Questions on blood and injections

[cheddar]

I'm doing research for a short story and I could use some information from people in the medical field or anyone else knowledgeable on this subject who would care to help out.

What I need is information regarding the range of reactions that people might experience if they were injected with a syringe-full of another person's blood. I already know about ABO blood typing and the Rh factor and how some people would have no reaction at all depending on the two blood types involved. And for the sake of this particular story blood-borne illnesses would not come into play--the donor's blood would be free of HIV or other such diseases.

I wasn't able to find articles on Google or Wikipedia pertaining to this specific scenario. Those seemed to deal with reactions to transfusions (thus involving a much larger amount of blood than what I have in mind).

For example, what might happen in this scenario: a person with Rh negative blood receives an injection of Rh positive blood (an injection equaling the volume of a single syringe--how large would that be from a type of syringe that is normally accessible in a hospital?) Would an injection of that size have the potential to cause harm, and if so what sorts of symptoms would the affected person exhibit? Over what time frame would these reactions manifest? (Instantly? Hours? Days?) Could this potentially cause death from just one injection, or from repeated injections over the course of a few days? Would someone who was already ill or had a weakened immune system be harmed by this more than a healthy person?

If this happened to someone without them knowing it, would a doctor be able to quickly figure out what had happened to them, or would it be difficult to diagnose the cause of their symptoms? For the story to work the perpetrator would need to be able to perform many of these injections over a period of time without anyone suspecting what they were doing.

If this story idea turns out to be unworkable based on the science involved, no big loss. It is rather icky.

 

[JoeTheJuggler]

What I need is information regarding the range of reactions that people might experience if they were injected with a syringe-full of another person's blood.

How big a syringe are you talking about? I'm not sure there would be any detrimental effect to an adult with Rh- blood that got an injection of Rh+ blood. The danger is to a baby (see below). And I don't think an Rh+ person is adversely affected by receiving Rh- blood at all. (Unless of course that Rh- blood was from someone already exposed to Rh+ blood and contains antibodies that would attack the Rh+ cells. In that case, I'm not sure what dose would be dangerous or even if it's a big concern in healthy adults.)

The issue with Rh factor in babies is the situation where the baby is Rh+ and the mother is Rh-, and the mother has had a Rh+ baby in the past (or has otherwise been exposed to RH+ blood, as in a transfusion). In this case, the mother's blood contains antibodies that will attack the baby's blood cells.

 

[athon]

How big a syringe are you talking about? I'm not sure there would be any detrimental effect to an adult with Rh- blood that got an injection of Rh+ blood. The danger is to a baby (see below).

There would definitely be a danger to the adult.

There are a number of antigens on the outside of red blood cells that act as markers. A, B and Rhesus are three, but there are others as well. A blood bank will always check your blood against potential matches regarding most of these.

If you're positive for a marker and receive blood that is negative for it, it won't matter, as there's no antigen for the body to recognise as foreign. On the other hand, if you're negative (such as for Rhesus) and have positive blood introduced, your body will recognise the cells as foreign and will mount an immune reaction.

As you said, however, the scale of this reaction will depend on the amount injected. I suspect it wouldn't take much for symptoms such as fever and joint pain to occur (perhaps as little as a few tens of millilitres, but I am guessing). These symptoms arise because the introduced blood cells would be destroyed by the immune response, spilling their contents and further promoting a response to the cell trauma. For death to occur, I'd imagine it would take a substantial transfusion. I seem to remember an experiment in the 17th century where the blood of a sheep was transfused into an adolescent boy, who survived. In operations, death would typically occur less because of the immune reaction, and more because the patient has already lost substantial blood and introduced blood is destroyed.

Happy to hear from an immunologist or a blood banker on this one to correct any of my mistakes.

Athon

 

[Dogdoctor]

I think the amount of reaction depends on exact types and previous sensitization to said blood types. I doubt a doctor could easily figure out what had happened if at all. If the immune system is allready primed to target that particular type of blood cells, the the reaction will be larger and quicker and if not then slower and less severe.

 

[JoeTheJuggler]

If you're positive for a marker and receive blood that is negative for it, it won't matter, as there's no antigen for the body to recognise as foreign. On the other hand, if you're negative (such as for Rhesus) and have positive blood introduced, your body will recognise the cells as foreign and will mount an immune reaction.

In the case of someone with Rh- blood receiving Rh+ blood, the danger is only if the recipient is a woman, and the danger is to her baby if she has one after she has been exposed to the Rh+ blood.

