Mechanisms of Hypercoagulability

Ola E. Dahl

doi:10.1055/s-0037-1615930

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1999; 82(02): 902-906
DOI: 10.1055/s-0037-1615930

Research Article

Schattauer GmbH

Mechanisms of Hypercoagulability

Ola E. Dahl

¹Department of Orthopaedics, Research Forum, Ullevaal University Hospital, Oslo, NORWAY

› Author Affiliations

Abstract

Introduction

Patients undergoing major traumas, major joint replacement surgery, and neurosurgery are at high risk for postoperative deep vein thrombosis (DVT). Even if modern low molecular weight heparin is given as prophylaxis, the frequency of DVT remains high in these patients.^1-7 This may indicate that some patients possess a certain “heparin resistance,” due probably due to an overwhelming procoagulant activity and/or because the hypercoagulable state lasts for a longer time than presently assumed. Tissue factor (TF) is the primary cellular initiator of blood coagulation and the most potent trigger of blood clotting known today.⁸ Adventitia surrounding the major blood vessels, the brain, and the bone marrow are structures with high levels of TF.⁹ Elective hip replacement surgery, which is a fairly well-standardized procedure that involves a great deal of damage to the bone marrow, is therefore, well-suited as a model to study the mechanisms of hypercoagulability.

Full Text

References

References
1 Stamatakis JD, Kakkar VV, Sagar S, Lawrence D, Nairn D, Bentley PG. Femoral vein thrombosis and total hip replacement. BMJ 1977; 2: 223-225.
2 Turpie AGG, Levine MN, Hirsh J, Carter CJ, Jay RM, Powers PJ, Andrew M, Hull RD, Gent M. A randomized controlled trial of a low-molecular-weight heparin (enoxaparin) to prevent deep-vein thrombosis in patients undergoing elective hip surgery. N Engl J Med 1986; 315: 925-929.
3 Kalondiki E, Domjan J, Nicolaides AN, Cunningham DA, al-Kutoubi A, Birch R, Harris N, Hunt D, Johnson J, Marx C. V/Q defects and deep venous thrombosis following total hip replacement. Clin Radiol 1995; 50: 400-403.
4 Geerts WH, Jay RM, Code KI, Chen E, Szalai JP, Saibil EA, Hamilton PA. A comparison of low-dose heparin with low-molecular-weight heparin as prophylaxis against venous thrombosis after major trauma. N Engl J Med 1996; 5: 701-707.
5 Nurmohamed MT, van Riel AM, Henkens CM, Koopman MM, Que GT, dÀzemar P, Buller HR, ten Cate JW, Hoek JA, van der Meer J, van der Heul C, Turpie AG, Haley S, Sicurella A, Gent M. Low molecular weight heparin and compression stockings in the prevention of venous thrombosis in neurosurgery. Thromb Haemost 1996; 75: 233-238.
6 Levine MN, Gent M, Hirsh J, Weitz J, Turpie AG, Powers P, Neemeh J, Wilian A, Skingley P. Ardeparin (low-molecular-weight heparin) vs graduated compression stockings for the prevention of venous thromboembolism. A randomized trial in patients undergoing knee surgery. Arch Intern Med 1996; 22: 851-856.
7 Agnelli G, Piovella F, Buoncristiani P, Severi P, Pini M, D`Angelo A, Beltrametti C, Damiani M, Andrioli GC, Pugliese R, Iorio A, Brambilla G. Enoxaparin plus compression stockings compared with compression stockings alone in the prevention of venous thromboembolism after elective neurosurgery. N Engl J Med 1998; 339: 80-85.
8 Camerer E, Kolstø AB, Prydz H. Cell biology of tissue factor the principal initiator of blood coagulation. Thromb Res 1996; 81: 1-14.
