Studies on the Haemostatic Defect in a Complicated Syndrome

Summary

The Stormorken syndrome is a multifacetted syndrome including a bleeding tendency. No deviations were found in the coagulation- or fibrinolytic systems. Platelet number was low normal, and size abnormal, whereas EM findings were unremarkable. Survival time was half normal. Clot retraction was initially rapid, but clearly decreased, whereas prothrombin consumption was also initially rapid, but complete. Membrane GP’s were normal, so was AA metabolism, PI-cycle, granule storage and secretion, and c-AMP function, whereas 5-HT uptake and storage was decreased. Optical platelet aggregation was low normal with all physiological agonists. The only clearly abnormal finding was that coagulant activity was present on non stimulated platelets at the same level as kaolin-stimulated normal platelets. This indicated a platelet abnormality which should lead to a thrombogenic, not to a haemorrhagic trait. This paradox may have its origin in rheology, because when challenged with in vivo shear rates in an ex vivo perfusion chamber, platelet cohesion was abnormally low. Further studies to better delineate the membrane abnormality are underway.

• References

• 1 Stormorken H, Sjaastad O, Langslet A, Sulg I, Egge K, Diderichsen J. A new syndrome: Thromhocylopalhia, muscle fatigue, asplenia, migraine, ichthyosis and dyslexia. Clin Genet 1985; 28: 367-374
• 2 MeKusiek VA. Mendelian inheritance in man. 8th ed" Johns Hopkins University Press, Baltimore 1988, No. 18507.
• 3 Sjaastad O, Aasly J, Stormorken H, Wysoeka-Bakowska MM, Hφrven I, Fredriksen TA. A new hereditary syndrome with a bleeding tendency, extreme miosis, spasms, dyslexia, thrombocytopathia etc. Pupillometric, evaporimetric, and ophtalmologieal observations. Acta Ophtalmol 1992; 70: 111-119
• 4 Sjaastad O. The hereditary syndrome of thrombopathia, bleeding tendency, extreme miosis, muscular fatigue, asplenia, headache etc. (Stormorken syndrome). I. The headache Headache 1994; 34: 221-225
• 5 Tysnes OB, Aarbakke GM, Verhoven AJ M, Holmsen H. Thin layer chromatography of phosphoinositides from platelet extracts: Interference of an unknown phospholipid. Thromb Res 1985; 40: 329-338
• 6 Lages B, Scrutton MC, Holmsen H. Studies on gel-filtered human platelets: Isolation and characterization in a medium containing no added Ca²⁺⁺, Mg²⁺⁺ and K⁺ . J Lab Clin Med 1975; 85: 811-825
• 7 Hagen I, Bjerrum OJ, Solum NO. Characterization of human platelet proteins solubilized with Triton X-100 by crossed immunoelectrophoresis. Reference patterns of extracts from whole platelets and isolated membranes Eur J Biochem 1979; 99: 9-22
• 8 Thorsen LI, Gaudernack G, Brosstad F, Pedersen TM, Solum NO. Identification of platelet antigens by monoclonal antibodies using crossed immunoelectrophoresis with immunoblotting of the monoclonal antibody. Thromb Haemost 1987; 57: 212-216
• 9 Solum NO, Aakhus A-M, Pedersen T, Gaudernack G. The Phast-system equipment used for crossed immunoelectrophoresis combined with immunoblotting of coprecipated monoclonal antibodies as studied with platelet membrane receptor proteins. Electrophoresis 1989; 10: 752-758
• 10 Anderson NG, Anderson NL. Analytical techniques for cell fractionation. XXL Two-dimensional analysis of serum and tissue proteins: Multiple isoelectric focusing Anal Biochem 1978; 85: 331-340
• 11 Anderson NL, Anderson NG. Two-dimensional analysis of serum and tissue proteins: Multiple gradient slab-gel electrophoresis,XXII Anal Biochem 1978; 85: 341-354
• 12 Jellum E, Thorsrud AK. Clinical applications of two-dimensional electrophoresis Clin Chem 1982; 28: 876-883
