Abstract
Patients with severe gastrointestinal motility disorders are often found to have intravenous access clots or deep venous thrombosis. It has previously been reported that many patients who have intravenous access thrombosis have concomitant thrombotic risk factors. In this study, the goal was to determine the underlying prevalence of hypercoagulable risk in a series of patients with documented gastroparesis. Investigators studied 62 consecutive patients (52 female; mean age, 42 y) who had symptoms of gastroparesis. All patients were evaluated for placement of a gastric neural stimulation device, or they had had one placed previously. Patients underwent a hematologic interview and standardized coagulation measures of thrombotic risk. Laboratory studies measured acquired elevations of Factor VII, Factor VIII, fibrinogen, lupus anticoagulant panel, antiphospholipid antibody panel, homocysteine (in the setting of kidney disease), and activated protein resistance. Investigators also measured congenital factors: Factor VIII (with C-reactive protein levels), antithrombin III, protein C, protein S (total and free), Factor II mutation, Factor V Leiden, methylenetetrahydrofolate reductase, and homocysteine. Fifty-five patients (89%) were found to have detectable hypercoagulable risk factors. Twentyfive of the 62 patients (40%) had a documented history of abnormal clotting, including deep venous thrombosis, intravenous access thrombosis, and pulmonary embolism. All patients with a previous history of thrombosis had detectable clotting abnormalities. Of 56 patients, 40 (71%) had hypercoagulability and did not have diabetes (P=.036), and 20 (36%) had hypercoagulability and no known history of infection. However, this value was not statistically significant when infection and hypercoagulability were compared (P=.408). A high prevalence of acquired and congenital hypercoagulable defects has been observed in patients with gastroparesis, which may predispose them to arterial and venous clots. This unique finding warrants consideration of coagulation evaluation in patients with severe gastroparesis, especially when these patients are placed in high-risk thrombophilic situations, such as hospitalization, prolonged intravenous access, and surgery.
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References
Prandoni P. Acquired risk factors for venous thromboembolism in medical patients.Pathophysiol Haemost Thromb. 2006; 35(1-2): 128–132.
Sylvia H. Venous thromboembolism in medical patients—the scope of the problem.Semin Thromb Hemost. 2003; 29: 17–22.
Miehsler W, Reinisch W, Valic E, et al. Is inflammatory bowel disease an independent and diseasespecific risk factor for thromboembolism?Gut. 2004; 53: 542–548.
Alkeshen M, Edick C, Hak L, et al. High incidence of protein S abnormalities in patients with catheter-related thrombosis.Gastroenterology. 2000; 118(Part 2): A1064.
Alkeshen M, Edick C, Hak L, et al. Patients with IV catheter-related thrombosis have multiple coagulation and autoimmune abnormalities on baseline diagnostic tests.Gastroenterology. 2000; 118(Part 2): A1331.
Kumar A, Lomas R, Abell T, Dugdale M, Voeller G, Smalley D. Serum autoantibodies predispose to superior venacaval syndrome associated with central access in gastroparesis.Gastroenterology. 1994; 106(Part 2): A528.
Werkman R, Smalley D, Duncan U, et al. Is thrombosis of central venous access in idiopathic upper GI dysmotility related to presence of circulating autoantibodies?Gastroenterology. 1995; 108: A734.
Dumenco LL, Blair AJ, Sweeney JD. The results of diagnostic studies for thrombophilia in a large group of patients with a personal or family history of thrombosis.Am J Clin Pathol. 1998; 110: 673–682.
Koeleman BPC, Reitsma PH, Bertina RM. Familial thrombophilia: a complex genetic disorder.Semin Hematol. 1997; 34: 256–264.
Seligsohn U, Lubetsky A. Genetic susceptibility to venous thrombosis.N Engl J Med. 2001; 344: 1222–1231.
Hoppener MR, Kraaijenhagen RA, Hutten A, Buller HR, Peters RJG, Levi M. Beta-receptor blockade decreases elevated F VIII:C in patients with deep vein thrombosis.J Thromb Haemost. 2004; 3: 1316–1320.
