PROC (BAYL UNIV MED CENT)

2022;35(6):832–833
Copyright # 2022 Baylor University Medical Center
https://doi.org/10.1080/08998280.2022.2101106

Caplacizumab in the successful management of cardiac

involvement in thrombotic thrombocytopenic purpura
Amir A. Mahmoud, MDa , Basant Eltaher, MDb , and Anas Hashem, MDa
a
Department of Internal Medicine, Rochester General Hospital, Rochester, New York; bDepartment of Hematology and Bone Marrow
Transplant, Ain Shams University, Cairo, Egypt

Cardiac involvement is well documented in thrombotic thrombocytopenic purpura (TTP). Management remains challenging due to
thrombocytopenia. Caplacizumab is a novel medication in TTP, but questions remain on its overall benefit in TTP patients. We report
a 76-year-old woman who was admitted for non–ST segment elevation myocardial infarction, left systolic ventricular dysfunction,
severe hemolytic anemia, and thrombocytopenia suggestive of TTP (PLASMIC score 7). Therapeutic plasma exchange (TPE) and
caplacizumab were started alongside an immunosuppressive regimen. After 3 days of treatment, repeat echocardiography showed
complete resolution of left ventricular dysfunction. We were able to stop TPE and start aspirin on the fourth day after normalization
of platelet count. Our report outlines the potential benefits of caplacizumab for the time-sensitive management of acute coronary
syndrome and the compromised volume status of heart failure patients, with early platelet recovery and lower duration of TPE.
KEYWORDS caplacizumab; cardiomyopathy; case report; NSTEMI; thrombotic thrombocytopenic purpura

T
hrombotic thrombocytopenic purpura (TTP) is a sub-
type of microangiopathic hemolytic disorders where
microthrombi develop, leading to widespread organ
damage. Cardiac involvement has been described in
TTP, and its management continues to be clinically challeng-
ing. The recent approval of the von Willebrand factor blocking
therapy caplacizumab provides an additional option to standard
therapy, with much promise in improving outcomes in TTP.
In this report, we present a case of TTP-induced myocardial
infarction and cardiomyopathy treated successfully with thera-
peutic plasma exchange (TPE) and caplacizumab.
CASE DESCRIPTION
A 76-year-old woman with a past medical history of dia-
betes, hypertension, and gastroesophageal reflux disease pre-
sented to the emergency department after a mechanical fall.
This was preceded by 3 days of generalized fatigue, confusion,
and lethargy. She had no recent complaints of chest pain, dys-
pnea, or palpitations. She was vitally stable but difficult to
arouse. Other than a generalized petechial rash, the physical
examination was unrevealing. An electrocardiogram showed
only sinus tachycardia. A computed tomography scan of her
head was unremarkable. The high-sensitivity troponin I level
was >5000 pg/mL; platelet count, 3000/lL; hemoglobin, 9.6
g/dL; and creatinine, 1.5 mg/dL. Prothrombin time, inter-
national normalized ratio, partial thromboplastin time, and
fibrinogen were within normal limits.
An emergent echocardiogram revealed left systolic ven-
tricular dysfunction (ejection fraction 28%) with focal wall
motion abnormalities. The patient was diagnosed with
non–ST segment elevation myocardial infarction (NSTEMI).
Antiplatelet therapy, anticoagulation, and cardiac catheteriza-
tion were deferred due to thrombocytopenia. Further workup
for anemia revealed indirect hyperbilirubinemia (1.8 mg/dL)
and consumed haptoglobin (<1 mg/dL). The reticulocyte
count (3.5%) and lactate dehydrogenase (LDH) (622 U/L)
were also elevated, suggesting hemolytic anemia. A review of
the smear revealed many schistocytes (>5 per high power
field; Figure 1), and a PLASMIC score of 7 put her at high
risk for TTP and severe ADAMTS13 deficiency.
TPE and caplacizumab were started immediately after
sending for ADAMTS13 and inhibitor levels. A 3-day course
of high-dose (500 mg) methylprednisolone was prescribed and

Corresponding author: Amir A. Mahmoud, MD, Department of Internal Medicine, Rochester General Hospital, 1200 East Ridge Road, Apt. 2, Rochester, NY
14621 (e-mail: allstar_amir@hotmail.com; amir.mahmoud@rochesterregional.org)
The authors report no funding or conflicts of interest. Informed consent to publish this case report was obtained from the patient’s grandchild (clos-
est relative).
Received June 8, 2022; Revised July 5, 2022; Accepted July 7, 2022.

