Hi,

I have a medical situation here that I would like opinions on.

The subject has some symptoms of a classic Deep Vein Thrombosis for
about a year.  These symptoms include swelling of the superficial
veins, pain, and swelling of the leg about 3 to 4 inches larger in
circumference than the normal leg size for this person.

Question 1:  Would it be medically competent to prescribe a patient
with these symtoms an NSAID, Diclofenac for the leg pain?

Here is a link to Diclofencac information: 
http://www.rxlist.com/cgi/generic/diclofen_ad.htm

Of particular interest is the fact that Diclofenac increases Platlet
aggregation and can cause statistically signifigant changes in
prothrombin and and partial thromboplastin times.  It is also stated
that "..all drugs that inhibit prostaglandin synthesis interfere with
platelet function to some degree; therefore, patients who may be
adversely affected by such an action should be carefully observed. "

With that being said, with the subject displaying symptoms of a blood
clot, or DVT, and also being prescribed Diclofenac, please answer the
following questions:

Question 2.  Could increased platlet aggregation worsen or lead to a DVT condition?
Question 3. Could changes in prothrombin and and partial
thromboplastin times lead to a worsening or occurance of the DVT
condition?

Hello tonyvu,

Before I begin my answer, I must direct your attention to the
disclaimer at the bottom of this page. I must also remind you that
this answer is for informational purposes only, and is not intended to
replace medical advice from a licensed physician.


====================================================================
Question 1:  Would it be medically competent to prescribe a patient
with these symtoms an NSAID, Diclofenac for the leg pain?
====================================================================

According to this Arthritis Central site, it is safe to take NSAIDs,
including diclofenac sodium, concurrently while taking coumadin. The
concern while taking NSAIDs is stomach irritation. Vioxx and Celebrex
are know to be milder on the stomach that diclofenac sodium, however.
?In patients who are taking Coumadin as an anticoagulant, only the
NSAIDs that are the least irritating to the gastrointestinal tract
should be utilized.  COX-2 selective inhibitors are preferable, but it
is still important to monitor the prothrombin times to make sure that
these are not adversely affected.  Also, the patient needs to be
monitored to make sure that there is no gastrointestinal bleeding
while on these medications in combination with an anticoagulant?
http://arthritiscentral.com/html/medsnsaids.htm

Contrary to the above site, this page, from The Newcastle Upon Tyne
Hospitals, says NOT to take NSAIDs, especially diclofen. (Page 5)
http://www.newcastle-hospitals.org.uk/v2/PDF/patientleaflets/Haematology/Large/deep%20vein%20thrombosis.pdf

If the patient in question IS on anticoagulants, this site recommends
avoiding diclofenac (as well as azapropazone, flurbiprofen,
indometacin, phenylbutazone, and piroxicam.
http://www.netdoctor.co.uk/medicines/showpreparation.asp?id=2796

NSAIDs (Non steroidal anti-inflammatory drugs) work by inhibiting
cyclooxygenase, abbreviated as COX, which is needed to produce
prostaglandins. Prostaglandins are responsible for the inflammation
and swelling that induce pain, as well as acting as a stimulant to
platelet formation. NSAIDs are known also as COX-Inhibitors and are
separated by classes. Cox-1, COX-2 recently, COX-3. COX-1 and COX-2
enzymes were discovered as recently as 1989!

 ?However, these COX-2 inhibitors do not decrease platelet aggregation
or thromboxane synthesis while decreasing production of prostacyclin
(an agent which decreases platelet aggregation). Therefore, concerns
have been raised that individuals chronically treated with COX-2
inhibitors are at increased risk for platelet aggregation- associated
adverse cardiovascular events?
http://www.aaaai.org/aadmc/currentliterature/selectedarticles/2003archive/selective_cox2_inhibitors.html

This page focuses on pain management of osteoarthritis but has some
good information on alternative pain relievers.
?Can prolong the half-life of warfarin sodium, so careful monitoring
of prothrombin time is recommended in patients taking warfarin sodium
who subsequently begin higher-dose acetaminophen treatment.
http://www3.aaos.org/research/imca/OAkneeContents/OA_knee_m5_4.htm


