Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in...
-
Upload
justine-lakeman -
Category
Documents
-
view
221 -
download
0
Transcript of Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in...
![Page 1: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/1.jpg)
Rami Khouzam, MD
![Page 2: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/2.jpg)
Interesting Historical Facts
(Blood Transfusion) 1492: Pope Innocent VIII, in
Rome, had an apoplectic stroke and went into a coma. His physician advised a Blood transfusion. Employing crude methods, the Pope did not benefit and died by the end of that year
1665: 1st recorded successful blood transfusion occurred when physician Richard Lower managed to keep dogs alive after transfusing blood from other dogs
Blundell's blood transfusion apparatus, 19th century
![Page 3: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/3.jpg)
1667: Jean-Baptiste Denis in France reported successful transfusions from sheep to humans
1678: Transfusion from animals to humans was deemed to be unsuccessful, and was outlawed by the Paris Society of Physicians because of reactions, many resulting in death Blood transfusion apparatus,
American 1920 1955
![Page 4: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/4.jpg)
1818: James Blundell, a British obstetrician, performed the first successful transfusion of human Blood to a patient for the treatment of postpartum hemorrhage. Using the patient's husband as a donor, he extracted a small amount of Blood from the husband's arm and, using a syringe, he successfully transfused the wife
1873-1880: Physicians in the US are documented to have transfused milk (from cows and goats) to humans Bottle from blood transfusion
apparatus 1914-1918
![Page 5: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/5.jpg)
1901: Karl Landsteiner an Austrian physician, and the most important individual in the field of Blood transfusion, documented the first three human Blood groups A, B & O
1908: French surgeon Alexis Carrel devised a way to prevent Blood clotting. His method was joining an artery in the donor, directly to a vein in the recipient with surgical sutures. He first used it to save the life of the son of a friend, using the father as donor. This procedure, not feasible for Blood transfusion, paved the way for successful organ transplantation, for which Carrel received the Nobel Prize in 1912
Alexis Carrel
![Page 6: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/6.jpg)
1932: The first facility functioning as a Blood bank was established in a Leningrad Russia hospital
1970s: blood transfusion had become the basis of much of modern medicine and voluntary blood donors now play an important role as co-health workers with medical professionals around the world
![Page 7: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/7.jpg)
Index Case 46 yo caucasian gentleman with HTN HIV + and HCV +
S/P AVR with a bioprosthetic valve (Carpentier Edwards) in 2001, following fungal endocarditis
Presents for a regular clinic F/U
Currently doing fine, denies any C/O
![Page 8: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/8.jpg)
Medications:
- Coumadin 9.5 mg qd - Atenolol 25 mg qd - Zantac - HIV meds: Zerit/ Epivir/ Kaletra
![Page 9: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/9.jpg)
PE: (Pertinent)
Neck: No JVD, No Bruit
CVS: S1S2 Regular rhythm @ 60 Systolic murmur II/VI over LSB, No g,r
Lungs: CTA bilat., No w, c, r
Ext: No e, c, c
![Page 10: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/10.jpg)
Medications:
- Coumadin 9.5 mg qd - Atenolol 25 mg qd - Zantac - HIV meds: Zerit/ Epivir/ Kaletra
![Page 11: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/11.jpg)
What’s missing?
