Immunological Complications of Blood Transfusion

Clare Taylor, MBBS, PhD, FRCP, FRCPath; Cristina Navarrete, PhD, FRCPath; Marcela Contreras, DBE, MD FRCPath, FRCPEdin, FRCP, FMedsci


Transfusion Alter Transfusion Med. 2008;10(3):112-126. 

In This Article


PTP is characterized by the development of severe, sudden and self-limiting thrombocytopenia occurring 5-10 days after a blood transfusion. The recipients always have a history of sensitization, mostly by pregnancy, and occasionally by blood transfusion. The diagnosis rests on the demonstration of potent antiplatelet reactivity in the patient's serum for a specific platelet antigen, usually HPA-1a. PTP therefore is a disease of adults, with no patients younger than 16 years of age being reported in the literature.[39] The female-to-male ratio is 5:1. The epidemiological findings are due to the requirement that a patient has previously been exposed to platelet-specific antigens before PTP can develop following a subsequent transfusion.

Clinical Presentation

In the majority of cases (over 80%), the platelet count drops around 1 week following the transfusion to less than 10 x 109 per liter. If random platelets or specific antigen-negative platelets are transfused, the increment is generally very poor or nonexistent.[40] One or two reports suggest that HPA-1a-negative platelets may be beneficial, and in cases of severe bleeding platelet transfusion should be considered.[41] Hemorrhage may occur from the gastrointestinal tract and epistaxis is common. Intracranial hemorrhage is responsible for the mortality rate which is around 9%. The differential diagnosis of PTP includes immune thrombocytopenic purpura (ITP), sepsis and DIC, bone marrow failure, drug-induced thrombocytopenia and thrombotic thrombocytopenic purpura (TTP). Drugs, infection and DIC are common causes of thrombocytopenia and these must be excluded. In straightforward alloimmunization to platelet, red cell or lymphocyte antigens, only the incompatible cells bearing the relevant alloantigen are destroyed by the reaction. The unique feature of PTP is destruction of autologous antigen-negative platelets in the presence of a platelet-reactive alloantibody. A source of indirect evidence of PTP as opposed to straightforward alloantibody-mediated platelet destruction is the response to therapy. IVIG infusion or plasma exchange has little effect on simple alloantibody-mediated platelet destruction, but these therapies are effective in PTP. The difficulty in proving a diagnosis of PTP means that the incidence of PTP is unclear, especially in the group of long-term platelet-dependent patients. The clinical spectrum of PTP may be very broad and mild cases may also not be noticed. Calculations of the theoretical frequency of occurrence of PTP based on the incidence of HPA-1a and other platelet antigens in the population, and on the frequency of alloimmunization through pregnancy, suggest a high incidence of PTP. In fact, it is quite rare, and it may be that other immune response factors may be necessary for individuals exposed to incompatible platelet antigens to develop the syndrome whereby autologous platelets are destroyed.


Several theories have been put forward to explain the destruction of autologous antigen-negative platelets in PTP. The first suggests that immune complexes are formed by the interaction of soluble platelet-specific antigen in donor plasma and platelet antibody in the patient.[42] These complexes then bind to autologous platelets through a high affinity Fc receptor mediating platelet destruction. A second theory maintains that an auto-antibody is developed in response to exposure to an incompatible platelet antigen and this antibody reacts not only with HPA-1a-positive cells but also with antigen-negative cells in the recipient. A third suggestion is that the soluble platelet antigen in donor plasma adsorbs onto the recipients' platelets, converting them to antigen-positive targets which are then destroyed by the alloantibody.[43] Soluble HPA-1a substances have certainly been identified in the plasma of HPA-1a-positive donors, however platelet antigen-antibody complexes have not been demonstrated in the serum of PTP patients. In support of the auto-antibody theory, platelet-associated IgG is increased in PTP. In addition, acute-phase PTP serum contained reactivity against a protein present in both HPA-1a-positive and HPA-1a-negative platelets. This reactivity occurred concurrently with anti-HPA-1a activity and disappeared after the acute phase of the illness, although the anti-HPA-1a persisted. Certainly, the response to therapy of PTP is similar to that of ITP, in which steroids, IVIG and splenectomy may be associated with elevations of the platelet count and decreases in platelet-associated IgG.

The diagnosis of PTP depends upon the finding of severe thrombocytopenia of less than 10 x 109/L approximately a week to 10 days post-transfusion. Normal red cell morphology rules out the possibility of TTP. Platelet antibody assays reveal serum antibody with HPA-1a specificity in most cases, although antibodies to other platelet-specific antigens are sometimes implicated.[44] Such patients frequently have antibodies to red cell and white cell antigens as well, and it may be that some individuals mount a generalized immune response encompassing a number of targets.


Treatments for PTP are hard to evaluate as the condition is generally self-limiting and untreated patients recover in approximately 2 weeks. Most patients with PTP are treated with corticosteroids during the acute phase at a dose of 2 mg/kg of prednisolone, or an equivalent dose of an alternative preparation.[45] There is little evidence of the efficacy of this treatment, although steroids may inhibit reticuloendothelial cell function or alternatively may result in a decreased antibody production. The most effective therapy for PTP is plasma exchange using some fresh frozen plasma as a replacement.[46] Recently, infusions of IVIG have become the first line in therapy for PTP, and a large proportion of patients respond well.[47] Only those unresponsive to IVIG now go on to plasma exchange. Recovery from PTP occurs 3-4 days after initiation of treatment with IVIG 0.5 g/kg for 2 days.


Prognosis is good with spontaneous recovery occurring in all cases. Mortality rates relate to the incidence of intracranial hemorrhage in a few patients. The incidence of recurrence of PTP with subsequent transfusions in an individual patient is extremely low, although, because of the potential severity of the reaction, patients with a documented history of PTP should receive antigen-negative blood products when at all possible.


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