Congenital protein c deficiency and myocardial infarction: Concomitant factor VII hyperactivity may play a role in the onset of arterial thrombosis

doi:10.1016/0049-3848(92)90261-8

Thrombosis Research

Volume 67, Issue 1, 1 July 1992, Pages 95-103

https://doi.org/10.1016/0049-3848(92)90261-8 Get rights and content

Abstract

A 29-year-old man with congenital protein C deficiency and acute myocardial infarction is reported. Four hours after the onset of chest pain, he was treated intravenously with tissue-type plasminogen activator. Subsequent coronary angiography revealed only slight stenosis of the left anterior descending coronary artery without any atherosclerosis. The propositus, his brother, and his mother, showed low levels of both protein C activity and antigen, while plasma thrombomodulin levels were normal. His grandfather had died from acute myocardial infarction at 38 years of age. We investigated several other risk factors for arterial thrombosis, including factor VII, fibrinogen, heparin cofactor II, lipoprotein (a), and anticardiolipin antibodies. No other haemostatic abnormalities apart from factor VI hyperactivity were detected in this family. To study the effects of protein C and factor VI on procoagulant activity, prothrombin time was measured after the addition of activated protein C and factor VI to protein C-deficient plasma. The prothrombin time ratio decreased along with an increase in the factor VII level. It also decreased with a decrease in the activated protein C level. These findings indicated that the procoagulant activity of factor VI was enhanced by low protein C levels, suggesting that concomitant factor VII hyper-activity may cause acute myocardial infarction in patients with protein C deficiency.

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Cited by (19)

