Blood in Times of Scarcity

grey-platelets, top is a lymphocyte (white cell)

We have all known times when we, or some loved one, needed blood and we could not get it. The reasons may be numerous. Perhaps the blood needed is of a rare blood group, or perhaps there are no real blood 'banks' nearby! Often times in developing nations the supply mechanisms are just not in place or not functioning. Then there's the ubiquitous shortage of blood donors!

Blood bankers are the people on the spot when blood has been prescribed for a patient but apparently the blood is not available. What do you do?

Fortunately, nature itself has given us a few 'tricks' that can prove useful in times of crisis! The first and foremost trick is to use the component parts of blood to treat specific needs. As mentioned in my previous post, blood component use can expand the utility of a limited resource (blood and blood donors) to provide help to 3 or 4 times as many patients. Especially in times of scarcity that's a huge, huge advantage!

harvesting PRP

Nature's boon to us is that "blood" (meaning 'whole' blood), can easily be divided up into its parts, or components. A simple centrifuge spin will show two clear divisions, with straw yellow watery plasma on top (less dense) and the dark red cells below. Using multiple bags, the plasma can be removed into a satellite bag. If we have spun the blood gently, then within the plasma will be found the platelets. Platelets can then be concentrated with a slightly harder spin yielding platelet poor plasma (PPP) on top and the platelet concentrate at the bottom. So now we have three components of blood. Very rarely do people need more than one of these at a time. Voila, 1 blood donor can help to treat 3 patients!

The plasma (PPP) with its clotting factors can be fast frozen (now called  "Fresh Frozen Plasma" or FFP) and then stored at -40C for up to one year. All the clotting factors will work!

Sometimes, we will choose to remove some of the clotting factors (V and VIII with fibrinogen) from the plasma and use these separately for treating people like hemophilia sufferers. And there we have it, easily up to 4 different patients can be benefited from one blood donation!

Nature also lends us a helping hand for patients with rarer blood groups (e.g. often rh negative blood and AB group blood can be hard to find as occurring in only a small percentage of donors). The basic 4 blood groups (A, B, AB & O) were discovered more than a century ago. Rh factors were detected in the 1940s-1950s and were first found from studying problematic pregnancies. Thus, the rh 'problem' for rh negative women has become a matter of common knowledge. Now, a whole science of blood group serology has grown out of these humble beginnings!

When we make blood components we first separate the plasma from the red cells. Here lies nature's second BIG gift to us. Factors like rh and A and B that are the basis of the blood groups, are found ONLY on the red blood cells. These factors do not exist in the plasma. What is found in the plasma, are plasma proteins (immunoglobulins) that can potentially attack their opposite red cell factors. We are born with some of these proteins (anti A and anti B, but not rh). People with a blood group A, for example, will have the A factor on their red cells BUT their plasma will have anti B. It is a bit difficult to understand at first but the tables below summarize the antigen factors (red cell) and antibodies (plasma) for the ABO groups.

So, how does this help?
Well, supposing your patient needs AB group blood (red cells) and you cannot find a blood donor of AB group, it's actually generally just as safe safe to transfuse (crossmatch compatible) washed A group, B group or even O group RED CELLS alone to this patient!!!

Simply put, whatever is on the patient's red cells - the corresponding antibodies in the plasma must be avoided. An A group patient can receive O or A group red cells safely but NOT B or AB.

Again the table below will clarify the mixes and matches for red cells (packed red cells as they are often called) and for plasma.  The reverse case is therefore true for patients needing plasma! Consider the last column of the same table to decide on plasma compatibility: As you can see, an A group patient can receive A or AB plasma, NOT B or O.

Patient’s Blood Group	Compatible Components
	Packed Red Cells, Platelet Concentrate	Plasma
A	A, O	A, AB
B	B, O	B, AB
AB	A, B, AB, O	Only AB
O	Only O	A, B, AB, O

Cell counters VERY important for PLT

For people needing whole blood, with a little immagination you can see that the combination of O group red cells and AB plasma are always acceptable (when the crossmatch is okay)! Other combinations will work too, e.g. an A group patient needing whole blood can have O or A red cells along with A or AB plasma.

A huge advantage of component separation is that when we fresh freeze plasma we can store large quantities of plasma to be used whenever needed! 'Packed' red cells can be safely stored for 35 to 42 days at +4C, and in fact with some extra technology (and cost) red cells can even be viably held at -80C (or in liquid nitrogen) for very long periods (up to 5 years).

The science of blood group serology has taught us that there are well over 300 different antigen factors found on red blood cells and (in other patients) corresponding antibodies found in plasma. Most of these are rare, but any active transfusion service will run into 1 or 2 a week. It is for these rarer cases that larger transfusion services will freeze and store away the rare donor red cells that come their way so that when a patient presents with a troublesome rare antibody, there is a better likelihood that compatible frozen red cells will save a life.  And that is another reason why crossmatch techniques have to be the best possible! You will not pick up any of these dangerous transfusions (or 'rare' donors) unless the crossmatching is always spot on! But we are now speaking of rarer difficulties (often 1:10,000 or rarer).

