Certain nonspecific agents can be used to minimize or control mucosal bleeding and for prophylactic treatment during the course of minor surgical interventions.

Antifibrinolytic agents, such as aminocaproic acid (Amicar^®) or tranexamic acid (Cyklokapron^®, Lysteda^®), reduce mucosal bleeding associated with epistaxis, menses or mucosal bleeding resulting from dental procedures.

Desmopressin acetate (DDAVP) effectively prevents bleeding in certain platelet dysfunction syndromes, likely due to its ability to induce release of endothelial cell VWF.⁶⁵ A preliminary trial of DDAVP, similar to DDAVP (Stimate^®) trials in von Willebrand disease, should be undertaken to determine individual response before its recommended use, since DDAVP has been found to trigger fibrinolysis in certain patients. The physician should evaluate effectiveness based on correction of the abnormal laboratory assay. When the platelet function analysis or platelet mapping assays are abnormal, we will use these as indicators because they are quick and easy to perform in the laboratory. However, if only the aggregation studies are abnormal, we will look for correction using only the agonists that were most impacted. In the initial paper documenting the effectiveness of DDAVP, the bleeding time was used;⁶⁵ however, few centers have the equipment or trained staff to perform this test, and we have found our approach to be equally predictive of DDAVP effectiveness.

Activated recombinant factor VII (rFVIIa or NovoSeven^®) is used to ameliorate or prevent bleeding associated with platelet dysfunction.^66-68 When used in combination with antifibrinolytic agents, minor bleeding can be controlled in certain patients. This treatment is often used prior to platelet transfusion to avoid blood product exposure and isoimmunization. In 2004, the European Medical Evaluation Agency (EMEA) approved the use of rFVIIa to treat patients in the European Union who have Glanzmann thrombasthenia with platelet antibodies and past and/or current history of platelet refractoriness.⁶⁷ In 2014 the Food and Drug Administration (FDA) approved the use of rFVIIa to treat patients with Glanzmann thrombasthenia with refractoriness to platelet transfusions, with or without antibodies.

According to recent data, Thrombopoietin (TPO) receptor agonists may help in the management of patients with inherited thrombocytopenias.^69,70 Some efficacy was observed in increasing platelet counts in certain disorders, including MYH9-related disorders and amegakaryocytic thrombocytopenia (CAMT), but results are highly variable in CAMT, most likely owing to the heterogeneous pathophysiology of this disease.²⁴

Platelet transfusion therapy will correct the bleeding defect in most cases of life-threatening bleeding episodes, even if only one single-donor apheresis unit is administered. Leukodepleted apheresis units (equivalent to approximately 6-8 pooled random donor units) are strongly recommended and preferred, to minimize multiple donor exposure and to decrease the risk of sensitization and a subsequent platelet refractory state.

To minimize long-term sensitization to human leukocyte antigen (HLA) class I proteins expressed on platelets, blood products should always be leuko-poor or leukodepleted.

In syndromes with complete absence of a membrane receptor, such as Glanzmann thrombasthenia or BSS, management strategies should include avoidance of excessive exposure to normal platelets due to the increased risk of development of isoantibodies specific for the missing receptor glycoproteins. Although isoimmunization in Glanzmann thrombasthenia is rare, the risk of alloimmunization remains a major concern. Isoantibodies are usually specific for multiple epitopes, some of which are functionally important sites of the receptor, and they bind to and neutralize these functional sites on any subsequently transfused normal platelets, rendering them ineffective.

Alloantibodies, on the other hand, are specific for polymorphisms in the receptor protein sequence, such as histidinol phosphate aminotransferase 1 (HPA-1, Pl^A1) on integrin b3. While these can cause immune clearance of alloantigen-positive, transfused platelets, donors can be selected who are genetically negative for the alloantigen(s) in question. Nonetheless, antibodies specific for platelet alloantigens or HLA Class I antigens have the potential to eventually make the multi-transfused patient completely refractory to future transfusions.