Hemochromatosis: preventing and solving problems with phlebotomy

Updated: January 5th, 2014.
Author: P. de Sterke, MSc, the Netherlands (not a doctor, just a patient).

Always consult your doctor before taking any medical action!!! I do not take any responsability for any problems caused by this article.
Comment are highly appreciated and can be sent to: pdesterke@hotmail.com

Remember: with most phlebotomies there will be no problems! Blooddonors do it all the time voluntarily!


Also read the general information on this topic from the Iron Disorders Institute: http://www.irondisorders.org/phlebotomy
Click here for: Latest news
 


Phlebotomy is the prefered treatment for most patients with hemochromatosis. Usually there are no problems with this treatment (1). It is the same procedure that people undergo voluntarily at the bloodbank. But there are some differences:
1: patients with hemochromatosis usually need a large number of phlebotomies in a relative short period
2: they are depending on the treatment
3: they cannot be sent away if it is impossible to remove the blood.
For this reason much energy should be devoted to the prevention and solving of problems with the phlebotomy and sometimes a different approach should be taken than the one is used with blooddonors.
This article is intended to help patients and medical staff to cope with problem situations and to prevent them.

Standard bloodbags versus vacuum bottles
For a phlebotomy at a bloodbank standard bloodbags with large needles are used.Bloodbag The reason for this is that these bloodbags are also used for standard blooddonations and with a small needle the red blood cells are damaged, making the blood unusuable for transfusion.
These big needles are not always ideal for patients with hemochromatosis. If their veins are damaged by the use of these big needles they have a very big medical problem. Maybe blood can be drawn without much problems now, but due to scarring it might become a problem in the future.
Scarring veins and other sticking problems can for a big part be prevented by the use of a smaller needle. When a smaller needle with a bloodbag is used the chances of clottng is higher. There are some solutions to this problem (more tips later in this article):
* Try more needle sizes to find the one that will work.
* Take an (baby) asperin 1/2-2 hour(s) before the phlebotomy, or in rare cases (for patients with a very high Hemoglobin) a blood thinner can be used.
* Drink enough.
* Use a vacuum bottle. The vacuum "sucks" the blood in the bottle, ensuring a constant bloodflow. Needles with size no. 19, 21, (23) should be used. A large needle (no. 16 or 17) as is used as with the usual blood donation bags should NOT be used as it might result in collapsing of the vein caused by the vacuum.
When removing the usual amount of 500 ml blood, best would be a vacuum bottle of minimal 600 ml to keep the vacuum pressure high enough to the end. Best is to mark the bottle at 500 ml so one knows when to stop. A vacuum bottle of 500 ml also is no problem, but when the blood flow is getting to low the hose should be connected to another "fresh" vacuum bottle. Vacuum bottles are dated and the old bottles should not be used as otherwise the vacuum may be lost. The bloodflow can be adjusted by experience depending on the individual patient. If the flow goes to fast a smaller needle can be used, and vice versa. The flow can also be adjusted with a blood pressure cuff (more on this later).
Ordering information for vacuumbottles (and needles)
* If Vacuum bottles are not available ask for them, if that does not give a result use a bloodbag. Preferably do not use a blood bag with a huge needle attached to it, but a bag where you can attach a smaller needle that fits your needs (protocol for use of 18 gauge needle (appendix 2). Experiment with the knowledge in this article and find the thinnest needle where the blood will not cloth in your situation! A blood bag with a luwer lock connection gives the option to connect every sice of needle (venflon). When a too small needle is used the bloodflow may stop. This problem can be solved by attaching a T-piece just after the needle. If the bloodflow stops a syringe can be attached immediately and by creating a bit of vacuum the flow is continued again.
TP using a non standard gauge; Canada, p. 8 of 8, appendix 2

Taking blood for the lab
Small prick in the finger Small prick in the finger Immediately before the phlebotomy always the hemoglobin (Hb) or hematocrit (Hct) should be measured. This can be done with a small prick in a finger! The Hb can be measured on the spot using for example a hemocue
Other lab values can be measured using the blood taken from the phlebotomy, for example by inserting a needle in the phlebotomy tube used. As a general rule, subjects undergoing phlebotomy whose values of Hb and Hct are less than 11.0 g/dL and 33%, respectively, are more likely to sustain undue fatigue and other immediate consequences of excessive blood removal and anemia (2, 14).

