From the Journals

Remote Canadian province has unusual prevalence of hereditary bleeding disorders



Isolated communities in the Canadian province of Newfoundland and Labrador have an “unusual prevalence” of certain hereditary bleeding disorders, a fact attributable to the province’s unique topography and settlement patterns, according to a new study.

A bleeding finger Crystal/Wikimedia Commons/Creative Commons Attribution 2.0

The prevalence of hemophilia A in Newfoundland and Labrador (NL) is 2.89 times higher than in the rest of Canada. Deficiencies in Factors V, XI, and XIII are 4.54, 5.44, and 9.22 times more prevalent in NL than mainland Canada, respectively. The study also found more cases than expected of the extremely rare hereditary bleeding disorder, Glanzmann thrombasthenia (n = 4). One case of Bernard-Soulier syndrome was also seen, the investigators reported in Transfusion and Apheresis Science.

“This comparatively high prevalence provides a potential pool of patients for genotype/phenotype research,” wrote Mary-Frances Scully, MD, a hematologist at Memorial University, St. John’s, Nfld., and her associates.

In addition to founding populations of indigenous Innu, Inuit, and Mi’kmaq populations, present-day residents of Canada’s easternmost province trace their lineages to about 28,000 settlers who came from southwest England and southeast Ireland for the area’s rich fisheries, explained Dr. Scully and her coauthors. The overall population density of NL is still very low, at about 1.38 individuals per square kilometer, less than half that of Canada overall and far less than the United States’ 36 per square kilometer.

Overall, the investigators reviewed records for 180 patients with hereditary bleeding disorders who were receiving specialty care in St. John’s. Most (n = 127) had hemophilia A; of these patients, those who had mutation testing primarily had the Val 2016A1 mutation. This was particularly true for patients with mild hemophilia A. More than 73% (83/111 patients) carried this mutation, demonstrating a founder effect, wrote Dr. Scully and her coauthors. The next most common hereditary bleeding disorder was Factor XI deficiency, seen in 29 patients.

Additionally, of the seven patients with Factor XIII deficiency, five were homozygous for the c.691-1 G greater than A mutation.

More males in NL than in global comparator data had Factor V deficiency and Glanzmann thrombasthenia, though Dr. Scully and her colleagues acknowledged that the numbers were low overall.

Coagulation tests performed at the time of diagnosis and before treatment initiation were used, when available, to ascertain the severity of the bleeding disorder. Patients were included whether they were heterozygous or homozygous for hereditary bleeding disorders, so long as their baseline coagulation factor levels were below predetermined cutoff levels.

Comparing the prevalence of all the hereditary bleeding disorders identified in the NL population against mainland Canada and that of four other reference countries – Iran, Ireland, the United Kingdom, and the United States – the increased prevalence rates in NL were highly statistically significant (P less than .0001) for all but the single case of Bernard-Soulier syndrome.

Hemophilia B was the only hereditary bleeding disorder seen less frequently in the NL population than in Canada or the other reference populations.

“These results show that NL’s unique geography and population distribution led to a genetic drift that increased the prevalence of some rare factor deficiencies,” wrote Dr. Scully and her colleagues.

The investigators plan to continue investigating and reporting genotype and phenotype correlations among their patient population; they also invite broader international collaboration into the prevalence of rare hereditary bleeding disorders in isolated populations.

The authors reported having no conflicts of interest and no outside sources of funding.

SOURCE: Scully M-F et al. Transfus Apher Sci. 2018 Dec;57(6):713-6.

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