt disorders in most cases. Its standardized prevalence was quite different in different villages, with values ranging from 1.5% to 6.8%, and was negatively correlated with the prevalence of a mild form of thrombocytosis, which ranged from 0.9% to 4.5%. Analysis of platelet counts across classes of age revealed that platelet number decreased progressively with aging. As a consequence, thrombocytopenia was nearly absent in young people and its prevalence increased regularly during lifetime. The opposite occurred for thrombocytosis.

Conclusions: Given the high genetic differentiation among Ogliastra villages with "high" and "low" platelet counts and the substantial heritability of this quantitative trait (54%), we concluded that the propensity to present mild and transient thrombocytosis in youth and to acquire mild thrombocytopenia during aging are new genetic traits.

Figure 1.

Ogliastra region. Geographical location of the ten villages participating in the epidemiological survey.

Figure 2.

(A) Platelet count in Ogliastra villages. Mean values are age- and sex-adjusted by ANOVA, (95% C.I.). (A) Age- and sex-adjusted platelet count densities in Ogliastra. Relative densities are plotted grouping villages as follows: Talana and Urzulei, (northern inner Ogliastra), Seui, Seulo and Ussassai (western Ogliastra), Baunei, Loceri, Perdasdefogu, Escalaplano and Triei (remainder).

Figure 3.

(A) Platelet count by age and sex. Mean platelet count, with 1 SD, in the overall sample. (B) Relationship of thrombocytopenia and thrombocytosis with age. Sex-adjusted age-specific prevalence of thrombocytopenia and thrombocytosis in the overall sample. (C) Relationship of thrombocytopenia and thrombocytosis with age by groups of villages. Proportions along with standard errors, are plotted grouping villages as follows: Talana and Urzulei, (northern inner Ogliastra), Seui, Seulo and Ussassai (western Ogliastra), Baunei, Loceri, Perdasdefogu, Escalaplano and Triei (remainder).