CONTACTS 

SUBJECTS
Anticoagulation Therapy Pulmonary Emboli Blood Clots Lungs Enlarged

3903 -
3903 -    ..
3904 - Summary/Objective
3905 -
390501 - Follow up ref SDS 3 KW45, ref SDS 2 TZ4I.
390502 -
390503 - Millie had a close call with the new prescription for Diflucan that is
390504 - experimenting to treat spread of rash on the left breast to the right
390505 - breast.  Diflucan evidently conflicts with Coumadin prescribed to
390506 - treat pulmonary embolism. ref SDS 0 XF77  This conflict increased INR
390507 - above 6 which presents a higher risk for hemorraging. ref SDS 0 4O5H
390508 - Instructions are to pause Coumadin for 3 days, with minor diet changes
390509 - increasing green vegetables and salads, ref SDS 0 4O67, then get
390510 - another blood test to see if this corrects the problem. ref SDS 0 XF6M
390511 -
390512 -     [On 070301 UCSF blood test on 070301 reports INR 2.5, but
390513 -     indicates range .9 - 1.2, which makes 2.5 more than double the
390514 -     target diagnostic, which seems equivalent of INR over 6 on
390515 -     Kaiser's scale where INR 3 is the upper target range. ref SDS 5
390516 -     R33I
390517 -
390518 -
390519 -
390521 -  ..
3906 -
3907 -
3908 - Progress
3909 -
390901 - INR 6.4 Coumadin Change Treatment Protocol Reduce Risk Hemoraging
390902 -
390903 - Gloria left a message saying that diagnostics on Millie's blood test
390904 - this morning show INR 6.4.
390906 -  ..
390907 - CA 15-3 cancer marker tested today along with INR, following up
390908 - meeting with the doctor on 061208, ref SDS 3 087J, results were not
390909 - reported in Gloria's message.
390910 -
390911 -        [On 061218 Millie asks doctor for results of the test today.
390912 -        ref SDS 4 FO9H
390914 -         ..
390915 -        [On 061218 Doctor reports that blood test results on CA 15-3
390916 -        for 061214, and later on 061218 are still pending. ref SDS 4
390917 -        HY5L
390919 -  ..
390920 - INR 6.4 is more than twice higher than any prior blood test in
390921 - Millie's patient history for the past 3 years.
390923 -  ..
390924 - Gloria said that INR increases above 6 is a danger zone for risk of
390925 - continual bleeding (hemorraging), which requires immediate treatment
390926 - to avoid death.
390927 -
390928 -        [On 061218 Millie notifies doctor of INR increased on Diflucan.
390929 -        ref SDS 4 5M5Y
390931 -         ..
390932 -        [On 061218 Doctor advises Millie to stop taking Diflucan.
390933 -        ref SDS 4 NT6J
390935 -         ..
390936 -        [On 100202 0301 Millie's INR 5.8 2nd highest in patient history
390937 -        risks hemoraging and death, ref SDS 7 K069, slipped through the
390938 -        cracks again due to conflicts in medications that were
390939 -        overlooked. ref SDS 7 LH6T
390941 -  ..
390942 - Millie should stop taking Coumadin for 3 days until Sunday, and then
390943 - take only 2 MG, rather the usual 4.
390945 -  ..
390946 - Millie needs another blood test on Monday, 061218 to review progress
390947 - bringing INR under control between 2.0 and 3.0.
390949 -  ..
390950 - Gloria cautioned Millie to be very careful to avoid doing anything
390951 - that may cause bleeding.  If bleeding occurs, and does not stop within
390952 - 5 minutes, then Millie must go for immediate treatment at the
390953 - Emergency Room Department.
390955 -  ..
390956 - Gloria requested feedback to verify Millie got the message and
390957 - verify accurate understanding of communications on performing changes
390958 - to treatment protocol.
390959 -
390960 -        [On 070307 Gloria indicated that feedback is an important
390961 -        process to authenticate accuracy of communications at Kaiser.
390962 -        ref SDS 6 ML3H
390963 -
390965 -  ..
3910 -
3911 -
3912 - 1537
3913 -
391301 - Millie called back and advised she got Gloria's message, per above.
391302 - ref SDS 0 4O5H
391304 -  ..
391305 - Gloria recommends eating green vegatables and salads, cabbage,
391306 - broccili, etc., the next few days, which will help lower the high INR
391307 - by thickening the blood.
