Glanzmann’s thrombasthenia (defective platelet integrin αIIb-β3): proposals for management between evidence and open issues

Giovanni Di Minno; Antonio Coppola; Matteo N. D. Di Minno; Man-Chiu Poon

doi:10.1160/TH09-04-0225

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2009; 102(06): 1157-1164
DOI: 10.1160/TH09-04-0225

Review Article

Schattauer GmbH

Glanzmann’s thrombasthenia (defective platelet integrin α_IIb-β₃): proposals for management between evidence and open issues

Giovanni Di Minno

¹Regional Reference Centre for Coagulation Disorders, Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy

,

Antonio Coppola

¹Regional Reference Centre for Coagulation Disorders, Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy

,

Matteo N. D. Di Minno

¹Regional Reference Centre for Coagulation Disorders, Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy

,

Man-Chiu Poon

²Departments of Medicine, Pediatrics and Oncology, University of Calgary and Southern Alberta Rare Blood and Bleeding Disorders Comprehensive Care Program, Calgary Health Region, Calgary, Canada

› Author Affiliations

Abstract

Summary

Glanzmann’s Thrombasthenia (GT) is a rare autosomal recessive bleeding disorder, characterized by a quantitative or qualitative defect of platelet surface α_IIb-β₃ integrin. Presently, no specific guideline/algorithm for clinical management for GT is available. Due to the rarity and heterogeneity of inherited platelet abnormalities, recommendations and guidelines are based on reports from opinions and clinical experience of panel of experts, and refer to the general management of platelet disorders. Based on the limited evidence in the area and on the strategies in clinical settings of inherited/acquired platelet defects, proposals for management of minor bleeding; moderate/major bleeding unresponsive to conservative management; major surgery; minor surgery and dental procedures for GT patients without, or with anti-platelet isoantibodies are reported. In addition to life-style advices and continuous patient education programs, when and how to employ/combine local measures, antifibrinolytic agents, hormone treatment, platelet transfusions and recombinant activated Factor VII is described. The prospective collection of treatments in GT patients recently established (Glanzmann’s Thrombasthenia Registry, GTR), based on a careful definition of clinical settings and outcomes, is likely to provide newer insight for optimising clinical management in GT.

Keywords

Anti-platelet antibodies - clinical management - Glanzmann’s thrombasthenia - platelet transfusion - recombinant activated factor VII

