Jay H. Herman

Clinical consequences of alterations in platelet transfusion dose: a prospective, randomized, double‐blind trial

BACKGROUND: The dose‐response relationship for platelet transfusion has become increasingly important as the use of platelet transfusion has grown.

Evaluation and management of postpartum hemorrhage : consensus from an international expert panel

Postpartum hemorrhage (PPH) remains one of the leading causes of maternal morbidity and mortality worldwide, although the lack of a precise definition precludes accurate data of the absolute prevalence of PPH.

Economic consequences of alterations in platelet transfusion dose: analysis of a prospective, randomized, double-blind trial

BACKGROUND : In recent years, decreasing financial resources led to the use of lower‐dose platelet components. However, the economic consequences of the use of such components have not been carefully studied.

RhIG for the treatment of immune thrombocytopenia: consensus and controversy (CME)

Anti‐D immune globulin (RhIG) is a front‐line option in North America for the treatment of immune thrombocytopenia (ITP) in children and adults. Recently, addition of a Food and Drug Administration‐mandated black box warning highlighted the risks of intravascular hemolysis, renal failure, and disseminated intravascular coagulation after anti‐D infusion, prompting concern within the medical community regarding its use. A working group convened in response to this warning to prepare a consensus document regarding the safety of RhIG because there has been no increased incidence of adverse events since the initial discovery of these reactions many years ago. The efficacy of anti‐D is well documented and only briefly reviewed. The estimated incidence and proposed mechanisms for the rare, major treatment‐related complications are discussed, and signal detection data associated with heightened risk of acute hemolytic reactions are presented. The importance of considering host factors, given the rarity of severe reactions, is emphasized. Safety profiles of parallel treatment options are reviewed. The working group consensus is that RhIG has comparable safety and efficacy to other front‐line agents for the treatment of children and adults with ITP. Safety may be further improved by careful patient selection.

Prevention of D sensitization after mismatched transfusion of blood components : toward optimal use of RhIG

Transfusion of D+ red blood cells (RBCs) into D− recipients, whether through whole blood, RBC, or platelet (PLT) transfusion, can lead to alloimmunization with associated risks of hemolytic reactions from subsequent mismatched transfusion. The incidence of D alloimmunization in various transfused patient populations may be different from that reported in normal subjects or in pregnancy, but prevention of D alloimmunization after mismatched transfusion can be achieved using RhIG. An optimal approach to the use of RhIG, however, has not been identified for the United States. Case histories and studies of volunteers reported over the past 40 years have established that alloimmunization to mismatched RBC transfusion can be successfully prevented with a dose of 20 µg of RhIG per 1 mL of D+ RBCs (per 2 mL of whole blood) when given within a window of opportunity that extends to at least 72 hours. Evidence from prospective studies of RhIG as a therapy for immune thrombocytopenic purpura suggests that such doses can be tolerably given by intravenous injections over short periods, with adverse event rates minimized when pretransfusion medication is given. For mismatched PLT transfusions, the lowest dose of standard preparations of RhIG (e.g., 125 or 300 µg) should be sufficient to prevent alloimmunization given the small D+ RBC volumes involved. This article reviews how our understanding of prevention of alloimmunization in mismatched transfusion has progressed over the years and outlines some practical considerations based on the currently available evidence.

Considerations in the Selection of a Platelet Component: Apheresis Versus Whole Blood-Derived

ASIC CONCEPTS in platelet transfusion continue to be debated in the absence of reliable scientific observations with which to direct this therapy. The relationship between platelet count and bleeding risk, and the cofactors that affect that relationship, are only superficially understood. ~ Fundamental issues such as indications, component selection, and preparation are controversial. 2,3 What constitutes an optimal platelet dose remains an outstanding question, as does what type of platelet component to use. Recent publications have recommended exactly opposite practices--transfusion of larger numbers of platelets at longer intervals, or support with small, frequent doses--to achieve the best control of thrombocytopenic bleeding. 4-6 It is no wonder that platelet transfusion practices are still based on tradition and experience and are

Lack of effect of donor-recipient ABO mismatching on outcome following allogeneic hematopoietic stem cell transplantation.

