What are platelets?
Platelets are an essential component of the blood that helps form the structure of a clot and aims to prevent and stop bleeding. Low platelet counts, or patients with dysfunctional platelets, are at an increased risk of bleeding. Patients with critically low platelets may even spontaneously bleed without injury.
Platelets (PLTs) are actually fragments broken off of large cells found in the bone marrow called Megakaryocytes. Megakaryocytes are found almost always within the bone marrow, where cytoplasmic fragments break off and enter the peripheral blood as platelets. Megakaryocytes are almost never seen in the peripheral blood (outside of the bone marrow). Their presence in peripheral blood would indicate more serious issues, such as leukemias.
Platelet Lifespan
Platelet Lifespan
A platelets lifespan in-vivo (inside the body) is ten days, on average. Megakaryocytes are constantly release platelets during their life cycle, producing thousands of individual platelets during its course.
How do Platelets Work
Through signaling, platelets respond to the site of endothelial (lining of blood vessels) injury, such as a cut, scrape, puncture, etc., and start to form a "platelet plug" or the beginning stages of a clot. This clot literally helps to initially plug the damaged endothelium and stop bleeding from occurring.
In normal circumstances, platelets are inhibited from activating and forming a clot through chemical signaling from the endothelial lining. Upon endothelium damage, platelets migrate to the injury and activate along with the rest of the coagulation cascade which is a very complex system involving the numerous steps and proteins involved with forming a stable end-stage clot.
A fully formed clot will have been stabilized by a protein called fibrin. Fibrin forms a stable mesh along and on top of the platelet plug to further stabilize the clot. It is evident then why platelets are so important. Without platelets, the initial plug would not be formed, nor would fibrin be able to come in and stabilize the clot, resulting in excessive bleeding.
A fully formed clot will have been stabilized by a protein called fibrin. Fibrin forms a stable mesh along and on top of the platelet plug to further stabilize the clot. It is evident then why platelets are so important. Without platelets, the initial plug would not be formed, nor would fibrin be able to come in and stabilize the clot, resulting in excessive bleeding.
Platelet Donation
Platelets are manufactured from centrifuged whole blood or from an apheresis procedure. When you donate blood, at say a blood drive, the vast majority of the time you are there to donate whole blood unless otherwise specified (like double or power reds, platelets, or plasma). The whole blood is then processed into three major components. Red Blood Cells, platelets, and plasma.
Whole Blood Derived Platelets
Platelets derived from whole blood are generally pooled together to form a single pooled platelet bag that is sufficient to act as one "dose" of platelets for an adult.
There are usually 4-6 donors pooled into one bag. The reason for this is that platelets harvested from whole blood are usually much lower volume (and less absolute amount of platelets) than what can be achieved during an apheresis donation and would not constitute a full adult 'dose' at that level.
It is rare for transfusion centers to have or use single whole blood derived units of platelets. Some hospitals may have their own donor centers and pool their own platelets and some may use the individual single whole blood derived units for pediatric uses.
Many hospitals will simply sterile split an apheresis derived unit to fit their pediatric transfusion needs.
Seasoned doctors may use the term "6 pack of platelets". This means a full adult dose which is equivalent to one apheresis unit of platelets or a pooled platelet unit of 4-6 separate donors. Most transfusion centers utilize an overwhelmingly high percentage of apheresis derived platelets rather than pooled platelets.
Whole Blood Derived Platelets
Platelets derived from whole blood are generally pooled together to form a single pooled platelet bag that is sufficient to act as one "dose" of platelets for an adult. There are usually 4-6 donors pooled into one bag. The reason for this is that platelets harvested from whole blood are usually much lower volume (and less absolute amount of platelets) than what can be achieved during an apheresis donation and would not constitute a full adult 'dose' at that level.
It is rare for transfusion centers to have or use single whole blood derived units of platelets. Some hospitals may have their own donor centers and pool their own platelets and some may use the individual single whole blood derived units for pediatric uses.
Many hospitals will simply sterile split an apheresis derived unit to fit their pediatric transfusion needs.
Seasoned doctors may use the term "6 pack of platelets". This means a full adult dose which is equivalent to one apheresis unit of platelets or a pooled platelet unit of 4-6 separate donors. Most transfusion centers utilize an overwhelmingly high percentage of apheresis derived platelets rather than pooled platelets.
