CHICAGO – Standard platelet aggregation studies were not sufficiently sensitive in detecting platelet function disorders in 40% of 35 adolescents with menorrhagia, a study has shown.
All 14 teens were subsequently diagnosed with dense granule platelet storage pool deficiency by electron microscopy, Dr. Lawrence Amesse said at the annual meeting of the North American Society for Pediatric and Adolescent Gynecology.
"Normal platelet aggregation testing in this subset does not exclude additional studies, particularly if there’s a high clinical suspicion and a family history of bleeding tendencies," he said. "Further studies to consider are electron microscopy or lumi-aggregometry, if available, to identify or exclude storage pool deficiencies."
He pointed out that electron microscopy is not feasible in all patients at roughly $500 vs. just $100 for standard platelet aggregation testing, which is increasingly being used to identify platelet function disorders (PFDs) as an etiology of menorrhagia.
Still, standard aggregation testing is difficult and time consuming to conduct, is subject to a wide range of variables, and lacks standardization. Testing with at least two agonists is associated with a significantly higher likelihood of detecting true PFDs, but also creates a clinical dilemma because it would exclude patients having impaired aggregation with only one agonist, explained Dr. Amesse, professor of obstetrics and gynecology and professor of pediatrics at Wright State University in Dayton, Ohio.
He reported on a retrospective analysis of 35 adolescents with PFDs and unexplained menorrhagia who underwent light transmission aggregometry studies using a PACKS-4 (Platelet Aggregation Chromogenic Kinetics System-4) aggregometer with five standard agonists. Aggregation was considered defective when the maximum percentage for platelet aggregation responsiveness was less than reference ranges with at least one agonist.
Interestingly, the girls had normal values of hematocrit, mean corpuscular volume, platelet counts and morphology, prothrombin time, and activated partial thromboplastin time, he said. They were negative for all von Willebrand factor assay studies and had an average pictorial blood loss assessment chart score of more than 100. Their average age was 14.5 years and they began menstruating at a mean age of 11.8 years. The majority (81%) were white and 84% had a family history of bleeding tendencies.
In all, 21 girls (60%) had abnormal aggregation responsiveness with at least one agonist, Dr. Amesse said. Nine girls (43%) had impaired responsiveness with one agonist, six girls (28.6%) with two agonists, and six girls (28.6%) with three or more agonists.
Epinephrine was the most common agonist to elicit reduced aggregation responsiveness (57%), followed by adenosine diphosphate, or ADP (48%), ristocetin (38%), arachidonic acid (24%), and collagen (9.5%).
Of the 14 girls who had impaired platelet aggregation responsiveness with epinephrine, 64% also had reduced aggregation responsiveness with other agonists. The same was true for 70% of the girls who had abnormal aggregation responsiveness with ADP, and for 100% with ristocetin, 80% with arachidonic acid, and 50% with collagen.
"Impaired agonist-induced aggregation patterns showed marked variability," he said.
Overall, 14 of the 35 teens (40%) had normal platelet aggregation responsiveness with all five agonists, and, as noted, were subsequently diagnosed with dense granule storage pool deficiency using electron microscopy. Dense granule deficiency is one of four major types of congenital platelet storage pool disorders that have been identified, and is thought to result in prolonged bleeding times because of reduced release of ADP by platelet-dense granules. Clinical features of storage pool disorders include nosebleeds, menorrhagia, easy bruising, recurrent anemia, and obstetric or surgical bleeding.
An audience member asked whether the girls had other bleeding symptoms and whether they started off with normal periods and developed menorrhagia later on. Dr. Amesse replied that two-thirds had other bleeding symptoms such as nosebleeds and easy bruising, and that most began menstruating normally. He pointed out that contrary to other studies in von Willebrand’s disease, all of the girls had normal hematocrit and hemoglobin levels, suggesting a chronic rather than an acute presentation.
When asked how the girls were treated, he said they were typically treated with oral contraceptives.
Dr. Amesse reported receiving a grant from the CSL Behring Foundation.