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:
  1. 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.
  2. 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
  3. 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.
  4. 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
  5. 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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