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Thromb Haemost 1998; 80(02): 233-238
DOI: 10.1055/s-0037-1615179
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Very Low Activated Factor VII and Reduced Factor VII Antigen in Familial Abetalipoproteinaemia

G. J. Miller
1   Medical Research Council Epidemiology and Medical Care Unit, London, England
,
K. A. Mitropoulos
1   Medical Research Council Epidemiology and Medical Care Unit, London, England
,
M. N. Nanjee
2   Department of Cardiovascular Biochemistry, St Bartholomew’s and the Royal London School of Medicine and Dentistry, London, England
,
D. J. Howarth
1   Medical Research Council Epidemiology and Medical Care Unit, London, England
,
J. C. Martin
1   Medical Research Council Epidemiology and Medical Care Unit, London, England
,
M. P. Esnouf
3   Nuffield Department of Clinical Biochemistry, Radcliffe Infirmary, Oxford, England
,
B. E. A. Reeves
1   Medical Research Council Epidemiology and Medical Care Unit, London, England
,
N. E. Miller
2   Department of Cardiovascular Biochemistry, St Bartholomew’s and the Royal London School of Medicine and Dentistry, London, England
,
J. A. Cooper
1   Medical Research Council Epidemiology and Medical Care Unit, London, England
› Author Affiliations
Further Information

Publication History

Received 13 October 1997

Accepted after resubmission 22 April 1998

Publication Date:
08 December 2017 (online)

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Summary

Abetalipoproteinaemia is a rare disorder of apolipoprotein B metabolism associated with extremely low plasma concentrations of triglyce-ride. To discover whether the general positive association between factor VII and triglyceride levels extends to this condition, 5 patients were compared with 18 controls. All patients had a triglyceride below 100 μmol/l. Plasma unesterified fatty acid concentration was normal. Although factor IX activity was only slightly reduced (mean 88% standard) and factor IX antigen was normal, mean activated factor VII in patients was strikingly reduced to 34% of that in controls, a level similar to that found in haemophilia B. The patients’ mean factor VII activity and factor VII antigen were also significantly reduced to 54% and 63% of those in controls, respectively. Mean factor XI activity and tissue factor pathway inhibitor activity were reduced in patients to 70% and 75% of control values respectively, while factor XII, factor XI antigen, factor X, prothrombin and protein C were normal.

 

  • References

  • 1 Miller GJ, Stirling Y, Esnouf M P, Heinrich J, van de Loo J, Kienast J, Wu KK, Morrissey JH, Meade TW, Martin JC, Imeson JD, Cooper JA, Finch A. Factor VII-deficient substrate plasmas depleted of protein C raise the sensitivity of the factor VII bio-assay to activated factor VII: an international study.. Thromb Haemost 1994; 71: 38-48.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 2 Ruddock V, Meade TW. Factor VII activity and ischaemic heart disease: fatal and non-fatal events.. Q J Med 1994; 87: 403-6.
    PubMedGoogle Scholar
  • 3 Junker R, Heinrich J, Schulte H, van de Loo J, Assmann G. Coagulation factor VII and the risk of coronary heart disease in healthy men.. Arterioscler Thromb Vasc Biol 1997; 17: 1539-44.
    CrossrefPubMedGoogle Scholar
  • 4 Constantino M, Merskey C, Kudzma DJ, Zucher MB. Increased activity of vitamin-K dependent clotting factors in human hyperlipoproteinaemia-association with cholesterol and triglyceride levels.. Thromb Haemost 1977; 38: 465-74.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 5 Fuller JH, Keen H, Jarrett RJ, Omer T, Meade TW, Chakrabarti R, North WRS, Stirling Y. Haemostatic variables associated with diabetes and its complications.. Br Med J 1979; 2: 964-6.
