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Semin Thromb Hemost 2013; 39(06): 684-692
DOI: 10.1055/s-0033-1353391
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Occurrence of Thrombosis in Rare Bleeding Disorders

Arlette Ruiz-Saez
1   National Haemophilia Center, Banco Municipal de Sangre, Caracas, Venezuela
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Publikationsdatum:
08. August 2013 (online)

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Abstract

Paradoxically, there are reports of thrombotic events for some rare bleeding disorders associated with significant bleeding tendency. Afibrinogenemia, factor (F) VII, or FXI deficiencies are those most commonly associated with venous or arterial thrombosis. Pathogenesis is multifactorial and the main conditions associated with this complication relate to the coexistence of inherited or acquired thrombotic risk factors linked to certain specific characteristics of the underlying defect. Patients with afibrinogenemia can develop severe, spontaneous, or recurrent thromboembolic disease. Up to 20% of congenital dysfibrinogenemia patients show predisposition to thrombosis. Thrombotic episodes, particularly deep vein thrombosis, have been reported in 3 to 4% FVII deficient patients, even those who were severely affected. These events have been reported either after infusion of plasma derived FXI concentrate or recombinant activated FVII in FXI deficient patients. So, in addition to factor level, replacement therapy must be individualized and should take into account past personal or family history of bleeding and thrombosis, and other prothrombotic risk factors. Treatment of thrombosis represents a challenge. For mild factor deficiencies, antithrombotic prophylaxis must be considered with or without concomitant use of replacement therapy. For all patients, it is also recommended to control known cardiovascular disease risk factors.

Keywords

rare bleeding disorders - thrombosis
 

  • References

  • 1 Franchini M. Thrombotic complications in patients with hereditary bleeding disorders. Thromb Haemost 2004; 92 (2) 298-304
    PubMedGoogle Scholar
  • 2 Dargaud Y, Meunier S, Negrier C. Haemophilia and thrombophilia: an unexpected association!. Haemophilia 2004; 10 (4) 319-326
    CrossrefPubMedGoogle Scholar
  • 3 Mannucci PM, Duga S, Peyvandi F. Recessively inherited coagulation disorders. Blood 2004; 104 (5) 1243-1252
    CrossrefPubMedGoogle Scholar
  • 4 Peyvandi F, Palla R, Menegatti M, Mannucci PM. Introduction. Rare bleeding disorders: general aspects of clinical features, diagnosis, and management. Semin Thromb Hemost 2009; 35 (4) 349-355
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 5 Peyvandi F, Palla R, Menegatti M , et al; European Network of Rare Bleeding Disorders Group. Coagulation factor activity and clinical bleeding severity in rare bleeding disorders: results from the European Network of Rare Bleeding Disorders. J Thromb Haemost 2012; 10 (4) 615-621
    CrossrefPubMedGoogle Scholar
  • 6 Peyvandi F, Duga S, Akhavan S, Mannucci PM. Rare coagulation deficiencies. Haemophilia 2002; 8 (3) 308-321
    CrossrefPubMedGoogle Scholar
  • 7 Naderi M, Eshghi P, Saneei Moghaddam E , et al. Safety of human blood products in rare bleeding disorders in southeast of Iran. Haemophilia 2013; 19 (2) e90-e92
    CrossrefPubMedGoogle Scholar
  • 8 Peyvandi F, Di Michele D, Bolton-Maggs PH, Lee CA, Tripodi A, Srivastava A. Project on Consensus Definitions in Rare Bleeeding Disorders of the Factor VIII/Factor IX Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. Classification of rare bleeding disorders (RBDs) based on the association between coagulant factor activity and clinical bleeding severity. J Thromb Haemost 2012; 10 (9) 1938-1943
