A 30-year-old white man comes to the emergency department with shortness of breath that began this morning. The patient has no chest pain, fevers, or chills. His medical history is insignificant, and he describes himself as healthy. He does not use tobacco or alcohol. The patient is physically active and has not traveled recently. His father died of a heart attack at age 45. Temperature is 36.1 C (97 F), blood pressure is 110/80 mm Hg, and pulse is 104/min. Chest auscultation indicates normal vesicular breath sounds. There are no heart murmurs. There is mild swelling of the right lower leg. ECG shows sinus tachycardia but is otherwise unremarkable. Laboratory results are as follows: Which of the following is the most likely contributor to this patient's current condition?

Question

A 30-year-old white man comes to the emergency department with shortness of breath that began this morning.  The patient has no chest pain, fevers, or chills.  His medical history is insignificant, and he describes himself as healthy.  He does not use tobacco or alcohol.  The patient is physically active and has not traveled recently.  His father died of a heart attack at age 45.  Temperature is 36.1 C (97 F), blood pressure is 110/80 mm Hg, and pulse is 104/min.  Chest auscultation indicates normal vesicular breath sounds.  There are no heart murmurs.  There is mild swelling of the right lower leg.  ECG shows sinus tachycardia but is otherwise unremarkable.  Laboratory results are as follows:  Which of the following is the most likely contributor to this patient's current condition?

Quizplus · Accepted Answer

11ec25c8_d41e_d51c_bc81_a73bd256641c_MD0003_00 Shortness of breath, right leg swelling, and sinus tachycardia with an elevated D-dimer are concerning for a pulmonary embolism (PE) that began as a deep venous thrombosis (DVT). The patient is young and has no obvious risk factors (eg, immobility, recent travel, trauma), so a hypercoagulable disorder should be considered. Testing is recommended in young (age <45) patients with a first-time unprovoked DVT/PE, patients with recurrent DVT/PE, and patients with unusual sites of thrombi (eg, cerebral, mesentery, portal veins). The most commonly found disorder is factor V Leiden (FVL), especially in Caucasian patients (4%-5% prevalence). Most patients with FVL have an autosomal dominant point mutation in the gene for factor V that makes it unable to respond to activated protein C, an innate anticoagulant. This mutation leads to slowed degradation of procoagulant active factor V, leading to continued thrombin formation and to slowed degradation of active factor VIII. Prothrombin time and activated partial thromboplastin time can be normal as the major procoagulant effects are due to continued thrombin formation; the elements of the coagulation cascade that can be assessed by these laboratory tests are less likely to be predominantly affected. Patients who inherit FVL are at an increased risk for DVT and PE, although not all express this phenotype as most are heterozygous. Those who are homozygous are at an even greater risk. (Choice B) Antiphospholipid antibodies (aPL Ab) cause venous and arterial thrombi, generally in patients with underlying conditions (eg, lupus). These patients usually have a prolonged activated partial thromboplastin time that fails to correct on a mixing study due to the presence of aPL Ab acting as an inhibitor. (Choice C) Antithrombin (AT) deficiency is usually acquired in the setting of disseminated intravascular coagulation, cirrhosis, or nephrotic syndrome. This patient has no evidence of any of these conditions. Inherited AT deficiency is rare. (Choice D) Patients with beta-thalassemia trait are generally asymptomatic and are not at increased risk for DVT/PE. Several studies have demonstrated that beta-thalassemia trait offers some protection against arterial thrombi due to lower blood viscosity from microcytic anemia. (Choice E) Increased prothrombin biosynthesis is from a prothrombin gene mutation, an autosomal dominant disorder that leads to the second-most common inherited thrombophilia, with especially high prevalence (2%) in Caucasian patients. It is less common than FVL. Educational objective: Factor V Leiden is the most commonly inherited hypercoagulable disorder in the Caucasian population, leading to increased risk of thrombosis. Testing should be considered for an unprovoked first-time thrombus in young (age <45) patients or those with an unusual site of thrombus. References: The anticoagulant function of coagulation factor V. (http://www.ncbi.nlm.nih.gov/pubmed/22116556) Impaired APC cofactor activity of factor V plays a major role in the APC resistance associated with the factor V Leiden (R506Q) and R2 (H1299R) mutations. (http://www.ncbi.nlm.nih.gov/pubmed/14976057) Factor V Leiden thrombophilia. (http://www.ncbi.nlm.nih.gov/pubmed/21116184)

A 30-Year-Old White Man Comes to the Emergency Department with Shortness