Bone Marrow Suppression Secondary to the COVID-19 Booster Vaccine: A Case Report

Authors: Toral Shastri 1Navkiran Randhawa 2Ragia Aly 3Masood Ghouse 3

PMID: 35210894 PMCID: PMC8863340DOI: 10.2147/JBM.S350290

Abstract

As of September 2021, SARS-CoV-2 booster shots became widely available in the US to ensure continued protection against the virus. A temporal relationship has been previously reported between the first or second dose of the COVID-19 vaccine and the development of thrombocytopenia. However, adverse events related to the third COVID-19 vaccine are still being reported and studied. We report a 74-year-old male who developed bone marrow suppression and pancytopenia recorded seven days after receiving the Pfizer SARS-CoV-2 vaccine. During his hospital stay, the patient’s hemoglobin, white blood cell, and platelet levels continued to trend downwards. However, all three levels showed improvement one week after discharge without robust intervention. Global vaccination is of utmost importance, as is understanding and documenting post-vaccination reactions including bone marrow suppression. Prompt evaluation and patient education are imperative to improve patient outcomes and combat hesitancy against vaccine administration.

Introduction

Since its emergence in December of 2019, the rapid spread of severe acute respiratory syndrome coronavirus (SARS-CoV-2) has quickly affected millions of lives across every continent.1 This highly transmittable and pathogenic viral infection has led to massive mitigation efforts and allocation of resources to prevent the spread of transmission and high mortality related to complications.2 The establishment of higher levels of community (herd) immunity and protection against SARS-CoV-2 via the widespread deployment of effective vaccines has become a global effort.3 In December of 2020, the FDA issued an Emergency use Authorization for the Pfizer-BioNTech and Moderna COVID-19 Vaccine as a two-dose series.4 In September 2021, booster vaccines became widely administered in the US due to waning immunity of the COVID-19 vaccines against variants of SARS-CoV-2 along with ensuring continued protection against the virus.5

Serious adverse events such as anaphylaxis, Guillain-Barre Syndrome, myocarditis, pericarditis, thrombocytopenia, and death have been previously reported following the first and/or second dose of vaccine.6 To our knowledge, no cases have been reported regarding bone marrow suppression related to the third COVID-19 vaccine. Adverse events reported between August 12-September 19, 2021 from the COVID-19 booster vaccine supported similar reactions to those after dose two.7 According to the Centers for Disease Control and Prevention (CDC), these initial findings indicate no unexpected patterns of adverse reactions after an additional dose of COVID-19 vaccination.7 However, adverse events related to the COVID-19 booster are still being reported and studied.6 This report presents a case of bone marrow suppression occurring after the third COVID-19 vaccine without a similar reaction after the first or second dose.Go to:

Case Report

A 74-year-old male with a history of polychondritis and hypothyroidism presented to the hospital after falling out of his chair and inability to ambulate. The patient was found to be mildly confused upon arrival to the emergency room, limiting our ability to obtain a full verbal history. Chart review revealed the patient had received his third Pfizer Covid vaccine shot seven days before admission followed by fatigue, decreased appetite, fever, and chills. The patient had received the second Pfizer Covid-19 shot nine months before the booster. No reactions to the previous two shots were noted.

Upon initial evaluation, vital signs were within normal limits and a physical exam revealed significant tenderness in the upper arm and no gross bleeding (Figure 1). Computed tomography (CT) imaging (Figure 2) was significant for enhancement of the left axillary lymph node. The patient’s initial complete blood count (CBC) was remarkable for a hemoglobin count of 9.9 g/dl and platelet count of 84 x 109/L; both values lower than his prior hemoglobin count of 13.7 g/dl and platelet count of 180 x 109/L from December of 2020. His mean corpuscular volume (MCV) was elevated at 101.3 femtolitres from his prior MCV value of 95.8 femtolitres in December of 2020. His white blood cell (WBC) count was recorded at 7.6 x 109/L.

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Figure 1

The patient’s upper arm showed erythema with no gross bleeding near the injection site

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Figure 2

The patient’s CT imaging of the thoracic region showed enhancement of the left axillary lymph node.

