Hamostaseologie 2008; 28(05): 299-311
DOI: 10.1055/s-0037-1617178
Hämostaseologie
Schattauer GmbH

Erworbene Plättchenfunktionsstörungen

Pathogenese, Klassifikation, Häufigkeit, Diagnostik und BehandlungAcquired platelet function disordersPathogenesis, classification, frequency, diagnosis, clinical management
R. E. Scharf
1   Institut für Experimentelle und Klinische Hämostaseologie, Hämotherapie und Transfusionsmedizin, Universitätsklinikum Düsseldorf, Biologisch-Medizinisches Forschungszentrum der Heinrich-Heine-Universität, Düsseldorf
› Author Affiliations
Further Information

Publication History

Publication Date:
29 December 2017 (online)

Zusammenfassung

Angesichts des hohen Medikamentenkonsums in unserer Gesellschaft überrascht es nicht, dass Pharmaka die Hauptursache erworbener Plättchenfunktionsstörungen darstellen. Neben den typischen Vertretern antithrombozytärer Medikamente wie Azetylsalizylsäure, Clopidogrel und ╒IIb®3 (GPIIb-IIIa)-Rezeptorantagonisten können auch andere häufig eingesetzte Medikamente wie nicht steroidale entzündungshemmende Substanzen, Antibiotika, Serotonin- Wiederaufnahme-Inhibitoren und Volumenexpander die Plättchenfunktion beeinträchtigen und eine Blutungsneigung bedingen oder verstärken. Daneben gibt es klinische Zustände, die mit Plättchenfunktionsstörungen einhergehen und eine hämorrhagische Diathese verursachen. Im Gegensatz zu angeborenen Thrombozytopathien treffen wir im klinischen Alltag sehr viel häufiger auf erworbene Plättchenfunktionsstörungen. Sie verdienen besondere Aufmerksamkeit. Ihre Pathogenese ist weitgestreut und reichlich heterogen. Die genaue Diagnostik kann schwierig sein, da manchmal überlappende Abweichungen bei der gleichen Krankheit bestehen. Darüber hinaus können erworbene Plättchenfunktionsstörungen in jedem Lebensalter auftreten und in ihrem Schweregrad von gering bis lebensbedrohlich reichen. Angesichts ihrer Heterogenität werden die erworbenen Thrombozytopathien im Zusammenhang mit der klinischen Situation bzw. Grunderkrankung besprochen.

Summary

Given the high consumption of pharmacological agents in western societies, it is not surprising at all that drugs represent the most common cause of acquired platelet dysfunction. While acetylsalicylic acid, clopigogrel and integrin ╒IIb®3 (GPIIb-IIIa) receptor antagonists are well-known as prototypes of antiplatelet drugs, other widely used agents including non-steroidal anti-inflammatory drugs, antibiotics, serotonin reuptake inhibitors, and volume expanders can also impair platelet function and cause or aggravate haemorrhages. Besides pharmacological agents, certain clinical conditions are often associated with qualitative platelet disorders and bleeding diathesis. Consequently, in contrast to inherited platelet disorders, acquired platelet function defects are much more frequent in clinical practice and deserve special attention. Their patho genesis is widespread and heterogeneous with various, sometimes overlapping abnormalities. Moreover, acquired platelet dysfunctions can occur at any age and range in severity from mild to life-threatening haemorrhages. Due to their heterogeneity, acquired platelet function disorders will be classified and discussed according to the underlying clinical setting or disease.

