Medical examiners on Thursday said a Miami Beach doctor who died after receiving the COVID-19 vaccine in December passed away from an immune disorder. Examiners noted it remains unclear whether his death was directly connected to the vaccine.
Dr. Gregory Michaelâs official cause of death stemmed from complications with immune thrombocytopenia, or ITP, a blood disorder caused by an immune reaction, after getting the Pfizer vaccine, the Miami-Dade County Medical Examiner Department said.
Michael, a Miami native who was a 56-year-old obstetrician-gynecologist, died on Jan. 3, about two weeks after he received the vaccine at Mount Sinai Medical Center in Miami Beach. His wife, Heidi Neckelmann, who has not responded to requests for comment from the Miami Herald, penned an anguished post on Facebook announcing her husbandâs death and to make the public aware of possible side effects of the vaccine.
Below is Heidi Necklemannâs true account of what exactly transpired during this nightmare that she or her husband couldnât have seen coming or to prepare for.Â
âThe love of my life, my husband Gregory Michael MDÂ an Obstetrician that had his office in Mount Sinai Medical Center in Miami Beach Died the day before yesterday due to a strong reaction to the COVID vaccine.â
âHe was a very healthy 56 year old, loved by everyone in the community delivered hundreds of healthy babies and worked tireless through the pandemic.â
He was vaccinated with the Pfizer vaccine at MSMC on December 18, 3 days later he saw a strong set of petechiae on his feet and hands which made him seek attention at the emergency room at MSMC. The CBC that was done at his arrival showed his platelet count to be 0 (A normal platelet count ranges from 150,000 to 450,000 platelets per microliter of blood.) he was admitted in the ICU with a diagnosis of acute ITP caused by a reaction to the COVID vaccine. A team of expert doctors tried for 2 weeks to raise his platelet count to no avail. Experts from all over the country were involved in his care. No matter what they did, the platelets count refused to go up. He was conscious and energetic through the whole process but 2 days before a last resort surgery, he got a hemorrhagic stroke caused by the lack of platelets that took his life in a matter of minutes.â
âHe was a pro vaccine advocate that is why he got it himself. â
âI believe that people should be aware that side effects can happened, that it is not good for everyone and in this case destroyed a beautiful life, a perfect family, and has affected so many people in the community. Do not let his death be in vain please save more lives by making this information news.â
Thrombocytopenia following Pfizer and Moderna SARSâCoVâ2 vaccination https://www.ncbi.nlm.nih.gov/
Thrombocytopenia following Pfizer and Moderna SARSâCoVâ2 vaccination
EunâJu Lee, Douglas B. Cines, […], and James B. Bussel
Associated Data
1.â
Cases of apparent secondary immune thrombocytopenia (ITP) after SARSâCoVâ2 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 2âweeks of vaccination in order to enhance our understanding of the possible relationship, if any, between SARSâCoVâ2 vaccination and development of ITP with implications for surveillance and management.
Twenty case reports of patients with thrombocytopenia following vaccination, 17 without preâexisting 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 , 4 and via direct communication with patients and treating providers. These cases were investigated as suspicious for new onset, postâvaccination secondary ITP; we could not exclude exacerbation of clinically undetected ITP. Search terms relating to âdecreased platelet countâ, âimmune thrombocytopeniaâ, âhemorrhageâ, âpetechiaeâ, and âcontusionâ were utilized to identify cases reported in VAERS.
The reports describing 19 of 20 patients included age (range 22â73âyears old; median 41âyears) 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 1â23âdays (median 5âdays) post vaccination. Platelet counts at presentation were available for all 20 cases with the majority being at or below 10 Ăâ109/L (range 1â36 Ăâ109/L; median 2 Ăâ109/L).
One patient had known ITP in remission; another had mildâmoderate thrombocytopenia in 2019 with note of positive antiâplatelet antibodies, a third had previous mild thrombocytopenia (145 Ă 109/L) while a fourth had inherited thrombocytopenia with baseline platelet counts of 40â60 Ăâ109/L. Three other patients had known autoimmune conditions including hypothyroidism, Crohns disease, or positive tests for antiâthyroglobulin antibodies. Treatment for suspected ITP was described in 15 of the cases, including corticosteroids n = 14, intravenous immune globulin (IVIG) n = 12, platelet transfusions n = 8, rituximab n = 2, romiplostim = 1, vincristine = 1, and aminocaproic acid (Amicar) n = 1; combination therapy was used in most patients. Initial outcomes were reported in 16 cases. An improvement in the platelet count was described in patients treated with platelet transfusion alone (n = 1), corticosteroids alone (n = 1), corticosteroids + platelet transfusion (n = 3), corticosteroids + IVIG (n = 3), corticosteroids + IVIG + platelet transfusion (n = 5), corticosteroids +IVIG + rituximab + vincristine + romiplostim (n = 1). The index patient passed away after a cerebral hemorrhage, as mentioned, notwithstanding having received emergent treatment with IVIG, steroids, rituximab and platelet transfusions. Another patient had no improvement in platelet counts after 3âdays, but treatment details are not specified.
