Low normal level of protein C or of antithrombin increases risk for recurrent cardiovascular events

Pelkonen, K Markus; Wartiovaara‐Kautto, Ulla; Nieminen, Markku S.; Ahonen, Kirsi; Sinisalo, Juha

doi:10.1097/01.mbc.0000169220.00679.13

Cited by 15 publications

(6 citation statements)

References 16 publications

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“…Only one study has previously investigated the role of antithrombin levels on recurrent ATE in CHD patients. In a prospective cohort study by Pelkonen et al on acute coronary syndrome patients, patients who had a recurrent arterial event had lower antithrombin levels than patients who had no recurrence [19]. However, these subjects were mostly male, and substantially older (64 ± 10 years) than in our study (43.6 ± 5.8 years).…”

Section: Discussioncontrasting

confidence: 67%

“…However, when using antithrombin activity as a binary variable with predefined cut-off of the median antithrombin level, a 46% increased risk of ATE was found in the adjusted analysis for the participants with low antithrombin levels (OR 1.46; 95% CI:1.09e1.96). Similar results were found in the CHD group (OR 1.43; 95% CI:1.01e2.02) and in the IS group (OR 1.48; 95% CI: 1.01e2 19)…”

supporting

confidence: 85%

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Antithrombin levels are associated with the risk of first and recurrent arterial thromboembolism at a young age

et al. 2018

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Section: Discussioncontrasting

confidence: 67%

supporting

confidence: 85%

Antithrombin levels are associated with the risk of first and recurrent arterial thromboembolism at a young age

et al. 2018

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“…These close associations might help explain clinical observations showing that low normal levels of these 2 inhibitors increase the risk of recurrent cardiovascular events in patients with ACS. 53 Previously, we have shown in this patient population that simulated Tf-initiated thrombin generation based upon factor composition can discriminate between acute and stable CAD. 22 We have also demonstrated that these ACS and CAD MI patients have circulating fXIa that correlates with markers of coagulation and inflammation.…”

Section: Discussionmentioning

confidence: 88%

Systemic blood coagulation activation in acute coronary syndromes

Undas

Szułdrzyński

Brummel‐Ziedins

et al. 2009

Blood

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We evaluated systemic alterations to the blood coagulation system that occur during a coronary thrombotic event. Peripheral blood coagulation in patients with acute coronary thrombosis was compared with that in people with stable coronary artery disease (CAD). Blood coagulation and platelet activation at the microvascular injury site were assessed using immunochemistry in 28 nonanticoagulated patients with acute myocardial infarction (AMI) versus 28 stable CAD patients matched for age, sex, risk factors, and medications. AMI was associated with increased maximum rates of thrombin-antithrombin complex generation (by 93.8%; P < .001), thrombin Bchain formation (by 57.1%; P < .001), prothrombin consumption (by 27.9%; P ‫؍‬ .012), fibrinogen consumption (by 27.0%; P ‫؍‬ .02), factor (f) Va light chain generation (by 44.2%; P ‫؍‬ .003), and accelerated fVa inactivation (by 76.1%; P < .001), and with enhanced release of platelet-derived soluble CD40 ligand (by 44.4%; P < .001). FVa heavy chain availability was similar in both groups because of enhanced formation and IntroductionAfter vascular injury, blood clotting is initiated when plasma factor (f) VIIa gains access to tissue factor (Tf). The resulting complex activates the plasma zymogens fIX and fX. 1 Factor Xa activates small amounts of thrombin, which activates platelets, and the procofactors fV and fVIII to their respective active forms. 2 These reactions result in the formation of the intrinsic fXase (fVIIIa-fIXa) and prothrombinase (fVa-fXa) on the activated platelet surface. 3 The major bolus of thrombin formed by the prothrombinase complex is largely responsible for the ultimate hemostatic process. 4 A potent, synergistic inhibitory system principally composed of tissue factor pathway inhibitor (TFPI), antithrombin (AT), and the thrombin-thrombomodulin (Tm)-catalyzed dynamic protein C (PC) system opposes thrombin generation. 5,6 The formation of fVa and its regulation by activated protein C (APC) are key processes for maintaining blood homeostasis. The fV activation process involves sequential cleavages to first produce a heavy chain (1-709) and subsequently a light chain resulting in the active cofactor. 7 The PC system inactivates fVa in a kinetically controlled series of cleavage reactions in which APC cleaves the heavy chain of fVa at 2 locations (R506 and R306); the resulting fVai can no longer function in the coagulation system. 8,9 The balance between activation and inactivation of fV is critical to the synergistic control of the coagulation process. 10 The activation of the Tf coagulation pathway appears to be central in arterial and venous thrombosis. 11 A major clinical manifestation of arterial thrombosis is represented by the acute coronary syndromes (ACS), which result from platelet-rich thrombus formation on the surface of ruptured or eroded atheromatosus plaque in the coronary artery. 12 Typical procoagulant abnormalities in ACS are increased circulating thrombin marker levels, such as prothrombin fragment 1.2 (F1.2) or thrombin-antithrombi...