 
  • Literatur

  • 1 Aguilar M, Hart R. Antiplatelet therapy for preventing stroke in patients with non-valvular atrial fibrillation and no previous history of stroke or transient ischemic atacks. Cochrane Database Syst Rev 2005; 4: CD001925.
  • 2 Ahrens I, Schwarz M, Peter K, Bode C. Therapeutic inhibitors of platelet aggregation – from aspirin to integrin blockers. Transf Med Hemother 2007; 34: 44-54.
  • 3 Antiplatelet Trialists’ Collaboration.. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. Br Med J 2002; 324: 71-86.
  • 4 Antman EM, Anbe DT, Armstrong PW. et al. ACC/ AHA Guidelines update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2004; 44: E1-E211.
  • 5 Besarab A, Bolton WK, Brown JK. et al. The effects of normal as compared with low hematocrit values in patients with cardia disease who are receiving hemodialysis and epoetin. N Engl J Med 1998; 339: 584-590.
  • 6 Bhatt DL, Topol EJ. Scientific and therapeutic advances in antiplatelet therapy. Nat Rev Drug Discov 2003; 2: 15-28.
  • 7 Bick RL. Hemostasis defects associated with cardiac surgery, prosthetic devices, and other extracorporeal circuits. Semin Thromb Hemost 1985; 11: 249-280.
  • 8 Boccardo P, Remuzzi G, Galbusera M. Platelet dysfunction in renal failure. Semin Thromb Hemost 2004; 30: 578-589.
  • 9 Boylan B, Chen H, Rathore V. et al. Anti-GPVI-associated ITP: an acquired platelet disorder caused by autoantibody-mediated clearance of the GPVI/ FcR©-chain from the human platelet surface. Blood 2004; 104: 1350-1355.
  • 10 Braunwald E, Antman E, Beasley J. et al. ACC/ AHA Guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction – 2002. American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2002; 106: 1893-1900.
  • 11 Budde U, Scharf RE, Franke P. et al. Elevated platelet count as a cause of abnormal von Willebrand factor multimer distribution in plasma. Blood 1994; 82: 475-482.
  • 12 Catella-Lawson F, Reilly MP, Kapoor SC. et al. Cyclooxygenase inhibitors and the antiplatelet effects of aspirin. N Engl J Med 2001; 345: 1809-1817.
  • 13 Cattaneo M. Inherited platelet-based bleeding disorders. J Thromb Haemost 2003; 1: 1628-1636.
  • 14 Chen ZM, Jiang LX, Chen YP. et al. Addition of clopidogrel to aspirin in 45 852 patients with acute myocardial infarction: randomised placebocontrolled trial. Lancet 2005; 366: 1607-1621.
  • 15 Coller BS, Peerschke EJ, Seligsohn U. et al. Studies on the binding of an alloimmune and two murine monoclonal antibodies to the platelet glycoprotein IIb-IIIa complex receptor. J Lab Clin Med 1986; 107: 384-392.
  • 16 Coller BS. Anti-GPIIb-IIIa drugs: current strategies and future directions. Thromb Haemost 2001; 86: 427-443.
  • 17 Cortelazzo S, Viero P, Finazzi O. et al. Incidence and risk factors for thrombotic complications in a historical cohort of 100 patients with essential thrombcythemia. J Clin Oncol 1990; 8: 556-562.
  • 18 Di Minno G, Coraggio F, Cerbone AM. et al. A myeloma paraprotein with specifity for platelet glycoprotein IIIa in a patient with a fatal bleeding disorder. J Clin Invest 1986; 77: 157-164.
  • 19 Eikelboom Hirsh J. Combined antiplatelet and anticoagulant therapy: clinical benefits and risks. J Thromb Haemost 2007; 5 (Suppl. 01) 255-263.
  • 20 Fuster V, Ryden LE, Cannon DS. et al. ACC/AHA/ ESC 2006 Guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society for Cardiology Committee for Practice Guidelines. Circulation 2006; 114: c257-c354.
  • 21 Gawaz MP, Dobos G, Spath M. et al. Impaired function of platelet membrane glycoprotein IIb- IIIa in end stage renal disease. J Am Soc Nephrol 1994; 5: 36-46.
  • 22 George JN, Shattil SJ. The clinical importance of acquired abnormalities of platelet function. N Engl J Med 1991; 324: 27-39.
  • 23 Greaves M, Watson HG. Approach to the diagnosis and management of mild bleeding disorders. J Thromb Haemost 2007; 5 (Suppl. 01) 167-174.
  • 24 Harker LA, Malpass TW, Branson HE. et al. Mechanism of abnormal bleeding in patients undergoing cardiopulmonary bypass: acquired transient platelet dysfunction associated with selective ╒-granule release. Blood 1980; 56: 824-834.
