J Med Cases
Journal of Medical Cases, ISSN 1923-4155 print, 1923-4163 online, Open Access
Article copyright, the authors; Journal compilation copyright, J Med Cases and Elmer Press Inc
Journal website https://www.journalmc.org

Case Report

Volume 13, Number 4, April 2022, pages 168-171


COVID-19 Presenting With a Challenging Combination of Thrombocytopenia and Thrombosis

Swapna Ravia, h, Sushmita Khadkab, Charumathi Subrahmanian Raghuc, Ananth Ravid, Sharmisha Vanukurie, Tapasya Mandalapuf, Vineela Kasireddyg

aDepartment of Internal Medicine, St. Luke’s Internal Medicine Associates, Duluth, MN, USA
bDepartment of Internal Medicine, Guthrie Clinic/Robert Packer Hospital, Sayre, PA, USA
cDepartment of Medicine, Washington Hospital Health Care System, Fremont, CA, USA
dDepartment of Radiology, Essentia Health-St. Mary’s Medical Center, Duluth, MN, USA
eDepartment of Medicine, Miami University, Miami, FL, USA
fDepartment of Medicine, HCA Houston Healthcare Conroe, Houston, TX, USA
gDepartment of Hematology and Oncology, Guthrie Clinic/Robert Packer Hospital, Sayre, PA, USA
hCorresponding Author: Swapna Ravi, Department of Internal Medicine, St. Luke’s Internal Medicine Associates, Duluth, MN 55802, USA

Manuscript submitted December 15, 2021, accepted January 15, 2022, published online March 25, 2022
Short title: Thrombocytopenia and Thrombosis in COVID-19
doi: https://doi.org/10.14740/jmc3886

Abstract▴Top 

Coronavirus disease 2019 (COVID-19) causes various hematological abnormalities, leading to several complications in the disease course. We report two COVID-19 cases presenting with a combination of thrombocytopenia and coagulopathy complications in late 2020. A 73-year-old male with a history of immune thrombocytopenic purpura (ITP) presented with acute ischemic stroke and acute thrombocytopenia in the setting of COVID-19. He was managed with steroids and intravenous immunoglobulin (IVIG) and had a subsequent acute ischemic stroke with microhemorrhages. Another 72-year-old female with a history of cryptogenic liver cirrhosis and chronic thrombocytopenia presenting with acute thrombocytopenia in the setting of COVID-19 was managed with steroids and IVIG. She had a coagulopathic complication of deep venous thrombosis (DVT) later in her disease course managed with inferior vena cava filter and low-dose enoxaparin, but she subsequently died with a bleeding complication of retroperitoneal hemorrhage. Despite the aggressive ongoing research, the treatment options for severe COVID-19 are limited to date and the mortality remains high. Both these cases are examples of challenging situations that the physicians are currently facing with COVID-19 pandemic.

Keywords: COVID-19; Thrombocytopenia; Coagulopathy; Thrombosis

Introduction▴Top 

Coronavirus disease 2019 (COVID-19) presents with varying severity and several complications, frequently involving hemostatic system [1]. Various hematological abnormalities are reported in COVID-19 patients, some of which have prognostic significance. Guan et al [2] reported lymphopenia in 83.2% of their study patients, thrombocytopenia in 36.2% and leukopenia in 33.7%, and the level of these abnormalities was directly correlated with severity of COVID-19. Platelet changes were commonly reported leading to several complications in the disease course such as thrombocytopenia, systemic hypercoagulability and thromboembolic events [1]. Here we report two challenging cases where COVID-19 presented with thrombocytopenia and thrombosis together, complicating the course and management of this disease.

Cases Reports▴Top 

Case 1

Investigations

A 73-year-old male with a past medical history of metastatic poorly differentiated lung adenocarcinoma status post two cycles of carboplatin + pembrolizumab, poorly controlled rheumatoid arthritis, chronic immune thrombocytopenic purpura (ITP), recent upper extremity deep venous thrombosis (DVT) and pulmonary embolism (PE) for which he was receiving anticoagulation therapy with apixaban, was admitted with acute change in mental status. His last dose of chemotherapy was more than a month before his initial presentation.