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“…There are several possible explanations for this finding. PAI-1 release has been associated with ischemic cardiovascular disease and heart failure (35,36); lower levels of protein C also are associated with ischemic cardiovascular disease (37)(38)(39). The presence of circulatory shock has been associated with lower levels of protein C in patients with ALI/ARDS (11).…”

Section: Discussionmentioning

confidence: 99%

From evidence to clinical practice: Effective implementation of therapeutic hypothermia to improve patient outcome after cardiac arrest*

Oddo

Schaller

Feihl

et al. 2006

Critical Care Medicine

503

230

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Objective-The coagulation and inflammatory cascades may be linked in the pathogenesis of acute lung injury and acute respiratory distress syndrome. However, direct evidence for the contribution of abnormalities in coagulation and fibrinolysis proteins to outcomes in patients with acute lung injury/acute respiratory distress syndrome is lacking.Design-Retrospective measurement of plasma levels of protein C and plasminogen activator inhibitor-1 in plasma samples that were collected prospectively as part of a large multicenter clinical trial. The primary outcome was hospital mortality. To evaluate the potential additive value of abnormalities of these biomarkers, the excess relative risk of death was calculated for each combination of quartiles of protein-C and plasminogen activator inhibitor-1 levels. Setting-Ten university medical centers.Patients-The study included 779 patients from a multicenter clinical trial of a protective ventilatory strategy in acute lung injury/acute respiratory distress syndrome and 99 patients with acute cardiogenic pulmonary edema, as well as ten normal controls. Measurements and MainResults-Compared with plasma from controls and patients with acute cardiogenic pulmonary edema, baseline protein-C levels were low and baseline plasminogen activator inhibitor-1 levels were elevated in acute lung injury/acute respiratory distress syndrome. By multivariate analysis, lower protein C and higher plasminogen activator inhibitor-1 were strong independent predictors of mortality, and ventilator-free and organ-failure-free days. Plasminogen activator inhibitor-1 and protein C had a synergistic interaction for the risk of death. Conclusions-Early acute lung injury/acute respiratory distress syndrome is characterized by decreased plasma levels of protein C and increased plasma levels of plasminogen activator inhibitor-1 that are independent risk factors for mortality and adverse clinical outcomes. Measurement of plasminogen activator inhibitor-1 and protein-C levels may be useful to identify those at highest risk of adverse clinical outcomes for the development of new therapies. NIH Public Access Keywordsacute respiratory distress syndrome; protein C; plasminogen activator inhibitor-1; coagulation; fibrinolysis Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening disorders characterized by severe inflammation in the lungs and frequent occurrence of multiple organ failure (1). Despite numerous randomized controlled trials of therapies aimed at modulating the inflammatory response in ALI/ARDS (2), the only therapy that has been proven to reduce mortality is a protective ventilatory strategy (3). Although mortality from ALI/ARDS has declined in clinical trials, epidemiologic studies that include all patients with ALI/ARDS still report mortality rates >50% (4). Insight into the pathophysiological derangements that characterize early clinical ALI/ARDS may help to guide the development of new therapies for this devastating disorder.The degree of alterations ...

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Low normal level of protein C or of antithrombin increases risk for recurrent cardiovascular events

Cited by 15 publications

References 16 publications

Antithrombin levels are associated with the risk of first and recurrent arterial thromboembolism at a young age

Antithrombin levels are associated with the risk of first and recurrent arterial thromboembolism at a young age

Systemic blood coagulation activation in acute coronary syndromes

From evidence to clinical practice: Effective implementation of therapeutic hypothermia to improve patient outcome after cardiac arrest*

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