    CrossrefPubMedGoogle Scholar
  • 6 Conlan MG, Folsom AR, Finch A, Davis CE, Sorlie P. Wu KK for the ARIC Study Investigators.. Correlation of plasma protein C levels with cardiovascular risk factors in middle-aged adults: The Atherosclerosis Risk in Communities (ARIC) Study.. Thromb Haemost 1993; 70: 762-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 ECAT Angina Pectoris Study Group.. ECAT angina pectoris study: baseline associations of haemostatic risk factors with extent of coronary arteriosclerosis and other coronary risk factors in 3000 patients with angina pectoris undergoing coronary angiography.. Eur Heart J 1993; 14: 8-17.
    PubMedGoogle Scholar
  • 8 Bruckert E, Ankri A, Jury M, Turpin G, De Gennes JL. Mild liver abnormalities with elevated plasma factor VII and protein C in hypertriglyceridaemic patients.. Eur J Med 1993; 2: 461-5.
    PubMedGoogle Scholar
  • 9 Meade TW, North WRS, Chakrabarti R, Stirling Y, Haines AP, Thompson SG. Haemostatic function and cardiovascular death: early results of a prospective study.. Lancet 1980; 1: 1050-4.
    PubMedGoogle Scholar
  • 10 Miller GJ, Walter SJ, Stirling Y, Thompson SG, Esnouf MP. Assay of factor VII activity by two techniques: evidence for increased conversion of VII to VIIa in hyperlipidaemia, with possible implications for ischaemic heart disease.. Br J Haematol 1985; 59: 249-58.
    CrossrefPubMedGoogle Scholar
  • 11 Folsom AR, Wu KK, Davis CE, Conlan MG, Sorlie PD, Szklo M. Population correlates of plasma fibrinogen and factor VII, putative cardiovascular risk factors.. Atherosclerosis 1991; 91: 191-205.
    CrossrefPubMedGoogle Scholar
  • 12 Elwood PC, Beswick AD, O’Brien JR, Yarnell JWG, Layzell JC, Limb ES. Inter-relationships between haemostatic tests and the effects of some dietary determinants in the Caerphilly cohort of older men.. Blood Coag Fibrinol 1993; 4: 529-36.
    CrossrefPubMedGoogle Scholar
  • 13 Negri M, Arigliano PL, Talamini G, Carlini S, Manzato F, Bonadonna G. Levels of plasma factor VII and factor VII activated forms as a function of plasma triglyceride levels.. Atherosclerosis 1993; 99: 55-61.
    CrossrefPubMedGoogle Scholar
  • 14 Green D, Chamberlain M A, Ruth K J, Folsom A R, Liu K. Factor VII, cholesterol, and triglycerides. The CARDIA study.. Arterioscler Thromb Vasc Biol 1997; 17: 51-5.
    CrossrefPubMedGoogle Scholar
  • 15 Wright D, Poller L, Thomson JM, Gowland E, Burrows GE. The interrelationship of factor VII and its activity state with plasma lipids in healthy adult males.. Br J Haematol 1993; 85: 348-51.
    CrossrefPubMedGoogle Scholar
  • 16 Hoffman CJ, Miller RH, Hultin MB. Correlation of factor VII activity and antigen with cholesterol and triglycerides in healthy young adults.. Arterioscler Thromb 1992; 12: 267-70.
    CrossrefPubMedGoogle Scholar
  • 17 Howard PR, Bovill EG, Pike J, Church WR, Tracy RP. Factor VII antigen levels in a healthy blood donor population.. Thromb Haemost 1994; 72: 21-7.
    PubMedGoogle Scholar
  • 18 Miller GJ. Risk of thrombosis and the prethrombotic state.. In: Atherosclerosis X, Woodford FP, Davignon J, Sniderman A. (eds) Amsterdam: Elsevier; 1995. pp 801-4.
    Google Scholar
  • 19 Miller GJ, Martin JC, Webster J, Wilkes H, Miller NE, Wilkinson WH, Meade TW. Association between dietary fat intake and plasma factor VII coagulant activity – a predictor of cardiovascular mortality.. Atherosclerosis 1986; 60: 269-77.