Diagnosis

His polymerase chain reaction (PCR) testing for COVID-19 was positive. Computed tomography (CT) scan of head without contrast showed chronic age-related microvascular changes without any acute intracranial pathology. Magnetic resonance imaging (MRI) of the brain with and without contrast showed left cerebral acute infarcts with microhemorrhages, punctuate right occipital infarct, left parietal signal abnormalities and punctate foci of enhancement. Initial lab testing revealed: white blood cell count of 5.03 × 109/L of which lymphocytes were 13%, D-dimer > 20 µg/mL, partial thromboplastin time (PTT) of 32.6 s, international normalized ratio (INR) of 1.2, platelet count of 60,000/mm3. His baseline platelet count was around 75,000/mm3. The etiology of his thrombocytopenia was presumed to be exacerbation of his chronic ITP in setting of COVID-19 infection. His platelet counts progressively trended down to below 40,000/mm3.

Treatment

Apixaban was held and he was given 3 days of intravenous (IV) dexamethasone 4 mg every 6 h followed by 2 days of intravenous immunoglobulin (IVIG) 1 g/kg. Platelet count slightly improved but remained below 60,000/mm3. His D-dimer was persistent at > 20 µg/mL; however, given his refractory thrombocytopenia, his anticoagulation was decided to be held. He was discharged home with oral prednisone 15 mg daily. He was re-admitted the very next day with blurred vision, and MRI of the brain showed interval evolution of previously seen infarct in the left cerebral hemisphere, large acute infarct in right temporal lobe with microhemorrhages.

Follow-up and outcomes

Given his multiple comorbidities with poor prognosis, he was placed on home hospice care and expired within few days.

Case 2

Investigations

A 72-year-old female with aortic stenosis status post bioprosthetic valve and cryptogenic liver cirrhosis with chronic thrombocytopenia (bone marrow biopsy in past excluded leukemia, aplastic anemia or lymphoproliferative disorder) had an initial hospital admission for COVID-19-related pneumonia and was treated with dexamethasone and remdesivir. During this admission, she was noted to have a platelet count of 11,000/mm3 without any signs and symptom of bleeding and D-dimer of 2.8 µg/mL. Her baseline platelet count was 40,000/mm3. She received a dose of IVIG 0.5 g/kg with slight improvement in platelet count and was discharged home. She had a second hospital admission for fall within couple of days, during which her WBC count was 10.49 × 109/L, lymphocytes were 5.2%, PTT was 25.5 s, INR was 1.4, platelet count was 24,000/mm3 without any signs of bleeding. She was treated with 90 mg of prednisone daily and was discharged with a plan to taper prednisone by10 mg every 3 days. Two days later, she had third hospital admission for worsening shortness of breath.

Diagnosis

CT ruled out PE and showed persistent bilateral lung infiltrates consistent with COVID pneumonia. Her platelet count during this admission was less than 25,000/mm3. Duplex of lower extremity showed bilateral occlusive DVT in femoral and popliteal veins extending up to right common femoral vein.

Treatment

Interventional radiology-guided inferior vena cava filter was placed. There was no improvement in platelet count with high-dose steroid or IVIG. Her bone marrow biopsy showed hypercellular bone marrow with adequate mature granulopoiesis and megakaryopoiesis without increased blasts, myelodysplastic syndrome, or marrow involvement by lymphoma. She was treated with two doses of romiplostim 100 µg, 4 days apart, after which platelet count increased to > 40,000/µL and she was placed on anticoagulation therapy with subcutaneous enoxaparin 0.5 mg/kg two times daily.

Follow-up and outcomes

Four days later, she was readmitted with retroperitoneal bleed, hypoxemic respiratory failure, and hypotension with a platelet count of 334,000/µL. She was placed on comfort care measures and expired.

Discussion▴Top 

Thrombocytopenia or thrombosis are commonly seen in COVID-19 patients, and the combination of these complications is particularly challenging.

Thrombocytopenia

Thrombocytopenia is reported to be mild to moderate in most COVID-19 cases without causing significant bleeding complications [3, 4]. Thrombocytopenia and platelet-to-lymphocyte ratio were reported to have a prognostic role in COVID-19 [4-6]. On admission, thrombocytopenia was reported in 35.8% of patients who had a composite outcome of admission to intensive care unit (ICU), requiring mechanical ventilation or death in 14 days, and 52.6% in patients who died in 14 days [5]. The in-hospital mortality was also directly correlated with severity of thrombocytopenia [6].

The causes of thrombocytopenia are unclear, but several mechanisms were proposed as described in Table 1 [1, 3, 4, 7].

