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2.
Br J Haematol ; 182(5): 621-632, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30117143

RESUMO

The inherited platelet glycoprotein deficiencies, Glanzmann thrombasthenia (GT) and Bernard Soulier syndrome (BSS) are rare but important long-term bleeding disorders. Once diagnosed, affected patients should be referred to a specialist centre for bleeding disorders for general advice and ongoing management. Patients do not require prophylactic treatment and so the management of GT and BSS focuses around prophylactic treatment prior to high risk procedures and treatment in response to non-surgical bleeding events and, in women, the management of menorrhagia and pregnancy. There is no consistent approach to the treatment or prevention of bleeding complications. Management must be tailored for each individual and the approach may not be the same for different events, even for the same patient, depending on the type of accident or invasive procedure, the extent of bleeding and the presence or not of platelet refractoriness.


Assuntos
Síndrome de Bernard-Soulier/patologia , Gerenciamento Clínico , Glicoproteínas da Membrana de Plaquetas/deficiência , Trombastenia/patologia , Adulto , Síndrome de Bernard-Soulier/terapia , Criança , Feminino , Hemorragia/etiologia , Hemorragia/terapia , Humanos , Masculino , Menorragia/etiologia , Menorragia/terapia , Medicina de Precisão/métodos , Gravidez , Trombastenia/terapia
3.
Blood Cells Mol Dis ; 72: 44-48, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30078718

RESUMO

BACKGROUND: Glanzmann thrombasthenia (GT) is a disorder of platelet function. Standard therapy includes platelet transfusions, which may be hampered by antiplatelet antibodies. AIMS: To assess potential correlation between bleeding and number of active platelets in GT patients undergoing surgery. Clinical peri- operative patients' hemostasis was compared with flow cytometry analysis (FC), and whole blood clot formation. METHODS: GT patients undergoing surgery were included. Blood counts, platelet activation studies, FC and rotational thromboelastography (ROTEM) were performed as ancillary tests to estimate the effectiveness of treatment. RESULTS: A total of 4 GT patients undergoing 5 surgeries were included. Consecutive FC analysis following platelet transfusions showed gradual decrease of donor platelets with a nadir of 3280 platelets in patients who experienced no post procedural bleeding following minor procedures. After major surgery, bleeding occurred when donor platelets decreased to 2600-4280. Decline in donor platelets was associated with reduced clot firmness as noted by ROTEM. CONCLUSION: Results suggest that very low number of active donor platelets may suffice to achieve proper hemostasis in certain procedures. Our study points to the potential role of consecutive FC examinations to demonstrate the number of donor platelets as an ancillary tool for decision making in GT patients undergoing surgery.


Assuntos
Assistência Perioperatória/métodos , Transfusão de Plaquetas/normas , Trombastenia/terapia , Doadores de Sangue , Tomada de Decisões , Feminino , Citometria de Fluxo , Hemostasia , Humanos , Masculino , Contagem de Plaquetas , Trombastenia/cirurgia
4.
Br J Haematol ; 181(2): 173-182, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29611179

RESUMO

Glanzmann thrombasthenia (GT) is caused by inherited defects of the αIIb ß3 platelet glycoprotein. This bleeding disorder can be treated with platelet transfusion therapy, but some patients will be immunized and begin to form anti-human leucocyte antigen (HLA) and/or anti-αIIb ß3 antibodies. These antibodies can bind and interfere with the function of the transfused platelets, rendering treatment ineffective. However, platelet transfusion refractoriness attributable to HLA antibodies may be managed by the selection of compatible donors, although they are not always readily available, particularly in an emergency. Thus, anti-αIIb ß3 antibodies represent one of the most severe complications in GT. Both genetic and environmental factors may contribute to the risk of anti-αIIb ß3 development, but the underlying pathogenic mechanisms are still unknown. This review will summarize the current knowledge of the risk factors for development of anti-αIIb ß3 antibodies in patients with GT and discuss how these findings may influence the clinical management of patients.