  • 25 Harker LA. Bleeding after cardiopulmonary bypass. N Engl J Med 1986; 314: 1446-1448.
  • 26 Hirsch AT, Haskal ZJ, Hertzer NR. et al. ACC/ AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mensentericä and abdominal aortic). Circulation 2006; 113: e463-e654.
  • 27 Italiano JE, Patell-Hett S, Hartwig JH. Mechanics of proplatelet elaboration. J Thromb Haemost 5 (Suppl. 01) 18-23.
  • 28 Joist JH, George JN. Hemostatic abnormalities in liver and renal disease. In: Colman RW, Hirsh J, Marder VJ. et al (eds). Hemo stasis and Thrombosis. Basic Principles and Clinical Practice. Philadelphia: Lippincott, Williams & Wilkins; 2004: 955-973.
  • 29 Koscielny J, Ziemer S, Radtke H. et al. A practical concept for preoperative identification of patients with impaired primary hemostasis. Clin Appl Thromb 2004; 10: 195-204.
  • 30 Mangano DT, Miao Vuylsteke A. et al. Mortality associated with aprotinin during five years following coronary artery bypass graft surgery. JAMA 2007; 297: 527-529.
  • 31 Mannuci PM. Desmopressin (DDAVP) in the treatment of bleeding disorders: the first 20 years. Blood 1997; 90: 2515-2521.
  • 32 May AE, Geisler T, Gawaz MP. Individualized antithrombotic therapy in high risk patients after coronary stenting. A double-edged sword between thrombosis and bleeding. Thromb Haemost 2008; 99: 487-493.
  • 33 Morath C, Hoffmann T, Kirchhoff EM. et al. Acquired Glanzmann’s thrombasthenia variant and immune thrombocytopenia in a renal transplant recipient receiving tacrolimus. Thromb Haemost 2005; 94: 879-880.
  • 34 Niessner H, Clemetson KJ, Panzer S. et al. Acquired thrombasthenia due to GPIIb-IIIa specific autoantibodies. Blood 1986; 68: 571-576.
  • 35 Nurden P, Nurden AT. Congenital disorders associated with platelet dysfunctions. Thromb Haemost 2008; 99: 253-263.
  • 36 Patrono C, Coller BS, FitzGerald GA. et al. Platelet- active drugs: the relationship among dose, effectiveness, and side effects. The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126: 234S-264S.
  • 37 Petrich BG, Fogelstrand P, Partridge AW. et al. The antithrombotic potential of selective blockade of talin-dependent integrin ╒IIb®3 (platelet GPIIb- IIIa) activation. J Clin Invest 2007; 117: 2250-2259.
  • 38 Rao AK. Acquired qualitative platelet defects. In: Colman RW, Hirsh J, Marder VJ. et al (eds). Hemostasis and Thrombosis. Basic Principles and Clinical Practice. Philadelphia: Lippincott, Williams & Wilkins; 2004: 905-919.
  • 39 Reimers HJ, Scharf RE, Baker RK. Thrombin pretreatment of human platelets impairs thromboxane A2 synthesis from endogenous precursors in the presence of normal cyclooxygenase activity. Blood 1984; 63: 858-865.
  • 40 Ruggeri ZM, Mendolicchio GL. Adhesion mechanisms in platelet function. Circ Res 2007; 100: 1673-1685.
  • 41 Ruggeri ZM. Platelet interactions with vessel wall components during thrombogenesis. Blood Cell Mol Dis 2006; 47: 1903-1910.
  • 42 Sabatine MS, Cannon CP, Gibson CM. et al. , CLARITY-TIMI 28 Investigators. Addition of clopidogrel to aspirin and fibrinolysic therapy for myorcardial infarction with ST-segment elevation. N Engl J Med 2005; 352: 1179-1189.
  • 43 Sacco RL, Adams R, Albers G. et al. Guidelines for prevention of stroke in patients with ischemic troke or transient ischemic attack: a statement for health care professionals from the American Heart Association/American Stroke Association Council on Stroke. Circulation 2006; 113: e409-e449.
  • 44 Sadler JE. Aortic stenosis, von Willebrand factor, and bleeding. N Engl J Med 2003; 349: 323-325.
  • 45 Savage B, Almus-Jacobs F, Ruggeri ZM. Specific synergy of multiple substrate-receptor interactions in platelet thrombus formation under flow. Cell 1998; 94: 657-666.
  • 46 Savage B, Ruggeri ZM. Selective recognition of adhesive sites in surface-bound fibrinogen by glycoprotein IIb-IIIa on nonactivated platelets. J Biol Chem 1991; 266: 11227-11233.
  • 47 Schafer AI. Bleeding and thrombosis in myeloproliferative disorders. Blood 1984; 64: 1-12.