About Diclofenac (Voltaren)
?Voltaren (Diclofenac sodium) is a nonsteroidal anti-inflammatory drug
(NSAID) that is used to treat inflammation, mild to moderate pain, and
fever. NSAID?s are called ?nonsteroidal? because they are not related
to the steroid drugs (synthetic drugs that closely resemble cortisol,
a hormone that is naturally produced by the adrenal glands). Steroids
work by suppressing the immune system, whereas NSAID?s work mainly by
preventing the formation of prostaglandins, hormone-like substances
which trigger pain and inflammation.?
?The conventional, first generation NSAID?s like Voltaren etc.
(Diclofenac sodium) work by inhibiting both COX-1 and COX-2 enzymes.
By blocking COX-2 they are effective in relieving pain and
inflammation, but by inhibiting COX-1 they often produce unacceptable
gastrointestinal side effects including diarrhea, bloating, heartburn,
upset stomach (dyspepsia) and ulcers. These first generation NSAID's
show different potencies against COX-1 compared with COX-2. Some, like
ketoprofen, are relatively COX-1 selective; others, like aspirin,
ibuprofen and naproxen, are equally selective; and some like
diclofenac are relatively COX-2 selective.?
http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a699002.html

http://www.vetmedpub.com/cp/pdf/symposium/nov_1.pdf


This Ingenta site refers to an obstetrical study that showed Vioxx to
have a smaller effect on platelet aggregation than diclofenac
?Conclusion: Besides having a smaller effect on platelet aggregation,
one oral dose of rofecoxib 50 mg given before surgery provided
postoperative analgesia similar to that given by three doses of
diclofenac 50 mg and was associated with less use of anti-emetics and
less surgical blood loss in gynaecological surgery compared with
diclofenac.?
http://www.ingenta.com/isis/searching/ExpandTOC/ingenta?issue=infobike://oup/bjaint/2004/00000092/00000004&index=11


?There are controversial results regarding the influence of diclofenac
on hemostasis?
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=411036


?Truly specific COX-2 inhibitors, celecoxib ( Celebrex, Pharmacia
corporation) , and Rofecoxib (Vioxx, Merck) are now commercially
available, and others are currently being researched?

http://www.arthritis.co.za/cox.html


This Medline site recommends   ?tell your doctor and pharmacist what
prescription and nonprescription medications you are taking,
especially other heart medications; antibiotics; aspirin and other
non-steroidal antiiflammatory drugs such as ibuprofen (Advil, Motrin)
and naproxen (Aleve, Naprosyn); cimetidine (Tagamet); medications for
cancer, depression, diabetes, digestive problems, epilepsy, gout, high
cholesterol, and thyroid problems; and vitamins. Many medications
interfere with the effectiveness of warfarin. It is important that you
tell your doctor every medication that you take, including
nonprescription medications. Do not take any new medications without
talking to your doctor.?

http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682277.html


It would therefore seem prudent to take acetominophen (Tylenol),
instead of diclofenac, for leg pain from DVT, or possibly aspirin, but
only if the patient is NOT on coumadin. (I can?t see a DVT patient NOT
taking an anti-coagulant!) Do NOT take aspirin AND coumadin. The
patient?s physician is the best source of information for proper pain
management in a DVT patient, as s/he is familiar with the patients
entire medical history.



=========================================================================
Question 2.  Could increased platlet aggregation worsen or lead to a DVT condition?
=========================================================================
Did know that the knifelets and forklets conglomerate while the
platelets aggregate? ;-)       (I couldn?t resist a bit of hospital
humor!)

The short answer to your question is yes. You want to avoid having
platelets aggregate or clump in DVT patients, as this could
precipitate clot formation. Aspirin, if the patient is NOT on
anticoagulants, is effective in reducing the ?stickiness? of
platelets.

