Wendy Lau

A comprehensive review of rFVIIa use in a tertiary care pediatric center.

Recombinant activated factor VII (rFVIIa) is a hemostatic agent developed for the treatment of bleeds in patients with hemophilia and inhibitors. Case reports/series document its growing use in patients without hemophilia. Such reports however do not accurately describe the proportion of rFVIIa used for various indications. We sought to document the complete use of rFVIIa at our institution over a 6‐year period (2000–2005).

Early Complications of Hyperleukocytosis and Leukapheresis in Childhood Acute Leukemias.

Hyperleukocytosis in children with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) is associated with early morbidity and mortality. The benefit from leukapheresis is controversial, and its complications are not well defined. We analyzed the frequency of early complications in children with ALL and AML presenting with white blood cell (WBC) count >100×109/L, and the type and frequency of complications related to leukapheresis. During a 12-year period, 84 of 634 (13%) ALL and 18 of 143 (12.5%) AML patients presented with hyperleukocytosis. Leukapheresis was performed in 18 ALL and 12 AML patients. The median initial WBC was 474×109/L in the leukapheresis group compared with 175×109/L in the nonleukapheresis group. Neurological leukostasis occurred in 6 ALL (7.1%) and 4 AML (22.2%) patients. Pulmonary leukostasis occurred in 16 ALL (19%) and 4 AML patients (22.2%). Neurological symptoms improved in few patients after leukapheresis, except in patients with very high WBC (>650×109/L in ALL and >400×109/L in AML). Leukapheresis improved respiratory symptoms in some patients but caused worsening symptoms in others. Early death was associated with neurological complications, AML diagnosis, and coagulopathy. Leukapheresis did not delay initiation of chemotherapy, nor did it impact early response to chemotherapy or long-term survival. Complications included femoral vein thrombosis, electrolyte imbalances, and hemodynamic instability, which were all reversible. The role of leukapheresis as a cytoreductive procedure in childhood hyperleukocytic leukemia remains to be well defined.

Glanzmann thrombasthenia platelets compete with transfused platelets, reducing the haemostatic impact of platelet transfusions

Glanzmann thrombasthenia (GT) is a severe, rare, predominantly mucocutaneous, autosomal recessive bleeding disorder. GT patients have normal platelet counts and morphology, but show absent/severely reduced platelet aggregation owing to defective function/absence of the fibrinogen receptor glycoprotein (GP) IIb-IIIa (integrin aIIbb3) (George et al, 1990; Nurden & Nurden, 2014). Management of GT involves preventing bleeds where possible plus the expeditious management of bleeds that do occur. For persistent or severe bleeding, despite use of local measures and non-specific haemostatic agents (e.g. anti-fibrinolytic agents) and/or recombinant factor VIIa (rFVIIa; NovoSeven, Novo Nordisk, Bagsværd, Denmark), or for patients undergoing major surgery, platelet transfusions are recommended (Poon et al, 2004). As GT patients have normal platelet counts, a post-transfusion platelet count is of limited predictive value to accurately assess the transfusion response, given normal fluctuations observed in platelet counts within all patients (Male et al, 2006). Thus, there is a need for an easily performed, readily available laboratory measure of the response to platelet transfusions in GT patients to ensure that the patient is not platelet refractory, particularly prior to surgery or when treating a lifethreatening bleed. Laboratory tests that can potentially be used to show improvement in primary haemostasis and/or platelet function include the bleeding time (Jennings et al, 1991), flow cytometry (Nurden et al, 2002; Cesar & Vecino, 2009), and global haemostatic assays, such as thromboelastography or thrombin generation assays (Male et al, 2006). However, these tests suffer from lack of availability and reproducibility, and they do not provide a quick turnaround result as would be required in acute situations. We evaluated the Platelet Function Analyser (PFA-100 ; Siemens, Malvern, PA, USA) as a possible laboratory measure of response to platelet transfusions in four patients with GT (Carcao et al, 1998; Favaloro, 2008). Institutional ethics approval was obtained to conduct the study. All patients (Table I) showed the typical aggregation response defects seen in GT, lacked CD41 (GPIIb) by flow cytometry and were compound heterozygotes for ITGA2B. These four patients underwent PFA-100 testing after platelet transfusions on seven separate occasions for bleeding that failed to respond to local measures along with repeated infusions of rFVIIa and tranexamic acid (five episodes) and prior to wisdom teeth extraction (two episodes) (Table I). For all seven platelet transfusions, no apparent reduction (i.e. improvement) in PFA-100 closure times (CTs) posttransfusion was observed. We assessed whether this lack of improvement in CTs in some of the episodes was due to: (i) low haemoglobin levels, secondary to acute blood loss; or (ii) to the presence of anti-platelet antibodies that caused the patients to be platelet refractory. With respect to these possibilities, it should be noted that in 3/7 episodes, patients demonstrated normal haemoglobin levels and that all four patients had undergone multiple screening tests for the presence of anti-platelet antibodies [both anti-human leucocyte antigen (HLA) and anti-GPIIb-IIIa] using a qualitative solid phase enzyme-linked immunosorbent assay (PAK 12 by GTI diagnostics, Waukesha, WI, USA) designed to detect antibodies to HLA class I antigens and to platelet GPIIb-IIIa, GPIaIIa and GPIb-IX. On all 13 occasions, patients tested negative for anti-HLA and anti-glycoprotein antibodies. Given these results, it is extremely unlikely that the lack of improvement in PFA-100 CTs could have been caused by anti-platelet antibodies. GT patients, when transfused with a standard amount of either pooled or aphaeresis platelets (10 ml/kg; approximately 10 9 10 platelets/kg) will have both circulating endogenous GT platelets and transfused ‘normal’ platelets. Using flow cytometry, Cesar and Vecino (2009) reported that after a single platelet transfusion in a 10-year-old girl with GT, only 17% of circulating platelets were the transfused normal platelets. Consequently, when GT patients are given a standard platelet transfusion in the setting of a bleed, most of the platelets adhering to the injury site will still be the endogenous GT platelets as these are in the majority and not the transfused normal platelets. In this situation, we hypothesize that the GT platelets, that are capable of adhering to sites of vascular injury but then are

