Expert opinions for COVID-19 vaccination in patients with non-malignant hematologic diseases (2023)

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Carlo Dufour, Helen Papadaki, Alan Warren, Colm Bradley, Cristina Mecucci, Jan Palmblad, Cornelia Zeidler, Francesca Fioredda, Sam Salek, Brigitte Schlegelberger and Daniela Guardo, on behalf of the EHA SWG on Granulocytes and Constitutional Marrow Failure Disorders; Carlo L. Balduini,Andreas Greinacher, Thomas Kühne and Francesco Rodeghiero, on behalf of the EHA SWG on Thrombocytopenias and Platelet Function Disorders; and Ali T. Taher, Achille Iolascon and Rayan Bou-Fakhredin, on behalf of the EHA SWG on Red Cells and Iron.

Diffusion of the new coronavirus SARS-CoV-2continues worldwide, reaching a peak in December 2020 [1].

Recently, three rapidly developed vaccines: BNT162b2 mRNA vaccine (manufactured by Pfizer BioNTec), the mRNA-1273 mRNA vaccine (manufactured by Moderna-NIH) and the ChAdOx1 nCoV-19 vaccine based on an adenoviral vector (manufactured by Astra-Zeneca) have been approved in Europe [2-4] and their availability is growing across European countries. These different vaccines have been approved in Europe for specific age groups and all require intramuscular injection.

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No data on efficacy and side effects of COVID-19 vaccines in patients with hematological non-malignant diseases are available, and thus most of present recommendations are not evidence based.

Some recommendations apply to all hematological non-malignant diseases, while others concern specific disorders.

General recommendations

1) Vaccination must not change precautionary behavior, such as the use of mask, hand disinfection and social distancing.

2) In patients with a history of anaphylactic reactions, the risk of a severe side effect should be carefully weighed against the expected benefit.

3) Influenza vaccination should also be administered to immunocompromised patients in order to reduce its circulation and possible dual infection.

4) COVID-19 antibodies assessment after vaccination, due to the lack of currently available validation, is not routinely recommended. However, data regarding its protective titres will hopefully be available soon thus making this evaluation a potential tool to assess efficacy.

Immunocompromised patients

1) Recommendations must take patients, their close contacts and health care workers (HCW) into equal consideration.

2) Immunosuppressed patients are probably unable to generate a fully protective immune response to SARS-CoV-2 vaccines approved for use in the general population; therefore, protection induced by COVID-19 vaccination may be lower. Some investigations might help clinicians to determine if a patient is likely to mount a protective immune response. These include WBC count, peripheral lymphocyte subsets, immunoglobulin serum levels, tetanus and pneumococcal titres. However, it has to be noted that these evaluations do not necessarily reflect the real clinical protection provided by a vaccine and as such their role remains uncertain. Despite this, in the absence of safety data no major adverse effects are expected with mRNA-based technology vaccines.

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3) Taking into account the above premises and based on current knowledge, vaccination might be useful in:

  • Patients with an increased risk of infections.
  • Patients with an increased risk of severe course of COVID-19 due to coexisting co-morbidities. like chronic lung disease, significant cardiac disease, severe obesity, diabetes and liver disease.
  • All close adult contacts (currently new coronavirus SARS-CoV-2 vaccines are not approved for subjects below age 16 years). Healthcare workers in direct contact with hematological patients.

4) Risk and benefits for immunocompromised patients should be weighed case-by-case and timing chosen in view of the individual therapeutic program; just as an example, SARS-CoV-2 vaccination should be prioritized over other vaccinations after B-cell depletion (e.g., rituximab) or HSCT and a timespan of 3‑6months may be taken prior to the vaccination.

Patients with Hemoglobin disorders, chronic iron deficiency or autoimmune hemolytic anemia

1) Patients with hemoglobin disorders are amongst patient-populations most vulnerable to the complications of the SARS-CoV-2 infection. If their appropriate clinical management is not safeguarded and if certain recommendations are not followed, the health and quality of life of these patients will be seriously impacted. Therefore, all adult patients with Sickle Cell Disease, all Thalassaemia patients with severe iron overload, all splenectomized patients and particularly those with one or more underlying co-morbidities should receive a COVID-19 vaccine [5]

2) There is no contraindication for splenectomized patients to being given the COVID-19 vaccine.

