**2. Pretransplant assessment protocol to establish personalized preventive strategies**

#### **2.1 Assessment of anti-HLA antibodies**

Human leukocyte antigen (HLA) antibodies are important to detect because they are associated with rejection after transplantation.

Recently, the International Society of Heart and Lung Transplantation (ISHLT) published the updated Guidelines for the care of heart transplant recipients [2–5]. Most common antibody screening is performed by sensitive solid phase assay. Single antigen bead assays have allowed virtual crossmatching.

Antibody mean fluorescent intensity (MFI) is a method to assess the sensitization and help to determine a positive cross-match. It is a measure of antibody-antigen binding or HLA molecule bead saturation; however, it is affected by biological and technical factors.

The C1q assay is useful to identify antibodies capable of fixing complement. If C1q binds DSA strongly, this correlates with a positive cytotoxic crossmatch and it is associated with early antibody-mediated rejection.

The recommendation is: The anti-HLA class I and II specificities should be defined. In the absence of international standards, each center must define the antibody threshold for unacceptable risk. A mean MFI of less than 5000 is considered to be an acceptable threshold (Class I, Level of Evidence C) [2].

## **2.2 Panel reactive antibody (PRA) and risk factors for antibody-mediated rejection (AMR) or early phase acute rejection**

The calculated panel reactive antibody (cPRA) is an estimation of the compatible donor pool collected when the recipient is evaluated for transplant and shows if the patient is sensitized or not. If the recipient has PRA > 10%, the patient is sensitized and has more risk to develop rejection after transplant as well as donor-directed antibodies [3].

There are some conditions where it is more common to have high PRA (**Table 1**).

It is important to monitor the cPRA because the serological presence of antibodies varies in the recipient over the time. For nonsensitized patients, HLA antibody screens are recommended every 6 months, and for sensitized patients every 3 months. For patients on mechanical assist support, after blood transfusions, infections, or using a desensitization therapy, HLA antibodies need to be evaluated every 1 to 2 weeks [2].

### **3. Desensitization methods: Brief protocols and outcome**

The desensitization strategies are to decrease antibodies, B cells, plasma cells, and complement activation. There is no randomized clinical trial to assess the efficacy of the therapy. Furthermore, memory response may occur after antibody depletion. The protocols include perioperative plasmapheresis, IV immunoglobulin, or eculizumab at transplant [2].

Some centers have a protocol to desensitize these recipients using specific drugs and procedures (**Table 2**).


**Table 1.** *Conditions for sensitized patients.*

*Strategies for Prevention and Management of Heart Transplant Rejection DOI: http://dx.doi.org/10.5772/intechopen.114145*


#### **Table 2.**

*Management for desensitization.*
