Download 19- dr.wesal VTE in cancer pt

Management of VTE
in The Cancer Patients
By
Dr: Wesal Mohamed
Associate Leucturer of
Clinical Oncology
Mansoura University
Annual At-Risk for VTE in U.S.Hospitals:
•
7.7 million Medical Service inpatients.
• 3.4 million Surgical Service inpatients.
Based upon ACCP guidelines for VTE prophylaxis
74% of VTEs present in outpatients.
42% of outpatient VTE patients have had recent surgery or
hospitalization.
40% had received VTE prophylaxis.
•Cancer patients found to have a 3-fold higher risk for recurrent
VTE than patients who had an initial VTE in the absence of
malignancy which is greatest in the first few months after
diagnosis of malignancy and can persist for many years.
•Cancer patients, once hospitalized, are at higher risk of developing
VTE. While receiving chemotherapy, cancer patients have a 7-fold risk
of developing VTE as compared with other patients without cancer.
Antiangiogenic agents as (bevacizumab, thalidomide and
lenalidomide) also contribute to thrombosis, through
endothelial cell, platelet activation and damage to the
vascular endothelium which is amplified by the coadministration of Ch.T. and steroids.
Bevacizumab administered concomitantly with Ch.T. is
associated with a 33% relative increase of VTE.
With regards to multiple myeloma, the highest incidence
of VTE observed in patients treated with thalidomideand doxorubicin-containing Ch.T.(VTE rate up to 34%).
There are two pathways: the contact activation pathway (also known as the
intrinsic pathway) and the tissue factor pathway (known as the extrinsic pathway).
Contact activation pathway: is disrupted by heparin, not working properly
in Haemophilia, and can be measured using the aPTT clotting test.
Tissue factor pathway: is interrupted by warfarin, and is measured
using INR or PT.
Prophylaxis Modalities
Reversible Risk Factors:
1. Nutrition:
eat fruits, veggies, fish; less red meat.
2. Quit cigarettes.
3. Lose weight/ exercise.
4. Prevent DM/ metabolic syndrome.
5. Control hypertension.
6. Lower cholesterol.
7. Avoid air pollution.
ASCO Guidelines
Hospitalized Patients with Cancer
Role of VTE Prophylaxis
Patients with cancer should
be considered candidates for
VTE prophylaxis with
anticoagulants (UFH,
LMWH, or fondaparinux) in
the absence of bleeding or
other contraindications to
anticoagulation
Evidence
Multiple RCTs of
hospitalized medical patients
with subgroups of patients
with cancer. The 8th ACCP
guidelines strongly
recommend (1A)
prophylaxis with either lowdose heparin or LMWH for
bed ridden patients with
active cancer.
Ambulatory Patients with Cancer Without
VTE Receiving Systemic Chemotherapy:
Role of VTE Prophylaxis
Evidence
Routine prophylaxis with an
antithrombotic agents is not
recommended except as noted
below
Routine prophylaxis in ambulatory
patients receiving chemotherapy is not
recommended due to conflicting trials,
potential bleeding, the need for laboratory
monitoring and dose adjustment, and the
relatively low incidence of VTE.
LMWH or adjusted dose warfarin
(INR ~ 1.5) is recommended in
myeloma patients on thalidomide
or lenalidomide plus ch.t. or
dexamethasone
This recommendation is based on
nonrandomized trial data and extrapolation
from studies of postoperative prophylaxis
in orthopedic surgery and a trial of
adjusted-dose warfarin in breast cancer
Patients with Cancer Undergoing Surgery:
Role of VTE Prophylaxis
Evidence
All patients undergoing major
surgical intervention for malignant
disease should be considered for
thromboprophylaxis with lowdose UFH, LMWH, or
fondaparinux starting as early as
possible for at least 7-10 days
unless contraindicated.
RCTs of UFH and those
comparing the effects of LMWH
and UFH on DVT rates on patients
with cancer indicate broadly
similar prophylactic efficacies for
these two agents
Mechanical methods may be added
to anticoagulation in very high risk
A Cochrane review of 19 studies
patients but should not be used
alone unless anticoagulation in
contraindicated.
