Mechanical circulatory support is associated with loss of platelet receptors glycoprotein Ibα and glycoprotein VI.

Essentials Relationship of acquired von Willebrand disease (VWD) and platelet dysfunction is explored. Patients with ventricular assist devices and on extracorporeal membrane oxygenation are investigated. Acquired VWD and platelet receptor shedding is demonstrated in the majority of patients. Loss of platelet adhesion receptors glycoprotein (GP) Ibα and GPVI may increase bleeding risk. SUMMARY: Background Ventricular assist devices (VADs) and extracorporeal membrane oxygenation (ECMO) are associated with bleeding that is not fully explained by anticoagulant or antiplatelet use. Exposure of platelets to elevated shear in vitro leads to increased shedding. Objectives To investigate whether loss of platelet receptors occurs in vivo, and the relationship with acquired von Willebrand syndrome (AVWS). Methods Platelet counts, coagulation tests and von Willebrand factor (VWF) analyses were performed on samples from 21 continuous flow VAD (CF-VAD), 20 ECMO, 12 heart failure and seven aortic stenosis patients. Levels of platelet receptors were measured by flow cytometry or ELISA. Results The loss of high molecular weight VWF multimers was observed in 18 of 19 CF-VAD and 14 of 20 ECMO patients, consistent with AVWS. Platelet receptor shedding was demonstrated by elevated soluble glycoprotein (GP) VI levels in plasma and significantly reduced surface GPIbα and GPVI levels in CF-VAD and ECMO patients as compared with healthy donors. Platelet receptor levels were also significantly reduced in heart failure patients. Conclusions These data link AVWS and increased platelet receptor shedding in patients with CF-VADs or ECMO for the first time. Loss of the platelet surface receptors GPIbα and GPVI in heart failure, CF-VAD and ECMO patients may contribute to ablated platelet adhesion/activation, and limit thrombus formation under high/pathologic shear conditions.

Prothrombin complex concentrates used alone in urgent reversal of warfarin anticoagulation.

BACKGROUND: Prothrombinex-VF (a three-factor prothrombin complex concentrate) contains little factor VII. Therefore, the Warfarin Reversal Consensus Guidelines from 2004 published by The Australasian Society of Haemostasis and Thrombosis recommend that it be administered with fresh frozen plasma to reverse warfarin anticoagulation. AIM: To evaluate the efficacy and safety of Prothrombinex-VF used alone in warfarin reversal. METHODS: Adult patients requiring urgent reversal of warfarin anticoagulation were defined as having achieved complete (target international normalized ratio (INR) <1.4) or partial reversal (target INR 1.4-2.0) of their anticoagulation. Prothrombinex-VF was given at doses of between 25 and 50 IU/kg based on the intent of reversal and an INR was obtained 30min post infusion. RESULTS: A total of 50 patients (mean age 72years, range 32-85years) was included. The median initial INR in the complete reversal arm (n= 35) was 3.5 (range 1.7-20) with 91% achieving the target INR (mean 1.1, range 0.9-1.4). In the partial reversal arm (n= 15) the mean initial INR was 5.6 (range 2.5-12) with 93% achieving the target INR (mean 1.6, range 1.4-2.2). There were no adverse effects attributed to Prothrombinex-VF. CONCLUSIONS: Prothrombinex-VF is very effective and safe when used alone to reverse warfarin anticoagulation. The supplementary use of fresh frozen plasma in these patients is not required. A review of the current Warfarin Reversal Consensus Guidelines is needed.

Laboratory testing, diagnosis, and management of von Willebrand disease. Current practice in Australasia. RCPA Quality Assurance Program in Haematology Scientific Haemostasis Advisory Panel.

We report an evaluation of current laboratory and clinical practice for the diagnosis and management of von Willebrand disease (VWD) for a wide geographic area including Australia, New Zealand, and parts of Southeast Asia. This assessment has been undertaken in conjunction with the RCPA Quality Assurance Program (QAP) in Haematology. This external QAP currently comprises around 550 participating laboratories, of which some 450 perform coagulation testing, and from which 32 laboratories were identified to be actively involved in testing for VWD. These laboratories were targeted and their current laboratory and clinical practice evaluated by using various questionnaires. Our overall findings indicate a wide variation in laboratory test practice for VWD-based investigations. There was considerable variation among laboratories in the tests and test methods used, the control and calibration material used, the reported test reference intervals and units used, and the composite test panels used to diagnose VWD. However, substantial consensus in the clinical evaluation process, as undertaken by hematologists, also was identified. Despite the observed variations, most laboratory professionals seemed to understand the complexities involved in the diagnosis and subclassification of VWD, and the laboratories can provide an effective diagnostic service.

Chlorpromazine-associated haemolysis in anorexia nervosa.

Chlorpromazine therapy in a patient with anorexia nervosa was associated with haemolytic anaemia. In vitro red cell findings included an increased degree of red cell autohaemolysis and a chlorpromazine-dependent Heinz body formation both corrected with exogenous glucose. Activities of red cell enzymes involved with the glycolytic pathway or glutathione metabolism were normal.

Dehydrated hereditary stomatocytosis--a report of two families and a review of the literature.

Two families with an unusual type of congenital hemolysis characterized by a normal to high hemoglobin, high reticulocyte count, the presence of target cells or small irregular cells on the peripheral blood smear, and bowl shaped cells in hypotonic wet preparations are described. The underlying abnormality appears to be an increased membrane permeability to both Na+ and K+, with consequent alteration of total cell cation and water content. Seven families previously reported are also reviewed. The entity is currently known as hereditary stomatocytosis with hydrated and dehydrated subtypes, but the diagnosis is frequently overlooked because of the variable morphology of the red cells, often without obvious stomatocytosis.

Alteration of human red blood cells stored in plastic packs. A case report with in vivo and in vitro studies.

An alteration of human red blood cells while stored in certain types of plastic packs occurs to such an extent that some patients' sera are incompatible with these altered cells. This report gives details of in vivo and in vitro studies in one such case. Our results indicate a significantly shortened red blood cell survival and a marked increase in antibody titer.