    CrossrefPubMedGoogle Scholar
  • 20 Salomaa V, Rasi V, Pekkanen J, Jauhiainen M, Vahtera E, Pietinen P, Korhonen H, Kuulasmaa K, Ehnholm C. The effects of saturated fat and n-6 polyunsaturated fat on postprandial lipemia and hemostatic activity.. Atherosclerosis 1993; 103: 1-11.
    CrossrefPubMedGoogle Scholar
  • 21 Silveira A, Karpe F, Blomback M, Steiner G, Walldius G, Hamsten A. Activation of coagulation factor VII during alimentary lipemia.. Arterioscler Thromb 1994; 14: 60-9.
    CrossrefPubMedGoogle Scholar
  • 22 Miller GJ, Martin JC, Mitropoulos KA, Esnouf MP, Cooper JA, Morrissey JH, Howarth DJ, Tuddenham EGD. Activation of factor VII during alimentary lipemia occurs in healthy adults and patients with congenital factor XII or factor XI deficiency, but not in patients with factor IX deficiency.. Blood 1996; 87: 4187-96.
    PubMedGoogle Scholar
  • 23 Baron JA, Mann J, Stukel T. Effect of weight loss on coagulation factors VII and X.. Am J Cardiol 1989; 64: 519-22.
    CrossrefPubMedGoogle Scholar
  • 24 Slabber M, Barnard HC, Kuyl JM, Badenhorst CJ. Effect of a short-term very low calorie diet on plasma lipids, fibrinogen, and factor VII in obese subjects.. Clin Biochem 1992; 25: 334-5.
    CrossrefPubMedGoogle Scholar
  • 25 Palareti G, Legnani C, Poggi M, Parenti M, Babini AC, Biagi R, Baraldi L, Luchi A, Capelli M, Coccheri S. Prolonged very low calorie diet in obese subjects reduces factor VII and PAI but not fibrinogen levels.. Fibrinolysis 1994; 8: 16-21.
    PubMedGoogle Scholar
  • 26 Elkeles RS, Chakrabarti R, Vickers M, Stirling Y, Meade TW. Effect of treatment of hyperlipidaemia on haemostatic variables.. Br Med J 1980; 2: 973-4.
    PubMedGoogle Scholar
  • 27 Simpson HCR, Mann JI, Meade TW, Chakrabarti R, Stirling Y, Woolf L. Hypertriglyceridaemia and hypercoagulability.. Lancet 1983; 1: 786-90.
    PubMedGoogle Scholar
  • 28 Bruckert E, Carvalho de Sousa J, Giral P, Soria C, Chapman M J, Caen J, deGennes J-L. Interrelationship of plasma triglyceride and coagulant factor VII levels in normotriglyceridemic hypercholesterolemia.. Atherosclerosis 1989; 75: 129-34.
    CrossrefPubMedGoogle Scholar
  • 29 Mitropoulos KA, Armitage JM, Collins R, Meade TW, Reeves BEA, Wallendszus KR, Wilson SS, Lawson A. Peto R for the Oxford Cholesterol Study Group.. Randomized placebo-controlled study of the effects of simvastatin on haemostatic variables, lipoproteins and free fatty acids.. Eur Heart J 1997; 18: 235-41.
    CrossrefPubMedGoogle Scholar
  • 30 Avellone G, di Garbo V, Cordova R, Ranelli G, de Simone R, Bompiani G. Effect of gemfibrozil treatment on fibrinolysis system in patients with hypertriglyceridemia.. Curr Therap Res 1992; 52: 338-48.
    CrossrefPubMedGoogle Scholar
  • 31 Avellone G, de Garbo V, Cordova R, Ranelli G, de Simone R, Bompiani G. Changes induced by pravastatin treatment on hemostatic and fibrinolytic patterns in patients with type IIβ hyperlipoproteinemia.. Curr Therap Res 1994; 55: 1335-44.
