Blood Transfusion in Medicine IV Renal Disease

Patients with renal disease who require blood transfusion impact a blood bank in several different ways. First, there is the question of appropriate transfusion support for patients who are potential renal transplant candidates. In recent decades there has been considerable change in the approach towards the type of red cell product transfused to these patients. In the 1950s, blood transfusions were routinely administered in order to improve symptomatic anemia. This practice was discouraged in the early 1960s, because of concerns regarding allosensitization to HLA antigens, which would result in subsequent renal allograft rejection. In the later 1960s, it became evident that patients who had been transfused pretransplant paradoxically showed an improved graft survival!! This was attributed to an immunomodulatory effect of blood transfusion. For this reason, blood transfusions (generally > 3 units) using standard nonleukoreduced red cells were intentionally given pretransplantation in this patient population, throughout the 1980s. With the availability of cyclosporine A, however, current thinking is that the risk of alloimmunization to HLA antigens from white cell rich red cell transfusions exceeds the benefit of the immunomodulation, such that "active transfusion" is no longer considered appropriate (Chapter 12). Therefore, the question arises as to what type of red cell product would be most appropriate, if needed, pretransplantation.

As shown in Table 18.1, the suggested product is a leukoreduced (filtered) red blood cell, preferably a prestorage leukoreduced product. This blood product will prevent primary HLA alloimmunization thus reducing allograft rejection. In addition, this product will also constitute effective prophylaxis for CMV transmission. Historically, washed red cells were requested on the basis that this will result in an reduction of HLA sensitization. Washing however, is very ineffective in removing allogeneic leukocytes (only about 70% are removed) and the preferred approach is the use of a filtered product, which removes 99.99% of leukocytes (Chapter 36).

Patients on chronic dialysis who are not transplant candidates present a different situation. In the past, transfusion of dialysis patients accounted for 3-5% of all red cells transfused in the U.S. Erythropoietin has greatly reduced the number of transfusions in this population. Despite this, there are some patients on dialysis who still require transfusion. Multiple transfusion of red cells in the patient sometimes results in the development of alloantibodies to red cells. This may cause difficulty in finding phenotypically compatible red blood cells. It has also been observed that autoantibodies to red cells may occur in this setting, which appear to be directed against an antigen, called N, within a red blood cell blood group

Table 18.1. Blood transfusion consideration in renal disease

I. Potential transplant candidates

Leukoreduced, preferably prestorage leukoreduced RBC to prevent HLA alloimmunization and CMV transmission by transfusion.

II. Chronic Dialysis

(a) Multiple alloantibodies to red blood cells may develop

(b) Autoantibodies to red blood cells can occur

(c) Controversy regarding washed red blood cells

III. Prophylaxis or management of bleeding disorders

(b) Cryoprecipitate

(c) Conjugated estrogens

(d) RBC transfusion to Hct > 35

(e) Recombinant human erythropoietin

IV. Management of hemolytic uremic syndrome (HUS)

(a) Therapeutic plasma exchange with either frozen plasma or cryosupernatant plasma as exchange fluid

(b) Staphylococcal protein A immunoabsorption for drug induced HUS

system, called the MNSS system. This antigen (Nf) may be modified by the formaldehyde used to sterilize the dialysis tubing. It is thought that this autoantibody (Nf) does not cause hemolysis in vivo, but it complicates the normal procedures for providing compatible red cells. A third consideration in patients on chronic dialysis is the occasional request for washed red blood cells. In general, the usefulness of washed red cells in this setting is related to the removal of the supernatant potassium. The supernatant concentration of K+ is about 40 mEq/L at the end of storage, but the absolute amount given per unit of red cells rarely exceeds 5 mEq. It is best whenever possible, therefore, to transfuse patients on dialysis, which will allow for the removal of any transfused potassium. If the patient is between dialysis treatments, however, and receiving large numbers of red blood cells over a short time period (e.g., acute hemorrhage), the potassium load delivered could be excessive. This is only likely in the context of massive transfusion of such patients. Irradiated blood (Chapter 37) is best avoided, if at all possible, particularly in this setting. It is preferable to transfuse fresh red cells less than 10 days old, in which the K+ concentration rarely exceeds 10 mEq/L, if multiple red cell transfusions are given over a short time period.

