From the Guidelines
Platelet refractoriness is primarily caused by alloimmunization due to antibodies against HLA antigens, and less commonly by platelet-specific antigens, as well as non-immune factors such as fever, infection, medications, and DIC. The management of platelet refractoriness involves identifying the underlying cause, which can be either immune-mediated or non-immune in nature. For non-immune causes, treatment should focus on resolving the underlying condition, such as infections, stopping implicated medications, or managing disseminated intravascular coagulation (DIC) [ 1, 1 ].
Immune-Mediated Refractoriness
For immune-mediated refractoriness, the use of HLA-matched or crossmatched platelets from compatible donors is recommended [ 1, 1 ]. If HLA-matched platelets are not available, ABO-matched platelets may be considered as an alternative. Immunosuppressive therapy, including corticosteroids (such as prednisone at 1-2 mg/kg/day), intravenous immunoglobulin (IVIG at 1 g/kg for 2 days), or rituximab (at 375 mg/m² weekly for 4 weeks), can help reduce antibody production [ 1, 1 ].
Non-Immune Factors
Non-immune factors contributing to platelet refractoriness include fever, infection, medications, and DIC. Managing these underlying conditions is crucial for improving platelet counts and reducing the need for transfusions [ 1, 1 ].
Prevention Strategies
Prevention strategies for platelet refractoriness include minimizing unnecessary platelet transfusions and considering leukoreduction of blood products to prevent HLA alloimmunization [ 1, 1 ]. Leukoreduction has been shown to decrease the incidence of alloantibody-mediated refractoriness to platelet transfusion, particularly in patients with acute myeloid leukemia (AML) receiving induction chemotherapy [ 1, 1 ].
Monitoring and Treatment
Platelet transfusions in refractory patients should be given at higher doses (twice the standard dose) and more frequently. Monitoring post-transfusion platelet counts at 10-60 minutes and 24 hours is essential to assess the response to transfusions [ 1, 1 ].
The occurrence of platelet refractoriness is attributed to the binding of antibodies to transfused platelets, leading to their rapid destruction by the reticuloendothelial system, or to non-immune factors that increase platelet consumption or sequestration [ 1, 1 ]. Understanding the cause and implementing appropriate management strategies are critical for improving outcomes in patients with platelet refractoriness.
From the FDA Drug Label
To detect antibody formation, submit blood samples to Amgen (1-800-772-6436). Amgen will assay these samples for antibodies to Nplate and thrombopoietin (TPO). The cause of Platelet (thrombocyte) Refractoriness is likely due to the formation of neutralizing antibodies to the drug, such as Nplate, or to thrombopoietin (TPO) 2.
- Hyporesponsiveness or failure to maintain a platelet response with Nplate should prompt a search for causative factors, including neutralizing antibodies to Nplate.
- The development of neutralizing antibodies can lead to a loss of response to the drug, resulting in platelet refractoriness. It is essential to investigate the cause of refractoriness and discontinue the drug if the platelet count does not increase to a level sufficient to avoid clinically important bleeding after 4 weeks at the highest weekly dose 2.
From the Research
Causes of Platelet Refractoriness
- Nonimmune causes, such as bleeding, medications, or diffuse intravascular coagulation, are responsible for the majority of platelet refractoriness cases 3
- Immune-mediated platelet refractoriness is caused by alloantibodies to human leukocyte antigens (HLAs) and/or human platelet antigens (HPAs) 4, 5, 3
- Antibodies to class I HLA molecules (A and B alleles) are responsible for most immune-based refractory cases, with antibodies to platelet antigens seen much less frequently 3
- Alloimmunization against Class I human leukocyte antigens (HLAs) or human platelet antigens (HPAs) can lead to platelet transfusion-refractoriness 4
Diagnosis and Management
- Platelet refractoriness is suggested when a 10-minute to 1-hour corrected count increment of less than 5 × 10(9)/L is observed after 2 sequential transfusions using ABO-identical, freshest available platelets 5
- Strategies for identifying compatible platelet units include HLA matching, crossmatching, and antibody specificity prediction 5
- Patients may be supported with either crossmatch-compatible or HLA-matched/compatible platelet units 3
- The antibody specificity prediction method can identify compatible units that lack antigens recognized by the patient's anti-HLA antibodies 3