RSS-Feed abonnieren
DOI: 10.1055/s-0037-1615075
Effects of Skin Mast Cells on Bleeding Time and Coagulation Activation at the Site of Platelet Plug Formation
Publikationsverlauf
Received
13. Mai 1997
Accepted after revision
19. November 1997
Publikationsdatum:
07. Dezember 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/199804/lookinside/thumbnails/10-1055-s-0037-1615075-1.jpg)
Summary
We studied the effects of stimulated skin mast cells on bleeding time and thrombin generation which was measured using prothrombin fragment F 1+2 (F 1+2) and thrombin-antithrombin-III-complex (TAT). In 10 patients with urticaria pigmentosa (chronic cutaneous mast cell accumulation) the mean bleeding time was significantly prolonged in wounds made on urticaria pigmentosa lesions vs. normal skin (460 ± 34 vs. 342 ± 27 s, p = 0.005). In 10 atopic subjects skin incisions were made on prick-tested sites 30, 60, 120 and 240 min after administration of an allergen (acute mast cell stimulation), histamine or vehicle. The mean bleeding time was significantly prolonged at all time points, being maximal at 120 min (60% prolonged) in wounds made on allergen-stimulated skin areas (p <0.01) compared with histamine or vehicle sites. Administration of allergen or histamine lowered the TAT concentration in the bleeding-time blood. Furthermore, TAT and F 1+2 levels in the bleeding-time blood were lower at 60, 120 and 240 min after allergen or histamine application in comparison with samples collected at 30 min. We conclude that skin mast cells can regulate primary hemostasis by prolonging bleeding time and by inhibiting thrombin generation.
-
References
- 1 Waldorf HA, Walsh LJ, Schecter NM, Murphy GF. Early cellular events in evolving cutaneous delayed hypersensitivity in humans. Am J Pathol 1991; 138: 477-86.
- 2 Galli SJ. New concepts about the mast cell. N Engl J Med 1993; 328: 257-65.
- 3 Kaartinen M, Penttilä A, Kovanen PT. Mast cells in rupture-prone areas of human coronary atheromas produce and store TNF-alpha. Circulation 1996; 94: 2787-92.
- 4 Kaartinen M, Penttilä A, Kovanen PT. Accumulation of activated mast cells in the shoulder region of human coronary atheroma, the predilection site of atheromatous rupture. Circulation 1994; 90: 1669-78.
- 5 Kovanen PT, Kaartinen M, Paavonen T. Infiltrates of activated mast cells at the site of coronary atheromatous erosion or rupture in myocardial infarction. Circulation 1995; 92: 1084-8.
- 6 Pejler G, Söderström K, Karlström A. Inactivation of thrombin by a com plex between rat mast-cell protease 1 and heparin proteoglycan. Biochem J 1994; 299: 507-13.
- 7 Schwartz LB, Bradford TR, Littman BH, Wintroub BU. The fibrinogenolytic activity of purified tryptase from human lung mast cells. J Immunol 1985; 135: 2762-7.
- 8 Maier M, Spragg J, Schwartz LB. Inactivation of human high molecular weight kininogen by human mast cell tryptase. J Immunol 1983; 130: 2352-6.
- 9 Hatanaka K, Minamiyama M, Tanaka K, Taguchi T, Tajima S, Kitamura Y, Yamamoto A. High susceptibility to ADP-induced thrombus formation in mast cell-deficient W/Wv mice. Thromb Res 1985; 40: 453-64.
- 10 Lassila R, Peltonen S, Lepäntalo M, Saarinen O, Kauhanen P, Manninen V. Severity of peripheral atherosclerosis is associated with fibrinogen and degradation of cross-linked fibrin. Arterioscler Thromb 1993; 13: 1738-42.
- 11 Teitel JM, Bauer KA, Lau HK, Rosenberg RD. Studies of the prothrombin activation pathway utilizing radioimmunoassays for the F2/F1+2 fragment and thrombin-antithrombin complex. Blood 1982; 59: 1086-97.
- 12 Szczeklik A, Milner PC, Birch J, Watkins J, Martin JF. Prolonged bleeding time, reduced platelet aggregation, altered PAF-acether sensitivity and increased platelet mass are a trait of asthma and hay fever. Thromb Haemost 1986; 56: 283-7.
- 13 Szczeklik A, Schmitz-Schumann M, Krzanowski M, Virchow C. Delayed generation of thrombin in clotting blood of atopic patients with hayfever and asthma. Clin Exp Allergy 1991; 21: 411-5.
- 14 Eichinger S, Wolzt M, Nieszpaur-Los M, Schneider B, Lechner K, Eichler H-G, Kyrle PA. Effects of a low molecular weight heparin (Fragmin® ) and of unfractioned heparin on coagulation activation at the site of plug formation in vivo. Thromb Haemost 1994; 72: 831-5.