Table 1.
Click to view
Table 1. Proposed Mechanisms of COVID-19-Associated Thrombocytopenia
 

Management of thrombocytopenia is usually supportive and depends on the cause of thrombocytopenia. Critical causes such as thrombotic thrombocytopenic purpura and heparin-induced thrombocytopenia must be excluded first [8]. ITP is a diagnosis of exclusion. Steroids such as prednisolone at a dose of 1 mg/kg tapered after 2 weeks is standard first-line therapy [8]. IVIG is second-line therapy in ITP patients who fail to respond appropriately to steroids [8]. Platelet transfusion should be avoided in patients without significant hemorrhage due to the risk of thrombosis in COVID-19 [8]. Thrombopoietin receptor agonists should also be avoided given the risk of thrombosis in COVID-19 patients [8]. Due to the risk of developing severe COVID-19, it is better to avoid immunosuppressant drugs [8].

Coagulopathy

Thrombosis is one of the dreaded complications and a major cause of morbidity and mortality in COVID-19 [9]. COVID-19 with acute respiratory distress syndrome was associated with more thrombotic complications [7]. Klok et al reported 27% venous thromboembolism and 3.7% arterial thrombosis in COVID-19 ICU patients despite at least standard dose thromboprophylaxis [10]. PE was reported to be most common [10].

Various coagulation abnormalities are hallmark of COVID-19 coagulopathy. Elevated D-dimer and fibrinogen, prolonged prothrombin time and activated PTT, mild thrombocytopenia were commonly reported [1, 9, 10]. High D-dimer and fibrin degradation product (FDP) levels, prolonged prothrombin time and activated partial thromboplastin time were associated with higher mortality rate [11]. Elevated D-dimer levels can also be used to predict risk of thrombosis [12]. In very severe cases, a disseminated intravascular coagulopathy (DIC) like state was reported with extremely elevated D-dimer; however, fibrinogen level is often normal or elevated in COVID-19 unlike in classic DIC [1, 9].

Platelets, endothelium and inflammatory cells were involved in COVID-19-associated coagulopathy, of which platelets were reported to have a significant role. Following are the proposed mechanisms of COVID-19-associated coagulopathy as described in Table 2 [1, 13].

Table 2.
Click to view
Table 2. Proposed Mechanisms of COVID-19-Associated Coagulopathy
 

Thromboprophylaxis was showed to lower incidence of DVT in COVID-19 hospitalized patients [12]. Thromboprophylaxis with heparin was associated with lower mortality in COVID-19 with elevated D-dimer and increased risk for thrombosis [14]. Physical therapy and hydration in addition to thromboprophylaxis during hospitalization are important measures to prevent thrombosis. Low-molecular-weight heparin is first-line standard thromboprophylaxis; however appropriate dose recommendation is not certain to date [1, 7, 9, 15]. Thromboprophylaxis is recommended in all COVID-19 hospitalized patients unless contraindicated in situations such as active bleeding, platelet count < 25 × 109/L or significantly low fibrinogen level [1]. Mechanical preventive measures can be used when anticoagulation is contraindicated [7]. Several trials are ongoing but currently there is no evidence supporting prophylactic use of antiplatelet agents to prevent COVID-19 thrombotic complications [1, 9]. Drugs such as argatroban seem to be promising agents theoretically in treating severe COVID-19 cases; however randomized trails are required to support evidence [16].

Therapeutic anticoagulation with either unfractionated or low-molecular-weight heparin is recommended to treat COVID-19 thrombosis [9, 15]. Oral anticoagulants should be avoided due to possible interactions with antiviral agents [15]. Antiplatelet agents are used in acute treatment of arterial thrombotic complications [9].

Treatment options for severe COVID-19 cases are limited to date. More randomized controlled trials are required to better understand the pathophysiology of this disease and develop better treatment options.

Learning points

Various hematological abnormalities associated with various complications are reported in COVID-19. A combination of thrombocytopenia and thrombosis as seen in the above reported cases, is particularly challenging.

Acknowledgments

None to declare.

Financial Disclosure

No funding to declare.

Conflict of Interest

No conflict of interest to disclose.

Informed Consent

Verbal consents were given by the patients or their significant others in the case where patient is not available to consent.

Author Contributions

Sushmita Khadka wrote up the case presentations. Swapna Ravi wrote up the rest of the manuscript. All other authors helped with literature review and formatting the manuscript.

Data Availability

The authors declare that data supporting the findings of this study are available within the article.


