Search

Autoimmune heparin-induced thrombocytopenia (aHIT) indicates the presence in patients of anti-platelet factor 4 (PF4)-polyanion antibodies that are able to activate platelets strongly even in the absence of heparin (heparin-independent platelet activation). Nevertheless, as seen with serum obtained from patients with otherwise typical heparin-induced thrombocytopenia (HIT), serum-induced platelet activation is inhibited at high heparin concentrations (10-100 IU mL -1 heparin). Furthermore, upon serial dilution, aHIT serum will usually show heparin-dependent platelet activation. Clinical syndromes associated with aHIT include: delayed-onset HIT, persisting HIT, spontaneous HIT syndrome, fondaparinux-associated HIT, heparin 'flush'-induced HIT, and severe HIT (platelet count of < 20 × 10 9  L -1 ) with associated disseminated intravascular coagulation (DIC). Recent studies have implicated anti-PF4 antibodies that are able to bridge two PF4 tetramers even in the absence of heparin, probably facilitated by non-heparin platelet-associated polyanions (chondroitin sulfate and polyphosphates); nascent PF4-aHIT-IgG complexes recruit additional heparin-dependent HIT antibodies, leading to the formation of large multimolecular immune complexes and marked platelet activation. aHIT can persist for several weeks, and serial fibrin, D-dimer, and fibrinogen levels, rather than the platelet count, may be helpful for monitoring treatment response. Although standard anticoagulant therapy for HIT ought to be effective, published experience indicates frequent failure of activated partial thromboplastin time (APTT)-adjusted anticoagulants (argatroban, bivalirudin), probably because of underdosing in the setting of HIT-associated DIC, known as 'APTT confounding'. Thus, non-APTT-adjusted therapies with drugs such as danaparoid and fondaparinux, or even direct oral anticoagulants, such as rivaroxaban or apixaban, are suggested therapies, especially for long-term management of persisting HIT. In addition, emerging data indicate that high-dose intravenous immunoglobulin can interrupt HIT antibody-induced platelet activation, leading to rapid platelet count recovery., (© 2017 International Society on Thrombosis and Haemostasis.)

Background: The THERAFLEX UV-Platelets pathogen reduction system for platelet concentrates (PCs) operates with ultraviolet C light (UVC; 254 nm) only without addition of photosensitizers. This phase I study evaluated safety and tolerability of autologous UVC-irradiated PCs in healthy volunteers., Methods: Eleven volunteers underwent two single (series 1 and 2) and one double apheresis (series 3). PCs were treated with UVC, stored for 48 h and retransfused in a dose-escalation scheme: 12·5, 25% and 50% of a PC (series 1); one complete PC (series 2); two PCs (series 3). Platelet counts, fibrinogen, activated partial thromboplastin time, prothrombin time, D-dimer, standard haematology, temperature, heart rate, blood pressure and clinical chemistry parameters were measured. One- and 24-h corrected count increments were determined in series 2 and 3. Platelet-specific antibodies were assessed before and at the end of the study., Results: Neither adverse reactions related to transfusions nor antibodies against UVC-treated platelets were observed. Corrected count increments did not differ between series 2 and 3., Conclusions: Repeated transfusions of autologous UVC-treated PCs were well tolerated and did not induce antibody responses in all volunteers studied. EudraCT No. 2010-023404-26., (© 2015 International Society of Blood Transfusion.)

Background: The anti-platelet factor 4 (PF4)/heparin immune response, which underlies heparin-induced thrombocytopenia (HIT), has several atypical features: relatively rapid onset even without previous heparin exposure, lack of immune anamnesis, and transience of antibody production., Study Design and Methods: We modified the enzyme-linked immunosorbent spot (ELISPOT) assay to investigate for PF4/heparin-specific memory B cells in cardiac surgery patients, in whom the high anti-PF4/heparin immunization rate made a prospective study feasible. The PF4-containing antigen complexes were attached to microtiter plates via a spacer, rather than using nitrocellulose, and the final reaction enzyme substrate was added in melted agarose which, after rapid hardening, localized color development of enzyme-tagged anti-immunoglobulin G (IgG) probes to single PF4/heparin-specific B cells. This modified ELISPOT assay was applied to 58 consecutive patients (testing blood from preoperative baseline and Postoperative Days 6 and 10), in which we compared detectability of PF4/heparin-specific B cells to tetanus toxin-specific B cells (comparator group with presumed vaccination)., Results: No patient had detectable PF4/heparin-specific memory B cells at baseline. In 2 of 30 patients (6.7%) who formed anti-PF4/heparin IgG, PF4/heparin-specific memory B cells (three to four spots/well) were detected by Postoperative Day 10, whereas tetanus toxin-specific memory B cells were found in 12 of 24 (50.0%) patients tested (3-25 spots/well; p < 0.001)., Conclusions: HIT lacks a strong memory B-cell response, perhaps explaining transience and lack of anamnesis of the anti-PF4/heparin immune response. The technical modifications we describe for the ELISPOT assay, which permit detection of B-cell reactions to complex antigens, could be useful for studying other immunohematologic disorders, for example, drug-dependent thrombocytopenia and acquired hemophilia.

The article reports that the immunotherapeutic strategies are emerging as novel therapeutic approaches in multiple myeloma with several monoclonal antibodies being in advanced stages of clinical development. CD38 targeting antibodies are promising and some of them are in the market in many countries. Therapeutic CD38-targeting antibodies were shown to interfere with pretransfusion laboratory tests due to weak expression of CD38 on human erythrocytes.