Platelet Function Screen (PFA-100)

The antiquated Bleeding Time test has been replaced with the PFA-100 Platelet Function Screen.
This test monitors the time to platelet plug formation (called closure time) in citrated whole blood
exposed to a collagen membrane in response to ADP, or epinephrine. For patients known to be on
therapeutic aspirin (ASA) or P2Y12 (Clopidogrel or Plavix), the Accumetrics Aspirin Platelet Inhibition
test, and the Accumetrics P2Y12 Platelet Inhibition test is recommended to detect platelet inhibition.
The PFA-100 assay can screen for unexpected ASA inhibition.

PFA-100 test results :

 abnormal in most cases of von Willebrand disease (vWD), and some congenital platelet defects,
but may also be abnormal if the platelet count, or hematocrit is low. Prolonged closure times in
these situations may never the less indicate decreased in vivo platelet function.
 a normal PFA result in the setting of a low hematocrit, or platelet count indicates a lack of
platelet dysfunction. PFA-100 is still significantly more accurate than the Bleeding Time.
 will not reliably detect Plavix or ReoPro antiplatelet effects, but the closure times may be
significantly prolonged immediately following a ReoPro bolus .

The collagen/epinephrine part of the test is used to detect intrinsic platelet defects, vWD and
exposure to platelet inhibiting agents, while the collagen/ADP component is used to determine if an
abnormal collagen/epinephrine test is due to Acetyl Salicylic Acid.

Results are reported in seconds with common situations as follows:

Normal ASA vWD Glanzmann’s thrombasthenia

Col/epi normal abnormal abnormal abnormal

Col/ADP normal normal abnormal abnormal

Test interferences: Hemolysis, marked lipemia, many drugs.

**None of these tests should replace clinical judgment. Accurate history of the type and pattern of
bleeding, whether acquired or inherited, and if drugs might be involved, is needed to determine the
appropriate type of testing. If the test result does not fit the clinical picture, further testing such as
formal platelet aggregation studies may be warranted.
  Platelet-function test finds fault with omeprazole/clopidogrel combo, but not with other PPIs

In Munich, Germany, a new study using platelet-aggregometry testing to assess the effects of
different proton-pump inhibitors (PPIs) on platelet response to clopidogrel suggests that omeprazole
might be alone in adversely interacting with the widely used antiplatelet therapy. The study,
Thrombosis and Haemostasis (Apr. 2009), hints that other PPIs tested pantoprazole and esomeprazole
might be a safer bet for minimizing gastrointestinal side effects and bleeding in patients requiring long-
term clopidogrel treatment.
The study was restricted to testing platelet response, using just one of many tests developed to
evaluate platelet function and that it included no hard clinical end points. According to Dr Dirk Sibbing
(Deutsches Herzzentrum, Munich, Germany), specifically designed and randomized clinical studies are
needed to define the impact of concomitant PPI treatment on adverse events after percutaneous
coronary intervention.
Using the Dynabyte Multiplate point-of-care impedance aggregometer in 1000 patients who
had undergone PCI and stenting and were taking dual antiplatelet therapy (aspirin and clopidogrel
75 mg/day), Sibbing and others performed platelet-function testing. Of these, 268 patients were also
taking PPIs at the time of testing (162 were taking pantoprazole, 64 omeprazole, and 42 esomeprazole);
the remainder were not taking a PPI.
As reported, platelet aggregation was significantly different between the four groups, with
platelet aggregation significantly higher in the omeprazole group than in the group not taking a PPI. By
contrast, patients in the pantoprazole and esomeprazole groups had similar platelet aggregation to
those in the group not taking a PPI. In multivariate analyses, only administration of omeprazole was
associated with a reduced response to clopidogrel.
"This is the first study comparing the impact of concomitant treatment with three PPIs (pantoprazole,
omeprazole, and esomeprazole) on platelet response to clopidogrel treatment in a large cohort of
patients with previous coronary stent placement," Sibbing told heartwire. "Diverging effects on
clopidogrel response for different PPIs in one and the same study population have never been
demonstrated before and are now shown by our study."