PLT concentrates in a horizontal shaker, temperature +22C

But, some more common problems that we face are also amenable to some 'trick' solutions! Take the case of a patient with low platelet counts who has started to bleed. The commonest causes might be a virus such as dengue, a drug (medication) reaction, or perhaps treatment for cancer. Whatever the case, platelets once needed are needed in some quantities, say 2-4 random donor platelet concentrates every 12 hours (the actual need will be decided by the physician and the clinical condition).

Finding donors can get especially difficult when the patient has a rarer blood group such as AB or rh negative. One unit of  Platelet Concentrate has about 50 to 70 mL of plasma but it also will contain a small amount of red cells, say 1 or 2 mL, and that's the reason for generally transfusing platelets according to 'red cell rules'. That small amount of red cells is enough to stimulate the production of antibodies like anti rh. Still, in a pinch, for MALE patients with life threatening bleeding, the physician may go ahead and transfuse blood group incompatible (but major crossmatch compatible) platelet concentrates.

Centrifuging blood in blood bags.

Where rh negative WOMEN patients are concerned, it gets complicated. Sometines women who have not had children have been found with rh antibody due to careless transfusions, pregnancies in the past, or other exposures to rh antigens. Still, a potential way out here is to use RhoGAM (which is nothing other than rh antibody) to bind the few problem-causing rh positive red cells found in platelet concentrates. In other words, we can do what we would do when an rh negative women is pregnant to prevent her own immune system from producing the rh antibody against the red cells from her fetus that may be crossing into her circulation!

Of course, the above are all purely medical decisions and only doctors can decide in each case what can and should be done. The blood banker's job is to make the solutions available to the physicians.

And as you can see, with sensible blood component technology backed with simple blood serology techniques, MUCH indeed can be done.  MOST IMPORTANTLY our blood needs can mainly be met using simple, ready to hand, inexpensive "third world ready" technologies.

The PRP on the left top has too many red cells (pink). QC is a must!

Blood bankers should always fine tune their crossmatch techniques to ensure that dangerous transfusions are avoided.

Building Confidence

Quality control is most critical in building physicians' confidence in your blood component program. The components, especially the very sensitive platelets, should have high enough counts in our PLT concentrates. We should aim to harvest 90% of the platelets from the donor blood into each concentrate and with the least contamination of red cells possible. The platelets should of course be viable, so gently spin out and gently agitate during storage while maintaining strict temperature control at +22C.

As the physicians' confidence grow, and as they see their difficult transfusion problems being solved with component technology and common sense, you will find that they will soon switch over to prescribing only blood components!

Manual Apheresis versus Automated Apheresis

Finally, a word on manual apheresis (much much less expensive) versus automated apheresis. I know that a significant amount of controversy was generated by my earlier post recommending manual apheresis in 3rd world countries, with some doubts even being expressed about the safety of the procedure. In India it is standard procedure at leading medical/hematology centers such as CMC Vellore. I refer the doubters to 2 out of many studies that have been published in leading transfusion medicine journals that prove that manual apheresis platelets are as safe (or safer) than those made with very fancy (& expensive!) automated equipment: See Vox Sang. 1989;57(1):25-8.In vitro and in vivo comparison of platelet concentrates collected by automated versus manual apheresis. Ross DG, Holme S, Heaton WA.Source American Red Cross Blood Services, Tidewater Region, Norfolk, Va.  &  Viability of platelets collected by apheresis versus the platelet-rich plasma technique: a direct comparison.by R A De Vries, M De Bruin, J J Marx, H C Hart, A Van De Wiel Transfusion Science (1993) Volume: 14, Issue: 4, Pages: 391-398  PubMed: 10146646 Available from www.ncbi.nlm.nih.gov

I think it is ridiculous to expect patients to cough up (India/Pakistan) Rs. 15,000 or more for each single-use disposable kit (for automated apheresis). At least encourage the use of random donor platelets if the manual apheresis technique is deemed "risky."  
My estimate of the cost of 2 units of platelets taken by manual apheresis at one donation by one donor is a minimum of Rs. 500 to a maximum of Rs. 1,000, depending mainly on whether the Blood Center is adding in overheads etc. to the 'bare' costs. That's for 2 units of platelet concentrate!