If the transfusion recipient is already sensitized (already has the antibodies from a previous exposure) the danger is mainly that the new blood will be attacked. Even so, according to this study, "the gross hemolysis of transfused blood may be entirely asymptomatic". It continues:

In one case a pint of blood was completely hemolyzed within two hours without producing symptoms. The only signs were hemoglobinuria, low grade jaundice, urobilinogenuria and a rising Rh antibody titer. The patient had previously been sensitized by a single pint of Rh-positive blood.

The same study says not every person who is Rh- negative that is exposed by transfusion to Rh+ blood is sensitized to the Rh factor. (It says "more than 50 percent" are.)

 

[athon]

Interesting. I stand corrected, Joe. It's surprising, and I would have said it countered what I was taught back in my blood banking days, but going on this I'm prepared to say I might have simply had the wrong end of the stick.

Thanks.

Athon

 

[JoeTheJuggler]

Interesting. I stand corrected, Joe. It's surprising, and I would have said it countered what I was taught back in my blood banking days, but going on this I'm prepared to say I might have simply had the wrong end of the stick.

Thanks.

Athon

Not really---from a blood banking perspective, you'd still do you best not to give mismatched Rh blood. From that same study:

The dangers of Rh sensitization can be avoided by routine Rh typing of all prospective recipients of transfusion, whether male or female, and by giving only Rh-negative blood to those who are Rh-negative.

Also, in the case where 100% of a pint of transfused blood was hemolyzed with no major symptoms had to have been a case where that blood wasn't really needed. If you're in a car wreck or something and have lost a lot of blood, it could be life-threatening if your transfused blood cells are all destroyed.

I just don't think the dangers of mismatched blood--especially wrt Rh factor-- are quite what Cheddar was thinking they are.

 

[Andrew Wiggin]

As far as quantity of blood needed to cause a transfusion reaction: I've seen reactions start within seconds, and blood transfusions are started very slowly. That means just a few milliliters, if that. Normally at this point, you'd be closely monitored, so the nurse would shut off the transfusion and treat the reaction. It can be dramatic, with instant fever, chills and rigors. This is with blood that was matched by the blood bank, so a relatively good match, but the patient still reacted for some reason. In the case of random unmatched blood, you'd almost certainly get a transfusion reaction right away. The extent and severity would depend on so many different factors that it's really impossible to predict.

A

 

[Capsid]

In addition to mothers reacting (mounting an antibody response) to the rhesus antigens of the foetus they can also generate antibodies to its HLA (human leukocyte antigens also known as major histocompatibility antigens) that it derives from the father and are not matched to those of the mother (this is highly likely given the large variability of HLA). You will also mount an antibody response after a blood transfusion if there is a mismatch of HLA antigens. You don't make immune responses to your own antigens due to immunological tolerance.

Most people who are transfused and multiparous women will make anti-HLA antibodies. If someone donates blood with anti-HLA antibodies and these antibodies react specifically with the recipient's own HLA, then this can lead to problems including thrombocytopaenia and TRALI (transfusion related acute lung injury).

So with regard to your story, if you had a syringe of high titre anti-HLA antibody and you injected a recipient with the HLA that the antibodies are specific for then this could cause complications including death which occur very soon after injection. I think you would only need the one injection to do this (I'm not medically qualified though) but I'm fairly sure they would need hospitalisation. I think it would be relatively easy to work out what was the cause if the contents of the syringe was known but usually TRALI is an accidental consequence because getting a match of the antibody with the HLA antigen is rare in most cases. If the perpetrator knew there was a match though he could claim innocence of that fact but still murder the recipient (presuming this is what you have in mind for your story).

 

[cheddar]

Thanks for the information. The specifics are helpful. All of this sounds like it is in keeping with my original assumptions.

 

[wilks]

As far as quantity of blood needed to cause a transfusion reaction: I've seen reactions start within seconds, and blood transfusions are started very slowly. That means just a few milliliters, if that. Normally at this point, you'd be closely monitored, so the nurse would shut off the transfusion and treat the reaction. It can be dramatic, with instant fever, chills and rigors. This is with blood that was matched by the blood bank, so a relatively good match, but the patient still reacted for some reason.
A

Certainly blood that is ABO incompatible could produce a very fast reaction like this. It is worth remembering that there are many other blood groups besides the ABO and Rhesus, some of them can produce similar reactions in patients who have the appropriate antibodies.
As to whether the doctor would be able to work out what had happened - it would be very difficult if they did not know that blood had been given (as in your story, I presume) but a biomedical scientist in the lab might be able to figure it out. If the donor cells were not all haemolysed then cells coated with antibody could be detected, as could the presence of mixed fields of cells, enabling them to guess that blood had been given.