The hemoglobin, WBC, and platelet count further down trended from his baseline (Figures 3​5).5). Anemia labs including ferritin levels (554 ng/mL), vitamin B12 (253 pg/mL), total bilirubin (0.5 mg/dL), and reticulocyte count (0.8%) were nonsignificant during the patient’s hospital stay. The patient’s left shoulder presented with extensive bruising, erythema, papular rash, warmth, and tenderness on palpation during the hospitalization. An improvement in WBC and platelet levels was noted on day 4 of hospitalization.

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Figure 3

The patient’s hemoglobin count throughout his hospital course and 6 days after discharge.

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Figure 4

The patient’s WBC count throughout his hospital course and 6 days after discharge.

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Figure 5

The patient’s platelet count throughout his hospital course and 6 days after discharge.

Before discharge, the patient was fully alert and oriented and reported improvement in his symptoms. Examination of his lateral left arm showed decreased erythema and bruising with slight petechiae. The patient was discharged due to stabilization of labs and encouraged to take oral vitamin B12 supplements. During his outpatient follow-up six days after hospitalization, his hemoglobin increased to 10.5 g/dl, WBC count increased to 4.9 x 109/L, and platelets increased to 101 x 109/L.

Discussion

This paper presents a patient with pancytopenia recorded seven days after receiving the Pfizer booster vaccine. Interestingly, this patient did not report any reactions after the first or second dose of the Pfizer vaccine against SARS-CoV-2. Pancytopenia refers to a decrease in all peripheral bloodlines and is present when all three cell lines are below the normal reference range.8 The patient’s physical exam showed no signs of active bleeding along with his labs indicating no evidence of hemolysis. The patient’s hemoglobin, platelet, and white blood cell count presented below baseline followed by a decrease and slight improvement during his hospital stay. Six days after hospitalization, all three cell lines showed improvement. The temporal association with the booster vaccine and negative infectious disease workup raised suspicion for vaccine-induced bone marrow suppression. In addition, the patient’s reticulocyte count and lactate dehydrogenase value were consistent with hypoproliferation within the bone marrow.

Currently, there is a gap in knowledge of adverse events specific to the third vaccine against SARS-CoV-2 due to the recent initiation of administration and ongoing reporting of events.6 To our knowledge, bone marrow suppression after any dose of vaccine against SARS-CoV-2 has not been previously reported. However, a prior case of pancytopenia after the third vaccination with a recombinant hepatitis B vaccine has previously been reported.9 The patient’s bone marrow biopsy within this case displayed a paucity of late myeloid elements and CD8+ T cells.9 It was believed the patient’s CD8+T cells were causing excessive production of IFN-γ; a stimulant of negative regulators of hematopoiesis such as tumor necrosis factor and lymphotoxin.10 IFN-γ has also previously been reported to create immunological effects comprising an upregulation of histocompatibility gene transcription and alteration in class I and II antigen expression at the cell surface.11 It was predicted these changes resulted in an autoimmune reaction causing suppression of maturation of hematopoietic progenitor cells and pancytopenia.9 Via a similar mechanism, we believe that our patient’s pancytopenia was immune-mediated, potentially triggered by the vaccination.

Vaccines against SARS-CoV-2 (first or second dose) and the induction of Idiopathic Thrombocytopenic Purpura (ITP) have also been recently acknowledged in multiple cases.12 Our patient presented with low platelet levels and associated petechiae and purpura at the site of the vaccination. However, the patient’s presentation of low hemoglobin and white blood cells along with normal reticulocyte levels was more indicative of pancytopenia secondary to bone marrow suppression. In patients presenting with pancytopenia, the history and the physical exam should help assess the severity of the pancytopenia and comorbid illnesses that may complicate the disorder.13 In addition, suspicious medications and exposure to toxic agents should be ruled out.13 Initial screening laboratory evaluation should include the patient’s complete blood count, peripheral blood smear examination, reticulocyte count, complete metabolic panel, prothrombin time/partial thromboplastin time, and blood type and screen. Common interventions to alleviate bone marrow suppression and pancytopenia include treating the underlying cause and utilizing supplements to boost red blood cell production if indicated.

