Hamostaseologie 2006; 26(04): 309-315
DOI: 10.1055/s-0037-1616976
Research Articles
Schattauer GmbH

Gerinnungsstörungen und Schlaganfall

Coagulation disorders and stroke
J. A. Zeller
1   Klinik für Neurologie (Direktor: Prof. Dr. med. Günther Deuschl), Universitätsklinikum Schleswig- Holstein, Campus Kiel
,
Ch. C. Eschenfelder
1   Klinik für Neurologie (Direktor: Prof. Dr. med. Günther Deuschl), Universitätsklinikum Schleswig- Holstein, Campus Kiel
,
R. Stingele
1   Klinik für Neurologie (Direktor: Prof. Dr. med. Günther Deuschl), Universitätsklinikum Schleswig- Holstein, Campus Kiel
› Author Affiliations
Further Information

Publication History

Publication Date:
27 December 2017 (online)

Zusammenfassung

Hereditäre und erworbene Gerinnungsstörungen können bei der Schlaganfallentstehung eine wichtige Rolle spielen. Wegen der Seltenheit der meisten erblichen Gerinnungsstörungen und der erheblichen Kosten, die sich aus einer unkritischen Indikationsstellung ergeben, ist eine maßgeschneiderte Diagnostik sinnvoll. Suggestive Hinweise auf eine Gerinnungsstörung sind niedriges Lebensalter, mehrfache Thrombosen in der Anamnese, altersuntypische Gefäßdegenerationen, vorherige Aborte bei Schlaganfallpatientinnen oder strukturelle Herzveränderungen (z. B. offenes Foramen ovale). Störungen von AT III, Protein C und S, APC-Resistenz, Prothrombinmutation, Homocysteinämie, Antiphospholipidantikörper und prokoagulatorische zelluläre Interaktionen werden diskuiert.

Summary

Hereditary and acquired coagulation disorders may play an important role in the pathophysiology of acute ischaemic stroke. Because of the low prevalence of these disorders and the considerable costs of unmindful diagnostic effort, a custom- tailored approach is desirable. Suggestive in favour of a possible prothrombotic clotting disorder are young patients, repeated episodes of thrombosis in the patient’s history, inappropriate atherosclerotic vascular changes, previous repeated miscarriages in stroke patients, or structural cardiac abnormalities as a patent foramen ovale. Disorders affecting antithrombin III, protein C und S, APC-resistance, the prothrombin mutation, homocysteinaemia, antiphospholipid antibodies, and procoagulatory cellular interaction are discussed.

