International collaboration as a tool for diagnosis of patients with inherited thrombocytopenia in the setting of a developing country

Background:\u2002Inherited thrombocytopenias (IT) are heterogeneous genetic disorders which frequently represent a diagnostic challenge. Requirement of highly specialized tests for diagnosis represents a particular problem in resource-limited settings. To overcome this difficulty, we applied a diagnostic algorithm and developed a collaboration program with a specialized international center in order to increase the diagnostic yield in a cohort of patients in Argentina. Methods:\u2002Based on the algorithm, initial evaluation included collection of clinical data, platelet size, blood smear examination and platelet aggregation tests. Confirmatory tests were performed according to diagnostic suspicion, and included platelet glycoprotein expression, immunofluorescence for myosin-9 in granulocytes and platelet thrombospondin-1 and molecular screening of candidate genes. Results:\u2002Thirty-one patients from 14 pedigrees were included, age was 32 (4-72) years, platelet count was 72 (4-147) x10(9) /L. Autosomal dominant inheritance was found in 9 (64%) pedigrees, 10 (71%) had large platelets and 9 (29%) patients presented with syndromic forms. A definitive diagnosis was made in 10 of 14 pedigrees and comprised MYH9-related disease in 4, while classic and monoallelic Bernard-Soulier syndrome, gray platelet syndrome, X-linked thrombocytopenia, Thrombocytopenia 2 (ANKRD26 mutation) and familial platelet disorder with predisposition to acute myelogenous leukemia were diagnosed in 1 pedigree each. Conclusions:\u2002Adoption of an established diagnostic algorithm and collaboration with an expert referral center proved useful for diagnosis of IT patients in the setting of a developing country. This initiative may serve as a model to develop international networks with the goal of improving diagnosis and care of patients with these rare diseases. \ua9 2012 International Society on Thrombosis and Haemostasis

Antithrombotic prophylaxis for surgery-associated venous thromboembolism risk in patients with inherited platelet disorders. The SPATA-DVT Study

none32Major surgery is associated with an increased risk of venous thromboembolism, thus the application of mechanical or pharmacologic prophylaxis is recommended. The incidence of venous thromboembolism in patients with inherited platelet disorders undergoing surgical procedures is unknown and no information on the current use and safety of thromboprophylaxis, particularly of low-molecular-weight-heparin in these patients is available. Here we explored the approach to thromboprophylaxis and thrombotic outcomes in inherited platelet disorders patients undergoing surgery at venous thromboembolism-risk participating in the multicenter SPATA study. We evaluated 210 surgical procedures carried out in 155 patients with well-defined forms of inherited platelet disorders (venous thromboembolism-risk: 31% high, 28.6% intermediate, 25.2% low, 15.2% very low). The use of thromboprophylaxis was low (23.3% of procedures), with higher prevalence in orthopedic and gynecological surgeries, and was related to venous thromboembolism-risk. The most frequently employed thromboprophylaxis was mechanical and appeared to be effective, as no patients developed thrombosis, including patients belonging to the highest venous thromboembolism-risk classes. Low-molecular-weight-heparin use was low (10.5%) and it did not influence the incidence of post-surgical bleeding or of antihemorrhagic prohemostatic interventions. Two thromboembolic events were registered, both occurring after high venous thromboembolism-risk procedures in patients who did not receive thromboprophylaxis (4.7%). Our findings suggest that venous thromboembolism incidence is low in patients with inherited platelet disorders undergoing surgery at venous thromboembolism-risk and that it is predicted by the Caprini score. Mechanical thromboprophylaxis may be of benefit in patients with inherited platelet disorders undergoing invasive procedures at venous thromboembolism-risk and low-molecular-weight-heparin should be considered for major surgery.nonePaciullo, Francesco; Bury, Loredana; Noris, Patrizia; Falcinelli, Emanuela; Melazzini, Federica; Orsini, Sara; Zaninetti, Carlo; Abdul-Kadir, Rezan; Obeng-Tuudah, Deborah; Heller, Paula; Glembotsky, Ana C; Fabris, Fabrizio; Rivera, Jose; Lozano, Maria Luisa; Butta, Nora; Favier, Remi; Cid, Ana Rosa; Fouassier, Marc; Podda, Gian Marco; Santoro, Cristina; Grandone, Elvira; Henskens, Yvonne; Nurden, Paquita; Zieger, Barbara; Cuker, Adam; Devreese, Katrien; Tosetto, Alberto; De Candia, Erica; Dupuis, Arnaud; Miyazaki, Koji; Othman, Maha; Gresele, PaoloPaciullo, Francesco; Bury, Loredana; Noris, Patrizia; Falcinelli, Emanuela; Melazzini, Federica; Orsini, Sara; Zaninetti, Carlo; Abdul-Kadir, Rezan; Obeng-Tuudah, Deborah; Heller, Paula; Glembotsky, Ana C; Fabris, Fabrizio; Rivera, Jose; Lozano, Maria Luisa; Butta, Nora; Favier, Remi; Cid, Ana Rosa; Fouassier, Marc; Podda, Gian Marco; Santoro, Cristina; Grandone, Elvira; Henskens, Yvonne; Nurden, Paquita; Zieger, Barbara; Cuker, Adam; Devreese, Katrien; Tosetto, Alberto; De Candia, Erica; Dupuis, Arnaud; Miyazaki, Koji; Othman, Maha; Gresele, Paol

