Spectrum of hemostatic disorders in Indian females presenting with bleeding manifestations.
Gupta A,Mishra P,Pati H P,Tyagi S,Mahapatra M,Seth T,Saxena R
International journal of laboratory hematology
INTRODUCTION:Hemostatic disorders are often missed in women with bleeding particularly menorrhagia. Preexisting hemostatic disorders are now known as common risk factor for postpartum hemorrhage and prolonged bleeding in puerperium. Females with bleeding complaints constitute an important population referred to hematology clinic. Hence, we aim to evaluate the type and frequency of hemostatic disorders among females presenting with bleeding in a tertiary care hospital and a basic hemostatic laboratory. METHODS:Three-year data were retrospectively analyzed for 200 females with various bleeding complaints. Due to resource constraints, a hemostatic workup was done with prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen assay, clot solubility test, mixing studies, specific factor assays, platelet function test, and von Willebrand factor antigen level. RESULTS:A total of 200 females were investigated to identify the cause of their bleeding. Thirty-five of 200 (17.5%) females were found with an underlying bleeding disorder. Of these 35 females, 65.7% presented with bleeding from more than 1 site. Most common bleeding manifestation was spontaneous bruising in 18 of 35 (51.4%) patients followed by petechiae (48.6%). Inherited bleeding disorders were noted in majority. The most common inherited bleeding disorder identified was von Willebrand disease (VWD) in 34.3% females. Second most common disorder was Glanzmann's thrombasthenia accounting for 22.8%. Rare coagulation factor deficiency, such as factors VII, X, and XIII deficiencies, was noted. Three cases revealed acquired causes of coagulation defects. CONCLUSION:Underlying hemostatic defects should be searched for in women with unexplained bleeding complaints. This will not only help in diagnosis but also in proper management for future hemostatic challenges.
10.1111/ijlh.12806
Endometriosis and Glanzmanns thrombasthenia.
Imperiale L,Manganaro L,Ticino A,Piacenti I,Anastasi E,Resta S,Benedetti Panici P,Porpora M G
Journal of biological regulators and homeostatic agents
Glanzmanns thrombasthenia (GT) is a rare bleeding syndrome characterized by deficiency or defect of platelet aggregation complex. The pathogenesis of endometriosis is controversial but the strongest evidence leans towards retrograde menstruation. GT probably predisposes to endometriosis. The management of women affected by this disease can be difficult due to the risk of bleeding complications, especially during surgical treatment. We describe the cases of three sisters affected by endometriosis and GT, referred to our Department, who received different therapeutic management.
Severe juvenile vaginal bleeding due to Glanzmann's thrombasthenia: case report and review of the literature.
Markovitch O,Ellis M,Holzinger M,Goldberger S,Beyth Y
American journal of hematology
Glanzmann's thrombasthenia is a rare inherited hematological disorder defined by deficiency or abnormality of the glycoprotein (GP) IIb-IIIa complex. Presenting symptoms are hemorrhagic events, mainly epistaxis, purpura, or menorrhagia. We describe the clinical course and management of a 14-year-old girl with Glanzmann's thrombasthenia and severe menorrhagia. Following treatment with 20 U of packed red blood cells, 37 U of platelets, 7 U of fresh frozen plasma, cryoprecipitate, intravenous estrogens, and methylergotrine maleate with no improvement, the uterine cavity was packed for 48 hr. This unusual procedure halted the bleeding and avoided the necessity for a hysterectomy. When treating acute menorrhagia in patients with Glanzmann's thrombasthenia, the physician should be familiar with the characteristics and all treatment modalities for this disorder.