Randomized controlled trial of short-term withdrawal of i.v. immunoglobulin therapy for selected children with human immunodeficiency virus infection.

Background: The aim of the present paper was to determine whether monthly i.v. immunoglobulin (IVIG) could be safely discontinued in antiretroviral‐treated human immunodeficiency virus (HIV)‐infected children.

Peanut and fish allergy due to platelet transfusion in a child

An 8-year-old boy with no history of allergies received craniospinal radiation and cycles of autologous transplantations, which included chemotherapy and blood product support, for the treatment of medulloblastoma. A few weeks after his third cycle, he experienced anaphylaxis within 10 minutes after

Utilization of frozen plasma, cryoprecipitate, and recombinant factor VIIa for children with hemostatic impairments: An audit of transfusion appropriateness

Blood transfusions and fractionated products are not without risk and may lead to acute and long‐term adverse events. The objective of this study was to evaluate the appropriateness of usage of frozen plasma (FP), cryoprecipitate (CRYO), and recombinant factor VIIa (rVIIa) in a pediatric setting.

ABO zygosity, but not secretor or Fc receptor status, is a significant risk factor for IVIG-Associated hemolysis

TO THE EDITOR: Although frequently effective[1][1],[2][2] and usually benign, high-dose (2 g/kg) intravenous immunoglobulin (IVIG) therapy can result in marked red blood cell (RBC) hemolysis, which in some cases is life threatening in severity.[3][3][⇓][4]-[5][5] The mechanism by which this

Interphase cytogenetic analysis of clonality in peripheral blood cells from a patient with Down syndrome and acute megakaryoblastic leukemia

A combination of fluorescence-activated cell sorting and interphase fluorescence in situ hybridization (FISH) techniques was used to detect a clonal chromosomal marker in blasts, granulocytes, and T and B lymphocytes of the peripheral blood from a patient with Down syndrome and acute megakaryoblastic leukemia (AMKL) associated with trisomy 8 as a karyotypic abnormality. Immunophenotypic studies with flow cytometry showed two populations of leukemic blasts distinguished by their expression of the CD34 antigen. Interphase FISH studies revealed clonal trisomy 8 FISH signals in almost all blast cells, regardless of CD34 expression, as well as in a small subpopulation of granulocytes. Normal chromosome 8 signal patterns were detected in T and B cells and in a great majority of granulocytes. The present study provides evidence for the clonal involvement of leukemic blasts in AMKL of Down syndrome, indicating that a trisomy 8 abnormality may be a primary event in leukemogenesis. The transformation occurs in progenitor cells with limited myeloid differentiation and without involvement of lymphoid lineage cells.

Specific IgEs passively transferred through a platelet transfusion caused two discrete allergic reactions to food

Case report A non-atopic 8 year old boy received multiple blood product transfusions as part of his treatment for meduloblastoma. He subsequently experienced anaphylaxis to salmon. Within minutes of eating salmon, he developed angioedema of the lip, facial erythema, throat discomfort and low blood pressure. Before this episode, he regularly ate fish with no reaction. The passive transfer of food specific IgE was suspected and he was advised to carry an epinephrine auto-injector and avoid all vertebrate fish. Specific IgE to salmon by ImmunoCAP was positive. Follow-up was arranged to follow his specific IgE to salmon with the expectation that his allergy would resolve. One week after his anaphylactic episode to fish, he developed an allergic reaction to peanuts. He ate a chocolate peanut butter cup and within 10 minutes he vomited, developed angioedema of the lip and experienced lethargy. Previously, he routinely ate peanuts without any symptoms. Skin prick testing showed positive results to peanut, salmon, mixed fish, and tree nut mix. He had a positive ImmunoCAP to peanut. Approximately 6 months later, he had undetectable ImmunoCAP results to both salmon and peanut. He resumed consumption of salmon and peanuts with no reaction. As part of the adverse event investigation by Canadian Blood Services all donors associated with the reaction were contacted and one donor stated that they have a severe allergy to peanuts, tree nuts, shellfish, and all fish including salmon. This information implicated one specific pooled platelet transfusion in which the platelets were suspended in the plasma of the atopic donor. The donor has been excluded from future donations. Conclusions