• 13 Guevara JrJ, Johnston DA K, Ramagali LS, Martin BA, Capetillo S, Rodrigues LV. Quantitative aspects of silver depositions in proteins resolved in complex polyacryl gels Electrophoresis 1982; 3: 197-205
• 14 Steen VM, Holmsen H. Synergism between thrombin and epinephrine in human platelets: Different dose-response relationship for aggregation and dense granule secretion Thromb Haemost 1985; 54: 680-683
• 15 Dangelmaier CA, Holmsen H. Determination of acid hydrolases in human platelets. Anal Biochem 1980; 108: 182-191
• 16 Holmsen H, Setkowsky-Dangelmaier C. Adenine nucleotide metabolism of blood platelets. X. Formaldehyde stops centrifugation-indueed secretion alter A 23187-stimulation and causes breakdown of metabolic ATP Biochem Biophys Acta 1977; 497: 46-61
• 17 Stormorken H, Lyberg T, Hakvaag L, Nakstad B. Dissociation of the aggregating and the inhibitory effect upon cyclic adenosine monophosphate accumulation by adrenaline and adenosine diphosphate in human platelets. Thromb Res 1987; 45: 363-370
• 18 Nordφy A, Lund S. Platelet factor 3 activity, platelet phospholipids and their fatty acid and aldehyde pattern in normal male subjects. Scand J Clin Lab Invest 1968; 22: 328-338
• 19 Sakariassen KS, Joss R, Muggli R, Kuhn H, Tschopp TB, Sage H, Baumgartner HR. Collagen type III induced ex vivo thrombogenesis in humans: Role of platelets and leukocytes in deposition of fibrin. Arteriosclerosis 1990; 10: 276-284
• 20 Thorsen LI, Gaudernack G, Hack N, Wilkinson JM, Brosstad F, Solum NO. Characterization of a monoclonal antibody ITI-PL I directed against human platelet membrane glycoprotein I lb using extracts of whole platelets and platelet surface and intracellular membranes. Brit J Haemat 1988; 68: 67-74
• 21 Stormorken H, Hellum B, Nakstad B, Thorsrud AK, Jellum E. Polymorphism of a platelet polypeptide. Thromb Res 1990; 60: 71-77
• 22 Tanaka Y, Schroit AJ. Insertion of fluorescent phosphatidylserine into the plasma membrane of red cells. J Biol Chem 1983; 258: 1135-1143
• 23 Schwartz RS, Tanaka Y, Fidler IJ, Chiu D, Lubin B, Schroit AJ. Increased adhesion of sickled and phosphatidylserine-enriched human erythrocytes to cultured human peripheral blood monocytes. J Clin Invest 1985; 75: 1965-1972
• 24 Weiss HJ, Vivic WJ, Lages BA, Rogers J. Isolated deficiency of platelet coagulant activity. Am J Med 1979; 67: 206-212
• 25 Rosing J, Bevers EM, Comfurius P, Hemker HC, van Dieijen G, Weiss HJ, Zwaal RF A. Impaired Factor X- and prothrombin activation associated with decreased phospholipid exposure in platelets from a patient with a bleeding disorder. Blood 1985; 65: 1557-1561
• 26 Roald HE, Sakariassen KS. Axial dependence of collagen-induced thrombus formation in Bowing non-anticoagulated human blood. Antiplatelet drugs impair thrombus growth and increase platelet-collagen adhesion Thromb Haemost 1995; 73: 126-131
• 27 Polanowska-Grabowska R, Gear ARL. Adhesion efficiency, platelet density and size. Brit J Haemat 1992; 82: 715-720
• 28 Mombers C, Verkleij AJ, De Gier J, van Deenen LL M. The interaction of spectrin, actin and synthetic phospholipids. II. The interaction with phosphatidylserine Biochem Biophys Acta 1979; 551: 271-281
• 29 Rybicki AC, Heath R, Lubin B, Schwartz RS. Human erythrocyte protein 4.1 is a phosphatidylserine binding protein. J Clin Invest 1988; 81: 255-260
• 30 Comfurius P, Bevers EM, Zwaal RF A. Interaction between phosphatidylserine and the isolated cytoskeleton of human platelets. Biochem Biophys Acta 1989; 983: 212-216
• 31 Bevers EM, Smets EF, Comfurius P, Zwaal RF A. Physiology of membrane lipid assymetry. Lupus 1994; 3: 235-240
• 32 Fraitag B, Bonard I, Duloray J, Garin NC. Effect of ketanserin on bleeding time: A comparison with aspirin. Thromb Res 1986; 44: 261-264