Five additional patients with âthrombocytopeniaâ or âimmune thrombocytopeniaâ post vaccination were identified in VAERS (last accessed 2/5/21), but either available information is insufficient for inclusion or the clinical scenarios suggest alternative processes contributing to thrombocytopenia. One 59âyearâold man was identified with âthrombocytopeniaâ at an unspecified time after receiving the Pfizer vaccine without additional details regarding platelet count, clinical course, or treatment. A 44âyearâold woman was hospitalized for nausea, vomiting and chest pain on the day that she received the Pfizer vaccine. Her laboratory values included a platelet count of 85 Ăâ109/L and a peak troponin level of 4 ng/mL (normal < =â0.04âng/mL). The patient was diagnosed with myocarditis but did not require treatment for thrombocytopenia. Her platelets were 61 Ăâ109/L on discharge, but subsequent platelet counts were not reported. The third is a patient without age or gender reported who was found to have thrombocytopenia, neutropenia and a pulmonary embolism at an unspecified time following the Pfizer vaccine. This patient was hospitalized and passed away; no additional details were available. A fourth patient, a 37âyearâold man, had âthrombocytopenia requiring hospitalization, meds and platelet infusionâ 4âdays following the Moderna vaccine with no details regarding presenting symptoms, platelet count, treatment or outcome. The last patient is an 80âyearâold man with multiple medical problems including recent transcatheter aortic valve replacement, hypothyroidism, and diverticulosis who presented 6âdays after the Pfizer vaccine with bloody diarrhea, hemoglobin 8.7 g/dL and platelets 60 Ăâ109/L. He received several units of packed red blood cells and two units of platelets with improvement to 101 Ăâ109/L and was discharged 5âdays later. There were a handful of reports with minimal additional details alluding to a male who passed away in December from brain hemorrhage following the Pfizer vaccine â these could be describing the index patient. We did not attempt to obtain information on patients with preâexisting active ITP who received a SARSâCoVâ2 vaccine for this report.
We identified additional reports of postâvaccination bruising or bleeding unrelated to the injection site, but no mention of platelet counts, or thrombocytopenia, was provided. Note, VAERS was last accessed on January 29, 2021 for this search. Fourteen patients reported âpetechiaeâ/âbruisingâ of whom three were evaluated in the office and one presented to the emergency room. There have been 51 reports ofâ bleedingâ/âhemorrhageâ (vaginal n = 11, conjunctival n = 13, cerebral n = 6, gingival n = 2, gastrointestinal n = 5, epistaxis n = 12, and cutaneous n = 2). There were 31 patients who did not seek additional evaluation, seven were seen via office visits, while 13 presented to the emergency room or were hospitalized. Two patients passed away in the hospital. No additional details are available.
Are these case of primary ITP coincident with or secondary ITP as a result of vaccination? In either case, the clinical presentations and the favorable response to âITPâdirectedâ therapies in most of the treated patients, such as corticosteroids and IVIG suggest an antibodyâmediated platelet clearance mechanism that is operative in ITP.
Is the relationship between vaccination and thrombocytopenia coincident or causal? It is not surprising that 17 possible de novo cases would be detected among the well over 20 million people who have received at least one dose of these two vaccines in the United States as of February 2, 2021. This would be less than one case in a million vaccinated persons, consistent with the absence of cases seen in the more than 70â000 subjects enrolled in the combined Pfizer and Moderna vaccine trials. 5 , 6 If we assume that these reports identify 17 cases of secondary ITP that developed following vaccination, this extrapolates to 17 Ăââ6 (because only cases that occurred during the first 2 months [December 2020 â January 2021] following vaccine rollout are captured) Ăâ15 to cover the fraction of the population that has been vaccinated [20 million of the 300+ million total US population]) = approximately 1500 cases of postâvaccine secondary ITP/year. There are approximately 50â000 adults who are diagnosed with ITP in the US each year. If we explored the temporal relationship of the 17 cases occurring within 1â2 weeks of vaccination, then we could extrapolate by multiplying by 26 or 52 weeks to look at the rate of ITP per year if the cases are totally âcoincidentalâ. This would be approximately 39,000 to 78,000 cases of ITP per year which is not far from the estimated total baseline incidence per year. Thus, the incidence of an immuneâmediated thrombocytopenia post SARSâCoVâ2 vaccination appears either less than or roughly comparable to what would be seen if the cases were coincidental following vaccination, perhaps enhanced somewhat by heightened surveillance of symptomatic patients. These estimates are very rough so this information should be considered very preliminary. It also assumes that all cases of clinically significant ITP are reported.
