Treatment of WAS
Coping with WAS
Prophylactic Platelet Transfusions
Prophylactic platelet transfusions are given prior to surgery or if a physician feels that the patient is at a risk for significant bleeding. Several issues in this area are controversial. There is not a uniform agreement on the platelet count at which platelet transfusions are given. Some physicians feel that transfusions are needed even if the number of platelets are adequate, because the platelets in WAS patients do not work well. There is also controversy about the use of alternatives to platelet transfusions. The criteria for when to transfuse has to individualized for each patient and the decision is made by the hematologist and the family.
When to Transfuse.
Most experts agree that in WAS (verbal communication with Dr. Candotti and Dr. Ochs), prophylactic transfusions are reserved for counts under 10,000/cu.mm5 in the absence of bleeding on a stable patient who is not ill. A stable patient means that the patient is not on any medication that can worsen a bleed and does not have an illness that increases the risk of bleeding. It may not always be appropriate to apply these guidelines for every patient at every time.
Patients who are considered to be at higher risk should be maintained at a higher platelet count with prophylactic transfusions.
Under individual circumstances, the hematologist may decide that the counts may be as low as 5,000/cu.mm6 prior to prophylactic transfusions in the absence of bleeding in a stable, well established patient whom they have been following for a while.
For counts from 10,000-20,000/cu.mm transfusions are given at the discretion of the hematologist who is taking care of the patient.
Most surgeries require that the platelet count7 is over 50,000/cu.mm prior to surgery except for surgeries involving the brain, spinal cord and eyes during which counts of over 100,000/cu.mm are required.
Risks associated with Transfusions
Platelet transfusions carry the same risk of INDUCING allergic reactions and infection as other transfusion products such as red blood cells or plasma, i.e. Hepatitis B, Hepatitis C and HIV. Platelet transfusions are associated with a higher rate of fever after transfusion and carry a higher risk of bacterial infection because platelets are stored at room temperature.
Platelet transfusions must be used judiciously in these patients to reduce the risk of developing resistance to future platelet transfusions. This is particularly true for patients who are to undergo transplant as it may complicate the transplant. When platelet transfusions are given to a patient, their immune system can view this as a foreign body (similar to bacteria and viruses) and form antibodies against these platelets and destroy them. When subsequent transfusions are given the body mounts an even quicker response to destroy the platelets, reducing the effectiveness of transfusions. This process by which a person develops antibodies to and destroys transfused platelets is called allo immunization.
All platelets that are given must be irradiated and from a CMV (cyto megalo virus) negative donor.
. CMV can cause serious infections in these patients and can cause complications if the patient undergoes a transplant. If CMV negative blood is not available, the platelets should be infused through a high efficiency leukocyte filter.
for these patients and allows for the best rise in platelet counts.
The use of a high efficiency leukocyte filter (a filter that removes remaining white cells from the donor) reduces the rate of sensitization to platelets.
Platelet counts are usually checked 10-60 minutes after the procedure to ensure an adequate rise in the platelet count. Platelets are found to survive for 4-5 days after transfusion. 7,000-10,000/cu.mm. of platelets are consumed during the normal processes everyday and the life span is therefore shortened further. If there is an inadequate rise in platelet count in the absence of auto-antibodies to platelets (ITP), infection, bleeding etc then allo-immunization is suspected and the patient may benefit from HLA matched or ABO (blood type) matched platelets.
Alternatives to platelet transfusion, especially in the absence of bleeding should be considered whenever possible5. Antifibrinolytic drugs, such as epsilon aminocaproic acid (amicar) and tranexamic acid), appear to lessen bleeding in some thrombocytopenic patients. These are medications that help reduce bleeding by stabilizing a clot once it is formed. As it requires a reasonable number of platelets in order to work, it may not be useful in all patients with WAS. In patients in whom it works, it is useful in reducing the number of platelet transfusions. Amicar is available as a liquid, tablet and for intra venous injections. It has also been incorporated into popsicles and used for oral bleeds. Tranexamic acid is used similarly and is available as tablet and for injections. Tranexamic acid has been made into a mouthwash9 that helps in the reduction in bleeding following dental extractions.
Desmopressin acetate has been shown to be useful in some patients and is sometimes useful when patients have been on medications that interfere with platelet activity such as aspirin. Recombinant factor VIIa (rFVIIa) has been used with some success. These medications are also useful adjuncts to platelet transfusions in the event of a bleed but there has been no specific experience in patients with WAS. One study showed that high dose IVIG and steroids were not effective in increasing platelet counts in children with WAS related thrombocytopenia (see table below)1.
Eltrombopag has been shown to be effective in patient with ITP and a trial conducted by Dr. Jim Bussell is underway currently for patients with WAS. This study will include patients who have thrombocytopenia related to WAS and those who have ITP and WAS. Eltrombopag, an oral medication, is a protein that stimulates the production of platelets and has been shown to be well tolerated in patients with ITP.
WAS and ITP
Patients with WAS can develop antibodies to their own platelets(auto antibodies). This condition is referred to as Immune Thrombocytopenia Purpura (ITP). This is an autoimmune disorder and can compounds the already existing low platelet issues. In such cases a trial of medications such as10 high dose IVIG, danazol, rituximab, romiplostim or corticosteroids, vincristine may be tried in an attempt to boost the platelet numbers and reduce the number of transfusions. High dose IVIG alone has been of limited value in patients with WAS who develop ITP11. Splenectomy is sometimes found to be helpful for these patients12. Some patients may need a transplant to cure them of their ITP and WAS13.
Therapeutic Platelet Transfusions
WHO Bleeding Scale
In general Grade 1 and 2 bleeds are considered to be due to the patients underlying WAS related thrombocytopenia. Grade 3 and Grade 4 is more often caused by other factors such as trauma, medications, infection etc In patients with WAS, platelet transfusions are usually indicated for bleeding that is greater than are equal to a WHO Grade II Bleed 6(World Health Organization). However, each patient is presents with a unique set of circumstances and decisions to transfuse have to be considered on an individual basis.The general consensus is that platelet counts should be maintained over 50,000/cu.mm for acute bleeding and over 100,000/cu.mm. in the event of multiple trauma or an intracranial bleed7.
Platelet transfusion may not always be effective in controlling the bleeding in these patients. In the SPRINT Trial17, WHO bleeding grades decreased in only 21% of the transfusions. Some patients may need a platelet infusion(a continuous drip of platelets) to help stop the bleed. In the event of an uncontrollable bleed, surgeons may perform an emergency splenectomy (verbal communication - Dr. Kurtzberg) in an attempt to increase the platelet counts and help stop the bleed. Other clot promoting agents such as Recombinant Factor VII (Novo Seven) or aminocaproic acid or tranexamic acid may be used as adjuncts to help control the bleeding.