 

[JoeTheJuggler]

As far as quantity of blood needed to cause a transfusion reaction: I've seen reactions start within seconds, and blood transfusions are started very slowly. That means just a few milliliters, if that.

But what is the reaction? It's not like a mismatched blood type is a toxin.

It's merely that the recipient has antibodies to protein markers on the transfused blood cells. So the new cells get attacked and destroyed. As I mentioned, this could be a very bad thing if getting that blood (including the cells, and not just the other stuff) is a matter of some importance, but it's not like the reaction causes the immune system to attack the recipient's own negative cells also.

The problem with an Rh+ fetus and an Rh- mother is that the mother's antibodies will attack the entire complement of the fetus' blood cells. That is, they're all potential targets for hemolysis.

 

[JoeTheJuggler]

It can be dramatic, with instant fever, chills and rigors. This is with blood that was matched by the blood bank, so a relatively good match, but the patient still reacted for some reason.

This sounds like an infection (or even something unrelated tot he transfusion--that's why anecdotes aren't as useful as studies). I know blood banks screen for HIV and hepatitis and so on, but it sounds like something else maybe got through.

Cheddar said not to consider infections, so I don't think the situation you describe applies.

 

[Capsid]

This sounds like an infection (or even something unrelated tot he transfusion--that's why anecdotes aren't as useful as studies). I know blood banks screen for HIV and hepatitis and so on, but it sounds like something else maybe got through.

Cheddar said not to consider infections, so I don't think the situation you describe applies.

I was thinking it could be an anaphylactic reaction?

 

[JoeTheJuggler]

In addition to mothers reacting (mounting an antibody response) to the rhesus antigens of the foetus they can also generate antibodies to its HLA (human leukocyte antigens also known as major histocompatibility antigens) that it derives from the father and are not matched to those of the mother (this is highly likely given the large variability of HLA). You will also mount an antibody response after a blood transfusion if there is a mismatch of HLA antigens. You don't make immune responses to your own antigens due to immunological tolerance.

And is this response symptomatic? Or would it just be a matter of making antibodies that will destroy future transfusions of mismatched blood?

Again, I'm not saying this reaction wouldn't be dangerous in some situations, but basically killing off transfused blood cells isn't life-threatening to a normal healthy adult that doesn't need a blood transfusion. (In fact, it's just the immune system doing what it ought do.)

Most people who are transfused and multiparous women will make anti-HLA antibodies. If someone donates blood with anti-HLA antibodies and these antibodies react specifically with the recipient's own HLA, then this can lead to problems including thrombocytopaenia and TRALI (transfusion related acute lung injury).

So with regard to your story, if you had a syringe of high titre anti-HLA antibody and you injected a recipient with the HLA that the antibodies are specific for then this could cause complications including death which occur very soon after injection. I think you would only need the one injection to do this (I'm not medically qualified though) but I'm fairly sure they would need hospitalisation. I think it would be relatively easy to work out what was the cause if the contents of the syringe was known but usually TRALI is an accidental consequence because getting a match of the antibody with the HLA antigen is rare in most cases. If the perpetrator knew there was a match though he could claim innocence of that fact but still murder the recipient (presuming this is what you have in mind for your story).

You're talking about an injection of the antibodies themselves and not whole blood, right?

 

[JoeTheJuggler]

I was thinking it could be an anaphylactic reaction?

But from something other than ABO or Rh, right? (He said the blood was matched, and at least that much compatibility is pretty routine.)

 

[Capsid]

And is this response symptomatic? Or would it just be a matter of making antibodies that will destroy future transfusions of mismatched blood?

Again, I'm not saying this reaction wouldn't be dangerous in some situations, but basically killing off transfused blood cells isn't life-threatening to a normal healthy adult that doesn't need a blood transfusion. (In fact, it's just the immune system doing what it ought do.)