Pain from the stick?
Inserting the needle can be made less painfull by using Emla creme 1 2 3 , a local anesthetic. Emla should be applied about 1 hour before the venipuncture. Emla is prescribed by your doctor, just ask for it.

The venipuncture
Patients with hemochromatosis depend on a phlebotomy for a good health for the rest of their life. Scarring of the veins would be a big health problem. For this reason the venipuncture in these patients should always be done by the most experienced staff members! Many patients make an appointment when the person that can stick them the best is on duty.

If there are problems to find a good vein to take the blood, for example due to a thin bloodvessel, there are a number of alternatives possible. Patients with cold hands have contracted veins. They can put their hands 5 minutes in warm water (3, p.85), or putting a warm water bottle on the arm. It is even possible to put a woolen sock over the arm (the end cut out) and putting this well in advance over the arm or putting a warm wet towel on the arm. Itching can be prevented by putting another sock unther the woollen one. There are also other possibilities why the bloodvessel can be not accessable. The following options may help: regularly pinching in a little bal, bowing the elbow with some force up and down for some time with a fist, massaging the arm with firm pressure, walking some stairs prior to the phlebotomy, shaking the arm 1-3 minutes below the heart. Taking niacine (NOT niacimide!) about 30 minutes before phlebotomies may help dilate veins. The dosage needed will be adjusted for the individual. Start with 100 mg (-->700-1000 mg). The niacine will release histamine and this will increase the bloodflow making the vein larger. Do not take it on a regular/daily basis. Consult your doctor!

In the case of a "rolling" vein it is helpfull to put a cuff below and above the venipuncture site. This will help keeping the vein at its place. The use of a blood pressure cuff is the most comfortable for the patient and also can help in controlling the bloodflow. Because often the blood pressure is measured before the phlebotomy the band can stay on to the upperarm. The pressure should be increased just before the venipuncture to have a good access. Immediately after the venipuncture the pressure should be released to a comfortable lower pressure. But the pressure should be so high that it helps the bloodflow. The best pressure is also something that can be noted in the patients personal journal. When the bloodflow begins to diminish pumping up the pressure a little bit can help to give the flow the extra boost that was needed or making a fist (or changing to a new vacuum bottle).

If it is impossible to find a good bloodvessel in the elbow region, other places should be looked for: the lower arm, hands, feet, underlegs, upper legs, neck. The veins in these regions are thinner, so always a small needle should be used (no. (19), 21 or 23). These needles are about the size of the needles used when a little bit of blood is drawn for the lab. When a thin needle is used controlling a constant bloodflow can be a problem (especially if thinner than no. 19). For this reason a relatively high and constant pressure from outside should be used. As explained before a vacuum bottle should be used to keep this pressure. The size of the needle used, the site of te venipuncture, and all other specific characteristics of the phlebotomy should be noted in the medical chart of the patient. The patient can also fill in a phlebotomy chart as is available from for example the Iron Disorders Institute (the personal health profile) or the AustralianHS, the EnglishHS or the DutchHS.

When using (the smallest possible) needle there is always a little chance of clotting. There are some precautions that can allmost always prevent this. The first thing is that the patient should be well hydrated. This can be done by drinking enough fluids in the 24 hours before a phlebotomy. These fluids should ideally not consist of coffee (or tea in a lesser degree), as it dehydrates. Best absorbed are fluids with 50% water and 50% juice and a LITTLE! salt (1). These can be ingested during the hours before the phlebotomy. A good option is a sport tonic (without iron!). Some patients also take 0.5 liter of the drink to the hospital and drink it the 30 minutes before the phlebotomy and drink another 0.5 liter during and after the phlebotomy. Drinking too much can be very dangerous with heart problems, so if this is the case a doctor should be consulted!
A phlebotomy should be postponed when the patient has diarrea (or is feeling ill)! When this takes to long, actions should be made to ensure that the patient is well hydrated!
A second precaution is that the doctor or nurse sits next to the patient and increasing the blood flow a little bit when it is too low by pumping up the pressure cuff a little bit. Sometimes it also helps to move the needle a little bit (very carefully) when the flow is getting less.
A third precaution is to thin the blood a little bit. This can be done by the use of (a natural) vitamin E (400-800IU) supplement. Vitamin E is also a very good anti-oxidant in iron overload (vit C supplements should be avoided > 200 mg!). Another option is to take one (baby) aspirin before the phlebotomy. In rare cases your doctor will subscribe a blood thinner. Usually after the first few initial phlebotomies the blood will get a little thinner. If the needle clots, the next time a little bigger needle may be tried.
If the blood flows to fast and you are using a bloodbag with a big needle it allso helps to lift the bloodbag a little (away from the floor).