391309 -  ..
391310 - Gloria advised that sudden increase in INR above the danger zone was
391311 - caused by the new treatment with Diflucan (fluconazole) prescribed on
391312 - 061208 to experiment diagnosing and treating spread of rash on the
391313 - left chest region to the right breast. ref SDS 3 KW45  Evidently
391314 - Diflucan (fluconazole) treatment interacts with Coumadin (warfarin) to
391315 - compound blood thinning that could cause hemorraging, ref SDS 0 4O9K,
391316 - and so requires timely intervention when INR rises above 6,
391317 - ref SDS 0 EM69, as reported today. ref SDS 0 4O5H
391319 -  ..
391320 - Risks and procedures to avoid conflicting prescriptions was recently
391321 - discussed with the primary care physician, citing prior problems
391322 - reported on 061020. ref SDS 1 YQ7L  Case study on 061024 indicates
391323 - better technology and practices can help avoid conflicts between
391324 - medications. ref SDS 2 NU5O  During the meeting on 061208, the doctor
391325 - described a new computer program Kaiser is using to avoid problems
391326 - like today by giving everyone timely notice of changes to medications.
391327 - ref SDS 3 C75F  On 060124 Gloria discussed challenges of timely notice
391328 - on such a great many critical details that occur in medical practice.
391329 - ref SDS 2 TZ4I
391330 -
391331 -        [On 100202 0301 Millie's INR 5.8 2nd highest in patient history
391332 -        risks hemoraging and death, ref SDS 7 K069, slipped through the
391333 -        cracks again due to conflicts in medications that were
391334 -        overlooked. ref SDS 7 LH6T
391336 -  ..
391337 - Gloria feels there may be some implementation issues rolling out a new
391338 - system.  She plans to ask Kaiser's pharmacy for timely notice to the
391339 - Coagulation Treatment Clinic when treatments are prescribed that
391340 - affect INR, as occurred today, per above. ref SDS 0 4O5H
391341 -
391343 -  ..
391344 - Research on the Internet...
391345 -
391346 -        American Family Physician, February 1, 1999
391347 -
391348 -              http://www.aafp.org/afp/990201ap/635.html
391350 -         ..
391351 -        Warfarin Therapy: Evolving Strategies in Anticoagulation
391352 -        JON D. HORTON, PHARM.D., and BRUCE M. BUSHWICK, M.D.
391353 -        York Hospital, York, Pennsylvania
391355 -         ..
391356 -        Warfarin (Coumadin) is the most frequently prescribed oral
391357 -        anticoagulant, the fourth most prescribed cardiovascular agent
391358 -        and the overall eleventh most prescribed drug in the United
391359 -        States, with annual sales of approximately $500 million.
391361 -         ..
391362 -        Approximately five days are required for the antithrombotic
391363 -        effect of warfarin to take effect.
391365 -         ..
391366 -        Even though four decades have passed since warfarin was first
391367 -        used to prevent thromboembolic disease, studies continue to
391368 -        discover and refine techniques that make therapy with this
391369 -        agent safer and more effective. Because warfarin has a complex
391370 -        dose-response relationship, family physicians need to
391371 -        understand the drug's pharmacology. This article presents the
391372 -        rationale for published dosing recommendations and suggests
391373 -        practical guidelines for the use of warfarin therapy.
391375 -         ..
391376 -        Warfarin has been shown to prevent 20 strokes for every
391377 -        bleeding episode associated with its use.
391379 -         ..
391380 -        The goal of anticoagulant therapy is to administer the lowest
391381 -        possible dose of anticoagulant to prevent clot formation or
391382 -        expansion.
391384 -         ..
391385 -        Pharmacology
391387 -         ..
391388 -        Warfarin is an antagonist of vitamin K, a necessary element in
391389 -        the synthesis of clotting factors II, VII, IX and X, as well
391390 -        as the naturally occurring endogenous anticoagulant proteins C
391391 -        and S. These factors and proteins are biologically inactive
391392 -        without the carboxylation of certain glutamic acid residues.
391393 -        This carboxylation process requires a reduced vitamin K as a
391394 -        cofactor. Antagonism of vitamin K or a deficiency of this
391395 -        vitamin reduces the rate at which these factors and proteins
391396 -        are produced, thereby creating a state of anticoagulation.
