| Abstract|| |
Introduction: While disseminated intravascular coagulation (DIC) is a serious complication of COVID-19, a close differential in critically ill patients with thrombocytopenia is Thrombotic thrombocytopenic purpura (TTP). Case Report: We describe the case of a middle-aged lady admitted with COVID-19 pneumonia who developed progressive thrombocytopenia, altered sensorium and renal failure. The absence of coagulation abnormalities alerted to the possibility of TTP, strengthened by presence of schistocytes in peripheral smear. Conclusions: This case highlights the need for high index of suspicion and to pay attention to normal tests as well that might give clues to the diagnosis. New onset thrombocytopenia in COVID-19 need not always indicate DIC. A careful examination of peripheral smear may help diagnosing TTP especially if coagulation profile is normal.
Keywords: Coagulation, COVID-19, disseminated intravascular coagulation, thrombotic thrombocytopenic purpura
|How to cite this article:|
Kesavan S, Eldho G C, Rahman N, Basheer A. Thrombotic thrombocytopenic purpura as an acute complication of COVID-19. Indian J Pathol Microbiol 2022;65:702-4
|How to cite this URL:|
Kesavan S, Eldho G C, Rahman N, Basheer A. Thrombotic thrombocytopenic purpura as an acute complication of COVID-19. Indian J Pathol Microbiol [serial online] 2022 [cited 2022 Aug 15];65:702-4. Available from: https://www.ijpmonline.org/text.asp?2022/65/3/702/351620
| Introduction|| |
Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy classically described as a pentad of fever, neurological abnormalities, renal dysfunction, thrombocytopenia and microangiopathic hemolytic anemia (MAHA). The basic pathophysiology is believed to be a deficiency of ADAMTS-13, a type 1 metalloprotease that cleaves Von Willebrand factor (VWF) and controls excessive platelet aggregation. While it may be idiopathic, it has also been described in association with a range of diseases including severe infections, chemotherapeutic medications and cancers. Here we report the case of a middle-aged lady with COVID-19 disease complicated by TTP.
| Case Report|| |
A 54-year-old lady presented with shortness of breath for 2 days. She had low grade fever but no history of sore throat, cough or chest pain. On examination, she was tachypneic and confused. Her pulse was 110/minute and blood pressure was140/90 mm Hg. She was diagnosed COVID-19 based on a positive antigen test. Her initial clinical features suggested severe COVID-19 illness and her other baseline blood investigations were as follows: hemoglobin – 7.5 g/dl, total leucocyte count –11630 cells/cu.mm., platelet count –1,72,000/cu.mm., blood urea –133 mg/dl, serum creatinine –7.4 mg/dl, serum bilirubin (total) –0.25 mg/dl, direct bilirubin –0.11 mg/dl, Alanine transaminase –12 IU/L, Aspartate transaminase –29 IU/L, Alkaline phosphatase –137 IU/L, serum albumin –3.3 g/dl, INR –1.06. Her chest radiograph showed bilateral non-homogenous opacities consistent with COVID pneumonia. She was initiated on intravenous dexamethasone 6 mg daily, oxygen supplementation, prophylactic dose of unfractionated heparin and other supportive measures. Subsequently her urine output declined progressively, requiring alternate day hemodialysis. Her serial laboratory tests revealed progressively worsening thrombocytopenia with normal coagulation profile [Table 1]. Lactate dehydrogenase (LDH) levels were elevated (973 IU/L). ANA and other autoimmune work up were negative. Coombs test was negative and reticulocyte count was 2.5%. D-Dimer levels were marginally elevated. Although an initial diagnosis of disseminated intravascular coagulation (DIC) was made, the lack of significant coagulation abnormalities suggested otherwise. Meanwhile the patient also developed disorientation to time and place that progressed to worsening of consciousness. She remained drowsy despite ongoing dialysis and improvement in pulmonary status. In view of persistent thrombocytopenia, renal dysfunction, altered mental status and normal coagulation profile, TTP was suspected and a peripheral smear was examined. Presence of numerous schistocytes in the smear strengthened the diagnosis [Figure 1]. Plasma ADAMTS-13 activity was not accessible, and option of plasmapheresis was declined by the patient's relatives. Hence, she was offered pulse intravenous methyl prednisolone (500 mg daily for 3 days) that led to marginal improvement in platelet count and sensorium. However, shortly afterwards she succumbed to multiorgan failure and shock.
| Discussion|| |
Over the last one year and more, clinicians have identified several complications of COVID-19. What began as a pandemic of unusual pneumonia has turned out to be a pandora's box in terms of spectrum of clinical presentations, acute complications and chronic sequelae.
Disseminated intravascular coagulation (DIC) has been recognized as an important complication. DIC is often diagnosed when patients develop thrombocytopenia with elevated prothrombin time and activated partial thromboplastin time. It may present with thrombosis or excessive bleeding. TTP is less often suspected and onset of thrombocytopenia with mild coagulation abnormalities often triggers a diagnosis of DIC. However, several authors have reported TTP in COVID-19 patients, either during the course of illness or as a presenting feature or a late sequela.,, In some cases, patients had other diseases known to trigger TTP such as cancer, and pregnancy. Several authors have reported cases of COVID-19 with initial presentation as TTP.,, TTP has also been reported weeks following COVID-19 disease; however the patient also had a past history of TTP. In some cases, TTP occurred in COVID-19 patients on precipitating medications like cyclosporine.