When there are problems with the blood pressure consult your doctor!!! If it is not serieus you can drink something with caffeine just before the phlebotomy (coke, coffee or tea). This may help to increase the blood pressure (Caffeine attenuates vasovagal reactions in female first-time blood donors (also consult your doctor!)).

If even a vacuum bottle does not work there are a few options left. One of them is the use of a special low vacuum bottle. This bottle ensures that the vacuum is not to high and that the vacuum stays at a low and constant pressure (for example 0.15-0.25 kg/cm2). This can also be done by using a large number of vacuum tubes that are used for lab drawings of blood.

Another option is the use of a (at least 2) syringes (the larger the better). In this case the (very small needle (no 21-23) is inserted with a tube connected to it (butterfly-needle). The doctor or nurse then has to pull the blood out very gently with a constant pressure, ensuring the vein does not collapse. When there is a third person, changing the tubes is more easily and the flow does not stop, so clotting is prevented. This third person can hand the phlebotomist the syringe and take and empty the filled one while the phlebotomist is filling the next one. Another picture
NEW: A video showing how to do a phlebotomy with thin needle (in German)
Another video with thin needle from Ireland.

When this also won't work the last option is a shunt, a permanent access to the bloodvessels. A tube is operated into a bloodvessel. Today this can also be done in the arm, in the past this was done in the chest. One of the risks of a shunt is a possible infection. This is the reason doctors are reluctant to use it. But for patients where nothing else works it is a real relief! Some links: 1 , 2 , 3

After the venipuncture the needle can best be held into place by a tape. If a small bandage is put below the needle this will help the needle to stay in the middle of the vein. It is also very important to change the venipuncture site every time to precent scarring. If there is scarring it might help to put a special cream on it for example contractubex.

Low hemoglobin
When there are problems with a low hemoglobin level there are a number of possibilities.
One of these possibilities could be a folic acid or vitamin B12 shortage. To prevent this problem some doctors advise to take a vit B complex and, (or including) about 200-800 mcg folic acid.
Other possibilities of a low hemoglobin can be a testosterone shortage, low erythropoiesis, to frequent phlebotomies, etc. And remember always exclude iron deficiency due to excessive phlebotomies (13)! If the cause can not be found, a hematologist should be consulted.

The hemoglobin will usually reach a "new normal" that will be somewhere from 1.0 to 2.0 g/dL lower than it was before the phleb was started.

In some cases when the hemoglobin can not get higher, desferal is used (usually secondary hemochromatosis). Desferal is an iron chelator that binds iron that is then excreted mainly in the urine. Desferal is injected subcutaneous and has some side effects. Desferal is also (sometimes) used in patients with heartproblems, mostly in combination with phlebotomy. I heard of a patient with heart problems who had a phlebotomy of appoximately 80cc, depending on HB level, per (weekly) visit. In this case 10cc vacuum tubes were used.

Drinking enough before the phlebotomy is usually enough to solve the problem of losing fluids during a phlebotomy.
But if there are problems for the patient to lose half a liter of fluid, often an IV of Saline is jused just before or during the phlebotomy.
In some cases erythropheresis can be used. Erythropheresis is a method where the blood is filtered and the red blood cells are removed. The rest of the blood is given back to the patient. Advantages of this method are the loss of less fluids and not loosing other components of the blood. It is also possible to remove more blood with one treatment (about 1 liter). Two disadvantages are the higher costs and the availability. (More info on this treatment: A recent article advocating for the use of (very expensive) Epo combined with Erythropheresisx(15,17) / Erythropherese (in German) or go to http://www.pheresis.org/ or read this article
Another option is a simple Volume replacement therapy. Here the fluids are given back using the other arm using a saline drip(?)
Some links on dehydration:
Dehydration

Fear of needles
Some patient have a great fear of needles. Hamilton (5) has written about this: (The needle Phobia Page). Emla creme, not looking at the procedure in any way and thin needles can be very helpfull in these situations.