Vaccines against SARS-CoV-2 undergo continuous safety monitoring; adverse events are very rare.14 However, vaccine hesitancy remains a barrier towards full population inoculation against SARS-CoV-2 and is influenced by misinformation regarding vaccine safety.15 One study using an anonymous online questionnaire found a person’s trust in the effectiveness of the vaccine was a major facilitative factor affecting willingness to vaccinate.16 The same study also found that 66.7% of unvaccinated participants thought the vaccine’s safety was not enough, making it the main reason for reluctance or hesitance to be vaccinated.16 Therefore, education of adverse events and available interventions post-vaccination is imperative to prevent the spread of misinformation and combat hesitancy towards vaccination.15

As of September 19, 2021, about 2.2 million people in the United States received a third vaccine against SARS-CoV-2.17 Among those who received the vaccine, 22,000 people reported the effects of the vaccine with no unexpected patterns of adverse reactions.17 Our patient demonstrates abnormal pancytopenia first recorded seven days after receiving the booster vaccine, possibly indicating a rare adverse event from the vaccination given the temporal relationship. While additional studies and observations are indicated to verify bone marrow suppression as an adverse reaction, this case report provides an opportunity for patient education and treatment planning before symptoms arise.

Conclusion

Our case report highlights pancytopenia secondary to bone marrow suppression following Pfizer vaccination against SARS-CoV-2. It is important to consider the possibility of bone marrow suppression following the third vaccine against SARS-CoV-2. Although additional studies are indicated to determine the risk factors and pathogenesis of vaccine-induced bone marrow suppression, prompt evaluation and initiation of interventions can improve patient outcomes

Consent for Publication

Institutional approval was not required to publish the case details. The publication of this study has been consented to by the patient.

Disclosure

The authors report no conflicts of interest in this work.

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How To Increase Platelet Count In COVID Patients? What Is Thrombocytopenia?

Authors: Ananya Varma

Platelets are said to play an important role in inflammatory signalling. Here is why it is important to keep a check of Platelet count in COVID patients. 

Given that COVID-19 is a relatively novel disease, newer research continues to emerge into its characteristics with scientists now linking rapidly decreasing platelets to be a symptom of the infectious virus. Genetically linked to the 2002 SARS-CoV-1 virus, research has now drawn a link between Thrombocytopenia (a condition with low platelets) to the severity of a COVID-19 infection. Here is why it is important to keep a check of Platelet count in COVID patients. 

Platelet Count in COVID patients

As per a recent study, Platelets are said to play an important role in inflammatory signaling as well as in the infectious response of Coronavirus. An analysis of 7,613 COVID-19 patients revealed that patients with severe COVID had a lower platelet count than those with the non-severe disease. Moreover, mild Thrombocytopenia was also detected in those who had severe cases of COVID-19, that is those patients with a lower platelet count. 

Thrombocytopenia & COVID

A normal platelet count in human body ranges from 150,000 to 450,000 platelets per microliter of blood. Having less than 150,000 platelets is known as Thrombocytopenia. Older research has shown that of the patients affected by the 2003 SARS epidemic, 20–55% had Thrombocytopenia and these patients experienced greater morbidity/mortality. In a similar way, Thrombocytopenia has also been detected in 5–41.7% of COVID-19 patients and mild Thrombocytopenia has been detected in 58–95% of severe cases of COVID-19. Notably, severely affected patients had a platelet count only 23 ×109/L to 31 ×109/L lower than those with the non-severe disease.

