Subscribe to RSS
DOI: 10.1160/TH05-06-0424
The influence of the haematocrit on primary haemostasis in vitro
Financial support: This work has been supported by the Bonizzi-Theler-Foundation, SwitzerlandPublication History
Received
16 June 2005
Accepted after resubmission
17 October 2005
Publication Date:
07 December 2017 (online)
Summary
Primary haemostasis consists of platelet adhesion to subendothelial collagen, their activation and aggregation and finally the formation of a platelet plug. Erythrocytes are involved in this process because they flow in the center of the vessel and push platelets towards the site of action on the vessel wall and enhance shear forces, which activate platelets. In the platelet function analyzer PFA-100® (Dade Behring, Düdingen, Switzerland), the in vivo situation is simulated in vitro with blood being aspirated at high shear rates (5000s-1) through a capillary into a membrane pore with a diameter of 150 μm coated with type I collagen and either epinephrine or adenosine diphosphate. Aggregating platelets plug the pore and stop the flow, which is measured as the closure time. We analysed the influence of erythrocytes on platelet function analyzer measurements by systematic variation of the haematocrit (20,30,40,and 50%) at constant platelet counts of 289±61 ×103/μl plasma, or 152±30 ×103/μl blood, 96±9 ×103/μl blood and 54±5 ×103/μl blood, respectively. An inverse correlation was found between haematocrit and closure time under all circumstances. A decrease of the platelet count by 50 ×103 /μl could be compensated for by a 10% increase in haematocrit. The haematocrit must, therefore, be taken into consideration for the correct interpretation of PFA-100® measurements. Our data also provide a pathophysiological rationale to reduce the risk of bleeding in patients with thrombocytopenia and anaemia by normalizing the haematocrit with erythrocyte transfusions.
-
References
- 1 Ruggeri ZM. Mechanisms initiating platelet thrombus formation. Thromb Haemost 1997; 78: 611-6.
- 2 Turitto VT, Weiss HJ. Red blood cells: their dual role in thrombus formation. Science 1980; 207: 541-3.
- 3 Turitto VT, Weiss HJ. Platelet and red cell involvement in mural thrombogenesis. Ann N Y Acad Sci 1983; 416: 363-76.
- 4 Duke WW. The relation of blood platelets to hemorrhagic disease: description of a method for determining the bleeding time and report of three cases of hemorrhagic disease relieved by transfusion. J Am Med Ass 1910; 55: 1185-92.
- 5 Hellem AJ, Borchgrevink CF, Ames SB. The role of red cells in haemostasis: the relation between haematocrit, bleeding time and platelet adhesiveness. Br J Haematol 1961; 7: 42-50.
- 6 Goldsmith HL. The flow of model particles and blood cells and its relation to thrombogenesis. Prog Hemost Thromb 1972; 1: 97-127.
- 7 Reimers RC, Sutera SP, Joist JH. Potentiation by red blood cells of shear-induced platelet aggregation: relative importance of chemical and physical mechanisms. Blood 1984; 6: 1200-6.
- 8 Santos MT, Valles J, Marcus AJ. et al Enhancement of platelet reactivity and modulation of eicosanoid production by intact erythrocytes. J Clin Invest 1991; 87: 571-80.
- 9 Valles J, Santos MT, Aznar J. et al Erythrocytes metabolically enhance collagen-induced platelet responsiveness via increased thromboxane production, ADP release, and recruitment. Blood 1991; 78: 154-62.
- 10 Kundu SK, Heilmann EJ, Sio R. et al Description of an in vitro platelet function analyzer–PFA-100. Semin Thromb Hemost 1995; 21 (Suppl. 02) 106-12.
- 11 Marshall PW, Williams AJ, Dixon RM. et al A comparison of the effects of aspirin on bleeding time measured using the Simplate method and closure time measured using the PFA-100, in healthy volunteers. Br J Clin Pharmacol 1997; 44: 151-5.
- 12 Wuillemin WA, Gasser KM, Zeerleder SS. et al Evaluation of a Platelet Function Analyzer in patients with a bleeding tendency. Swiss Medical Weekly 2002; 132: 443-8.