Apheresis Derived Platelets
Apheresis platelets are harvested a bit different than platelets from a whole blood donation. Donations typically take place at a blood center, rather than a mobile donation site. The reason for this is apheresis procedures require a machine to do most of the work. In this procedure, you're whole blood will be drawn from your arm by the machine and fed into a centrifuge within the machine. The apheresis machine will then centrifuge and separate the parts of your blood into individual components. The component that is intended on being collected will feed into collection bags. Then, the rest of the blood will be returned back into the patient.
If platelets are being collected, most of the plasma and red cells sent into the machine will be fed back after collection. Some plasma is kept in the collection bag, as platelets are typically suspended in roughly 200ml of plasma in a collection bag. New technologies are replacing this plasma with additive solution. Apheresis units are able to collect enough platelets to meet the equivalent of a pooled platelet, and is considered a full single dose.
If platelets are being collected, most of the plasma and red cells sent into the machine will be fed back after collection. Some plasma is kept in the collection bag, as platelets are typically suspended in roughly 200ml of plasma in a collection bag. New technologies are replacing this plasma with additive solution. Apheresis units are able to collect enough platelets to meet the equivalent of a pooled platelet, and is considered a full single dose.
After infectious disease testing is performed, the PLT units are sent to the transfusion center, usually a hospital blood bank. From time of collection, platelet units have a very short shelf life. Remember, platelets only survive roughly 10 days in the body already. New technologies, such as "large volume delayed sampling" has allowed for a few extra days of shelf life once they reach hospital blood banks, as well as better peace of mind that the platelet is free of bacterial contamination.
How long are platelets good for?
On average, the platelets received at a hospital Blood Bank expire within three days due to the time it takes to perform infectious disease testing, bacterial testing, and shipping the platelets. This is why a constant stream of platelet donations is CRUCIAL to maintaining the supply of platelets.
If donations dwindle, hospitals will very quickly find themselves in a platelet shortage due to the short outdate of the units. The major reason for platelets outdating so quickly is that they must be kept at room temperature. Unlike RBCs which can be refrigerated, or plasma which can be frozen, current technologies only allow for platelets to remain at room temperature (20-24 degrees Celsius).
Additionally, being kept at room temperature means that there is a much higher risk of bacterial growth within the platelet bag, if it were somehow contaminated during collection. The transfusion of bacterially contaminated platelets is very rare, but like other transfusion related reactions, it can happen.
If donations dwindle, hospitals will very quickly find themselves in a platelet shortage due to the short outdate of the units. The major reason for platelets outdating so quickly is that they must be kept at room temperature. Unlike RBCs which can be refrigerated, or plasma which can be frozen, current technologies only allow for platelets to remain at room temperature (20-24 degrees Celsius).
Additionally, being kept at room temperature means that there is a much higher risk of bacterial growth within the platelet bag, if it were somehow contaminated during collection. The transfusion of bacterially contaminated platelets is very rare, but like other transfusion related reactions, it can happen.
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| Platelets rocking on a rotator. Platelet units must be constantly and gently agitated back and forth to ensure their quality. Rocking back and forth allows for oxygen to enter the bag and CO2 to leave the bag. This gas exchange is essential to keeping the platelets alive and usable. (Yes, platelet bags are gas permeable!) |
Check out the following page for more information about the platelet additive solutions that are commonly used in apheresis platelets today. Platelet Additive Solutions allow for the removal of nearly 65% of the plasma in a platelet bag. The plasma is replaced with Platelet Additive Solutions which not only helps to maintain better health and shelf-life for the platelets but can reduce the amount of transfusion reactions seen with platelets as well.
Transfusing Platelets
If you're physician decides to transfuse, you can expect it to take roughly one hour to infuse. It takes much less time to transfuse than red cells because the viscosity of the product is much lower and thus can be transfused at a higher rate, safely. If you are prone to mild allergic transfusion reactions, the physician may opt to transfuse at a slower rate, or premedicate prior to transfusion to prevent itching,hives,fever that may occur from a low lever 'allergic' type reaction.
Blood cancer patients may require platelet transfusions several times a week to maintain a safe count until they are off chemo and their counts rise!