DeGiorgio R, Guerrini S, Barbara G, et al. Inflammatory neuropathies of the enteric nervous system.Gastroenterology. 2004; 126: 1872–1883.
Rozen R. Genetic predisposition to hyperhomocysteinemia: deficiency of methylenetetrahydrofolate reductase (MTHFR).Thromb Haemost. 1997; 78: 523–526.
Addendum References General Methods
Thomas RH. Update on thrombophilic disorders.Lab Med. 2003; 9: 34.
National Committee for Clinical Laboratory Standards.Procedures for Handling and Processing of Blood Specimens. Approved Guideline. 2nd ed, Vol 19. Wayne, Pa: NCCLS; 1999.
College of American Pathologists. Proficiency testing and accreditation requirements. Available at: http://www.cap.org/apps/cap.portal. Accessed 2004.
Health Care Financing Administration, Public Health Service (Centers for Disease Control and Prevention). Clinical laboratory improvement amendments of 1988 (Final Rule, 42:CFR 493, etc.), HSQ-176-FC (57 FR 7002). Issued February 28, 1992, effective September 1, 1992, plus additional amendments through 2002. Baltimore Md: Centers for Medicare & Medicaid Services (formerly HCFA). Available at: www.cms.hhs.gov/clia.
Addendum References Factor VII
Iacoviello L, Di Castelnuovo A, De Kniff P, et al. Polymorphisms in the coagulation Factor VII gene and the risk of myocardial infarction.N Engl J Med. 1998; 338: 79–85.
Meade TW, Ruddock V, Stirling Y, Chakrabarti R, Miller GJ. Fibrinolytic activity, clotting factors, and long-term incidence of ischaemic heart disease in the Northwick Park Heart Study.Lancet. 1993; 342: 1076–1079.
Corral J, Gonzalez-Conejero R, Lozano ML, Rivera J, Vicente V. Genetic polymorphisms of Factor VII are not associated with arterial thrombosis.Blood Coagul Fibrinolysis. 1998; 9: 267–272.
Larsen LF, Bladbjerg EM, Jespersen J, Marckmann P. Effects of dietary fat quality and quantity on postprandial activation of blood coagulation Factor VII.Arterioscler Thromb Vasc Biol. 1997; 17: 2904–2909.
Addendum References Factor VIII
O’Donnell J, Tuddenham EGD, Manning R, Kemball-Cook G, Johnson D, Laffan M. High prevalence of elevated Factor VIII levels in patients referred for thrombophilia screening: role of increased synthesis and relationship to the acute phase reaction.Thromb Haemost. 1997; 77: 825–828.
Catto AJ, Carter AM, Barrett JH, Bamford J, Rice PJ, Grant PJ. von Willebrand Factor and Factor VIII:C in acute cerebrovascular disease: relationship to stroke subtype and mortality.Thromb Haemost. 1997; 77: 1104–1108.
Kamphuisen PW, Eikenboom JCJ, Bertina RM. Elevated Factor VIII levels and the risk of thrombosis.Arterioscler Thromb Vasc Biol. 2001; 21: 732–738.
Kamphuisen PW, Lensen R, Houwing-Duistermaat JJ, et al. Heritability of elevated Factor VIII antigen levels in Factor V Leiden families with thrombophilia.Br J Haematol. 2000; 109: 519–522.
Conlan MG, Folson AR, Finch A, et al. Associations of Factor VIII and von Willebrand Factor with age, race, sex, and risk factors for atherosclerosis (the atherosclerosis risk in communities [ARIC] study).Thromb Haemost. 1993; 70: 380–385.
O’Donnell J, Mumford AD, Manning RA, Laffan M. Elevation of F VIII:C in venous thromboembolism is persistent and independent of the acute phase response.Thromb Haemost. 2000; 83: 10–13.
Kamphuisen PW, Eikenaboom JC, Vos HLA, et al. Increased levels of F VIII and fibrinogen in patients with venous thrombosis are not caused by acute phase reactions.Thromb Haemost. 1999; 81: 680–683.