- 13 Franchini M. The platelet-function analyzer (PFA-100) for evaluating primary hemostasis. Hematology 2005; 10: 177-81.
- 14 Favaloro EJ. Clinical application of the PFA-100. Curr Opin Hematol 2002; 9: 407-15.
- 15 Fressinaud E, Veyradier A, Truchund F. et al Screening for von Willebrand disease with a new analyzer using high shear stress: A study of 60 cases. Blood 1998; 91: 1325-31.
- 16 Mammen EF, Comp PC, Gosselin R. PFA-100 system: a new method for assessment of platelet dysfunction. Semin Thromb Hemost 1998; 24: 195-202.
- 17 Cattaneo M, Federici AB, Lecchi A. et al Evaluation of the PFA-100 system in the diagnosis and therapeutic monitoring of patients with von Willebrand disease. Thromb Haemost 1999; 82: 35-9.
- 18 Chakroun T, Gerotziafas G, Robert F. et al In vitro aspirin resistance detected by PFA-100 closure time: pivotal role of plasma von Willebrand factor. Br J Haematol 2004; 124: 80-5.
- 19 Koscielny J, Ziemer S, Radtke H. et al A practical concept for preoperative identification of patients with impaired primary hemostasis. Clin Appl Thromb Hemost 2004; 10: 195-204.
- 20 Cristiaens L, Macchi L, Herpin D. et al Resistance to aspirin in vitro at rest and during exercise in patients with angiographically proven coronary artery disease. Thromb Res 2003; 108: 115-9.
- 21 Grau AJ, Reiners S, Lichy C. et al Platelet function under aspirin, clopidogrel, and both after ischemic stroke. A case-crossover study. Stroke 2003; 34: 849-55.
- 22 Reiter RA, Mayr F, Blazicek H. et al Desmopressin antagonizes the in vitro platelet dysfunction induced by GPIIb/IIIa inhibitors and aspirin. Blood 2003; 102: 4594-9.
- 23 Alberts MJ, Bergman DL, Molner E. et al Antiplatelet effect of aspirin in patients with cerebrovascular disease. Stroke 2004; 35: 175-8.
- 24 Sambola A, Heras M, Escolar G. The PFA-100 detects sub-optimal antiplatelet response in patients on aspirin. Platelets 2004; 15: 439-46.
- 25 Borzini P, Lazzaro A, Mazzucco L. Evaluation of the haemostatic function of stored platelet concentrates using the platelet function analyzer (PFA-100TM). Haematologica 1999; 84: 1104-9.
- 26 Pontiggia L, Lassila R, Pederiva S. et al Increased platelet-collagen interaction associated with double homozygosity for receptor polymorphisms of platelet GPIa and GPIIIa. Arterioscler Thromb Vasc Biol 2002; 22: 2093-8.
- 27 Lanza GA, Sestito A, Iacovella S. et al Relation between platelet response to exercise and coronary angiographic findings in patients with effort angina. Circulation 2003; 107: 1378-82.
- 28 Mimidis K, Papadopoulos V, Kartasis Z. et al Assessment of platelet adhesiveness and aggregation in mild acute pancreatitis using the PFA-100TM system. J Pancreas 2004; 5: 132-7.
- 29 Escolar G, Cases A, Vinas M. et al Evaluation of acquired platelet dysfunctions in uremic and cirrhotic patients using the platelet function analyzer (PFA-100): influence of hematocrit elevation. Haematologica 1999; 84: 614-9.
- 30 Mischke R, Keidel A. Influence of platelet count, acetylsalicylic acid, von Willebrand’s disease, coagulopathies, and haematocrit on results obtained using a platelet function analyzer in dogs. Vet J 2003; 165: 43-52.
- 31 Aarts PAAM, Heethaar RM, Sixma JJ. Blood platelets are concentrated near the wall and red blood cells, in the center in flowing blood. Arteriosclerosis 1988; 8: 819-23.
- 32 Yeh C, Eckstein EC. Transient lateral transport of platelet-sized particeles in flowing blood suspensions. Biophys J 1994; 66: 1706-16.
- 33 Brash JL, Brophy JM, Feuerstein IA. Adhesion of platelets to artificial surfaces: effect of red cells. J Biomed Mater Res 1976; 10: 429-43.