    CrossrefPubMedGoogle Scholar
  • 32 Marckmann P, Sandstrom B, Jespersen J. Effects of total fat content and fatty acid composition in diet on factor VII coagulant activity and blood lipids.. Atherosclerosis 1990; 80: 227-33.
    CrossrefPubMedGoogle Scholar
  • 33 Miller GJ, Stirling Y, Howarth DJ, Cooper JA, Green FR, Lane A, Humphries SE. Dietary fat intake and plasma factor VII antigen concentration.. Thromb Haemost 1995; 73: 893.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 34 Broijersen A, Hamsten A, Silveira A, Fatah K, Goodall AH, Eriksson M, Angelin B, Hjemdahl P. Gemfibrozil reduces thrombin generation in patients with combined hyperlipidaemia, without influencing plasma fibrinogen, fibrin gel structure or coagulation factor VII.. Thromb Haemost 1996; 76: 171-6.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 35 Mitropoulos KA, Miller GJ, Watts GF, Durrington PN. Lipolysis of triglyceride-rich lipoproteins activates coagulant factor XII: a study in familial lipoprotein-lipase deficiency.. Atherosclerosis 1992; 95: 119-25.
    CrossrefPubMedGoogle Scholar
  • 36 Marckmann P, Sandstrom B, Jespersen J. Low fat, high-fiber diet favorably affects several independent risk markers of ischaemic heart disease: observations on blood lipids, coagulation, and fibrinolysis from a trial of middle-aged Danes.. Am J Clin Nutr 1994; 59: 935-9.
    CrossrefPubMedGoogle Scholar
  • 37 Brace LD, Gittler-Buffa C, Miller GJ, Cole TG, Schmeisser D, Prewitt TE, Bowen PE. Factor VII coagulant activity and cholesterol changes in premenopausal women consuming a long-term cholesterol-lowering diet.. Arterioscler Thromb 1994; 14: 1284-9.
    CrossrefPubMedGoogle Scholar
  • 38 Kasim SE, Martino S, Kim PN, Khilnani S, Boomer A, Depper J, Reading BA, Heilbrun LK. Dietary and anthropometric determinants of plasma lipoproteins during a long-term low-fat diet in healthy women.. Am J Clin Nutr 1993; 57: 146-53.
    CrossrefPubMedGoogle Scholar
  • 39 Campos H, Dreon DM, Krauss RM. Association of hepatic and lipoprotein lipase activities with changes in dietary composition and low density lipo-protein subclasses.. J Lipid Res 1995; 36: 462-72.
    PubMedGoogle Scholar
  • 40 Sharp D, Blinderman L, Combs KA, Kienzle B, Ricci B, Wager-Smith K, Gil CM, Turck CW, Bouma M-E, Rader DJ, Aggerbeck LP, Gregg RE, Gordon DA, Wetteran JR. Cloning and gene defects in microsomal triglyceride transfer protein associated with abetalipoproteinaemia.. Nature 1993; 365: 65-9.
    CrossrefPubMedGoogle Scholar
  • 41 Kane JP, Havel RJ. Disorders of the biogenesis and secretion of lipoproteins containing the β apolipoproteins.. In: The Metabolic Basis of Inherited Diseases.. Scriver CR, Beaudet AL, Sly WS. (eds) 6th ed. New York: McGraw-Hill; 1989. pp 1139-64.
    Google Scholar
  • 42 Slack J, Nair S, Traisman H, Becker G, Mahler S, Yi-Yung Hsia D. Lipo-protein lipase in cystic fibrosis of the pancreas.. J Lab Clin Med 1962; 59: 302-8.
    PubMedGoogle Scholar
  • 43 Kuo PT, Bassett DR, di George AM, Carpenter GG. Lipolytic activity of post-heparin plasma in hyperlipemia and hypolipemia.. Circ Res 1965; 16: 221-9.