 
  • Literatur

  • 1 Adams RJ, McKie VC, Hsu L. et al. Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography. N Engl J Med 1998; 339: 5-11.
  • 2 Adams RJ, Ohene-Frempong K, Wang W. Sickle cell and the brain. Hematology 2001; 31-46.
  • 3 Austin H, Chimowitz MI, Hill HA. et al. Cryptogenic stroke in relation to genetic variation in clotting factors and other genetic polymorphisms among young men and women. Stroke 2002; 33: 2762-8.
  • 4 Brey RL. Antiphospholipid antibodies in young adults with stroke. J Thromb Thrombol 2005; 20: 105-12.
  • 5 Brey RL, Stallworth CL, McGlasson DL. et al. Antiphospholipid antibodies and stroke in young women. Stroke 2002; 33: 2396-400.
  • 6 Bushnell CD, Goldstein LB. Diagnostic testing for coagulopathies in patients with ischemic stroke. Stroke 2000; 31: 3067-78.
  • 7 Casas JP, Bautista LE, Smeeth L. et al. Homocysteine and stroke: evidence on a causal link from mendelian randomisation. Lancet 2005; 365: 224-32.
  • 8 Cervera R, Piette JC, Font J. et al. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1000 patients. Arthritis Rheum 2002; 46: 1019-27.
  • 9 Cronin S, Furie KL, Kelly PJ. Dose-related association of MTHFR 677T allele with risk of ischemic stroke: evidence from a cumulative meta-analysis. Stroke 2005; 36: 1581-7.
  • 10 Crowther MA, Ginsberg JS, Julian J. et al. A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome. N Engl J Med 2003; 349: 1133-8.
  • 11 De Stefano V, Rossi E, Paciaroni K. et al. Screening for inherited thrombophilia: indications and therapeutic implications. Haematologica 2002; 87: 1095-108.
  • 12 Derksen RH, de Groot PG, Kappelle LJ. Low dose aspirin after ischemic stroke associated with antiphospholipid syndrome. Neurology 2003; 61: 111-4.
  • 13 Dykes AC, Walker ID, McMahon AD. et al. A study of Protein S antigen levels in 3788 healthy volunteers: influence of age, sex and hormone use, and estimate for prevalence of deficiency state. Br J Haematol 2001; 113: 636-41.
  • 14 Furie K, Kelly PJ, Kistler JP. Coagulation Studies. In: Chaturvedi SR. Levine (eds). Transient Ischemic Attacks. Blackwell Futura Publishing; 2004: 213-4.
  • 15 Gao XG, Huo Y, Liu XZ. et al. Gene polymorphism of platelet glycoprotein I balpha in Chinese patients with large- and small-artery subtypes of ischemic stroke. Eur Neurol 2005; 54: 73-7.
  • 16 Grossmann R, Geisen U, Merati G. et al. Genetic risk factors in young adults with ‘cryptogenic’ ischemic cerebrovascular disease. Blood Coagul Fibrinolysis 2002; 13: 583-90.
  • 17 Hankey GJ, Eikelboom JW, Loh K. et al. Is there really a power shortage in clinical trials testing the ,,homocysteine hypothesis?“. Arterioscler Thromb Vasc Biol 2004; 24: e147.
  • 18 Hankey GJ, Eikelboom JW, van Bockxmeer FM. et al. Inherited thrombophilia in ischemic stroke and its pathogenic subtypes. Stroke 2001; 32: 1793-9.
  • 19 Homocystein Studies Collaboration.. Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA 2002; 288: 2015-22.
  • 20 Hsieh K, Funk M, Schillinger M. et al. Vienna Stroke Registry. Impact of the platelet glycoprotein Ib alpha Kozak polymorphism on the risk of ischemic cerebrovascular events: a case-control study. Blood Coagul Fibrinolysis 2004; 15: 469-73.
  • 21 Janardhan V, Wolf PA, Kase CS. et al. Anticardiolipin antibodies and risk of ischemic stroke and transient ischemic attack: the Framingham cohort and offspring study. Stroke 2004; 35: 736-41.
  • 22 Juul K, Tybjaerg-Hansen A, Steffensen R. et al. Factor V Leiden: The Copenhagen City Heart Study and 2 meta-analyses. Blood 2002; 100: 3-10.
  • 23 Kelly PJ, Rosand J, Kistler JP. et al. Homocysteine, MTHFR 677C→T polymorphism, and risk of ischemic stroke: results of a meta-analysis. Neurology 2002; 59: 529-36.
  • 24 Khamashta MA, Cuadrado MJ, Mujic F. et al. The management of thrombosis in the antiphospholipid- antibody syndrome. N Engl J Med 1995; 332: 993-7.
  • 25 Kobelt K, Biasiutti FD, Mattle HP. et al. Protein Z in ischaemic stroke. Br J Haematol 2001; 114: 169-73.
  • 26 Levine JS, Branch DW, Rauch J. The antiphospholipid syndrome. N Engl J Med 2002; 346: 752-63.
  • 27 Levine SR, Brey RL, Tilley BC. et al. Antiphospholipid antibodies and subsequent thromboocclusive events in patients with ischemic stroke. JAMA 2004; 291: 576-84.
  • 28 Lichy C, Kropp S, Dong-Si T. et al. A common polymorphism of the protein Z gene is associated with protein Z plasma levels and with risk of cerebral ischemia in the young. Stroke 2004; 35: 40-5.
  • 29 Lindsberg PJ, Grau AJ. Inflammation and infections as risk factors for ischemic stroke. Stroke 2003; 34: 2518-32.