The incidence of secondary ITP following other types of vaccines provides an inconsistent picture. It is estimated that approximately 1:40â000 children develop secondary ITP after receiving measlesâmumpsârubella (MMR) vaccine. 7 Wellâdocumented cases of acquired immune thrombocytopenia have been reported after varicella and other vaccinations as well, including one described in this issue of the American Journal of Hematology following Shingrix recombinant Zoster vaccine. 8 , 9 , 10 On the other hand, the only caseâcontrolled study of adult recipients of all vaccines published 10âyears ago was interpreted as indicating no discernable increase in ITP within 1 year post vaccination. 11In the absence of preâvaccination platelet counts and given the variable time post vaccination to discovery of thrombocytopenia, it is impossible to precisely estimate the incidence of secondary ITP post SARSâCoVâ2 vaccination at this time. However, it is notable that all but one of the cases identified thus far occurred after the initial dose of SARSâCoVâ2 vaccine. One would assume that if the vaccination was unrelated to development of ITP, case occurrences would divide more evenly between the two doses. It is also likely that the actual incidence of thrombocytopenia, including mild asymptomatic cases, may be higher and go unreported.
Even in view of the uncertain relationship between SARSâCoVâ2 vaccination and secondary ITP, it is worth considering possible mechanisms by which this might occur. Thrombocytopenia has been reported after treatment with some antiâsense oligonucleotides, 12 , 13 but it would seem that a far higher, sustained level of RNA reaching dendritic cells in lymph nodes and elsewhere would be required to generate an immune response than is likely seen based on a single intramuscular injection. This is also inconsistent with the very rapid onset of thrombocytopenia in the index and additional cases.
Another possibility is that some individuals may have preâformed antibodies, including those directed against polyâethyleneâglycol or to other components of the outer lipid layer of the nanoparticles. This presumes that antibodies directed against a novel antigen formed by attachment of vaccine particles on a small number of platelets trigger a reaction involving âallâ platelets, which seems unlikely. Recent articles identified antibodies detected post Covidâ19 infection that activated platelets 14 and an ITPâlike syndrome following natural infection 15 , 16; both findings require confirmation and the relationship to the post vaccination ITP cases reported here is uncertain.
Third, some patients may have had mild âcompensatedâ thrombocytopenia of diverse causes, for example, preâexisting ITP or hereditary thrombocytopenia. For example, one of the patients reported in this issue of the American Journal of Hematology had a documented borderline platelet count (145 Ăâ109/L) 2 months prior to receipt of the vaccine raising the question of preâexisting subclinical ITP. 3 The other patient reported in this issue of the American Journal of Hematology had chronic, hereditary thrombocytopenia, with a last known exacerbation 12âyears prior to the present episode.4 An additional patient identified in VAERS had platelets of 55â115 Ăâ109/L in 2019. Severe thrombocytopenia in these patients or others may have been induced by enhancement of macrophageâmediated clearance or impaired platelet production as part of a systemic inflammatory response to vaccination. 8 , 17 This is compatible with patients in whom severe thrombocytopenia was first noted 1â3âdays postâvaccination. Transient drops in platelet counts post vaccinations for influenza and other viruses is a not uncommon observation in patients with ITP and other causes of thrombocytopenia.
Lastly, postâvaccination ITP remains possible, especially in those with onset 1â2 weeks after exposure. One patient in our series had a normal platelet count documented in the week prior to receipt of the vaccine and only developed symptomatology 13âdays post vaccination compatible with vaccine related secondary ITP.
The reported cases also provide insight into diagnosis and treatment. Most of the patients responded to treatment with corticosteroids and IVIG but showed little benefit from platelet transfusion, a pattern consistent with that of ITP. There was no response in the two patients treated with rituximab but they were only evaluable for up to 2âweeks; in addition, rituximab would impair the response to vaccination, if given within days to 2 weeks of the vaccination and for at least 4â6 months subsequently. The first of two patients (with sufficient information available) continued to have a platelet count of 1â2 Ăâ109/L and died of intracranial bleeding 16âdays post vaccination and 13âdays post presentation of ITP despite receiving platelet transfusions, steroids, IVIG, and rituximab. The second patient presented 1 day after vaccination and still had a count of 1 Ăâ109/L 7âdays later despite receiving the same combination of the four ITP treatments; however, she responded following addition of vincristine and romiplostim. The suggestion might be (from this very limited information) to give IVIG and high dose steroids as initial treatment. If this does not work and the platelet count remains very low, it would seem appropriate to institute other treatments within the first week including a thrombopoietic agent perhaps starting above the lowest dose often recommended to initate therapy and potentially vinca alkaloids depending upon response. Excluding rituximab from initial treatment seems appropriate in most cases given that response can take up to 8âweeks 18 and response to vaccination can be impaired. Once a platelet response is seen, patients could be managed as if they were typical cases of primary ITP. Whether such cases will prove to be selfâlimiting or persist and lead to chronic ITP remains uncertain.