    CrossrefPubMedGoogle Scholar
  • 44 Illingworth DR, Alam SS, Alam NA. Lipoprotein lipase and hepatic lipase activity after heparin administration in abetalipoproteinemia and hypobetalipoproteinemia.. Metabolism 1983; 32: 869-73.
    CrossrefPubMedGoogle Scholar
  • 45 Barnard G, Fosbrooke AS, Lloyd JK. Neutral lipids of plasma and adipose tissue in a-betalipoproteinaemia.. Clin Chim Acta 1970; 28: 417-22.
    CrossrefPubMedGoogle Scholar
  • 46 Novotny WF, Girard TJ, Miletich JP, Broze GJ. Purification and characterization of the lipoprotein associated coagulation inhibitor from human plasma.. J Biol Chem 1989; 264: 18832-7.
    PubMedGoogle Scholar
  • 47 Mitropoulos KA, Reeves BEA, Miller GJ. The activation of factor VII in citrated plasma by charged long-chain saturated fatty acids at the interface of triglyceride-rich lipoproteins.. Blood Coag Fibrinol 1993; 4: 943-51.
    CrossrefPubMedGoogle Scholar
  • 48 Narcisi TME, Shoulders CC, Chester SA, Read J, Brett DJ, Harrison GB, Grantham TT, Fox MF, Povey S, de Bruin TWA, Erkelens DW, Muller DPR, Lloyd JK, Scott J. Mutations of the microsomal triglyceride-transfer-protein gene in abetalipoproteinemia.. Am J Hum Genet 1995; 57: 1298-310.
    PubMedGoogle Scholar
  • 49 Nanjee MN, Miller NE. Sequential microenzymatic assay of cholesterol, triglycerides and phospholipids in a single aliquot.. Clin Chem 1996; 42: 915-26.
    PubMedGoogle Scholar
  • 50 Havel RJ, Eder HA, Bragdon JH. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum.. J Clin Invest 1955; 34: 1345-53.
    CrossrefPubMedGoogle Scholar
  • 51 Dole VP, Meinertz H. Microdetermination of long chain fatty acids in plasma and tissues.. J Biol Chem 1960; 235: 2595-9.
    PubMedGoogle Scholar
  • 52 Mitropoulos KA, Miller GJ, Martin JC, Reeves BEA, Cooper J. Dietary fat induces changes in factor VII coagulant activity through effects on plasma free stearic acid concentration.. Arterioscler Thromb 1994; 14: 214-22.
    CrossrefPubMedGoogle Scholar
  • 53 Morrissey JH, Macik BG, Neuenschwander PF, Comp PC. Quantitation of activated factor VII levels in plasma using a tissue factor mutant selectively deficient in promoting factor VII activation.. Blood 1993; 81: 734-44.
    PubMedGoogle Scholar
  • 54 Mitropoulos KA, Reeves BEA, O’Brien DP, Cooper JA, Martin JC. The relationship between factor VII coagulant activity and factor XII activation induced in plasma by endogenous or exogenously added contact surface.. Blood Coagul Fibrinol 1993; 4: 223-33.
    CrossrefPubMedGoogle Scholar
  • 55 Denson KWE. The specific assay of Prower-Stuart factor and factor VII.. Acta Haematol 1961; 25: 105-20.
    CrossrefPubMedGoogle Scholar
  • 56 Denson KWE, Borrett R, Biggs R. The specific assay of prothrombin using the Taipan snake venom.. Br J Haematol 1971; 21: 219.
    CrossrefPubMedGoogle Scholar
  • 57 von Clauss A. Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens.. Acta Haematol 1957; 17: 237-46.