BLOOD COMPONENT SUMMARY:
RED CELLS (packed red cells PRBC) 180 mL to 200 mL, ~80% cells, <10% plasma, ~15% anticoagulant-additive (storage at +4C up to 42 days).
FRESH FROZEN PLASMA (FFP) 200 to 220 mL plasma, 30 mL anticoagulant, < <0 -40c="" .5="" 1="" at="" cells="" p="" red="" storage="" to="" up="" year="">PLATELET CONCENTRATE (PLT) 50 to 70 mL plasma, each 1 mL typically contains  120,000,000 platelets, and a minimum of 5.5 x 10 (10) in 50 to 70 mL of plasma with less than 1 mL red cells. (storage at +22C with gentle agitation for 5 days). For an average adult patient of 70 kg weight, the 'normal' blood volume would be 5 liters, and one unit of platelet concentrate should raise the count by ~ 10,000/microliter.


BLOOD COMPONENTS ARE A MATTER OF LIFE! 

NOTES:
1. Please do keep in mind that platelets once opened for transfusion cannot be stored. They should never be refrigerated even for short periods of time. Only +22C storage! If you use a part of a PLT concentrate, say for an infant, please discard the remainder and do not attempt to keep this for later use as the risk of bacterial contamination is extremely high! Once transfused, the platelets will usually take some time, a few hours, to equilibrate and start working to stop bleeding - an important point when preparing a patient for surgery!
2. A good antibody screen can be sometimes substituted for, or added to the crossmatch to make it even safer.
3. The standard amount of blood drawn for component preparation is usually 450 mL
4. I have not mentioned autologous blood transfusion here as this post is not really about blood for elective procedures, BUT the overall demand on donors for a transfusion center/blood bank will somewhat reduce if surgeons are also utilizing prior autologous transfusions.
5. A good read on the dengue epidemic in the Lahore area,  Dingi (Dengue) Fever in Lahore by Prof Farakh A. Khan It is very down to earth, see: http://networkedblogs.com/nE6gF
6. The Merck Manual has a useful summary of blood component use in clinical practice -  http://www.merckmanuals.com/professional/hematology_and_oncology/transfusion_medicine/blood_products.html
7. Be proactive and prepared! Find the phone numbers of the blood banks in your area (the ones that have stock of blood components) and store them up in your mobile for instant use. In an emergency, getting blood components fast can save lives.
8. Blood donors can encourage their blood banks to process blood into components. Ask your blood banker the next time you donate blood, whether they are routinely making blood components so that each time you donate, you will help to save 3 or even 4 lives.

Incidentally, I am a blood bank technical consultant and not a medical doctor. I will be happy to discuss the technical aspects of blood/blood components with anyone, but for medical advice please talk to your physician! You can mail me with any questions at samlcarr@gmail.com or call me, +91-8144068393

Platelets in Developing Countries

Blood saves lives BUT wrong responses to blood needs are horribly wasteful, even criminally wasteful, and especially so in developing nations where the tech may not even work.

My present concern was ignited by a recent bit of news from Pakistan that the government was responding to the #DENGUE crisis (an epidemic affecting many thousands) in populous Lahore.  Like many viruses that cause bleeding, dengue can be most deadly in its hemorrhagic form, and the main cause of bleeding comes down to dropping platelet counts - and platelets are blood components that are the body's first line of defense against bleeds. The government proposes tossing out 40,000,000 (40 million!) rupees to purchase top-of-the-line blood cell separators as the cries for platelets from dengue sufferers have grown to a crescendo.

Sounds good, doesn't it! People desperately need platelets, so the government immediately jumps into action to meet that need... Well, unfortunately that's all it does is to 'sound' good!

And thats how complicated the 10k apheresis kit is!

In the first place, the machines themselves are very expensive. Perhaps the government will be able to buy a couple dozen machines for that money. But what's really very sad, such machines do not work at all on their own. You need to use 1 disposable kit for each donation. EACH platelet concentrate from one donor (single donor platelets or SDP) requires a (single use) kit and EACH kit costs anywhere from 10,000 to 20,000 Pak Rupees.

And that my friends, means that only the richest patients will be able to afford this treatment. In short, eventually, the government would have spent your public's tax money on a bunch of utterly useless machinery.

Being a blood banker, I also know that the time to implementation for blood cell separator tech is approximately a minimum of 3 months, so even supposing the government does something really brave, like subsidizing the cost of the kits, the whole setup will only go into action after the dengue is  long gone...

After 1 spin PRP above RBC

Of course, the spin-doctors might leave the public admiring the government's caring responsiveness, but ultimately the same thousands WILL DIE for lack of platelets.

Oh, I am not even going to harp much on the fact that properly using these machines requires a LOT of training, with a heck of a lot of infrastructure. These machines will not function safely on generators, and so will need large UPS backup. Then, doctors need to be trained in how to prescribe these SDP, which is a whole lot different from using the commonly available (random donor) platelet concentrate! And then there's the little practicalities like maintaining and servicing some very sophisticated machinery. In my experience, when asked to do after sales service, the sellers/manufacturers/agents found in 3rd world nations are so often adept at playing hard to get!

