Discussion:
Here we present a case of COVID-19 which was complicated by TTP which is
an extremely rare complication of COVID-19 as per the current
information available in the literature. The widespread thrombus
formation in COVID-19 together with low grade MAHA signified by low
hemoglobin, raised LDH, increase in bilirubin and presence of
schistocytes mimics TTP which is a part of
TMA.[3]
TTP is classified as either primary/idiopathic or secondary/acquired,
with acquired being the more common variant of the
disease.[6] Acquired
TTP has female preponderance and affects women intra and postpartum with
an estimated prevalence of 1 in 25,000
pregnancies.[6,
7] Autoantibody induced destruction or
suppression of a disintegrin and metalloproteinase with a thrombospondin
type I motif, member 13 (ADAMTS13), an enzyme that splits large
multimers of von willebrand factor, is considered the precursor for TTP.
TTP can also be precipitated by infections with literature citing case
reports showing association between TTP and H1N1 as well as
between TTP andArboviruses. [8,
9] SARS-CoV-2 has also been associated
with TTP and literature review has revealed three such cases.
A case of relapsing TTP (history of TTP 30 years ago) due to COVID was
reported by Capecchi et al in a 55 year old male patient from Italy with
generalized weakness, shortness of breath and chest discomfort. TTP was
suspected due to rapidly dropping platelet counts 184,000/µL to
14000/µL, along with decrease in hemoglobin level 11.4 to 7.4 g/dl and
presence of schistocytes on peripheral blood smear. Plasma ADAMTS13
levels were undetectable and PLEX was initiated promptly in combination
with Caplacizumab, a humanized antibody against von willebrand factor.
In this patient two nasopharyngeal PCR for SARS-CoV-2 were negative but
COVID antibody against SARS-CoV-2 was positive. Hospital stay got
complicated because of acute right parietal lobe infarct and hemoptysis
due to ectatic artery with a fistulous tract in right main bronchus for
which angioembolization of culprit artery was performed. 14 sessions of
PLEX were done and glucocorticoids along with Caplacizumab were
continued for 12 days. Patient was discharged home after 31 days with
normal platelet
counts.[10]
Albiol et al reported a case of 57-year old Spanish woman with history
of breast cancer who presented with fever and anosmia. Two
nasopharyngeal samples for SARS-CoV-2 were negative but IgG antibodies
for SARS-CoV-2 were positive. On 5th day of hospital stay patient
developed severe thrombocytopenia and low hemoglobin. TTP was
established on the basis of MAHA, low platelet counts and very low
activity of ADAMTS13. Patient responded to PLEX and was discharged
home.[11]
Similarly, Hindilerden et al from Turkey reported a case of 74-year old
lady who presented with cough and generalized weakness. PCR for
SARS-CoV-2 was positive. On arrival, she had hemoglobin of 6.6 g/dl and
platelet counts of 48,000/µL. Peripheral blood smear showed
schistocytes. Patient was managed on lines of presumed acquired TTP by
initiation of PLEX and methylprednisolone pulse therapy. ADAMTS13 levels
were reported to be < 0.2% and ADAMTS13 inhibitor
concentration was more than 90%. Patient received 11 sessions of PLEX
and was discharged home on a hemoglobin levels of 10.6g/dl and platelet
counts of
398,000/µL.[12]
To the best of our knowledge this is the fourth case of TTP associated
with COVID 19 and first from South Asia. Our patient is unique in
several aspects as our patient had no comorbid conditions prior to this
illness. He presented with fever and decreased level of consciousness.
He was intubated and managed in intensive care unit. Our patient
developed low hemoglobin, platelets and deranged renal function on 6th
hospital stay. The 3 case reports mentioned in literature predominately
showed hematological manifestations of TTP while deranged renal function
and neurological symptoms have not been described. Our patient
demonstrated significant renal dysfunction and neurological symptoms
along with hematological derangements of TTP. All the symptoms either
resolved completely or improved with treatment. However, in our case we
were not able to do ADAMTS13 levels because of unavailability of this
test in our institute. However, Plasmic score was calculated in order to
estimate ADAMTS13 deficiency. Our patient responded well to PLEX and
glucocorticoids and a seven sessions of PLEX were done in total.
COVID-19 was treated symptomatically as patient had no overt respiratory
symptoms. A retrospective study done at our hospital included 25
patients with TTP treated with PLEX. The study concluded that
neurological and renal involvement in TTP was a strong predictor of
outcomes and clinical improvement. However, a delay in initiation of
PLEX due to late presentation was a major
obstacle.[13] Our
patient also received one dose of Rituximab at a dose of 375
g/m2. A study done in China showed that adding
rituximab to PLEX and steroids increases the platelet counts in
approximately 80% of patients and also reduces mean time to attain a
normal platelet
count.[14] This
study also illustrated that prognosis is better if rituximab is
administered within 3 days of treatment initiation. Rituximab was
originally used in TTP for refractory disease but it is now used as
first line with PLEX based on observational studies signifying that
rituximab may accelerate recovery and reduces the risk of
relapse.[15]Further doses of Rituximab were withheld due to development of hospital
acquired infections. Hospital stay got complicated with Candida
glabrata in blood for which intravenous Amphotericin B was started. Of
the three previous studies only one has described any complication but
none has shown hospital acquired infections.