391398 -         ..
391399 -        Therapeutic doses of warfarin reduce the production of
391400 -        functional vitamin K-dependent clotting factors by
391401 -        approximately 30 to 50 percent. A concomitant reduction in the
391402 -        carboxylation of secreted clotting factors yields a 10 to 40
391403 -        percent decrease in the biologic activity of the clotting
391404 -        factors. As a result, the coagulation system becomes
391405 -        functionally deficient.
391407 -         ..
391408 -        TABLE 3
391409 -        Selected Warfarin-Drug Interactions
391411 -  ..
391412 - This is a long list of perhaps 40 drugs or classes of drugs with minor
391413 - to major interaction with warfarin (Coumadin), including...
391415 -         ..
391416 -        Antifungal agents
391417 -
391418 -           Severity:       Major
391419 -           Onset:          Delayed
391420 -           Evidence:       Good
391422 -            ..
391423 -           Mechanism:      Fluconazole (Diflucan), ketoconazole
391424 -                           (Nizoral) and miconazole (Monistat)
391425 -                           decrease warfarin metabolism
391427 -            ..
391428 -           Management of   Monitor INR when azole antifungals are
391429 -           Interaction     added or withdrawn.
391431 -  ..
391432 - Another article....
391433 -
391434 -        Australian Prescriber (2001;24:86-9)
391435 -
391436 -              http://www.australianprescriber.com/magazine/24/4/86/9/
391438 -         ..
391439 -        Management of over-anticoagulation
391440 -
391441 -        Over-anticoagulation increases the risk of haemorrhage. The
391442 -        first step in managing this problem is to identify the cause.
391443 -        Common causes include starting or stopping an interacting
391444 -        medication, deteriorating liver function, and patient error
391445 -        (such as taking the wrong dose or confusing different strength
391446 -        tablets). Many of these causes are preventable.
391448 -         ..
391449 -        The approach to a raised INR should be individualised, paying
391450 -        attention to the indication for the warfarin, the patient's
391451 -        risk of bleeding and whether it is safe to continue therapy at
391452 -        all. Some patients need to be admitted to hospital, while
391453 -        others just need to miss a dose of warfarin.
391455 -         ..
391456 -        Guidelines for managing over-anticoagulation (Table 5) are
391457 -        based on the recently published recommendations from the
391458 -        Australasian Society of Thrombosis and Haemostasis.10 The
391459 -        half-life of vitamin K is shorter than that of warfarin, so
391460 -        the INR may rebound 24-48 hours after giving vitamin K. The
391461 -        intravenous preparation of vitamin K can be administered
391462 -        orally or subcutaneously with equal efficacy, and these routes
391463 -        are usually safer and more convenient in patients who are not
391464 -        actively bleeding.
391466 -         ..
391467 -        Guidance When Patient is Not Bleeding
391469 -         ..
391470 -        INR 4 - 5.9      Withhold warfarin and measure INR next day
391472 -         ..
391473 -        INR 6 - 9        Vitamin K 1 - 2.5 mg orally or subcutaneously.
391474 -                         The intravenous preparation may be given
391475 -                         orally or subcutaneously with safety and
391476 -                         efficacy.  Not all community pharmacies have
391477 -                         the intravenous formulation of vitamin K and
391478 -                         it may be worth keeping a supply in the
391479 -                         practice rooms. (Avoid intramuscluar
391480 -                         injections of vitamin K to prevent local
391481 -                         injection side bleeding which also reduces
391482 -                         bioavailability.)
391484 -                          ..
391485 -                         Recheck INR next day.
391487 -         ..
391488 -        INR >9           Hospitalize
391489 -
391490 -                         Fresh frozen plasma 2 units.  This may be
391491 -                         given with a factor II, VII, IX concentrate.
391492 -                         Fresh frozen plasma and concentrates of
391493 -                         clotting factors are blood products and may
391494 -                         carry a small risk of viral contamination.
391495 -
391497 -         ..
391498 -        Patient Bleeding Moderate to Severe
391500 -         ..
391501 -        INR >1.5         Vitamin K 5 - 10 mg intravenously
391502 -
391503 -                         Fresh frozen plasma 2 units immediately
391504 -
391505 -                         Recheck INR after 6 - 8 hours and then daily
391506 -                         for 3 days (may need further vitamin K if INR
391507 -                         rises)
391508 -
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