This document is a summary of pharmacology related to venous thromboembolism (VTE) including
- definition of VTE
- diagram of normal blood coagulation cascade
- prophylaxis of VTE
- treatment of VTE
- regimens for anticoagulant medications including bridge and overlap therapy
- VTE treatme...
Venous Thromboembolism·
Venous thromboembolism (VTE) is an umbrella term for two types of clots. A deep vein thrombosis (DVT) is a clot Vessels have a layer of collagen
·
that forms in deep veins, and a pulmonary embolism (PE) is a clot in the lungs. and tissue factor (TF) around
them that maintains a balance
between clotting and bleeding.
Normal blood clotting is shown on the right. Regulation mechanisms include: ⑪ It’s separated from circulating
• A complex of Protein C and S, which inactivate factors 5 (V) and 8 (VIII) coagulation factors by
• Antithrombin, which inactivates factor 10 (X) and thrombin (Factor 2 (II)) epithelium.
• Heparan Sulfate, which upregulates antithrombin When the epithelium is
• tissue factor pathway inhibitor, which inhibits tissue factor. damaged during vessel
&
injury, that layer of tissue
factor and collagen becomes
Plasmin is a protein that breaks fibrin down, weakening the fibrin mesh and causing the clot to break down. As a exposed to circulating
byproduct, fibrin will release D-Dimer. D-Dimer is a good lab to run to RULE OUT VTE, not diagnose. If levels of D- coagulation factors,
Dimer are low, venous thromboembolism is unlikely. initiating the process to form
a blood clot.
Risk factors for VTE are known as Virchow’s Triad:
• Blood Stasis Tissue factors combines. With
• Hypercoaguable disorders activated Factor 7 (VII) to
• Blood vessel injury
m - 11
Extrinsic
Tenase
form extrinsic Tenase.
Extrinsic Tenase activates
factors 9 (IX) and 10 (X).
Prevention Special populations
LMWH or May use IPC LMWH and UFH are preferred
=m
Medically ill Pregnant
fondaparinux instead of meds and don’t pass the placenta
LMWH and Warfarin are Factor 10 (X). Combines with
Stockings or
TKA/THA DOAC or ASA Pediatric activated factor 5 (V) to form a
IPC w/ meds preferred Prothrombinase prothrombinase complex.
Emma
Remember, an ending of -ase
Hip fracture Stockings or LMWH monotherapy: Dalteparin 200U/Kg indicates an enzyme. In this
LMWH or Cancer q24hr for 30 days, followed by 150U/Kg Prothrombin
IPC w/ meds case, prothrombinase
Repair UFH q24hr or weight based enoxaparin dosing. enzymatically cuts
prothrombin to form thrombin,
Other LWMH or Stockings or Kidney UFH or Warfarin due to lack also known as activated factor
surgery UFH IPC w/ meds impairment of renal adjusments 2 (II).
• compression stockings are used to help promote • VTE prophylaxis should be used post-partem for *
Thrombin
venous blood flow to prevent blood stasis after at least 6 weeks following delivery.
surgery • cancer increases the risk of VTE occurrence,
• IPC is a series of cuffs wrapped around a patient’s therefore VTE prophylaxis in cancer patients
legs that inflate to compress their legs and promote should continue as long as cancer is “active” or Thrombin (Factor 2 (II)) will
activate factors 5 (V) and 8
venous blood flow every 1-2 minutes. These should chemotherapeutic drugs are being used.
*
Thrombin (VIII).
be worn for at least 18 hours per day. • Cancer patients may switch to warfarin or a
• Prevention in medically ill patients is short term to DOAC after 3-6 months of using a LMWH.
reduce the risk of bleeding due to anticoagulants • DOACs can also be used in kidney impairment if
• Prevention in surgery patients is long term and renally adjusted
should be initiated within 6-12 hours of surgery and
for at least 10 days, and up to 42 days. -
• If able to, encourage patients to walk.
• Rivaroxaban can also be used in medical patients if Factor 8 (VIII) combines
an alternative is needed. Intrinsic Tenase with factor 9 (IX) from
before to form intrinsic
Anticoagulant Dosing - Tenase, which will active
more factor 10 (X).
Now that we have a lot
Binds to antithrombin and enhances its Prothrombinase more factor 10 (X) thanks
Heparin to the previous step, a lot
inhibitory affects on coagulation cascade
Emma
more can combine with
Prothrombin factor 5 (V) to form more
LMWH Heparins that selectively inhibit factor Xa prothrombinase, which
Fondaparinux will enzymatically cut
more prothrombin, which
will form more thrombin
Inhibits VKORC1, an epoxidase that is
*
(Factor 2 (II)).
Warfarin necessary to recycle vitamin K to
activate factors II, VII, IX, and X
Dabigatran Directly inhibit thrombin, therefore Thrombin enzymatically
will cut fibrinogen to form
*
Argatroban fibrinogen is not cleaved to make fibrin, which is the protein
Bivalriudin fibirn that forms a meshwork
over a clot and stabilizes
Thrombin Fibrinogen the clot.
Factor Xa Inhibit factor Xa, therefore
Inhibitors prothrombinase is not generated
·
• caution taking DOACs and PgP inducers/inhibitors Fibrin
• Caution with rivaroxaban and apixaban with CYP3A4 inhibitors/inducers.
• Take rivaroxaban with food to improve absorption Once the site of vessel injury
• Andaxanet is a reversal agent for factor Xa inhibitors has been plugged by a blood
#
• Protamine is a reversal agent for UFH and LMWH clot, the barrier of tissue
factor and collagen is NO
• Vitamin K is a reversal agent for Warfarin LONGER in contact with
• Discontinue DOACs 2 days before surgery to restore hemostasis circulating coagulation
• Discontinue warfarin 5 days before surgery to restore hemostasis factors. Therefore, no more
• First episode of VTE with a provokable cause is treated for 3 months blood should be clotting, as
well as no bleeding should be
• Second episode of VTE or a VTE of unprovoked cause is treated for more than 3 months occurring.
• Treat VTE only if CONFIRMED. Avoid treatment if only suspected due to the risk of bleeding with
anticoagulant agents. A D-dimer level of greater than 4 is an indication to perform imaging for a VTE.
• Enoxaparin dosing is 1 mg/kg BID or 1.5 mg/kg once daily
• Fondaparinux dosing is 5 mg daily if < 50 kg, 7.5 mg daily if 50-100 kg, and 10 mg daily if > 100 kg.
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