Assuntos
Autoanticorpos , Imunização , Complexo Glicoproteico GPIIb-IIIa de Plaquetas , Transfusão de Plaquetas/efeitos adversos , Trombastenia , Reação Transfusional , Autoanticorpos/sangue , Autoanticorpos/imunologia , Humanos , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/imunologia , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Fatores de Risco , Trombastenia/sangue , Trombastenia/imunologia , Trombastenia/terapia
5.
BMC Womens Health ; 18(1): 45, 2018 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-29486748

RESUMO

BACKGROUND: Glanzmann's Thrombasthenia (GT) is an inherited genetic disorder caused by defects in the platelet membrane glycoproteins IIb/IIIA, and is associated with heavy menstrual bleeding (HMB). HMB is a common complication in female patients, and many adolescent girls with this disease have issues with HMB beginning at menarche. The available treatment modalities including anti-fibrinolytics, nonsteroidal anti-inflammatory drugs (NSAIDs) and hormonal therapies though are effective, their associated side effects, limited efficacy and the poor compliance is a challenge in management of HMB. Levonorgestrel-releasing intrauterine system (LNG-IUS) has been a potential alternative to overcome this challenge. The use of the LNG-IUS for the management of HMB in adolescents with GT is explored in this case series. CASE PRESENTATION: Two adolescents diagnosed with GT and received the LNG-IUS as treatment modality for management of HMB is discussed in this case series. CONCLUSIONS: For patients with poor compliance to oral hormonal therapies, the use of LNG-IUS is associated with a significant reduction of menstrual blood loss along with improved quality of life. These findings support the use of LNG-IUS to control adolescent GT-related HMB.


Assuntos
Anticoncepcionais Femininos/uso terapêutico , Dispositivos Intrauterinos Medicados , Levanogestrel/uso terapêutico , Trombastenia/terapia , Adolescente , Preparações de Ação Retardada , Feminino , Humanos , Qualidade de Vida , Projetos de Pesquisa , Trombastenia/prevenção & controle
6.
Blood Coagul Fibrinolysis ; 29(3): 327-329, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29474205

RESUMO

: We report herein the successful perioperative management of a 57-year-old man with a type I Glanzmann thrombasthenia undergoing coronary artery bypass graft surgery and right carotid endarterectomy. The patient suffered from several lesions in the three major coronary arteries and in the right carotid necessitating surgery. Prophylactic human leukocyte antigen (HLA)-matched platelets transfusions were continuous administrated before, and through the immediate perioperative period. Posttransfusion platelet recovery was monitored using flow cytometry to determine the percentage of circulating platelet expressing CD61 (ß3). No bleeding complications occurred during and following the procedure. The patient did not develop HLA antibodies or αIIbß3 antibodies. Thrombophilia screening revealed a heterozygous G20210A prothrombin gene mutation. The patient also suffered from an atrial fibrillation, necessitating anticoagulation therapy. During the hospital stay, a treatment with vitamin K antagonists for stroke prevention was initiated. The patient was discharged 8 days following surgery, and no further complications occurred during the 6 months follow-up.


Assuntos
Artérias Carótidas/cirurgia , Ponte de Artéria Coronária , Vasos Coronários/cirurgia , Período Perioperatório , Trombastenia/terapia , Fibrilação Atrial/tratamento farmacológico , Antígenos HLA/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Transfusão de Plaquetas , Acidente Vascular Cerebral/prevenção & controle , Trombofilia/genética , Resultado do Tratamento
8.
Ann Card Anaesth ; 20(4): 468-471, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28994690

RESUMO

A 30-year-old male patient presented with Glanzmann's thrombasthenia and mitral valve prolapse. He was in acute decompensated congestive heart failure due to severe mitral and tricuspid regurgitation. After his cardiac failure had been stabilized, the patient was subjected to mitral and tricuspid valve repair. His transfusion requirements were guided by thrombelastography and his bleeding disorder was managed by infusing single donor plasmapheresed platelet transfusions in the perioperative period. The patient underwent surgery uneventfully.


Assuntos
Ponte Cardiopulmonar/métodos , Valva Mitral/cirurgia , Trombastenia/complicações , Trombastenia/terapia , Adulto , Transfusão de Sangue , Procedimentos Cirúrgicos Cardíacos , Ecocardiografia , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/etiologia , Humanos , Masculino , Valva Mitral/diagnóstico por imagem , Prolapso da Valva Mitral/diagnóstico por imagem , Prolapso da Valva Mitral/cirurgia , Transfusão de Plaquetas , Trombastenia/diagnóstico por imagem , Tromboelastografia , Insuficiência da Valva Tricúspide/complicações , Insuficiência da Valva Tricúspide/diagnóstico por imagem
9.
Ann Afr Med ; 16(4): 196-198, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29063905

