TOC for HIT in DVT

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1/23/2019
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What is the drug of choice for DVT prophylaxis in a patient with a con rmed
history of heparin induced thrombocytopenia (HIT)?
Comment by InpharmD Researcher
When selecting an agent for DVT prophylaxis in a patient with a history if
heparin induced thrombocytopenia the only recommendation is to select a
non-heparin agent. Based on the meta-analysis of non-heparin
anticoagulant data, our primary literature focuses on fondaparinux and
apixaban as the agents with most e cacy or e cacy and safety data
respectively compared to low molecular weight heparin. Depending on
individual patient factors (convenience, cost, compliance, renal and hepatic
function, etc) and guidelines not recommending one medication over the
other, either agent is a reasonable alternative.
Search Strategy
All
Background
Relevant Prescribing Information
Literature Review
Discus
Background
According to the American College of Chest Physician
(ACCP) guidelines, the choice for DVT prophylaxis
should include the following characteristics, ease of
administration, e ectiveness, safety, and costhttps://inpharmd.com/what-is-the-drug-of-choice-for-dvt-prophylaxis-in-a-patient-with-a-confirmed-history-of-heparin-induced-thrombocytopenia-hit
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e ectiveness. ACCP does not recommend a speci c
agent but suggests selecting from the following
pharmaceutical agents: low dose unfractionated
heparin, low molecular weight (LMW) heparins,
fondaparinux, and, where available, oral factor Xa or
direct thrombin inhibitors. [1]
In the case of heparin-induced thrombocytopenia,
according to the America Society of Hematology (ASH)
guideline panel, it is recommended that patients
receive a non-heparin anticoagulant for VTE
prophylaxis. One agent is not preferred over the other
but ASH suggests choosing from the following,
argatroban, bivalirudin, danaparoid, fondaparinux,
direct oral anticoagulants. [2]
Based on the American College of Chest Physician
(ACCP) guidelines alternative anticoagulants for
thromboprophylaxis, such as fondaparinux,
danaparoid, warfarin, and the new oral anticoagulants,
dabigatran and rivaroxaban, should be used. As there
is limited studies evaluating fondaparinux and new oral
anticoagulants in HIT, further studies would be
bene cial. [1]
When choosing an agent for DVT prophylaxis in HIT, the
guidelines don’t recommend one non-heparin agent
over another. We reviewed a meta-analysis comparing
e cacy and safety of alternative choices for
anticoagulants, in the prevention of venous
thromboembolism after hip and knee arthroplasty,
comparing all available options. The authors found that
fondaparinux, rivaroxaban, and apixaban may be more
e ective in the prevention of VTE than enoxaparin so
we include the data for these agents below. When
apixaban was compared to the standard treatment of
enoxaparin 40 mg once daily, it showed 0.51 odds ratio
for VTE incidence (95% CI 0.39-0.68). When
fondaparinux was compared to enoxaparin 40 mg once
daily there was an odds ratio of 0.38 for VTE incidence
(95% CI 0.28-0.5) and when rivaroxaban 10 mg once
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daily was compared to the standard enoxaparin dosing
there was an odds ratio of 0.38 for VTE incidence (95%
CI 0.29-0.5). While fondaparinux and rivaroxaban were
associated with a higher risk of major or clinically
relevant non-major (CRNM) bleeding than enoxaparin,
apixaban showed a lesser incidence. Apixaban
compared to fondaparinux in the same dosing showed
an odds ratio of 0.56 for major/CRNM bleeding (95%
0.39-0.82) and for rivaroxaban the odds ratio was 0.65
(95% CI 0.5-0.86). Considering the history of HIT in a
patient, heparin agents would be excluded from agent
selection and the data shows the non-heparin agent
that is superior in both safety and e cacy is apixaban.
While rivaroxaban and fondaparinux showed
superiority in e cacy, they appear to have a higher
incidence of major or CRNM bleeding. [3]
References:
1. Linkins LA, Dans AL, Moores LK, et al. Treatment and
prevention of heparin-induced thrombocytopenia:
Antithrombotic Therapy and Prevention of Thrombosis, 9th ed:
American College of Chest Physicians Evidence-Based Clinical
Practice Guidelines. Chest. 2012;141(2 Suppl):e495S-530S.
2. Cuker A, Arepally GM, Chong BH, et al. American Society of
Hematology 2018 guidelines for management of venous
thromboembolism: heparin-induced thrombocytopenia. Blood
Adv. 2018;2(22):3360-3392.