Several recently published studies have suggested that patients who undergo ABO mismatched hematopoietic stem cell transplantation may be at increased risk for relapse, graft-versus-host disease, transplant-related mortality, and/or all-cause mortality. To investigate this issue further, we analyzed potential associations between the donor–recipient ABO mismatch pattern and the above outcome measures among 240 consecutive patients who underwent allogeneic hematopoietic stem cell transplantation at our institution. Our analyses uncovered no significant associations between donor–recipient ABO mismatch pattern and overall survival, event-free survival, transplant-related mortality, incidence of acute graft-versus-host disease (GVHD), or incidence of chronic GVHD. Our data do not support recent assertions that donor–recipient ABO mismatching is a major risk factor for patients undergoing allogeneic transplant, nor do they support recent assertions that ABO matching should be an important consideration in selecting allogeneic hematopoietic stem cell donors.

Early‐Onset Heparin‐Induced Thrombocytopenia After a 165‐Day Heparin‐Free Interval: Case Report and Review of the Literature

Early‐ or abrupt‐onset immune‐mediated heparin‐induced thrombocytopenia (HIT) is defined as HIT that occurs less than 5 days after exposure to heparin in patients who have received heparin within the previous 100 days. We identified no reports in the literature of early‐onset HIT in patients who had a heparin‐free interval longer than 100 days. However, we report a case of early‐onset immune‐mediated HIT illustrated by a positive HIT result with serotonin release and enzyme‐linked immunosorbent assays, and a decrease in platelet count to less than 100 times 103/mm3 with no evidence of thrombosis, approximately 165 days after the patients last exposure to heparin. We conclude that clinicians should choose alternative forms of anticoagulation in patients with even a remote history of HIT. If clinicians are compelled to reexpose patients to heparin, they should confirm a negative HIT assay result, monitor for clinical signs of HIT, and provide appropriate treatment if HIT is suspected.

Transfection of Human Platelets with Short Interfering RNA

Platelets contain mRNAs and are capable of translating mRNA into protein, and it has been previously demonstrated that platelets increase their levels of integrin β3 overtime while in blood bank storage conditions. We are unaware of prior attempts to introduce nucleic acids into platelets. Considering the potential clinical and research utility of manipulating platelet gene expression, we tested whether small interfering RNAs (siRNAs) could be transfected into normal human platelets. Multiple conditions were tested, including lipofectamine versus electroporation, different amounts of siRNA, the effect of different buffers and the presence of plasma during transfection, and the time for optimal siRNA incorporation after transfection. Using flow cytometry to assess transfection efficiency, we found that optimal transfection was obtained using lipofectamine, washed platelets, and 400 pmoles siRNA. Cell sorting of transfected platelets suggested that the incorporated siRNA was able to knockdown the level of a targeted mRNA. This is the first ever demonstration that nucleic acids can be introduced directly into platelets, and offers proof of concept for manipulating gene expression in platelets by nonviral methods. Future technical improvements may permit improving the quality and/or lifespan of stored human platelets. Clin Trans Sci 2011; Volume 4: 180–182

Autoimmunity in transfusion babesiosis: a spectrum of clinical presentations.

Transfusion‐acquired babesiosis can be an asymptomatic or self‐limited febrile hemolytic illness in a healthy host. A persistent, relapsing, and/or fulminant course with the development of life‐threatening complications may be seen in immunocompromised or splenectomized patients. As in malaria, erythrocyte parasitemia is often associated with nonimmune hemolysis, and can be treated with erythrocytapheresis. Just as warm autoantibodies have been reported in malaria infection, the development of autoantibody‐mediated immune hemolysis has been reported in babesiosis. We treated a previously healthy male with multiple injuries from a motor vehicle accident necessitating massive transfusion. Late in the hospitalization, his blood smear revealed Babesia microti, confirmed by PCR study and serology. This was eventually traced to a unit of blood from an asymptomatic blood donor that was transfused during his initial trauma care. Specific antibiotic therapy was begun, and severe hemolysis from a high parasite burden required red blood cell exchange which led to rapid abatement of the hemolysis. He had a positive DAT (IgG with a pan‐reactive eluate) but no serum autoantibody. This persisted for 10 days following cessation of hemolysis, and became negative while still on antibiotics while his parasite burden became undetectable. Reports of autoimmunity associated with community acquired babesiosis often have severe hemolysis from their autoantibodies, but our case shows that autoantibodies may also follow transfusion‐acquired babesiosis. The nature of the autoantigen is unknown. J. Clin. Apheresis, 2010.