Figure 1. Peripheral smear with numerous schistocytes seen.
Differential Diagnosis
The patient initially presented with normal platelet count and with
normal mentation. The rapid onset of thrombocytopenia and renal failure
in the context of severe COVID19 infection raised the concern for
possible thrombocytopenia induced by consumptive process due to her
underlying infection. In addition, COVID19-induced thrombotic angiopathy
without TTP was also considered on account of the patient’s
coagulopathic and inflammatory changes. The presence of a significant
number of schistocytes on peripheral smear raised the concern for
thrombotic thrombocytopenic purpura (TTP), despite initial presentation
with normal platelet count and concurrent COVID19 infection. Due to a
high clinical and laboratory suspicion for TTP, plasma exchange with FFP
was initiated with pending ADAMTS13 results. The patient experienced a
significant improvement in her clinical status, biochemically, by
laboratory values and with significant decrease in schistocyte per high
power field. The patient’s coagulation profile was not consistent with
disseminated intravascular coagulation (DIC). On account of normal
ADAMTS13 levels, yet clear laboratory and pathologic evidence of a
thrombotic microangiopathy, our patient was diagnosed with
COVID19-induced thrombotic angiopathy, which responded briskly to plasma
exchange intervention.
Discussion
Patients with COVID19 infection have been found to exhibit a wide array
of symptoms and complications, as published in the literature in 2020.
There is a known association with COVID19 infection and a unique
coagulopathy. It is postulated that this coagulopathy may be related to
endothelial activation and microvascular thrombosis/hemolysis. There is
evidence that viruses play an important role as a trigger in the
pathogenesis of thrombotic angiopathies. The mechanism of this remains
unclear; it has been suggested that direct endothelial injury by
cytokine storm and immune complex mediated events along with ADAMTS13
inhibitors are implicated as underlying triggers of viral activated
thrombotic microangiopathy [1].
A study evaluating secondary thrombotic microangiopathy in
COVID19-infected patients found that patients with low ADAMTS13 levels,
elevated LDH, presence of schistocytes and elevated von Willebrand
factor levels were more likely to indicate severe infection and high
likelihood of death [2].
There are case reports of secondary TTP due to COVID19 infection. There
is also a report by Albiol et al. of a 57-year-old woman diagnosed with
acquired autoimmune TTP following the diagnosis of Covid-19 [3].
Another case is reported by Hindilerden et al. of a case of TTP which
was diagnosed following COVID19 infection [4].
Martinelli et. al carried out a retrospective study on 50 admitted
patients with COVID19 infection in which they evaluated various
laboratory values. They found that about 2-4% of patients had
documentation of schistocytes on peripheral smears. They also found a
mild decrease in ADAMTS13 level in most of the subjects (47% with 95%
CI 40–55). This was the first study suggesting ADAMTS13 impairment in
COVID19 infection [5].
Our patient had a COVID-19-associated thrombotic microangiopathy that
exhibited a dramatic response to plasma exchange. The current report
adds to a growing body of literature reporting improvement with plasma
exchange in severely ill patients with COVID19 infection [6][7].
It is conceivable that plasma exchange accounts for cytokine removal of
inflammatory mediators in the plasma and reinstitution of immune
homeostasis. While employing plasma exchange as a therapeutic modality
for COVID-19 is sure to pose significant challenges, the emerging
evidence warrants further scientific consideration. Plasma exchange used
on a limited scale, particularly for patients with COVID-19
microangiopathy, may represent a useful treatment for a particularly
devastating manifestation of COVID-19.
References:
- Lopes da Silva R. Viral-associated thrombotic
microangiopathies. Hematol. Oncol. Stem Cell Ther. 2011;4(2):51–59.
doi: 10.5144/1658-3876.2011.51.
- Sweeney JM, Barouqa M, Krause GJ, Gonzalez-Lugo JD, Rahman S, Gil MR.
Evidence for secondary thrombotic microangiopathy in COVID-19.
Preprint. medRxiv . 2020;2020.10.20.20215608. Published 2020 Oct
23. doi:10.1101/2020.10.20.20215608
- Albiol N., Awol R., Martino R. Autoimmune thrombotic thrombocytopenic
purpura (TTP) associated with COVID-19. Ann. Hematol. 2020 May
28:1–2. doi: 10.1007/s00277-020-04097-0.
- Hindilerden, Fehmi et al. “Covid-19 associated autoimmune thrombotic
thrombocytopenic purpura: Report of a case.” Thrombosis research vol.
195 (2020): 136-138. doi:10.1016/j.thromres.2020.07.005
- Martinelli, N., Montagnana, M., Pizzolo, F., Friso, S., Salvagno, G.,
Forni, G., Luca et al. (2020). A relative ADAMTS13 deficiency supports
the presence of a secondary microangiopathy in COVID 19. Thrombosis
Research. 193. . 2020 Sep; 193: 170–172
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followed by intravenous immunoglobin in a critically ill patient with
2019 novel coronavirus infection. Int J Antimicrob Agents.
2020:105974. doi: 10.1016/j.ijantimicag.2020.105974.
- Zhang L., Zhai H., Ma S., Chen J., Gao Y. Efficacy of therapeutic
plasma exchange in severe COVID-19 patients. Br J Haematol. 2020 doi:
10.1111/bjh.16890