Levels of intrinsic coagulation factors and the risk of myocardial infarction among men: Opposite and synergistic effects of factors XI and XII.

In order to assess the clinical implications of hereditary F XII deficiency, all available members of Swiss families with F XII deficiency were investigated. Based on the F XII:C values and the family pedigree, the 74 subjects, aged 8-82 years, were classified as homozygotes/double heterozygotes for F XII deficiency (n = 18), as obligatory (n = 20) or possibly (n = 25) heterozygotes, respectively, and as normals (n = 11). None of the 18 subjects with F XII:C less than 0.01 U/ml and only one possibly heterozygous woman had an abnormal bleeding tendency, confirming the notion that Hageman trait generally does not result in a hemorrhagic diathesis. Two of the 18 subjects with severe F XII deficiency had suffered from venous thromboembolic disease at age less than 40 years. One heterozygous woman had a leg ulcer probably due to venous thrombosis. Thus, whereas homozygous F XII deficiency may be associated with an increased risk for venous thromboembolic disease, partial F XII deficiency is not, by itself, a strong risk factor for thrombosis. Whereas 17 of the 18 subjects with F XII:C less than 0.01 U/ml had no detectable F XII:Ag, one cross reacting material-positive F XII deficient subject (F XII:Ag = 0.11 U/ml) was identified. The dysfunctional F XII, present in this subject's plasma and tentatively called F XII Bern, is the fourth abnormal F XII molecule identified so far.

Thromboembolism and bleeding tendency in congenital factor XII deficiency--a study on 74 subjects from 14 Swiss families.

One hundred and three patients suffering from recurrent venous thrombosis, recurrent arterial thromboembolism and/or recurrent myocardial infarction and 50 healthy subjects were tested for Hageman factor (FXII) coagulant activity and antigen Among the 103 patients we identified 15 subjects with FXII deficiency (15%), 3 with protein C deficiency (3%) and 3 with protein S deficiency (3%) Combined FXII and protein C, protein S or antithrombin III deficiency was not observed The 103 patients were divided into subgroups according to the type of thrombotic complication Among patients with exclusively recurrent venous thromboembolism 8% (p = 0153) were deficient in FXII Among patients suffering from recurrent arterial thromboembolism and/or myocardial infarction, the incidence of FXII deficiency was significantly higher (20%, p less than 0003) In 67% of the patients with FXII deficiency a positive family history of thrombosis could be established In contrast, only 32% of all venous and 28% of all arterial thrombosis patients had a positive family history We believe that reduced levels of FXII should be considered as a risk factor in the development of thromboembolism Consequently, more attention should be payed to the measurement of FXII when evaluating thromboembolic risk factors especially in cases of recurrent arterial thromboembolism and/or myocardial infarction

The prevalence of factor XII deficiency in 103 orally anticoagulated outpatients suffering from recurrent venous and/or arterial thromboembolism.

In acute coronary events, plaque rupture and the subsequent formation of the catalytic tissue factor-factor VIIa complex is considered to initiate coagulation. It is unknown whether clotting factors XI and IX are activated in acute coronary events. Therefore, we prospectively investigated the activation of clotting factors XI and IX as well as activation of the contact system and the common pathway in 50 patients with acute myocardial infarction (AMI), in 50 patients with unstable angina pectoris (UAP), and in 50 patients with stable angina pectoris (SAP). Factor XIa-C1 inhibitor complexes, which reflect acute activation of factor XI, were detected in 24% of the patients with AMI, 8% of the patients with UAP, and 4% of the patients with SAP (P<0.05), whereas factor XIa-alpha(1)-antitrypsin complexes, which reflect chronic activation, were observed equally in all 3 study groups. Factor IX peptide levels were significantly higher in the patients with AMI and UAP compared with the patients with SAP (P<0.01). No differences regarding markers of the common pathway were demonstrated. Fibrinopeptide A levels were elevated in patients with AMI compared with patients with UAP and those with SAP (P<0.01). Factor XIIa- or kallikrein-C1 inhibitor complexes were not increased. In conclusion, this is the first demonstration of the activation of clotting factors XI and IX in patients with acute coronary syndromes. Because these clotting factors are considered to be important for continuous thrombin generation and clot stability, their activation might have clinical and therapeutic consequences.

Activation of Clotting Factors XI and IX in Patients With Acute Myocardial Infarction

Background Coronary artery disease (CAD) mostly occurs in persons older than 45 years of age In India, CAD manifests almost a decade earlier than in Western countries This study was done to study the risk factors and angiographic profile in young patients presenting with acute myocardial infarction (AMI) Patients and Methods: One hundred and twenty four consecutive patients presenting with AMI at less than 40 years of age were studied for risk factors Coronary angiography was done in all Results: Out of 124 patients, 123 were male Mean age was 3594 ± yrs One hundred and eighteen had ST elevation myocardial infarction (MI) (9516%) and six had non ST elevation MI (584%) Anterior wall MI was present in 88 patients (7097%), inferior wall MI in 31 patients (25%) and lateral wall MI in five patients (403%) Seventy three patients (588%) were smoker, 55 were hypertensive (4435%), 10 were diabetic (806%) Family history of CAD was present in 22 (177%) patients Low High-density lipoprotein (HDL) was seen in 53 patients (427%), and high triglycerides in 60 patients (4838%) Significant CAD was found in 88 (7096%) patients, 13 (1048%) had normal coronaries Single vessel disease was seen in 57 patients, two-vessel disease in 15 patients and three-vessel disease in eight patients Total 125 lesions were seen and left anterior descending (LAD) was the commonest vessel involved, with 78 lesions (624%) Conclusion: AMI in young almost exclusively occurs in male, and ST elevation MI is the main presentation Anterior wall MI is most common, with LAD being involved in around 2/3 patients Smoking, hypertension, low HDL and high triglycerides are the major risk factors

Myocardial infarction in young adults-risk factors and pattern of coronary artery involvement.

A 17 year old girl had a myocardial infarction. Three days later coronary angiography showed an occlusive thrombus in the circumflex and anterior descending arteries. The coronary arteries themselves appeared to be normal, and this was confirmed at repeat angiography three months later. Tests of haemostasis showed a deficiency of factor XII.

https://heart.bmj.com/content/heartjnl/53/2/230.full.pdf

Myocardial infarction with normal coronary arteries and factor XII deficiency.

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Myocardial infarction with normal coronary arteries and factor XII deficiency.