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| Typical adult guidelines for platelet transfusion |
What is Thrombocytopenia?
Thrombocytopenia is a term that means low level of platelets in the blood.
If your doctor suspects low platelets (thrombocytopenia) they will likely order a CBC or Complete Blood Count. One of the parameters of the CBC is the platelet count. Normal platelet (PLT) counts range anywhere from 150,000 to 450,000 platelets per microliter of blood. On a lab result report it would usually be reported as something like 150x103/uL rather than writing out the entire number. Numbers lower than 150, would put the patient in thrombocytopenic territory.
There are varying trigger points for transfusion depending on the clinical picture of the patient and is up to the ordering physician. Heme/Onc patients sometimes won't be transfused unless their PLT count gets down to 10 or 20,000. Patients at high risk for bleeding, cardiac patients, brain bleed patients, patients on aspirin, etc., may be transfused at higher counts. It isn't uncommon for physicians to want cardiac or neurosurgery patients to be at 100,000 or above. A patient with a PLT count below 10,000 runs the risk of spontaneous bruising or bleeding. One single dose of platelets (1 apheresis unit or 1 pooled unit with 4-6 single units) will typically raise a patients platelet count by 20,000-30,000. Patients with conditions in which platelet are being destroyed or have decreased survival, may see less of an improvement per platelet dose.
There are varying trigger points for transfusion depending on the clinical picture of the patient and is up to the ordering physician. Heme/Onc patients sometimes won't be transfused unless their PLT count gets down to 10 or 20,000. Patients at high risk for bleeding, cardiac patients, brain bleed patients, patients on aspirin, etc., may be transfused at higher counts. It isn't uncommon for physicians to want cardiac or neurosurgery patients to be at 100,000 or above. A patient with a PLT count below 10,000 runs the risk of spontaneous bruising or bleeding. One single dose of platelets (1 apheresis unit or 1 pooled unit with 4-6 single units) will typically raise a patients platelet count by 20,000-30,000. Patients with conditions in which platelet are being destroyed or have decreased survival, may see less of an improvement per platelet dose.
Signs of thrombocytopenia / low platelets
- Bruising easily or without known blunt mechanical trauma
- Petechiae -- bleeding just under the skin that results in reddish/brown/purple spots that may resemble a rash
- Excessively long bleeding times from cuts and other traumas
- Bleeding gums or nose bleeds (epistaxis)
- Rectal/GI bleeds
- Blood in urine or vomit
Causes of thrombocytopenia
There are numerous reasons for thrombocytopenia to occur within a patient.
Thrombocytopenia can manifest as a decrease in PLT production, increase in platelet destruction, consumption of platelets through certain processes, a combination of the three, or other rare issues.
Chemotherapies
Chemotherapies, especially those used to treat hematologic malignancies such as leukemias, lymphomas, etc., will tend to cause thrombocytopenia as part of their action. Since chemo drugs are working on the bone marrow to suppress proliferation of cancerous cells, other cells in the bone marrow can be affected by this chemical bone marrow suppression as well.
Low platelet levels are a very common and sometimes expected side affect of chemotherapeutic agents acting on the bone marrow. A significant percentage of platelet transfusions are to those with cancer and/or on chemotherapies.
Liver failure / cirrhosis patients
alcoholic or non alcoholic liver damages-- The liver is responsible for making proteins, thrombopoietin included. Thrombopoietin is a hormone that tells the bone marrow to make additional megakaryocytes. This is addition of megakaryocytes will then create more platelets once platelets are sent into the peripheral blood. Patients with a low functioning liver may not create thrombopoietin as well as someone with a healthy liver.
Leptospirosis infection
Viral infections
Certain viral infections can have an influence on platelet levels. Viruses like HIV, CMV, and Hepatitis C can infect megakaryocyte cells, which in turn could cause a decrease in platelets due to megakaryocytes being the origin of platelets. Some viruses can alter thrombopoietin production, affecting how megakaryocytes are made in the bone marrow. Additionally, platelets may be destroyed or used up/removed from circulation due to direct contact with certain viruses.Hematological Malignancies
Leukemias,MDS, Multiple Myeloma, etc.
