Richard A. Savage, MD
DNA analysis be done on cremated remains?
The question of DNA identification of cremains or partially incinerated
remains comes up surprisingly often for those who perform DNA typing
on skeletal remains.
very difficult to completely incinerate human remains. Commercial
crematoriums typically expose bodies to 2,000°C for two hours.
Under these conditions, the ashes will not yield DNA. Most remains
recovered from building fires, however, are not totally incinerated
and will contain DNA.
DNA within bone
is very stable and can withstand temperatures of several hundred
degrees or more for short time periods. DNA cannot be recovered,
however, when a bone becomes calcined. Calcined bone, often described
as porcelain-like, has been reduced to its white or blue mineral
constituents, indicating all organic material has been destroyed.
blackened bones may or may not yield DNA and generally should be
tested. Many DNA analysts have been surprised to find a typable
result when it appeared that the bone was not worth testing.
DNA is destroyed
by progressive fragmentation. This may result in some DNA identification
markers being successful when others are not, so one may be left
with a partial set of DNA identity markers. In such cases, the discriminatory
power may be reduced, yet a likelihood of identity established.
Most DNA identity
testing involves short tandem repeat analysis that is performed
on the nuclear (chromosomal) DNA, but in these cases mitochondrial
DNA testing may be required. Mitochondrial DNA tests are more likely
to be successful because a cell may have only one copy of nuclear
DNA but hundreds or thousands of copies of mitochondrial DNA in
the cytoplasm of the cell. Mitochondrial DNA testing, however, is
less discriminating, more expensive than short tandem repeat nuclear
DNA analysis, and performed by only a few laboratories.
Victor Walter Weedn, MD, JD
Principal Research Scientist
Director of Biotechnology and Health Initiatives
Carnegie Mellon University, Pittsburgh
Q. Many articles state that the half-life of low-molecular-weight heparin
is longer than that of unfractionated heparin, but they do not give a specific
figure for the half-life. What is the half-life of LMWH? LMWH is monitored by
the anti-Xa inhibition test. What is the principle behind the chromogenic anti-Xa
A. The answer to your first question is clear-cut. The half-life
of low-molecular-weight heparin is three to four hours.1,2
second question requires a longer explanation. The heparin assay
depends on the inhibition of factor Xa. A 1998 article in the Archives
of Pathology and Laboratory Medicine3 summarized
the heparin assay very well, stating:
determination of the functional activity of heparin are based
on the ability of heparin to accelerate the inhibition of a standard
concentration of an activated coagulation enzyme, such as factor
Xa or thrombin, in the presence of enough AT [antithrombin] to
complex all available heparin. The ease, accuracy, and precision
of these assays have been improved by the development of enzyme-specific
chromogenic and fluorogenic substrates. The signal generated is
proportional to the amount of residual factor Xa (or thrombin)
remaining after neutralization by the AT-heparin complex and is
thus inversely proportional to concentration of heparin. The signal
may be measured by endpoint or kinetic techniques. Functional
heparin assays should be simple, reliable, reproducible, highly
sensitive, and easily adapted to automation. These assays also
should be relatively easy to standardize among laboratories; however,
there is still variability reported. Some of this variability
may be due to preanalytical differences. Many of the newer multipurpose
coagulation instruments can perform heparin assays concurrently
with other routine coagulation assays without requiring major
instrument adjustments or reagent preparation. The chromogenic
assays based on factor Xa inhibition have also been shown to be
effective for the measurement of low-molecular-weight heparin.
In the United
States, the APTT remains the most commonly used test for monitoring
unfractionated heparin. On the 2002-CG-2B proficiency testing challenge,
fewer than 200 laboratories reported results for a heparin assay.
The heparin assay is most frequently used only in uncommon settings
when the APTT will not suffice. LMWH does not usually need to be
monitored, but when monitoring is necessary, only the factor Xa
inhibition method can currently be used.
