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\begin{document}

\title{Old is gold, sometimes! Apixaban after Bariatric Surgery}



\author[1]{zouheir Bitar}%
\author[2]{Ossama Maadarani}%
\author[1]{mohammed Mohsen}%
\author[1]{Nawal alkazemi}%
\affil[1]{Ahmadi Hospital}%
\affil[2]{Affiliation not available}%


\vspace{-1em}



  
  \date{May 27, 2024}


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\selectlanguage{english}
\begin{abstract}
A 39-year-old woman was admitted with right leg deep venous thrombosis
(DVT). She was started on apixaban tablets but developed pulmonary
embolism. The medical history showed sleeve gastrectomy. The failure of
the antithrombotic drug shed light on the efficacy and pharmacodynamic
changes of DOACs after bariatric surgery%
\end{abstract}%



\sloppy


Old is gold, sometimes! Apixaban after Bariatric Surgery

\textbf{Authors}

Zouheir Ibrahim Bitar FRCP, EDIC Critical care Unit, Ahmadi hospital,
Kuwait oil company POBOx 46468 , Postal code 64015 Fahaheel
zbitar2@hotmail.com

\textbf{2 Ossama Sajeh Maadarani, FRCP}

Critical care Unit, Ahmadi hospital, Kuwait oil company

POBOx 46468 , Postal code 64015 Fahaheel ossamamaadarani@yahoo.com

\textbf{3 Mohamed Jaber Mohsen, MRCP uk}

Critical Care unit , Ahamdi hospital, Kuwait oil company

momohsen@kockw.com 4 \textbf{Nawal Usamah Alkazemi ,RN}Nursing
department, Ahmadi hospital Nkazemi@kockw.com

\textbf{Corresponding author}

Zouheir Ibrahim Bitar FRCP, EDIC Critical care Unit, Ahmadi hospital,
Kuwait oil company POBOx 46468 , Postal code 64015 Fahaheel
zbitar@kockw.com

Abstract

A 39-year-old woman who was taking contraceptive pills was admitted with
right leg deep venous thrombosis (DVT). She was started on apixaban
tablets, and after 8 days, she developed proximal progression of DVT and
pulmonary embolism. Her past medical history later showed a history of
sleeve gastrectomy. The patient responded to a vitamin K antagonist
after heparin. The failure of the antithrombotic drug shed light on the
efficacy and pharmacodynamic changes of DOACs after bariatric surgery in
the absence of commercially available blood monitoring tests.

\textbf{Key words} Apixaban, Bariatric Surgery, thromboembolism

\textbf{Key Clinical Message}

Bariatric surgeries lead to complicated changes in pharmacodynamics of
DOACs.

The absence of clinical data on the efficacy of DOACs after various
bariatric procedures make it difficult to justify their use after
bariatric surgery

Case report

A 39-year-old woman with a 6-month history of oral contraceptive pills
presented with left pain and mild swelling. There was no chest pain and
no hemoptysis.

Doppler of the right leg showed a thrombus in the right distal popliteal
vein up to the confluence of the peroneal and posterior tibial veins.
ECG and echocardiography results were normal.

She was started on 10 mg apixaban bid for one week, which was decreased
to 5 mg bid on day 8. This was followed on day 9 by increasing pain and
extension of the swelling into the left thigh with difficulty breathing.

Physical exam showed the same swelling of the right lower limb, a weight
of 104 kg, a BMI of 34 kg/m2, normal vital signs and normal O2
saturation in room-temperature air.

CT angiography showed an acute angled filling defect in the posterior
and medial segmental arteries of the right lung lower lobe and
subsequent subsegmental arteries. An acute angled filling defect was
noted in the posterior segmental artery of the right lung upper lobe.
The right ventricle/left ventricle ratio was 0.85.

Repeated Doppler of the right lower limb showed persistence of popliteal
vein thrombosis with no recanalization. Cranial extension of the
popliteal thrombus was noted in the distal superficial femoral vein at
the adductor canal. Calf veins (muscular veins) were partially
thrombosed in the proximal and mid-calf.

Upon direct questioning of the patient, she admitted bariatric surgery 4
years ago in another facility that was not mentioned in her previous
medical records.

All her lab tests were normal, including CBC, ProBNP and troponin. The
results of factor V Leiden mutation, prothrombin G20210A mutation,
protein S deficiency, protein C deficiency, antithrombin deficiency and
antiphospholipid syndrome were all negative.

The patient was started on heparin infusion for one week and was
maintained on warfarin for 6 months, without any further adverse events
or provoked attacks.

Discussion

Bariatric surgery encompasses a variety of procedures, including sleeve
gastrectomy (SG), the most common bariatric procedure performed
(51.7\%); adjustable gastric banding (AGB); Roux-en-Y gastric bypass
(RYGB); and biliopancreatic diversion with duodenal switch (BPD-DS) (1).
Bariatric surgeries result in weight loss through 1) restriction of
caloric intake by reducing the volume of the stomach (SG and AGB), 2)
malabsorption by reducing the effective intestinal surface area
(BPD-DS), or 3) a combination of restriction and malabsorption (RYGB and
BPDDS).