- 34 Alkhamis TM, Beissinger RL, Chediak JR. Artificial surface effect on red blood cells and platelets in laminar shear flow. Blood 1990; 75: 1568-75.
- 35 Joist JH, Bauman JE, Sutera SP. Platelet adhesion and aggregation in pulsatile shear flow: effects of red blood cells. Thromb Res 1998; 92 (Suppl. 02) S47-52.
- 36 Karino T, Goldsmith HL. Adhesion of human platelets to collagen on the walls distal to a tubular expansion. Microvasc Res 1979; 17: 238-62.
- 37 Jordan A, David T, Homer-Vanniasinkam S. et al The effect of margination and red cell augmented platelet diffusivity on platelet adhesion in complex flow. Biorheology 2004; 41: 641-53.
- 38 Alkhamis TM, Beissinger RL, Chediak JR. Red blood cell effect on platelet adhesion and aggregation in low-stress shear flow. Myth or fact?. ASAIO Trans 1988; 34: 868-73.
- 39 Posan E, McBane RD, Grill DE. et al Comparison of PFA-100 testing and bleeding time for detecting platelet hypofunction and von Willebrand disease in clinical practice. Thromb Haemost 2003; 90: 483-90.
- 40 Cattaneo M, Lecchi A, Agati B. et al Evaluation of platelet function with the PFA-100 system in patients with congenital defects of platelet secretion. Thromb Res 1999; 96: 213-7.
- 41 Fressinaud E, Veyradier A, Sigaud M. et al Therapeutic monitoring of von Willebrand disease: interest and limits of a platelet function analyser at high shear rates. Br J Haematol 1999; 106: 777-83.
- 42 Cariappa R, Wilhite TR, Parvin CA. et al Comparison of PFA-100 and bleeding time testing in pediatric patients with suspected hemorragic problems. J Pediatr Hematol Oncol 2003; 25: 474-9.
- 43 Boldt J, Hüttner I, Suttner S. et al Changes of haemostasis in patients undergoing major abdominal surgery- is there a difference between elderly and younger patients?. Br J Anaesth 2001; 87: 435-40.
- 44 Forestier F, Coiffic A, Mouton C. et al Platelet function point-of-care tests in post-bypass cardiac surgery: are they relevant?. Br J Anaesth 2002; 89: 715-21.
- 45 Chien S. Blood rheology and its relation to flow resistance and transcapillary exchange with special reference to shock. Advances in Microcirculation 1969; 2: 89-103.
- 46 Livio M, Gotti E, Marchesi D. et al Uraemic bleeding: Role of anaemia and beneficial effect of red cell transfusion. Lancet 1982; 2: 1013-5.
- 47 Fernandez F, Goudable C, Sie P. et al Low haematocrit and prolonged bleeding time in uraemic patients: Effect of red cell transfusions. Br J Haematol 1985; 59: 139-48.
- 48 Ordinas A, Escolar G, Cirera I. et al Existence of a platelet-adhesion defect in patients with cirrhosis independent of hematocrit: Studies under flow conditions. Hepatology 1996; 24: 1137-42.
- 49 Michiels JJ, Bernemann ZN, Schroyens W. et al Pathophysiology and treatment of platelet-mediated microvascular disturbances, major thrombosis and bleeding complications in essential thrombocythaemia and polycythaemia vera. Platelets 2004; 15: 67-84.
- 50 Erikssen G, Thaulow E, Sandvik L. et al Haematocrit: a predictor of cardiovascular mortality?. J Intern Med 1993; 234: 493-9.
- 51 Gagnon DR, Zhang TJ, Brand FN. et al Hematocrit and the risk of cardiovascular disease–the Framingham study: a 34-year follow-up. Am Heart J 1994; 127: 674-82.
- 52 Lowe G, Rumley A, Norrie J. et al Blood rheology, cardiovascular risk factors, and cardiovascular disease: the West of Scotland Coronary Prevention Study. Thromb Haemost 2000; 84: 553-8.
- 53 Brown DW, Giles WH, Croft JB. Hematocrit and the risk of coronary heart disease mortality. Am Heart J 2001; 142: 657-63.