notes by dr Claudio Italiano
The therapy with oral anticoagulants is indicated in the prevention of thromboembolic risk in certain diseases and / or particular conditions, since it has been seen that this treatment leads to a reduction in the risk of embalming for the patient of embolic events, in fact. In other words, the formation of clots is avoided which, starting in the circulation (emboli), can cause obstruction in arterial vessels with damage (eg ictus cerebri). There are also conditions that are associated by rule with a high thromboembolic risk, for example in the operated patient of valvular prosthesis, especially if these are old mechanical valves that could determine the risk of embolism. There are Centers for the surveillance of oral anticoagulant therapy that must prescribe it and monitor patients.
Generally, access to the clinic after a blood sampling and the INR or Normalized Ratio, ie a universal index to measure the coagulability of the patient's blood, must remain in a range (therapeutic range) in general between 2 and 3, ie partially scoagulated, while in the subject not subject to treatment the value of the INR is given to 1. In the event that this goes back to values of 6-7, there is a real risk of bleeding and the patient should be treated with anti-haemorrhagic vitamin K (konakion drops for example).
The drug for TAO, that is, for the treatment with oral anticoagulants works, in fact, antagonizing the action of vitamin K, diet of patients with TAO) which is the vitamin responsible for coagulation, which is important in the liver in the synthesis (construction) of coagulation factors.
These drugs work by blocking the reduction of Vitamin K-epoxide to Vitamin K in the hepatocytes by competitive inhibition of the enzyme epoxide-reductase. In this way the gamma-carboxylation of factors II, VII, IX, X, already synthesized by liver cells, is prevented, carboxylation which is essential for their biological activity. This effect is proportional to the dose of drug taken, given the many other biological and clinical conditions.
The patient who uses oral anticoagulants should know
1. In case of doubt, never hesitate to ask the Reference Center.
2. Always carry a card with you, among the documents, that clearly indicates
that you use oral anticoagulants.
3. Do not take medicines (including herbal medicine) without first talking to
your doctor or pharmacist, remembering that you use anticoagulants.
Avoid intramuscular injections.
4. Take the oral anticoagulant at the same time (about an hour before dinner or
about 3 hours after dinner).
5. Adopt a certain system so as not to confuse you in taking the drug (for
example, mark on the calendar the dose to be taken in the following days and
check immediately after taking the drug). You can choose the system that suits
you best, but it must be safe!
6. Always respect the times prescribed between a check and the other (if you "jump"
check the risk of problems increases).
7. Follow the diet you prefer, but be consistent in the use of the foods listed
in the following table.
8. Avoid sports or risky activities due to trauma or injury.
9. In case of minor bleeding, apply a strong pressure with a clean gauze or
gauze to stop or reduce bleeding (if nasal bleeding forcefully compress the tip
of the nose with two fingers for at least 3-4 minutes of watch and then wait
before blowing off your nose). If bleeding seems important to go to the
emergency room; if bleeding persists without being important contact your doctor
or go to the emergency room; if the bleeding stops easily communicate the fact,
however, without urgency, to the doctor.
10. Notify the doctor in case of:
a) very dark or reddish urine,
b) blackish stools,
c) appearance of "stomach disorders" not previously present,
d) menstruation clearly more abundant than usual.
dieta per la tao
The patient must take a diet without significant variations in the vit content.
K; in case of important changes in eating habits (eg becoming vegetarian), the
doctor must be informed in advance.
To avoid parsley (allowed only as "ornament"), savoy. Attention to broccoli,
sprouts, cabbage, spinach, variations> 100 g turnip greens, shoots, lettuce.
Attention for asparagus, avocado, peas, lentils, soybeans, considerable
variations other green salad, liver
Oral anticoagulant drugs currently available in Italy: characteristics and their
choice. The dicumarolic derivatives with anticoagulant activity currently
available in Italy are: a) sodium warfarin [3- (a-acetonylbenzyl)
-4-hydroxychumarin], (COUMADIN C r i n o s Industry Farmacobiologica SpA, Como,
5 mg tablets);
b) acenocoumarol [3- (a-acetonyl - p - nitrobenzyl) - 4 - hydroxic umarina], [SINTROM
Ciba-Geigy SpA, Saronno (VA)], 4 mg tablets and, from June 1995, 1 mg tablets .
Cardiac valvular prostheses: Chronic treatment with AO significantly reduces the
risk of embolism in patients with valvular heart prostheses.
Mechanical Prostheses: For patients with prosthetic valve prosthetics an endless
treatment with INR between 3 and 4.5 is recommended.