Full Text

References

References
1 Caen JP, Castaldi PA, Leclerc JC. et al. Congenital bleeding disorders with long bleeding time and normal platelet count. 1. Glanzmann’s thrombasthenia. Am J Med 1966; 41: 4-18.
2 Nurden AT, Caen JP. An abnormal platelet glycoprotein pattern in three cases of Glanzmann’s thrombasthenia. Br J Haematol 1974; 28: 253-260.
3 Di Minno G, Thiagarajan P, Perussia B. et al. Exposure of platelet fibrinogen binding sites by collagen, arachidonic acid and ADP: inhibition by a monoclonal antibody to the ?IIb-β3 IIb-IIIa complex. Blood 1983; 61: 140-148.
4 Reichert N, Seligsohn U, Ramot B. Clinical and genetic studies of Glanzmann’s thrombasthenia in Israel. Thromb Diath Haemorrh 1975; 34: 806-820.
5 Khanduri U, Pulimood R, Sudarsanam A. et al. Glanzmann’s thrombasthenia. A review and report of 42 cases from South India. Thromb Haemost 1981; 46: 217-221.
6 Awidi AS. Congenital hemorrhagic disorders in Jordan. Thromb Haemost 1984; 51: 331-333.
7 Toogeh G, Sharifian R, Lak M. et al. Presentation and pattern of symptoms in 382 patients with Glanzmann thrombasthenia in Iran. Am J Hematol 2004; 77: 198-199.
8 George JN, Caen JP, Nurden AT. Glanzamann’s thrombasthenia: the spectrum of clinical disease. Blood 1990; 75: 1383-1395.
9 Stormorken H, Gostrad GO, Solum NO, Pande H. Diagnosis of heterozygotes in Glanzmann’s thrombasthenia. Thromb Haemost 1982; 48: 217-221.
10 Caen JP. Glanzmann’s Thrombasthenia. Baillieres Clin Haematol 1989; 02: 609-625.
11 D’Andrea G, Colaizzo D, Vecchione G. et al. on behalf of the Glanzmann’s Thrombasthenia Italian Team (GLATIT). Glanzmann’s Thrombasthenia: identification of 19 new mutations in 30 patients. Thromb Haemost 2002; 87: 1034-1042.
12 Glanzmann Thrombasthenia Database. last update February 12, 2009, available at http://sinaicentral.mssm.edu/intranet/research/glanzmann/menu last accessed on March, 31, 2009.
13 Ghosh K, Kulkarni B, Nair S, Mohanty B. Human platelet alloantigen polymorphism in Glanzmann’s thrombasthenia and its impact on the severity of the disease. Br J Haematol 2002; 119: 348-353.
14 D’Andrea G, Margaglione M. for the Glanzmann’s Thrombasthenia Italian Team (GLATIT). Glanzmann’s thrombasthenia: modulation of clinical phenotype by alpha2C807T gene polymorphism. Haematologica 2003; 88: 1378-1382.
15 Coppola A, De Stefano V, Tufano A. et al. Longlasting severe intestinal bleeding in an old patient with multiple mucosal vascular abnormalities and Glanzmann’s thrombasthenia. Three-yr pharmacological management. J Int Med 2002; 252: 271-275.
16 Poon M-C, d’Oiron R, Von Depka M. et al. Prophylactic and therapeutic recombinant factor VIIa administration to patients with Glanzmann’s thrombasthenia: results of an international survey. J Thromb Haemost 2004; 02: 1096-1103.
17 Bolton-Maggs PHB, Chalmers EA, Collins PW. et al. A review of inherited platelet disorders with guidelines for their management on behalf of the UKHCDO. Br J Haematol 2006; 135: 603-633.
18 Hayward CPM, Rao AK, Cattaneo M. Congenital platelet disorders: overview of their mechanisms, diagnostic evaluation and treatment. Haemophilia 2006; 12 (Suppl. 03) 128-136.
19 Società Italiana per lo Studio dell’Emostasi e della Trombosi. Trattamento delle emorragie e preparazione alle manovre invasive nel paziente con piastrinopatia e/o piastrinopenia ereditaria od acquisita. Last update 4 June 2007 [Article in Italian]. Available at www.siset.org/lineeguida/LG4.pdf last accessed on March 31, 2009.
20 Nurden P, Nurden A. Congenital disorders associated with platelet dysfunctions. Thromb Haemost 2008; 99: 353-363.
21 Lefebvre JM, Qanadli SD, Kacher S. et al. A new vascular sealant (Sealgel) to achieve rapid hemostasis after percutaneous angioplasty in anticoagulated patients: clinical feasibility and preliminary results. Eur Radiol 2001; 11: 454-459.
22 Stael von Holstein CCS, Eriksson SBS, Kallen R. Tranexamic acid as an aid to reducing transfusion requirements in gastric and duodenal bleeding. Br Med J 1987; 294: 7-10.
