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Table of Contents
CASE REPORT
Year : 2021  |  Volume : 14  |  Issue : 3  |  Page : 138-141

Thromboprophylaxis causing spontaneous bleeds in COVID patients


Department of General Surgery, Rashid Hospital, Dubai, UAE

Date of Submission16-Apr-2021
Date of Decision01-Jun-2021
Date of Acceptance10-Jun-2021
Date of Web Publication01-Oct-2021

Correspondence Address:
Samreen Kidwai
Villa U4, District 9, Jumeirah Parks, Dubai
UAE
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/hmj.hmj_20_21

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  Abstract 


COVID-19 is an ongoing pandemic that was identified in December 2019 in Wuhan, China. Patients admitted to the hospital with COVID-19 present with many coagulation abnormalities, precipitating a hypercoagulable state which exposes them to thrombosis for which they receive thromboprophylaxis therapy with enoxaparin. Over the course of this therapy, some patients develop spontaneous bleeding episodes in different regions of the body of varying degrees and sometimes require radiological angioembolisation to control the bleed. This case series sheds light on three patients who were admitted in Rashid Hospital, Dubai, UAE, with COVID-19 and developed spontaneous bleeds. Amongst the three patients, two of them developed retroperitoneal bleed and one patient developed a chest wall haematoma. One of them underwent radiological intervention (angioembolisation), while the other two underwent conservative management and were monitored for haemodynamic changes. There are limited studies demonstrating the correlation between high dose of enoxaparin and bleeding episodes amongst COVID-19 patients. However, we advise the need for further guidelines and data to advocate the relation between enoxaparin and bleeding episodes.

Keywords: Bleeding, COVID-19, enoxaparin, low-molecular weight heparin, retroperitoneal bleed, spontaneous bleed, thromboprophylaxis


How to cite this article:
Kidwai S, Anuff H, Salem A, Al-Ozaibi L. Thromboprophylaxis causing spontaneous bleeds in COVID patients. Hamdan Med J 2021;14:138-41

How to cite this URL:
Kidwai S, Anuff H, Salem A, Al-Ozaibi L. Thromboprophylaxis causing spontaneous bleeds in COVID patients. Hamdan Med J [serial online] 2021 [cited 2021 Dec 7];14:138-41. Available from: http://www.hamdanjournal.org/text.asp?2021/14/3/138/327425




  Introduction Top


Since COVID-19 and its systemic complications are still being studied worldwide, this is a unique case series since these are complications seen in patients who were started on thromboprophylaxis therapy for COVID-19. There are a few studies done on this around the world but the first to be done in the UAE.

Clinicians always maintain a high index of suspicion, with patients who are on anticoagulation therapy. Significant morbidity and mortality can be precipitated if there is any delay or failure in diagnosing this condition.

This case series will be discussing about three COVID-19-positive patients admitted in Rashid Hospital, Dubai, UAE, and were placed on different doses of COVID thromboprophylaxis therapy primarily consisting of enoxaparin (low-molecular weight heparin [LMWH]). Through the course of the hospital stay, each patient experienced an episode of spontaneous bleeding.


  Case Reports Top


Case 1

A 49-year-old female, known case of hypertension and dyslipidaemia was admitted with COVID pneumonia. She was treated in the intensive care unit and started on 60 mg enoxaparin twice daily. She was referred after 2 weeks of her stay due to the presence of right upper abdominal swelling. She had a drop in haemoglobin level from 9 to 5.2 g/dL. Her PT, partial thromboplastin time, international normalised ratio (INR) and D-dimer are given in [Table 1]. A computed tomography (CT)–abdominal angiogram was done which demonstrated a bilateral rectus sheath haematoma with extension into the lateral and anterior abdominal walls [Figure 1]. The patient was treated conservatively for the rectus sheath haematoma. Other medications she was given were atorvastatin 20 mg and amlodipine 10 mg.
Table 1: Levels of PT, PTT, INR and D-Dimer through the course of the patient's stay

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Figure 1: Rectus sheath hematoma

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Case 2

A 41-year-old male with no previous comorbid conditions was admitted with COVID pneumonia. He was initiated on a 40 mg BD of enoxaparin and had an elevated D-Dimer level of 7.82ug/mL fibrinogen equivalent unit (FEU). He was referred due to his complaints of right-sided abdominal pain. Physical examination showed rebound tenderness with tachycardia and hypotension. An abdominal CT scan showed findings that were consistent with a haematoma on the right psoas muscle leading to pressure being placed on the urinary bladder and inferior vena cava [Figure 2]. His other laboratory values are shown in [Table 2].
Figure 2: Right psoas muscle hematoma

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Table 2: Levels of PT, PTT, INR and D-Dimer through the course of the patient's stay

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The patient underwent superselective angiogram with embolisation of network between the fourth and fifth lumbar arteries. Following this, the patient showed stable recovery without any deterioration. He was also given amlodipine 5 mg and was treated for alcohol withdrawal and electrolyte imbalance during the course of his stay.