However, our patient presented primarily with typical respiratory symptoms of COVID-19 and developed TTP during the course of illness. Very few such cases have been reported as acute complication of COVID-19 in patients who otherwise had no predisposing factors for TTP., A high index of suspicion in such cases may help clinch the diagnosis. Associated neurological abnormalities like altered mental status or seizures and new onset or worsening of existing renal dysfunction should alert to this possibility. A peripheral blood smear is invaluable in supporting the diagnosis if it reveals schistocytes in significant numbers. Schistocytes indicate microangiopathic hemolytic anemia due to physical damage to red cells as they pass through vessel lumen altered by microthrombi. This along with a conspicuous absence of abnormalities of the coagulation pathway (normal PT/INR and aPTT) is usually sufficient to make a diagnosis of TTP on a background of underlying predisposing illnesses.
While ADAMTS-13 assays have been proposed and are being routinely done for diagnosis in many centers, several hospitals do not have access to it. Neither is it a pre-requisite for diagnosis and initiating treatment. Therefore, given the high mortality associated with untreated TTP, a prompt diagnosis based on available clinical and laboratory features and initiation of plasmapheresis may be lifesaving. In our case, patient's relatives decided against plasmapheresis and she succumbed to the illness. There is now good quality evidence to suggest plasmapheresis as the treatment of choice for TTP.
This case highlights the need to think beyond what is common when it comes to a master masquerader like COVID-19. It emphasizes the role of clinical reasoning and using the right pieces of information from clinical and laboratory data to solve diagnostic puzzles. Sometimes, laboratory investigations that are normal stand out and may be more important clues that abnormal ones, like the normal coagulation profile in this case. It might be tempting to fall trap to cognitive bias and pattern recognition while dealing with the same underlying disease (such as COVID-19 during this pandemic) too frequently; clinicians must consciously try to break free and think “what else” before premature closure of diagnosis. While the outcome of this patient was not what one would have hoped for, many lives could be saved with a timely diagnosis of TTP, a close differential in critically ill patients with persistent thrombocytopenia.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Page EE, Kremer Hovinga JA, Terrell DR, Vesely SK, George JN. Thrombotic thrombocytopenic purpura: Diagnostic criteria, clinical features, and long-term outcomes from 1995 through 2015. Blood Adv 2017;1:590-600.
Zander CB, Cao W, Zheng XL. ADAMTS13 and von Willebrand factor interactions. Curr Opin Hematol 2015;22:452-9.
Beaulieu M-C, Mettelus DS, Rioux-Massé B, Mahone M. Thrombotic thrombocytopenic purpura as the initial presentation of COVID-19. J Thromb Haemost 2021;19:1132-4.
Albiol N, Awol R, Martino R. Autoimmune thrombotic thrombocytopenic purpura (TTP) associated with COVID-19. Ann Hematol 2020;1-2.
Tehrani HA, Darnahal M, Vaezi M, Haghighi S. COVID-19 associated thrombotic thrombocytopenic purpura (TTP) ; A case series and mini-review. Int Immunopharmacol 2021;93:107397. doi: 10.1016/j.intimp. 2021.107397.
Darnahal M, Azhdari Tehrani H, Vaezi M, Haghighi S. Covid-19 and thrombotic thrombocytopenic Purpura: A case report. Int J Hematol Oncol Stem Cell Res 2021;15:72-4.
Aminimoghaddam S, Afrooz N, Nasiri S, Motaghi Nejad O, Mahmoudzadeh F. A COVID-19 pregnant patient with thrombotic thrombocytopenic purpura: A case report. J Med Case Rep 2021;15:104.
Altowyan E, Alnujeidi O, Alhujilan A, Alkathlan M. COVID-19 presenting as thrombotic thrombocytopenic purpura (TTP). BMJ Case Rep 2020;13:e238026. doi: 10.1136/bcr-2020-238026.
Dhingra G, Maji M, Mandal S, Vaniyath S, Negi G, Nath UK. COVID 19 infection associated with thrombotic thrombocytopenic purpura. J Thromb Thrombolysis 2021;
Capecchi M, Mocellin C, Abbruzzese C, Mancini I, Prati D, Peyvandi F. Dramatic presentation of acquired thombotic thrombocytopenic purpura associated with COVID-19. Haematologica 2020;105:e540.
Al-Ansari RY, Bakkar M, Abdalla L, Sewify K. Critical care COVID-19 patient with a picture of thrombotic thrombocytopenic purpura. Eur J Case Rep Intern Med 2020;7:002143. doi: 10.12890/2020_002143.
Nicolotti D, Bignami EG, Rossi S, Vezzani A. A case of thrombotic thrombocytopenic purpura associated with COVID-19. J Thromb Thrombolysis 2021;52:468-70.
Hindilerden F, Yonal-Hindilerden I, Akar E, Kart-Yasar K. Covid-19 associated autoimmune thrombotic thrombocytopenic purpura: Report of a case. Thromb Res 2020;195:136-8.
George JN. Measuring ADAMTS13 activity in patients with suspected thrombotic thrombocytopenic purpura: When, how, and why? Transfusion 2015;55:11-3.
George JN. How I treat patients with thrombotic thrombocytopenic purpura: 2010. Blood 2010;116:4060-9.
D. M. Wayanad Institute of Medical Sciences, Wayanad - 673 577, Kerala
Source of Support: None, Conflict of Interest: None