Blood donation and dermatology: What a dermatologist should know?

1) Blood donation and skin diseases

The suitability of prospective donors with skin diseases should be assessed if the skin condition reflects an underlying systemic disease, poses a risk of infection or if the donor is undergoing medication. According to WHO guidelines for blood transfusion, blood donation should be temporarily deferred if the venepuncture site is affected, the disease is severe or in the presence of secondary infection.³ While it’s impractical to enumerate all dermatologic diseases, we have summarised relevant conditions in Table 1.^1,2,4–8

Premalignant and malignant skin conditions

As most of the malignant conditions spread to distant sites (metastasis) either through blood or lymphatics, and even a single neoplastic cell can seed a tumour, patients having a history of malignant conditions are permanently deferred.⁵ However, exceptions are made for basal cell carcinoma (rodent ulcer), which is locally invasive and does not spread through the blood, and Bowen’s disease (squamous cell carcinoma in situ), which remains confined to the epidermal basement membrane.⁵ Consequently, individuals who have been cured of these conditions can safely donate blood.^4,7

Porphyrias

Patients with acute porphyrias, such as variegate porphyria and hereditary coproporphyria, may be associated with skin lesions in addition to increased levels of blood porphyrin irrespective of acute attacks.⁷ Since the recipient of the blood may theoretically get skin lesions, they are disqualified if they already have active skin lesions.⁷

Porphyria cutanea tarda is an acquired condition associated with underlying liver disease, often viral hepatitis B and C (HBV, HCV) or of unknown origin. They are disqualified due to ethical guidelines prohibiting donors from receiving direct or indirect benefits.¹ Therefore, therapeutic phlebotomy, which benefits the donor, could potentially compromise the reliability of the donor interview and the safety of the blood recipient due to the possibility of inaccurate risk behaviour disclosure.^4,5 Moreover, there exists a risk of transmitting HBV and HCV.

In erythropoietic protoporphyria and congenital erythropoietic porphyria, patients are often anaemic.⁴ Additionally, the presence of porphyrins in red blood cells reduces their lifespan and renders the blood unsuitable for donation.⁴

In summary, any individuals suffering from porphyrias are permanently deferred from donating blood.

Sexually Transmitted Infections and Human Immunodeficiency Virus Infections

Certain sexually transmitted infections (STIs) can also be transmitted through blood. Therefore, screening and deferring individuals who may be affected is crucial.⁵ Additionally, sexual contact may necessitate deferral.¹

Treponema pallidum, the causative organism of syphilis, is released into the bloodstream intermittently during infection and destroyed within 72 hours of storage at 40°C.¹ Therefore, the risk of transmission of syphilis through the transfused blood is low. However, it can still be transmitted through fresh blood and platelets.¹ While a recent Indian guideline mandates a deferral interval of one year following the date of cure, WHO still suggests permanent deferral of affected individuals.^1,2

Neisseria gonorrhoeae, the causative organism of gonorrhoea, is not transmissible through blood transfusion.¹ Despite this, many national and WHO guidelines mandate a temporary deferral of one year for affected individuals.¹ However, the Indian guidelines (2017) prohibit such individuals permanently from donating blood.¹⁰

HIV is primarily transmitted through direct blood-to-blood contact (with an infectivity rate of approximately 95%) or via sexual intercourse.¹ It is neither contagious nor spread by the faecal-oral route.¹ Therefore, there is no need to defer household contacts.⁵

Deferral intervals of various STIs and HIV are mentioned in Table 2.

• Pre-exposure prophylaxis or post-exposure prophylaxis for HIV

A person should be deferred if he has received pre-exposure prophylaxis or post-exposure prophylaxis in the last three months, as it interferes with testing for HIV by delaying seroconversion or producing ambiguous results in a positive donor.⁴

• High-risk sexual behaviours

It is crucial to screen potential blood donors whose sexual behaviour places them at increased risk of acquiring infectious diseases transmitted through blood.¹ High-risk behaviours include having multiple sex partners, engaging in transactional sex (exchange of money or drugs for sex), sex workers and their clients, men having sex with men (MSM) and females having sex with MSM.^1,2 MSM represent the largest subgroup affected by HIV in many developed countries.¹ MSM and blood donation accounts for a special mention.

• MSM and blood donation

For a considerable period, many countries upheld a policy of indefinitely deferring blood donations from MSM, citing their higher HIV risk compared to the general population.¹ However, this policy faced criticism in several countries, prompting adjustments that now permit donations from sexually active MSM under certain conditions, such as limitations on the number of sexual partners.⁵ On 7 August 2023, the American Red Cross implemented the FDA’s latest guidelines, mandating individual donor assessments for all prospective blood donors irrespective of their gender or sexual orientation.^3,5 This change effectively ended restrictions that had previously prevented sexually active gay and bisexual men from donating blood.⁵ Those previously deferred under MSM guidelines can now seek reinstatement by contacting the Red Cross Donor and Client Support Center.⁵

2) Blood donation and procedures

Invasive cosmetic procedures like tattooing, piercing, botulinum toxin injections, fillers, thread-lifts, semi-permanent makeup and electrolysis carry a risk of blood-borne infections unless performed under sterile conditions.¹ Blood donation centres should define deferral periods based on the safety and sterility of the procedure, and if it is not possible, individuals should be deferred for 12 months.¹

Once the raw areas have healed after laser treatment, the donor may be accepted.⁴

Deferral intervals of dermatological procedures are mentioned in Table 3.

