81. A 44-year-old man presents to your office complaining of right leg pain and swelling of 3 days’ duration.
The patient was well until he had a wreck while riding his dirt bike 1 week ago. The patient states that
he injured his right leg in this accident. Initially, his leg was moderately sore on weight bearing, but swelling and persistent pain have now developed. On physical examination, you note an extensive bruise on the patient’s right calf and 2+ edema from the foot to the midthigh. You suspect trauma-asso-ciated deep vein thrombosis (DVT).
Which of the following statements regarding DVT is true?
❏ A. Thrombi confined to the calf are large and typically result in pul-monary venous thromboembolism (VTE)
❏ B. The postthrombotic syndrome is a rare sequela of DVT and is associat-ed with low morbidity
❏ C. Most patients presenting with a new DVT have an underlying inherit-ed thrombophilia
❏ D. The most common cause of inherited thrombophilia associated with this illness is activated protein C resistance (factor V Leiden)
Key Concept/Objective: To understand the general features of DVT
Seventy percent of patients with symptomatic pulmonary embolism have DVT, which is usually clinically silent. Thrombi confined to calf veins are usually small and are rarely associated with pulmonary embolism. An inherited thrombophilic defect known as acti-vated protein C resistance, or factor V Leiden, has now been established as the most com-mon cause of inherited thrombophilia, occurring in about 5% of whites who do not have a family history of venous thrombosis and in about 20% of patients with a first episode of venous thrombosis. The second most common thrombophilic defect is a mutation (G20210A) in the 3’ untranslated region of the prothrombin gene that results in about a 25% increase in prothrombin levels. This mutation is found in about 2% of whites who have no family history of venous thrombosis and in about 5% of patients with a first episode of venous thrombosis. Elevated levels of clotting factors VIII and XI and of homo-cysteine also predispose patients to thrombosis. Although inherited thrombophilia is a well-described and important cause of venous thrombosis, the large majority of patients with venous thrombosis do not have an inherited thrombophilia. The postthrombotic syn-drome occurs as a long-term complication in about 25% (and is severe in about 10%) of patients with symptomatic proximal vein thrombosis in the 8 years after the acute event, with most cases developing within 2 years. Clinically, the postthrombotic syndrome may mimic acute venous thrombosis but typically presents as chronic leg pain that is associat-ed with associat-edema and that worsens at the end of the day. Some patients also have stasis pig-mentation, induration, and skin ulceration; a smaller number of patients have venous claudication on walking, caused by persistent obstruction of the iliac veins. (Answer: D—
The most common cause of inherited thrombophilia associated with this illness is activated protein C resistance [factor V Leiden])
82. A 43-year-old man presents to the emergency department complaining of chest pain of 2 hours’ dura-tion. The patient denies having any dyspnea. He has no significant medical history, nor does he have a family history of early coronary artery disease. He is a nonsmoker and an avid jogger. His chest pain is constant, is pleuritic, and does not radiate. His chest x-ray is clear, and his ECG reveals only sinus tachy-cardia. Blood gas measurements reveal a partial pressure of oxygen (PO2) of 58 mm Hg with a widened alveolar-arterial difference in oxygen (A-aDO2). Helical CT reveals segmental and subsegmental filling defects in the right lung.
Which of the following statements regarding anticoagulation and thrombolysis for thromboem-bolism is true?
❏ A. When using unfractionated heparin, the therapeutic range for the acti-vated partial thromboplastin time (aPTT) is 2.5 to 3.5 times the normal value
❏ B. Low-molecular-weight heparin (LMWH) is safe and effective for the treatment of pulmonary thromboembolism
❏ C. Because of a delay in achieving a therapeutic INR with lower doses, a starting dose of warfarin should be no less than 10 mg
❏ D. In contrast to other thrombolytic agents, recombinant tissue plasmino-gen activator (rt-PA) stimulates antibody production and can induce allergic reactions
Key Concept/Objective: To understand individual therapies for pulmonary thromboembolism
When using unfractionated heparin, the dose should be adjusted as necessary to achieve a therapeutic range, which for many aPTT reagents corresponds to an aPTT ratio of 1.5 to 2.5. The published research on LMWHs, which includes over 3,000 patients treated with either once-daily or twice-daily subcutaneous doses, has established this class of anticoag-ulants as being safe, effective, and convenient for treating venous thrombosis and pul-monary embolism. Evidence indicates that it might be safer to use a starting dose of 5 mg of warfarin because, compared with 10 mg, the 5 mg starting dose does not result in a delay in achieving a therapeutic INR and is associated with a lower incidence of suprather-apeutic INR values during the first 5 days of treatment. Because streptokinase is a bacteri-al product, it stimulates antibody production and can prompt bacteri-allergic reactions.
Antistreptococcal antibodies, which are present in variable titers in most patients before streptokinase treatment, induce an amnestic response that makes repeated treatment with streptokinase difficult or impossible for a period of months or years after an initial course of treatment. (Answer: B—Low-molecular-weight heparin [LMWH] is safe and effective for the treat-ment of pulmonary thromboembolism)
83. A 72-year-old man presents to the hospital with a hip fracture. An orthopedist is planning surgical repair and asks you to see the patient in consultation for preoperative assessment and advice. In particular, the orthopedist asks you to assess the patient’s need for prophylaxis against venous thrombosis and to com-ment on the best prophylactic regimen for the patient.
