Heparinas

Introdução
• Unfractionated heparin (UFH) has been used for the prevention and
treatment of thrombosis since the 1930s. It is a mixture of sulfated
glycosaminoglycans of variable lengths and weights. Anticoagulant
efficacy and pharmacologic properties vary with the size of the
molecules. Heparin is obtained from porcine intestine and bovine
lung tissues.

• Low-molecular-weight heparins (LMWHs), derived from UFH by

depolymerisation, were introduced in Europe in the 1980s.Because
of several clinical advantages, LMWHs have gradually replaced
UFH for most indications. However, UFH continues to be used
during cardiovascular surgery and catheter-based interventional
procedures.
 Farmacologia
• Heparins and heparinoids are parenteral agents,
administered either intravenously or subcutaneously.
UFH binds to plasma proteins, platelets (platelet factor
4), macrophages, and endothelial cells. This limits
bioavailability and accounts for the highly variable
anticoagulant response. LMWHs have reduced binding
to plasma proteins, platelets, and other cells. As a result,
LMWHs have a more predictable dose response.The
need for parenteral administration makes these agents
both inconvenient and costly for long-term use,
especially outside the hospital setting
 Moléculas da heparina
• Each LMWH product has a specific molecular
weight distribution. This distribution determines
its anticoagulant activity and duration of action,
so each agent is considered a unique drug.
Indications for LMWHs vary — one product
cannot always be substituted for another.
LMWHs in current use globally include
enoxaparin, dalteparin, nadroparin,
tinzaparin, certoparin, reviparin, and bemiparin.
Heparina
Heparinases
 Ligação da heparina a um antidoto

www.usciences.edu/.../Faculty/Pophristic.aspx
 Ligação da heparina

Nature Reviews Drug Discovery 1, 140-148 (February 2002)

 Danaparoide
• Danaparoid, available in several countries,
is classified as a heparinoid. It is
composed of sulfated glycosaminoglycans
and can be used as an alternative to
heparin in patients suffering from an
antibody-mediated form of heparin-
induced thrombocytopenia (HIT).
 Modo de ação
• Heparin and its derivatives bind to a plasma
cofactor, antithrombin (AT), to inactivate
several coagulation enzymes, including Factors
IIa (thrombin), Xa, IXa, XIa, and XIIa. Thrombin
and Factor Xa are most responsive to inhibition
by the heparin-AT complex.101 The efficacy of
heparin-based anticoagulants increases as
selectivity for Factor Xa increases: LMWH is
superior to unfractionated heparin, and
fondaparinux is superior to LMWH.
 Efeitos adversos
• Bleeding is the most common adverse event
with heparin therapy. Major bleeding occurs in
0.8% of patients receiving full-dose UFH, but it is
less frequent with low-dose subcutaneous
heparin. LMWH has been reported to cause
bleeding less frequently, but this finding has not
been consistent across trials. Major bleeding
occurs in less than 3% of patients and varies
with product, indication, patient population, and
dose
 Efeitos adversos
• One area of special concern is the risk of epidural haematoma with spinal
anaesthesia. This risk is greater with LMWH than with UFH. Careful timing of dosing
is essential when epidural or spinal anaesthesia is used.103

• If a patient on heparin develops severe bleeding, the anticoagulant effect can be

reversed with protamine administered intravenously. Protamine neutralises heparin
by forming a stable salt. Because protamine binds preferentially to larger heparin
molecules, it is not as effective in reversing the effect of LMWHs.101

• There are two forms of thrombocytopenia seen in patients receiving heparin.

Nonimmune heparin-associated thrombocytopenia is benign; platelet counts rarely
drop below 100,000/mm3 and return to normal, even on continued heparin therapy. It
is not necessary to discontinue therapy. In contrast, immune-allergic heparin-induced
thrombocytopenia (HIT) is a serious condition requiring urgent treatment. In HIT,
antibodies form against the heparin-platelet factor 4 complex, leading to widespread
thrombosis. HIT usually occurs in the first three weeks of therapy, so platelet counts
should be monitored in patients receiving heparin for more than a few days.
Treatment involves immediate replacement of heparin with a parenteral direct
thrombin inhibitor (either argatroban or lepirudin) or with danaparoid.