M, Green D, Van Cott EM, et al. College of American Pathologists
Conference XXXI on laboratory monitoring of anticoagulant therapy:
the clinical use and laboratory monitoring of low-molecular-weight
heparin, danaparoid, hirudin and related compounds, and argatroban.
Arch Pathol Lab Med. 1998; 122: 799–807.
- Hirsh J, Levine MN. Low molecular weight heparin. Blood.
- Olson JD, Arkin CF, Brandt JT, et al. College of American Pathologists
Conference XXXI on laboratory monitoring of anticoagulant therapy:
laboratory monitoring of unfractionated heparin therapy. Arch
Pathol Lab Med. 1998;122: 782–798.
John D. Olson, MD, PhD
Professor and Director of Clinical Laboratories
Department of Pathology, University of Texas
Health Science Center, San Antonio
Chair, CAP Coagulation Resource Committee
Q. How can the Centers for Medicare and Medicaid Services
justify reimbursing for blood and components at a rate below that charged by
the hospital’s supplier?
let’s note that even under the fee-for-service payment system
that predated inception of the Medicare prospective payment system,
or PPS, in 1983, Medicare and other third-party payers typically
paid only about 80 percent of costs, with the remainder covered
by the patient.
CMS uses the
same methodology to reimburse hospitals for blood products and services
under the PPS as it does to reimburse hospitals for other products
and services. Medicare does not reimburse hospitals for the cost
of acquiring blood products per se. Instead, Medicare pays flat
amounts for specific types of hospital discharges, defined by diagnosis
related groups. Each DRG payment is intended to represent the bundle
of costs involved in caring for a patient whose stay is categorized
under that DRG. The payment level for each of the more than 500
DRGs is a function of a base payment rate for each hospital and
the relative weight of each DRG, both of which are updated annually.
(Hospital costs are just one component used to update a national
standardized payment amount, which is subject to area- and hospital-specific
adjustments to yield a hospital’s base payment rate.)
The DRG weights
are recalibrated each year to reflect relative changes in the resources
required to provide care among the respective DRGs. This recalibration
does not increase overall Medicare payments; it simply provides
a way to reallocate Medicare payments in the inpatient PPS. Here’s
the kicker for blood payments: These DRG weights are based on the
charges, not costs, that hospitals report to Medicare each year.
The Medicare inpatient PPS is based on the assumption that reported
charges are good proxies for the relative resource use among DRGs.
CMS only knows what hospitals report to the agency. If charges are
not reported or if the charge amounts for a product or service are
low, then the charges on which DRG payments are based will be underrepresented.
(The DRG updates generally lag behind the charge data by two years.)
reported that only 48 percent of hospitals billed for one or both
of the blood-related cost centers in their Medicare reports to CMS.
Our analysis found great disparities in how often hospitals bill
for blood products and services and in the charges they use when
blood is billed. On average, the hospital markup of charges over
costs for blood products and services is less than half the markup
for other hospital products and services. Together, these factors
significantly underrepresent the costs to hospitals of blood products
and services in Medicare’s determinations of DRG weights and
the reimbursement for blood-intensive DRGs, accordingly.
CMS has acknowledged
the importance of paying appropriately for blood products and services.
The Department of Health and Human Services Advisory Committee on
Blood Safety also has endorsed appropriate payment rates, specifically
in reference to the outpatient payment system. Medicare is keenly
aware that many of its billing rules are complex and that this may
have contributed to inadequate hospital coding and billing.
to be interested in simplifying these rules and informing hospitals
how to implement them. The health care sector welcomes such efforts
by CMS. At the same time, however, it is unlikely that Medicare
will establish a special mechanism to pay for blood products and
services under the PPS. The accounting for blood-related costs in
the Medicare PPS will not improve until CMS obtains more complete
and accurate charge data from hospitals. CMS should, therefore,
work with hospitals, blood collection and banking organizations,
and other stakeholders to provide clear, comprehensive guidance
for coding and billing of blood products and services.
Clifford Goodman, PhD
Vice President, Senior Scientist
The Lewin Group, Falls Church, Va.