Case 3

A 51-year-old male, known case of hypertension and dyslipidaemia was admitted to the hospital COVID-19 pneumonia. He was started on 40 mg enoxaparin BD which was later increased to 80 mg BD. His D-Dimer was 0.5ug/mL FEU and INR levels 1.12. Three weeks after admission, the patient was referred due to ecchymosis on the chest wall and a drop haemoglobin level from 13.5 g/dL to 11.8 g/dL. His other laboratory values are as follows in [Table 3].
Table 3: Levels of PT, PTT, INR and D-Dimer through the course of the patient's stay

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Physical examination showed that a 6 cm × 4 cm ecchymosis was found extending from the anterior chest wall to the left upper abdominal wall. An abdominal CT scan showed a right pectoralis minor muscle haematoma having no vascular leak [Figure 3]. Furthermore, the patient was treated conservatively. He also received salvage therapy with multiple treatment modalities including convalescent plasma, tocilizumab 4 mg/kg BID and subcutaneous and inhalational interferon 250 mcg 12 hourly and antibiotics during his course of stay.
Figure 3: Right pectoralis minor muscle hematoma without vascular leak

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  Discussion Top


Coronavirus enters the cell and binds to the angiotensin-converting enzyme 2 which is found on the alveolar epithelium and endothelium, after which it activates the endothelial cell which is said to be the primary source of activation of the coagulation cascade. These viral inclusion bodies have been identified in endothelial cells in a variety of organs, from the lung to the gastrointestinal tract.[1]

Although various factors such as inflammatory processes can increase the D-Dimer levels, it most probably points towards intravascular thrombosis in COVID-19 patients.[2],[3]

In initial studies, there were high rates of venous thromboembolism in critically ill patients with COVID-19, despite consistent use of standard prophylactic doses of heparin-based anticoagulants and in autopsy reports in some patients described microthrombosis in multiple organs.

To prevent a serious complication of thrombosis, the COVID patients are started on thromboprophylaxis therapy with enoxaparin of varying doses, either standard dose or therapeutic dose thromboprophylaxis.

A study was conducted between two groups of patients, one who was COVID-19-positive and one who was not. The former group had elevated D-dimer levels (up to more than six times the upper limit of normal) showed lower mortality rates when started on 40–60 mg enoxaparin per day than those without it. A similar management plan was given to our patients who were started on around 40–60 mg enoxaparin twice daily per day. Some studies advocate the use of higher doses of enoxaparin (0.5 mg/kg) twice daily as the recommended dosage.[4]

Another observational study showed that there are lower mortality rates when patients are given LMWH and it is suggested that all severely ill COVID-19 patients should undergo weight-based thromboprophylaxis. Higher doses of enoxaparin 0.5 mg/kg twice daily are the recommended dosage. Considering the fact that thrombocytopenia in COVID-19 patients is less profound than other existing sepsis syndromes, prophylactic anticoagulation is likely to be feasible.[5]

Similar study took place in Denmark stating that increased mortality was seen amongst 449 severe COVID-19 hospitalised patients on 40–60 mg enoxaparin. Mortality levels were lower amongst patients on anticoagulation therapy and having sepsis-induced coagulopathy and those with more than six-fold elevated D-dimer.[6]

Since there is a risk of sepsis-induced DIC, it is suggested that anticoagulation should be started for the COVID-19 patients with high D-dimer levels (above four times the upper limit). The recommended dosage is 100 IU/kg BD of LMWH, for at least 3–4 days. Exceptions to these are those who have any contraindication for anticoagulation.[7]

Anticoagulant therapy with LMWH is linked with a better prognosis in patients with severe COVID-19 disease who have markedly elevated D-Dimer levels.[8]

Any patient admitted with COVID-19 and has been initiated on thromboprophylaxis therapy should be monitored for signs such as progressive anaemia and unstable vital signs, as this could be a sign of a developing spontaneous retroperitoneal bleed, a complication of anticoagulant therapy, which was seen with our second patient.[9]