Yes, it's a normal immune reaction. People who make anti-HLA antibodies remain asymptomatic. But you have it backwards, the problem arises when their blood is used to transfuse a recipient and that recipient has HLA that is specifically recognised by the anti-HLA antibodies of the donor. What you are referring to is when an an anti-HLA antibody positive individual receives a blood transfusion. I assume, that in this case the anti-HLA antibodies would destroy the cells of the transfused blood but only when the HLA of the donor is concordant with the recipient's pre-existing anti HLA antibody specificity.

You're talking about an injection of the antibodies themselves and not whole blood, right?

Yes, although whole blood will still contain antibodies in the plasma of whole blood.

 

[wilks]

But what is the reaction? It's not like a mismatched blood type is a toxin.

It's merely that the recipient has antibodies to protein markers on the transfused blood cells. So the new cells get attacked and destroyed. As I mentioned, this could be a very bad thing if getting that blood (including the cells, and not just the other stuff) is a matter of some importance, but it's not like the reaction causes the immune system to attack the recipient's own negative cells also.

The reaction is a strong inflammatory response and in cases of severe transfusion reaction the patients are more likely to be killed by shock than by loss of red cells.

And unfortunately, in some cases, the reaction CAN haemolyse the patients own negative cells. In incompatibilities with the Kidd (Jk) blood group system, for example, complement is activated and that can produce an innocent bystander reaction in which the patient's own red cells are also destroyed.

 

[Deetee]

Plenty of components can trigger reactions.
Perhaps something along the following lines might do?

Allergic and Anaphylactic Reactions

These reactions occur in response to plasma proteins in the blood components administered, and represent a type 1 hypersensitivity response, i.e. an immediate allergic reaction following a second or further contact with an antigen which may vary on a scale from urticaria to anaphylaxis.[7] Hypersensitivity responses occur very rapidly following contact with the relevant antigens and recur on subsequent occasions. The primary antigen exposure stimulates plasma cells to produce specific IgE. This IgE binds to mast cells via its Fc receptor and sensitizes them. Representation of the antigen causes crosslinking of surface IgE stimulating degranulation of mast cells. The organ systems affected include skin, and the mucosa of the gastrointestinal and respiratory tracts, which are where mast cells are normally distributed. Stimulation of the sensory nerves causes itch and flare reactions while smooth muscle contraction causes vascular leakage and tissue edema. Arterial dilatation may cause headache and hypotension, while bronchoconstriction can cause respiratory distress. The mediators of this response from endogenous sources include histamine, serotonin and bradykinin, the analphylatoxins C3a and C5a, lymphokines and leukotrienes.[21] Cutaneous allergic transfusion reactions occur in 1-3% of plasma-containing blood components, including red cells and platelets. The cardinal signs and symptoms are local erythema, urticaria and pruritus. Soluble proteins in donor plasma are generally responsible but specific etiologies are rarely identified. Occasionally it has been discovered that the donor has ingested a food allergen or drug to which the recipient is sensitized.[21] Treatment includes antihistamines and occasionally hydrocortisone; antihistamines may be used prophylactically 1 hour before transfusion, to prevent future episodes.
Anaphylactic transfusion reactions are much less common, occurring once per 20,000-400,000 units of blood or components transfused. The cause is generally an IgG anti-IgA in an IgA-deficient recipient who is transfused with IgA-containing blood products. The formation of IgG/IgA immune complexes leads to the activation of complement and the subsequent release of C3a and C5a anaphylotoxins.[22] The signs and symptoms include a feeling of apprehension and impending doom, generalized flushing, nausea, vomiting, diarrhea and abdominal cramps, laryngeal edema, bronchospasm and dyspnea, profound hypotension, shock and potential cardiopulmonary arrest. The transfusion should be stopped immediately and adrenaline 1 in 1000 (0.3-0.5 mL) given immediately. Supportive therapy for the circulation and respiratory system may be necessary. The differential diagnosis for such an acute and severe transfusion reaction must include ABO-incompatibility with an AHTR, TRALI and perhaps bacterial contamination. IgA deficiency occurs in approximately 1 in 700 of the population in the UK and is defined as less than 0.05 mg/dL of IgA. The frequency of IgA deficiency with IgA antibodies is 1 in 1200; often anti-IgA is found in subjects who have never been pregnant or received a blood transfusion. Less than 20% of suspected cases of anti-IgA in a recipient reveal this to be the cause of the reaction.
Diagnosis must be made by reliably demonstrating deficiency of IgA and the detection of an anti-IgA. Once the diagnosis has been made, the patient must be clearly identified both on the hospital notes and on a wrist band or bracelet, and he/she must be fully informed of the implications. In future such patients should receive only IgA-deficient components which are collected from a special panel of IgA-deficient donors. In the absence of IgA-deficient donors, washed red cells may be administered with appropriate prophylactic measures taken beforehand in case of a mild reaction. Autologous transfusion may be considered in appropriate circumstances.