9 Giercksky KE. The procoagulant activity of adipose tissue. Scand J Haematol 1977; 19: 385-395.
10 Schaub G, Lynch PR, Stewart GJ. The response of canine veins to three types of abdominal surgery: A a scanning and transmission electron microscopic study. Surgery 1978; 83: 411-424.
11 Stewart GJ, Stern HR, Schaub RG. Endothelial alterations, deposition of blood elements and increased accumulation of 131 I-albumin in canine jugular veins following abdominal surgery. Thromb Res 1978; 12: 555-563.
12 Stewart GJ, Stern HR, Lynch PR, Malmud LS, Schaub RG. Response of canine jugular veins and carotid arteries to hysterectomy: Increased increased permeability and leukocyte adhesion and invasions. Thromb Res 1980; 20: 473-489.
13 Stewart GJ, Alburger PD, Stone EA, Soszka TW. Total hip replacement induces injury to remote veins in a canine model. J Bone Joint Surg 1983; 65-A: 97-102.
14 Fenton II JW. Thrombin functions and antithrombotic intervention. Thromb Haemost 1995; 74: 493-498.
15 Galdal KS, Evensen SA. Effects of divalentedivalent cations and various vasoactive haemostatically active agents on the integrity of monolayers of cultured human endothelial cells. Thromb Res 1981; 21: 273-28448.
16 Comerota AJ, Stewart GJ, Alburger PD, Smalley K, White JV. Operative venodilation: A a previously unsuspected factor in the cause of postoperative deep vein thrombosis. Surgery 1989; 106: 301-309.
17 Muller WA, Gimbrone MA. Plasmalemma proteins of cultured vascular endothelial cells exhibit apical-basal polarity: analysis by surface selective iodination. J Cell Biol 1986; 103: 2389-2402.
18 Modig J, Bush C, Olerud S, Saldeen T, Waernbaum G. Arterial hypotension and hypoxia during total hip replacement: The the importance of thromboplastic products, fat embolism and acrylic monomer. Acta Anaesthesiol Scand 1975; 19: 28-43.
19 Christie J, Burnett R, Potts HR, Pell ACH. Echocardiography of transatrial embolism during cemented and uncemented hemiarthroplasty of the hip. J Bone Joint Surg 1994; 76-B: 409-412.
20 McGrath BJ, Hsia J, Boyd A, Shay P, Graeter J, Conry K, Campbell D, Naulty JS. Venous embolization after deflation of lower extremity tourniquets. Anesth Analg 1994; 78: 349-353.
21 Giercksky KE, Bjørklid E, Prydz H, Renck H. Circulating tissue thromboplastin during hip surgery. Eur Surg Res 1979; 11: 296-300.
22 Dahl OE, Molnar I, Vinje A, Rø JS, Kierulf P, Andersen Å-B, Dalaker K, Prydz H. Studies on coagulation, fibrinolysis, kallikrein-kinin and complement activation in systemic and pulmonary circulation during hip arthroplasty with acrylic cement. Thromb Res 1988; 50: 875-884.
23 Dahl OE, Johnsen H, Kierulf Molnar I, Rø JS, Vinje A, Mowinckel P. Intrapulmonary thrombin generation and its relation to monomethylmethacrylate plasma levels during hip arthroplasty. Acta Anaesthesiol Scand 1992; 36: 331-335.
24 Dahl OE, Pedersen T, Kierulf P, Westvik Å-B, Lund P, Arnesen H, Seljeflot I, Abdelnoor M, Lyberg T. Sequential intrapulmonary and systemic activation of coagulation and fibrinolysis during and after total hip replacement surgery. Thromb Res 1993; 70: 451-458.
25 Dahl OE, Aspelin T, Lyberg T. The role of bone traumatization and methylmethacrylate monomer cytotoxicity in the initiation of proximal deep vein thrombosis during cemented hip replacement surgery in pigs. Blood Coagul Fibrinol 1995; 6: 709-717.
