Ashok Tholpady

Analysis of prolonged storage on coagulation Factor (F)V, FVII, and FVIII in thawed plasma: Is it time to extend the expiration date beyond 5 days?

BACKGROUND: According to AABB standards, fresh‐frozen plasma (FFP) should be thawed at 30 to 37°C and expire after 24 hours. An increase in the aggressive management of trauma patients with thawed plasma has heightened the risk of plasma waste. One way to reduce plasma waste is to extend its shelf life, given that the full range of therapeutic efficacy is maintained. We evaluated the effect of prolonged storage at 1 to 6°C on the activity of Factor (F)V, FVII, and FVIII in plasma thawed at 37 or 45°C.

Systemic hypersensitivity reaction mimicking anaphylaxis after first filgrastim administration in a healthy donor

Recombinant human granulocyte–colony-stimulating factor (rHuG-CSF) is approved for use to accelerate neutrophil recovery after myelosuppressive therapy and to mobilize hematopoietic progenitor cells from the marrow into the blood to facilitate peripheral blood stem cell (PBSC) collection. Commercially available forms of G-CSF include filgrastim (Neupogen, Amgen, Thousand Oaks, CA) and lenograstim (Granocyte, Chugai, Tokyo, Japan), both of which are manufactured by recombinant DNA technology. Filgrastim is a nonglycosylated Escherichia coli–derived 175-amino-acid glycoprotein with an extra N-terminal methionine group, and lenograstim is a Chinese hamster ovary–derived 174-amino-acid glycoprotein with 4% carbohydrate, indistinguishable from native G-CSF. Modest and reversible side effects of rHuG-CSF are common, including bone pain, myalgias, and headache. More severe adverse effects, including splenic rupture, have been described in a handful of healthy donors.1 Anaphylactoid episodes associated with a first dose of rHuG-CSF in healthy donors have only been reported twice, once after filgrastim and once after lenograstim,2,3 although additional reports of hypersensitivity reactions in patients receiving myeloablative therapy are described.4,5 In these latter cases, confounding effects of multiple concomitant drugs made attribution of causality uncertain. We describe a second case of severe systemic hypersensitivity reaction mimicking anaphylaxis after filgrastim administration in a healthy donor. A 17-year-old healthy Haitian female PBSC donor presented to the outpatient clinic to receive her first dose of filgrastim. She had no history of allergies and met all institutional criteria for sibling allogeneic stem cell donation. She received 720 mg (10 mg/kg) of filgrastim subcutaneously and remained in the clinic, feeling well, for 75 minutes. Fifteen minutes after leaving (90 min after the filgrastim injection), she developed difficulty breathing and throat tightness. She was transported back to clinic by wheelchair by her mother. Upon arrival, she complained of severe cramping abdominal pain and developed diarrhea with lightheadedness and extreme diaphoresis. She was tachycardic (pulse, 144) and hypotensive (80/40), with normal oxygen saturation and no rash. She rapidly became confused, then unresponsive, with an undetectable blood pressure. Intramuscular epinephrine and intravenous diphenhydramine, ranitidine, methylprednisolone, and saline were given. Her symptoms and vital signs stabilized rapidly and she was admitted for over-night observation, continuing to receive steroids and H1 and H2 receptor blockers every 8 hours. Serum tryptase, measured within 3 hours of the event, and 24-hour urinary N-methylhistamine were both within the reference range. She was discharged 30 hours after the incident without further sequelae. A severe anaphylactoid reaction to filgrastim in a healthy allogeneic donor has only been reported once in the past, 50 minutes after a first drug dose in a 16-year-old granulocyte donor whose symptoms and response to therapy were identical to those in our donor.2 Similar reactions have been reported in patients with malignancies after a first or subsequent filgrastim dose, but confounding conditions and medications rendered causality problematic.4,5 Prior sensitization to E. coli derivatives has been assumed to be the cause of these events, but one case of anaphylaxis after lenograstim has also been reported in a healthy donor,3 so that the inciting immunogen is uncertain. The cause of the reaction could be rHuG-CSF itself or another component of the drug preparation such as polysorbate 80 (Tween 80), which has been implicated in hypersensitivity reactions.6 The clinical course and response to therapy in our donor were consistent with an anaphylactoid event. However, laboratory testing with serum tryptase and urinary N-methylhistamine provided strong objective data that the reaction was not due to mast cell or basophil activation and degranulation. Our case serves as a reminder that filgrastim administration may be associated with severe hypersensitivity reactions mimicking anaphylaxis and that such reactions should be treated promptly with antianaphylaxis medications. Initial doses of filgrastim should be given in a monitored medical setting, followed by at least an hour of observation.