An important contribution
The role and relative value of different platelet-function tests continue to prompt debate; the
authors of the current study point out that their findings corroborate those of the OCLA study, which
used a different type of assay to gauge clopidogrel responsiveness. "Both assays provided similar results
regarding the impact of omeprazole on clopidogrel response, which is a strong clue for the effect
observed," they note.
Sibbing told heartwire that the point-of-care assay used for platelet-function testing in this study "is
widely used and accepted." Other recent work by Sibbing's group has also demonstrated the ability of
the same assay to predict the occurrence of stent thrombosis and other ischemic events following PCI in
more than 1600 patients [2].
An editorial accompanying Sibbing et al's paper by Drs Victor Serebruany (Johns Hopkins University,
Baltimore, MD) and Shinya Goto (Tokai University, Kanagawa, Japan) [3] calls the study a "timely,
elegant, well-designed . . . important contribution to the field."
Drs Serebruany and Goto point out that PPIs are widely prescribed by physicians for symptomatic relief
rather than as therapy for a confirmed diagnosis of a range of gastrointestinal syndromes. Sibbing et al's
study, on top of other recent studies, suggests that omeprazole, but not other PPIs, diminish the
antiplatelet potency of clopidogrel—the upshot being that physicians could be putting patients at risk
for little gain. "Use of [a] clopidogrel and PPI combination is difficult to justify, since the gastrointestinal
protection comes at the expense of reducing the vascular benefit of clopidogrel," they write. For now,
they conclude, the combination "cannot be recommended until more randomized and mechanistic data
become available."
That advice directly contradicts current guidelines, which recommend prescription of a PPI in all patients
taking dual antiplatelet therapy. "Findings of the present study may have important clinical implications
in terms of PPI selection in patients under dual antiplatelet treatment," Sibbing et al write.
Sibbing also agreed that the way omeprazole and clopidogrel interact requires further study. "Based on
the clinical and platelet-function data available, it must be assumed that the adverse effects of
omeprazole are, to a significant proportion, related to platelet effects," he said. "Other mechanisms,
however, cannot be excluded and warrant further investigations."
They also offer the caveat that although their study showed similar results for both pantoprazole and
esomeprazole, the study was only powered to consider pantoprazole treatment.
More answers are expected at the upcoming SCAI meeting in Las Vegas, NV, where investigators for the
Clopidogrel Medco Outcomes Study, addressing the effects of clopidogrel and individual PPIs, will be
releasing new results.

 New Test Screens for Bacteria in Blood Platelets

The first rapid test to detect bacterial contamination in blood platelets destined for transfusion
has been approved by the U.S. Food and Drug Administration.

Platelets are frequently transfused to prevent or stop bleeding in people who have surgery,
have had a major bodily trauma, or who are receiving chemotherapy. Platelets contaminated with
bacteria put recipients are risk of a life-threatening infection called blood poisoning. The infection must
be treated quickly to prevent its spread to the heart and lungs.

The risk of someone receiving a platelet transfusion contaminated with bacteria is about one in
5,000, which is greater than either the risks of acquiring the hepatitis C virus (one in 1.6 million) or HIV
(one in 1.9 million) via contaminated platelets, the FDA said.

The Platelet PGD Test System is produced by Verax Biomedica Inc. of Worcester, Mass.

 Array Medical Receives FDA Clearance for New Coagulation Testing System

Array Medical received FDA clearance to market their new Actalyke(TM) Activated Clotting Time
Test (ACT) System. Designed for use at the point of patient care to monitor heparin anticoagulation
therapy, the Actalyke system is comprised of a portable, battery-operated instrument and disposable
tubes. Test results are provided within minutes, making it a valuable diagnostic tool during medical
procedures such as cardiopulmonary bypass surgery, cardiac catheterization and angioplasty,
Interventional radiology and hemodialysis.
 In addition, the Actalyke system provides unique capabilities and improved product features at
substantial savings over other ACT systems on the market. This strategy of a value-added system at a
more affordable price meets the demands of today's changing healthcare environment
Array Medical also markets the Ichor(TM) hematology analyzer, a powerful miniaturized cell counter for
performing Complete Blood Count.
In cryptography, a mode of operation that combines the ciphertext of one block with the
plaintext of the next block. ) at the point of patient care. It is the first such system to bring this test to
the clinical environment for the purpose of blood transfusion triage.

 New strategies for reperfusion therapy

PCI (Percutaneous Coronary Intervention )is the preferred strategy in acute myocardial
infarction when performed by an experienced team as soon as possible after first medical contact. A
STREAM trial currently underway looks to ascertain whether the best strategy for patients who
cannot receive P-PCI is early fibrinolysis together with mandated angiography.

STREAM Trial- is used in order to ascertain once and for all whether the best strategy for patients who
cannot receive P-PCI in early fibrinolysis, together with mandated angiography.