Retroperitoneal and spontaneous rectus sheath haematomas are recognised but rare complications of therapeutic anticoagulation.[10] They carry a mortality rate of up to 20%.[11]

In a study talking about thromboprophylaxis in the medical ward for non-COVID patients, minor bleeding events were observed in 11% of the patients who received thromboprophylaxis. There were no deaths, surgical procedures or need for blood transfusions in any of those patients. They were given enoxaparin 50 mg once daily.[12]

In conclusion, thromboprophylaxis should be started in COVID-19 patients because of the high risk of thrombosis. The dosage given to them is the same and/or a little higher compared to the dosage given to non-COVID patients, but the incidence of post-thromboprophylaxis bleeds is more in COVID patients as opposed to non-COVID patients. Physicians should also keep a lookout for any signs or symptoms of spontaneous bleeds in any part of the body, as it is shown that there is a higher risk of bleed due to thromboprophylaxis in the COVID-19 patients as compared to the non-COVID-19 patients. There is yet to be a standardised dosage for thromboprophylaxis, and whether it should be weight based or not. There are limited studies to show this worldwide and it is the first study of this kind to be done in the UAE.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) have given their consent for their images and other clinical information to be reported in the journal. The patients understand that the name and initials will not be published and due efforts will be made to conceal identity of the patient.

Acknowledgement

We, Dr. Samreen Kidwai and Dr. Heena Anuff, would like to express our great appreciation to Dr. Ali Salem and Dr. Labib Al Ozaibi for their valuable and constructive suggestions during the planning and development of this case series Their willingness to give their time so generously has been very much appreciated. We would also like to thank the staff of Rashid Hospital, Dubai, to enable us to visit the patient's ward and use the Electronic Medical Record System (Salama).

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Conti CB, Henchi S, Coppeta GP, Testa S, Grassia R. Bleeding in COVID-19 severe pneumonia: The other side of abnormal coagulation pattern? Eur J Intern Med 2020;77:147-9.  Back to cited text no. 1
    
2.
Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet 2020;395:1417-8.  Back to cited text no. 2
    
3.
Leonard-Lorant I, Delabranche X, Severac F, Helms J, Pauzet C, Collange O, et al. Acute pulmonary embolism in COVID-19 patients on CT angiography and relationship to D-dimer levels. Radiology 2020;296:E189-91.  Back to cited text no. 3
    
4.
Cui S, Chen S, Li X, Liu S, Wang F. Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. J Thromb Haemost 2020;18:1421-4.  Back to cited text no. 4
    
5.
Aryal MR, Gosain R, Donato A, Pathak R, Bhatt VR, Katel A, et al. Venous Thromboembolism in COVID-19: Towards an ideal approach to thromboprophylaxis, screening, and treatment. Curr Cardiol Rep 2020;22:52.  Back to cited text no. 5
    
6.
Dalager-Pedersen M, Bodilsen J. Thromboprophylaxis for medical inpatients with coronavirus disease 2019. Clin Microbiol Infect 2020;26:1125-6.  Back to cited text no. 6
    
7.
Rico-Mesa JS, Rosas D, Ahmadian-Tehrani A, White A, Anderson AS, Chilton R. The role of anticoagulation in COVID-19-induced hypercoagulability. Curr Cardiol Rep 2020;22:53.  Back to cited text no. 7
    
8.
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;18:1094-9.  Back to cited text no. 8
    
9.
Yamamura H, Morioka T, Yamamoto T, Kaneda K, Mizobata Y. Spontaneous retroperitoneal bleeding: A case series. BMC Res Notes 2014;7:659.  Back to cited text no. 9
    
10.
Agarwal S, Lamani YP, Goudar BV, Kalburgi EB, Bhavi BK. Rectus sheath haematoma secondary to enoxaparin injection - A rare case report. J Clin Diagn Res JCDR 2017;11:PD11-2.  Back to cited text no. 10
    
11.
González C, Penado S, Llata L, Valero C, Riancho JA. The clinical spectrum of retroperitoneal hematoma in anticoagulated patients. Medicine (Baltimore) 2003;82:257-62.  Back to cited text no. 11
    
12.
Mahlab-Guri K, Otman MS, Replianski N, Rosenberg-Bezalel S, Rabinovich I, Sthoeger Z. Venous thromboembolism prophylaxis in patients hospitalized in medical wards: A real life experience. Medicine (Baltimore) 2020;99:e19127.  Back to cited text no. 12
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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