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3)Data on the COVID-19 vaccine in the context of chronic iron deficiency is still scarce. However, it is advisable to correct the iron deficiency before administration of the COVID-19 vaccine”

4) Auto-antibodies directed to the red blood cell membrane have been found in SARS-CoV-2 infection and there have been several reports describing the association between SARS-CoV-2 infection and autoimmune hemolytic anemia (AHIA). A study by Algassim et al. revealed that COVID-19 patients with AIHA are linked to poor prognosis and longer hospital stay, mainly when their hemoglobin level is below 12 g/L [6]. Since individuals affected with AIHA could have a worsen form of the disease, we recommend that these patients receive the COVID-19 vaccine. However, there are no studies on the possible role of vaccination on aggravation of chronic AHIA.

Patients with thrombocytopenia or platelet function disorders

1) Vaccination is particularly useful in these condition for two reasons:

  • a reduction of platelet count is common in COVID-19 and this could aggravate the bleeding risk of patients with pre-existing platelet defects;
  • anticoagulant therapy may be a life-saving treatment in some COVID-19 patients, but this treatment is contraindicated in people with severe platelet defects.

2) Like other vaccinations [7], COVID-19 vaccine could cause worsening or recurrence of immune thrombocytopenias in rare instances. However, as with other vaccinations, the benefit of COVID-19 vaccination is expected to be greater than the risks of infection.

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3) The intramuscular injection required for COVID-19 vaccines presently available in Europe could cause hematomas in patients with platelet defects. However, it is commonly accepted that minimally invasive procedures are not contraindicated in subjects with platelet counts higher than 30 x 109/L [8]. The attending physician may decide to vaccinate individuals with platelets lower than this threshold when they do not have a clinically significant bleeding tendency. In subjects with platelet function defects, bleeding history indicates whether intramuscular injection is contraindicated.

In patients with less than 30 x 109 platelets/L, the attending physician should decide whether to try to increase their number with non-immunosuppressive drugs (for instance, intravenous Ig or TPO-receptor agonists for immune thrombocytopenia and TPO-receptor agonists for inherited thrombocytopenias known to respond to this treatment) prior to vaccination. In patients with Glanzmann Thrombasthenia, concomitant application of rFVIIa lowers the risk of severe intramuscular bleeding. The risk of hematoma after intramuscular injection in subjects receiving antiplatelet drugs is low and the decision whether or not to interrupt treatment will depend on the specific clinical situation. In the event that vaccines that can be administered by routes other than intramuscularly become available in the future, they will be used preferentially in cases with clinically relevant platelet defects.


  1. Von Lilienfeld-Toal, M., et al., Coronavirus-Infektion (COVID-19) bei Patienten mit Blut- und Krebserkrankungen. ONKOPEDIA Leitlinien von DGHO, OeGHO, SGMO und SGH+SSH, Status Dezember 2020.
  2. Polack, F.P., et al., Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med, 2020. 383(27): p. 2603-2615.
  3. Baden, L.R., et al., Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med, 2020.
  4. Voysey, M., et al., Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet, 2020.
  5. TIF Position Statement on the COVID-19 Vaccines & Haemoglobinopathies (2020) Nicosia, Cyprus
  6. Algassim AA, Elghazaly AA, Alnahdi AS, Mohammed-Rahim OM, Alanazi AG, Aldhuwayhi NA, Alanazi MM, Almutairi MF, Aldeailej IM, Kamli NA, Aljurf MD. Prognostic significance of hemoglobin level and autoimmune hemolytic anemia in SARS-CoV-2 infection. Annals of Hematology. 2021 Jan;100(1):37-43.
  7. Valerio Cecinati, Nicola Principi, Letizia Brescia, Paola Giordano, Susanna Esposito. Vaccine administration and the development of immune thrombocytopenic purpura in children. Hum Vaccin Immunother. 2013;9:1158-62.
  8. British Committee for Standards in Haematology General Haematology Task Force. Guidelines for the investigation and management of idiopathic thrombocytopenic purpura in adults, children and in pregnancy. Br J Haematol. 2003;120(4):574-96
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Does the COVID vaccine affect hematology? ›

We only observed an increased risk of leukopenia following the second dose of BNT162b2 (aOR 1.58, 95% CI 1.24-2.02; day 0-14, IRR 2.21; 95% CI 1.59-3.08). There was no increased risk of any hematological abnormalities after CoronaVac vaccination.