Kraaijenhagen RA, Pieternella S, Anker INT, et al. High plasma concentration of F VIIIC is a major risk factor for venous thromboembolism.Thromb Haemost. 2000; 85: 5–9.
Laffan MA, Manning R. The influence of Factor VIII on measurement of activated Protein C resistance.Blood Coagul Fibrinolysis. 1996; 7: 761–765.
Addendum References Fibrinogen
Mead TW, Mellows S, Brozovic M, et al. Haemostatic function and ischaemic heart disease: principal results of the Northwick Park Heart Study.The Lancet. 1986; 2: 533–537.
Cushman M, Yanez D, Psalty BM, et al. Association of fibrinogen and coagulation Factors VII and VIII with cardiovascular risk factors in the elderly.Am J Epidemiol. 1996; 43: 665–676.
Rosendaal FR. Thrombosis in the young: epidemiology and risk factors. A focus on venous thrombosis.Thromb Haemost. 1997; 78: 1–6.
Wilhelmsen L, Svardsudd K, Korsan-Bengtsen K, et al. Fibrinogen as a risk factor for stroke and myocardial infarction.N Engl J Med. 1984; 311: 501–505.
Addendum References Proteins C and S
Esmon CT, Schwarz HP. An update on clinical and basic aspects of the protein C anticoagulant pathway.Trends Cardiovasc Med. 1995; 5: 141–148.
Koster T, Rosendaal FR, Briet E, et al. Protein C deficiency in a controlled series of unselected outpatients: an infrequent but clear risk factor for venous thrombosis (Leiden thrombophilia study).Blood. 1995; 85: 2756–2761.
Comp PC, Esmon CT. Recurrent venous thromboembolism in patients with a partial deficiency of protein S.N Engl J Med. 1984; 311: 1525–1528.
Schwartz H, Fischer M, Hopmeier P, Batard MA, Griffin HH. Familial protein S deficiency is associated with recurrent thrombosis.Blood. 1984; 64: 1297–1300.
Schwarz HP, Heeb MJ, Wencel-Drake JD, Griffin JH. Identification and quantification of protein S in human platelets.Blood. 1995; 66: 1452–1455.
Addendum References Homocysteine
Clark R, Daly L, Robinson K, et al. Hyperhomocysteinemia: an independent risk factor for vascular disease.N Engl J Med. 1991; 324: 1149–1155.
Boers GHJ. Hyperhomocysteinemia as a risk factor for arterial and venous disease.Thromb Haemost. 1997; 78: 520–522.
Selhub J, D’Angelo A. Hyperhomocysteinemia and thrombosis: acquired conditions.Thromb Haemost. 1997; 78: 527–531.
Welch GN, Loscalzo J. Review article: homocysteine and atherothrombosis.N Engl J Med. 1998; 338: 1042–1050.
Nygard O, Vollset SE, Refsum H, et al. Total plasma homocysteine and cardiovascular risk profile. The Hordaland Homocysteine Study.JAMA. 1995; 274: 1526–1533.
Rassoul F, Richter V, Janke C, et al. Plasma homocysteine and lipoprotein profile in patients with peripheral arterial occlusive disease.Angiology. 2000; 51: 189–196.
Nygard O, Nordrehaug JE, Refsum H, et al. Plasma homocysteine levels and mortality in patients with coronary artery disease.N Engl J Med. 1997; 337: 230–236.
Addendum References APC Resistance and FV Leiden
Dahlback B, Carlsson M, Svensson PJ. Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C.Proc Natl Acad Sci USA. 1993; 90: 1004–1008.
Griffin JH, Evatt B, Wideman C, Fernandez JA. Anticoagulant protein C pathway defective in majority of thrombophilic patients.Blood. 1993; 82: 1989–1993.
Wasserman LM, Edson JR, Key NS, Chibbar R, McGlennen RC. Detection of the Factor V Leiden mutation.Am J Clin Pathol. 1997; 108: 427–433.