After the phlebotomy
First lay down for about 10-20 minutes after the phlebotomy and drink (and eat) something.
It is advised to keep it easy the day(s) after a phlebotomy en to avoid intensive exercise. The body should be given the chance to make new blood and recover from the phlebotomy. Especially the first 24 hours after the phlebotomy it is advised to do it easy. It is advised to avoid carrying heavy objects with the arm where the stick was made at least an hour after the phlebotomy.

How much blood
Ideally the amount of blood taken should be adjusted to the individual patient. For example for small patients a phlebotomy of 500 ml may be to much. The average blood to be removed can be adjusted & the general rule of thumb is 5-7ml/kg. However, many teens can tolerate as much as an adult, it just depends on their size & physical condition.

The number of phlebotomies needed to de-iron can be roughly calculated by deviding the ferritin by 25-50. It will give an estimate of the number of phlebotomies needed. When the ferritin is measured more often during the de-ironing a better estimate can be made. But remember the ferritin will usually decrease slower the lower it gets (4). It is not unusual for the ferritin to decrease with 100 points every phlebotomy if the ferritin is well over 1000 ug/l.

The rate of phlebotomy (2)
Initial "de-ironing" therapy may require many months in some cases, a few in others. Regardless of the degree of iron overlaod, however, the "de-ironing" must be accomplished as soon as feaseble (preferably within 1 year). Typically, one unit of blood is removed weekly. Some individuals, especially males and those with larger body mass, tolerate the removal of two units per week. Many females, smaller persons, the elderly, and those with co-existing anemia or heart or pulmonary problems tolerate the removal of only 0.5 units/week. After a few units of initial phlebotomy, the bone marrow produces new red blood cells at a greater rate, permitting more blood to be removed more frequently. In unusual cases, stimulation of the developing red blood cells in the bone marrow by the hormone erythropietin (taken by regular injection) facilitates the recovery of the red blood cells after phlebotomy. However this is expensive therapy and is unecessary for most patients.

When to start and when to stop phlebotomy?
The first step is the de-ironing process. To de-iron a patient completely is a real art that ideally should be supervised by a hemochromatosis expert (or a doctor who knows what he is doing). If this is not possible it is usually safe to de-iron until the ferritin is below 50 ug/l. A "hemochromatosis expert" will usually lower the ferritin a bit more in the first fase of de-ironing, keeping a close look at the Hb, ferritin, T.S.%, MCV and how the patient feels. A drop in Hb below a certain level and staying in the low range for 2-3 weeks will indicate that the patient is de-ironed. If the procedure is not very carefully done the patients health can be negatively influenced! It is not uncommon that the Hb will stay low for several months if too much iron is removed. The reason for this is not clear. In this case a iron rich diet, iron supplements or even a bloodtransfusion may be needed. Needless to say that this should be avoided.
"Occasionally, in a few patiŽnts in whom HH is accurately diagnosed, iron does not reaccumulate for reasons that are unclear" (16).
Another new method for de-ironing is using the Hb and MCV as a guide. This is explained in the following article: MCV as a guide to phlebotomy therapy for hemochromatosis jun 2001)
After de-ironing the ferritin should be kept in about the 20-50 ug/l range (6-7). This is lower than for people who have no hemochromatosis and mainly has to do with the accompaning T.S.% that is too high for hemochromatosis patients when their ferritin is higher. The best value for ferritin is sometimes adjusted to an individual. Some patients report to be feeling best with a very low ferritin. also there are patients that feel when they need a phlebotomy. The timespan between phlebotomies is very individual for each patient. Some patients need 2 phlebotomies per year after de-ironing and others 10, the average being 6 per year. To find a good strategy the first (1/2) year after de-ironing the ferritin should be measured more often, say every 3 months until a good timespan between phlebotomies is found. Thereafter measuring every 6 months may be enough.