    CrossrefPubMedGoogle Scholar
  • 58 Ford RP, Esnouf MP, Burgess AI, Sarphie AF. An enzyme linked immunosorbent assay (ELISA) for the measurement of activated factor XII (Hageman Factor) in human plasma.. J Immunoassay 1996; 17: 119-31.
    PubMedGoogle Scholar
  • 59 Sandset PM, Larzen ML, Abildgaard U, Lindahl AK, Odegaard OR. Chromogenic substrate assay of extrinsic pathway inhibitor (EPI): levels in the normal population and relation to cholesterol.. Blood Coagul Fibrinol 1991; 2: 425-33.
    CrossrefPubMedGoogle Scholar
  • 60 Scanu AM, Aggerbeck LP, Kruski AW, Lim CT, Kayden HJ. A study of the abnormal lipoproteins in abetalipoproteinemia.. J Clin Invest 1974; 53: 440-53.
    CrossrefPubMedGoogle Scholar
  • 61 Aguie GA, Rader DJ, Clavey V, Traber MG, Torpier G, Kayden HJ, Fruchart JC, Brewer HB, Castro G. Lipoproteins containing apolipoprotein β isolated from patients with abetalipoproteinemia and homozygous hypobetalipoproteinemia: identification and characterization.. Atherosclerosis 1995; 188: 183-91.
    PubMedGoogle Scholar
  • 62 Lim CT, Chung J, Kayden HJ, Scanu AM. Apoproteins of human serum high density lipoproteins. Isolation and characterization of the peptides of Sephadex fraction V from normal subjects and patients with abeta-lipoproteinemia.. Biochem & Biophys Acta 1976; 420: 332-41.
    PubMedGoogle Scholar
  • 63 Illingworth DR, Connor WE, Miller RG. Abetalipoproteinemia: report of two cases and review of therapy.. Arch Neurol 1980; 37: 659-62.
    CrossrefPubMedGoogle Scholar
  • 64 Caballero FM, Buchanan GR. Abetalipoproteinemia presenting as severe vitamin K deficiency.. Pediatrics 1980; 65: 161-3.
    PubMedGoogle Scholar
  • 65 Wildgoose P, Nemerson Y, Hansen LL, Nielsen FE, Glazer S, Hedner U. Measurement of basal levels of factor VIIa in hemophilia A and hemophilia B patients.. Blood 1992; 80: 25-8.
    PubMedGoogle Scholar
  • 66 Mitropoulos KA, Esnouf MP. The prothrombin activation peptide regulates synthesis of the vitamin K-dependent proteins in the rabbit.. Thromb Res 1990; 57: 541-9.
    CrossrefPubMedGoogle Scholar
  • 67 Mitropoulos KA, Miller GJ, Howarth DJ, Reeves BE, Cooper JA. The effects of intravenous Triton WR-1339 on factor VII coagulant activity and plasma lipoproteins in normocholesterolaemic and hypercholesterolaemic rabbits.. Blood Coagul Fibrinol 1994; 5: 583-91.
    PubMedGoogle Scholar
  • 68 Novotny WF, Brown SG, Miletich JP, Rader DJ, Broze GJ. Plasma antigen levels of the lipoprotein-associated coagulation inhibitor in patient samples.. Blood 1991; 78: 387-93.
    PubMedGoogle Scholar
  • 69 Hallberg D. Studies on the elimination of exogenous lipids from the blood stream.. Acta Physiol Scand 1964; 62: 407-10.
    CrossrefPubMedGoogle Scholar
  • 70 Boberg J, Carlson LA. Determination of heparin-induced lipoprotein lipase activity in human plasma.. Clin Chim Acta 1964; 10: 420-7.
    CrossrefPubMedGoogle Scholar
  • 71 Miller GJ, Esnouf MP, Burgess AI, Cooper JA, Mitchell JP. Risk of coronary heart disease and activation of factor XII in middle-aged men.. Arterioscler Thromb Vasc Biol 1997; 17: 2103-6.
    CrossrefPubMedGoogle Scholar