Antigen levels of coagulation factor XII, coagulation factor XI and prekallikrein, and the risk of myocardial infarction and ischemic stroke in young women

Siegerink, Bob; Rosendaal, Frits R.; Algra, Ale

doi:10.1111/jth.12531

Cited by 50 publications

(53 citation statements)

References 38 publications

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“…Therefore, levels of these complexes do not necessarily correlate with fXII:c or fXII:Ag levels and, indeed, recent data from the RATIO study have indicated that high fXII antigen levels do not correlate with activated protein-inhibitor complexes. 34 Furthermore, as allued to previously, the consequences of moderate and severe fXII deficiency may be very different. 15 …”

Section: Fxiimentioning

confidence: 99%

“…25 Unlike the case with fXII, the use of an antigen assay to measure plasma fXI levels (fXI:Ag) was in agreement with the conclusion using enzymeinhibitor complexes. 34 Therefore, the available data overall seem to support a link between high fXI levels and IS risk.…”

Section: Fximentioning

confidence: 99%

“…John Hageman's death from pulmonary embolism occurred 12 days after he sustained pelvic fractures, during which time he was largely 20 Age Ͼ45 y (462) Low fXII (fXII:Ag) VTE No VTE also not associated with high fXII NPHS-II 24 Males age 50-63 y at intake (2997) Low fXII (fXIIa-C1-INH) IS Yes RATIO 25 Females age 18-50 y with IS (175) High fXII (fXIIa-C1-INH) IS Yes Risk further increased by OCPs RATIO 34 Females age 18-50 y with IS (175) High fXII (fXII:Ag) IS No fXII:Ag not correlated with fXIIa-C1-INH ARIC 26 Age 45-54 y at intake (15 792) High fXII (fXII:c) IS No Case-control within ARIC cohort NPHS-II 29 Males age 50-63 y at intake (2997) High fXII (fXIIa:Ag) CHD Yes NPHS-II 24 Males age 50-63 y at intake (2997) High fXII (fXIIa-C1-INH) CHD No RATIO 25 Females immobile. 10 Although fXII deficiency per se was considered to be a risk factor for VTE, 11 in retrospect, this conclusion was likely explained by reporting bias.…”

Section: Vte Fxiimentioning

confidence: 99%

“…25 The same conclusion was reached when fXII:Ag levels were measured in these patients. 34 In the Study of Myocardial Infarctions Leiden (SMILE) study, levels of fXII:c were evaluated as a risk factor for MI in 560 men and 646 controls younger than 70 with a first MI. 30 Factor XII:c levels were lower in cases than in controls.…”

Section: Fxiimentioning

confidence: 99%

“…However, when fXII:Ag levels were assayed in the same patients and controls, no association with stroke risk was apparent, suggesting that the analyte being measured likely accounted for the divergent conclusions. 34 In the Atherosclerosis Risk in Communities (ARIC) Study, baseline fXII:c levels were measured in 89 incident stroke cases (42% male, 24% African American) and 406 random sample subjects. 26 No difference between the mean values in the 2 groups could be discerned.…”

Section: Fxiimentioning

confidence: 99%

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Epidemiologic and clinical data linking factors XI and XII to thrombosis

Key

2014

Hematology

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Currently available evidence supports the contention that elevated levels of factor XI (fXI) are associated with a greater risk of venous thromboembolism and ischemic stroke, but, less convincingly, with myocardial infarction. Conversely, reduced plasma levels of fXI seem to offer some protection from venous thromboembolism and stroke, but not myocardial infarction. Factor XI-deficient patients are at risk for certain types of bleeding, particularly posttraumatic hemorrhage on mucosal surfaces where there is a high endogenous fibrinolytic activity. In contrast, the situation with fXII in human thrombosis remains enigmatic. Deficiency of fXII is clearly not associated with any bleeding risk, but neither does it seem to be protective against thrombosis. The longstanding debate as to whether partial fXII deficiency represents a risk factor for thrombosis remains unresolved, with seemingly conflicting results depending on study design, type of assay used, and analyte evaluated. The possibility that elevated fXII levels represent a risk factor for thrombosis is not borne out in the literature.

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Section: Fxiimentioning

confidence: 99%

Section: Fximentioning

confidence: 99%

Section: Vte Fxiimentioning

confidence: 99%

Section: Fxiimentioning

confidence: 99%

Section: Fxiimentioning

confidence: 99%

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Epidemiologic and clinical data linking factors XI and XII to thrombosis

Key

2014

Hematology

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BAY 1213790, a fully human IgG1 antibody targeting coagulation factor XIa: First evaluation of safety, pharmacodynamics, and pharmacokinetics

Thomas

Thelen

Kraff

et al. 2019

Research and Practice in Thrombosis and Haemostasis

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Background Coagulation factor XI ( FXI ) contributes to the development of thrombosis but appears to play only a minor role in hemostasis and is therefore an attractive anticoagulant drug target. Objectives To evaluate the safety, pharmacodynamic, and pharmacokinetic properties of BAY 1213790, a fully human immunoglobulin (Ig) G1 antibody targeting activated coagulation FXI ( FXI a), in healthy men. Methods In this phase 1, single‐blind, parallel‐group, placebo‐controlled, dose‐escalation study, 83 healthy Caucasian men were randomized 4:1 to receive a single 60‐minute intravenous infusion of BAY 1213790 (0.015‐10 mg/kg) or placebo. Adverse events, pharmacodynamic parameters (including activated partial thromboplastin time [ aPTT ]) and pharmacokinetic parameters were determined. Volunteers were followed up for 150 days. Results BAY 1213790 demonstrated favorable safety and tolerability; there were no observed cases of bleeding or clinically relevant antidrug antibody formation. One volunteer (1.2%) experienced an infusion reaction. Following intravenous administration of BAY 1213790, dose‐dependent increases in aPTT (maximal mean increase relative to baseline: 1.85 [conventional method] and 2.17 [kaolin‐triggered method]) and rotational thromboelastometry whole blood clotting time were observed, as well as dose‐dependent reductions in FXI activity. Bleeding times did not increase following administration of BAY 1213790 and were similar for all dose cohorts, including placebo. Measurable and dose‐dependent increases in systemic exposure were detected for all doses of BAY 1213790 of 0.06 mg/kg or higher. Conclusions Based on these safety, pharmacodynamic, and pharmacokinetic results, further evaluation of BAY 1213790 in patients with, or at risk of, thrombosis is warranted.

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