26 Ereth MH, Weber JG, Abel MD, Lennon RL, Lewallen DG, Ilstrup DM, Rehder K. Cemented versus noncemented total hip arthroplasty. Embolism, hemodynamics and intrapulmonary shunting. Mayo Clin Proc 1992; 67: 1066-1074.
27 Ries MD, Lynch F, Rauscher LA, Richman J, Mick C, Gomez M. Pulmonary function during and after total hip replacement. Findings in patients who have insertion of a femoral component with and without cement. J Bone Joint Surg 1993; 75-Am: 81-587.
28 Dahl OE, Garvik L, Lyberg T. Toxic effects of methylmethacrylate monomer on leukocytes and endothelial cells in vitro. Acta Orthop Scand 1994; 65: 147-153.
29 Dahl OE, Aspelin T, Lyberg T. Evidence for induction of cardiorespiratory and vascular complications by methylmethacrylate monomer in hip replacement surgery. Laboratory and animal investigations. Hip Int 1997; 4: 158-168.
30 Dahl OE, Westvik Å-B, Kierulf P, Lyberg T. Effect of monomethyl- methacrylate on procoagulant activities of human monocytes and umbilical vein endothelial cells in vitro. Thromb Res 1994; 74: 377-387.
31 Miller CL, Graziano C, Lim RC, Chin M. Generation of tissue factor by patient monocytes: Correlation to thromboembolic complications. Thromb Haemost 1981; 489-495.
32 Brox HJ, Østerud B, Bjørklid E, Fenton II JW. Production and availability of thromboplastin in endothelial cells: The effects of thrombin, endotoxin and platelets. Br J Haematol 1984; 57: 239-246.
33 Mulder AB, Hegge-Papping KSM, Magielse CPE, Blom NR, Smit JW, van der Meer J, Halie MR, Bom VJJ. Tumor necrosis factor alpha-induced endothelial tissue factor is located on the cell surface rather than in the subendothelial matrix. Blood 1994; 84: 1559-1565.
34 Narahara N, Enden T, Wiiger M, Prydz H. Polar expression of tissue factor in human umbilical vein endothelial cells. Arterioscler Thromb 1994; 11: 1815-1820.
35 Planes A, Vochelle N, Fagola M. Total hip replacement and deep vein thrombosis. A venographic and necropsy study. J Bone Joint Surg 1990; B 72: 9-13.
36 Sharrock NE, Go G, Sculco TP, Ranawat CS, Maynard MJ, Harpel PC. Changes in circulatory indices of thrombosis and fibrinolysis during total knee arthroplasty performed under tourniquet. J Arthroplasty 1995; 10: 523-528.
37 McNally MA, Bahadur R, Cooke EA, Mollan RAB. Venous haemodynamics in both legs after total knee replacement. J Bone Joint Surg 1997; 79-B: 633-637.
38 Dahl OE, Aspelin T, Arnesen H, Seljeflot I, Kierulf P, Ruyter R, Lyberg T. Increased activation of coagulation and formation of late deep venous thrombosis following discontinuation of thromboprophylaxis after hip replacement surgery. Thromb Res 1995; 4: 299-306.
39 Planes A, Vochelle N, Darmon JY, Fagola M, Bellaud M, Huet Y. Risk of deep-venous thrombosis after hospital discharge in patients having undergone total hip replacement: double blind randomised comparison enoxaparin versus placebo. Lancet 1996; 348: 224-228.
40 Dahl OE, Andreassen G, Aspelin T, Muller C, Mathiessen P, Nyhus S, Abdelnoor M, Solhaug JH, Arnesen H. Prolonged thromboprophylaxis following hip replacement surgery. Thromb Haemost 1997; 1: 26-31.
41 Egeberg O. Inherited antithrombin III deficiency causing thrombophilia. Thromb Diath Haemorrh 1965; 13: 516-30.
