M.Economou1, A.Adramerina1, A.Teli1, S.Symeonidis1, S.Vakalopoulou2

11st Pediatric Department and 22nd Propedeutic Department of Internal Medicine, Medical School of Aristotle University of Thessaloniki, Hippokration General Hospital of Thessaloniki, Greece

Background:

Rare bleeding disorders (RBDs) represent approximately 3–5% of all inherited coagulation deficiencies and are usually transmitted as autosomal recessive traits. Τheir clinical phenotype is characterized by considerable heterogeneity.

Aim:

To report on the experience of a referral center following pediatric patients with RBDs.

Methods:

Records of 18 children diagnosed with RBDs were retrospectively reviewed. Both clinical and laboratory data , covering a 10-year period, were reported as tο:

  • Gender
  • Cause of investigation
  • Age at diagnosis
  • Factor level
  • Comorbidities
  • Bleeding phenotype

Results:

Out of 18 patients 11 (61.1%) were males. Diagnosis was made at a mean age of 7.4 years (2-16 years). In 4 patients (22.2%) comorbidities were reported (deafness, histocytosis, cystic nephropathy or leukodystrophy).

FVII deficiency was the most common RBD reported, observed in 7/18 patients (38.9%) presenting with a mean factor level of 15.6U/dL (3-36.4U/dL). FX and FXII deficiency were each reported in 3 patients (16.7%), who presented with a mean factor level of 36U/dL and 27U/dL, respectively. FV and FXI deficiency were each reported in 2 patients, with a mean factor level of 40U/dL and 35U/dL, respectively. Hypofibrinogenemia was diagnosed in 1 patient (fibrinogen levels 75mg/dl).

Diagnosis was made following:

  1. bleeding manifestations in 4 patients (22.2%),ranging from epistaxis and bleeding from oral cavity to macroscopic hematuria and muscle hematoma
  2. abnormal pre-operative or routine laboratory screening in 7 patients (38.7%), and
  3. investigation due to a positive family history in the rest 7 patients (38.7%).

After diagnosis mild bleeding episodes were reported in 11/18 cases (61.1%), of which 7 (38.9%) resolved without intervention, 2 (11.1%) required tranexamic acid and 2 (11.1%) replacement therapy with the missing factor VII. 3/18 (16.7%) patients underwent mild operations, all of which concerning FVII deficiency. Surgery was performed under replacement therapy, without reported events.

Bleeding phenotype was variable, while correlation between missing factor levels and bleeding tendency was not always clear.

Conclusion:

This long-term single center study confirms clinical variability of RBDs. Most pediatric patients present with a mild bleeding manifestation, however, more severe cases may be encountered. Multi-center registries may help towards better understanding and management of such rare diseases.