In summary, we cannot exclude the possibility that the Pfizer and Moderna vaccines have the potential to trigger de novo ITP (including clinically undiagnosed cases), albeit very rarely. Distinguishing vaccineâinduced ITP from coincidental ITP presenting soon after vaccination is impossible at this time. Additional surveillance is needed to determine the true incidence of thrombocytopenia post vaccination. If the incidence of thrombocytopenia post vaccination is higher than that based on available case reports, we anticipate that many more cases will be reported in the coming weeks as a higher proportion of the population is vaccinated. It may be worthwhile to see whether exacerbations of other conditions considered to have an autoimmune pathophysiology occur as well to gain a better understanding of host response to vaccination.
Notwithstanding these concerns, the incidence of symptomatic thrombocytopenia post vaccination is well below the risk of death and morbidity from SARSâCoVâ2 infection as also described on the Platelet Disorder Support Association (PDSA) website in the statement from the Medical Advisory Board. We echo recommendations from the PDSA and the American Society of Hematology that strongly encourage reporting this and other potential complications through VAERS and in any other way deemed appropriate. Finally, we recommend immediately checking a platelet count in anyone who reports abnormal bleeding or bruising following vaccination and consulting a hematologist.
Management of vaccination in patients with preâexisting ITP is complex and is not explored here. The opinion of the Medical Advisory Board of PDSA is that in most, but not necessarily all, patients the benefit of vaccination exceeds the risk of exacerbating ITP. At this time, for patients with ITP it appears reasonable to obtain a baseline count before vaccination and then obtain additional platelet count(s) following vaccination based on patient clinical and treatment history. In patients who present with severe thrombocytopenia soon after vaccination in the absence of other likely causes, we believe it would be appropriate to pursue aggressive treatment for presumed ITP. Whether to administer a second dose of vaccine or whether a change to a different vaccine is warranted in patients who develop thrombocytopenia or substantial worsening of preâexisting thrombocytopenia with the initial dose requires further study.
AUTHOR CONTRIBUTIONS
EunâJu Lee, James B Bussel, and Douglas B Cines contributed to the data acquisition, interpretation of data and wrote the manuscript. Terry Gernsheimer, Craig Kessler, Marc Michel, Michael D Tarantino, John W Semple, Donald M Arnold, Bertrand Godeau, Michele P Lambert provided input on the manuscript and approved the final version for submission.
NEW DELHI: Low platelet count is one of the common features of viral infections. But, in most cases, the platelets reach normal levels as soon as the infection subsides. However, in the case of Covid-19, doctors have come across patients who continue to exhibit low platelet counts for weeks after recovery.Jul 11, 2021
Listen to today’s top stories from the Miami Herald:Â
Family members told the medical examiners that Michael was in perfect health. He did not take prescription medication, suffer from mental illnesses, have allergies or have any surgeries or hospitalizations. He also did not have any flu-like symptoms, according to the examinerâs report.
After getting partially inoculated in mid-December, he had bruising and noticed pinpoint spots in his lower body, the report read. He was then taken to Mount Sinai where he was diagnosed with thrombocytopenia â a condition in which the bodyâs autoimmune system reacts against blood platelets.
Mount Sinai and Pfizer did not immediately respond for comment.
Medical examiners say one cause of this condition is drug reactions, some of which were linked to COVID-19.
â…given the general mechanism and pathophysiology of vaccination, it is likely that vaccination could also trigger ITP [thrombocytopenia],â the examinerâs report read.
In Michaelâs case, there is no evidence that infections, immunodeficiencies or malignancies spurred the condition that led to his death, examiners said. Although, they noted itâs both difficult and rare to prove that him receiving a vaccination was the reason.
Michael ran his own private practice at Mount Sinai for 12 years, according to his website. He also worked as a clinical instructor and faculty member for the physician assistant program at Barry University and Miami Dade College.
What to know about Pfizer, Moderna and J&J COVID-19 vaccines
There are three COVID-19 vaccines authorized for emergency use in the U.S.: Pfizer-BioNTech, Moderna and Johnson & Johnson. All three prevent severe disease and death but there are some differences on how each vaccine works. Here’s what to know. By Daniel A. Varela | Michelle Marchante
Miami Herald Real Time Reporter Devoun Cetoute covers breaking news, Florida theme parks and general assignment. He attends the University of Florida and grew up in Miami. Theme parks are on his mind in and out of the office.
My personal condolences go out to Heidi for experiencing such a devastating challenge in her life losing her wonderful husband Dr. Gregory Michael so soon. ~ Natalie 04/12/2021