Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (641 page)
Authors: Mary A. Williamson Mt(ascp) Phd,L. Michael Snyder Md
When assessing a patient for coagulopathy (usually an acquired coagulopathy), the most common laboratory tests ordered are a prothrombin time (PT)/international normalized ratio (INR) and an activated partial thromboplastin time (aPTT). The PT is very sensitive and will be abnormal before coagulopathy will result in bleeding. Generally, an increase in bleeding is not usually seen until the PT is >1.3 times the upper limit of the normal range (which usually corresponds to an INR of approximately 2). In nonbleeding patients with an elevated INR due to warfarin use, vitamin K can be used to correct the coagulopathy (over 6–24 hours) without plasma transfusion. It is also important to note that plasma transfusion is significantly more effective in decreasing a patient’s INR when the INR is significantly elevated. As the patient’s INR gets closer to or below 2, a large amount of plasma will result in a much smaller decrease in the INR than the same volume of plasma given to the same patient at a higher INR. Another important consideration when transfusing plasma, especially prior to an invasive/surgical intervention, is that the plasma should be transfused within a few hours of the intervention. The in vivo half-life of some of the coagulation factors that need correction (such as factor 7) is a few hours and correcting the coagulopathy with plasma transfusion >8 hours prior to transfusion will likely be of little benefit. Additionally, the use of plasma for warfarin reversal will likely decrease significantly with the recent approval of four factor prothrombin complex concentrate (PCC) in the United States.
CRYOPRECIPITATED AHF TRANSFUSION
A unit of cryoprecipitated AHF (also known as cryoprecipitate) is prepared from a unit of plasma. When frozen plasma is placed in a refrigerator and starts to thaw, there is precipitation of some proteins. This precipitate contains a significant proportion of the factor VIII, von Willebrand factor, fibrinogen, fibronectin, and factor XIII that is present in the unit of plasma. Subsequently, the unit is centrifuged to separate the precipitate from the supernatant plasma. The cryoprecipitate is then frozen until it is necessary to transfuse.
Who Should Be Suspected?
In the past, cryoprecipitate was used to treat patients who had hemophilia A. But due to safer alternatives, cryoprecipitate is no longer used for this purpose in the United States. The primary use for cryoprecipitate today is to replete fibrinogen in patients with hypofibrinogenemia or disfibrinogenemia (e.g., patients with DIC, patients requiring massive transfusion).
Fibrinogen levels between 50 and 100 mg/dL are generally adequate in patients to achieve hemostasis. However, levels <100 mg/dL may cause in vitro laboratory testing abnormalities. The volume of a unit of cryoprecipitate is approximately 15 mL, and for transfusions in adults, generally 10 units are pooled for an adequate dose. However, it is possible to calculate the exact number of units needed to reach a specific fibrinogen level if the patient’s fibrinogen level is known. Occasionally, cryoprecipitate is also used in uremic patients and in patients with von Willebrand disease as a source of von Willebrand factor.
PLATELET TRANSFUSION
Platelet transfusion is generally performed to correct an abnormality of platelet function or platelet count in order to prevent bleeding or treat active bleeding. The most common indication for platelet transfusion is prophylaxis in thrombocytopenic patients. Although there are no well-accepted guidelines in regard to prophylactic platelet transfusion, some consensus has been achieved and many institutions follow similar practices.
In patients who are severely thrombocytopenic and do not have additional risk factors for bleeding, a threshold platelet count of 10,000/μL is commonly accepted. In patients who are having an invasive CNS, ophthalmologic, or possibly a pulmonary procedure, a count of 100,000/μL is often targeted. Even though most experts agree that this count is higher than needed to achieve hemostasis, it is still considered a reasonable target because it protects against a precipitous drop in platelet count that can result in bleeding into these organs causing serious morbidity or mortality. For other invasive or surgical procedures, most authorities concur that platelet counts above 50,000/μL are generally adequate.