3. Hur M, Park SK, Koo CH, et al. Comparative e cacy and safety
of anticoagulants for prevention of venous thromboembolism
after hip and knee arthroplasty. Acta Orthop. 2017;88(6):634-641.
Relevant Prescribing Information
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Thrombocytopenia can occur with the administration of
fondaparinux sodium. Thrombocytopenia of any
degree should be monitored closely. Discontinue
fondaparinux sodium if the platelet count falls below
100,000/mm3. Moderate thrombocytopenia (platelet
counts between 100,000/mm3 and 50,000/mm3)
occurred at a rate of 3.0% in patients given
fondaparinux sodium 2.5 mg in the peri-operative hip
fracture, hip replacement, or knee replacement surgery
and abdominal surgery clinical trials. Severe
thrombocytopenia (platelet counts less than
50,000/mm3) occurred at a rate of 0.2% in patients
given fondaparinux sodium 2.5 mg in these clinical
trials. During extended prophylaxis, no cases of
moderate or severe thrombocytopenia were reported.
Moderate thrombocytopenia occurred at a rate of 0.5%
in patients given the fondaparinux sodium treatment
regimen in the DVT and PE treatment clinical trials.
Severe thrombocytopenia occurred at a rate of 0.04%
in patients given the fondaparinux sodium treatment
regimen in the DVT and PE treatment clinical trials.
Occurrences of thrombocytopenia with thrombosis that
manifested similar to heparin-induced
thrombocytopenia have been reported with the use of
fondaparinux sodium in postmarketing experience. [1]
No relevant monitoring recommendations are included
in the apixaban prescribing information.
References:
1. Fondaparinux sodium [package insert]. Princeton, NJ.:Dr.
Reddy’s Laboratories. INC.;2018
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Literature Review
A search of the published medical literature revealed 3
studies investigating the researchable question:
What is the drug of choice for DVT prophylaxis in a
patient with a con rmed history of heparin induced
thrombocytopenia (HIT)?
Please see Tables 1-3 for your response.
Table 1
Table 2
Table 3
Postoperative fondaparinux versus preoperative en
venous thromboembolism in elective hip-replaceme
double-blind comparison.
Design
Randomized Controlled Double-Blind
Objective
To evaluate the e cacy and safety of f
in prophylaxis of VTE pre-surgically for
surgery.
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Study Groups
Patients 18 years of age or older who w
replacement surgery or for revision of
surgery
Exclusion Criteria - One of the followin
endocarditis, documented congenital
current ulceration or angssiodysplastic
or brain, spinal, or ophthalmic surgery
planned indwelling intrathecal or epid
hours after the end of surgery, hypers
porcine products, or iodinated contras
anticoagulant treatment, concomitant
be combined with contrast media, add
creatinine in serum that was greater th
patient, and a platelet count of less tha
patients who needed anticoagulant th
anticoagulant or brinolytic therapy or
preceding the rst administration of th
before the study was not prohibited.
N=2309 patients
Patients assessed = 1827 (per protoco
Methods
Patients were randomized in blocks of
to be in once daily sub q injections of e
mg/day started 6H after surgery) plus
volume of enoxaparin syringe, or enox
preoperatively)
Treatment lasted 5-9 days post surger
primary e cacy outcome assessed be
occurred in person, by mail, or by pho
Treatment could be extended with any
after venography was completed. VTE
needed treatment was left to the discr
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Duration
Trial - 1 year (December 1998 - January
Assessment - 6 weeks including follow
Outcome
Measures
Primary E cacy Outcome - VTE up to d
thrombosis detected by mandatory bi
symptomatic deep-vein thrombosis, o
pulmonary embolism.
Safety Outcomes - Bleeding and death
Baseline
Characteristics
Safety
Safety
analysis
analysis
fondaparinux enoxapar
Age
n= 1140
n= 1133
66
67
Women 647
660
Weight
(kg)
75
75
Hx of
VTE
45
56
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Results
Study met power estimated to be 800
VTE occurrence by day 11 fondaparinux 37/908 (4%)
Enoxaparin 85/919 (9%) 95% CI -5.2(-8
Bleeding w/ Bleeding index ≥ 2
Fondaparinux 42/908 (4%)
Enoxaparin 29/919 (3%)
Adverse
Events
Common Adverse Events: N/A
Serious Adverse Events: N/A
Percentage that Discontinued due to A
Study Author
Conclusions
Study authors conclude that fondapar
e cacious agent than enoxaparin for
InpharmD
Researcher
While this study is dated, it shows that
two arms of the study group, and may
they also do not conclude that there m
bleeding in fondaparinux group (illustr
Critique
Discussion (0)
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