832 Volume 35, Number 6


Figure 1. Schistocytes on blood smear.
then tapered to oral prednisone. Complete normalization of
platelet count (>150,000/lL) was achieved on day 4 of ther-
apy, leading to discontinuation of TPE and starting aspirin for
NSTEMI. The LDH dropped below 2 times the upper limit
of normal, and repeat echocardiography on day 3 showed
resolution of wall motion abnormalities and a near-normal
ejection fraction of 50%. The ADAMTS13 level resulted on
day 4 and confirmed severe TTP (<5%). The patient then
completed 4 doses of weekly rituximab and 30 days of caplaci-
zumab. She developed mild thrombocytosis (562,000/lL)
during the second week of treatment but gradually returned
to normal levels shortly afterward. ADAMTS13 follow-up
results showed adequate response after 1 week of treatment
(28%) and complete resolution at 1 month (74%). Bleeding
complications included self-resolving mild epistaxis and a sub-
cutaneous hematoma near the elbow joint after a mechanical
fall. At 3- and 6-month follow-up, she remained in durable
remission, and she had no new cardiac insults.
DISCUSSION
In TTP, platelet microthrombi form in various organs,
mediating organ damage. Cardiac involvement occurs mainly
through microvascular microthrombosis and has been found in
a sizable portion of deceased TTP patients on autopsy.1
Similar to our case, the majority of patients do not present
with typical symptoms suggestive of myocardial ischemia, while
an increase in troponin level is the more common finding.2
The von Willebrand factor blocking therapy caplacizu-
mab has been recently incorporated into the medical man-
agement of TTP.3 In two landmark trials, caplacizumab was
shown to be associated with reduced time to platelet recov-
ery, fewer TPE sessions, and fewer exacerbations, albeit with
a greater frequency of relapse and a higher bleeding risk. In
terms of organ damage, the data suggest a trend toward
slightly more rapid improvement of markers such as LDH
and troponin, with a median time to normal troponin level
being 9 days in caplacizumab-treated patients compared to
27 days in the standard treatment groups.4–6
Picod et al proposed a strategy where a high probability
on predictive scoring (PLASMIC score) warrants early initi-
ation of caplacizumab.7,8 Other experts have suggested
November 2022 Caplacizumab in the successful management of cardiac involvement in thrombotic thrombocytopenic purpura
initiating caplacizumab only when severe features such as crit-
ical illness, neurologic findings, or high troponin levels are
present.9 While there have been advancements in the evi-
dence-based management of acute coronary syndrome and
cardiomyopathy in recent years, the use of this targeted man-
agement approach has not been well investigated in TTP
patients. Aspirin has been generally considered beneficial in
TTP patients with acute coronary syndrome; however, a plate-
let count threshold of 50  109/L is usually needed for safe
use.10 While caplacizumab offers an opportunity to reach that
threshold faster and more consistently, the use of aspirin and
caplacizumab concurrently has not been studied and may
entail a theoretically higher bleeding risk. Caplacizumab does
seem to be an attractive option for TTP patients presenting
with heart failure, as it offers the opportunity for earlier stop-
page of TPE with a lower total volume of plasma infusion and
hence less volume overload and pulmonary congestion.
ORCID
Amir A. Mahmoud http://orcid.org/0000-0002-0630-1117
Basant Eltaher http://orcid.org/0000-0003-1255-0408
Anas Hashem http://orcid.org/0000-0002-2008-7110
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