For patients at high risk of bleeding (such as those above 65 years or with a
history of gastrointestinal bleeding, renal failure, etc.), a therapeutic range
of INR between 2 and 3 has been proposed.
Biological Prostheses: In patients with biological implants, treatment with AO
(INR 2-3) is generally recommended for the first three months after surgery, a
period in which the incidence of embolic phenomena is highest. Instead, the TAO
should be continued in patients with chronic atrial fibrillation, presence of
intra-atrial thrombi at the time of surgery or embolism during treatment; in
this last case a continuation of the TAO for 12 months is recommended (INR 2-3).
Heart valve diseases. For these diseases the TAO is recommended with INR between
2 and 3. However, some clarifications are necessary. Mitral prolapse does not
require any antithrombotic therapy unless associated with atrial fibrillation or
a history of embolism. Similarly, uncomplicated aortic valvulopathies do not
require any prophylaxis.
Cardiac endocavitary thrombosis. Regardless of the associated pathology, in case
of thrombosis of the cardiac cavities the TAO (INR 2-3) is indicated for all the
time in which the thrombosis is detectable. Following the recent technical
development of echocardiography (via transesophageal)
Atrial fibrillation (FA)
A) In the FA associated with valvulopathy the indication to the TAO is mandatory.
INR is recommended between 2 and 3 but if embolic episodes occur during a
correct treatment, the combination of aspirin (100 mg / day) or dipyridamole
(400 mg / day) is indicated in case of aspirin intolerance.
B) TAO with INR 2-3 in the absence of haemorrhagic risk is indicated in the
patient with non-valvular AF between 65 and 75 years. In subjects over 75 years
of age with additional thromboembolic risk factors (diabetes, arterial
hypertension, heart failure, left atrial dilatation, left ventricular systolic
dysfunction), TAO is indicated with INR 2-3.
C) As far as paroxysmal AF is concerned, there are no specific studies on large
cases regarding embolic risk. However, a recent collaborative analysis of the 5
main studies available in non-valvular AF indicates that there is no difference
in the risk of stroke among patients with paroxysmal and chronic AF. For this
reason the indications of point B) can also be used for paroxysmal AF.
D) Recently occurring atrial fibrillation (FA) to undergo electrical or
pharmacological cardioversion
Systemic embolism is the most serious complication of FA cardioversion. Anticoagulation is indicated when the arrhythmia has arisen for more than 48-72 hours. In emergency conditions, heparin is used in anticoagulant doses followed by TAO. In the election, the TAO (INR 2-3) is performed for 3 weeks before cardioversion. Treatment should be continued for at least 3-4 weeks after cardioversion because the resumption of atrial contractility may require, sometimes, even two weeks from the restoration of sinus rhythm. It is important to underline that the aforementioned period (at least three weeks before, at least three weeks later) should be understood starting from the reaching of the therapeutic range. In the other hyperkinetic arrhythmias the indication to the TAO exists only in cases that also present phases of AF.
There is no agreement to date on TAO treatment of these patients. Therefore the
use of TAO (INR 2-3, indefinite period of time) should be restricted to patients
with high embolic risk (presence of atrial fibrillation, previous embolic
episodes, echocardiographic evidence of endocavitary thrombosis).
Acute myocardial infarction
Patients with myocardial infarction who have an increased thromboembolic risk (large
acinetic area, wall thrombosis, history of embolism and FA) should receive
anticoagulant therapy with heparin followed by TAO (INR 2-3) for at least 3
months, with continuation sine die in the chronic FA.
TAO is not indicated in the management of patients undergoing surgical coronary
revascularization or PTCA
Arterial thromboembolism
For the conditions of arterial thromboembolism, particularly relapsing the FCSA,
in line with previous, classic recommendations, suggests a high level of
anticoagulation (INR 3-4.5) indefinitely.
Prevention of Deep Venous Thrombosis
Prophylaxis with oral anticoagulants is generally to be reserved for patients at
very high risk (prior DVT / pulmonary embolism, major orthopedic surgery) In
light of recent studies, in orthopedic surgery TAO is currently considered
second choice as an alternative to low molecular weight heparin.
Treatment of Deep Vein Thrombosis and pulmonary embolism and relapse prophylaxis The usefulness of long-term oral anticoagulation (INR 2-3) after heparin in DVT and pulmonary embolism has been unequivocally demonstrated in several clinical studies.