?Platelets begin the formation of blood clots by clumping together (a
process called aggregation). Platelet clumps are then strengthened and
expanded by the action of clotting factors (coagulants) that result in
the deposition of protein (fibrin) among the platelets?
http://www.medicinenet.com/Heart_Attack/page3.htm

As platelets pass through a vein with DVT, they adhere to the injured
area. The platelets that collect then trigger a chain reaction;
thrombin is produced, which produces fibrin strands, the strands clump
together into a web. This web then entraps passing red blood cells and
other platelets, and a clot is born!  Vitamin C is thought to reduce
platelet aggregation, while smoking and consuming sugar may increase
platelet stickiness!
http://www.docguide.com/news/content.nsf/news/8525697700573E1885256BC200721D3E

?Eating foods high in sugar increases the content of serotonin in
platelets. It is known that platelets with increased quantities of
serotonin are more likely to have stickiness. Therefore, it can be
concluded that the use of large quantities of sugar in the diet would
increase platelet stickiness and therefore increase the likelihood of
having intravascular clotting. (Ref. Diabetes 40 (suppl. I):588A May,
1991)?
http://www.ucheepines.org/blood_clotting.htm
http://www-als.lbl.gov/als/science/sci_archive/69platelet.html

You may be also be referring to the platelet aggregation test. A
platelet aggregation test is a way to determine clotting and bleeding
problems. Normal results are  >60% of platelets aggregate with each
agonist used for testing.
http://www.mgh.harvard.edu/labmed/lab/coag/handbook/CO003900.htm

 ?There are many medications that can affect the results of the
platelet aggregation test. The patient should discontinue as many as
possible beforehand. Some of the drugs that can decrease platelet
aggregation include aspirin, some antibiotics, beta blockers, dextran
(Macrodex), alcohol, heparin (Lipo-Hepin), nonsteroidal
anti-inflammatory drugs (NSAIDs), tricyclic antidepressants, and
warfarin (Coumadin).?
http://www.healthatoz.com/healthatoz/Atoz/ency/platelet_aggregation_test.html


There is an animation on this page depicting the blood clotting
process. Click onto the video called ?How a Blood Clot Forms? (Of
course the others are informative too!)
http://www.dvt.net/preventionCenter/animations.jsp?id=27


====================================================================
Question 3. Could changes in prothrombin and and partial
thromboplastin times lead to a worsening or occurance of the DVT
condition?
====================================================================

Pro Time and PTT
The protime (PT) and PTT (Partial thromboplastin time) results
themselves have no bearing on DVT, but a change in the results of a PT
can indicate the need for a coumadin dosage change. The PTT test is
only useful while the patient is on IV heparin. Once a hospitalized
patient comes home, the IV heparin is stopped, and oral coumadin
begins. (Heparin is administered only via IV, as it is not stable in
oral form)

Pro times ARE useful in DVT patients. However, patients taking
coumadin for DVT would be expected to have a longer PT than
non-medicated patients, and this is desirable. The INR is the portion
of the Pro time result that the doctor is interested in, as opposed to
the results. An INR result of  2 to 3 is a target range for a patient
on coumadin for DVT. If the patient is taking too much coumadin, the
INR will be become elevated, indicating the need to decrease the
amount of anti-coagulant medication If the INR gets too low,
indicating that not enough coumadin is being taken, yes, the risk of
aggravating DVT esists. The dose of anti-coagulant therapy is
increased if this occurs.
http://www.nlm.nih.gov/medlineplus/ency/article/000156.htm

INR
The INR (International Normailzed Ratio) was developed, I?m
*guestimating*, about 10 years ago, for the purpose of standardizing
PT  results between labs. As each lab has its own methodology and
normal ranges, a way to correlate results from different labs was
needed. The INR is, simply put, a ratio derived from the patients PT
results, the control results and an internationl standard factor.
http://health.ucsd.edu/labref/P609.html

http://www.newlinemedical.com/pro%20time%20table.html


D-dimer
Another helpful test for monitoring DVT is the D-dimer, sometimes
called Fragment D-dimer or Fibrin degradation fragment,  which is
elevated in DVT patients. D-dimer indicates that there is a there is
clotting and fibrinolysis (clot break down) process occurring in the
circulatory system. The normal range, indicating no DVT or pulmonary
empbolism, for D-dimer is < 0.41 µg/mL