Validation of the ISTH/SSC bleeding assessment tool for inherited platelet disorders: a communication from the Platelet Physiology SSC

Careful assessment of the bleeding history is the first step in the evaluation of patients with mild/moderate bleeding disorders, and the use of a bleeding assessment tool (BAT) is strongly encouraged. Although a few studies have assessed the utility of the ISTH-BAT in patients with inherited platelet function disorders (IPFD) none of them was sufficiently large to draw conclusions and/or included appropriate control groups

Analysis of 339 pregnancies in 181 women with 13 different forms of inherited thrombocytopenia

Pregnancy in women with inherited thrombocytopenias is a major matter of concern as both the mothers and the newborns are potentially at risk of bleeding. However, medical management of this condition cannot be based on evidence because of the lack of consistent information in the literature. To advance knowledge on this matter, we performed a multicentric, retrospective study evaluating 339 pregnancies in 181 women with 13 different forms of inherited thrombocytopenia. Neither the degree of thrombocytopenia nor the severity of bleeding tendency worsened during pregnancy and the course of pregnancy did not differ from that of healthy subjects in terms of miscarriages, fetal bleeding and pre-term births. The degree of thrombocytopenia in the babies was similar to that in the mother. Only 7 of 156 affected newborns had delivery-related bleeding, but 2 of them died of cerebral hemorrhage. The frequency of delivery-related maternal bleeding ranged from 6.8% to 14.2% depending on the definition of abnormal blood loss, suggesting that the risk of abnormal blood loss was increased with respect to the general population. However, no mother died or had to undergo hysterectomy to arrest bleeding. The search for parameters predicting delivery-related bleeding in the mother suggested that hemorrhages requiring blood transfusion were more frequent in women with history of severe bleedings before pregnancy and with platelet count at delivery below 50 7 109/L

Validation of the ISTH/SSC bleeding assessment tool for inherited platelet disorders : a communication from the Platelet Physiology SSC

Background: Careful assessment of bleeding history is the first step in the evaluation of patients with mild/moderate bleeding disorders, and the use of a bleeding assessment tool (BAT) is strongly encouraged. Although a few studies have assessed the utility of the ISTH-BAT in patients with inherited platelet function disorders (IPFD) none of them was sufficiently large to draw conclusions and/or included appropriate control groups. Objectives: The aim of the present study was to test the utility of the ISTH-BAT in a large cohort of patients with a well-defined diagnosis of inherited platelets disorder in comparison with two parallel cohorts, one of patients with type-1 von Willebrand disease (VWD-1) and one of healthy controls (HC). Patients/Methods: We enrolled 1098 subjects, 482 of whom had inherited platelet disorders (196 IPFD and 286 inherited platelet number disorders [IT]) from 17 countries. Results: IPFD patients had significantly higher bleeding score (BS; median 9) than VWD-1 patients (median 5), a higher number of hemorrhagic symptoms (4 versus 3), and higher percentage of patients with clinically relevant symptoms (score > 2). The ISTH-BAT showed excellent discrimination power between IPFD and HC (0.9 < area under the curve [AUC] < 1), moderate (0.7 < AUC < 0.9) between IPFD and VWD-1 and between IPFD and inherited thrombocytopenia (IT), while it was inaccurate (AUC  64 0.7) in discriminating IT from HC. Conclusions: The ISTH-BAT allows to efficiently discriminate IPFD from HC, while it has lower accuracy in distinguishing IPFD from VWD-1. Therefore, the ISTH-BAT appears useful for identifying subjects requiring laboratory evaluation for a suspected IPFD once VWD is preliminarily excluded