    CrossrefPubMedGoogle Scholar
  • 9 Girolami A, Ruzzon E, Fabris F, Varvarikis C, Sartori R, Girolami B. Myocardial infarction and other arterial occlusions in hemophilia a patients. A cardiological evaluation of all 42 cases reported in the literature. Acta Haematol 2006; 116 (2) 120-125
    CrossrefPubMedGoogle Scholar
  • 10 Girolami A, Tezza F, Scapin M, Vettore S, Casonato A. Arterial and venous thrombosis in patients with von Willebrand's disease: a critical review of the literature. J Thromb Thrombolysis 2006; 21 (2) 175-178
    CrossrefPubMedGoogle Scholar
  • 11 Girolami A, Ruzzon E, Tezza F, Scandellari R, Vettore S, Girolami B. Arterial and venous thrombosis in rare congenital bleeding disorders: a critical review. Haemophilia 2006; 12 (4) 345-351
    CrossrefPubMedGoogle Scholar
  • 12 Dolan G. The challenge of an ageing haemophilic population. Haemophilia 2010; 16 (Suppl. 05) 11-16
    CrossrefPubMedGoogle Scholar
  • 13 Biere-Rafi S, Zwiers M, Peters M , et al. The effect of haemophilia and von Willebrand disease on arterial thrombosis: a systematic review. Neth J Med 2010; 68 (5) 207-214
    PubMedGoogle Scholar
  • 14 Biere-Rafi S, Tuinenburg A, Haak BW , et al. Factor VIII deficiency does not protect against atherosclerosis. J Thromb Haemost 2012; 10 (1) 30-37
    CrossrefPubMedGoogle Scholar
  • 15 Ragni MV, Moore CG. Atherosclerotic heart disease: prevalence and risk factors in hospitalized men with haemophilia A. Haemophilia 2011; 17 (6) 867-871
    CrossrefPubMedGoogle Scholar
  • 16 Todd T, Perry DJ. A review of long-term prophylaxis in the rare inherited coagulation factor deficiencies. Haemophilia 2010; 16 (4) 569-583
    PubMedGoogle Scholar
  • 17 Matsumoto T, Wada H, Tamaru S , et al. Central venous catheter-related thrombosis after replacement therapy for intracranial bleeding in a patient with afibrinogenaemia. Haemophilia 2008; 14 (1) 153-156
    CrossrefPubMedGoogle Scholar
  • 18 Coppola A, Franchini M, Makris M, Santagostino E, Di Minno G, Mannucci PM. Thrombotic adverse events to coagulation factor concentrates for treatment of patients with haemophilia and von Willebrand disease: a systematic review of prospective studies. Haemophilia 2012; 18 (3) e173-e187
    CrossrefPubMedGoogle Scholar
  • 19 Roberts HR. Recombinant factor VIIa (Novoseven) and the safety of treatment. Semin Hematol 2001; 38 (4) (Suppl. 12) 48-50
    CrossrefPubMedGoogle Scholar
  • 20 Girolami A, de Marinis GB, Bonamigo E, Lombardi AM. Recombinant FVIIa concentrate-associated thrombotic events in congenital bleeding disorders other than hemophilias. Hematology 2012; 17 (6) 346-349
    CrossrefPubMedGoogle Scholar
  • 21 Köhler M. Thrombogenicity of prothrombin complex concentrates. Thromb Res 1999; 95 (4) (Suppl. 01) S13-S17
    CrossrefPubMedGoogle Scholar
  • 22 Ozelo MC. Surgery in patients with hemophilia: is thromboprophylaxis mandatory?. Thromb Res 2012; 130 (Suppl. 01) S23-S26
    CrossrefPubMedGoogle Scholar
  • 23 Marchi R, Walton BL, McGary CS , et al. Dysregulated coagulation associated with hypofibrinogenaemia and plasma hypercoagulability: implications for identifying coagulopathic mechanisms in humans. Thromb Haemost 2012; 108 (3) 516-526
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 24 García-Noblejas A, Osorio S, Durán AI , et al. Pulmonary embolism in a patient with severe congenital deficiency for factor V during treatment with fresh frozen plasma. Haemophilia 2005; 11 (3) 276-279
    CrossrefPubMedGoogle Scholar
  • 25 Ten Cate H, Brandjes DP, Smits PH, van Mourik JA. 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; 1 (2) 394-395
    CrossrefPubMedGoogle Scholar