Below are the numbers of the latest "consensus" protocols on iron levels.
Remember the scientific basis for these numbers are non existent!!, but on the other hand the protocols were made by the top specialists on hemochromatosis.
Update: Theses guidelines are now being reassessed and the preliminary conclusion (in the Netherlands) is to keep the ferritin below the general normal values (up to 300 ug/l) after deironing!!!!

* NEW: MCV as a guide to phlebotomy therapy for hemochromatosis jun 2001) (Table 3 has an overview of guidelines for de-ironing!)

Current Approaches to the Management of Hemochromatosis (Pierre Brissot, 2006)
De-ironed: ferritin ≤ 50 ug/l
Maintenance: ferritin ≤ 50 ug/l and T.S:% < 75%.
http://www.asheducationbook.org/cgi/content/full/2006/1/36

* Bacon; Gastroenterology 2001 Mar;120(3):718-725
Hemochromatosis: Diagnosis and Management.
De-ironed: ferritin < 50 ug/l and T.S.% < 50%.

* Brissot, e.a. in Transfusion Science from dec 2000:
De-ironed: ferritin < 50 ug/l and T.S.% < 20%, unless Hb lower than 110 g/l
Maintenance: ferritin < 50 ug/l and T.S:% < 35%.
a/tr/3.pdf

* Consensus Sorrento in Hepatology 2000:
De-ironed: ferritin < 20-50 ug/l and T.S.% < 30%
a/consensus.pdf

* British Committee for Standards in Haematology (2000)
De-ironed: ferritin < 20 ug/l and T.S.% < 16%
Maintenance: ferritine < 50 ug/l AND T.S.% < 50%
http://www.bcshguidelines.com/pdf/chpt9B.pdf

* Barton, e.a. Annals of Internal Medicine dec. 1998:
De-ironed: ferritin 10-20 ug/l, unless Hb 3 weeks lower than 110 g/l
Maintenance: ferritine < 50 ug/l
http://www.acponline.org/journals/annals/01dec98/mgmthemo.htm

How quick will my ferritin and T.S.% drop? --> see image below
 

More info:

Letter about de-ironing!
Another Letter from Larry about the effects of a phlebotomy on lab values!
A Letter from a patient with questions about high T.S.% and low ferritin answered by another patient!

Allso consider that the effect of treatment with phlebotomies may alter the need for medications.(See allso letter from FHHF-list) (for example patients with diabetes often need less insulin after treatment)

Bloodbanks
Until now in most countries blood from patients with hemochromatosis is thrown away. The reason is that the blood is not donated completely altruistic. But rules are slowly changing and there is good hope that in the near future more and more countries will allow patients with hemochromatosis to donate their blood (8-12).
Here are some articles on the use of blood by bloodbanks.

For more information on phlebotomy here are some links:
Center for Phlebotomy education
More Phlebotomy Links
A letter form a patient with some extra tips!

If you have comments on the content or use of language please mail me at: pdesterke@hotmail.com or to fill in this form

I want to thank all the participants on the excess-iron, FHHF-list and Larry for their help in making this article.

Always consult your doctor before taking any medical action!!! I do not take any responsibility for any problems caused by this article.