http://www.labtestsonline.org/understanding/analytes/d_dimer/test.html

http://www.medicalpost.com/mpcontent/article.jsp?content=/content/EXTRACT/RAWART/3734/47A.html

http://www.pathology.vcu.edu/clinical/coag/ranges.html

?D-Dimer levels remain elevated in DVT for about 7 days. Patients
presenting late in their course, after clot organization and adherence
have occurred, may have low levels of D-dimer. Similarly, patients
with isolated calf-vein DVT may have a small clot burden and low
levels of D-dimer below the analytic cut-off value of the assay. This
accounts for the reduced sensitivity of the D-dimer assay in the
setting of confirmed DVT.?
Emedicine
http://www.emedicine.com/EMERG/topic122.htm


MD Alert says about the D-dimer test
o?Do not rely solely on a negative D-dimer test to exclude DVT when a
patient has more than one of the characteristics listed above.
Patients with more than one of these factors are considered to be at
higher risk of DVT. For these higher-risk patients, the negative
predictive value of a D-dimer test is only 89%. When D-dimer tests are
negative in such patients, compression leg ultrasound tests should
still be obtained to confirm the absence of DVT.
oConfirm that your laboratory is using an appropriate D-dimer assay.
The assays with the best negative predictive values for DVT are the
SimpliRED and IL-Test.
http://praxis.md/index.asp?page=alertsarchive&news_id=5693&alert=MD



====================================================================
Additional Reading:
====================================================================

An excellent description of the physiology and metabolic pathways of
COX inhibitors.
http://www.emedicine.com/med/topic3096.htm

From DVT net, download several informative documents on DVT.
http://www.dvt.net/preventionCenter/preventionGuides.jsp?id=23

http://www.weissortho.com/glossary/

http://www.spineuniverse.com/displayarticle.php/article2482.html

http://www.healthinaging.org/public_education/pef/deep_venous_thrombosis.php

This site has a good illustration of how NSAIDs work:
http://elfstrom.com/arthritis/nsaids/actions.html


I hope this is the information you were seeking! If any part of my
answer is unclear, or if I have duplicated information you already
had, please request an Answer Clarification, before rating. This will
enable me to assist you further, if possible.

Regards,
crabcakes


Search Terms
DVT NSAIDs
DVT
Thrombolytics
Diclofenac DVT
Nasaids coumadin concurrently
Platelet aggregation
Diclofenac effect platelets
Coagulation labs

Good information.  Thank you very much.

There seems to be a little confusion in the question.  The asker
states that diclofenac increases platelet aggregation.  In normal
doses it actually decreases platelet aggregation.  As stated in the
website which the asker cited, it increases platelet aggregation time,
which is a lab test of how long it takes the platelets to aggregate,
or clump, under specific conditions.  Diclofenac inhibits the
aggregation, and thus increases the amount of time it takes.  In
itself this could be helpful for a patient prone to DVTs, as it would
make them less likely to occur.  However those patients are usually on
anticoagulants, most commonly coumadin (warfarin), and adding
diclofenac or other NSAIDs, such as ibuprofen, or aspirin, could cause
the opposite problem, i.e. inability to clot sufficiently, resulting
in uncontrolled bleeding.  Patients on coumadin are usually followed
closely with lab tests which measure clotting ability and are
sensitive to effects of coumadin dose, other medications, and even
diet.  Thus if the patient is on coumadin it is usually best to avoid
other medications which affect bleeding or can affect coumadin levels
in the blood.  For this reason, it is important for the doctor to be
aware of all medications and monitor for interactions.

One further note, you state the patient has had symptoms of DVT and
wonder if a patient with these symptoms should be put on this
medication.  The first question should be whether the patient has a
DVT or has some other condition which produces the same symptoms.  If
DVT has been looked for and ruled out, then it  shouldn't matter, but
if the patient definitely has DVTs the above info would have to be
carefully considered.  And if the possibility of DVT has not been
investigated and either ruled in or out, that needs to be done before
prescribing medications.

Certainly though, this needs to be brought to the attention of the
doctor doing the prescribing, since it is impossible to provide
complete and accurate advice without the full information, including
examination, etc.

Thank you for the stars!

Regards,
crabcakes