  • 26 Akbalik M, Duru F, Fisgin T , et al. Cerebral thrombosis associated with heterozygous factor V Leiden mutation and high lipoprotein(a) level in a girl with factor XIII deficiency. Blood Coagul Fibrinolysis 2007; 18 (4) 371-374
    CrossrefPubMedGoogle Scholar
  • 27 de Moerloose P, Neerman-Arbez M. Congenital fibrinogen disorders. Semin Thromb Hemost 2009; 35 (4) 356-366
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 28 Bolton-Maggs PHB, Perry DJ, Chalmers EA , et al. The rare coagulation disorders—review with guidelines for management from the United Kingdom Haemophilia Centre Doctors' Organisation. Haemophilia 2004; 10 (5) 593-628
    CrossrefPubMedGoogle Scholar
  • 29 Lak M, Keihani M, Elahi F, Peyvandi F, Mannucci PM. Bleeding and thrombosis in 55 patients with inherited afibrinogenaemia. Br J Haematol 1999; 107 (1) 204-206
    CrossrefPubMedGoogle Scholar
  • 30 Acharya SS, Coughlin A, Dimichele DM. North American Rare Bleeding Disorder Study Group. Rare Bleeding Disorder Registry: deficiencies of factors II, V, VII, X, XIII, fibrinogen and dysfibrinogenemias. J Thromb Haemost 2004; 2 (2) 248-256
    CrossrefPubMedGoogle Scholar
  • 31 Simsek I, de Mazancourt P, Horellou MH , et al. Afibrinogenemia resulting from homozygous nonsense mutation in A alpha chain gene associated with multiple thrombotic episodes. Blood Coagul Fibrinolysis 2008; 19 (3) 247-253
    CrossrefPubMedGoogle Scholar
  • 32 Castaman G, Lunardi M, Rigo L, Mastroeni V, Bonoldi E, Rodeghiero F. Severe spontaneous arterial thrombotic manifestations in patients with inherited hypo- and afibrinogenemia. Haemophilia 2009; 15 (2) 533-537
    CrossrefPubMedGoogle Scholar
  • 33 Bornikova L, Peyvandi F, Allen G, Bernstein J, Manco-Johnson MJ. Fibrinogen replacement therapy for congenital fibrinogen deficiency. J Thromb Haemost 2011; 9 (9) 1687-1704
    CrossrefPubMedGoogle Scholar
  • 34 Ni H, Denis CV, Subbarao S , et al. Persistence of platelet thrombus formation in arterioles of mice lacking both von Willebrand factor and fibrinogen. J Clin Invest 2000; 106 (3) 385-392
    CrossrefPubMedGoogle Scholar
  • 35 Remijn JA, Wu YP, Ijsseldijk MJ, Zwaginga JJ, Sixma JJ, de Groot PG. Absence of fibrinogen in afibrinogenemia results in large but loosely packed thrombi under flow conditions. Thromb Haemost 2001; 85 (4) 736-742
    PubMedGoogle Scholar
  • 36 de Bosch NB, Mosesson MW, Ruiz-Sáez A, Echenagucia M, Rodriguez-Lemoin A. Inhibition of thrombin generation in plasma by fibrin formation (Antithrombin I). Thromb Haemost 2002; 88 (2) 253-258
    PubMedGoogle Scholar
  • 37 Haverkate F, Samama M. Familial dysfibrinogenemia and thrombophilia. Report on a study of the SSC Subcommittee on Fibrinogen. Thromb Haemost 1995; 73 (1) 151-161
    PubMedGoogle Scholar
  • 38 Hayes T. Dysfibrinogenemia and thrombosis. Arch Pathol Lab Med 2002; 126 (11) 1387-1390
    PubMedGoogle Scholar
  • 39 Shapiro SE, Phillips E, Manning RA , et al. Clinical phenotype, laboratory features and genotype of 35 patients with heritable dysfibrinogenaemia. Br J Haematol 2013; 160 (2) 220-227
    CrossrefPubMedGoogle Scholar
  • 40 Travlou A, Gialeraki A, Merkouri E, Politou M, Sfyridaki A, Neerman-Arbez M. Coexisting dysfibrinogenemia (gamma Arg275His) and FV Leiden associated with thrombosis (Fibrinogen Crete). Thromb Res 2010; 126 (2) e162-e164
    CrossrefPubMedGoogle Scholar
  • 41 Miesbach W, Scharrer I, Henschen A, Neerman-Arbez M, Spitzer S, Galanakis D. Inherited dysfibrinogenemia: clinical phenotypes associated with five different fibrinogen structure defects. Blood Coagul Fibrinolysis 2010; 21 (1) 35-40
    CrossrefPubMedGoogle Scholar
  • 42 Peyvandi F. Epidemiology and treatment of congenital fibrinogen deficiency. Thromb Res 2012; 130 (Suppl. 02) S7-S11