Which of the following statements regarding primary prophylaxis against venous thrombosis and thromboembolism is true?
❏ A. Oral anticoagulation is the method of choice for moderate-risk general surgical and medical patients
❏ B. Prophylactic therapy should typically be discontinued at the time of discharge for patients who have undergone major orthopedic surgery
❏ C. LMWH is more effective than standard low-dose heparin in patients undergoing elective hip surgery
❏ D. For patients undergoing genitourinary, neurologic, or ocular surgery, the most appropriate method of prophylaxis is oral anticoagulation
Key Concept/Objective: To know the correct methods of prophylaxis for venous thrombosis and thromboembolism in medical and surgical patients
Low-dose-heparin prophylaxis is the method of choice for moderate-risk general surgical and medical patients. It reduces the risk of VTE by 50% to 70% and is simple, inexpensive, convenient, and safe. Extended prophylaxis with LWMH or warfarin for an additional 3 weeks after hospital discharge should be considered after major orthopedic surgery.
Extended prophylaxis is strongly recommended for high-risk patients (e.g., those with pre-vious VTE or active cancer). LMWH is more effective than standard low-dose heparin in general surgical patients, patients undergoing elective hip surgery, and patients with stroke or spinal injury. For those undergoing genitourinary, neurologic, or ocular surgery, intermittent pneumatic compression, with or without graduated compression stockings, is effective prophylaxis against venous thrombosis and does not increase the risk of bleed-ing. (Answer: C—LMWH is more effective than standard low-dose heparin in patients undergoing elec-tive hip surgery)
84. An 80-year-old patient of yours is scheduled to undergo total knee replacement. He is in excellent health, and except for osteoarthritis, his medical history is not significant. The orthopedic surgeon asks you for advice regarding VTE prophylaxis.
What would you advise for this patient?
❏ A. LMWH is contraindicated because of the risk of bleeding; intermittent pneumatic compression devices would be preferable
❏ B. Intermittent pneumatic compression devices are contraindicated because of the location of the surgery; LMWH is preferable
❏ C. Aspirin, 325 mg q.d., should be started immediately after surgery
❏ D. LMWH and intermittent pneumatic compression devices are equally effective in preventing VTE after knee surgery
❏ E. The risk of VTE after knee replacement is so low as to make prophylax-is unnecessary
Key Concept/Objective: To know the prophylaxis for DVT after knee-replacement surgery LMWH and intermittent pneumatic compression devices have been shown to be equally effective in preventing DVT after knee-replacement surgery. Aspirin has been shown to decrease the risk of DVT after hip fracture, but its efficacy relative to LMWH or intermit-tent pneumatic compression devices has never been studied, and the standard of care for postoperative DVT prophylaxis in North America does not call for its use. After knee-replacement surgery, the risk of postoperative DVT is 10% to 20%, and the rate of fatal pul-monary embolism is 1% to 5%, so prophylaxis is indicated. Prophylaxis is also cost-effec-tive. (Answer: D—LMWH and intermittent pneumatic compression devices are equally effective in pre-venting VTE after knee surgery)
85. A 28-year-old woman who is 18 weeks pregnant and is G1P0 is referred to you by her obstetrician for advice regarding management of a possible VTE diathesis. Although she has no personal history of VTE, she reports that her mother and a cousin both had blood clots during pregnancy; she does not know whether they were tested for clotting disorders. She is feeling well, and her physical examination is remarkable only for her pregnancy.
Which of the following actions would you take for this patient?
❏ A. Educate her about the symptoms of VTE and advise her to seek care immediately if she notes one of them; otherwise, no further testing or treatment is necessary
❏ B. Start warfarin therapy with a target INR of 2 to 3
❏ C. Start LMWH, 100 anti-10a U/kg subcutaneously q.d.
❏ D. Start aspirin therapy, 325 mg q.d.
❏ E. Test for antithrombin-III deficiency; if she has the deficiency, start LMWH therapy
Key Concept/Objective: To understand the management of inherited thrombophilias in pregnancy It is possible that this woman has an inherited thrombophilia. Pregnant women with antithrombin-III deficiency have an especially high rate of VTE. If this patient tests posi-tive, she should receive prophylactic anticoagulation therapy throughout the rest of her pregnancy. The benefits of prophylactic anticoagulation in pregnant women with protein C or protein S deficiency outweigh the risks only if they have a history of VTE. Because this patient has never had VTE, the results of testing her for these disorders would not lead to a change in management. In pregnant women with factor V Leiden mutation or G20210A prothrombin mutation, no anticoagulation therapy is recommended unless they develop a clot during the current pregnancy. In any case, LMWH is preferable to warfarin therapy because of the teratogenic effects of warfarin. Aspirin does not provide effective anticoagulation therapy for VTE. Although this woman should be educated about the signs and symptoms of VTE, this alone is not sufficient. (Answer: E—Test for antithrombin-III deficiency; if she has the deficiency, start LMWH therapy)
For more information, see Kearon C, Hirsch J: 1 Cardiovascular Medicine: XVIII Venous Thromboembolism. ACP Medicine Online (www.acpmedicine.com). Dale DC, Federman DD, Eds. WebMD Inc., New York, December 2003