Platelets Indications and Dosing

Blood platelets are currently manufactured in one of two ways. Whole blood donors may donate a unit of blood from which a platelet concentrate is manufactured. In this process, the unit of blood is subjected to two centrifugational steps. The first step is called a soft spin, which makes platelet rich plasma and a concentrated (packed) red cell. The platelet rich plasma is expressed from the bag and then subjected to a second centrifugation called a hard spin, after which the platelets are concentrated into a small amount of plasma (35-60 mls). In some European countries, the centrifugation is reversed, and the platelets are manufactured from the layer between the red cells and plasma, called the buffy coat. Either way, the end product is called a unit of platelets or a random donor platelet unit.

Alternatively, donors may have their blood anticoagulated and drawn into special machines, called apheresis machines. In this procedure, platelets are separated by centrifugation, and the red cells returned to the blood donor together with most of the plasma. This procedure takes 50-90 minutes. The correct name for this product is platelet pheresis, but is more commonly known as single donor platelets or apheresis platelets. Platelet pheresis, or single donor platelets, have a higher content of platelets (absolute number, yield or potency) than are present in a unit of platelets (random donor platelets) derived from a whole blood donation. Approximately 5-8 random donor units of platelets are equivalent to one apheresis product. The characteristics of platelet products are shown in Table 28.1.

The clinical indications for platelet transfusions are to prevent or stop bleeding in patients with low platelet counts (thrombocytopenia) or less commonly, in patients with dysfunctional platelets (thrombocytopathy). These indications occur in several different types of clinical settings. First, patients with severe throm-bocytopenia. The most common indication in this setting is to prevent spontaneous bleeding, particularly spontaneous intracranial bleeding. Most current literature now shows that this is unlikely to occur unless the platelet count decreases below 10 x 109/L (10,000/mm3) and a high risk is not present until the platelet count decreases below 5 x 109/L (5,000/mm3). In the past, a threshold value of 20 x 109/L (20,000/mm3) was commonly used by hematologists to prevent spontaneous bleeding in patients with acute leukemia and bone marrow transplantation, but this is now obsolete. The second clinical situation is thrombocytopenia in a patient for whom an invasive diagnostic procedure is imminent, such as liver biopsy, colonoscopy with biopsy, bronchoscopy with biopsy, etc. The transfusion trigger platelet count is unknown, but is commonly considered to be 50 x 109/L or lower. Patients with platelet counts below 50 x 109/L, may, therefore, be appropriate candidates for prophylactic platelet transfusions in this setting, although many such procedures can be performed without platelet transfusion, depending on the

Table 28.1. Platelets

Product:

Human platelets suspended in plasma. The platelets comprise only 2-4% of the total volume; the remainder, 96-98% is plasma.

Characteristics:

Whole Blood Donation Apheresis_Donation

Potency 5 - 8 x 1010 40 x 1010

Labeling Platelets Platelets, pheresis

Common Usage Random Donor Units Single Donor Unit

Pharmacological Effect:

Increase the Platelet Count and Prevent or Stop Bleeding

Indications:

1. Thrombocytopenia (5 - 20 x 109/L) to prevent spontaneous bleeding

2. Thrombocytopenia (< 50 x 109/L) with active bleeding or prior to invasive procedure

3. Normal platelet count: Qualitative (abnormal) platelet function Doses:

1 unit/10 Kg weight; 4 units/m2 Surface Area 1 Platelets, Apheresis

skill of the operator. A third clinical situation is the presence of thrombocytope-nia in a patient prior to a surgical procedure. In this situation, the underlying cause of the thrombocytopenia and the nature of the surgical procedures are important. A preoperative trigger count of 50 x 109/L (50,000/mm3) is often used but a lower trigger may be appropriate. Considerations are whether the procedure in itself is ordinarily associated with excessive blood loss; whether the bleeding can be well visualized and controlled by local surgical measures; or whether small amounts of bleeding in a closed space would create a residual functional problem for the patient, for example, neurosurgical procedures or ophthalmic surgery. In these latter situations, a preoperative trigger of 80-100 x 109/L (80,000-100,000/mm3) is sometimes advocated for such surgery. A fourth clinical situation is a thrombocytopenic (< 100 x 109/L or 100,000/mm3) patient who is actively bleeding, for example, acute gastrointestinal bleeding. There is very little data available to guide platelet transfusion in this context. The concern is that the low platelet count could be either a significant contributing cause to or exacerbation of the degree of blood loss. In this setting, it is probably wise to treat if the platelet count is less than 50 x 109/L and, possibly, if the platelet count is less than 100 x 109/L. If large volumes of red cells are transfused, platelet transfusion will certainly be required on account of hemodilution and may need to be repeated. A fifth situation arises when the platelet count is normal but the platelets are considered to be dysfunctional, such as in a patient with excessive chest tube drainage after cardiopulmonary bypass (for example, in excess of 300 ml/hour). Empiric