42 Florell SR, Rodgers GM. Inherited thrombotic disorders: An update. Am J Hematol 1997; 54: 53-60.
43 Koster T, Rosendaal FR, Briet E, van der Meer FJM, Colly LP, Trienekens PH, Poort SR, Reitsma PH, Vandenbroucke JP. Protein C deficiency in a controlled series of unselected outpatients: An an infrequent but clear risk for venous thrombosis (Leiden Thrombophilia Study). Blood 1995; 85: 2756-2761.
44 Ridker PM, Hennekens CH, Lindpainter K, Stampfer MJ, Eisenberg PR, Miletich JP. Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke, and venous thrombosis in apparently healthy men. N Engl J Med 1995; 332: 912-917.
45 Dahlback B, Carlsson M, Svensson PJ. Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: Prediction prediction of a cofactor to activated protein C. Proc Natl Acad Sci USA 1993; 90: 1004-1008.
46 Bertina RM, Koeleman BPC, Koster T, Rosendaal FR, Dirven RJ, de Ronde H, van der Velden PA, Reitsma PH. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-67.
47 Svensson PJ, Dahlback B. Resistance to activated protein C as a basis for venous thrombosis. N Engl J Med 1994; 330: 517-522.
48 Poort S, Rosendaal F, Reitsma P, Bertina R. A common genetic variation in the 3˘-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 1996; 88: 3698-3703.
49 Leroyer C, Mercier B, Oger E, Chenu E, Abgrall J-F, Ferec C, Mottier D. Prevalence of 20210 allele of the prothrombin gene in venous thromboembolism patients. Thromb Haemost 1998; 80: 49-51.
50 Huges GRV. The antiphospholipid syndrome: ten years on. Lancet 1993; 342: 341-344.
51 Rees MM, Rodgers GM. Homocysteinemia association of a metabolic disorder with vascular disease and thrombosis. Thromb Res 1993; 71: 337-359.
52 den Heijer M, Koster T, Blom HJ, Bos GMJ, Briet E, Reitsma PH, Vandenbroucke JP, Rosendaal FR. Hyperhomocysteinemia as a risk factor for deep venous thrombosis. N Engl J Med 1996; 334: 759-762.
53 Mandel H, Brenner B, Berant M, Rosenberg N, Lanir N, Jakobs C, Fowler B, Seligsohn U. Coexistence of hereditary homocysteinuria and factor V Leiden – Effect on thrombosis. N Engl J Med 1996; 334: 763-768.
54 Faioni EM, Razzari C, Martinelli I, Panzeri D, Franchi F, Mannucci PM. Resistance to activated protein C in unselected patients with arterial and venous thrombosis. Am J Hematol 1997; 55: 59-64.
55 Ridker PM, Glynn RJ, Miletich JP, Goldhaber SZ, Stampfer MJ, Hennekens CH. Age-specific incidence rates of venous thromboembolism among heterozygous carriers of factor V Leiden mutation. Ann Intern Med 1997; 126: 528-531.
56 Kristensen SR, Andersen-Randberg K, Bathum L, Jeune B. Factor V Leiden and venous thrombosis in Danish centenarians. Thromb Haemost 1998; 80: 860-861.
57 Heijmans TB, Westendorp RGJ, Knook DL, Kluft C, Slagboom PE. The risk of mortality and the factor V Leiden mutation in a population-based cohort. Thromb Haemost 1998; 80: 607-609.
58 Cushman M, Rosendaal FR, Psaty BM, Cook EF, Valliere J, Kuller LH, Tracy RP. Factor V Leiden is not a risk factor for arterial vascular disease in the elderly: results from the cardiovascular health study. Thromb Haemost 1998; 79: 912-915.
59 Sakkinen PA, Cushman M, Psaty BM, Kuller LH, Bajaj SP, Sabharwal AK, Boineau R, Macy E, Tracy RP. Correlates of antithrombin, protein C, Protein S and TFPI in a healthy elderly cohort. Thromb Haemost 1998; 80: 134-139.
