Class Prof Sam 19/01/2023

Types of anticoagulants
 Unfractionated Heparin (UFH): These include heparin, make complexes with antithrombin 3,
and inactivates thrombin and factor Xa. Its onset of action is rapid, has a short half-life, and
can be monitored using activated partial thromboplastin (aPTT), activated clotting time, and
anti-factor 10a activity. The recommended target ratio of aPTT is 1.5 to 2.2 times the
patients' aPTT.
 Low Molecular Weight Heparin (LMWH): These are enoxaparin, dalteparin, tinzaparin,
nadroparin. Reduced action on thrombin but inactivates factor Xa. They have a longer length
of action, long half-life, and can be monitored using anti-factor Xa activity. However,
monitoring is not indicated except in certain conditions like pregnancy and renal failure.
 Vitamin K Dependent Antagonists (VKA): Warfarin, one of the most common anticoagulants
available. It acts by inhibiting vitamin K epoxide reductase (VKOR), which is needed for the
gamma-carboxylation of vitamin K-dependent factors (factors 2, 7, 9, 10, protein C and S). It
has a narrow therapeutic window of dosing, and its effect is profoundly altered by certain
factors including diet (leafy green vegetables, fruits like avocado, kiwi), medications, and
genetic mutations in the VKOR complex which leads to resistance. It requires frequent
monitoring with an international normalized ratio (INR).
 Direct Thrombin Inhibitors: Bivalirudin, argatroban, and dabigatran are direct thrombin
inhibitors; these inhibit the cleavage of fibrinogen to fibrin by thrombin. All products are
renally metabolized.
 Direct Factor 10a Inhibitors: These include rivaroxaban, apixaban, edoxaban, and
betrixaban. Mechanism of action involves inhibition of the cleavage of prothrombin to
thrombin by binding directly to factor Xa. These products are only orally administered.

Molecular structure of heparin

 Heparin: sulfated polysaccharide. Molecular weight of 3000 to 30000 Da.
 LMWH: derived from heparin by chemical or enzymatic depolymerization to yield fragments
approximately 1/3 the size of heparin. Molecular weight of 4500 to 5000 Da.

Action of anticoagulants
INR
INR is derived from prothrombin time (PT) which is calculated as a ration of the patient’s PT to a
control PT standardised for the potency of the thromboplastin reagent.
Formula: INR = Patient PT/Contol PT

APTT
APTT measures the time taken for blood to clot after adding and activator. It directly measures the
intrinsic and common pathway which are factors I, II, V, VIII, X, XI and XII. On the other hand PT
measures the extrinsic pathway and common pathway.

General indication of anticoagulation

 Acute Myocardial Infarction (AMI). Early anticoagulation (AC) with heparin is indicated for
all patients with a documented diagnosis of acute myocardial infarction or acute coronary
syndrome. The choice of AC (heparin, unfractionated heparin (UFH), low-molecular-weight
heparin, fondaparinux, or bivalirudin) depends on the therapy instituted. AC has been found
to lower the risk of thrombus formation when it started early and continued for more than
48 hours. Heparin (UFH) is indicated for patients undergoing percutaneous coronary
intervention (PCI). For those patients receiving fibrinolytic therapy, heparin is also indicated
and continued for at least two days. Patients not undergoing PCI should be treated with low
molecular weight heparin such as enoxaparin or parenteral heparin (UFH).
 Left Ventricular (LV) Thrombus. Studies have suggested the benefits of early initiation of
anticoagulation in patients with documented LV thrombus to prevent embolization of
thrombus. Anticoagulation therapy should be continued for three to four months as the risk
of embolization was found to be highest within the first 3-4 months. Although no extensive
randomized studies have been conducted with the NOACs in this disease state, as compared
to warfarin, it is recommended that NOACs be used due to the convenience of dosing.
Vitamin K-dependent anticoagulants like warfarin with a therapeutic target INR of 2-3,
continue to be used most commonly.
 Atrial Fibrillation. Anticoagulation reduces the embolic risk in patients with atrial fibrillation.
The risk for embolization is the same for patients with paroxysmal, persistent, or chronic
atrial fibrillation. Atrial fibrillation is an independent risk factor for stroke. It is present in
approximately 20% of patients with a first-time stroke and contributes to increased mortality
and disability. The embolic risk for patients with atrial fibrillation can be assessed using
scoring systems like the CHA2DS2-VASc score.
 Left Ventricular Aneurysm. A left ventricular aneurysm can be a complication of acute
myocardial infarction. Patients with a left ventricular aneurysm are at high risk for a
thromboembolic event. Among other medical therapies, anticoagulation reduces
thromboembolic events, especially in those with arrhythmia.
 Prosthetic Heart Valve. Anticoagulation therapy is indicated in patients with a prosthetic
heart valve. Vitamin K-dependent anticoagulants are recommended for patients with
prosthetic heart valves in addition to the use of unfractionated heparin or low-molecular-
weight heparin at any point when vitamin K antagonist therapy is interrupted. Direct oral
anticoagulants are not indicated in patients with a prosthetic heart valve. The ideal level of
vitamin K-dependent anticoagulants varies depending on the diseased valve and the
presence of additional thromboembolic risk factors.
 Venous Thromboembolism Treatment. Anticoagulation is used in the treatment of venous
thromboembolism (deep vein thrombosis and pulmonary emboli). The duration for
anticoagulation in these clinical states depends on the precipitating circumstances, and
additional thromboembolic risk and comorbidities.
 Venous Thromboembolism Prophylaxis. Anticoagulants are indicated for the prevention of
venous thromboembolism in selected patient populations (hospitalized patients, post-
 operative state, cancer patients). Adverse events like thromboembolism are reduced in
patients receiving prophylactic anticoagulation.
 Treatment of Venous Thromboembolism in Patients with Cancer. Thromboembolism is a
frequent complication in cancer patients due to the release of procoagulants from neoplastic
cells. Several studies have demonstrated that LMWH is superior to VKAs in the treatment of
VTE in cancer patients.
 Pregnancy. Anticoagulants are indicated in pregnancy for the treatment of acute venous
thromboembolism, valvular heart disease, and pregnancy-related complications in women
with antiphospholipid antibody syndrome, antithrombin deficiency, or other thrombophilias
who had a prior VTE. Warfarin is more efficacious than unfractionated heparin for the
prevention of thromboembolism in pregnant ladies with mechanical valves. But, warfarin
therapy in the first trimester of pregnancy is associated with a significant increase in fetal
anomalies.