Successful surgery using recombinant factor VIIa for recurrent, idiopathic nonulcer duodenal bleeding in a patient with Glanzmann's thrombasthenia.
van Buuren Henk R,Wielenga Jenne J
Digestive diseases and sciences
A 68-year-old man with Glanzmann's thrombasthenia suffered from recurrent cryptogenic bleeding originating in the upper duodenal flexure. Extensive endoscopic procedures and medical treatments were unsuccessful and proximal duodenectomy was proposed. In preceding years platelet transfusions had often had a suboptimal result and were complicated by allergic reactions. Surgery was carried out while he was being treated with recombinant Factor VIIa. Neither major blood loss nor other complications occurred. Histological examination of the bleeding site failed to show abnormalities and the nature of this patient's bleeding problem remained unexplained. Glanzmann's thrombasthenia is a rare autosomal recessive disorder of platelet aggregation characterized by a lifelong bleeding tendency due to abnormalities of the glycoprotein IIb-IIIa membrane complex. Common clinical manifestations include purpuric type bleeding, epistaxis, menorrhagia and gingival bleeding. Spontaneous bleeding is uncommon but posttraumatic and postoperative hemorrhage may be particularly serious. There is no specific treatment. Prophylactic and therapeutic platelet transfusions are the cornerstone of supportive treatment. In many patients the efficacy of this approach is diminished by allo-anti-platelet antibodies. We report on a patient with Glanzmann's disease with recurrent nonulcer duodenal bleeding refractory to conservative medical treatment. Despite documented suboptimal effectiveness of platelet transfusions, he underwent successful surgery with administration of recombinant factor VIIa (rFVIIa).
10.1023/a:1019605803467
Glanzmann's thrombasthenia: pathogenesis, diagnosis, and current and emerging treatment options.
Solh Tia,Botsford Ashley,Solh Melhem
Journal of blood medicine
Glanzmann's thrombasthenia (GT) is a genetic platelet surface receptor disorder of GPIIb/IIIa (ITG αIIbβ3), either qualitative or quantitative, which results in faulty platelet aggregation and diminished clot retraction. Spontaneous mucocutaneous bleeding is common and can lead to fatal bleeding episodes. Control and prevention of bleeding among patients with GT is imperative, and remains challenging. Local measures, including anti-fibrinolytic therapy, with or without platelet transfusions, used to be the mainstay of therapy. However, in recent years the use of recombinant factor VIIa (rFVIIa) has increased significantly, with excellent response rates in treating and preventing hemorrhage among GT patients. Gene therapy and stem cell transplantation offer a potential cure of this disease, but both are costly and remain experimental at this point. This manuscript offers a comprehensive review of our understanding of GT and the available treatment options.
10.2147/JBM.S71319
The spectrum of bleeding disorders in women with menorrhagia: a report from Western India.
Trasi Sucheta A,Pathare Anil V,Shetty Shrimati D,Ghosh Kanjaksha,Salvi Vinita,Mohanty Dipika
Annals of hematology
In order to evaluate the incidence of hereditary bleeding disorders in patients presenting with menorrhagia, where the usual gynecological and endocrinal causes of bleeding were ruled out by various local ultrasonography (USG) and relevant endocrine investigations, 120 women aged between 18 and 35 years presenting with menorrhagia without any discernable cause were studied using an open design, where the investigators knew that these patients had menorrhagia. These patients were investigated for inherited coagulation defects. Of the 120 women investigated, 19.16% (23 cases) had an inherited coagulation disorder to account for their menorrhagia. Although a majority (11.6%) are patients with von Willebrand's disease (VWD), other rare platelet disorders such as Glanzmann's thrombasthenia (3.3%), Bernard-Soulier syndrome (0.83%), coagulation factor deficiencies such as factor VIII (0.83%), factor X (0.83%), and factor XI (0.83%), and immune thrombocytopenia (0.83%) were also found. Taking a detailed history for bleeding from other sites however minor, paternal consanguinity as well as family history of bleeding tendencies appeared as a very strong predictor for such kinds of disease in patients with menorrhagia. Patients with menorrhagia without a discernable cause, therefore, need evaluation for the congenital coagulation disorders.
10.1007/s00277-004-0905-4
Screening bleeding disorders in adolescents and young women with menorrhagia.
