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.