Anticoagulants and Antiplatelets

Starting from a case in our clinical practice {the patient was using Aspirin as a “blood thinner” and was concerned that their Prothrombin Level (INR increased) was not dropping}.

It is difficult to explain that by using Aspirin as an antiplatelet, we do not expect the Prothrombin Level (INR) to change. And just as difficult for him to accept.

In our clinical practice, we are obliged to use “blood thinners” (and in foreign literature, the term “Blood Thinner” is found) for Anticoagulants and Antiplatelets. In fact, this term is used so the patient can understand the problem more easily, but it complicates our work.

None of these anticoagulant and antiplatelet preparations actually thin the blood in the true sense of the word. If you have a mixture of 1 kg rice with 1 kg water and you want to thin it, you either need to add more water for the same amount of rice, or reduce the amount of rice for the same amount of water. These preparations neither change the number of blood cells nor the volume of plasma, hence they do not cause “Blood Thinning”.

They act at different stages of Hemostasis, which is “a complex process, normally activated immediately after damage to the blood vessel wall and that ensures the cessation of blood flow (hemorrhage) and then the restoration of circulation in this vessel (vessels) after the damage has been repaired”. It involves the interactions of blood vessels (the structures of the blood vessel walls and endothelial cells that line these vessels from the inside) and blood (platelets and coagulation factors).

This is where the difficulty in explaining begins.

For ease of study, Hemostasis is divided into 3 stages (artificial division, as the whole process of hemostasis is continuous):

1. Primary Hemostasis.
2. Coagulation (Secondary Hemostasis).
3. Fibrinolysis.

For practical ease in our country:

The most commonly used antiplatelets in hospital and outpatient settings are: Aspirin and Plavix (Clopidogrel). Their action involves blocking the function of platelets (preventing the aggregation of platelets in the blood vessel wall), thus intervening in the first phase of Hemostasis = Primary Hemostasis.

Their effect is irreversible, meaning it will last as long as the platelet lives; 8-10 days. This means; if you stop them today, their effect will last until the last platelet with blocked function from them dies (8-10 days), not forgetting that new platelets are continuously produced that do not have the blocked function as long as the antiplatelet preparation is no longer used (assuming it has also been eliminated from the body). Therefore, before a planned surgical intervention (or other invasive procedures), they are discontinued a few days earlier. They do not affect the number of platelets, except in special cases as side effects.

There is no antidote for them (in case of need, platelet measures with limited efficacy are used: and these transfused platelets, if the preparation is still in circulation, may have their function blocked). The efficacy of these preparations is measured by Thromboelastography, which is not used in our country (with one exception). Indirectly we evaluate them with the Bleeding Time (at the ear), which in norm is 2-4 minutes and if it is longer (always when performed by a qualified specialist), it may be affected by these preparations.

Anticoagulants in the true sense of the word, intervene in the Coagulation Cascade, Secondary Hemostasis.

The most commonly used in our practice are:

1. Heparin – used only in hospital conditions, so its control is much better. Its effect is assessed by measuring APTT. It has an antidote (Protamine) and furthermore, the half-life of Heparin is short (2 hours). Platelets are monitored, as in some cases it may cause HIT (Heparin-Induced Thrombocytopenia).
2. Low Molecular Weight Heparins – there are several. Most often in our practice (in hospital and outpatient settings) Enoxaparin (Clexane) is used. They have no marker to follow them, the effect lasts on average 12 hours. For LMWH they have a half-life of 12 hours, no antidote. Platelets are monitored, as in some cases, much rarer than Heparin, it may cause HIT (Heparin-Induced Thrombocytopenia).
3. Oral Anticoagulants (Sintrom and Warfarin used in our hospital and outpatient practice). Their effect is related to the antagonism (inhibition) of Vitamin K which activates coagulation factors II, VII, IX, X, Protein C, and S. They do not affect the amount of production, only in their non-activation. The effect appears after 2-4 days and also takes as many days to be eliminated. They are monitored with the Prothrombin Level (PT/INR). PT should be kept at 25-35% (INR 2-3). If PT < 20% (INR > 5) there is a risk of hemorrhagic phenomena. The preparation is discontinued (keeping in mind that the effect continues for another 2-4 days). The antidote is Vitamin K which when taken orally shows its effect after 12-24 hours and when taken intravenously after about 12 hours, therefore in emergency cases, the immediate use of activated coagulation factors (Plasma Transfusion) is the only possibility until the effect of the preparation is eliminated.
   
   

   Here arise two discussions:

   1. The effect of Vitamin K is taken in the best case after 12 hours when indeed the cause of the hemorrhage is related to its deficiency or antagonism, so do not expect when you have a bleeding and go to a medical service and they give you Vitamin K and it stops the hemorrhage immediately.
   2. If PT is maintained under medication at 25-35% and a person has a PT of 50% and has a nosebleed, the hemorrhage is not from the lower level of PT compared to the norm (70-120%). The hemorrhage can be justified when PT < 20% (INR >5).
   
   
4. Direct Inhibitors of Activated Factor X (Rivaroxaban, Xarelto) have started to be regularly used to replace Sintrom and Warfarin. PT/INR is not monitored, it is not affected by foods. There is no antidote. It is eliminated quickly with a half-life of elimination 5-9 hours.
5. Rarely, in hospital conditions, in case of HIT and the need to continue anticoagulation, Direct Thrombin Inhibitors are used. Out of curiosity, they originate from Hirudo medicinalis – leeches, which produce the peptide hirudin from the salivary glands, with anticoagulant effect.

In conclusion, we agreed on a practical solution, the patient to use Aspirin (the minimum amount to achieve the antiplatelet effect is 75 mg/day) if needed and not to waste money and “bleed unnecessarily”, by doing the Prothrombin Level analysis.