In other words, stuff like this is simply not appropriate for 3rd world economies. It is a simple thing to have blood cell separators (US 'apheresis' machines) as standard equipment for any US/European/Japanese blood transfusion service, but in those economies our 10,000 rupees is just $110, what an American might spend dining out just once, while to a Pakistani or an Indian that's one month's wages, and for just 1 day's treatment with SDP.

harvesting the platelet rich plasma

I also hardly need to remind folks that in all the 'fancy' countries there's insurance cover, or the governments there treat even their citizens' tertiary health problems with nationalized free treatment - and which developing nations can afford to do either of those things???

Now, I can't altogether blame the government for this fiasco. But then I can! It is typically the health ministry's responsibility to get proper advice from genuine experts and find workable and effective solutions to emergencies like the present dengue/platelet crisis. Solutions do so often exist; workable solutions, and much less expensive ones!

What would have been a more effective solution in Lahore? Encourage the existing network of blood banks in Pakistan to coordinate the supply of 'ordinary' platelet concentrates. Here, the technology is simple. Many blood banks will already have the centrifuges, and "triple bag" kits are readily available at very reasonable prices. It's also easy to train the technicians to make 'ordinary' platelet concentrate. Best of all, the end user cost is only a mere Rs 300/- to 500/- per platelet concentrate, of which a doctor may need to use just 1 or 2 every 12 hours to maintain the platelet count in a safe range, i.e. a cost to the patient of Rs 1,000 to 2,000 per day, (that's still expensive) to stay safely alive until the self-limiting dengue virus hopefully makes a quiet exit.

We, in third world countries, are often witness to much of such government over-enthusiasm. And it often enough isn't the result of stupidity, is it?  So very often we find that some extra-smart 'expert' government adviser somewhere has quietly pocketed a hefty commission (kickback/baksheesh) for suggesting a brilliant but useless scheme!

But, at what cost to the nation, and particularly at the cost of how many lives?


And so, to end the sermon, do try to work with locally effective technology rather than doing stuff that will only be a donation to some foreign manufacturer of completely useless-to-you white elephants. Think about it.

In the meantime, I would also urge all blood bankers to really, really, switch to blood components. Of course, you will not be able to do that unless physicians and surgeons start insisting on using only blood components! Coordinate - Educate!

So called 'whole' blood is a killer when used to treat drops in platelet counts. Whole blood can dangerously load the circulation as you are putting in an extra 350 mL of blood (and completely unneeded red cells lead to hemoconcentration) to get an effect equal to the platelets found in just 50 to 70 mL of platelet concentrate.
I've personally witnessed volume overloads  and very high hematocrits resulting from such whole blood mistransfusions that literally killed patients!

I would simultaneously urge all blood donors to request their blood banks to collect blood in multiple bags so that blood component processing becomes simple and safe. If you see just a single bag without 'satellite bags' attached, go ahead and donate, but then go and meet the blood bank director and tell that person that you will feel much more motivated to be a regular donor if they quickly move to blood components - BECAUSE, your one blood donation (made into components) can serve 3 to 4 patients, and is in any case always safer and more effective than 'whole' blood!

Wouldn't you want to save many precious lives each time you donate your precious blood? I certainly do...

P.S. Blood Components : From 1 unit (450 mL) of 'whole' blood = Red Cells (180 mL) + Fresh Frozen Plasma (200 mL) + Platelet Concentrate (max 70 mL). Sometimes the plasma can further be split to provide clotting factor VIII concentrate and plain plasma (without this clotting factor). So, 1 blood donation made into it's components can help save at least 3 lives or even more!


PLATELET STORAGE & TRANSPORT
The platelets in 'whole' blood get killed when the blood temperature drops below +20 C. Whole blood is typically stored at +4 C. So unless the 'whole' blood is fresh and uncooled, it's totally useless for platelets anyway! However, once platelet concentrate is made from fresh warm blood, it is good for at least 5 days at +22 C, so can also be transported to from central processing units to wherever the demand exists. Platelets need to be maintained at this temperature of +22 C and be gently agitated.

PLATELET DONORS:
Should have a healthy platelet count. Should not have any bleeding disorder. Should not have smoked, taken aspirin or Aggrenox for at least 48 hours, or any antiplatelet meds like Plavix (clopidogrel) for 10 days before donation and of course should meet the other general requirements for blood donation (minimum height-weight etc.).

* Pics on the left show parts of the 'low' tech processing of blood manually to get the blood components safely out and this is all done within a closed sterile blood bag system. The triple bag is most commonly used to provide the 3 main blood components.

Another timelapse - make peace and be at peace!

The Unseen Sea from Simon Christen on Vimeo.


Lovely and peaceful.