Ruiz-Arguelles GJ, Garces-Eisele J, Alarcon-Segovia D, Ruiz-Arguelles A. Activated protein C resistance phenotype and genotype in patients with primary antiphospholipid syndrome.Blood Coagul Fibrinolysis. 1996; 7: 344–348.
Press RD, Liu XY, Beamer N, Coull BM. Ischemic stroke in the elderly: role of the common Factor V mutation causing resistance to activated protein C.Stroke. 1996; 27: 44–48.
Fisher M, Fernandez JA, Ameriso SF, Xie D, Gruber A. Activated protein C resistance in ischemic stroke not due to Factor V arginine 506-gulatamine mutation.Stroke. 1996; 27: 1163–1166.
Bertina RM. Laboratory diagnosis of resistance to activated protein C (APC resistance).Thromb Haemost. 1997; 78: 478–482.
Dahlback B. Resistance to activated protein C caused by the Factor V R 506 Q mutation is a common risk factor for venous thrombosis.Thromb Haemost. 1997; 78: 483–488.
Brandt JT, Barna LK, Triplett DA. Laboratory identification of lupus anticoagulants: results of the Second International Workshop for Identification of Lupus Anticoagulants.Thromb Haemost. 1995; 74: 1597–1603.
Wilson WA, Gharavi AE, Koike T, et al. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop.Arthritis Rheum. 1999; 42: 1309–1311.
Addendum References Lupus Anticoagulant, Antiphospholipid Syndrome
Esmon NL, Smirnov MD, Esmon CT. Thrombogenic mechanisms of antiphospholipid antibodies.Thromb Haemost. 1997; 78: 79–82.
Galli M, Finazzi G, Barbui T. Antiphosplipid antibodies: predictive value of laboratory tests.Thromb Haemost. 1997; 78: 75–78.
Galli M, Dlott J, Norbis F, et al. Lupus anticoagulants and thrombosis: clinical association of different coagulation and immunologic tests.Thromb Haemost. 2000; 84: 1012–1016.
Levine JS, Branch DW, Rauch J. Medical progress: the antiphospholipid syndrome [review article].N Engl J Med. 2002; 436: 752–763.
Cronin ME, Biwas RM, Van Der Straeton C, Fleisher TA, Klippel JH. IgG and IgM anticardiolipin antibodies in patients with lupus with anticardiolipin antibody associated clinical syndromes.J Rheumatol. 1998; 15: 795–798.
Triplett DA. Protean clinical presentation of antiphospholipid-protein antibodies (APA).Thromb Haemost. 1995; 74: 329–337.
Forastiero R, Martinuzzo M, Pombo G, Puente D, Rossi A. A prospective study of antibodies to beta2 glycoprotein 1 and prothrombin, and risk of thrombosis.J Thromb Haemost. 2005; 3: 1231–1238.
Zoghlami-Rintelen C, Vormittag R, Sailer T, et al. The presence of IgG antibodies against beta2-glycoprotein 1 predicts the risk of thrombosis in patients with the lupus anticoagulant.J Thromb Haemost. 2005; 3: 1160–1165.
Martinelli I. Risk factors in venous thrombosis.Thromb Haemost. 2001; 86: 395–403.
Triplett DA. Thrombophilia: laboratory evaluation.AACC Clinical Laboratory News. 2002; 28: 12–13.
Rodeghiero F, Tosetto A. The epidemiology of inherited thrombophilia: the Vita Project.Thromb Haemost. 1997; 78: 634–636.
Copper DN, Tuddenham EGH. Molecular genetics of familial venous thrombosis.Br Med Bull. 1994; 50: 833–850.
Seligsohn U, Zivelin A. Thrombophilia as a multigenic disorder.Thromb Haemost. 1997; 78: 297–301.
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Lobrano, A., Blanchard, K., Rock, W. et al. Assessing thrombosis risk in patients with idiopathic, diabetic, and postsurgical gastroparesis. Adv Therapy 23, 750–768 (2006). https://doi.org/10.1007/BF02850315
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DOI: https://doi.org/10.1007/BF02850315