Hereditary Heparin Cofactor II Deficiency and the Risk of Development of Thrombosis

Bertina, R. M.; Linden, I K van der; Engesser, L.; Müller, H.; Brommer, E.J.P.

doi:10.1055/s-0038-1651093

Cited by 113 publications

(44 citation statements)

References 11 publications

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“…We identified 12 eligible reports (114-125) on plasminogen deficiency types 1 and 2, 7 on dysfibrinogenemia (126-132), 9 on decreased fibrinolytic activity due to decreased tissue plasminogen activator release or increased plasminogen activator inhibitors (133)(134)(135)(136)(137)(138)(139)(140)(141), 3 on heparin cofactor II deficiency (142)(143)(144), and 1 on increased histidine-rich glycoprotein (145). The result of a review analysis using the Mantel Haenszel test and an estimate of the common odds ratio are shown in Table 1.…”

Section: Other Biochemical Abnormalitiesmentioning

confidence: 99%

Familial Thrombophilia: A Review Analysis

Belt¹,

Prins²,

Huisman

et al. 1996

Clin Appl Thromb Hemost

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The correct approach to the management of the asymptomatic carrier with a recognized inherited thrombophilic disorder is uncertain because reliable in formation of the risk of spontaneous (unprovoked) throm bosis in these disorders is not available. To determine the best available estimate of the annual incidence of spon taneous thrombosis in asymptomatic carriers of disorders that have been linked to familial thrombophilia, we per formed a literature review. Using Medline search from 1965 to 1992, supplemented by manual searches, we re trieved all articles that presented data on antithrombin III, protein C, protein S, dysfibrinogenemia, plasmino gen, histidine-rich glycoprotein, heparin cofactor II, and fibrinolysis in relation to thrombosis. Publications were included in the analysis if they (1) reported one or more probands with thrombotic disease and a heterozygous biochemical abnormality of the hemostatic system, (2) assessed the presence of this abnormality in family mem bers independent of the presence or absence of a history of thrombotic disease, and (3) assessed the presence of a history of thrombotic disease in all available family mem bers. The biochemical status and clinical details of all family members reported were extracted from each eligi ble article. For each abnormality the odds ratio for throm bosis was compared in family members with and without the biochemical abnormality. If applicable, thrombosis- free survival and age-specific incidences of thrombosis were calculated. The thrombotic episodes were classified as spontaneous or secondary to a recognized risk factor, and the proportion of spontaneous episodes was calcu lated. The influence of diagnostic suspicion bias in symp tomatic patients with a family history of thrombosis was reduced by recalculating the absolute incidence of throm bosis from the odds ratio after adjusting the incidence of venous thrombosis in nonaffected family members to that observed in the general population. Statistically signifi cant associations between the presence of a biochemical abnormality and a history of venous thrombosis were found for antithrombin III deficiency types 1 and 2a and 2b, protein C deficiency type 1, and protein S deficiency type I. Dysfibronogenemia was statistically significantly associated with venous as well as arterial thrombosis. Thirty-five to 67% of the events were classified as being provoked, as they occurred following exposure to a rec ognized risk factor for thrombosis. The recalculated an nual incidence of spontaneous thrombosis was 0.6 to 1.6%/year. It is concluded that this relatively low inci dence does not warrant life-long continuous use of anti coagulant prophylaxis since the reported risk of major and fatal bleeding associated with the use of oral antico agulants is 2-3 and 0.4%/year, respectively.

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Section: Other Biochemical Abnormalitiesmentioning

confidence: 99%

Familial Thrombophilia: A Review Analysis

Belt¹,

Prins²,

Huisman

et al. 1996

Clin Appl Thromb Hemost

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“…Although administration of exogenous dermatan sulfate to experimental animals produces a potent antithrombotic effect by activation of HCII in the circulation (34), humans with partial HCII deficiency do not appear to have an increased incidence of venous thromboembolic disease (35,36). These observations support the hypothesis that HCII inhibits thrombin in the extravascular milieu (15), where it could modulate actions of thrombin in wound healing or inflammation.…”

