ABSTRACTProtein C has an important role in exerting anticoagulatory effects.
Its deficiency can be congenital or acquired, and results in increased risk of thrombosis. Hereditary protein C deficiency is a rare autosomal dominant disorder, that leads to a hypercoagulable state at birth. Homozygous individuals usually develop symptoms in infancy; while heterozygous protein C deficient individuals usually presents in adult life. Heterozygous Protein C deficient individuals are at increased risk of thrombosis and pulmonary embolism. Reporting here is a case report of a young gentleman with heterozygous Protein C deficiency who developed myocardial infarction, in the absence of other risk factors.
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INTRODUCTIONProtein C is a vitamin K dependent glycoprotein that is synthesized in the liver. It is one of the main inhibitors of the coagulation system. In the blood, it circulates as an inactive zymogen. The activation of zymogen into activated protein C is catalyzed by thrombin when it is bound to endothelial glycoprotein thrombomodulin. Activated protein C inhibits coagulation factor Va and VIIIa, which are essential for thrombin formation and activation of factor X. A vitamin K dependent cofactor protein S is responsible for the catalytic activity of activated protein C.
Deficiency of Protein C leads to prothrombotic state, hence vascular thrombosis. Venous thromboembolism is one of the main manifestation of Protein C deficiency. Besides that, arterial stroke and myocardial infarction in young adults have also been reported (1). CASE REPORTA 30 year old gentleman who is moderately built and is a non smoker, with no known medical illness prior to this presented with sudden onset of shortness of breath and retrosternal chest pain radiating to his jaws. He also had profuse sweating.
He was immediately brought to casualty. On presentation, his Blood pressure was 128/80mmHg, and his Electrocardiogram showed anterior wall myocardial infarction. His troponin T and I levels were markedly raised. An angiogram was done and it showed the presence of a thrombus at the distal left anterior descending artery. Subsequently, a Percutaneous coronary intervention was done. On further assessment, his BMI was 23, and he had no other risk factors for coronary artery disease. His father had history of deep vein thrombosis few years ago. His baseline blood pressure was about 130/86mmHg.
Other blood investigations, such as full blood count, renal profile, liver function, coagulation profile (PT and APTT), HBA1c, fasting blood sugar, and fasting lipid profile were normal. On further investigations noted his plasma Protein C activity was low. However, his Protein S activity and antithrombin activity were normal. DISCUSSION Protein C deficiency is found in 1 in 200 to 1 in 500 individuals in the general population.
Homozygous protein C deficiency is a rare condition, in which newborns usually present with purpura fulminans and disseminated intravascular coagulation in neonatal period, leading to death if not promptly treated. Most individuals are asymptomatic throughout their life. The main feature of heterozygous protein C deficiency is venous thromboembolism. However, pulmonary embolism, myocardial infarction, and arterial thrombosis has been reported in some. This patient did not have any significant risk factors to develop myocardial infarction. Hence, it is highly likely that Protein C deficiency can cause thrombus formation in the arterial system even in the absence of atherosclerosis. Besides the hereditary form, Protein C deficiency is also seen in some acquired cases.
Sepsis and infection with gram-negative organisms or Staphylococcus species are the most common causes of the acquired type (Gurses and Ozkan, 1988). The diagnosis of protein C deficiency can be straight forward, however there are other factors that may influence the plasma Protein C levels. This includes vitamin K-based anticoagulant therapy, severe infections, liver disease, oral contraceptive use, and presence of autoantibody.
These has been excluded in this case. There are many therapeutic alternatives for long-term management of hereditary protein C deficiencies. According to a study done by Syed Maqbool et al, most of the patients with myocardial infarction due to Protein C deficiency were thrombolysed. In the patient reported in this case, he underwent percutaneous coronary intervention. In the treatment of heterozygous Protein C deficiency, oral anticoagulation with a coumarin derivative or heparin is the gold standard treatment. Treatment with oral anticoagulants for 6 months after the occurrence of the first thrombotic episode is recommended, but patients who experience subsequent thrombotic episodes need lifelong anticoagulation treatment to prevent a hypercoagulable state. While, fresh frozen plasma and protein C concentrate or coumarin derivatives may be given for homozygous patients. In addition, individuals with hereditary Protein C deficiency can also be given low-molecular-weight heparin and steroids.
Liver transplantation may be beneficial in some. In cases with significant positive family history, including death from venous thromboembolism, genetic counseling should be implemented, and appropriate thrombo-prophylaxis has to be in consideration for asymptomatic carriers. As in this case, the patients father had history of deep vein thrombosis several years ago, unfortunately, his father was not investigated further for protein C deficiency.
CONCLUSIONIn conclusion, a patient with Protein-C deficiency can present with myocardial infarction even though if there are no comorbids or major risk factors for coronary artery disease. Hence, it is essential to evaluate the Protein C levels in young adults with acute myocardial infarction especially in the absence of other risk factors. Early recognition of protein C deficiency would help the prevent further recurrence of venous thromboembolism, thrombotic episodes or infarctions.