RESUMO

BACKGROUND: Glanzmann's thrombasthenia (GT) is a rare bleeding disorder, which is characterized by a lack of platelet aggregation. It is characterized by qualitative or quantitative abnormalities of the platelet membrane glycoprotein IIb/IIIa. Physiologically, this platelet receptor normally binds several adhesive plasma proteins, and this facilitates attachment and aggregation of platelets to ensure thrombus formation at sites of vascular injury. The lack of resultant platelet aggregation in GT leads to mucocutaneous bleeding whose manifestation may be clinically variable, ranging from easy bruising to severe and potentially life-threatening hemorrhages. OBJECTIVE: To highlight this rare but potentially life-threating disorder, GT. CASE REPORT: We report a case of GT that was first detected because of the multiple episodes of gum bleeding. The patient was an 18-year-old girl who presented with a history of repeated episodes of gum bleeding since childhood. Till the first visit to our hospital, she had not been diagnosed with GT despite a history of bleeding tendency, notably purpura in areas of easy bruising, gum bleeding, and prolonged bleeding time after abrasions and insect stings. GT was diagnosed on the basis of prolonged bleeding time, lack of platelet aggregation with adenosine di phosphate, epinephrine and collagen. CONCLUSION: GT should always be considered as differential diagnosis while evaluating any case of bleeding disorder.


Assuntos
Transfusão de Plaquetas , Trombastenia/diagnóstico , Trombastenia/terapia , Ácido Tranexâmico/administração & dosagem , Adolescente , Feminino , Humanos , Trombastenia/genética , Resultado do Tratamento
10.
Int J Hematol ; 105(2): 221-225, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27696190

RESUMO

Perioperative hemostatic management is a challenge in patients with Glanzmann thrombasthenia (GT). The standard means of preventing surgical bleeding in GT patients is platelet transfusion. However, GT patients often possess alloantibodies against GPIIb/IIIa and/or HLA, which cause resistance to platelet transfusion. HLA-matched platelet transfusion, plasmapheresis, or recombinant human-activated factor VII (rFVIIa) are alternative interventions in such cases. Monitoring of hemostasis is also critical in the management of GT patients who undergo surgery. Here, we report the case of a 56-year-old female GT patient with anti-HLA antibodies, who underwent a right total mastectomy without significant blood loss under HLA-matched platelet transfusion. Bleeding at the surgical site, which occurred on the 18th postoperative day, was successfully treated by immediate bolus administration of rFVIIa and subsequent HLA-matched platelet transfusion. The perioperative hemostatic state was monitored in combination with bleeding time, platelet aggregation assay, and flow cytometric analysis of GPIIb/IIIa expression. Although a flow cytometric analysis is not a functional assay, it enabled the estimation of transfused platelet counts, and helped to inform the decision regarding whether to perform the surgery. Thus, perioperative hemostasis was successfully managed in our GT patient by HLA-matched platelet transfusion, rFVIIa administration, and the close monitoring of hemostasis.


Assuntos
Hemostasia , Mastectomia Radical/métodos , Assistência Perioperatória/métodos , Trombastenia/sangue , Gerenciamento Clínico , Fator VIIa/administração & dosagem , Fator VIIa/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Transfusão de Plaquetas , Proteínas Recombinantes/administração & dosagem , Trombastenia/terapia
11.
Transfus Med Rev ; 30(2): 92-9, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26968829

RESUMO

Glanzmann thrombasthenia (GT) is a rare inherited autosomal recessive bleeding disorder of platelet function caused by a quantitative or qualitative defect of platelet membrane glycoprotein IIb/IIIa (integrin αIIbß3), a fibrinogen receptor required for platelet aggregation. Bleeds in GT are variable and may be severe and unpredictable. Bleeding not responsive to local and adjunctive measures, as well as surgical procedures, is treated with platelets, recombinant activated factor VII (rFVIIa), or antifibrinolytics, alone or in combination. Although platelets are the standard treatment for GT, their use is associated with the risk of blood-borne infection transmission and may also cause the development of platelet antibodies (to human leukocyte antigens and/or αIIbß3), potentially resulting in platelet refractoriness. Currently, where rFVIIa is approved for use in GT, this is mostly for patients with platelet antibodies and/or a history of platelet refractoriness. However, data from the prospective Glanzmann's Thrombasthenia Registry (829 bleeds and 206 procedures in 218 GT patients) show that rFVIIa was frequently used in nonsurgical and surgical bleeds, with high efficacy rates, irrespective of platelet antibodies/refractoriness status. The mechanisms underpinning rFVIIa effectiveness in GT have been studied. At therapeutic concentrations, rFVIIa binds to activated platelets and directly activates FX to FXa, resulting in a burst of thrombin generation. Thrombin converts fibrinogen to fibrin and also enhances GT platelet adhesion and aggregation mediated by the newly converted (polymeric) fibrin, leading to primary hemostasis at the wound site. In addition, thrombin improves the final clot structure and activates thrombin-activatable fibrinolysis inhibitor to decrease clot lysis.