What disease is contraindicated for COVID vaccine? ›

a history of allergy. anaphylaxis to food, drugs, venom or latex. allergic conditions, including asthma, atopic dermatitis (eczema) or allergic rhinitis (hay fever).

Can you have the COVID vaccine if you have a blood disorder? ›

Most people who have well controlled ITP/Thrombocytopenia/TTP (eg platelet count over 30) are able to have the vaccine following the general precautions. Contact the centre for further advice if you are unsure. My bleeding disorder isn't mentioned here.

Is the COVID vaccine safe for anemia patients? ›

During the approval process, MHRA deemed that all of the vaccines currently available are suitable and safe for people who are immunocompromised. We understand that for people with aplastic anaemia, there is a small risk of relapse associated with all vaccinations, and research is still ongoing into this.

Does COVID vaccine affect red blood cell count? ›

Partial vaccination did not alleviate the anemia, but fully vaccinated patients demonstrated higher RBC counts and lower RDWs with significance, albeit the patient ratios with deranged hematological data showed no difference from those without vaccination.

What rare blood disorder is linked to the COVID vaccine? ›

Symptoms related to thrombocytopenia such as bruising and petechiae are common. More serious bleeding has generally occurred after anticoagulation was initiated. Routine testing of platelet counts following COVID-19 vaccination is not suggested due to the rarity of the syndrome.

What neurological disorders are linked to the COVID vaccine? ›

COVID-19 vaccination also affects the cranial and peripheral nerves and causes side effects such as Bell's palsy (facial nerve palsy—7 cranial nerve), abducens nerve palsy (lateral rectus ocular muscle nerve palsy—6 cranial nerve), impaired vision, olfactory, hearing, Guillain–Barre syndrome (GBS), small fiber ...

What are underlying conditions for Covid patients? ›

Like adults, children with obesity, diabetes, asthma or chronic lung disease, sickle cell disease, or who are immunocompromised can also be at increased risk for getting very sick from COVID-19.

Does the COVID shot cause immunosuppression? ›

According to European Medicines Agency recommendations, frequent COVID-19 booster shots could adversely affect the immune response and may not be feasible.

What blood disorder is linked to vaccine? ›

It's also referred to as 'vaccine-induced immune thrombotic thrombocytopenia' (VITT). Thrombosis is the formation of a blood clot, which prevents blood flowing normally through the body. Thrombocytopenia is a condition where there aren't enough platelets in the blood.

Can the COVID vaccine cause platelets to drop? ›

The Medical and Healthcare products Regulatory Agency (MHRA) had previous reported low platelet counts in combination with blood clots following vaccination with the Oxford-AstraZeneca vaccine, estimated to occur at a rate of approximately 13 per million first doses.

Can you get COVID vaccine if you have polycythemia vera? ›

Yes. Experts recommend getting the vaccine even if you have a condition such as polycythemia vera.

What are the hematological effects of COVID-19? ›

In nonsevere cases, hematological changes are subtle, included mainly lymphocytopenia (80.4%). In severe, critically ill patients and those with cytokine storm, neutrophilia, lymphocytopenia, elevated D-dimer, prolonged PT, and reduced fibrinogen are predictors of disease progression and adverse outcome.

Can COVID affect hemoglobin levels? ›

COVID-19 combines the so-called anemic hypoxia (low hemoglobin concentration), with the hypoxic hypoxia (low hemoglobin saturation). Oxygen deprivation and iron accumulation in lung tissues generate pulmonary vasoconstriction and neoshunting formation, regardless of the incurring pneumonia.

What effect does Covid have on blood cells? ›

Some people infected with SARS-CoV-2 develop abnormal blood clotting. “In some people with COVID-19, we're seeing a massive inflammatory response, the cytokine storm that raises clotting factors in the blood,” says Galiatsatos, who treats patients with COVID-19.


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