How anti-c in a D- patient prompted lifesaving work between a transfusion service and a blood center reference laboratory.

This case report showcases an extraordinary collaboration to support the transfusion needs of a patient with a rare phenotype and long-standing anemia due to gastrointestinal bleeding. This report describes the Immunohematology Reference Laboratory testing and logistics of rare blood provision over an 11-year period, as well as a summary of the hematologic, gastroenterologic, and surgical interventions. This case illustrates how a strong collaboration among the clinical team, laboratory, blood center, and the rare donor community facilitated successful management of this patient's anemia until the patient could receive life-changing treatment.

Examining intrafamilial communication of colorectal cancer risk status to family members and kin responses to colonoscopy: a qualitative study.

Background: First-degree relatives (FDRs) of probands with colorectal cancer (CRC) may be at increased risk of CRC and require colonoscopy. Proband disclosure about this risk and need for colonoscopy is essential for FDRs to take appropriate action. Low colonoscopy rates are reported among FDRs and little is known about the proband disclosure process.

HCMV DNA detection and quantitation in the plasma and PBL of lung transplant recipients: COBAS Amplicor HCMV monitor test versus in-house quantitative HCMV PCR.

Background: Human cytomegalovirus (HCMV) reactivation may cause severe disease in immunosuppressed patients. Quantitation of HCMV viral load in the blood has been shown to be important in predicting for HCMV disease, however the particular blood compartment that should be tested, plasma versus peripheral blood leukocytes (PBL), has been subject to debate.

Objectives: To simultaneously compare HCMV viral loads in the PBL using an in-house quantitative HCMV polymerase chain reaction (PCR) assay and in the plasma using the commercially available COBAS Amplicor HCMV monitor test, in a cohort of lung transplant recipients (LTR).

Discrimination of von Willebrands disease (VWD) subtypes: direct comparison of von Willebrand factor:collagen binding assay (VWF:CBA) with monoclonal antibody (MAB) based VWF-capture systems.

Discrimination of von Willebrand's Disease (VWD) subtypes is important since it influences management. Qualitative [ie Type 2A, 2B, 2M] defects exhibit von Willebrand factor (VWF) discordance and give high VWF:Ag to VWF:'activity' ratios. Classically, VWF:'activity' is assessed using the VWF:RCof assay.

Type 2B von Willebrand's disease in thirteen individuals from five unrelated Australian families: phenotype and genotype correlations.

Type 2B von Willebrand's disease (VWD) is due to a qualitative defect in von Willebrand factor (VWF) in which there is an increased affinity for the platelet glycoprotein Ib-IX-V receptor complex. Spontaneous binding of type 2B VWF to platelets and subsequent clearance from the plasma is thought to account for the characteristic phenotype of type 2B VWD. These gain-of-function mutations are due to single amino substitutions that are clustered within the functionally important A1 domain of VWF.

Structure and function of the von Willebrand factor A1 domain: analysis with monoclonal antibodies reveals distinct binding sites involved in recognition of the platelet membrane glycoprotein Ib-IX-V complex and ristocetin-dependent activation.

Binding of the adhesive glycoprotein, von Willebrand factor (vWf), to the platelet membrane glycoprotein (GP) Ib-IX-V complex initiates platelet adhesion and aggregation at high shear stress in hemostasis and thrombosis. In this study, the GP Ib-IX-V binding site within the vWf A1 domain was analyzed using a panel of murine monoclonal antibodies raised against a 39/34-kd vWf fragment (Leu-480/Val-481-Gly-718) encompassing the A1 domain. One antibody, 6G1, strongly inhibited ristocetin-dependent vWf binding to platelets, but had no effect on botrocetin- or jaracetin-dependent binding, or asialo-vWf-dependent platelet aggregation.

Use of a novel platelet function analyzer (PFA-100) with high sensitivity to disturbances in von Willebrand factor to screen for von Willebrand's disease and other disorders.

The PFA-100 is a new platelet function analyzer which uses whole blood and high shear stress blood flow to simulate primary hemostasis and assess platelet function. A small volume of blood is introduced into a disposable cartridge, and forced through a capillary tube. Platelet adhesion and aggregation is then initiated following exposure to either collagen/ADP [C/ADP] or collagen/epinephrine [C/Epi] coated membranes.

Identification and characterization of a novel mutation in von Willebrand factor causing type 2B von Willebrand's disease.

Type 2B von Willebrand's disease (VWD) is a variant in which the structurally abnormal von Willebrand factor (VWF) has an increased affinity for the platelet glycoprotein Ib-IX-V complex. Spontaneous binding of type 2B VWF to platelets and their subsequent clearance from the plasma appear to account for the characteristic phenotype of type 2B VWD. Several type 2B mutations have been described and shown to be grouped along the amino edge of the beta sheet of the VWF A1 domain.

The molecular mechanism of platelet adhesion.

One of the most primitive of host-defence mechanisms is haemostasis, the ability to control blood loss. In response to vascular trauma, platelets rapidly adhere to the exposed subendothelial matrix, a process that ultimately results in the sealing of the vessel by a plug of platelets stabilised by fibrin. Paradoxically, it is the same cascade of events that leads to thrombosis and vessel occlusion, resulting in heart attack and stroke.

Laboratory assessment of von Willebrand factor. Use of different assays can influence the diagnosis of von Willebrand's disease, dependent on differing sensitivity to sample preparation and differential recognition of high molecular weight VWF forms.

Three separate laboratory assays for von Willebrand Factor (VWF), a standard "antigen" (antisera-ELISA-based) assay (VWF:Ag), a standard ristocetin-dependent-platelet-agglutination procedure (VWF:RCof), and an ELISA-based collagen-VWF binding assay (VWF:CBA), have been evaluated for their ability to detect alterations in VWF levels following differential processing of blood for testing, and specifically in (1) serum compared to plasma and (2) filtered plasma compared to nonfiltered plasma. Although all assays tended to detect some change, sensitivity of detection varied between assays, with the VWF:CBA most consistently able to detect large decreases in VWF levels in serum and filtered plasma. The authors propose that the increased sensitivity of the VWF:CBA assay to VWF depleted in these circumstances is that this assay selectively detects higher molecular weight forms (ie, those known to be more functionally relevant), and that assay results reflect the preferential incorporation of these forms in in the platelet-fibrin-gel during the clotting process, and onto the filter matrix during filtration.

CD13 (GP150; aminopeptidase-N): predominant functional activity in blood is localized to plasma and is not cell-surface associated.

This study is the first to report the presence of CD13/glycoprotein 150 (GP150)/aminopeptidase-N activity in cell-free plasma. We have determined that aminopeptidase-N in plasma provides, quantitatively, aminopeptidase-N's predominant functional activity within flowing blood. Thus, while aminopeptidase-N activity observed in whole blood can be partly, but significantly, blocked by the CD13 monoclonal antibody (MAB) WM15, the magnitude of such inhibition is low (< 25%) and similar to that observed using washed cell fractions selectively enriched for neutrophils (30.