Andrea Artoni1, Angelo Selicorni2, Serena M Passamonti1, Anna Lecchi1, Paolo Bucciarelli1, Marta Cerutti3, Paola Cianci2, Francesca Gianniello1, Ida Martinelli4. 1. Department of Internal Medicine and Medical Specialties, A. Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy; 2. Pediatric Unit, San Gerardo Hospital, Monza, Italy; and. 3. Pediatric Clinic 1, Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy. 4. Department of Internal Medicine and Medical Specialties, A. Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy; martin@policlinico.mi.it.
Abstract
BACKGROUND: A bleeding diathesis is a common feature of Noonan syndrome, and various coagulation abnormalities have been reported. Platelet function has never been carefully investigated. METHODS: The degree of bleeding diathesis in a cohort of patients with Noonan syndrome was evaluated by a validated bleeding score and investigated with coagulation and platelet function tests. If ratios of prothrombin time and/or activated partial thromboplastin time were prolonged, the activity of clotting factors was measured. Individuals with no history of bleeding formed the control group. RESULTS: The study population included 39 patients and 28 controls. Bleeding score was ≥2 (ie, suggestive of a moderate bleeding diathesis) in 15 patients (38.5%) and ≥4 (ie, suggestive of a severe bleeding diathesis) in 7 (17.9%). Abnormal coagulation and/or platelet function tests were found in 14 patients with bleeding score ≥2 (93.3%) but also in 21 (87.5%) of those with bleeding score <2. The prothrombin time and activated partial thromboplastin time were prolonged in 18 patients (46%) and partial deficiency of factor VII, alone or in combination with the deficiency of other vitamin K-dependent factors, was the most frequent coagulation abnormality. Moreover, platelet aggregation and secretion were reduced in 29 of 35 patients (82.9%, P < .01 for all aggregating agents). CONCLUSIONS: Nearly 40% of patients with the Noonan syndrome had a bleeding diathesis and >90% of them had platelet function and/or coagulation abnormalities. Results of these tests should be taken into account in the management of bleeding or invasive procedures in these patients.
BACKGROUND: A bleeding diathesis is a common feature of Noonan syndrome, and various coagulation abnormalities have been reported. Platelet function has never been carefully investigated. METHODS: The degree of bleeding diathesis in a cohort of patients with Noonan syndrome was evaluated by a validated bleeding score and investigated with coagulation and platelet function tests. If ratios of prothrombin time and/or activated partial thromboplastin time were prolonged, the activity of clotting factors was measured. Individuals with no history of bleeding formed the control group. RESULTS: The study population included 39 patients and 28 controls. Bleeding score was ≥2 (ie, suggestive of a moderate bleeding diathesis) in 15 patients (38.5%) and ≥4 (ie, suggestive of a severe bleeding diathesis) in 7 (17.9%). Abnormal coagulation and/or platelet function tests were found in 14 patients with bleeding score ≥2 (93.3%) but also in 21 (87.5%) of those with bleeding score <2. The prothrombin time and activated partial thromboplastin time were prolonged in 18 patients (46%) and partial deficiency of factor VII, alone or in combination with the deficiency of other vitamin K-dependent factors, was the most frequent coagulation abnormality. Moreover, platelet aggregation and secretion were reduced in 29 of 35 patients (82.9%, P < .01 for all aggregating agents). CONCLUSIONS: Nearly 40% of patients with the Noonan syndrome had a bleeding diathesis and >90% of them had platelet function and/or coagulation abnormalities. Results of these tests should be taken into account in the management of bleeding or invasive procedures in these patients.
Authors: Francesca Di Candia; Valeria Marchetti; Ferdinando Cirillo; Alessandro Di Minno; Carmen Rosano; Stefano Pagano; Maria Anna Siano; Mariateresa Falco; Antonia Assunto; Giovanni Boccia; Gerardo Magliacane; Valentina Pinna; Alessandro De Luca; Marco Tartaglia; Giovanni Di Minno; Pietro Strisciuglio; Daniela Melis Journal: Orphanet J Rare Dis Date: 2021-12-02 Impact factor: 4.123