Assuntos
Trombastenia/terapia , Antígenos de Plaquetas Humanas/imunologia , Segurança do Sangue , Patógenos Transmitidos pelo Sangue , Gerenciamento Clínico , Fator VIIa/farmacocinética , Fator VIIa/uso terapêutico , Feminino , Terapia Genética , Transplante de Células-Tronco Hematopoéticas , Hemorragia/etiologia , Hemorragia/terapia , Técnicas Hemostáticas , Humanos , Masculino , Complexo Glicoproteico GPIIb-IIIa de Plaquetas , Transfusão de Plaquetas/efeitos adversos , Proteínas Recombinantes/farmacocinética , Proteínas Recombinantes/uso terapêutico , Trombastenia/complicações , Trombastenia/tratamento farmacológico , Trombina/biossíntese
12.
Exp Clin Transplant ; 14(6): 688-690, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26134714

RESUMO

Glanzmann thrombasthenia is an inherited auto-somal recessive disorder characterized by normal platelet count but lack of platelet aggregation due to absence of platelet glycoprotein IIb/IIIa. The disease usually is associated with mild bleeding, but severe fatal hemorrhage may occur. Allogeneic stem cell transplant is the only curative method of treatment. A literature search showed 18 previously reported cases of Glanzmann thrombasthenia treated with allogeneic hematopoietic stem cell transplant. We report an 18-year-old woman with severe Glanzmann thrombasthenia who was treated with allogeneic hematopoietic stem cell transplant from her sister. After 24-month follow-up, the patient was well, had no bleeding tendency, and had mild chronic skin graft-versus-host disease.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Trombastenia/terapia , Adolescente , Feminino , Doença Enxerto-Hospedeiro , Hemorragia , Humanos , Trombastenia/fisiopatologia , Fatores de Tempo , Transplante Homólogo
14.
Platelets ; 26(7): 702-4, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25548835

RESUMO

Glanzmann thrombasthenia (GT) is a rare, autosomal recessive coagulopathy characterized by either qualitative or quantitative abnormalities of the membrane glycoprotein αIIbß3 complex leading to bleeding tendencies, ranging from purpura to life-threatening hemorrhage. Although patients can be managed with supportive measures including platelet transfusions, complications such as alloimmunization are possible. Allogeneic stem cell transplantation (ASCT) can be indicated in severe cases of GT. We report the case of an eight-month-old girl diagnosed with moderate-severe GT, who was successfully treated with a reduced-intensity, human leukocyte antigen (HLA)-identical ASCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Trombastenia/terapia , Plaquetas/imunologia , Plaquetas/metabolismo , Feminino , Antígenos HLA/genética , Antígenos HLA/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Teste de Histocompatibilidade , Humanos , Lactente , Índice de Gravidade de Doença , Irmãos , Trombastenia/diagnóstico , Condicionamento Pré-Transplante , Transplante Homólogo , Resultado do Tratamento
15.
J Indian Soc Pedod Prev Dent ; 32(2): 181-4, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24739923

RESUMO

Glanzmann's thrombasthenia (GT) is a rare, congenital, and moderate to severe platelet disorder. The bleeding time is increased, due to lack of platelet aggregation, since the patients with GT have deficient or dysfunctional integrin membrane glycoproteins IIb and IIIa essential for platelet aggregation. Children with GT are mostly diagnosed very early in life due to the spontaneous and unexplained mucocutaneous bleeding. It is quite a challenging task when any surgery is indicated for children with GT. This case report is about the medical and surgical management of an 11-year-old girl diagnosed with Glannzmann's thrombasthenia who had to undergo a maxillary cyst enucleation.


Assuntos
Trombastenia/sangue , Trombastenia/terapia , Criança , Feminino , Humanos
16.
Akush Ginekol (Sofiia) ; 53(5): 49-51, 2014.
Artigo em Búlgaro | MEDLINE | ID: mdl-25558673

RESUMO

Glanzmann thrombasthenia (GT) is a rare autosomal recessive disorder which deficiency of the platelet glycoprotein IIb - III a. The disorder usually manifests as severe mucocutaneus bleeding in the chaildhood, menstrual patterns in pubertal--adolescent years, rarely life-threatening. Pregnancy and delivery in patients with TG are very rare and are associated with high risk for mother and fetus due to intra - and post-partum hemorrhage. We present a case 30, a patient with TG, emergency births by caesarean section, with intra- and postpartum haemorrhage managed through the use of recombinant factor VIIa, transfusion of packed red blood cells and platelets.


