Interstitial 11q Deletions and Terminal 11q Duplications Cause a Bleeding Tendency due to Platelet Dysfunction That...

Jacobsen syndrome, resulting from a terminal deletion of chromosome 11 (11q), may lead to an increased bleeding tendency due to low platelet counts or platelet dysfunction. Currently, information on bleeding tendency and platelet function in patients with nonterminal 11q-aberrations such as larger deletions, interstitial 11q-deletions, or 11q-duplications is lacking.

We investigated the bleeding symptoms in relation to platelet numbers and function in 14 patients: 10 patients with a terminal 11q-deletion, one terminal 11q-duplication, two interstitial 11q-deletions, and one with an interstitial 11q-duplication.

Twelve patients reported bleeding complications (12/14, 86%), most frequently perioperative bleeding (21%), hematomas (17%), epistaxis (13%), prolonged bleeding, and severe bruising (11%) and heavy menstrual bleeding in 4/5 postmenarcheal women (80%). Seven (50%) had platelet counts below normal values (median 62 × 10⁹/L). Strikingly, the seven patients with a normal platelet count reported more frequent perioperative bleeding complications, as well as atypical bleeding such as intramuscular hematoma after injection than the group with low platelet counts. Platelet dysfunction was detected in all (100%) patients by light transmission aggregometry (LTA). Mass-spectrometry (MS) analysis showed an overrepresentation of NUBP2 and ATP5S, both involved in mitochondrial ATP synthesis. Electron microscopy (EM) confirmed abnormal granules in some.

We demonstrated increased bleeding tendency due to platelet disorders in the majority of patients with terminal 11q-deletions but also in nonterminal 11q-aberrations. This is confirmed by abnormal platelet function tests and MS. We therefore recommend screening of patients with all forms of 11q-disorders and, when indicated, preventive preoperative measurements and counseling for heavy menstrual bleeding in females.