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Factor V Leiden: How great is the risk of venous thromboembolism?

Cleveland Clinic Journal of Medicine. 2012 April;79(4):265-272 | 10.3949/ccjm.79a.11072
April 1, 2012|Cleveland Clinic Journal of Medicine
Khaldoon Shaheen, MD;M. Chadi Alraies, MD, FACP;Abdul Hamid Alraiyes, MD, FCCP;Richard Christie, MD
Author and Disclosure Information

Khaldoon Shaheen, MD
Department of Medicine, Case Western Reserve University–St. Vincent Charity Medical Center, Cleveland, OH

M. Chadi Alraies, MD, FACP
Clinical Assistant Professor of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, and Department of Hospital Medicine, Cleveland Clinic, Cleveland, OH

Abdul Hamid Alraiyes, MD, FCCP
Department of Pulmonary, Critical Care, and Environmental Medicine, Tulane University Health Sciences Center, New Orleans, LA

Richard Christie, MD
Program Director, Internal Medicine Residency, Department of Medicine, Case Western Reserve University–St. Vincent Charity Medical Center, Cleveland, OH

Address: Khaldoon Shaheen, MD, Department of Internal Medicine, St. Vincent Charity Medical Center, 2351 East 22nd Street, Cleveland, OH 44115; e-mail Khaldoon.Shaheen@stvincentcharity.com

ABSTRACTThe factor V Leiden mutation, the most common inherited cause of thrombophilia, causes a mild hypercoagulable state. We describe a 29-year-old man, heterozygous for factor V Leiden, who developed extensive pulmonary emboli with concomitant bilateral deep venous thrombosis, likely provoked by prolonged immobility during a car trip. We then review the diagnosis, therapy, screening, and prognosis of venous thromboembolism related to factor V Leiden.

KEY POINTS

  • The pathogenesis of venous thromboembolism is complex and multifactorial, often reflecting the interplay between environmental, clinical, and genetic factors.
  • Factor V Leiden increases the risk of venous thromboembolism but by itself does not appear to increase the risk of arterial thrombosis.
  • Often, people with factor V Leiden may have additional risk factors that increase the rate of venous clots, such as older age, surgery, obesity, immobility, prolonged travel, hospitalization, oral contraceptive use, hormonal replacement therapy, pregnancy, and malignancy.
  • General measures and precautions are needed to minimize the risk of venous thromboembolism in people with the factor V Leiden mutation, especially when modifiable factors are present, such as obesity and long periods of immobilization.

A 29-year-old white man with no chronic medical problems presents to the emergency department with shortness of breath, left-sided pleuritic chest pain, cough, and hemoptysis. These symptoms began abruptly 1 day ago and have persisted. He also has mild pain and swelling in both calves. He denies having any fever, night sweats, or chills. On further questioning, he reports having taken a long, nonstop driving trip that lasted 8 hours 1 week ago.

His medical history is negative, and he specifically reports no history of deep venous thrombosis or pulmonary embolism. He underwent appendectomy 10 years ago but has had no other operations. He does not take any medications. His family history is noncontributory and is negative for venous thromboembolism. He smokes and uses alcohol occasionally but not illicit drugs.

Examination. He appears to be in considerable distress because of his chest pain. His temperature is 100.4°F (38.0°C), blood pressure 125/70 mm Hg, heart rate 125 beats per minute, respiratory rate 26 breaths per minute, oxygen saturation 92% on room air, and body mass index 19 kg/m2.

Chest examination reveals diminished vesicular breathing in the left base, which is normal to percussion without added sounds. Both calves are swollen and tender to palpation without skin discoloration. The rest of his examination is normal.

Laboratory values:

  • White blood cell count 9.3 × 109/L (reference range 4.5–11.0)
  • Hemoglobin 15.9 g/dL (14.0–17.5)
  • Platelets 205 × 109/L (150–350)
  • Sodium 140 mEq/L (136–142)
  • Potassium 3.9 mEq/L (3.5–5.0)
  • Chloride 108 mEq/L (96–106)
  • Bicarbonate 23 mEq/L (21–28)
  • Blood urea nitrogen 14 mg/dL (8–23)
  • Creatinine 0.9 mg/dL (0.6–1.2)
  • Glucose 95 mg/dL (70–110)
  • International normalized ratio (INR) 0.90 (0.00–1.2)
  • Partial thromboplastin time 27.5 seconds (24.6–31.8)
  • Creatine phosphokinase 205 U/L (39–308)
  • Troponin T < 0.015 ng/mL (0.01–0.045).

Pulmonary embolism is diagnosed

Figure 1. The patient’s chest radiograph shows small atelectatic changes in the left lung base (arrow).
Electrocardiography shows sinus tachycardia. Chest radiography shows small atelectatic changes at the left lung base (Figure 1). Pulmonary embolism is suspected, and a serum Ddimer level is obtained; it is 4,054 ng/mL (reference range < 500). Computed tomography of the chest confirms bilateral acute pulmonary emboli (Figure 2). Doppler ultrasonography of both legs reveals bilateral deep venous thrombosis. Echocardiography shows mildly elevated right ventricular systolic pressure at 47 mm Hg.
Figure 2. Computed tomography of the chest showed numerous filling defects within the upper and lower branches of the pulmonary artery (arrows), the right and left sides, suggestive of extensive acute pulmonary embolism. The main portions of the right and left main pulmonary artery and main central pulmonary artery are patent without embolus.

Factor V Leiden is diagnosed, and the patient recovers with treatment

Anticoagulation is started in the emergency department.

Given this patient’s young age and clot burden, a hypercoagulable state is suspected. Thrombophilia screening is performed, with tests for the factor V Leiden mutation, the prothrombin G20210A mutation, and antiphospholipid and lupus anticoagulant antibodies. The rest of the thrombophilia panel, including antithrombin III, factor VIII, protein C, and protein S, is deferred because the levels of these substances would be expected to change during the acute thrombosis.

The direct test for factor V Leiden mutation is positive for the heterozygous type. The test for the prothrombin G20210A mutation is negative, and his antiphospholipid antibody levels, including the lupus anticoagulant titer, are within normal limits.

The patient is kept on a standard regimen of unfractionated heparin, overlapped with warfarin (Coumadin) until his INR is 2.0 to 3.0 on 2 consecutive days. His hospital course is uneventful and his condition gradually improves.

He is discharged home to continue on oral anticoagulation for 6 months with a target INR of 2.0 to 3.0. Two weeks after completing his anticoagulation therapy, his levels of antithrombin III, factor VIII, protein C, and protein S are all within normal limits.

FACTOR V LEIDEN IS COMMON

Factor V Leiden is the most common inherited thrombophilia, with a prevalence of 3% to 7% in the general US population,1 approximately 5% in whites, 2.2% in Hispanics, and 1.2% in blacks.2 Its prevalence in patients with venous thromboembolism, however, is 50%.1,3 The annual incidence of venous thromboembolism in patients with factor V Leiden is 0.5%.4,5

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