Aplastic anemia
Damage to the bone marrow which can be autoimmune related, environmental such as chemical or radiation exposure, or may have been an issue present from birth. Aplastic anemia causes the bone marrow to produce less cells, megakaryocytes included, thus patients with AA will typically see a decrease in all cell lines, platelets included.
Sepsis
A patient with a bacterial infection in their blood will often find themselves with thrombocytopenia. There are many mechanics in play as to why this may occur. One of the major reasonings is that a body in a state of sepsis and septic shock is in a heavily pro-inflammatory state. This causes the platelets to activate and bind to the endothelium. The platelets are then taken out of usable circulation and will eventually be targeted for removal.
Direct interaction with bacteria has also been shown to cause platelet activation and the platelets can actually trap bacteria in a web of activated platelets. Sepsis can also cause other issues in which platelets are destroyed and broken apart. Patients with severe thrombocytopenia in the setting of sepsis have a worse prognosis than those who do not, generally.
TTP
Thrombotic Thrombocytopenic Purpura -- a severe disease in which platelets are used up and form clots throughout the body as well as "purpura", purple rash-like spots on the skin that are the result of bleeding from small vessels. The clots can then travel through the body causing organ damage or even death in blood flow is severely impacted. TTP is generally acquired and is usually autoimmune based, though it can be triggered by medications, pregnancy, infections, etc. Some cases of TTP have unknown etiologies or causes/triggers.
In autoimmune TTP, an antibody forms against a protein complex that helps to break down large platelet complexes from forming in the blood. The antibody essentially disables this protein complex, allowing platelets to be used up and form more and larger clots throughout the body. However, if you do have TTP, it usually NOT RECOMMENDED to transfuse platelets in TTP patients. This is because any additional platelets added to circulation would likely contribute to additional clots throughout the body.
The underlying cause must be determined first. Many patients with autoimmune TTP will undergo plasma exchange therapy which is a form of apheresis, which replaces the patients plasma will donor plasma. This allows causative antibody to be removed from circulation and allow platelets to start to function normally.
In autoimmune TTP, an antibody forms against a protein complex that helps to break down large platelet complexes from forming in the blood. The antibody essentially disables this protein complex, allowing platelets to be used up and form more and larger clots throughout the body. However, if you do have TTP, it usually NOT RECOMMENDED to transfuse platelets in TTP patients. This is because any additional platelets added to circulation would likely contribute to additional clots throughout the body.
The underlying cause must be determined first. Many patients with autoimmune TTP will undergo plasma exchange therapy which is a form of apheresis, which replaces the patients plasma will donor plasma. This allows causative antibody to be removed from circulation and allow platelets to start to function normally.
ITP
Immune (or Idiopathic) Thrombocytopenic Purpura. Somewhat similar to TTP, but in ITP there is generally an antibody towards the platelet, or a part of the platelet itself. An antibody attaching to the to platelet signals it for destruction and the body clears the platelets out of circulation unable to be used. Platelet transfusion is not always recommended in ITP, because they will simply be destroyed by the antibodies once transfused. In emergency situations when spontaneous bleeding is likely, platelets may be transfused. It makes more sense to try to suppress the antibody's activity to restore platelet counts.
Lupus
Lupus is a systemic autoimmune disorder caused by autoantibodies towards numerous different possible sites throughout the body. In some Lupus patients, they may develop an autoantibody towards platelets, causing a lowered count. Additionally, some medications given to help with Lupus symptoms, may in turn suppress platelet production as well.
Bernard–Soulier syndrome
A genetic mutation characterized by unusually large platelets within the blood. This mutation causes platelets to lose their ability to adhere to the site of injury. Thrombocytopenia is common with this condition. Other conditions similar to BSS causing large platelets and lowered counts include May-Hegglin anomaly and Medich syndrome.Other Conditions
Patients may also be transfused if they have a normal PLT count but have conditions in which they have dysfunctional platelets, leading them to have a bleeding tendency. Some conditions in this category include Glanzmann thrombasthenia and Chediak-Higashi syndrome. Patient regularly taking aspirin will also sometimes have impaired clotting due to aspirins anti-platelet effect. Patient's with dysfunctional platelet disorders that maintain a normal PLT count usually will not require regular transfusions, but may in the setting of a bleed, trauma, or other emergencies.
This is by no means an exhaustive list. There are many reasons for thrombocytopenia and thus many indications for transfusion!