Syndrome of protein C deficiency and anterior wall acute myocardial infarction at a young age from a single coronary occlusion with otherwise normal coronary arteries
2003, American Journal of Cardiology
Silent cerebral infarcts in basal ganglia are advanced in congenital protein C-deficient heterozygotes with hypertension
2001, American Journal of Hypertension
Congenital protein C deficiency is now widely recognized as a genetic risk for venous thrombosis. However, it remains uncertain whether this condition also confers risk for arterial thrombosis. We evaluated the association of congenital protein C deficiency with hypertension and silent cerebrovascular disease using brain magnetic resonance imaging (MRI) (T1- and T2-weighted and proton density images) in a large family pedigree of protein C deficiency diagnosed by gene analysis, compared with 46 non-pedigree related control subjects with normal protein C levels (≥ 75%) who were selected from among 55 asymptomatic hypertensive subjects matched for age and cardiovascular risk factors. Of the 58 living subjects in this pedigree, we measured plasma protein C levels in 45 subjects, and found 2 cerebral infarctions in the 24 heterozygotic subjects, whereas there was no stroke in the 21 normal homozygotic subjects. We performed brain MRI in 14 asymptomatic hypertensive subjects without any cardiovascular disease and in two patients with cerebral infarction, and found 28 cerebral infarcts (two corresponded to the patient neurologic deficits and 26 were silent). All were lacunar infarcts < 10 cm in size. A total of 25 silent lacunar infarcts were found in nine heterozygotic subjects, whereas only one was found in the seven normal homozygotic subjects (2.8 v 0.14 lacunes per person, P = .002). No advanced white matter hyperintense lesions in T2-weighted images were found in either group. The prevalence of silent lacunar infarcts in the heterozygotic subjects was also significantly higher than that in normal control subjects (1.0 per person, P = .01). Concerning the distribution of silent infarcts, the number of lacunes located in the basal ganglia was higher in the heterozygotic subjects (2.3 per person, P < .001) than in the seven normal homozygotic subjects (0.14 per person) or in the control group (0.28 per person), whereas the number of lacunes in the white matter was not different among the groups. In conclusion, congenital protein C deficiency may accelerate the progression of silent cerebral infarct formation in hypertension, particularly in the basal ganglia, and may be a potential risk for stroke or vascularly induced dementia.
Analysis of 45 episodes of arterial occlusive disease in Japanese patients with congenital protein C deficiency
1999, Thrombosis Research
Hereditary protein C deficiency is associated with a predisposition to venous thrombosis. It is not clear whether the deficiency is involved in arterial occlusion. In the present study, we screened for protein C amidolytic activity in patients admitted to the National Cardiovascular Center Hospital, and we identified among them 43 probands and 51 relatives with heterozygous protein C deficiency. Among them, 34 patients with heterozygous protein C deficiency had manifested 45 episodes of arterial occlusive disease. Venous thrombotic diseases were less common. In the examination of whether protein C deficiency hastens arterial occlusion, we found a significant difference $p=0.02$ in the age at onset of acute myocardial infarction between the patients with protein C deficiency $n=10; 49.4±14.8 years$ and a group of patients with normal protein C levels $n=42; 60.5±10.6 years$ . Acute myocardial infarction occurred before 40 years of age in a significantly greater proportion of the patients with protein C deficiency (3:10, 30%) as compared with the controls (2:42, 5%) $χ^{2} =5.9, p=0.015$ . At the onset of atherothrombotic cerebral infarction the patients with protein C deficiency were significantly $p=0.022$ younger $n=11; 57.4±12.8 years$ than those with normal protein C levels $n=48; 64.6±10.1 years$ . Venous thrombosis was the most frequent clinical manifestation (21 of 31 episodes) in the patients with antithrombin III deficiency $n=26; 68% of the total$ , who were admitted to our hospital. Thus, our study suggests that congenital protein C deficiency contributes to earlier onset of arterial occlusive diseases, especially acute myocardial infarction, in Japanese subjects.
Recurrent restenosis after percutaneous transluminal coronary angioplasty in a patient with congenital protein C deficiency and high activated factor VII level
1996, Thrombosis Research
Congenital protein C deficiency is known to be associated with increased risk of venous thrombosis and pulmonary embolism (1). However, it is controversial whether the protein C deficiency increases the risk of arterial diseases. Clinically, more than 75% of all thrombotic episodes in congenital protein C deficiency patients are deep venous thrombosis and pulmonary embolism, and arterial diseases such as myocardial infarction or stroke are very rare (2%, and 1%, respectively) (2). There have been only a few cases reported about this deficiency in patients with myocardial infarction (3, 4) or brain infarction (5). We describe a patient with protein C deficiency and a high level of activated factor VII who presented with myocardial infarction and restenosis that recurred 6 times after percutaneous transluminal coronary angioplasty (PTCA).
Activated protein C resistance: Prevalence and implications in peripheral vascular disease
1996, Journal of Vascular Surgery
Purpose: Activated protein C (APC) is a naturally occurring anticoagulant that interacts with factors V and VIII to inhibit the clotting cascade. Resistance to APC (APC-R), hypothesized to occur as a result of an abnormal factor V, has been documented in up to 40% of patients with venous thrombotic events, but its prevalence in patients with arterial disease remains ill defined.
Methods: With an assay of APC resistance that expresses the ratio of the activated partial thromboplastin time with and without the addition of exogenous APC, APC resistance ratios were quantitated in 200 individuals comprising 177 patients with vascular disease and 23 control subjects. An abnormal activated partial thromboplastin time was present in four patients who were excluded from analysis. The 173 remaining patients formed the study population and were divided into diagnostic subgroups on the basis of the most symptomatic problem.
Results: APC resistance was documented in 20 individuals, representing 11.6% of the study group. The highest prevalence of APC resistance was observed in patients with lower extremity occlusive disease, with the APC-R ratio below 2.0 in 13.%. Within the subgroup of individuals with lower extremity disease, 76 patients (10 with APC-R, 13.2%) underwent infrainguinal bypass and were monitored a mean of 47±8 months. Occlusion of the arterial reconstruction occurred in 22 patients (29%). Six (60%) of the patients with APC-R had failed reconstructions, versus 16 (24%) of 66 patients without APC-R (p=0.02).
Conclusions: These findings suggest that APC-R is relatively common in patients with peripheral vascular disease, especially in those with lower extremity occlusive disease. APC-R appears to be a risk factor for failure of infrainguinal bypass. These observations suggest that screening for APC-R may be useful in patients with peripheral vascular disease, providing the opportunity to restore the normal thrombogenic balance with anticoagulant therapy in susceptible individuals.
Syndrome of protein c deficiency and anterior wall acute myocardial infarction at a young age from a single coronary occlusion with otherwise normal coronary arteries
2023, Case Reports in Cardiology: Coronary Heart Disease and Hyperlipidemia

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PaperCongenital protein c deficiency and myocardial infarction: Concomitant factor VII hyperactivity may play a role in the onset of arterial thrombosis

Abstract

Am J Cardiol

Lancet

Lancet

Thromb Res

Am J Cardiol

Thromb Res

Blood

Blood

Thromb Res

Thromb Res

Blood

A thrombotic state due to an abnormal protein C

N Engl J Med

Hereditary protein C deficiency: a review of the genetics, clinical presentation, diagnosis and treatment

Blood Coag Fibrinol

Arterial thrombosis as clinical manifestation of congenital protein C deficiency

Ann Hematol

Deficiency of protein C in congenital thrombotic state

J Clin Invest

Paper
Congenital protein c deficiency and myocardial infarction: Concomitant factor VII hyperactivity may play a role in the onset of arterial thrombosis