Platelet-Rich Plasma is normally utilized in an autologous application, with the huge benefits of accessibility, affordability and the fact that it practically eliminates the risk of allergic reactions in the patient, since the product is a derived of its own blood. However, just like a routine blood transfusion, PRP can also be transfused from a donor to a recipient to treat any disease or condition that causes active bleeding and coagulation disorders, such as liver disease, neoplasia, hemorrhagic trauma, tick-borne diseases, inherited diseases, among others (except immune-mediated thrombocytopenia, where PRP transfusion is not indicated unless there is a life-threatening bleeding episode). It is important to mention that most post-transfusion allergic reactions are mostly caused by antigens located on the red cell membrane or leukocytes, so even though the risk to develop this type of complication is not 0%, it still is very unlikely to happen, making it a pretty safe procedure.
Most of the diseases that affect coagulation are caused by thrombocytopenia—low platelet levels in blood, while other conditions don’t necessarily imply a lack of platelets, but a malfunction, or deficiency of other clotting factors that keep the existing platelets from activating themselves. PRP transfusion can be used in three different ways, depending on the condition being treated:
- As a critical care measure, when the patient DOES NOT need red cell transfusion just yet—or has already received one—, but has an active haemorrhagic process caused by trauma or underlying disease.
- As a precautionary measure if blood count shows a dangerous level of thrombocytopenia (acute or chronic cases).
- As a regular treatment in cases of chronic or inherited coagulopathies.
The procedure is rather simple, since it requires the same material that a blood transfusion does. The only difference relies on the fact that the volume to transfuse is a lot less. Please review our Get Started Section to learn step by step how to obtain platelet-rich plasma from a patient (note that in some cases, one could skip the final step of the Separation step and apply the whole plasma fraction, especially when albumin or clotting factor VIII is are needed). The PRP transfusion should be performed as follows:
- Test the donor’s blood for any sub-clinic disease.
- Order blood count of the recipient’s blood to calculate the approximate amount of platelets needed. The following formula might be useful in this step, considering that a drop of PRP should contain from 10 to 15 platelets:
PI x BV x 1.5
Platelet dose (x 1011) = 100
PI = Platelet Increase (expected)
BV = Blood Volume of the Patient (calculate weight in kg x 0.8)
1.5 = Splenic Uptake
- Obtain platelet-rich plasma from healthy donor.
- Have a venous catheter in the recipient.
- Apply fresh PRP intravenously, in bolus or infusion (using saline solution), depending on the volume of PRP.
- Keep the patient hospitalized for observation, check vitals every 30 minutes to make sure no allergic reactions are happening.
- Order blood count of the patient’s blood to determine if platelet increase has been achieved.
- Always keep record of results.
Common diseases where PRP Transfusion might be needed
Several liver diseases, such as cirrhosis, lymphoma, cholangiocarcinoma, hepatoma, hepatocellular carcinoma and histiocytosis can cause low platelet counts, which derives in a deficient clotting capability. In such cases, PRP transfusion can be performed every now and then (intervals depending on treatment individualization and medical judgment) to prevent hemorrhagic episodes.
It is highly important to check platelets levels if a liver biopsy is scheduled, since severe thrombocytopenia might require PRP Transfusion before or during the procedure.
Neoplasia and Chemotherapy
A wide variety of tumors, as well as the chemotherapy drugs used to treat them, can be cause of thrombocytopenia. Statistically, carcinomas, hemic neoplasias, and lymphoid neoplasias generate the highest risk of developing thrombocytopenia; spleen and bone marrow tumors have a huge impact on platelets. Very special attention should be offered in terms of platelet counts when treating a patient with hemangiosarcoma, and also with patients under treatment for melanoma, since the chemotherapy used in these cases tends to cause strong decreases in platelet counts, as well as affect the functionality of the surviving platelets.
Following, a list of the types of tumors with risk of developing thrombocytopenia, in order, from highest to lowest risk:
- Melanoma (mostly induced by chemotherapy, not so much by the tumor itself)
- Nasal carcinoma
- Pulmonar carcinoma
- Squamus cell carcinoma
- Non-lymphoid hematopoietic tumors
- Mast cell tumor
- Endocrine neoplasia
- Brain neoplasia
- Benign neoplasia
Several authors agree on the fact that in many cases, thrombocytopenia in patients with other types of tumors may be caused by consumptive passive coagulation, where other blood count numbers may or may not be altered. It is highly important to monitor platelet blood counts on every oncologic patient, in order for the veterinarian to detect thrombocytopenic disorders on time. This will allow the medical personnel to make a timely decision to perform PRP transfusion before a life-threatening hemorrhagic episode is developed.