![Page 12: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/12.jpg)
![Page 13: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/13.jpg)
Clinical Use
Market share
Mechanical60%
Bio40%
![Page 14: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/14.jpg)
>60.000 cardiac valve replacement/ year in the US
Mechanical valves: expected to last 20-30 years
Tissue valves: 30% of heterograft 10-20% of homograft
fail in 10-15 yrs Vongpatansin, et al. NEJM 1996
![Page 15: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/15.jpg)
Mechanical Valves
1- Starr-Edwards caged-ball
2- Medtronic-Hall tilting-disc
3- St. Jude Medical bileaflet
4- CarboMedics bileaflet
5- Omniscience tilting-disc
6- Bjork-Shiley (previously used in the US, continued to be used in other areas)
![Page 16: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/16.jpg)
Tissue Valves(Biologic)
Heterograft
Porcine
1- Carpentier-Edwards porcine
2- Medtronic-Hancock porcine
3- Biocor 4- Intact
5- Mosaic
Bovine Pericardial
Carpentier-Edwards pericardial
![Page 17: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/17.jpg)
Tissue Valves
Homograft
Cryopreserved aortic homograft
Autograft
Pulmonary autograft
![Page 18: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/18.jpg)
![Page 19: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/19.jpg)
Pathophysiology and mechanisms of Thrombosis
(+) Charged surfaces favor thrombus formation
(-) Charged surfaces : thromboresistant
Artificial surfaces with a net + charge: highly adsorptive of plasma proteins (& blood cells) e.g Fibrinogen (1st. Protein)
![Page 20: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/20.jpg)
Virchow’s triad/ tetrad
1- Vascular endothelial surface abnormality
2- Stasis of blood flow 3- Abnormalities within circulating blood
4- Artificial surface
![Page 21: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/21.jpg)
Components of Virchow’s vary according to:
a) Etiology, presence, duration, and extent of VHD
b) Prosthetic materials used
c) Position of valvular insertion (aortic, mitral, both)
![Page 22: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/22.jpg)
Aortic valve: Blood flow typically rapid Acceleration & high shear stress
- platelets activation - RBCs membranes damage - ADP release - platelet activation and aggregation ( contribution of coagulation factors 2ry)
![Page 23: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/23.jpg)
![Page 24: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/24.jpg)
Mitral valve:
Blood flow comparatively slow (esp. if MS, LAE, MR and LV dilatation)
stasis and contact of coagulation factors with damaged endocardial or prosthetic surface
(contribution of platelets 2ry)
![Page 25: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/25.jpg)
![Page 26: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/26.jpg)
Natural history of PHV thrombosis... Potential fate: 1- Partial/ complete lysis 2- Organization: platelets, fibrin & neutrophils (48 hrs) monocytes (phagocytes:engulfing
RBCs & platelets) (1st week) SMCs & CTM (2nd week) 3- Re-endothelialization
![Page 27: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/27.jpg)
Dream valve in Dreamland
Ideal prosthetic valve: - Normal hemodynamic profile - Lives forever - Nonthrombogenic
(Ideal valve … like Ideal husband Still DOES NOT EXIST)
![Page 28: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/28.jpg)
Tissue-Engineered Heart Valve (TEHV) In Study...
With human marrow stromal cells on the trileaflet heart valves fabricated from rapidly absorbable polymers
Hoerstrup SP, et al. Circ. 2002
Cultivated human venous endothelial cells onto cadaver human allografts (homografts) that had been preserved in antibiotic-enriched Earle’s medium 1999 and decellularized
Cebotari S, et al. Circ. 2002
![Page 29: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/29.jpg)
Aortic valve interstitial cells to repopulate aortic valve leaflets that had been decellularized aortic valve leaflets
Morphological and mechanical properties similar to human native heart
Bertipaglia, et al. Ann. Thorac Surg. 2003
![Page 30: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/30.jpg)
![Page 31: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/31.jpg)
General Considerations1- Age
2- Anticoagulation
3- Child-bearing potential
4- Chamber/annulus size
5- Concomitant CABG
(tissue may be better)
6- Psychosocial
7- Patient preference
![Page 32: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/32.jpg)
![Page 33: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/33.jpg)
Mechanical Valves
I Expected long life span
I Mechanical valve in another position
IIa Renal failure, hemodialysis,
hypercalcemia
IIa Requiring warfarin for risk factors
IIa AVR < 65 y, MVR < 70 y
IIb Thrombosed tissue valve replacement
III CI or unwillingness to take warfarin
ACC/AHA Guidelines 2001
![Page 34: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/34.jpg)
Tissue Valves
I CI or unwillingness to take warfarin
I AVR > 65 y and no risk factors
IIa Anticipated noncompliance with coumadin
IIa MVR > 70 y and no risk factors
IIb Thrombosed mechanical valve replacement
IIb < 65 y
III Renal failure, hemodialysis, hypercalcemia
III Growing adolescentsACC/AHA Guidelines 2003
![Page 35: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/35.jpg)
![Page 36: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/36.jpg)
![Page 37: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/37.jpg)
General
Risk factors
1- Atrial fibrillation
2- Previous thromboembolism
3- Hypercoagulable state
4- LV dysfunction (controversial)
![Page 38: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/38.jpg)
The History of Warfarin Farmers in the northern prairie states of
Canada and the USA began planting sweet clover plants imported from Europe
Although the sweet clover proved to be nutritious, it also brought a fatal disease of cattle herds
Sweet clover disease: affected cattle: relentless, spontaneous bleeding
![Page 39: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/39.jpg)
Coumadin (Warfarin): How Farmers With Moldy Hay and An Attempt at Suicide
Transformed the Face of Medicine
The name Warfarin was created from Wisconsin Alumni Research Foundation and the rin from the word coumarin