Therapeutic plasmapheresis and red blood cell exchange in a sickle cell trait patient with rhabdomyolysis.

We report a case of a 16‐year‐old African‐American male with sickle cell trait and a past medical history significant for asthma that was transferred to our hospital for management of respiratory failure. On the fourth day of hospitalization, the patient was found to have increased creatine kinase (CK) levels and urine myoglobin levels consistent with rhabdomyolysis. No clear etiology was identified. Aggressive standard hydration and urine alkalization were applied without response. On the sixth day of hospitalization, the patient underwent a 1–1.5 plasma volume therapeutic plasma exchange (TPE) resulting in a transient reduction of serum CK and myoglobin by 50%, which became elevated once again within 4 h. Since his clinical presentation resembles exertional rhabdomyolysis documented in patients with sickle cell trait, RBC exchange was performed. The patient tolerated the procedure without complications. In addition to his improved overall condition, the patients post‐exchange CK and serum myoglobin levels dropped dramatically without rebound. To our knowledge, this case represents the first reported case of TPE followed by RBC exchange in a SCT patient with rhabdomyolysis. J. Clin. Apheresis 2012.

Utility of bone marrow examination for workup of fever of unknown origin in patients with HIV/AIDS

Aims The utility of bone marrow aspiration and biopsy (BMAB) as a diagnostic tool in patients with HIV/AIDS and fever of unknown origin (FUO) is a subject of debate. Because highly active antiretroviral therapy has reduced incidence of opportunistic infections, it is important to reassess the efficacy of BMAB for this diagnostic purpose. To our knowledge, no such studies have been performed in Harris County which has the highest incidence of HIV in the state of Texas. Methods We reviewed all BMABs from patients with HIV/AIDS and FUO or persistent cytopenia(s) from 2007 to 2011. Results Of 57 evaluable patients, BMAB was positive in 24 samples by acid fast bacilli (AFB) or Gomori methenamine silver (GMS) stains (17.5%), presence of granuloma and/or lymphohistiocytic aggregates (31.6%), culture (21.0%) or a combination. Cultures demonstrated Mycobacterium avium/intracellulare (4), M tuberculosis (2), M gordonae (1), Histoplasma capsulatum (3) and Cryptococcus neoformans (2). There were three cases in which a pathogen was grown in culture but that had a negative of ‘direct examination’ on tissue sections (negative AFB and GMS special stains, no morphological evidence of granuloma/lymphohistiocytic infiltrates). Conclusions This study supports the use of diagnostic BMAB as a rapid decision-making tool in patients with HIV and FUO in the proper clinical setting. BMAB demonstrated infection-related evidence prior to positive bone marrow culture in 75% of cases. Special stains and blood cultures had similar diagnostic yield, but BMAB offers faster results. Thus, this procedure assists in clinical decision making and the refinement of treatment in a more timely manner.

High false-positive rate for monoclonal gammopathy using capillary electrophoresis (CAPILLARYS 2) alone

Capillary zone electrophoresis (CZE) is a newer method of performing serum protein electrophoresis and is considered to be faster and more efficient than agarose gel method. We decided to evaluate CZE as an efficient screening tool for monoclonal gammopathies, and we began recommending immunofixation studies in cases with such minor/subtle distortions to avoid missing monoclonal gammopathies.