Acute occlusion of a major coronary artery due to disruption of an atheromatous plaque and the
formation of occlusive thrombus has major clinical implications. At the moment of cessation of the
blood flow, heart muscle cells start to die. From the early days of treating acute myocardial infarction
(now known as "ST segment elevation myocardial infarction"- or- "STEMI") with clot busting (fibrinolytic)
drugs it has been clear that time is of the essence in obtaining optimal reperfusion of the myocardium
through dissolution of the clot formed within the coronary artery- the original GISSI studies showed
there was benefit of these agents out to 6 hours, later extended to 12 hours following trials such as the
"LATE study". Real world, one month mortality fell from 18% pre fibrinolysis to 9-10% with the use of
aspirin and fibrinolysis. In the early and mid 1990s, and during an era when angioplasty was becoming
increasingly used to treat fixed coronary atheromatous obstruction in patients with angina, angioplasty
or PCI (percutaneous coronary intervention) become the subject of research trials to test whether this
technique (Primary-PCI) could be used to treat both the clot and the underlying atheromatous
narrowing and in many benchmark studies was compared with fibrinolysis. Better flow with P-PCI and
treatment of the underlying lesion led to beneficial differences in outcome favouring P-PCI. 
Evidence has led the ESC to suggest that P-PCI is the preferred strategy in acute myocardial
infarction when performed by an experienced team as soon as possible after first medical contact.

(SRC: http://www.physorg.com/news170942920.html)
  TEG Tests vs Standard Coagulation Tests 

Recent advances in the understanding of coagulation mechanisms have allowed for a

reappraisal and a questioning of the value of the previous standards of the PT and APTT while giving
credence to the value of the whole-blood monitoring technique of the TEG analyzer. The older view of a
separate intrinsic and extrinsic coagulation system has been abandoned along with the waterfall
descriptions of coagulation mechanisms with one enzyme working after another and with some
mechanisms of feedback amplification and inhibition derived in a plasma milieu. None of this theory was
actually applicable in moving blood. These concepts have been replaced by a concept of enzyme
complexes existing on the surface of cells, passing one another their substances until the final product,
fibrin, is formed. The cell surfaces of importance are those of the platelets, which are activated and
adhere to the site of the injury. They localize the clotting process, enhance their activities, and protect
the enzyme complexes from inhibitors that circulate to protect against propagation of the clotting
activation downstream. 

The surface concept provides an explanation of how some individuals with only a few percent of
plasma coagulation factors can maintain hemostasis, while these same individuals will hemorrhage if
their platelet function is compromised. Since PT and APTT are plasma tests designed with substitutes for
platelet surfaces, it can readily be understood why these tests would not agree with the whole-blood

TEG analysis- uses the actual cellular surfaces to monitor coagulation.  Once the importance of the
platelet surfaces and of other cellular surfaces and their interactions with the coagulation process are
understood, the value of the PT or APTT in clinical management should be questioned

TEG analyzer- is sensitive to platelet function, plasma factors, activators and inhibitors of coagulation,
it represents an ideal monitor for hemostasis. 
-allows acquisition of continuous quantitative information on the developing clot; the
time it takes for the first fibrin to develop, the kinetics of clot development, the strength and stability of
the clot, taking into consideration all the components that make blood clot or lyse. Ignoring the
interactive nature of hemostasis, analyzing separated blood components such as plasma, RBC, WBC,
platelets, fibrinogen level, or factor assays, can result in artifacts that do not match the clinical
condition. This should serve as a caution against basing therapy on these analyses, especially since there
are significant risks associated with blood transfusions. 
(SRC: http://www.haemoscope.com/interp.html)

 Platelet Concentration System accelerates patient recovery

CAPTION(TM) Disposable Platelet Concentration System simplifies and expedites the collection
of platelet rich concentrate (PRC) and eliminates cross- contamination risks. It is used by the surgical
staff to concentrate the platelets from a sample of the patient's blood. Product concentrates platelets
from patient's blood sample, creating PRC of up to 4X original level that can be applied to surgical site to
help jumpstart body's natural healing response. System arrives sterile, and all materials are disposed of
after use. 
 The CAPTION system (develped by Smith & Nephew is a global medical technology business,
specializing in Orthopaedic Trauma & Clinical Therapies, Orthopaedic Reconstruction, Endoscopy and
Advanced Wound Management products)  creates a PRC of up to four times the original level and takes
40% less time than standard centrifugation. Furthermore, the disposable CAPTION system arrives sterile
and all materials are disposed after use, eliminating the risk of cross-contamination. The PRC made by
the CAPTION system consists of platelet cells suspended in a proprietary solution.