3) Blood donation and medication

What constitutes a medication deferral period? Drugs and their metabolites in transfused blood can exert unintentional pharmacological effects on the recipient.¹ A medication deferral period signifies the duration during which individuals who have taken certain medications are temporarily ineligible to donate blood.⁵ This precautionary measure aims to avert any potential adverse effects on the recipients of donated blood.

Christian had proposed deferral periods based on factors such as the pharmacodynamic and pharmacokinetic properties of the drug as well as the type of blood product used, its plasma content and dilution upon transfusion.¹¹

1) Pharmacological properties of the drug

To determine the eligibility of drugs for blood donation purposes, they can be categorised based on their pharmacokinetic and pharmacodynamic profiles [Table 4].¹¹

2) Concentration of drug in donor’s plasma and its dilution upon transfusion

The concentration of drugs in a donor’s plasma during blood donation depends on various factors, including drug intake, dose, mode of administration, drug preparation and pharmacokinetic properties.¹¹ Both t_max (the time interval between drug intake and maximum plasma concentration) and t_1/2 (the plasma elimination half-life) are crucial here. While t_max is determined by the release and absorption of the drug, t_1/2 is affected by the distribution, metabolism and excretion of a drug. Drug concentrations at 3% and 0.000001% of therapeutic levels are considered safe for non-teratogenic and teratogenic drugs, respectively.¹² Based on these safety margins, waiting periods can be calculated based on the drug’s pharmacokinetics and with/without blood components to be prepared.

3) Type of the blood product used

Blood products can be classified as:

• i.

  Blood products containing up to 50 mL/U single-donor plasma(e.g. red blood cell concentrates, pooled plasma).¹¹

• ii.

  Blood products containing more than 50 mL/U single-donor plasma (average 250 mL/U)(e.g. whole blood, fresh frozen plasma, platelet concentrates).¹¹

Basis of deferral interval for a drug

1) Class 1 drugs

Following a period equivalent to t_max + 5t_1/2, approximately 97% of the drug is eliminated, resulting in a residual plasma drug concentration of approximately 3% of the therapeutic level, and further dose-dependent clinical effects are not anticipated at this level.¹¹ When blood products containing an average of 250 mL plasma from a single donor are transfused into adolescents >12 years of age and adults (5000mL blood volume, 2500mL plasma volume), the donor plasma is diluted about tenfold and the resultant drug level in the recipient’s plasma could reach around 10%.¹¹ To comply with the intended safety margin of 3%, a deferral interval of five plasma elimination half-lives is warranted.¹ In contrast, when blood products containing 50 mL single-donor plasma are transfused into adolescents >12 years of age and adults (5000mL blood volume, 2500mL plasma volume), the donor plasma is diluted about 50-fold and the resultant drug level in the recipient’s plasma is close to 2% of the therapeutic drug concentration, and that’s why no deferral is needed.¹¹

In summary, the transfusion of blood products containing teratogenic, fetotoxic or embryotoxic substances to pregnant women poses minimal risk to the foetus if the final concentration in the mother’s plasma remains below 3% of the therapeutic level.¹¹ This can be ensured either through the dilution of plasma in the recipient or by implementing donor deferral intervals equivalent to t_max + 5 t_1/2.¹¹

2) Class 2 drugs

In essence, defining threshold levels for genotoxicity presents a challenge due to the potential impact even a single molecule reaching the DNA may have.¹¹ Thus, rather than focusing on dilution factors post-transfusion, the total dose of the genotoxic drug remains pertinent in this context. A maximum daily intake of up to 1.5 mcg of a genotoxic drug is generally considered to be safe, given the resulting low risk of genotoxicity.¹¹ For this reason, a deferral period equivalent to t_max + 24 t_1/2 is warranted as it results in a genotoxic drug concentration of 1 mcg in the donor plasma or 0.000001% of therapeutic levels, which is considered safe.^11,12

3) Class 3 drugs

They do not require any deferral period.¹¹

4) Class 4 drugs

Drugs like non-steroidal anti-inflammatory drugs (NSAIDs) cause reversible inhibition of platelet aggregation. For such drugs, deferral periods of t_max + 5 t_1/2 are sufficient.¹¹

However, the impact of drugs such as aspirin, clopidogrel and ticlopidine extends beyond their elimination from the body as they inhibit platelet aggregation irreversibly.¹¹ Consequently, the restoration of the normal hemostasis relies on the generation of fresh platelets. Human platelets have an average lifespan of ten days, with approximately 10% of circulating platelets being replenished daily. Hence, such medications necessitate a deferral period of tendays.¹¹

Based on the aforementioned discussion, certain drugs and their deferral periods after the last dose are given in Table 5.

Corticosteroid therapy needs special mention. Donors should be deferred temporarily if:

• 1.

  Topical corticosteroids or tacrolimus/pimecrolimus are applied over large areas (>9%) or received tablets or injections for more than three weeks in the last six months

• 2.

  Donor needed systemic steroids for more than six months within the last 12 months.²

High-dose steroid therapy leads to immunosuppression, potentially masking infectious and inflammatory conditions that would otherwise disqualify donation.¹ Additionally, prolonged steroid use can lead to temporary adrenal dysfunction.¹ A 12-month waiting period after the final dose is recommended to ensure adrenal gland recovery.¹

Impact of deferral on blood donors

Studies indicate that deferral negatively affects future donor return rates, particularly among first-time donors and those who have deferred for more than a year.⁵ It is crucial to advise temporarily deferred donors on when they can donate and encourage their return.¹ Blood donors are less likely to return if the reasons for their deferral are communicated unclearly or unsatisfactorily. Providing counselling to deferred blood donors can enhance their compliance with follow-up medical care.