Section: Fig 6 Conversion Of Meizothrombin-hcii To Thrombin-hcii Bymentioning

confidence: 79%

Inhibition of Meizothrombin and Meizothrombin(desF1) by Heparin Cofactor II

Han

Côté

Tollefsen

1997

Journal of Biological Chemistry

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Meizothrombin and meizothrombin(desF1) are intermediates formed during the conversion of prothrombin to thrombin by factor Xa, factor Va, phospholipids, and Ca 2؉ (prothrombinase). These intermediates are active toward synthetic peptide substrates but have limited ability to interact with platelets or macromolecular substrates such as fibrinogen. Meizothrombin and meizothrombin(desF1) activate protein C, however, and may exert primarily an anticoagulant effect. In this study, we investigated the inhibition of meizothrombin and meizothrombin(desF1) by two glycosaminoglycandependent protease inhibitors, heparin cofactor II (HCII) and antithrombin (AT). Purified recombinant meizothrombin and meizothrombin(desF1) were inhibited by HCII in the presence of dermatan sulfate with maximal second-order rate constants of 8 ؋ 10 6 M ؊1 ⅐min ؊1 and 1.8 ؋ 10 M؊1 ⅐min ؊1, respectively, but were inhibited less than one-tenth as fast by AT in the presence of heparin. Similarly, the products of the prothrombinase reaction were inhibited in situ more effectively by HCII than by AT. When HCII and dermatan sulfate were present continuously during the prothrombinase reaction, meizothrombin was trapped as a sodium dodecyl sulfate-stable complex with HCII and no amidolytic activity could be detected with a thrombin substrate. Our findings indicate that HCII is an effective inhibitor of meizothrombin and meizothrombin(desF1) and, therefore, might regulate the anticoagulant activity of these proteases.Thrombin is a key enzyme in several biological processes, including blood coagulation, wound healing, and inflammation (1). Factor Xa converts human prothrombin to thrombin by cleavage of the peptide bonds following Arg-271 and Arg-320 (2). The order in which these bonds are cleaved depends on assembly of the prothrombinase complex. In the presence of factor Xa and Ca 2ϩ , prothrombin is first cleaved after Arg-271, giving rise to fragment 1⅐2 and prethrombin 2 (3). When factor Xa and its cofactor, factor Va, are assembled on a membrane surface in the presence of Ca 2ϩ , factor Xa first cleaves after Arg-320, giving rise to meizothrombin (4, 5). Cleavage of the second factor Xa-sensitive bond in either prethrombin 2 or meizothrombin yields thrombin. Meizothrombin has been shown recently to be a major intermediate formed during coagulation of whole blood in vitro (6).Meizothrombin retains the N-terminal ␥-carboxyglutamic acid domain of prothrombin, which enables it to bind to membrane phospholipids in the presence of Ca 2ϩ . Cleavage of the thrombin-sensitive peptide bond following Arg-155 in meizothrombin removes the ␥-carboxyglutamic acid domain and generates meizothrombin(desF1) (7). In contrast to prothrombin or prethrombin 2, meizothrombin and meizothrombin(desF1) hydrolyze synthetic peptide substrates at rates comparable with that of thrombin (8 -10). Meizothrombin and meizothrombin(desF1) are much less active with respect to fibrinogen clotting, platelet activation, and activation of the thrombinactivable fibrinolysis inhibitor (9 -11...

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“…For coagulation, fibrinogen levels were consistently found higher in women than in men (123,126). No differences were found for factors V and VIIIc (127), for von Willebrand factor (127), heparin cofactor II (128), and thrombomodulin (129). On the contrary, contradictory data were published for factor VII (123,126,130,131), antithrombin III (127,132,133), and protein C (127,132,134).…”

Section: Sex-related Differences In Hemostatic Factorsmentioning

confidence: 99%

State-of-the-Art Review : Sex and Cardiovascular Risk Factors

Prisco

Caciolli

Pace

et al. 1996

Clin Appl Thromb Hemost

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It is well known that the incidence of coronary heart disease (CHD) is lower in women than in men, especially in those younger than 50 years of age (1). During the past 20 years, there has been a significant reduction of CHD in western countries attributable not only to improved therapies but also to primary prevention (2).Even if many risk factors for CHD are common in men and women, the impact of each risk factor on the incidence and manifestation of disease may be different. Although many studies have considered the effect of different factors in men, only a limited number of studies contain a significant percentage of women and, finally, very few studies examine separately data from men and from women. This lack of information derives from the less frequent participation of women in research studies. This difference is due in part to the exclusion of women of child-bearing age and in part to the exclusion of elderly women because of their frequent coexisting illnesses (3).We review data in the literature related to the different impact of the risk factors for coronary and other vascular diseases in women in comparison with men. In some cases, we also consider data (when available) concerning the effect of risk-factor modifications.It is now clear that cigarette smoking is associated with CHD in women as in men (4,5). As a consequence of arousing public interest in the risk of smoking, the prevalence of smokers has declined markedly in western countries in the past 20 years, but the decline has been less pronounced in women than in men (6-8) and, in particular, adolescent smokers are more frequently girls (9). In women younger than 65 years of age, the proportion of deaths from CHD directly attributable to smoking has actually increased in the United States from 26% in 1965 to 41% in 1985 (10). The Nurses' Health Study has documented a relative risk of fatal CHD of 5.4 for smokers of --25 cigarettes per day as compared with women who had never smoked (11). Similar data were available for nonfatal myocardial infarction, with a relative risk of 5.8. The association of smoking habit with angina pectoris was weaker, with a relative risk of two to three times in women smoking > 15 cigarettes per day (11). However, even the lightest smokers (1-4 cigarettes per day) had a significantly increased risk of CHD (relative risk 2.4; 11). The risk of CHD tended to be somewhat higher among older women and among women with a parental history of CHD (11).In ex-smokers, a decline in the risk to a level approximating that of women who had never smoked occurred within 3 or 4 years after the cessation of smoking, and it was independent of the amount smoked, the duration of smoking, or the presence of other predisposing factors for myocardial infarction (12,13). Hermanson et al. (14) studied the effects of cessation of smoking in patients with CHD from the CASS Study and found in women, as in men who continued smoking, a higher mortality and a higher risk of myocardial infarction (cumulative relative risk of 1.5) as compared with t...

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Hereditary Heparin Cofactor II Deficiency and the Risk of Development of Thrombosis

Cited by 113 publications

References 11 publications

Familial Thrombophilia: A Review Analysis

Familial Thrombophilia: A Review Analysis

Inhibition of Meizothrombin and Meizothrombin(desF1) by Heparin Cofactor II

State-of-the-Art Review : Sex and Cardiovascular Risk Factors

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