References▴Top 
  1. Wool GD, Miller JL. The impact of COVID-19 disease on platelets and coagulation. Pathobiology. 2021;88(1):15-27.
    doi pubmed
  2. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708-1720.
    doi pubmed
  3. Xu P, Zhou Q, Xu J. Mechanism of thrombocytopenia in COVID-19 patients. Ann Hematol. 2020;99(6):1205-1208.
    doi pubmed
  4. Zhang Y, Zeng X, Jiao Y, Li Z, Liu Q, Ye J, Yang M. Mechanisms involved in the development of thrombocytopenia in patients with COVID-19. Thromb Res. 2020;193:110-115.
    doi pubmed
  5. Maquet J, Lafaurie M, Sommet A, Moulis G. Thrombocytopenia is independently associated with poor outcome in patients hospitalized for COVID-19. Br J Haematol. 2020;190(5):e276-e279.
    doi pubmed
  6. Yang X, Yang Q, Wang Y, Wu Y, Xu J, Yu Y, Shang Y. Thrombocytopenia and its association with mortality in patients with COVID-19. J Thromb Haemost. 2020;18(6):1469-1472.
    doi pubmed
  7. Mei H, Luo L, Hu Y. Thrombocytopenia and thrombosis in hospitalized patients with COVID-19. J Hematol Oncol. 2020;13(1):161.
    doi pubmed
  8. Pavord S, Thachil J, Hunt BJ, Murphy M, Lowe G, Laffan M, Makris M, et al. Practical guidance for the management of adults with immune thrombocytopenia during the COVID-19 pandemic. Br J Haematol. 2020;189(6):1038-1043.
    doi pubmed
  9. Gu SX, Tyagi T, Jain K, Gu VW, Lee SH, Hwa JM, Kwan JM, et al. Thrombocytopathy and endotheliopathy: crucial contributors to COVID-19 thromboinflammation. Nat Rev Cardiol. 2021;18(3):194-209.
    doi pubmed
  10. Klok FA, Kruip M, van der Meer NJM, Arbous MS, Gommers D, Kant KM, Kaptein FHJ, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020;191:145-147.
    doi pubmed
  11. Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020;18(4):844-847.
    doi pubmed
  12. Zhang L, Feng X, Zhang D, Jiang C, Mei H, Wang J, Zhang C, et al. Deep vein thrombosis in hospitalized patients with COVID-19 in Wuhan, China: prevalence, risk factors, and outcome. Circulation. 2020;142(2):114-128.
    doi pubmed
  13. Zhang S, Liu Y, Wang X, Yang L, Li H, Wang Y, Liu M, et al. SARS-CoV-2 binds platelet ACE2 to enhance thrombosis in COVID-19. J Hematol Oncol. 2020;13(1):120.
    doi pubmed
  14. Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost. 2020;18(5):1094-1099.
    doi pubmed
  15. Miesbach W, Makris M. COVID-19: Coagulopathy, Risk of Thrombosis, and the Rationale for Anticoagulation. Clin Appl Thromb Hemost. 2020;26:1076029620938149.
    doi pubmed
  16. Aliter KF, Al-Horani RA. Thrombin inhibition by Argatroban: potential therapeutic benefits in COVID-19. Cardiovasc Drugs Ther. 2021;35(2):195-203.
    doi pubmed


This article is distributed under the terms of the Creative Commons Attribution Non-Commercial 4.0 International License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Journal of Medical Cases is published by Elmer Press Inc.

 

Browse  Journals  

 

Journal of Clinical Medicine Research

Journal of Endocrinology and Metabolism

Journal of Clinical Gynecology and Obstetrics

 

World Journal of Oncology

Gastroenterology Research

Journal of Hematology

 

Journal of Medical Cases

Journal of Current Surgery

Clinical Infection and Immunity

 

Cardiology Research

World Journal of Nephrology and Urology

Cellular and Molecular Medicine Research

 

Journal of Neurology Research

International Journal of Clinical Pediatrics

 

 
       
 

Journal of Medical Cases, monthly, ISSN 1923-4155 (print), 1923-4163 (online), published by Elmer Press Inc.                     
The content of this site is intended for health care professionals.
This is an open-access journal distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License, which permits unrestricted
non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Creative Commons Attribution license (Attribution-NonCommercial 4.0 International CC-BY-NC 4.0)


This journal follows the International Committee of Medical Journal Editors (ICMJE) recommendations for manuscripts submitted to biomedical journals,
the Committee on Publication Ethics (COPE) guidelines, and the Principles of Transparency and Best Practice in Scholarly Publishing.

website: www.journalmc.org   editorial contact: editor@journalmc.org
Address: 9225 Leslie Street, Suite 201, Richmond Hill, Ontario, L4B 3H6, Canada

© Elmer Press Inc. All Rights Reserved.