Cakı Kılıç Suar,Sarper Nazan,Zengin Emine,Aylan Gelen Sema
Turkish journal of haematology : official journal of Turkish Society of Haematology
OBJECTIVE:Chronic menorrhagia causes anemia and impairment of life quality. In this study the aim was the screening of bleeding disorders in adolescents and young women with menorrhagia. MATERIALS AND METHODS:The study was performed prospectively by pediatric hematologists. A form including demographic characteristics of the patients, bleedings other than menorrhagia, familial bleeding history, characteristics of the menorrhagia, and impairment of life quality due to menorrhagia was filled out by the researcher during a face-to-face interview with the patient. A pictorial blood assessment chart was also used for evaluation of blood loss. All patients underwent pelvic ultrasound sonography testing and women also received pelvic examination by gynecologists. Whole blood count, peripheral blood smear, blood group, serum transaminases, urea, creatinine, ferritin, PFA-100, PT, aPTT, INR, TT, fibrinogen, VWF:Ag, VWF:RCo, FVIII, and platelet aggregation assays were performed. Platelet aggregations were studied by lumiaggregometer. RESULTS:Out of 75 patients enrolled, 60 patients completed the study. The mean age was 20.68±10.34 (range: 10-48) years and 65% (n=39) of the patients were younger than 18 years. In 18 (46%) of the adolescents, menorrhagia subsided spontaneously. In 20% (n=12) of the patients, a bleeding disorder was detected (1 case of type 3 von Willebrand disease, 2 patients with low VWF:Ag, 1 case of probable von Willebrand disease, 3 cases of Bernard-Soulier syndrome, 2 cases of Glanzmann thrombasthenia, 2 cases of immune thrombocytopenic purpura, 1 case of congenital factor VII deficiency). CONCLUSION:In patients with menorrhagia, at least complete blood count, peripheral smear, aPTT, PT, VWF:Ag, VWF:RCo, FVIII, and fibrinogen assays must be performed. When there is history of nose and gum bleeding, platelet function assay by lumiaggregometer must also be performed. In nearly 50% of adolescents, menorrhagia is dysfunctional and transient. Detailed coagulation assays can be postponed in adolescents if bleeding history other than menorrhagia and/or family history of bleeding and/or parental consanguinity is absent. All subjects with menorrhagia must consult with gynecologists and hematologists. CONFLICT OF INTEREST:None declared.
10.4274/Tjh.2011.0048
Evaluation of the Hemostatic Disorders in Adolescent Girls with Menorrhagia: Experiences from a Tertiary Referral Hospital.
Karaman Kamuran,Ceylan Nesrin,Karaman Erbil,Akbayram Sinan,Akbayram Hatice Tuba,Kaba Sultan,Garipardıç Mesut,Öner Ahmet Fayik
Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion
Bleeding disorders are a common cause of menorrhagia in the adolescent age group. We aimed to evaluate the incidence of hemostatic disorders, using clinical and laboratory findings of bleeding disorders in adolescent girls with menorrhagia. A retrospective chart review used to evaluate adolescent girls with menorrhagia who were referred to Yuzuncu Yil University Pediatric Hematology clinic between January 2010 and December 2014. Out of 52 patients referred for investigation, 50 patients were included in the study. The mean age and mean menarche age were 14.8 ± 1.42 (range: 12-17) and 12.47 ± 0.55, respectively. In 42 % (n = 21) of patients, anemia was detected. In 22 % (n = 11) of patients, a bleeding disorder was detected: five cases with von Willebrand disease, two cases with acute immune thrombocytopenic purpura, one case with Bernard-Soulier syndrome, one case with Glanzmann thrombasthenia, one case with aplastic anemia and one case with factor X deficiency. The remaining 39 out of the 50 patients were finally diagnosed with dysfunctional uterine bleeding. When compared the patients with bleeding disorders and without bleeding disorders, bleeding from other sites, including gingival bleeding or epistaxis, low platelet counts and prolonged activated partial thromboplastin time were found statistically more frequent in patients with bleeding disorders (p < 0.05). Menorrhagia in adolescents is frequently associated with underlying bleeding disorders. Adolescents with heavy menstrual bleeding and a history of nose or gingival bleeding should be evaluated for congenital bleeding disorders.
10.1007/s12288-015-0583-5
Recombinant Activated Factor VII (Eptacog Alfa Activated, NovoSeven®) in Patients with Rare Congenital Bleeding Disorders. A Systematic Review on its Use in Surgical Procedures.