  • 30 Lopaciuk S, Bykowska K, Kwiecinski H. et al. Protein Z in young survivors of ischemic stroke. Thromb Haemost 2002; 88: 536.
  • 31 Margaglione M, D’Andrea G, Giuliani N. et al. Inherited prothrombotic conditions and premature ischemic stroke: sex difference in the association with factor V Leiden. Arterioscler Thromb Vasc Biol 1999; 19: 1751-6.
  • 32 Mas JL, Arquizan C, Lamy C. et al. Recurrent cerebrovascular events associated with patent foramen ovale, atrial septal aneurysm, or both. N Engl J Med 2001; 345: 1740-6.
  • 33 Mayer SA, Sacco RL, Hurlet-Jensen A. et al. Free protein S deficiency in acute ischemic stroke. A case-control study. Stroke 1993; 24: 224-7.
  • 34 McNulty H, Doweyle RC, Strain JJ. et al. Riboflavin lowers homocysteine in individuals homozygous for the MTHFR 677C→T polymorphism. Circulation 2006; 113: 74-80.
  • 35 Moser FG, Miller ST, Bello JA. et al. The spectrum of brain MR abnormalities in sickle-cell disease: a report from the Cooperative Study of Sickle Cell Disease. AJNR Am J Neuroradiol 1996; 17: 965-72.
  • 36 Nabavi DG, Junker R, Wolff E. et al. Prevalence of factor V Leiden mutation in young adults with cerebral ischaemia: a case-control study on 225 patients. J Neurol 1998; 245: 653-8.
  • 37 Papp E, Havasi V, Bene J. et al. Glycoprotein IIIA gene (PlA) polymorphism and aspirin resistance: is there any correlation?. Ann Pharmacother 2005; 39: 1013-8.
  • 38 Prengler M, Pavlakis SG, Prohovnik I. et al. Sickle cell disease: the neurological complications. Ann Neurol 2002; 51: 543-52.
  • 39 Reich LM, Bower M, Key NS. Role of the geneticist in testing and counseling for inherited thrombophilia. Genet Med 2003; 5: 133-43.
  • 40 Rosendaal FR, Doggen CJ, Zivelin A. et al. Geographic distribution of the 20210 G to A prothrombin variant. Thromb Haemost 1998; 79: 706-8.
  • 41 Rosove MH, Brewer PM. Antiphospholipid thrombosis: clinical course after the first thrombotic event in 70 patients. Ann Intern Med 1992; 117: 303-8.
  • 42 Sacco RL, Ellenberg JH, Mohr JP. et al. Infarcts of undetermined cause: the NINCDS Stroke Data Bank. Ann Neurol 1989; 25: 382-90.
  • 43 Slooter AJ, Rosendaal FR, Tanis BC. et al. Prothrombotic conditions, oral contraceptives, and the risk of ischemic stroke. J Thromb Haemost 2005; 3: 1213-7.
  • 44 Staton J, Sayer M, Hankey GJ. et al. Protein Z gene polymorphisms, protein Z concentrations, and ischemic stroke. Stroke 2005; 36: 1123-7.
  • 45 Tait RC, Walker ID, Reitsma PH. et al. Prevalence of protein C deficiency in the healthy population. Thromb Haemost 1995; 73: 87-93.
  • 46 The Antiphospholipid Antibodies in Stroke Study (APASS) Group.. Anticardiolipin antibodies are an independent risk factor for first ischemic stroke. The Antiphospholipid Antibodies in Stroke Study (APASS) Group. Neurology 1993; 43: 2069-73.
  • 47 Toole JF, Malinow MR, Chambless LE. et al. Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. JAMA 2004; 291: 565-75.
  • 48 Tosetto A, Ruggeri M, Castaman G. et al. Inherited abnormalities of blood coagulation in juvenile stroke. A case-control study. Blood Coagul Fibrinolysis 1997; 8: 397-402.
  • 49 Vasse M, Guegan-Massardier E, Borg JY. et al. Frequency of protein Z deficiency in patients with ischaemic stroke. Lancet 2001; 357: 933-4.
  • 50 Wagner KR, Giles WH, Johnson CJ. et al. Platelet glycoprotein receptor IIIa polymorphism P1A2 and ischemic stroke risk: the Stroke Prevention in Young Women Study. Stroke 1998; 29: 581-5.
  • 51 Weber R, Busch E. Thrombophilias in patients with ischemic stroke. Indication and calculated costs for evidence-based diagnostics and treatment. Nervenarzt 2005; 76: 193-201.
  • 52 Weimar C, Glahn J, von Reutern GM. et al. Treatment of ischemic stroke in 14 neurologic stroke units. An evaluation of the stroke databank of the German Stroke Aid Foundation. Nervenarzt 2002; 73: 342-8.
  • 53 Wells PS, Blajchman MA, Henderson P. et al. Prevalence of antithrombin deficiency in healthy blood donors: a cross-sectional study. Am J Hematol 1994; 45: 321-4.
  • 54 Wilson WA, Gharavi AE, Koike T. et al. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop. Arthritis Rheum 1999; 42: 1309-11.
  • 55 Zeller JA, Lenz A, Eschenfelder CC. et al. Plateletleukocyte interaction and platelet activation in acute stroke with and without preceding infection. Arterioscler Thromb Vasc Biol 2005; 25: 1519-23.
  • 56 Zunker P, Hohenstein C, Plendl HJ. et al. Activated protein C resistance and acute ischaemic stroke: relation to stroke causation and age. J Neurol 2001; 248: 701-4.