Patients with renal disease also impact the blood bank on account of the bleeding disorder associated with uremia. Patients with uremia have an acquired bleeding tendency, the underlying cause of which is not clear, but thought to be related to platelet dysfunction. A clinical surrogate marker for the severity of this bleeding disorder has been the bleeding time. Strategies, therefore, which are known to shorten the bleeding time have been clinically justified in ameliorating the bleeding disorder of uremia. These strategies are outlined in Table 18.1, in more detail in Table 18.2, and are dealt with more extensively in Chapter 23. Desmopressin (DDAVP) will shorten the bleeding time within one hour of intravenous administration, but the duration of action is only 6-8 hours. A subsequent dose may be necessary, if bleeding continues. It is most often used prophylactically prior to surgery or an invasive diagnostic procedure. Although multiple dosing of DDAVP is known to result in the phenomenon of tachyphylaxis (reduction in effect with repeated doses) in Hemophilia A or von Willebrand's disease, it is unknown if this occurs in renal failure. Subcutaneous or intranasal DDAVP (the latter in higher dose) may also be administered, though there is less data available on the efficacy of DDAVP administered using these routes. Cryoprecipitate has also been shown to decrease the bleeding time. It is important to appreciate that cryoprecipitate has a delayed onset of peak action, as judged by the bleeding time, i.e., approximately 6-18 hours after administration. The effect, however, may persist for 1-2 days. The time relationship, therefore, between administration and benefit differs between DDAVP and cryoprecipitate. The dose of cryoprecipitate traditionally has been 10 units. Repeated doses could theoretically be administered, although there is no data available with regard to efficacy of multiple doses. Conjugated estrogens given by mouth (premarin 5 mg po) have also shown benefit in uremia. The onset of action is much later than either cryoprecipitate or DDAVP, occurring 24-48 hours after oral administration. The duration of action, however, may persist for 2-4 days and this strategy is useful if there is a planned elective procedure. In uremic patients with a prolonged bleeding time, there is an inverse relationship between the prolonged bleeding time and the hematocrit, and therefore, simply transfusing red blood cells to increase the hematocrit has been shown to normalize the bleeding time. This will usually occur when the hematocrit exceeds 35. If the bleeding time is a true surrogate marker for clinical bleeding events, then the transfusion of red cells should be effective in preventing excessive bleeding. Related to this is the use of erythropoietin to increase red cell mass in uremia; the resulting increased hematocrit will decrease the bleeding time. The use of alloge-neic platelets in the management of the bleeding disorder of uremia is not known to be beneficial (i.e., shortening of the bleeding time has not been shown). This practice has probably arisen since the uremic defect is a "platelet defect". However, the "platelet defect" is an extrinsic platelet defect, resulting from the uremic environment, and allogeneic platelets transfused to the uremic patient will be exposed

Table 18.2. Treatment of the bleeding disorder in uremia

Onset of Peak Duration of

Agent Dose Action (hours) Action (hours) Action (hours)

Table 18.2. Treatment of the bleeding disorder in uremia

Onset of Peak Duration of

Agent Dose Action (hours) Action (hours) Action (hours)

DDAVP

0.3 - 0.4 ^g/Kg in 50 ml saline over 30 minutes

1/2

1-2

6-8

Cryoprecipitate

10 units IV

1

6-8

24-48

Conjugated Estrogens

Premarin 5 mg p.o. QID

24

48-72

?

Red Cell Transfusion

To achieve Hct > 35

-

-

-

rh Epo

To achieve Hct > 35

-

-

-

to the same environment. Therefore, the use of allogeneic platelets is not reasonable, has no empiric clinical justification and is wasteful.

The hemolytic uremic syndrome (HUS) is an acute renal failure in which fragmented red cells are a prominent feature. This entity occurs predominantly in children. Although some cases of HUS resolve spontaneously, plasma exchange in a dose of 1-2 plasma volume exchange on a daily basis until clinical improvement is employed in severe cases. The exchange fluid in HUS has conventionally been fresh frozen plasma, and the role of cryosupernatant as an exchange fluid (which is gaining popularity in thrombotic thrombocytopenic purpura) remains unclear (Chapter 40). In the adult population, HUS can occur in association with drugs such as mitomycin C in the treatment of cancer or cyclosporine A in the posttransplant population. In this setting, HUS is sometimes treated with staphylococcal protein A immunoabsorption therapy in which both IgG and IgG-com-plexes are selectively removed from plasma (Chapter 40).

Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

Get My Free Ebook


Post a comment