Molecular Diagnosis of Cardiovascular Disorders - Applications of Biotechnology in Cardiovascular Therapeutics - page 142

screening or diagnostic test for Factor V Leiden. Although the clotting assay
compares well with PCR-RFLP, follow-up molecular testing is recommended in
samples showing borderline or abnormal results, to rule out other causes of functional
APC resistance and to accurately distinguish heterozygotes from homozygotes. The
latter is a critical distinction, as the thrombotic risk for homozygotes is about ten
times higher than the already elevated risk in Factor V Leiden heterozygotes.
PCR-based methods for the detection of factor V Leiden mutation show 100%
concordance in the results in that all of the laboratories could reliably identify the
single base pair substitution. Invader assay (Hologic Inc) amplifies linearly without
the need for PCR or gel electrophoresis and has been shown to detect this mutation
reliably in a THROMBO study. An ELISA-like assay has been developed by
Exiqon to detect the mutation in PCR-amplified genomic DNA using LNAs. In
2003, FDA approved the first DNA-based laboratory tests for this mutation −
Factor V Leiden and the Factor II (prothrombin) G20210A kit.
Pulmonary Embolism
Pulmonary embolism (PE) is a blockage of one or more of the pulmonary arteries
by blood clot, which is a common and highly lethal condition that is a leading cause
of death in all age groups. PE is the third most common cause of death in the USA
with at least 650,000 cases occurring annually. Currently, more cases of PE are
missed than are actually diagnosed because of vague and nonspecific symptoms.
It is the first or second most common cause of unexpected death in most age
groups. The highest incidence of unrecognized PE occurs in hospitalized patients.
Autopsy results show as many as 60% of patients dying in the hospital have a PE,
but the diagnosis is missed in about 70% of the cases.
Triage latex-agglutination D-Dimer Test (Biosite Inc) is a portable and easy-to-
use, point-of-care (POC) diagnostic test that can be used in the emergency depart-
ment or at the patients' bedside. A POC clinical protocol for the evaluation of PE
using D-Dimer test doubled the number of patients evaluated for PE and decreased
length of stay in the emergency department, without increasing the need for vascu-
lar imaging. This test can play an important role in helping emergency department
physicians rapidly evaluate patients with suspected pulmonary embolism, which
should result in better patient management.
Companies Involved in Cardiovascular Molecular Diagnosis
A selection of companies developing molecular diagnostics for cardiovascular
diseases is shown in Table 5.1 .