Prolonged platelet preservation by transient metabolic suppression

Abstract

Introduction: Different clinical studies have shown that transfusion of stored platelets results in better haemostasis in patients with thrombocytopenia with and without a platelet function defect.

Objectives: Current preservation procedures aim to optimally preserve the metabolic status of platelets during prolonged storage at 4°C. Currently most Blood banks isolate and store platelet concentrates (PC's) at 22°C. Working at room temperature, has several advantages. It is obviously very simple, and the survival of PC's post transfusion is higher than with chilled-rewarmed PLTs. These advantages are useful when the blood banks and hospitals have enough patients to use freshly isolated PC's immediately. However, there is never a so called 'demand-supply balance' between the blood banks and hospitals. When more PC's are supplied than demanded, blood banks have to store PC's for sometime.

Storage at room temperature has also dis-advantages. Currently, with PC's stored at room temperature for more than 5 days there is the problem of microbial multiplication. This is the reason that so that the FDA limits the storage time to less than 5 days. Another pitfall of storage at room temperature is that it introduces changes in platelets indicative for premature activation, and in GPIb damages and initiation of apoptosis. Improvements have been sought in lowering the storage temperature to below 4°C (in the presence of glucose) but this treatment severely reduces the survival of transfused platelets. A main feature of platelet chilling-rewarming is the gradual increase in the sphere to disc shape change, actin assembly, a gradual increase in [Ca2+]i concomitant with spontaneous agglutination, insensitivity to disaggregating agents, and GPIb clustering.

This thesis describes how metabolic suppression improves the preservation of platelet function during prolonged storage. The mechanism of arrest of energy generation prior to cold storage is described (Chapter 2); and how transient metabolic blockade prior to cold storage might be involved in the delay of apoptotic activities and their correlations to platelet binding and phagocytosis (Chapter 3). Furthermore, the different steps in the mechanism of stimulus response coupling are discussed in relation to the role of P-selectin expression, changes in GPIbα expression and PS exposure (Chapter 4). After introduction of metabolic suppression in absence of metabolic inhibitors we adjusted metabolic suppression to conditions compatible with blood bank procedures (Chapter 5). Finally the pilot studies in the blood banks revealed that our developed metabolic suppression prior to cold better preserves platelet functions compared to controls after 18 days storage.