Di Minno Matteo Nicola Dario,Ambrosino Pasquale,Myasoedova Veronika,Amato Manuela,Ventre Itala,Tremoli Elena,Minno Alessandro Di
Current pharmaceutical design
In the absence of definite guidelines in the area, we have carried a systemic review to provide a thorough overview concerning the efficacy and safety of recombinant activated factor VII (rFVIIa, NovoSeven®, Novo Nordisk A/S, Bagsværd, Denmark) in patients with Glanzmann's thrombasthenia (GT) and FVII deficiency, undergoing surgical procedures. PubMed, Web of Science, Scopus and EMBASE databases was employed for the search. Three multicenter registries were identified: the Glanzmann's Thrombasthenia Registry (GTR), the Seven Treatment Evaluation Registry (STER), and a German post-marketing surveillance registry (the WIRK study). In addition, data from 10 case-series and/or single-center experiences have been summarized. We have found that the following; perioperatively, the hemostatic effectiveness of rFVIIa was high in GT patients and in those with FVII deficiency undergoing both minor and major surgical procedures. Moreover, in all studies, rFVIIa was well tolerated. Thus, the current evidence shows an optimal perioperative safety/efficacy profile of rFVIIa in the setting of these rare bleeding disorders, and provides the rationale for further studies aimed at evaluating the optimal perioperative anti-hemorrhagic prophylaxis with rFVIIa in GT and in FVII deficient patients.
10.2174/1381612822666161230143612
Recombinant activated factor VII in clinical practice: a 2014 update.
Franchini Massimo,Crestani Silvia,Frattini Francesco,Sissa Cinzia,Bonfanti Carlo
Journal of thrombosis and thrombolysis
Recombinant activated factor VII (rFVIIa) was initially developed to treat bleeding episodes in patients with congenital hemophilia and inhibitors. Due to the initial success in this clinical setting, its use has been extended to other coagulopathies characterized by impaired thrombin generation, i.e. acquired hemophilia, inherited factor VII deficiency and Glanzmann's thrombasthenia, for which it is currently licensed. Extensive research in the last decade has increased our knowledge of the mechanisms utilized by rFVIIa to restore normal hemostasis. This paper reviews current understanding of the mechanisms of action of rFVIIa before summarizing the clinical experience, in terms of safety and efficacy, to date in its licensed indications.
10.1007/s11239-014-1114-1
Use of recombinant factor VIIa (NovoSeven) in patients with Glanzmann thrombasthenia.
Poon M C,d'Oiron R,Hann I,Négrier C,de Lumley L,Thomas A,Karafoulidou A,Demers C,Street A,Huth-Kühne A,Petrini P,Fressinaud E,Morfini M,Tengborn L,Marquès-Verdier A,Musso R,Devecioglu O,Houston D S,Lethagen S,Van Geet C,von Depka M,Berger C,Beurrier P,Britton H A,Gerrits W,Guthner C,Kuhle S,Lorenzo J J,Makris P E,Nohe N,Paugy P,Pautard B,Torchet M F,Trillot N,Vicariot M,Wilde J,Winter M,Chambost H,Ingerslev J,Peters M,Strauss G
Seminars in hematology
Recombinant factor VIIa (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) appears effective and relatively safe for the treatment of bleeding and for surgical prophylaxis in patients with Glanzmann thrombasthenia as reported to the International Registry on rFVIIa and Congenital Platelet Disorders. One of the shortcomings of the Registry data is the heterogeneity of treatment protocol, including dosage, number of doses used, duration of treatment before declaration of failure, and mode of rFVIIa administration (bolus v continuous infusion). The data are not yet sufficient to define optimal regimens for various indications such as the type of bleeding or the type of procedures. The place of this drug compared to platelet transfusion in the overall management of patients with Glanzmann thrombasthenia will need to be determined in relationship to a number of challenges and unresolved issues in the clinical care of these patients. These issues include: how to improve local measures for patients with mucosal bleeds, optimal management of young women during menarche, optimal platelet transfusion regimens for various indications, the relationship between antiplatelet antibodies detected by monoclonal antibody-specific immobilization of platelet antigens (MAIPA) and effectiveness of platelet transfusion, whether there are other biological tests that may correlate with effectiveness of platelet transfusion, and management of pregnancy and delivery regarding antiplatelet immunization.
10.1016/s0037-1963(01)90143-x