D-Dimer Test Is Less Informative in Older Patients

Abstract

Jane Salodof MacNeil is a senior editor with Elsevier Global Medical News. ATLANTA — Elderly people have much higher rates of venous thromboembolism than younger people do. They also tend to have elevated levels of D-dimer—which can make D-dimer testing less useful in predicting the risk of recurring blood clots when patients are aged 65 and older. The relationship between exponentially increasing venous thromboembolism (VTE) rates in the elderly and rising D-dimer levels presents a diagnostic dilemma, according to speakers at a symposium on how thrombosis in the elderly presents “a public health and scientific problem of unrecognized dimensions.” “Older age reduces the clinical usefulness of D-dimer testing. … We probably need age-adjusted cutoffs in older people,” Dr. Kenneth A. Bauer, a professor of medicine at Harvard Medical School, Boston, said during the special session at the annual meeting of the American Society of Hematology. “We really do need more work done in D-dimer, though it is the most promising of the markers that we see in predicting recurrence risk,” said Dr. Bauer, who is also chief of the hematology section at the Veterans Affairs Boston Healthcare System and director of thrombosis research at Beth Israel Deaconess Medical Center, Boston. VTE is three times more common in people aged 65 years and older, compared with those aged 45–64 years, reported Dr. Mary Cushman of the University of Vermont, Burlington. When VTE patients are stratified by age, 70% are 60 years and older. Just why VTE incidence increases with age is not clear, said Dr. Cushman. Despite limited data, she said, the evidence to date makes clear that the impact is also high in the elderly, with rates of death, recurrence, post-thrombotic syndrome, and treatment complications rising with each decade of life. The elderly “are more likely to fail treatment than those under age 65,” she said. In healthy elderly individuals, however, researchers have found high levels of many coagulation activation markers, including D-dimer, a fibrin degradation product released when blood clots. “D-dimer really is a composite of thrombin activation and then plasma dissolution of the fibrin that is normally formed. There are low levels of D-dimer that we measured in normal healthy people,” Dr. Bauer said. The fact that D-dimer is heterogeneous has led to issues in using and standardizing D-dimer assays, he noted, contrasting it with other coagulation markers that are discrete polypeptides with defined molecular weights. “D-dimer is a physiological variable and can vary over time,” Dr. Bauer said, discussing a study of centenarians conducted in Italy (Blood 1995;85:3144–9). Investigators compared 25 healthy centenarians with two control groups of healthy people aged 18–50 years and 51–69 years. Each of these groups was also made up of 25 people. The healthy centenarians showed laboratory signs of coagulation activation, including high levels of proteins that can predict cardiovascular disease in middle-aged people. Notably, the D-dimer concentrations were highly elevated in the centenarians: 323 ng/mL, compared with 29 ng/mL in the younger control group and 50 ng/mL in the middle group. That healthy centenarians have significantly higher levels of D-dimer suggests that increased D-dimer “is not necessarily a bad thing. It is consistent with long life,” Dr. Bauer commented. While many coagulation activation markers increase with age, he focused on D-dimer because it has the potential to stratify recurrence risk in patients after treatment for their first idiopathic VTE and thereby identify who would benefit from extended anticoagulation. Among several studies showing higher recurrence risk in patients with elevated D-dimer levels, he highlighted a multicenter investigation conducted in Italy (N. Engl. J. Med. 2006;355:1780–9). In that study, D-dimer levels were tested 1 month after anticoagulation was stopped in patients who had a first unprovoked deep vein thrombosis or pulmonary embolism. Patients with normal levels did not resume therapy. Those with “abnormal” D-dimer levels were randomly assigned to resuming or staying off treatment. Of the patients with elevated D-dimer levels, 74% were aged 65 years and older. At a median follow-up of 1.4 years, 10.7% of untreated patients with abnormal D-dimer levels had a recurrence, compared with 4.4% of those with normal levels (hazard ratio 2.27). When untreated patients were stratified by age, Dr. Bauer said the risk of recurrence was less in the elderly; they had a hazard ratio of 1.63, compared with 4.40 for those younger than age 65. Among patients with normal D-dimer levels, however, he said recurrence was higher in the elderly. In an interview immediately after the session, he cautioned against taking an alarmist stance when elderly patients present with high D-dimer levels. “We are getting a lot of elderly referred because they have chronically elevated D-dimers with no history of thrombosis,” he said. “One needs to be aware that [this is] probably something that goes along with age.”