For More Information: https://www.republicworld.com/india-news/general-news/how-to-increase-platelet-count-in-covid-patients-what-is-thrombocytopenia.html

Thrombocytopenia following Pfizer and Moderna SARS‐CoV‐2 vaccination

Authors: Eun‐Ju Lee, 1 Douglas B. Cines, 2 Terry Gernsheimer, 3 Craig Kessler, 4 Marc Michel, 5 Michael D. Tarantino, 6 John W. Semple, 7 Donald M. Arnold, 8 Bertrand Godeau, 5 Michele P. Lambert, 9 , 10 and James B. Bussel 11

Cases of apparent secondary immune thrombocytopenia (ITP) after SARS‐CoV‐2 vaccination with both the Pfizer and Moderna versions have been reported and reached public attention. Public alarm was heightened following the death of the first identified patient from an intracranial hemorrhage, which was reported on the Internet, then in USA Today 1 and then in The New York Times. 2 Described below, we have collected a series of cases of very low platelet counts occurring within 2 weeks of vaccination in order to enhance our understanding of the possible relationship, if any, between SARS‐CoV‐2 vaccination and development of ITP with implications for surveillance and management.

Twenty case reports of patients with thrombocytopenia following vaccination, 17 without pre‐existing thrombocytopenia and 14 with reported bleeding symptoms prior to hospitalization were identified upon review of data available from the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), agencies of the U.S. Department of Health and Human Services (HHS) Vaccine Adverse Events Reporting System (VAERS), published reports, 3 and via direct communication with patients and treating providers. These cases were investigated as suspicious for new onset, post‐vaccination secondary ITP; we could not exclude exacerbation of clinically undetected ITP. Search terms relating to “decreased platelet count”, “immune thrombocytopenia”, “hemorrhage”, “petechiae”, and “contusion” were utilized to identify cases reported in VAERS.

The reports describing 19 of 20 patients included age (range 22–73 years old; median 41 years) and gender (11 females and 8 males). Nine received the Pfizer vaccine and 11 received the Moderna vaccine. All 20 patients were hospitalized and most patients presented with petechiae, bruising or mucosal bleeding (gingival, vaginal, epistaxis) with onset of symptoms between 1–23 days (median 5 days) post vaccination. Platelet counts at presentation were available for all 20 cases with the majority being at or below 10 × 109/L (range 1–36 × 109/L; median 2 × 109/L).

For More Information: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014568/

Platelet Gene Expression and Function in COVID-19 Patients

Authors: Bhanu Kanth Manne (University of Utah, United States) Frederik Denorme (Molecular Medicine Program, University of Utah, United States), Elizabeth Middleton (University of Utah, United States), Irina Portier (University of Utah, United States) Jesse Rowley (University of Utah, United, States) Chris Stubben (University of Utah, United States) Aaron Petrey (University of Utah, United States) Neal Tolley (University of Utah, United States) Li Guo (University of Utah, United States) Mark Cody (University of Utah, United States) Andrew Weyrich (University of Utah, United States) Christian Yost (Department of Pediatrics, University of Utah, United States) Matthew Rondina (University of Utah Health Sciences Center, United States) Robert Campbell (University of Utah, United States).

Abstract:

There is an urgent need to understand the pathogenesis of coronavirus disease 2019 (COVID-19). In particular, thrombotic complications in
patients with COVID-19 are common and contribute to organ failure and mortality. Patients with severe COVID-19 present with hemostatic
abnormalities that mimic disseminated intravascular coagulopathy associated with sepsis with the major difference being increased risk of
thrombosis rather than bleeding. However, whether SARS-CoV-2 infection alters platelet function to contribute to the pathophysiology of COVID19 remains unknown. In this study, we report altered platelet gene expression and functional responses in patients infected with SARS-CoV-2.
RNA sequencing demonstrated distinct changes in the gene expression profile of circulating platelets of COVID-19 patients. Pathway analysis
revealed differential gene expression changes in pathways associated with protein ubiquitination, antigen presentation and mitochondrial
dysfunction. The receptor for SARS-CoV-2 binding, ACE2, was not detected by mRNA or protein in platelets. Surprisingly, mRNA from the SARSCoV-2 N1 gene was detected in platelets from 2/25 COVID-19 patients, suggesting platelets may take-up SARS-COV-2 mRNA independent of
ACE2. Resting platelets from COVID-19 patients had increased P-selectin expression basally and upon activation. Circulating platelet-neutrophil, –
monocyte, and -T-cell aggregates were all significantly elevated in COVID-19 patients compared to healthy donors. Furthermore, platelets from
COVID-19 patients aggregated faster and showed increased spreading on both fibrinogen and collagen. The increase in platelet activation and
aggregation could partially be attributed to increased MAPK pathway activation and thromboxane generation. These findings demonstrate that
SARS-CoV-2 infection is associated with platelet hyperreactivity which may contribute to COVID-19 pathophysiology.