The duration of therapy is still not completely defined: thromboembolic
relapses would certainly be reduced if anticoagulant therapy was conducted
without interruption for all patients, but many of these would be unnecessarily
exposed to the risk of bleeding and costs that however burden the TAO. A 3-6
month treatment period is generally recommended for patients without major
thromboembolic, longer (or indefinite) risk factors in continuous risk cases (deficiencies
of physiological inhibitors, recurrent DVT, etc.). A separate case is
represented by the antiphospholipid antibody syndrome; Retrospective studies
indicate the need to maintain a higher therapeutic range in these patients if
they have spontaneous venous or arterial thrombosis.
Patients with thromboembolic stroke and small or moderate injury, in whom a CT scan performed at least 48 hours after onset of symptoms, excludes intracranial haemorrhage, should be treated with heparin followed by TAO (INR 2-3). In hypertensive patients or with an extended ischemic focus it is advisable to wait two weeks before the start of anticoagulant treatment. In patients with non-valvular AF as a presumable cause of stroke, which have a low risk of early embolic recurrence, TAO establishment is indicated directly after the 48-hour TAC. Oral anticoagulant therapy is not indicated in non-embolic cerebrovascular diseases.
An exception is the antiphospholipid antibody syndrome
Peripheral Ateropathies A further field of use of oral anticoagulant therapy,
although not coded, is in vascular reconstructive surgery. After elective
surgery for chronic femoral-popliteal arteriopathy 11 a reduction in mortality
from myocardial infarction and vascular death of about 50% was demonstrated with
a very long-term treatment and therapeutic interval, reconstructed a posteriori,
between INR 2.5 and 4 , 5. The use of TAO in peripheral arterial disease is not
recommended due to the lack of adequate clinical studies. In this pathology it
is preferable to use anti-platelet drugs.
4. WHEN TAO IS CONTROLLED
To obtain the maximum effectiveness and safety for the TAO:
1) reliable laboratory,
2) expert doctor,
3) collaborating patient.
absolute
In the following circumstances, oral anticoagulant treatment should not be used
under any circumstances:
Pregnancy
Oral anticoagulants should not be administered during the first trimester of
pregnancy, due to the known fetal malformations that may induce, and in the last
4-6 weeks, the risk of bleeding in the newborn due to the anticoagulant passing
through the placenta.
Major bleeding within 1 month from the onset of the event, especially if at risk
of life.
Non-compliance of the patient
Gastrointestinal hemorrhages / active peptic ulcer
Uncontrolled arterial hypertension
Pregnancy (excluding period of absolute contraindication)
Severe alcoholism
Severe liver failure
Vascular malformations that can cause significant bleeding
coagulopathies
General psychiatric diseases
alcoholism
Diseases of bacterial endocarditis
cardiovascular pericarditis
severe heart failure
Kidney disease severe renal insufficiency
recent renal biopsy
Diseases recent brain accident of non-embolic nature
neurological cerebral aneurysms
advanced arteriosclerosis
Esophageal varic diseases
gastrointestinal hiatal hernia
diverticulosis of the colon
Liver diseases biliary diseases
recent liver biopsy
Diseases pre-existing hemostasis defects
hematological thrombocytopenia
piastrinopatia
Miscellaneous lumbar puncture
arterial injections
advanced age (> 80 years)
controlled arterial hypertension
severe hemorrhoids
malnutrition
steatorrhea
diets for weight loss
thyrotoxicosis
myxedema
less-metrorragie
retinopathy
inflammatory bowel diseases
Before starting the TAO, it is recommended to evaluate (if available)
or have the following investigations carried out:
• basic coagulation tests (PT, APTT);
• complete blood count with platelets and sideremia (to ascertain a possible
condition of sideropenic microcytic anemia);
• transaminase, gamma-GT, bilirubin, cholinesterase (as evaluation of liver
function);
• creatinine, blood sugar, uricemia, cholesterol, triglycerides;
• pregnancy tests in all women of childbearing age.
Interview with the patient when starting the TAO
It is essential that the doctor has an interview with the patient before the TAO
begins, in order to provide him with important information and to clarify the
most relevant aspects of the conduct of the TAO in a comprehensive and
comprehensible manner.
In particular, the general aims of treatment with
anticoagulants, their mechanism of action and the risks associated with such
therapy must be illustrated, distinguishing in this regard between the possible
occurrence of minor bleeding (epistaxis, menorrhagia, hematuria, gingival
bleeding, etc.). and of the major ones, which require immediate medical
intervention.
Remember to avoid consuming large quantities of foods rich in vitamin K, such as
vegetables, broccoli, eggs, etc.
Patients of child - bearing potential must be informed about the teratogenic risk that TAO entails, especially in the early stages of pregnancy. You should advise them to inform the doctor in advance about a pregnancy intention and in any case to immediately communicate a possible beginning of pregnancy, or even a delay of the menstrual cycle