60 Zehnder JL, Woolson ST, Maloney J. Factor V Leiden and risk of post-operative deep venous thrombosis after total joint replacement. Thromb Haemost 1997; (Suppl) 309.
61 Ryan DH, Crowther MA, Ginsberg JS, Francis CW. Relation of factor V Leiden genotype to risk for acute deep venous thrombosis after joint replacement surgery. Ann Int Med 1998; 128: 270-276.
62 Philipp CS, Dilley A, Saidi P, Evatt B, Austin H, Zawadsky J, Harwood D, Ellingsen D, Barnhart E, Phillips DJ, Hooper WC. Deletion polymorphism in the angiotensin-converting enzyme gene as a thrombophilic risk factor after hip arthroplasty. Thromb Haemost 1998; 80: 869-873.
63 Svensson PJ, Benoni G, Fredin H, Bjorgell O, Nilsson P, Hedlund U, Nylander G, Bergqvist D, Dahlback B. Female gender and resistance to activated protein C (FV: Q506) as potential risk for thrombosis after elective hip arthroplasty. Thromb Haemost 1997; 78: 993-996.
64 Bergqvist D, Benoni G, Bjorgell O, Fredin H, Hedlund U, Nicolas S, Nilsson P, Nylander G. Low-molecular-weight heparin (enoxaparin) as prophylaxis against venous thromboembolism after total hip replacement. N Engl J Med 1996; 335: 696-700.
65 Johnson R, Green JR, Charnley J. Pulmonary embolism and its prophylaxis following the Charnley total hip replacement. Orthop Rel Res 1978; 127: 123-132.
66 Havig Ø. Deep vein thrombsisthrombosis and pulmonary embolism. Acta Chir Scand 1977; (Suppl) 478.
67 Karwinski B, Svendsen E. Comparison of clinical and postmortem diagnosis of pulmonary embolism. J Clin Pathol 1989; 42: 135-139.
68 Horgan MJ, Fenton JW, Malik AB. Alpha thrombin-induced pulmonary vasoconstriction. Am Physiol Soc 1987; 1993-2000.
69 Dahl OE. Cardiorespiratory and vascular dysfunction related to major reconstructive orthopedic surgery. Acta Orthop Scand 1997; 68: 607-614.
70 Sharrock NE, Go G, Harpel PC, Ranawat CS, Sculco TP, Salvati EA. The John Charnley Award. Thrombogenesis during total hip arthroplasty. Clin Orthop 1995; 319: 16-27.
71 Gold HK, Torres FW, Garabedian HD, Werner W, Jang IK, Khan A, Hagstrom JN, Yasuda T, Leinbach RC, Newell JB. Evidence for rebound coagulation phenomenon after cessation of a 4-hour infusion of a specific thrombin inhibitor in patients with unstable angina pectoris. J Am Coll Cardiol 1993; 21: 1039-1047.
72 Granger CB, Miller JM, Bovill EG, Gruber A, Tracy RP, Krucoff MW, Green C, Berrios E, Harrington RA, Ohman EM. Rebound Increase in thrombin generation and activity after cessation of intravenous heparin in patients with acute coronary syndromes. Circulation 1995; 1: 1929-1935.
73 Schøning B, Schulitz KP, Pfluger T. Statistical analysis of perioperative and postoperative mortality of patients with prosthetic replacement of the hip. Arch Orthop Traumat 1980; 97: 21-26.
74 Warwick D, Williams MH, Bannister GC. Death and thromboembolic disease after total hip replacement.: a series of 1162 cases with no routine chemical prophylaxis. J Bone Joint Surg 1995; 77-B: 6-10.
75 Hunter JB, Frostick SP. Dalteparin (Fragmin) for the prevention of early mortality after orthopaedic surgery. Thromb Haemost 1995; 73: 977.
76 Fender D, Harper WM, Thompson JR, Gregg PJ. Mortality and fatal pulmonary embolism after primary total hip replacement. Results from a regional hip register. J Bone Joint Surg 1997; 79-B: 896-899.