  • 48 Scharf RE. (ed). Progress and Challenges in Transfusion Medicine, Hemostasis, and Hemotherapy. Basel, Freiburg: Karger; 2008
  • 49 Scharf RE, Schneider W. Evaluation of platelet secretion and thrombin generation in patients with chronic renal failure. Thromb Haemost 1985; 50: 10.
  • 50 Scharf RE, Suhijar D, Del Zoppo GJ. Analysis of platelet aggregation defects: characterization of dysfunctional GPIIb-IIIa using conformationspecific antibodies. Thromb Haemost 1993; 69: 1018.
  • 51 Scharf RE, Zotz RB. Blood platelets and myocardial infarction: do hyperactive platelets really exist?. Transf Med Hemother 2006; 33: 189-199.
  • 52 Scharf RE. Congenital and acquired platelet function disorders. Hämostaseologie 2003; 23: 170-180.
  • 53 Scharf RE. Erworbene Plättchen-Speicher - granula -Defekte: Klinische und experimentelle Betrachtungen. Alexander-Schmidt-Gedächtnis- Vorlesung. In: Wenzel E, Hellstern P, Morgenstern E. et al (Hrsg). Rationelle Therapie und Diagnostik von hämorrhagischen und thrombotischen Diathesen. Stuttgart: Schattauer; 1986: 1.27-1.44.
  • 54 Scharf RE. In vitro thromboxane synthesis of depleted platelets following renal transplantation. Thromb Haemost 1990; 64: 161-164.
  • 55 Scharf RE. Molecular basis and clinical aspects of hereditary megakaryocyte and platelet membrane glycoprotein disorders. Hämostaseologie 1996; 16: 114-138.
  • 56 Scharf RE. Thrombozyten und Mikrozirkulationsstörungen. Klinische und experimentelle Untersuchungen zum Sekretionsverhalten und Arachidonsäurestoffwechsel der Blutplättchen. Stuttgart: Schattauer; 1986
  • 57 Schrör K, Hohlfeld T. Acetylsalicylic acid. Weinheim: Wiley VCH 2008:; 109
  • 58 Spivak JL. Polycythemia vera and other myeloproliferative diseases. In: Kasper DL, Braunwald E, Fauci AS. et al (eds). Harrison’s Principles of Internal Medicine. 16th ed. New York: McGraw- Hill; 2005: 626-631.
  • 59 Steering Commiittee of the Physicians’ Health Study Research Group.. Final report on the aspirin component of the ongoing Physicians’ Health Study. N Engl J Med 1989; 321: 129-135.
  • 60 Stockschläder M, Scharf RE. Failure of preactivated human blood platelets to restore defective thromboxane synthesis despite prolonged incubation in plasma. Thromb Haemost 1989; 62: 16-22.
  • 61 Sucker C, Feindt P. Scharf. Aortic stenosis, von Willebrand factor, and bleeding. N Engl J Med 2003; 349: 1773-1774.
  • 62 Tcheng JE, Ellis SG, George BS. et al. Pharmacodynamics of chimeric glycoprotein IIb/IIIa integrin antiplatelet antibody Fab 7E3 in high-risk angioplasty. Circulation 1994; 90: 1757-1764.
  • 63 Varon D, Gitel SN, Varon N. et al. Immune Bernard- Soulier-like syndrome with an anti-glycoprotein- IX antibody. Am J Hematol 1992; 41: 67-68.
  • 64 Vincentelli A, Susen S, Le Torneau T. et al. Acquires von Willebrand syndrome in aortic stenosis. N Engl J Med 2003; 349: 343-349.
  • 65 Wehmeier A, Daum I, Jamin H, Schneider W. Incidence and clinical risk factors for bleeding and thrombotic complications in myeloproliferative disorders. A retrospective analysis of 260 patients. Ann Hematol 1991; 63: 101-106.
  • 66 Wehmeier A, Fricke S, Scharf RE, Schneider W. A prospective study of haemostatic parameters in relation to the clinical cours of myeloproliferative disorders. Eur J Haematol 1990; 45: 191-197.
  • 67 Wehmeier A, Tschöpe D, Esser I. et al. Circulating activated platelets in myeloproliferative disorders. Thromb Res 1991; 61: 271-278.
  • 68 Wisloff F, Godal HC. Prolonged bleeding time with adequate platelet count in hospital patients. Scand J Haematol 1981; 27: 45-50.
  • 69 Xiao T, Takagi J, Coller BS. et al. Structural basis for allostery in integrins and binding to fibrinogen- mimetic therapeutics. Nature 2004; 432: 59-67.
  • 70 Yusuf S, Zhao F, Mehta SR. et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001; 345: 494-502.
  • 71 Zotz RB, Scharf RE. Recombinant factor VIIa in patients with platelet function disorders or thrombocytopenia. Hämostaseologie 2007; 27: 251-262.