Drug absorption will be affected after bariatric surgeries as well as
bioavailability depending on the chemical properties of the drug (i.e.,
molecular size and solubility)(2) and on changes in the properties of
the gastrointestinal tract (PH, intestinal flow time and surface area of
absorption)(3).

Certain DOACs (rivaroxaban) require food to increase absorption and
hence bioavailability, reaching \textgreater{} 80\% when administered
with food (4). When undertaking restrictive diets after bariatric
surgeries, the absorption of therapeutic rivaroxaban is reduced (4).
This effect is not observed with other DOACs and warfarin. Dabigatran
requires an acidic environment for absorption; therefore, (5) after
bariatric surgery, the pH in the gastric pouch is more alkaline because
of the reduced volume for gastric acid secretion, which could affect
dabigatran dissolution and resultant absorption (6).

The anatomy of the gastrointestinal tract changes in different ways
after different bariatric surgeries, which may affect the location of
drug absorption; in the absence of dedicated studies, indirect evidence
can be utilized, such as the location of drug absorption (table 1). For
example, apixaban is primarily absorbed in the proximal small intestine,
with some gastric absorption (7,8); dabigatran is absorbed in the lower
stomach and duodenum (9); edoxaban is absorbed in the proximal small
intestine(10); and rivaroxaban is primarily absorbed in the proximal
small intestine, with some gastric absorption(11).

The use of DOACs in the setting of postbariatric surgery is not
supported by enough literature. One case reported the successful use of
rivaroxaban following bariatric surgery with a high venous
thromboembolism risk, and the anti-Xa levels were monitored (12). In a
total of 6 patients who underwent sleeve gastrectomy (SG) and 6 patients
who underwent Roux-en-Y-gastric bypass (RYGB), the pharmacokinetic and
pharmacodynamic parameters were assessed and compared with those in
patients prebariatric surgery; the type of surgery~did not appear to
affect the pharmacokinetics or pharmacodynamics of 10 mg prophylactic
rivaroxaban once daily, which was well tolerated and considered safe in
this trial (13). For apixaban, there is no approved dosing for obese
patients, especially when considering surgical interventions such as
bariatric surgery. There is an ongoing study (ClinicalTrials.gov
Identifier: NCT02406885) to determine the durability or changes in the
pharmacokinetics and pharmacodynamics of apixaban in patients with a
body mass index (BMI) of 35 kg/m2 or greater following one of two
bariatric surgical procedures (preoperative versus postoperative
vertical sleeve gastrectomy or Roux-en-Y gastric bypass patients).

Our case report showed that in the absence of other causes of apixaban
failure, a history of SG might cause subtherapeutic levels of the drug,
leading to the progression of DVT and pulmonary embolism. The
complicated changes in PKs/pharmacodynamics (PDs) and the absence of
clinical data on the efficacy of DOACs after various bariatric
procedures as well as the lack of widely available monitoring tests for
DOACs make it difficult to justify their use after bariatric surgery. On
the other hand, as the anticoagulant effect of warfarin can be routinely
monitored, it is the preferred agent to use in patients after bariatric
surgery. If DOACs must be used in patients after bariatric surgery, we
suggest checking the drug-specific peak and trough levels. If the
drug-specific level is not within the expected range, then VKA should be
used.

Conclusion

There is little literature available on the effects of bariatric surgery
on therapeutic anticoagulation. The changes in drug disposition after
bariatric surgery are not predictable without independent studies of
individual drugs. At present, it appears most prudent to use a vitamin K
antagonist rather than a DOAC for therapeutic oral anticoagulation after
bariatric surgery, as VKAs can be easily monitored, and the dose can be
easily adjusted.

\emph{Ethical/consent statements:}The ethical board of Ahmadi hospital,
Kuwait, had approved the case report , and the concerned patient had
been given full information and consent gave for the case report
publication

Contribution

Zouheir I Bitar wrote the article, Ossama S. Maadarani shared in the
discussion and with M Mohsen and N \textbf{Alkazemi} in collecting the
data and revision of the manuscript

References

\begin{enumerate}
\tightlist
\item
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\item
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\item
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\item
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\item
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\item
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\item
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\end{enumerate}

Table 1 Location of absorption of Antithrombotic Agents\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
\begin{minipage}[b]{0.47\columnwidth}\raggedright\strut
Agent\strut
\end{minipage} & \begin{minipage}[b]{0.47\columnwidth}\raggedright\strut
Location of Absorption\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Apixaban\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Primarily the proximal small intestine; some gastric absorption\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Dabigatran\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Lower stomach and duodenum\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Edoxaban\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Proximal small intestine\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Rivaroxaban\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Primarily the proximal small intestine; some gastric absorption\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Warfarin\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Proximal\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

.

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