Some of the causes of qualitative defects of platelet function include congenital diseases (e.g., Glanzmann thrombasthenia, Bernard-Soulier disease), medications (e.g., aspirin, clopidogrel), and dysfunction due to medical device interaction (e.g., cardiopulmonary bypass). In these patients, the platelet counts may be normal, but due to abnormal platelet function, transfusion of one unit of apheresis platelets (or an equivalent dose of whole blood–derived platelets) is often appropriate. In patients on antiplatelet medications who present with acute bleeding, especially bleeding into the central nervous system, two apheresis platelets (or equivalent) are often transfused.
Platelet products can be collected using apheresis technology or can be produced by separation from whole blood collections. For adult patients, 4–8 units of whole blood–derived platelets must be pooled for one transfusion dose or alternatively a single apheresis unit collected from one donor can be transfused. Both types of platelet products are commonly used, and each one has some advantages and disadvantages. One significant advantage of apheresis platelet products is that they are collected from a single donor and can be used to transfuse patients who require HLA-selected platelet products.
Patients who get immunized to HLA antigens due to pregnancy, organ transplantation, or previous exposure to blood products may not respond adequately to platelet transfusion. Platelets have HLA class 1 (A and B) antigens on their surface, and if the recipient has antibodies to the HLA antigens of the donor, there may be no increment in platelet count posttransfusion. The most effective way to prevent immunization to HLA antigens is by leukoreduction of blood products. However, if a patient is already immunized to HLA antigens, there are several strategies that can be employed to transfuse these refractory patients. These include platelet crossmatching, HLA matching, and selection of platelet products from donors who lack the cognate HLA antigens to which the patient has antibodies. However, prior to attaining HLA-selected platelet units, it might be reasonable to transfuse fresh ABO identical apheresis platelets as ABO incompatibility and older age of transfused platelets have been reported to decrease posttransfusion platelet increments.
Platelet crossmatching is performed by mixing a sample of the patient’s plasma with platelet products that may potentially be transfused and checking for a reaction between them. If reactivity is present, the crossmatch is interpreted as positive and the platelet product is not transfused to the patient. If necessary, additional platelet products can be crossmatched with the patient until a product that does not have reactivity with the patient’s plasma is procured. One substantial benefit to HLA crossmatching is that it is possible to find compatible platelet products without determining the patient or the donors HLA type. However, HLA crossmatching can only be performed on platelet products that are ABO compatible, and the data available comparing HLA crossmatching with HLA matching show that platelet crossmatching is likely an inferior strategy.
HLA matching is performed by HLA typing patients as well as platelet donors. Once HLA typing data are available, platelet products that either completely match or are very similar for HLA class 1 (A and B) antigens are selected for transfusion. The HLA match of the recipient to the donor can be rated from A (all four antigens match) to D (two or more antigen mismatch). HLA matching of platelets is effective in achieving good count increments when the donors are very well matched (A or B level matches) to the patient. However, if a patient is widely immunized and the platelet product is not well matched (C or D level matches), the patient will likely not respond to the platelet transfusion. Additionally, HLA matching may be difficult in smaller institutions that do not have HLA laboratories or large platelet inventories.
A third strategy that is as successful as HLA matching and likely superior to crossmatching is selection of platelet products that avoids HLA antibodies present in the patient. In order to use this strategy, the patient must be tested for HLA antibodies. Once the specificity of the HLA antibodies in the patient is determined, platelet products from donors that lack cognate HLA antigens are selected for transfusion. This strategy can be very effective for patients who are refractory, even if an institution has a limited platelet inventory. However, if the patient is widely immunized to HLA antigens, donors with compatible HLA types will need to be recruited or compatible apheresis platelet products will need to be brought in from large blood centers with extensive inventories of platelets. This strategy has the additional benefit of determining whether the patient is refractory due to the presence of HLA antibodies or other causes. It is also important to reassess the patient every few weeks to check for any changes in the HLA antibodies present.