platelet transfusions may be appropriate in these patients and useful in avoiding a surgical re-exploration. A common situation is the patient with a normal platelet count who has taken aspirin and or similar drugs and requires a surgical procedure or an invasive diagnostic procedure. Deferral of the procedure for 48-72 hours is optimal since platelet function will return to normal if aspirin is discontinued for this time. For other nonsteroidal drugs, 6-8 hours may be adequate, since the effect is reversible more quickly. This is because aspirin irreversibly acetylates an enzyme, cyclo-oxygenase, in the platelet and 2-3 days are required for the bone marrow to produce 20-30% normal (nonacetylated) platelets. Other nonsteroidal drugs reversibly inhibit this enzyme, and the effect disappears when the drug has been cleared. Ticlopidine (Ticlid®) and Clopidogrel (Plavix®) have a different mechanism of action and discontinuation of these drugs for at least 10 days is needed in order to reverse the antiplatelet effect. If an urgent surgical procedure is required, it is best to have platelets available for possible transfusion and if mi-crovascular oozing is observed intraoperatively, transfusion may be appropriate. In neurosurgery or ophthalmic surgery, however, where minimal amounts of excessive blood loss could cause severe functional problems, prophylactic platelet transfusion may be appropriate before surgery. The dose of platelets needed to reverse an aspirin effect is known to be less than "standard dose" since as few as 15-20% of nonaspirinized platelets will suffice. The dose, therefore, should not normally exceed four units.

Platelet dosing is very controversial and there is no such thing as a "standard platelet dose". Surveys of different institutions indicate that between 5-10 units of platelets or equivalent is fairly routinely administered per transfusion. The generally recommended dose is 1 unit of platelets per 10 kg body weight or 4 units/m2 surface area. If platelet pheresis is available, the dose is the content of the single donor product. As with red cells, it is useful to consider the clinical situation, the pretransfusion platelet count, the desired posttransfusion platelet count and the size of the intravascular volume of the recipient (body weight). A generally suggested dose of random donor platelets might be five units. Higher doses of platelets have traditionally been transfused, such as 8-10 units, but this may have arisen because of less attention to quality control in manufacturing of platelets in the past and may have resulted in lower quality products (i.e., lower platelet content). Increasing the number of units, therefore, was to compensate for this uncertainty and increase the likelihood of an adequate response. This is no longer the situation in most Blood Centers. The dose used should have a reasonable expectation of success, i.e., absolute increase in the platelet count of 20-40 x 109/L. A suggested platelet algorithm for adult dosing is shown in Figure 28.1.

New developments in blood collection technology point to the increasing use of apheresis machines for the collection of all blood components. If this is the case, a 'standard apheresis product' could become the only product available in the future.

One of the more complicated problems encountered in clinical practice is the management of patients refractory to platelet transfusions (Table 28.2). These patients are typically cancer patients or bone marrow transplant patients receiving

Table 28.2. Causes of refractoriness to platelet transfusion and management strategies

1. Antibiotic agents (especially vancomycin or cephalosporins). Considering discontinuing or changing these drugs.

2. Amphotericin B: Evaluate for continuing need.

3. ABO incompatible platelets: Transfuse ABO identical platelets and monitor the response in platelet increase of 10-60 minutes.

4. Hypersplenism: Consider lowering the trigger for transfusion.

5. Fresh platelets (less than 36 hours old) may provide better platelet increases.

6. HLA alloantibodies: Consider HLA selected (matched) platelets or crossmatched platelets, if available.

7. Platelet-specific antibodies: Consider crossmatched platelets, if available.

8. For all patients: Consider transfusing red cells to maintain a minimum Hct of 32-35.

Atomic Layer Deposition System

Fig. 28.1. Suggested algorithm for initial adult platelet dosing in different clinical situations. This dose assumes a 70 Kg recipient and blood volume of 5 liters. Subsequent doses should be determined by the clinical circumstances.

Fig. 28.1. Suggested algorithm for initial adult platelet dosing in different clinical situations. This dose assumes a 70 Kg recipient and blood volume of 5 liters. Subsequent doses should be determined by the clinical circumstances.

platelet transfusions as prophylaxis for spontaneous bleeding. In this situation, little or no increase in the platelet count is observed after the transfusion of a platelet product and an actual decrease may sometimes be observed! This is a perplexing problem for both the Blood Bank and the treating physician. There are many causes of this problem, but in some recipients the refractoriness is due to alloantibodies against class I HLA antigens or platelet specific antigens (immune case). In assessing these patients, nonimmune causes should be sought such as the use of antibiotics and antifungals especially vancomycin and amphotericin, or splenomegaly. ABO incompatibility should be considered; e.g., transfusing A or B platelets to an O recipient. HLA selected platelets should only be requested after these have been evaluated. It has also been suggested that these patients respond better to fresh (less than 36 hours) platelets, when available. In many instances, the response to HLA selected (matched) platelets is disappointing. These patients should be managed by transfusing at least one dose of platelets daily in order to meet the "endothelial" need for platelets; the actual increment observed need be of less concern. This concept of "endothelial" need is that a small percentage (7%) of the platelet mass is consumed in normal (healthy) subjects daily in sealing breaks in endothelial integrity. In thrombocytopenic patients, this same mass (or more) of platelets is still required, and must be supplied by allogeneic platelets since the autologous platelets mass is inadequate. In addition, red blood cells should be transfused to maintain a hematocrit at between 32-35. This reduces plasma volume thereby effectively increasing the concentration of platelets. There is data that this approach improves one surrogate test of platelet function, the bleeding time. The practice of transfusing massive doses or multiple daily doses of platelets to these patients is wasteful, does not have any empiric justification, and should be resisted.

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