Patients with Cancer
Undergoing Surgery (continued):
Role of VTE Prophylaxis
Evidence
Recent RCTs suggest that
LMWH for up to 4 weeks may be
prolonging prophylaxis up to 4
considered after major
weeks is more effective than shortabdominal/pelvic surgery with
course prophylaxis in reducing
residual malignant disease, obesity,
postoperative VTE by 60% without
and a previous history of VTE
Increasing risk of bleeding.
•Several studies suggest that in cancer patients LMWH
and UFH appear to be equally effective and safe. These
results have been confirmed by at least three studies ,one
of them specifically designed for surgical cancer patients
•There are important advantages of LMWH because they
can be administered once daily, have a better
pharmacokinetic profile and are less likely to cause
heparin induced thrombocytopenia(HIT). So, LMWH can
be considered as the first choice in this setting.
therapeutic Modalities
Treatment of Patients with Established VTE
to Prevent Recurrence:
Role of VTE Prophylaxis
LMWH is the preferred approach for the
initial 5-10 days in cancer patient with
established VTE.
LMWH for at least 6 months is preferred
for long-term anticoagulant therapy.
Vitamin K antagonists are acceptable
when LMWH is not available.
The CLOT study demonstrated a relative risk
reduction of 49% with LMWH Vs. a vitamin K
antagonist.
Evidence
LMWH for 3-6 months is
more effective than
vitamin K antagonists
given for a similar
duration for preventing
recurrent VTE.
Treatment of Patients with Established VTE
to Prevent Recurrence (continued):
Role of VTE Prophylaxis
Anticoagulation for an indefinite
period should be considered for
patients with active cancer
(metastatic disease, continuing
chemotherapy)
Evidence
In the absence of clinical trials,
benefits and risks of continuing
LMWH beyond 6 months is a
clinical judgment in the individual
patient. Caution is urged in elderly
patients and those with intracranial
malignancy.
Inferior vena cava filters are
reserved for those with
Consensus recommendations due to
contraindications to anticoagulation lack of date in cancer-specific
or PE despite adequate long-term
populations
LMWH.
Therapeutic Anticoagulation Treatment for
VTE:
Stage 1 (Immediate): At diagnosis or during
diagnostic evaluation:
•
•
•
•
•
Low-molecular-weight heparin (LMWH):
Dalteparin (200 units/kg subcutaneous daily).
Enoxaparin (1 mg/kg subcutaneous every 12 hours).
Tinzaparin (175 units/kg subcutaneous daily).
Fondaparinux: (5 mg [<50 kg]; 7.5 mg [50-100 kg]; 10 mg [> 100
kg] subcutaneous daily.
•
Unfractionated heparin: (IV) (80 units/kg load, then 18 units/kg
per hour, target : aPTT of (2.0-2.5) x control . A full dose of heparin
is continued for at least 5 days & suspended when full
anticoagulation by VKA (i.e. INR >2.0) is achieved for at
least two consecutive days.
Therapeutic Anticoagulation Treatment for
VTE:
Stage 2 Acute: Short term, during transition to
chronic phase:
► LMWH (category 1) is preferred as monotherapy, without warfarin
in patients with proximal DVT or PE and prevention of recurrent
VTE in patients with advanced or metastatic cancer.
► If UFH or factor Xa antagonist, transition to LMWH or warfarin.
Warfarin: (2.5-5 mg every day initially, subsequent dosing based on
INR value; target INR 2.0-3.0). started within 24 h from initiating
heparin (UFH or LMWH) administration.
It is well known that LMWH is cleared only by the kidneys
and has a significant accumulative effect in patients with
impaired renal function (creatinine clearance <30 ml/min).
Patients with a creatinine clearance of <30 ml/min who are
treated with standard therapeutic doses of enoxaparin have
elevated levels of anti-Xa and an increased risk for major
Bleeding, so in these patients on UFH i.v. or LMWH with
anti-Xa activity monitoring is recommended.