    PubMedGoogle Scholar
  • 43 Mosesson MW. Dysfibrinogenemia and thrombosis. Semin Thromb Hemost 1999; 25 (3) 311-319
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 44 Flood VH, Al-Mondhiry HA, Farrell DH. The fibrinogen Aalpha R16C mutation results in fibrinolytic resistance. Br J Haematol 2006; 134 (2) 220-226
    CrossrefPubMedGoogle Scholar
  • 45 Wada Y, Lord ST. A correlation between thrombotic disease and a specific fibrinogen abnormality (A alpha 554 Arg→Cys) in two unrelated kindred, Dusart and Chapel Hill III. Blood 1994; 84 (11) 3709-3714
    PubMedGoogle Scholar
  • 46 Marchi R, Lundberg U, Grimbergen J , et al. Fibrinogen Caracas V, an abnormal fibrinogen with an Aalpha 532 Ser→Cys substitution associated with thrombosis. Thromb Haemost 2000; 84 (2) 263-270
    PubMedGoogle Scholar
  • 47 Kotlín R, Reicheltová Z, Malý M , et al. Two cases of congenital dysfibrinogenemia associated with thrombosis - Fibrinogen Praha III and Fibrinogen Plzen. Thromb Haemost 2009; 102 (3) 479-486
    PubMedGoogle Scholar
  • 48 Kotlín R, Reicheltová Z, Suttnar J , et al. Two novel fibrinogen variants in the C-terminus of the Bβ-chain: fibrinogen Rokycany and fibrinogen Znojmo. J Thromb Thrombolysis 2010; 30 (3) 311-318
    CrossrefPubMedGoogle Scholar
  • 49 Koopman J, Haverkate F, Grimbergen J , et al. Abnormal fibrinogens IJmuiden (B beta Arg14----Cys) and Nijmegen (B beta Arg44----Cys) form disulfide-linked fibrinogen-albumin complexes. Proc Natl Acad Sci U S A 1992; 89 (8) 3478-3482
    CrossrefPubMedGoogle Scholar
  • 50 Hill M, Dolan G. Diagnosis, clinical features and molecular assessment of the dysfibrinogenaemias. Haemophilia 2008; 14 (5) 889-897
    CrossrefPubMedGoogle Scholar
  • 51 Morris TA, Marsh JJ, Chiles PG , et al. High prevalence of dysfibrinogenemia among patients with chronic thromboembolic pulmonary hypertension. Blood 2009; 114 (9) 1929-1936
    CrossrefPubMedGoogle Scholar
  • 52 Mariani G, Herrmann FH, Schulman S , et al; International Factor VII Deficiency Study Group. Thrombosis in inherited factor VII deficiency. J Thromb Haemost 2003; 1 (10) 2153-2158
    CrossrefPubMedGoogle Scholar
  • 53 Marty S, Barro C, Chatelain B , et al. The paradoxical association between inherited factor VII deficiency and venous thrombosis. Haemophilia 2008; 14 (3) 564-570
    CrossrefPubMedGoogle Scholar
  • 54 Mariani G, Napolitano M, Dolce A , et al. Adverse events in treatment of inherited factor VII deficiency: final analysis of the STER. [ASH abstract 2279]. ASH Annual Meeting Abstracts 2012;120.
    PubMedGoogle Scholar
  • 55 Giansily-Blaizot M, Marty S, Chen SW, Pellequer JL, Schved JF. Is the coexistence of thromboembolic events and Factor VII deficiency fortuitous?. Thromb Res 2012; 130 (Suppl. 01) S47-S49
    CrossrefPubMedGoogle Scholar
  • 56 Girolami A, Tezza F, Scandellari R, Vettore S, Girolami B. Associated prothrombotic conditions are probably responsible for the occurrence of thrombosis in almost all patients with congenital FVII deficiency. Critical review of the literature. J Thromb Thrombolysis 2010; 30 (2) 172-178
    CrossrefPubMedGoogle Scholar
  • 57 Girolami A, Candeo N, Bonamigo E, Fabris F. Arg 304 Gln (FVII Padua) and Ala 294 Val mutations are equally present in patients with FVII deficiency and thrombosis. Eur J Haematol 2011; 87 (1) 92-94
    CrossrefPubMedGoogle Scholar
  • 58 Girolami A, Bertozzi I, Rigoni I, Muzzolon R, Vettore S. Congenital FVII deficiency and thrombotic events after replacement therapy. J Thromb Thrombolysis 2011; 32 (3) 362-367
    CrossrefPubMedGoogle Scholar
  • 59 Girolami A, Scarparo P, Bonamigo E, Treleani M, Lombardi AM. Homozygous FVII deficiencies with different reactivity towards tissue thromboplastins of different origin. Hematology 2012; 17 (6) 350-354
