Skip to main content

Severe immune thrombocytopenia following diphtheria, tetanus, pertussis and polio vaccination in a 36-year-old Caucasian woman: a case report

Abstract

Background

Immune thrombocytopenia (ITP) is a rare autoimmune disorder characterized by low platelet counts and increased bleeding risk. The disease may be induced by other disorders, including malignancies, autoimmune diseases, infectious agents or drugs. However, ITP has also been described following vaccinations, such as the measles–mumps–rubella vaccination. In rare cases, ITP may occur in children who received a DTaP-IP (diphtheria, tetanus, acellular pertussis vaccine and inactivated poliovirus) vaccine. Hereinafter, we report the first well-documented cases of ITP in an adult patient in the temporal context of a DTaP-IP vaccination.

Case presentation

This case report attempts to capture the life-threatening picture of a 36-year-old otherwise healthy Caucasian woman with newly diagnosed severe immune thrombocytopenia in the temporal context of a DTaP-IP vaccination. Four days after receiving the vaccine, the women presented to her primary care physician with malaise, fever and recurrent epistaxis. Clinical examination revealed oral petechiae, ecchymoses, and non-palpable petechiae on both legs. The patient was immediately referred to a local hematology unit where she developed hematuria and an intestinal bleeding (WHO Bleeding Grade III) requiring multiple transfusions. After receiving oral corticosteroids and intravenous immunoglobulins, her platelets gradually recovered. Common causes of secondary ITP were ruled out by laboratory investigations, bone marrow and peripheral blood examinations. This raises the possibility of a (secondary) vaccination-associated thrombocytopenia. To the best of our knowledge, this is the first well-documented case of a DTaP-IP vaccination-related ITP in an adult patient in the English literature.

Conclusion

Although a causal connection between both entities may not be established, we would like to raise awareness in clinicians that ITP following DTaP-IP vaccinations is potentially not limited to children, but may also occur in adults. Users of DTaP-IP booster vaccines should be alert of the possibility of such adverse reactions.

Background

Immune thrombocytopenia (ITP) is a rare autoimmune disorder characterized by low platelet counts and an increased bleeding risk [1, 2]. Expertise in the management of affected patients is not widely spread [1] and ITP is usually a diagnosis of exclusion [2]. Patients who develop thrombocytopenia (as defined by a platelet count < 100,000 platelets per microliter) with no clear underlying cause are usually diagnosed with (isolated) primary ITP [2], whereas secondary ITP is defined as an ITP induced by other disorders or treatments [2, 3]. These may include autoimmune disorders [1, 2], solid tumors and lymphoproliferative diseases [4, 5] as well as infectious agents [6], transfusions and drugs (such as interferon) [2, 7]. ITP has also been described in children following vaccinations [8], although this is exceedingly rare [2].

This case reports attempts to capture the clinical picture of a potentially vaccine-associated ITP in an adult patient. In light of the scarce literature with regard to this particular topic, this article intends to elucidate potential barriers to its diagnosis and presents a cases characterized by life-threatening complications due to a vaccine induced ITP.

Case presentation

A 36-year-old Caucasian woman presented to her primary care physician's office to receive a DTaP-IP booster vaccination (diphtheria and tetanus toxoids and acellular pertussis adsorbed and inactivated poliovirus). Her physical examination and medical history were unremarkable. In the past, she received all recommended vaccinations in accordance with the national immunization schedule developed by the German “Ständige Impfkommission”. The patient was a non-smoker and did not receive any regular medication. Vital parameters were normal and the woman denied any signs of infection. She received the vaccination (“Boostrix Polio”, AC39B145AA, Glaxo Smith Kline, manufactured in Rixensart, Belgium) and was discharged home shortly after.

A few hours later, the woman developed chills, malaise and discomfort. Moreover, she also suffered from agonizing myalgias.

At first, she did not consult a medical professional, but symptoms gradually worsened and 4 days later, she presented again to her doctor’s office after noticing red stains in her mouth and after experiencing epistaxis. The patient denied any signs of blood in urine or stools.

Medical examination revealed multiple oral petechiae (1–2 mm in size) and ecchymoses (approximately 1–2 cm in diameter) as well as multiple flat, non-palpable petechiae on both legs (particularly at the front of both shins). Vital parameters were within the normal range, however, after measuring blood pressure multiple new petechiae appeared on the right arm. Examination of the lungs revealed normal resonance and vesicular breath sounds bilaterally. Heart sounds were normal, without pathological murmurs. Examination of the abdomen revealed the anterior wall to be soft and flat. Bowel sounds were normal and there was no tenderness or palpable mass. Finally, there were no focal neurological deficits.