- 15 Eichinger S, Wolzt M, Schneider B, Nieszpaur-Los M, Heinrichs H, Lechner K, Eichler H-G, Kyrle PA. Effects of recombinant hirudin (r-hirudin HBW 023) on coagulation and platelet activation in vivo. Comparison with unfractioned heparin and a low-molecular-weight heparin preparation (Fragmin). Arterioscler Thromb Vasc Biol 1995; 15: 886-92.
- 16 Keyzer JJ, de Monchy JGR, van Doormaal JJ, van Voorst Vader PC. Improved diagnosis of mastocytosis by measurement of urinary histamine metabolites. N Engl J Med 1983; 309: 1603-5.
- 17 Metcalfe DD, Soter NA, Wasserman SI, Austen KF. Identification of sulfated mucopolysaccharides including heparin in the lesional skin of a patient with mastocytosis. J Invest Dermatol 1980; 74: 210-5.
- 18 Lassila R, Lindstedt K, Kovanen PT. Native macromolecular heparin proteoglycans exocytosed from stimulated rat serosal mast cells strongly inhibit platelet-collagen interactions. Arterioscler Thromb Vasc Biol 1997; 17: 3578-87.
- 19 Wester J, Sixma JJ, Geuze JJ, van der Veen J. Morphology of the early hemostasis in human skin wounds. Influence of acetylsalicylic acid. Lab Invest 1978; 39: 298-311.
- 20 Weiss HJ, Lages B. Studies of thromboxane B2, platelet factor 4, and fibrinopeptide A in bleeding-time blood of patients deficient in von Willebrand factor, platelet glycoproteins Ib and IIb-IIIa, and storage granules. Blood 1993; 82: 481-90.
- 21 Slack SM, Weiss HJ, Lages B, Turitto VT. Mathematical analysis of bleeding time data in patients with platelet disorders and von Willebrand disease. Platelets 1995; 6: 169-75.
- 22 Szczeklik A, Musial J, Undas A, Swadzba J, Gora PF, Piwowarska W, Duplaga M. Inhibition of thrombin generation by aspirin is blunted by hypercholesterolemia. Arterioscler Thromb Vasc Biol 1996; 16: 948-54.
- 23 Thorngren M, Shafi S, Born GVR. Thromboxane A2 in skin-bleeding-time blood and in clotted venous blood before and after administration of acetylsalicylic acid. Lancet 1983; I: 1075-8.
- 24 Kyrle PA, Westwick J, Scully MF, Kakkar VV, Lewis GP. Investigation of the interaction of blood platelets with the coagulation system at the site of plug formation in vivo in man – effect of low-dose aspirin. Thromb Haemost 1987; 57: 62-6.
- 25 Kyrle PA, Eichler HG, Jäger U, Lechner K. Inhibition of prostacyclin and thromboxane A2 generation by low-dose aspirin at the site of plug formation in man in vivo. Circulation 1987; 75: 1025-9.
- 26 Gerrard JM, Taback S, Singhroy S, Docherty JC, Kostolansky I, McNicol A, Kobrinsky NL, McKenzie JK, Rowe R. In vivo measurement of thromboxane B2 and 6-keto-prostaglandin F1α in humans in response to a standardized vascular injury and the influence of aspirin. Circulation 1989; 79: 29-38.
- 27 Michelson AD, Ellis PA, Barnard MR, Matic GB, Viles AF, Kestin AS. Downregulation of the platelet surface glycoprotein Ib-IX complex in whole blood stimulated by thrombin, adenosine diphosphate, or an in vivo wound. Blood 1991; 77: 770-9.
- 28 Abrams CS, Ellison N, Budzynski AZ, Shattil SJ. Direct detection of activated platelets and platelet-derived microparticles in humans. Blood 1990; 75: 128-38.
- 29 Weiss HJ, Lages B. Evidence for tissue factor-dependent activation of the classic extrinsic coagulation mechanism in blood obtained from bleeding time wounds. Blood 1988; 71: 629-35.
- 30 Baldwin AL, Thurston G. Changes in endothelial actin cytoskeleton in venules with time after histamine treatment. Am J Physiol 1995; 269: H1528-37.
- 31 Hirokawa K, Aoki N. Up-regulation of thrombomodulin by activation of histamine H1-receptors in human umbilical-vein endothelial cells in vitro. Biochem J 1991; 276: 739-43.
- 32 Bombeli T, Mueller M, Haeberli A. Anticoagulant properties of the vascular endothelium. Thromb Haemost 1997; 77: 408-23.
- 33 Hamilton KK, Sims PJ. Changes in cytosolic Ca2+ associated with von Willebrand factor release in human endothelial cells exposed to histamine. Study of microcarrier cell monolayers using the fluorescent probe indo-1. J Clin Invest 1987; 79: 600-8.
- 34 Moake JL, Turner NA, Stathopoulos NA, Nolasco LH, Hellums JD. Involvement of large plasma von Willebrand factor (vWF) multimers and unusually large vWF form as derived from endothelial cells in shear stress-induced platelet aggregation. J Clin Invest 1986; 12: 1456-61.
- 35 Meyer D, Girma J-P. von Willebrand factor: structure and function. Thromb Haemost 1993; 70: 99-104.