Assuntos
Fator VIIa/uso terapêutico , Hemorragia Pós-Parto/terapia , Complicações Hematológicas na Gravidez/terapia , Trombastenia/terapia , Adulto , Cesárea , Transfusão de Eritrócitos , Feminino , Humanos , Transfusão de Plaquetas , Gravidez , Proteínas Recombinantes/uso terapêutico
17.
Artigo em Inglês | MEDLINE | ID: mdl-24319190

RESUMO

Inherited platelet disorders (IPDs) are a heterogeneous group of diseases affecting platelet production, morphology, and function. The degree of thrombocytopenia and functional abnormality of platelets determines the clinical manifestations. Although severe deficiencies may cause excessive bleeding beginning in early childhood, most of IPDs have mild bleeding tendencies and therefore are not always easy to distinguish from acquired platelet disorders. The diagnosis of IPD may require extensive laboratory investigation, because current routine laboratory tests are not satisfactory for differential diagnosis in some cases, and most of the specific tests are not readily available in many countries. This review summarizes the classification and clinical and molecular characteristics of known IPDs, including Bernard-Soulier syndrome and Glanzmann thrombasthenia, with a focus on current challenges in the laboratory diagnosis and management of bleeding in these patients.


Assuntos
Síndrome de Bernard-Soulier/diagnóstico , Hemorragia/diagnóstico , Trombastenia/diagnóstico , Síndrome de Bernard-Soulier/sangue , Síndrome de Bernard-Soulier/patologia , Síndrome de Bernard-Soulier/terapia , Plaquetas/metabolismo , Plaquetas/patologia , Diagnóstico Diferencial , Hemorragia/sangue , Hemorragia/patologia , Hemorragia/terapia , Humanos , Trombastenia/sangue , Trombastenia/patologia , Trombastenia/terapia
18.
Semin Thromb Hemost ; 39(6): 642-55, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23929305

RESUMO

Glanzmann thrombasthenia (GT) is the principal inherited disease of platelets and the most commonly encountered disorder of an integrin. GT is characterized by spontaneous mucocutaneous bleeding and an exaggerated response to trauma caused by platelets that fail to aggregate when stimulated by physiologic agonists. GT is caused by quantitative or qualitative deficiencies of αIIbß3, an integrin coded by the ITGA2B and ITGB3 genes and which by binding fibrinogen and other adhesive proteins joins platelets together in the aggregate. Widespread genotyping has revealed that mutations spread across both genes, yet the reason for the extensive variation in both the severity and intensity of bleeding between affected individuals remains poorly understood. Furthermore, although genetic defects of ITGB3 affect other tissues with ß3 present as αvß3 (the vitronectin receptor), the bleeding phenotype continues to dominate. Here, we look in detail at mutations that affect (i) the ß-propeller region of the αIIb head domain and (ii) the membrane proximal disulfide-rich epidermal growth factor (EGF) domains of ß3 and which often result in spontaneous integrin activation. We also examine deep vein thrombosis as an unexpected complication of GT and look at curative procedures for the diseases, including allogeneic stem cell transfer and the potential for gene therapy.


Assuntos
Plaquetas/metabolismo , Mutação , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/genética , Trombastenia/genética , Terapia Genética/métodos , Hemorragia/genética , Hemorragia/terapia , Humanos , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Transplante de Células-Tronco/métodos , Trombastenia/diagnóstico , Trombastenia/terapia , Transplante Autólogo
20.
Expert Rev Hematol ; 5(5): 487-503, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23146053

RESUMO

Glanzmann thrombasthenia (GT) is characterized by mucocutaneous bleeding due to platelets that fail to aggregate in response to physiologic stimuli. GT, a rare inherited disease, is caused by quantitative or qualitative deficiencies of αIIbß3, an integrin receptor for adhesive proteins. Coded by the ITGA2B and ITGB3 genes, αIIbß3 mediates platelet-to-platelet attachment, aggregation and clot retraction. Despite widespread mutation analysis, the reason for the extensive variation in both the severity and intensity of bleeding among affected individuals remains poorly understood. Although genetic defects of ITGB3 affect other tissues where ß3 is present as αvß3 (the vitronectin receptor), the bleeding phenotype continues to dominate. The authors now examine the relationship between genotype and phenotype in classic and variant forms of GT, and reassess if the nature of the gene mutation influences bleeding and treatment aimed at restoring hemostasis.


Assuntos
Integrina alfa2/genética , Integrina beta3/genética , Trombastenia/genética , Humanos , Integrina alfa2/química , Integrina alfaVbeta3/química , Integrina alfaVbeta3/genética , Integrina beta3/química , Mutação , Agregação Plaquetária , Polimorfismo de Nucleotídeo Único , Estrutura Terciária de Proteína , Trombastenia/diagnóstico , Trombastenia/terapia
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