23 Bartholomew JR, Salgia R, Bell WR. Control of bleeding in patients with amegakaryocytic thrombocytopenia. Arch Intern Med 1989; 149: 1959-1961.
24 Shpilberg O, Blumenthal R, Sofer O. et al. A controlled trial of tranexamic acid therapy for the reduction of bleeding during treatment of acute myeloid leukaemia. Leuk Lymphoma 1995; 19: 141-144.
25 Bonnar J, Sheprad BL. Treatment of menorrhagia during menstruation: randomized controlled trial of ethamsylate, mefenamic acid and tranexamic acid. Br Med J 1996; 313: 579-582.
26 Walsh PN, Rizza CR, Matthews JM. et al. Epsilon Aminocaproic acid therapy for dental extractions in haemophilia and Christmas disease: a double blind controlled trial. Br J Haematol 1971; 20: 463-475.
27 Sindet-Pedersen S, Stenbjerg S. Effect of local antifibrinolytic treatment with tranexamic acid in hemophiliacs undergoing oral surgery. J Oral Maxillofac Surg 1986; 44: 703-707.
28 Kantarci A, Cebeci I, Firatli E. et al. Periodontal management of Glanzmann’s thrombasthenia: report of 3 cases. J Periodontol 1996; 67: 816-820.
29 Sundqvist SB, Nilsson IM, Svanberg L, Cronberg S. Pregnancy and parturition in a patient with severe Glanzmann’s thrombasthenia. Scand J Haematol 1981; 27: 159-164.
30 Bisch FC, Bowen KJ, Hanson BS. et al. Dental considerations for a Glanzmann’s thrombasthenia patient: case report. J Periodontol 1996; 67: 536-540.
31 Kettner SC, Panzer OP, Kozek SA. et al. Use of abciximab-modified thrombelastography in patients undergoing cardiac surgery. Anesth Analg 1999; 89: 580-584.
32 Male C, Koren D, Eichelberger B. et al. Monitoring survival and function of transfused platelets in Glanzmann thrombasthenia by flow cytometry and thrombelastography. Vox Sang 2006; 91: 174-177.
33 Monte S, Lyons G. Peripartum management of a patient with Glanzmann’s thrombasthenia using Thrombelastograph^® . Br J Anaesth 2002; 88: 734-738.
34 Nurden A, Combrié R, Nurden P. Detection of transfused platelets in a patient with Glanzmann thrombasthenia. Thromb Haemost 2002; 87: 543-544.
35 Bell JA, Savidge GF. Glanzmann’s thrombasthenia proposed optimal management during surgery and delivery. Clin Appl Thromb Haemost 2003; 09: 167-170.
36 MacLennan S, Williamson LM. Risks of fresh frozen plasma and platelets. J Trauma 2006; 60 (Suppl. 06) S46-S50.
37 Seghatchian J. Universal leucodepletion: an overview of some unresolved issue and highlights of lesson learned. Transf Apher Sci 2003; 29: 105-117.
38 Makris M, Conlon CP, Watson HG. Immunization of people with bleeding disorders. Haemophilia 2003; 09: 541-546.
39 Conte R, Cirillo D, Ricci F. et al. Platelet transfusion in a patient affected by Glanzmann’s thrombasthenia with antibodies against GpIIb-IIIa. Haematologica 1997; 82: 73-74.
40 Vivier M, Treisser A, Naett M. et al. Glanzmann thrombasthenia and pregnancy. Contribution of plasma exchange before scheduled cesarean section. J Gynecol Obstetr Biol Reprod. (Paris) 1989; 18: 507-513.
41 Léticée N, Kaplan C, Lémery D. Pregnancy in mother with Glanzmann’s thrombasthenia and isoantibody against GPIIb-IIIa: is there a foetal risk?. Eur J Obst Gynecol Reprod Biol 2005; 121: 139-142.
42 Lisman T, Adelmeijer J, Heijnen F. et al. Recombinant factor VIIa restores aggregation of alphaIIbbeta3 deficient platelets via tissue factor-independent fibrin generation. Blood 2004; 103: 1720-1727.
43 Hedner U. Factor VIIa and its potential therapeutic use in bleeding-associated pathologies. Thromb Haemost 2008; 100: 557-562.
44 Tengborn L, Peturson B. A patient with Glanzmann’s thrombasthenia and epistaxis successfully treated with recombinant factor VIIa. Thromb Haemost 1996; 75: 981-982.
45 Poon M-C, Demers C, Jobin F, Wu JW. Recombinant factor VIIa is effective for bleeding and surgery in patients with Glanzmann thrombasthenia. Blood 1999; 94: 3951-3953.
46 Almeida AM, Khair K, Hann I, Liesner R. The use of recombinant factor VIIa in children with inherited platelet function disorders. Br J Haematol 2003; 121: 477-481.