Clinical and serological responses following plasmapheresis in bullous pemphigoid: Two case reports and a review of the literature

Plasmapheresis has been proven to be an effective treatment for a variety of conditions, especially those in which circulating antibodies are known or thought to be involved in pathogenesis. The current American Society For Apheresis (ASFA) guidelines1 make recommendations on 120 specific indications encompassing a total of 68 distinct disease processes. Among the autoimmune blistering disorders of the skin, pemphigus vulgaris is the sole entity included and plasmapheresis is considered a category IV indication (disorders in which published evidence demonstrates or suggests apheresis to be ineffective or harmful). In pemphigus vulgaris auto-antibodies are directed against the adhesion molecule desmoglein2, whereas in a related entity known as bullous pemphigoid (BP) auto-antibodies are targeted against the hemidesmosome components BP1803 and BP2304. Although no formal recommendation exists for BP, plasmapheresis has been deployed successfully as adjunctive therapy5–8. In describing our own institution’s recent experience in treating BP we add to the growing evidence supporting the use of plasmapheresis under appropriate conditions. We also include an examination of serial BP180 and BP230 titres measured by enzyme-linked immunosorbent assay (ELISA) during plasmapheresis therapy.

Preoperative autologous blood collection before bone marrow harvests in haploidentical related donors: Is it justified?

With the increasing safety of allogeneic blood supply and declining need for transfusion due to patient blood management, the practice of preoperative autologous donation (PAD) continues to decline. The practice gained popularity during the 1980s and 1990s with the emergence of transfusion‐transmitted human immunodeficiency virus and hepatitis C. At the peak of this public concern, the National Marrow Donor Program recommended that marrow donors have 1 to 3 autologous units of blood collected before their marrow harvest to minimize the likelihood of allogeneic transfusion. After three decades, the practice remains prevalent in marrow donors. We aimed to study the efficacy of PAD in healthy marrow donors.

Cancer type predicts alloimmunization following RhD-incompatible RBC transfusions

Immunosuppressed, RhD‐negative oncology patients tend to have lower rates of sensitization to the D antigen when they receive transfusion with RhD‐positive blood components. Clinical factors associated with alloimmunization to the D antigen in RhD‐negative oncology patients when they receive transfusion with RhD‐positive red blood cells (RBCs) have not been well defined.

Platelet aggregometry cannot identify uremic platelet dysfunction in heart failure patients prior to cardiac surgery

Patients with heart failure often have concomitant renal disease which can result in uremic platelet dysfunction. Determining whether uremia has affected platelets by platelet aggregometry can be challenging in these patients since they are often on antiplatelet medications. This study was undertaken to determine if platelet aggregation studies could identify heart failure patients at risk for uremic bleeding prior to cardiac surgery.

Use of an Intravascular Warming Catheter during Off-Pump Coronary Artery Bypass Surgery in a Patient with Severe Cold Hemagglutinin Disease.

Cold hemagglutinin disease with broad thermal amplitude and high titers presents challenges in treating cardiac-surgery patients. Careful planning is needed to prevent the activation of cold agglutinins and the agglutination of red blood cells as the patients temperature drops during surgery. We describe our approach to mitigating cold agglutinin formation in a 77-year-old man with severe cold hemagglutinin disease who underwent off-pump coronary artery bypass surgery without the use of preoperative plasmapheresis. This experience shows that the use of an intravascular warming catheter can maintain normothermia and prevent the activation and subsequent formation of cold agglutinins. To our knowledge, this is the first reported use of this technique in a patient with cold hemagglutinin disease. The chief feature in this approach is the use of optimal thermal maintenance-rather than the more usual decrease in cold-agglutinin content by means of therapeutic plasma exchange.