For More Information: https://medicine.utah.edu/internalmedicine/generalmedicine/files/campbell-covid-platelet-blood-2020.pdf

SARS-CoV-2 binds platelet ACE2 to enhance thrombosis in COVID-19

Authors: Si Zhang 1Yangyang Liu 2Xiaofang Wang 2Li Yang 3Haishan Li 4Yuyan Wang 5Mengduan Liu 2Xiaoyan Zhao 2Youhua Xie 5Yan Yang 6Shenghui Zhang 7Zhichao Fan 8Jianzeng Dong 2Zhenghong Yuan 5Zhongren Ding 2Yi Zhang 9Liang Hu 10

Abstract

Background: Critically ill patients diagnosed with COVID-19 may develop a pro-thrombotic state that places them at a dramatically increased lethal risk. Although platelet activation is critical for thrombosis and is responsible for the thrombotic events and cardiovascular complications, the role of platelets in the pathogenesis of COVID-19 remains unclear.

Methods: Using platelets from healthy volunteers, non-COVID-19 and COVID-19 patients, as well as wild-type and hACE2 transgenic mice, we evaluated the changes in platelet and coagulation parameters in COVID-19 patients. We investigated ACE2 expression and direct effect of SARS-CoV-2 virus on platelets by RT-PCR, flow cytometry, Western blot, immunofluorescence, and platelet functional studies in vitro, FeCl3-induced thrombus formation in vivo, and thrombus formation under flow conditions ex vivo.

For More Information: https://pubmed.ncbi.nlm.nih.gov/32887634/

The Impact of COVID-19 Disease on Platelets and Coagulation

Authors: Geoffrey D Wool 1Jonathan L Miller 2

Abstract

Coronavirus disease 2019 (COVID-19) causes a spectrum of disease; some patients develop a severe proinflammatory state which can be associated with a unique coagulopathy and procoagulant endothelial phenotype. Initially, COVID-19 infection produces a prominent elevation of fibrinogen and D-dimer/fibrin(ogen) degradation products. This is associated with systemic hypercoagulability and frequent venous thromboembolic events. The degree of D-dimer elevation positively correlates with mortality in COVID-19 patients. COVID-19 also leads to arterial thrombotic events (including strokes and ischemic limbs) as well as microvascular thrombotic disorders (as frequently documented at autopsy in the pulmonary vascular beds). COVID-19 patients often have mild thrombocytopenia and appear to have increased platelet consumption, together with a corresponding increase in platelet production. Disseminated intravascular coagulopathy (DIC) and severe bleeding events are uncommon in COVID-19 patients. Here, we review the current state of knowledge of COVID-19 and hemostasis.

For More Information: https://pubmed.ncbi.nlm.nih.gov/33049751/

Dr. Charles Hoffe issues Vaccine warning… Deep dive on endothelial damage to blood vessels…

Author: Dr. Charles Hoffe

in a Coronavirus, that spike protein becomes part of the viral capsule. In other words, the cell wall around the virus, called the viral capsule. But it’s not in the virus. It’s in your cells. So it therefore becomes part of the cell wall of your vascular endothelium. Which means that these cells that line your blood vessels, which are supposed to be smooth so that blood flows smoothly, now have these little spikey bits sticking out.

So it is absolutely inevitable that blood clots will form. Because your blood platelets circulate around in your blood vessels. And the purpose of blood platelets is to detect a damaged vessel and block that vessel to stop bleeding. So when the platelet comes through the capillary, it suddenly hits all these all these Covid spikes that are jutting into the inside of the vessel, it is absolutely inevitable that a blood clot will form to block that vessel. That’s how platelets work.

For More Information: https://citizenfreepress.com/breaking/dr-charles-hoffe-issues-vaccine-warning/