47 Kaleelrahman M, Minford A, Parapia LA. Use of recombinant factor VIIa in inherited platelet disorders. Br J Haematol 2004; 125: 95-96.
48 Ito K, Yoshida H, Hatoyama H. et al. Antibody removal therapy used successfully at delivery of a pregnant patient with Glanzmann’s thrombasthenia and multiple anti-platelet antibodies. Vox Sang 1991; 61: 40-46.
49 Martin I, Kriaa F, Proulle V. et al. Protein A Sepharose immunoadsorption can restore the efficacy of platelet concentrates in patients with Glanzmann’s thrombasthenia and anti-glycoprotein IIb-IIIa antibodies. Br J Haematol 2002; 119: 991-997.
50 Vijapaurkar M, Mota L, Shetty S, Ghosh K. Menorrhagia and reproductive health in rare bleeding disorders: a study from the Indian subcontinent. Haemophilia 2009; 15: 199-202.
51 Mannucci PM. Desmopressin (DDAVP) in the treatment of bleeding disorders: the first 20 years. Blood 1997; 90: 2515-2521.
52 Coppola A, Di Minno G. Desmopressin (DDAVP) in inherited disorders of platelet function. Haemophilia 2008; 14 (Suppl. 01) 31-39.
53 Chuansumrit A, Suwannuraks M, Sri-Udomporn Po N. et al. Recombinant activated factor VII combined with local measures in preventing bleeding from invasive dental procedures in patients with Glanzmann thrombasthenia. Blood Coagul Fibrinolysis 2003; 14: 187-190.
54 Kenet G, Lubetsky A, Luboshitz J. et al. A new approach to treatment of bleeding episodes in young haemophilia patients: a single bolus megadose of recombinant activated factor VII (NovoSeven). J Thromb Haemost 2003; 01: 450-455.
55 Gremmel T, Steiner S, Seidinger D. et al. Comparison of methods to evaluate clopidogrel-mediated platelet inhibition after percutaneous intervention with stent implantation. Thromb Haemost 2009; 101: 333-339.
56 Lak M, Scharling B, Blemings A. et al. Evaluation of rFVIIa (NovoSeven) in Glanzmann patients with thromboelastogram. Haemophilia 2008; 14: 103-110.
57 Dargaud Y, Bordet JC, Trzeciak MC. et al. A case of Glanzmann’s thrombasthenia successfully treated with recombinant factor VIIa during a surgical procedure: observations on the monitoring and the mechanism of action of this drug. Haematologica 2006; 91: ECR20
58 Spronk HMH, Dielis AWJH, De Smedt E. et al. Assessment of thrombin generation II: Validation of the Calibrated Automated Thrombogram in platelet-poor plasma in a clinical laboratory. Thromb Haemost 2008; 100: 362-364.
59 Coppola A, Tufano A, Agangi A. et al. Recombinant Factor VIIa in a patient with Glanzmann’s thrombasthenia undergoing gynecological surgery: open issues in the light of a successful treatment. Thromb Haemost 2004; 92: 1450-1452.
60 Shpilberg O, Rabi I, Schiller K. et al. Patients with Glanzmann Thrombasthenia lacking platelet glycoprotein αIIBβ3 (GPIIb/IIIa) and αvβ3 receptors are not protected from atherosclerosis. Circulation 2002; 105: 1044-1048.
61 Ten Cate H, Brandjes DP, Smits PH. et al. The role of platelets in venous thrombosis: a patient with Glanzmann’s thrombasthenia and a factor V Leiden mutation suffering from deep venous thrombosis. J Thromb Haemost 2003; 01: 394-395.
62 Gruel Y, Pacouret G, Bellucci S, Caen J. Severe proximal deep vein thrombosis in a Glanzmann thrombasthenia variant successfully treated with a low molecular weight heparin. Blood 1997; 90: 888-890.
63 Philips R, Richards M. Venous thrombosis in Glanzmann’s thrombasthenia. Haemophilia 2007; 13: 758-759.
64 Seretny M, Senadheera N, Miller E, Keeling D. Pulmonary embolus in Glanzmann’s thrombasthenia treated with warfarin. Haemophilia 2008; 14: 1138-1139.
65 Shekelle PG, Woolf SH, Eccles M, Grimshaw J. Clinical guidelines: developing guidelines. Br Med J 1999; 318: 593-596.
66 Poon MC, Zotz R, Di Minno G, Abrams ZS. et al. Glanzmann’s thrombasthenia treatment: a prospective registry on the use of recombinant human activated Factor VII and other hemostatic agents. Semin Hematol 2006; 43 (Suppl. 01) S33-36.