There is a great discrepancy between authors whether PRP transfusion is indicated during an acute hemorrhagic trauma. Some believe that whole blood transfusion is a better choice, while others recommend checking red cell and platelet levels, and transfusing PRP only when the red cells are not significantly low yet.
It must be remembered that PRP transfusion supplies the body with a significant amount of platelets in low volume applications. This concept is key to assess which treatment is indicated for each patient, since trauma is incredibly variable, biologically speaking. Evaluation of the presence of hypovolemia and low hematocrit will be the determinant factors for choosing a whole blood transfusion over the PRP transfusion, until the patient is stable. Once the blood volume expansion is achieved, the cause of hemorrhage should be looked for, and if not corrected yet, then PRP transfusion should be administered so that clotting assistance can be provided without overloading the blood vessels.
Babesiosis, ehrlichiosis, anaplasmosis and borreliosis (Lyme desease) are four of the most important tick-borne diseases in canine and feline patients, and can cause severe thrombocytopenia by different mechanisms. The key to decide whether PRP transfusion would be helpful or not is to know that the answer to this question is variable from patient to patient, and that it depends on understanding the current mechanism causing the low platelet count.
Hereunder, a very simple scheme is provided to understand the different mechanisms by which these microbiological agents can cause thrombocytopenia, and the indication or contraindication of PRP transfusion of each one:
- Splenomegaly: most of the tick-borne diseases cause an inflammation or enlargement of the spleen, which is normally a reservoir of platelets and erythrocytes. Splenomegaly leads to a higher rate of platelets and erythrocytes held captive (platelet sequestration), since the organ mass is bigger but still functional, so even if the cells are still functional, they are not available in the blood stream. In time, these cells will be destroyed by the spleen macrophages, with the ending result being the same: no platelet function. This thrombocytopenic mechanism merits PRP transfusion when the platelet count is dangerously low. Please note that this kind of low blood levels can happen without showing hemorrhagic clinical signs, so the choice has to be made based exclusively on laboratory blood count results.
- Consumptive thrombocytopenia: rickettsial infections tend to attack endothelial cells, causing vascular damage and exposing the subendothelial tissue, which activates the coagulation cascade. When this happens mildly—having a stable patient, but alarming low platelet counts—, a PRP transfusion might be indicated to restock the blood with functioning platelets, and at the same time helping the vascular tissue regenerate. However, when this thrombocytopenic mechanism becomes chronic or aggressively acute, the coagulation cascade is activated very sharply, consuming large amounts of platelets and clotting factors, and consequently generating DIC (disseminated intravascular coagulation), which consists in both hemorrhage and clotting within the microcirculation, leading to thrombi. In this case, the patient will not be stable, and PRP transfusion is contraindicated, since it would worsen the DIC.
- Low platelet production: ehrlichiosis frequently generates bone marrow damage, leading to anemia, platelet production suppression and abnormal levels of neutrophils (high or low, depending on chronicity); these alterations can cause fatal secondary infections, as well as life-threatening hemorrhage of the respiratory system. PRP transfusion might be indicated when signs of bone marrow damage are detected, so that regeneration and restock can be attempted. Intraosseous administration of PRP can also be performed in some cases to accelerate the bone marrow regeneration, but this must be with autologous PRP, not from a donor.
- Platelet infection: Anaplasma platys (formerly known as Ehrlichia platys) infects running platelets directly, causing almost immediate destruction; on the other hand, Borrelia burgdorferi, the spirochete that causes Lyme disease, only infects activated platelets. In these cases, PRP transfusion is only indicated when alarming low platelet levels are noticed in blood count. If thrombocytopenia is found, but it is not life-threatening, PRP transfusion should be avoided, since the adhesion of the infectious agents to the platelets might contribute to the hematogenous dissemination onto other organs.
- Immune-mediated destruction: some of the rickettsial diseases generate antiplatelet antibodies, causing thrombocytopenia due to autodestruction. In these cases PRP is contraindicated, since it would exacerbate the condition.
It is very important to highlight that PRP transfusion, when indicated, might be helpful to maintain healthy levels of platelets in the blood stream, but does not replace the infection treatment. The thrombocytopenia will continue to manifest itself until the underlying cause is eliminated.
Most of the inherited coagulopathies are clotting factor deficiencies. Most of them are ligated to the X chromosome, explaining why they are more frequently observed in males.
- Factor II deficiency. Commonly observed in Cocker Spaniels and Boxer breeds, this disease shows absence of prothrombin or dysfunctional thrombin. Frequent clinical signs include epistaxis, oral cavity hemorrhages, dermatitis and easy bruising. If the patient has normal hematocrit levels, PRP transfusion with pharmacological activation (see Get Started Section for Activation methods) may be helpful. If red cell levels are low, whole blood transfusion would be a better choice. Autologous PRP will not be functional on these patients.