(1) Factors affecting the rate of iron mobilization during venesection therapy for genetic hemochromatosis; Adams, P.; American journal of hematology; 1998; 58, pp. 16-9.
(2) Therapeutic Phlebotomy for hereditary hemochromatosis: a practical guide for patients and health care personnel; Barton, J.C.; not officially published article.
(3) Practice Parameters for Hereditary hemochromatosis; Witte, D.L., Crosby, W.H., e.a.; Clinica Chimica Acta 1996 (245) pp. 139-200.
(4) Erythropoietin and iron; Kaltwasser, J., Gottschalk, R.; Kidney International 1999; vol. 55, suppl. 69; pp. S-49-S-56.
(5) Needle Phobia: A neglected diagnosis; Hamilton, J.; The Journal of Family Practice 1995 August; vol. 41, no. 2: pp. 169-75.
(6) Management of hemochromatosis (FULL TEXT!!!); Barton, J., McDonnell, S., e.a.; Annals of Internal Medicine, 1 december 1998 (supplement); 129: pp. 932-39.
(7) Molecular medicine and hemochromatosis: At the crossroads; Bacon, B., Powell, L., e.a.; Gastroenterology 1999; 116: pp. 193-207.
(8) Blood from patients with hereditary hemochromatosis---a wasted resource? (PDF!); Jeffrey, G., Adams, P.; Transfusion 1999, vol 39, june, pp. 549-50.
(9) Hemochromatosis and blood donors: a perspective (PDF!); Sacher, R.A.; Transfusion 1999, vol 39, june, pp. 551-4.
(10) Hemochromatosis probands as blood donors (PDF!); Barton, J., Grindon, A., e.a.; Transfusion 1999, vol 39, june, pp. 578-85.
(11) A survey of phlebotomy among persons with hemochromatosis (PDF!); McDonnell, S., Grindon, A., e.a.; Transfusion 1999, vol 39, june, pp. 651-656.
(12) Use of blood therapeutically drawn from hemochromatosis patients (PDF!); Tan, L., Khan, M. and Hawk, J.; Transfusion, vol 39, sept 1999.
(13) Iron deficiency due to excessive therapeutic phlebotomy in hemochromatosis; Barton JC, Bottomley SS, Am J Hematol 2000 Nov;65(3):223-226.
(14) Management of hemochromatosis (full text); Barton JC, McDonnell SM, e.a., Annals of Internal Medicine 1998 1 Dec; 129:932-939.
(15) Erythrocytapheresis with recombinant human erythropoietin in hereditary hemochromatosis therapy: a new alternative. (full text); Kohan A, Niborski R, e.a., Vox Sang 2000;79(1):40-5.
(16) Hemochromatosis: Diagnosis and Management; Bacon BR, Gastroenterology 2001 Mar;120(3):718-725.
(17) In hereditary hemochromatosis, red cell apheresis removes excess iron twice as fast as manual whole blood phlebotomy. ; Muncunill J, Vaquer P, e.a., J Clin Apheresis 2002;17(2):88-92

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Latest News:
More and more patients tell me that after having enormous problems with phlebotomies, their doctor started giving a acid reflux inhibitor. For some patients this seems to be a good alternative. Consult your doctor!!! More information on: http://www.hemochromatosis.co.uk/phlebotomy/proton07.pdf
Venflon Pro Safety:

Phlebotomy at home: phlebotomy\phleb-home.pdf

There are 2 new blood bags developed especially for hemochromatosis patients! The producer is Macopharma (
Macopharma.com (REF VSL7000YQ) or here).

Blood bag 1: with a standard big needle (16G) attached --> when there are enough requests Macopharma can also make these bags with gauge 17 and/or gauge 18 needles

1: very sharp and VERY smooth 16 gauge needle (standard size, also used for blood donations)
feel yourself to beleive it!
2: "stopper". When the bloodbag is full enough, with 1 click the bag is closed
3: for lab tests blood can be drawn with this attachment, making an extra stick obsolete
4: protection for the needle before it is used
5: protection from the needle for after the donation. Just pull the hose back and this devise will enclose the needle and nobody can be sticked incidentially
6: The bloodbag, for max 600ml of blood.
7: Numbers on the bag: REF VSL7000PQ

Blood bag 2: with a luwerlock attached, making it possible to use any needle size!
(click on image for bigger picture)

1: luwerlock connection to connect any type of needle (see also article below)!
2: "stopper". When the bloodbag is full enough, with 1 click the bag is closed
3: for lab tests blood can be drawn with this attachment, making an extra stick obsolete
4: The bloodbag, for max 600ml of blood.
7: Numbers on the bag: REF VSL7000YQ

Also thin needle systems available from: http://www.kawasumiamerica.com

Canadian protocol with instructions to use 18 Gauge needle
In this article from dr. Barton and Adams the standard use of a 19-gauge butterfly needle is mentioned!

VeinViewer avoids multiple needle sticks: http://medgadget.com/archives/2007/03/first_hospital.html and here a Video
 


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