With signs for severe hemorrhage, the patient was immediately referred to a local hospital with an established hematology unit. Laboratory findings demonstrated severe thrombocytopenia (1000 platelets per microliter of blood; normal range 140,000–440,000/µl) and a normal hemoglobin count (13.4 g/dl; normal range, 11.7–15.7 g/dl). Pseudothrombocytopenia was ruled out using a sodium citrate tube.

Table 1 shows other laboratory hematological parameters that were obtained on admission. The standard biochemistry profile and other laboratory parameters may be obtained from Table 2.

Table 1 Laboratory hematological parameters obtained on admission: an overview
Table 2 Standard biochemistry profile and other parameters obtained on admission

An electrocardiogram revealed a regular heart rhythm at a rate of 97 beats per minute. Abdominal sonography revealed ascites and a slightly enlarged spleen (12 × 3.5 cm). There were no signs of liver cirrhosis or portal hypertension.

The patient also underwent bone marrow aspiration (Fig. 1). Bone marrow cytology displayed lymphocytes, granulocytes and erythrocytes in normal quantity and morphology. However, megakaryocyte count was significantly elevated with 6–7 /field of view at tenfold magnification (normal range 1–2 megakaryocytes) [9]. Bone marrow immunophenotyping revealed no evidence of lymphoma or significant blast population. Peripheral blood smear showed peripheral depletion of platelets.

Fig. 1
figure 1

Bone marrow findings

Additional blood tests revealed non-elevated antinuclear antibodies (ANA titer < 1:80) and a negative HIV-screening. Furthermore, laboratory tests for Hepatitis B virus, Hepatitis C virus, Epstein–Barr virus, cytomegalovirus, and parvovirus B19 were negative. Screening for HIT (heparin-induced thrombocytopenia) antibodies (targeting the complex of platelet factor 4 and heparin) was negative, as well. Serum vitamin B12 levels and folate were within normal range (Additional file 1).

The patient was diagnosed with immune thrombocytopenia and received oral corticosteroids (dexamethasone, 40 mg p.o. daily) in accordance with the 2019 international consensus report on the management of immune thrombocytopenia [10]. As shown in Fig. 2, platelets initially remained low, although dexamethasone (40 mg) was given for 4 days.

Fig. 2
figure 2

Platelet count timeline

Within the next 2 days, the patient developed hematuria. On day 2, she also reported melena and abdominal discomfort. Hemoglobin values dropped from baseline (13.4 g/dl) to 9.1 g/dl and 7.1 g/dl on the third and fourth day, respectively.

Despite a critically low hemoglobin count (5.1 g/dl) in the evening on day 4, the patient refused endoscopy. In light of the substantial clinical bleeding tendency and the low platelet count, the patient was given additional intravenous immunoglobulins (0.5 g/kg per day, see Fig. 2). Furthermore, several platelet concentrates and erythrocyte concentrates were administered.

Under a therapy regimen that included both oral corticosteroids and intravenous immunoglobulins, platelets finally increased on day 5 (Fig. 2). Subsequently, the therapy was changed to prednisolone (p.o., 100 mg daily) on day 5 from admission. Intravenous immunoglobulins were given for 5 days in total. Platelet count increased gradually and the patient was discharged after another 4 days. The patient recovered well without any sequelae.

Discussion and conclusions

This case report attempts to capture the life-threatening picture of a 36-year-old otherwise healthy woman with newly diagnosed severe immune thrombocytopenia in the temporal context of a DTaP-IP booster vaccination. The patient was hospitalized for a period of 9 days and suffered from recurrent epistaxis, hematuria and an intestinal bleeding (WHO Bleeding Grade III) that required multiple transfusions.

The etiology remains unknown, although many common causes of secondary immune thrombocytopenia were ruled out by laboratory investigations (such as hepatitis, HIV and other viral infections) as well as by bone marrow and peripheral blood examinations (including lymphoproliferative syndromes and immune-mediated thrombocytopenias such as HIT). Moreover, it is also important to emphasize that the patient had an unremarkable past medical history prior to her hospital admission. This raises the possibility of a (secondary) vaccination-associated thrombocytopenia following the DTaP-IP booster vaccination the patient received 3 days prior to hospital referral.

Sudden and severe onset of thrombocytopenia has been occasionally associated with vaccinations [2], however, mainly in children receiving a measles–mumps–rubella vaccine [11]. Furthermore, there are also cases reporting severe thrombocytopenia occurring after influenza vaccinations in adults [12, 13] and after SARS‐CoV‐2 vaccinations with both the Pfizer and Moderna versions [14, 15], although ITP may also be a complication of an infection with COVID-19 itself [16].

Cases of secondary immune thrombocytopenia in the temporal context of DTaP-IP vaccinations are exceedingly rare and, to the best of our knowledge, so far only reported in children and young adolescents [17,18,19,20].

