PBL Sessions: Vascular Diseases 2
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Page 10
Final Discussion of Case:
Tasks
Discuss the cause(s) for chest pain in this patient.
Review the causes for his systemic arterial disease and explain how they occur.
Discuss the cause(s) for this patient's pulmonary disease.
Discuss the laboratory findings which help to explain why this patient continued to have pulmonary disease.
Prepare for the case wrap up session.
Vascular PBL - Case Summary
The case illustrates risk factors and complications for atherosclerosis, particularly coronary atherosclerosis, with an acute myocardial infarction. The young age of the patient for development of complications, along with the high serum cholesterol (in the high 300 to 400 range), suggests that he has familial hypercholesterolemia. The heterozygous form of this disease has a frequency of about 1 in 500 persons of European ancestry. His coronary angiogram reveals a high grade stenosis of the right coronary artery, and the microscopic sections representative of the coronary artery show marked lumenal narrowing. The microscopic sections of the myocardium show the range of changes from infarction about a day in age, to an intermediate age of about 10 days, to a scar a month or more old. The students can match these to the time course of the patient's history. The students are to work on identifying and describing risk factors and complications of atherosclerosis, explaining the pathophysiology of atherogenesis. We are not focusing specifically on treatment, but the students can suggest possible therapies or lifestyle modifications for the patient. Of course, in the history they are given that he received a "statin" drug for his hypercholesterolemia.
There is a second diagnosis in the case. The patient has deep vein thrombosis and pulmonary thromboembolism. This could be related to being immobilized from his heart disease. On the other hand, it is occurring at a young age, and there is a history that suggests it may have occurred before and in other family members. The students must speculate in the first session about possible causes for thrombosis, and they can describe acquired and inherited conditions. At the beginning of the second session the students will be given laboratory data that definitively identifies the problem as a prothrombin gene mutation. Inherited thrombotic disorders are not common, but must be considered when there is recurrent thrombosis, unexplained thrombosis, or onset at a young age. A table of causes for hypercoagulable states is shown below.
Hypercoagulable States
| Disorder | Mechanism
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| Antiphospholipid syndrome | There are circulating antibodies that bind plasma proteins with an affinity for phospholipid surfaces, and this can cause thrombosis and in women stillbirth. This syndrome is most often acquired in adulthood, either from an underlying disease or as an idiopathic condition. The two subsets of this syndrome, as defined by laboratory testing, are: lupus anticoagulant (which may or may not be seen with SLE), and anti-cardiolipin antibody
| | Factor V Leiden mutation | This is the most common inherited form of hypercoagulability. The mutation, which leads to activated protein C resistance, is present in 5% of Caucasians but is rare in persons of African and Asian ancestry. Heterozygotes have a mild risk for thrombosis, but the rare homozygotes have a marked risk. A point mutation leads to impaired inactivation of factor V by activated protein C. Recurrent venous thrombosis can occur, starting even in young persons, and in women stillbirth.
| | Elevated factor VIII | This condition is as common as factor V Leiden mutation. There may be genetic and environmental factors causing it. Oral contraceptive use increases factor VIII levels. The result is deep venous thrombosis.
| | Malignant neoplasms | Neoplastic cells may elaborate a factor, such as a thromboplastin-like substance, that can increase the risk for thrombosis. This is one form of paraneoplastic syndrome, with the name Trousseau's syndrome. There can be venous (more likely) or arterial thrombosis.
| | Protein C, Protein S, antithrombin III deficiencies | These conditions are autosomal dominant and lead to recurrent venous thrombosis, even starting in young persons. Thrombosis is often spontaneous, without other precipitating events. They can be detected by laboratory testing for the respective coagulation factor
| | Sticky platelet syndrome | This is an autosomal dominant disorder that can lead to both arterial and venous thrombosis. Stillbirth may occur in women. Stress is a precipitating event.
| | Homocystinemia | Persons with elevated plasma homocysteine levels not only have increased problems with atherosclerosis, but also arterial and venous thrombosis. Stillbirth may occur in women.
| | Prothrombin mutation | The prothrombin G20210A mutation increases the level and activity of prothrombin that mildly increases the risk for arterial and venous thrombosis. The mutation occurs more often in persons of southern European ancestry.
| | Plasminogen abnormalities | Plasminogen, which has an anticoagulant effect, can be deficient. The features resemble protein C or S deficiency. Also, tissue plasminogen activator can be deficient. Plasminogen activator inhibitor can be increased.
| | Congenital dysfibrinogenemia | This rare autosomal dominant disorder may cause either thrombosis or hemorrhage.
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