- Factor III deficiency. Beagles, Schnauzers, Bulldogs, Boxers and Alaskan Malamutes are the dog breeds that may present this disease, which is characterized by a deficiency of proconvertin. Active or spontaneous bleeding is rarely seen in these cases, and the diagnosis is mostly incidentally made by observing delayed PT activity with normal ACT in clotting lab tests. Donor’s PRP or autologous PRP transfusion is indicated on these patients as a prophylactic measure during surgical procedures, in order to avoid prolonged bleeding after the procedure.
- Hemophilia A (Factor VIII). This is the most common inherited coagulopathy in canine and feline patients, and consists in a deficiency of the antihemophilic factor. Because of its link to the X chromosome, males show clinical signs, while females only act as asymptomatic carriers and transmitters. Feline patients may present hematomas, but more often persisting hemorrhage after surgery; same applies for small and toy breed dogs. In canine patients, the German Shepherd is the number one hemophiliac breed, and clinical signs frequently observed include subcutaneous hematomas, peritoneal effusions, pericardial and pleural effusions, and hemarthrosis (being the last one the most common). Other signs may be excessive hemorrhage after nail trimming, trauma or surgery. Laboratory clotting tests in these patients reveals prolonged ACT activity. When an active bleeding episode is manifested, the main goal is to stabilize the patient with whole blood transfusion until hematocrit acceptable levels are achieved. After that, normovolemia should be attempted with colloid solutions, and frozen plasma or PRP can be transfused every 8 hours until the hemorrhage is stopped. Whenever a patient is diagnosed with Hemophilia A, prophylactic PRP transfusions should be performed before any activity or medical procedure that could cause the smallest trauma.
- Hemophilia B (Factor IX). Also known as Christmas factor deficiency, Hemophilia B is also linked to the X chromosome. It is commonly seen in Siamese and British Shorthair felines, as well as in German Shepherds and Labrador Retrievers. The clinical signs are very similar to the Hemophilia A signs, but manifested in a milder way, making the diagnosis pretty difficult. Most patients die at birth because of persisting umbilical cord hemorrhage, or years later due to acute bleeding into body cavities, muscular hemorrhage, or stroke. In case of diagnosing a B hemophiliac patient before these acute affections, hematocrit and normovolemia should be managed, and then continue with frozen plasma or PRP transfusion until bleeding is controlled.
- Factor X deficiency. Observed in Cocker Spaniels and Jack Russels, as well as in Shorthair cats, these patients usually die at birth. If not, treatment should be performed as in Hemophilia A and B.
- Hemophilia C (Factor XI). The main characteristic that differentiates Hemophilia C from other inherited coagulopathies is that it is shown several days after trauma or surgery, with the leading cause being fibrinolysis; so the coagulation cascade happens correctly, but the clot generated ruptures after a few days (generally 4). PRP transfusion can be performed in these patients prophylactically after surgery, in an attempt to accelerate tissue regeneration and preserve the existing clots, although there are not enough studies that say if it is actually useful or not. This disease has been observed in Springel Spaniel dogs, Weimaraners and Great Pyrenees.
- Factor XII deficiency. Incredibly difficult to diagnose, this disease, also known as Hageman factor deficiency, has been detected in cats and Miniature Poodle dogs. There are not enough evident hemorrhagic clinical signs that allow an early diagnosis, and the physiopathology is more inclined towards alterations of inflammatory mediators. PRP is not recommended in these cases, since it may worsen the inflammatory response, but there are still studies to be made in order to really understand this disease.
- vonWillebrand Disease. This is probably the most important and common coagulopathy in dogs. This disease consists in a deficiency of the Von Willebrand factor, which should be normally produced by endothelial cells and also found in platelets. It is worth highlighting that dogs have 3% VWf in their platelets, while cats have 20%. The VWf plays an important role in the coagulation process, since it actively participates in the adhesion between the platelets and collagen; it also performs the same functions that fibrinogen does, and carries factor VIII throughout the blood, so its deficiency will result in hemophilia A clinical signs, as well as constant hemorrhage of fragile mucous membranes (nasal, vaginal, oral). The most common dog breeds that present this disease are, in the first place, the Doberman Pinscher, and following the Airedale Terrier, Corgi and Scottish Terrier. When acute bleeding occurs, red cells should be normalized, and after that, frozen plasma, fresh plasma and PRP transfusions are indicated to control bleeding, as well as desmopressin acetate. PRP transfusion is especially helpful, since small volumes provide more platelets than frozen plasma, so that 3% of VWf resting inside platelets from healthy donors can be really exploited without overloading the blood vessels. Also, patients with vWD require transfusions very frequently, so PRP transfusions are useful to reduce the risk of post transfusion reactions towards red cell antigens.
There are many other inherited coagulopathies that remain to be studied, where PRP has still not been tried.