According to the Wisconsin Alumni Research Foundation, one snowy morning in 1933 a farmer named Ed Carlson showed up at the lab of Dr. Karl P. Link
![Page 40: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/40.jpg)
The farmer had with him a dead calf and a milk can of blood that would not coagulate
The farmer had been feeding his cattle sweet clover hay. Storage had caused the sweet clover hay to spoil and eating it had killed the calf
Link and his colleagues discovered that coumarin in the hay was being chemically transformed into dicoumarol
![Page 41: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/41.jpg)
1921: Schofield, a veterinary pathologist in Alberta, reported that the disease was caused by consumption of spoilt sweet clover hay
![Page 42: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/42.jpg)
1940: The mystery of why spoilt hay caused the disease was solved by Karl Paul Link & his co-workers: in mouldy hay, coumarin is oxidised to 4-hydroxycoumarin and then coupled with formaldehyde and another coumarin moiety to form dicoumarol, an anticoagulant
![Page 43: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/43.jpg)
1941: Dicoumarol was patented and was therapeutically used as an anticoagulant
![Page 44: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/44.jpg)
1951: a navy recruit unsuccessfully attempted suicide with 567 mg of warfarin. His surprising full recovery induced research into the anticoagulant potency of warfarin in humans
![Page 45: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/45.jpg)
1954: Warfarin was introduced commercially and Clinicians quickly discarded dicoumarol in favor of "rat poison"
In that same year: President Eisenhower was treated with warfarin following a heart attack
Today: warfarin is the standard treatment for long term oral anticoagulant therapy
![Page 46: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/46.jpg)
Link: "My rule is, never overstate your case in print. It's better to understate it and let the facts speak for themselves."
![Page 47: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/47.jpg)
Rat Poison…
or
Wonder Drug?
![Page 48: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/48.jpg)
Brand names Coumadin® (USA) and Marevan® (UK) and as its generic version Warfarin Sodium
It is sold as colored tablets, each color indicating the strength of the dose
![Page 49: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/49.jpg)
By the way…
If you can't remember the name Warfarin just use the chemical name:
4-Hydroxy-3-(3-oxo-1-phenyl-butyl)-chromen-2-one
![Page 50: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/50.jpg)
Another large application as rat poison
Effective in controlling Norway (Brown) rats and house mice
Rodents continue to consume it until its anticlotting properties have produced death through internal haemorrhaging
![Page 51: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/51.jpg)
![Page 52: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/52.jpg)
![Page 53: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/53.jpg)
Warfarin is a vitamin K antagonist. It produces its anticoagulant effect by interfering with the vitamin K cycle
It interacts with the KO reductase enzyme so that vitamin KO cannot be recycled back to vitamin K
This leads to a depletion of vitamin KH2, limiting the γ- carboxylation of the coagulation factors
![Page 54: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/54.jpg)
Efficacy 1983: A system of standardising the PT in
oral anticoagulant control was introduced by the World Health Organisation (WHO)
The INR is calculated:
INR = (patient PT / control PT) ISI
ISI = International Sensitivity Index and is the correction factor which includes effects of the reagent used
![Page 55: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/55.jpg)
Interactions with other drugs: Drugs which potentiate the anticoagulant
effect include anabolic steroids, cimetidine, fluconazole, miconazole, metronidazole, propanolol, tetracycline, flu vaccine, aspirin & Cranberry.
Other drugs inhibit the action of warfarin and include barbiturates, rifampin, carbamazepine, cholestyramine and even high-vitamin K-content foodstuff
![Page 56: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/56.jpg)
Side Effects
Hemorrhage
Necrosis of the skin or other tissues
Purple Toes Syndrome
![Page 57: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/57.jpg)
Other adverse reactions: fever, urticaria, taste perversions, rash, dark urine, sores in mouth or throat & priapism
Pregnancy: relatively contraindicated. Fatal hemorrhage to fetus in utero & birth malformation ??
Narrow Therapeutic Range (NTR) drug
![Page 58: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/58.jpg)
The Future Alternatives: acenocoumarol (nicoumalone)
& phenindione; very rarely used
Warfarin (branded or generic) remains the most widely used oral anticoagulant
Coumadin achieved sales of over $400 million in 1999. For the last 50 years, warfarin has dominated the market of oral anticoagulants
![Page 59: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/59.jpg)
New drug Exanta (Ximelagatran) by AstraZeneca. The first investigational oral anticoagulant to reach Phase III trials in more than 50 years
Works by interfering with thrombin: Direct Thrombin Inhibitor (DTI)
Avoids stringent dietary restrictions or the need for constant laboratory tests to ensure safe levels of medicine. Fewer interactions with food and other drugs
![Page 60: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/60.jpg)
Some analysts believe it could become a $3 billion-a-year drug
Ximelagatran: Currently in clinical trial
DVT: Prophylaxis and treatment Arch Int. Med. 2001
Atrial fibrillation: prevention of stroke Post-MI: 2nry. Prophylaxis
ESTEEM, Lancet 2003
![Page 61: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/61.jpg)
"If Exanta is approved, I think people taking Coumadin (warfarin) will switch to it and that Coumadin will slowly fade away after 60 years on the market," said Dr. Jack Ansell, a researcher from Boston University School of Medicine, in a Reuters interview
![Page 62: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/62.jpg)
So are we seeing the last days of warfarin?