Although a causal connection between the vaccination and the ITP may not be established, this case suggests that severe thrombocytopenia can potentially develop secondarily to a DTaP-IP vaccination in adults. Based on an extensive literature research using two scientific databases (PubMed and Google Scholar), we conclude that this is one of the first well-documented cases of immune thrombocytopenia in an adult patient in the temporal context of DTaP-IP vaccination.

ITP is an autoimmune disorder characterized by autoantibodies that inhibit platelet production and impair circulating platelets [21, 22]. This leads to thrombocytopenia and subsequent bleeding. ITP may be found secondary to other conditions, such as infections, but it has also been rarely described following different types of vaccinations [23]. David and Shoenfeld recently summarized potential pathways how vaccines could lead to ITP [23]. These include molecular mimicry, epitope spreading, and finally polyclonal activation, especially in cases of attenuated virus stimulation [23,24,25]. Apparently, genetic predisposition may also potentially play a role, as well [26].

While it is beyond the scope of this case report to discuss molecular pathways in detail, we believe that this case is of paramount importance for clinicians, as it emphasizes the possibility of a potentially vaccine-associated ITP in the context of DTaP-IP vaccination in an adult.

Although a recent Japanese study suggested no significant ITP risk following vaccinations or simultaneous vaccination in any age group [27], we would like to raise awareness that ITP following DTaP-IP vaccinations may not be limited to children but can potentially occur in adults as well. Prescribers and users of DTaP-IP booster vaccines should be alert of the possibility of such adverse reactions.

Availability of data and materials

All data associated with this paper will be made available upon reasonable request.

Abbreviations

DTaP-IP:

Diphtheria and tetanus toxoids and acellular pertussis adsorbed and inactivated poliovirus

ITP:

Immune thrombocytopenia

References

  1. Matzdorff A, Meyer O, Ostermann H, Kiefel V, Eberl W, Kühne T, et al. Immune thrombocytopenia–current diagnostics and therapy: recommendations of a joint working group of DGHO, ÖGHO, SGH, GPOH, and DGTI. Oncol Res Treat. 2018;41(Suppl 5):1–30.

    Article  PubMed  Google Scholar 

  2. Cines DB, Liebman H, Stasi R. Pathobiology of secondary immune thrombocytopenia. Semin Hematol. 2009;46(1 Suppl 2):S2-14.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009;113(11):2386–93.

    CAS  Article  PubMed  Google Scholar 

  4. Podda GM, Fiorelli EM, Birocchi S, Rambaldi B, Di Chio MC, Casazza G, et al. Treatment of immune thrombocytopenia (ITP) secondary to malignancy: a systematic review. Platelets. 2020;23:1–7.

    Google Scholar 

  5. Colović M, Jurisić V, Colović N, Miljić P. Thrombotic thrombocytopenic purpura: clinic–pathologic characteristics and therapy. Srp Arh Celok Lek. 2003;131(7–8):337–44.

    PubMed  Google Scholar 

  6. Stasi R, Willis F, Shannon MS, Gordon-Smith EC. Infectious causes of chronic immune thrombocytopenia. Hematol Oncol Clin North Am. 2009;23(6):1275–97.

    Article  PubMed  Google Scholar 

  7. Colovic M, Jurisic V, Jankovic G, Jovanovic D, Nikolic LJ, Dimitrijevic J. Interferon alpha sensitisation induced fatal renal insufficiency in a patient with chronic myeloid leukaemia: case report and review of literature. J Clin Pathol. 2006;59(8):879–81.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. Perricone C, Ceccarelli F, Nesher G, Borella E, Odeh Q, Conti F, et al. Immune thrombocytopenic purpura (ITP) associated with vaccinations: a review of reported cases. Immunol Res. 2014;60(2–3):226–35.

    CAS  Article  PubMed  Google Scholar 

  9. Fuchs R. Manual hämatologie. 32nd ed. Berlin: Stolberg: Nora Verlag; 2022.

    Google Scholar 

  10. Provan D, Arnold DM, Bussel JB, Chong BH, Cooper N, Gernsheimer T, et al. Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv. 2019;3(22):3780–817.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Hamiel U, Kventsel I, Youngster I. Recurrent immune thrombocytopenia after influenza vaccination: a case report. Pediatrics. 2016. https://doi.org/10.1542/peds.2016-0124.

    Article  PubMed  Google Scholar 

  12. Yamamoto Y, Ohara Y, Iwai A, Hara R, Matsuki T, Fukushima K, et al. Influenza vaccination—associated acute thrombocytopenia and diffuse alveolar hemorrhage. Intern Med. 2020;59(13):1633–7.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Nagasaki J, Manabe M, Ido K, Ichihara H, Aoyama Y, Ohta T, et al. Postinfluenza vaccination idiopathic thrombocytopenic purpura in three elderly patients. Case Rep Hematol. 2016;2016:7913092.