Thrombolytic treatment should be
considered for specific subgroups of
patients such as those with PE presenting
with severe right ventricular dysfunction,
and for patients with massive ilio-femoral
thrombosis at risk for limb gangrene,
where rapid venous decompression and
flow restoration may be desirable.
Urokinase, streptokinase and tissuetype plasminogen activator are able to
achieve a rapid lysis of fresh pulmonary
emboli.
 HIT,
an antibody-mediated syndrome, is associated with
significant morbidity and mortality.
 Considered rare in the past, unrecognized by many
clinicians.
 Diagnoses can be difficult to confirm.
 Serologically proven HIT occurs in (1.5-3)% of patients
with heparin exposure.
 Present with mucocutaneous bleeding, ranging from
(petechiae and ecchymoses) to life-threatening
gastrointestinal and intracranial hemorrhage.
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Paradoxically, HIT, an immune reaction to an anticoagulant that
lowers platelet count, rarely causes bleeding, it causes thromboses,
and platelet transfusions are contraindicated.
Heparin, the most powerful anticoagulant, saving uncountable lives
and limbs, it produces the most extreme hypercoagulable disorder,
costing thousands yearly their lives and limbs.
Health professionals should know about a reaction that is common,
often iatrogenic, catastrophic preventable and treatable.
Venous thrombosis developed may result in:
•Bilateral deep venous thrombosis of the legs.
•Pulmonary embolism.
•Venous gangrene of fingers, toes, penis, or nipples.
•Myocardial infarction, stroke.
•Mesenteric arterial thrombosis.
•Limb ischemia and amputation.
Therapeutic Anticoagulation Failure
Therapeutic
INR
Patient
on
warfarin
Check
INR
Subtherapeutic
INR
Switch to
heparin (LMWH
preferred) or
fondaparinux
Increase warfarin
dose and treat
with parenteral
agent until INR
target achieved or
consider switching
to heparin (LMWH
preferred) or
fondaparinux
Therapeutic Anticoagulation Failure
Therapeutic
PTT
Patient
on
heparin
Check
aPTT
levels
Subtherapeutic
aPTT
Increase dose of heparin
or Switch to LMWH
or Switch to
fondaparinux
and Consider placement
of IVC filter
and Consider HIT
Increase dose of
heparin to reach
therapeutic level
Anticoagulant therapy in patients with recurrence of VTE:
Cancer patients have a 3-fold risk of recurrent VTE and a 3- to 6fold risk of major bleeding while receiving anticoagulant treatment
with a VKA, as compared with patients without Cancer.
Patients on long-term anticoagulation with VKA who develop VTE
when their INR:
• In the subtherapeutic range: retreated with UFH or LMWH until
VKA anticoagulation achieves a stable INR (2-3).
•In the therapeutic range : there are two options: (i) either shift to
another method of anticoagulation, such as s.c. UFH maintaining a
therapeutic aPTT (aPTT ratio from 1.5 to 2.5), or LMWH at a
weight-adjusted dose; or (ii) or increase the INR (to a target of 3.5).
Warfarin mechanism & SE:
Warfarin is an oral anticoagulant, a drug that inhibits the clotting
of blood. It prevents the formation of blood clots by reducing the
production of factors by the liver that promote clotting, factors II,
VII, IX, and X, and the anticoagulant proteins C and S. The
production of these factors by the liver are dependent on adequate
amounts of vitamin K. Warfarin reduces the production of the
factors because it antagonizes vitamin K.
Treatment usually is started at 2 to 5 mg once daily and the dose is
adjusted based in INR tests. Patients typically require 2 to 10 mg
of warfarin daily.
Certain foods and beverages can make warfarin less effective in preventing
blood clots, SO avoid eating or drinking large amounts of vit K containing
food
•
•
•
•
•
•
•
Spinach,
Brussels sprouts,
Parsley,
Collard greens,
Mustard greens,
Chard,
Green tea.
Certain drinks can increase the effect of warfarin, leading to
bleeding problems. Avoid or drink only small amounts of these drinks
when taking warfarin:
Cranberry juice.
There is no evidence to recommend the use of
anticoagulation to influence prognosis of cancer
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