Or:

TRALI [transfusion related acute lung injury]

TRALI is a life-threatening complication of transfusion which may have a very dramatic clinical presentation indistinguishable from adult respiratory distress syndrome.[23] In most cases it begins within 2 hours of transfusion but may be up to 4 or 6 hours following administration of a plasma-containing blood component. Symptoms generally include fever, hypotension, chills, cyanosis, non-productive cough and dyspnea. Chest X-ray shows severe bilateral pulmonary edema or perihilar and lower lung field infiltration, without cardiac enlargement or involvement of the vessels. The X-ray findings may be much more severe than the auscultatory changes on examination. Severe hypoxia is usual, with very low arterial oxygen tensions, and the patient frequently requires mechanical ventilation. In contrast to patients with circulatory overload, those with TRALI have normal central venous pressure and normal or low pulmonary wedge pressure. It is possible that milder cases of TRALI may occur and not be recognized. Approximately 80% of patients with TRALI improve both clinically and physiologically within 2 or 3 days with adequate supportive care. Overall mortality appears to be in the region of 5-8%, in contrast to ARDS (adult respiratory distress syndrome), which has a mortality rate of 40-50%. Differential diagnosis includes circulatory overload, anaphylactic transfusion reaction and bacterial contamination.[7,9]
The true incidence of TRALI is unknown although there is a much quoted figure of 1 in 5000 plasma-containing transfusions.[24] This figure is likely to be an underestimate as milder cases may pass relatively unnoticed and severe cases may still be misdiagnosed, being attributed to circulatory overload. The precise mechanism involved in the development of TRALI is not clear, but two possible mechanisms have been postulated: an antibody-mediated and a soluble mediator-mediated. These mechanisms both involve the activation of granulocytes and the triggering of an inflammatory process, leading to the sequestration of neutrophils in the lung. In the vast majority of cases, investigators have demonstrated the presence of HLA class I and class II or granulocyte-specific antibodies in the donor.[25] In about half the cases studied, the HLA antibodies in the implicated donor correspond with one or more of the HLA antigens in the recipient. In other cases, neutrophil-specific antibodies (HNA1, HNA-3a) have been identified in the plasma of implicated units.[25,26] These antibodies are most commonly found in the donations of multiparous women. It seems that the granulocytes interact with activated complement causing aggregation and blockage of the pulmonary microvasculature. Pulmonary leukosequestration leads to transient changes in vascular permeability and pulmonary edema. In a small number of reported cases, similar antibodies are found in the pre-transfusion serum of the recipient and in such cases TRALI is more frequent after granulocyte transfusions.[27] In some cases clinically diagnosed as TRALI, no antibody has been identified. It has been suggested that in these cases the granulocyte activation is mediated by a soluble lipid substance, which accumulates during the storage of the products.[28] In any case, it is likely that a number of factors determine the final clinical response of a patient and these may include the characteristics of the antibody, nature and distribution of the related antigen, the extent of complement activation (in particular liberation of C5a) and the immune status of the recipient.
Diagnosis and Treatment

There is no diagnostic test or pathognomonic finding for TRALI, so the diagnosis is one of exclusion. Other causes of respiratory distress and pulmonary edema in the transfusion setting must be fully investigated, including myocardial infarction, circulatory overload and bacterial infection. The measuring of central venous and pulmonary wedge pressures is very helpful. A proper work-up of TRALI should include testing of the donor and recipient sera for granulocyte (HNA) and lymphocyte (HLA) antibodies.
Antibody specificity can be determined and HLA or HNA typing of the recipient's or donors' cells can also be carried out. The presence of a positive reverse lymphocyte crossmatch between donor serum and patient lymphocytes provides further supportive evidence. The treatment of TRALI includes intensive respiratory and circulatory support.[23] In almost all cases, oxygen supplementation is necessary, although mechanical ventilation may not always be required. Some reports suggest that the administration of corticosteroids may be beneficial.

Sourced from medscape. For TRALI, also see wiki for details

 

[Criticalist]

I think TRALI would be very unlikely after injection of a just a syringe of blood;A significant transfusion is usually involved, and certainly massive transfusion is one of the risk factors.