    CrossrefPubMedGoogle Scholar
  • 60 Giansily-Blaizot M, Verdier R, Biron-Adréani C , et al; Study group of FVII deficiency. Analysis of biological phenotypes from 42 patients with inherited factor VII deficiency: can biological tests predict the bleeding risk?. Haematologica 2004; 89 (6) 704-709 Erratum in: Haematologica 2007;92(11):1584
    PubMedGoogle Scholar
  • 61 Seligsohn U. Factor XI deficiency in humans. J Thromb Haemost 2009; 7 (Suppl. 01) 84-87
    CrossrefPubMedGoogle Scholar
  • 62 Salomon O, Steinberg DM, Koren-Morag N, Tanne D, Seligsohn U. Reduced incidence of ischemic stroke in patients with severe factor XI deficiency. Blood 2008; 111 (8) 4113-4117
    CrossrefPubMedGoogle Scholar
  • 63 Salomon O, Steinberg DM, Zucker M, Varon D, Zivelin A, Seligsohn U. Patients with severe factor XI deficiency have a reduced incidence of deep-vein thrombosis. Thromb Haemost 2011; 105 (2) 269-273
    PubMedGoogle Scholar
  • 64 Mannucci PM, Bauer KA, Santagostino E , et al. Activation of the coagulation cascade after infusion of a factor XI concentrate in congenitally deficient patients. Blood 1994; 84 (4) 1314-1319
    PubMedGoogle Scholar
  • 65 Kenet G, Lubetsky A, Luboshitz J , et al. Lower doses of rFVIIa therapy are safe and effective for surgical interventions in patients with severe FXI deficiency and inhibitors. Haemophilia 2009; 15 (5) 1065-1073
    CrossrefPubMedGoogle Scholar
  • 66 Girolami A, Candeo N, Vettore S, Lombardi AM, Girolami B. The clinical significance of the lack of arterial or venous thrombosis in patients with congenital prothrombin or FX deficiency. J Thromb Thrombolysis 2010; 29 (3) 299-302
    CrossrefPubMedGoogle Scholar
  • 67 Nurden A, Mercié P, Zely P, Nurden P. Deep vein thrombosis, Raynaud's phenomenon, and Prinzmetal angina in a patient with Glanzmann thrombasthenia. Case Rep Hematol 2012; 2012: 156290
    PubMedGoogle Scholar
  • 68 Rezende SM. Secondary prophylaxis with warfarin for recurrent thrombosis in a patient with Glanzmann thrombasthenia and F5 G1691A. Br J Haematol 2012; 156 (1) 144
    CrossrefPubMedGoogle Scholar
  • 69 Tullu MS, Vaideeswar P, Pandit SP, Lahiri KR. Glanzmann thrombasthenia with endomyocardial fibrosis: a thrombotic paradox. Int J Cardiol 2007; 114 (3) 401-402
    CrossrefPubMedGoogle Scholar
  • 70 Girolami A, Sambado L, Bonamigo E, Vettore S, Lombardi AM. Occurrence of thrombosis in congenital thrombocytopenic disorders: a critical annotation of the literature. Blood Coagul Fibrinolysis 2013; 24 (1) 18-22
    CrossrefPubMedGoogle Scholar
  • 71 Sheth S, Soff G, Mitchell B , et al. Managing incidentally diagnosed isolated factor VII deficiency perioperatively: a brief expert consensus report. Expert Rev Hematol 2012; 5 (1) 47-50
    CrossrefPubMedGoogle Scholar
  • 72 Mannucci PM, Schutgens RE, Santagostino E, Mauser-Bunschoten EP. How I treat age-related morbidities in elderly persons with hemophilia. Blood 2009; 114 (26) 5256-5263
    CrossrefPubMedGoogle Scholar
  • 73 Tuinenburg A, Damen SA, Ypma PF, Mauser-Bunschoten EP, Voskuil M, Schutgens RE. Cardiac catheterization and intervention in haemophilia patients: prospective evaluation of the 2009 institutional guideline. Haemophilia 2013; 19 (3) 370-377
    CrossrefPubMedGoogle Scholar
  • 74 Schuepbach RA, Meili EO, Schneider E, Peter U, Bachli EB. Lepirudin therapy for thrombotic complications in congenital afibrinogenaemia. Thromb Haemost 2004; 91 (5) 1044-1046
    PubMedGoogle Scholar
  • 75 Rugeri L, Quélin F, Chatard B, De Mazancourt P, Negrier C, Dargaud Y. Thrombin generation in patients with factor XI deficiency and clinical bleeding risk. Haemophilia 2010; 16 (5) 771-777
    CrossrefPubMedGoogle Scholar