    PubMed  PubMed Central  Google Scholar 

  14. Lee E-J, Cines DB, Gernsheimer T, Kessler C, Michel M, Tarantino MD, et al. Thrombocytopenia following pfizer and moderna SARS-CoV-2 vaccination. Am J Hematol. 2021;96(5):534–7.

    CAS  Article  PubMed  Google Scholar 

  15. Helms JM, Ansteatt KT, Roberts JC, Kamatam S, Foong KS, Labayog J-MS, et al. Severe, refractory immune thrombocytopenia occurring after SARS-CoV-2 vaccine. J Blood Med. 2021. https://doi.org/10.2147/JBM.S30704.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Bhattacharjee S, Banerjee M. Immune thrombocytopenia secondary to COVID-19: a systematic review. SN Compr Clin Med. 2020;2(11):2048–58.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  17. Arya LS, Ghai OP, Saraya AK. Thrombocytopenic purpura following DPT vaccination. Pediatr Hematol Oncol. 1993;10(4):381–3.

    CAS  Article  PubMed  Google Scholar 

  18. Bhowmik A, Biswas T. Immune thrombocytopenia following diphtheria pertussis–tetanus and oral polio vaccine. Indian Pediatr. 2016;53(10):934–5.

    PubMed  Google Scholar 

  19. Hsieh Y-L, Lin L-H. Thrombocytopenic purpura following vaccination in early childhood: experience of a medical center in the past 2 decades. J Chin Med Assoc. 2010;73(12):634–7.

    Article  PubMed  Google Scholar 

  20. Jadavji T, Scheifele D, Halperin S, Canadian paediatric society/health cananda immunization monitoring program. Thrombocytopenia after immunization of Canadian children. Pediatr Infect Dis J. 2003. https://doi.org/10.1097/01.inf.0000048961.08486.d1.

    Article  PubMed  Google Scholar 

  21. Lambert MP, Gernsheimer TB. Clinical updates in adult immune thrombocytopenia. Blood. 2017;129(21):2829–35.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  22. Samson M, Fraser W, Lebowitz D. Treatments for primary immune thrombocytopenia: a review. Cureus. 2019;11(10):e5849.

    PubMed  PubMed Central  Google Scholar 

  23. David P, Shoenfeld Y. ITP following vaccination. Int J Infect Dis. 2020;1(99):243–4.

    Article  Google Scholar 

  24. Guimarães LE, Baker B, Perricone C, Shoenfeld Y. Vaccines, adjuvants and autoimmunity. Pharmacol Res. 2015;100:190–209.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Kivity S, Agmon-Levin N, Blank M, Shoenfeld Y. Infections and autoimmunity–friends or foes? Trends Immunol. 2009;30(8):409–14.

    CAS  Article  PubMed  Google Scholar 

  26. Cecinati V, Principi N, Brescia L, Giordano P, Esposito S. Vaccine administration and the development of immune thrombocytopenic purpura in children. Hum Vaccin Immunother. 2013;9(5):1158–62.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Yokomichi H, Tanaka-Taya K, Koshida R, Nakano T, Yasui Y, Mori M, et al. Immune thrombocytopenic purpura risk by live, inactivated and simultaneous vaccinations among Japanese adults, children and infants: a matched case-control study. Int J Hematol. 2020;112(1):105–14.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

Open Access funding enabled and organized by Projekt DEAL. The authors received no additional financial support for the research, authorship, and/or publication of this article.

Author information

Affiliations

Authors

Contributions

OK and MAS designed the paper. OK, JS and JG were responsible for patient care and clinical management. OK, JS, JG and MAS contributed to the analysis and interpretation of data and preparation of the manuscript. OK is the guarantor of this case report. All authors reviewed and approved the final manuscript. Funding: MAS. All authors agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Maximilian Andreas Storz.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

The patient gave oral and written consent to the authors to publish her de-identified case.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1.

The patient kindly declined to share her perspective on the treatment(s) she received. The CARE guidelines were followed for this case report. The CARE Guidelines Checklist is available as a supplementary file. The ISPE guidelines for submitting adverse event reports for publication were followed, as well.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Küster, O., Schmohl, J., Greiner, J. et al. Severe immune thrombocytopenia following diphtheria, tetanus, pertussis and polio vaccination in a 36-year-old Caucasian woman: a case report. Eur J Med Res 27, 63 (2022). https://doi.org/10.1186/s40001-022-00686-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s40001-022-00686-z

Keywords

  • Vaccination
  • Diphtheria
  • Tetanus
  • Pertussis
  • Polio
  • Immune thrombocytopenia
  • Bleeding
  • Platelets
  • Adverse effect
  • Case report