Only the future will tell...
![Page 63: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/63.jpg)
Recommendations
From the 6th ACCP Consensus Conference
![Page 64: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/64.jpg)
Management of Patients with Prosthetic Heart Valves
Anticoagulation
A) Mechanical Valves: Systemic embolization (Mitral valve 2 x risk of Aortic valve)
No anticoagulation: 4.0% per patient per year Aspirin: 2.2% Warfarin: 0.7 to 1.0%
Cannegieter, SC et al. NEJM 1995
![Page 65: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/65.jpg)
Mechanical Valves
First 3 months:
INR 2.5-3.5
After 3 months: Aortic:
Bileaflet or Medtronic Hall: INR 2-3
Risk Factor or other valves: INR 2.5-3.5 Mitral: INR 2.5-3.5
![Page 66: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/66.jpg)
B) Bioprosthetic Valves: Major advantage is freedom from
anticoagulation
However, low level anticoagulation (INR 2.0-3.0) is recommended in first 3 months to lessen thromboembolic complications arising from factors such as lack of endothelialization of the suture line during the early postoperative period
![Page 67: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/67.jpg)
Tissue Valves
First 3 months:
INR 2.5-3.5 (sometimes not done for
aortic)
After 3 months:
No risk factor: None
Risk factor + aortic: INR 2-3
Risk factor + mitral: INR 2.5-3.5
![Page 68: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/68.jpg)
Warfarin + Aspirin
Recommendations from the 6th Consensus Conference on Antithrombotic therapy:
Mechanical valve + thromboembolic event despite adequate anticoagulation
Caged ball or caged disk valve
![Page 69: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/69.jpg)
Mechanical valves + additional risk factors: Prior thromboembolism Atrial fibrillation Large left atrium Coronary heart disease Left atrial thrombus Ball valve > 1 mechanical prosthetic valve Mechanical prosthesis in the mitral position
Stein, PD, Alpert, JS, et al. Chest 2001
![Page 70: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/70.jpg)
PHV in Nonagenarians Study: 35 (aged 90-<100 years old) had PHV
between 1986 & 2000
30-day mortality: 17.1%
2-year survival: 74.3%
No operative mortality
![Page 71: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/71.jpg)
At a mean of 2.53 years (range. 0.16-7.1 years) after PHV survival was 81%
Bachetta MD, et al. Ann Thorac. Surg. 2003
![Page 72: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/72.jpg)
In 2000, nonagenarians in the US totaled 1.6 million and centenarians numbered 72.000
By 2050 numbers expected to be 8.8 million and 1.1 million respectively
![Page 73: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/73.jpg)
PHVs and Pregnancy
Mechanical PHVs: incidence of warfarin embroyopathy is low (average 3.9%)
0-12 wks: unfractionated heparin
13-38 wks: Warfarin OK
39-40 wks: unfractionated heparin
![Page 74: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/74.jpg)
Ten studies: 427 pregnancies, incidence was zero
FDA: warning about the use of low-molecular-weight heparin during pregnancy
Pregnancy & bioprosthesis: associated with SVD (structural valve deterioration); 24% during or shortly after pregnancy
SVD at 10 years was 55-76% Hung L. et al. Circ. 2003
![Page 75: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/75.jpg)
Summary Mechanical PHV: Coumadin ASA (alone): not enough Thrombogenicity: caged ball >tilting disk > bileaflet Thrombogenicity: Mitral area > Aortic area High risk pts: Coumadin + ASA (81- 100mg) Bioprosthetic valves: Coumadin x 3 months & > x risk factors New thrombin inhibitors (Ximelagatran) might overthrown
Coumadin
![Page 76: Rami Khouzam, MD. Interesting Historical Facts (Blood Transfusion) Z 1492: Pope Innocent VIII, in Rome, had an apoplectic stroke and went into a coma.](https://reader036.fdocuments.net/reader036/viewer/2022081514/56649c9e5503460f9495eb23/html5/thumbnails/76.jpg)