Servizio di Ematologia USL 58 - Palermo
Centro Ustioni USL 58 - Palermo, Italia

SUMMARY. Haemocoagulative complications after serious bums are a constant feature, and very often represent a considerable clinical problem. Our preliminary observations of 15 patients sent to us by the U.S.L. 58 Bums Centre indicate that the burn lesion gives rise to a series of haematological modifications, beginning with a phase of hypercoagulability immediately after the burn injury, followed by activation of fibrinolysis and finally a coagulative rebound. In some cases the appearance of shock, sepsis or the liberation into the bloodstream of tissue activators can precipitate an acute condition of intravascular coagulation, whose diagnostic predictability using the tests currently available for haemocoagulative studies is in any case uncertain, and possibly even controversial.
Among traditional tests an important place is occupied by the study of thromboeytosis and platelet function. Our efYorts are therefore now directed at the search for valid parameters which through simple and straightforward investigations will make it possible to make a more precise assessment of haemostatic disorders, with a view to preventing any subsequent more serious haemocoagulative imbalances. We therefore believe that the inclusion of tests for Protein C evaluation, 17PA and antifibrinolysins in standard laboratory protocol, together with the study of the bone marrow and RES clearance, when possible, will provide us with more useful and more complete data for better clinical surveillance and a more rational therapy.

Introduction

The modification of routine haemocoagulative parameters in burn pathology is a fairly common finding.
As a result of marked imbalances in haemostatic equilibrium, there may sometimes be cases of severe haemorrhage which represent a grave clinical problem, possibly even leading to the death of the burn victim.
The subject of this paper is the monitoring of the common haemocoagulative parameters and the interpretation of their modifications in the course of burn pathology.

Materials and methods

We studied 15 patients with burned BSA over 30%, aged between é and é5 years. All of these had 2nd or 3rd degree burns.
Blood samples were taken immediately upon admission, then every other day during the first 2 weeks and then weekly until the patient was discharged from the intensive care unit.
The blood was removed from the artery or vein and was placed in a test tube with K3 EDTA (1 mg/ml) for  haemochromocytometric study and platelet count, and in a test tube with Na Citrate 0.1 M (1:10) for prothrombin time (PT), activated partial thromboplastin time (aPTT) and fibrinogen. The Quick method (1) was used for PT, bovine cephalin and ellagic acid for aPTT, the Clauss method (2) for fibrinogen, and the latex method (3) for fibrinogen/fibrin degradation products (FDP). All haemocoagulative findings were obtained with the aid of an MLA Electra 750 semiautomatic coagulometer.

Results

Of the 15 patients studied, é died, 4 as a result of infective complications and 2 of kidney failure. Among the 9 survivors PT and aPTT remained within normal limits 48-72 hours after the burn lesion, then increased gradually to reach a peak between the 9th and 13th day. These values returned to normal in 2-3 weeks (Figs. 1, 2). Fibrinogen concentration was low in the first 24 hours, then increased progressively to a peak on day 9, returning to normal in the next 3 weeks (Fig. 3). The FDP were normal in the first 3-5 days after the burn and then remained at high values in the following 4 weeks, peaking between days 9 and 12 (Fig. 4). Initial thrombocytosis was followed by a rapid drop in the platelet count, which reached its lowest point on day 5, after which there was a gradual return to normality, or in some cases slightly higher than normal values, in the next 3-4 weeks.
In the 4 patients who died as a result of infective complications, we observed a progressive deterioration of the haemocoagulative parameters, especially with regard to thrombocytosis. These modifications of haemostatic equilibrium seemed to be connected with the onset of sepsis. In one case there was disseminated intravascular coagulopathy.

Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5

Discussion

The findings show that the haemocoagulative condition of the burn patients varied in relation to the modification of their physiopathological conditions.
In the first phase, in the hours immediately following the bum lesion, we observed a hypercoagulative modification due mainly to the massive liberation of thromboplastin tissue factors and to haemoconcentration.
During this phase we recorded thrombocytosis, normal MP, PT and aPTT values and hypofibrinogenaemia, the latter being due to increased consumption in the burned areas and to the sequestrum in the interstitial space.
This was followed by a phase of hypocoagulability beginning about the 2nd to the 5th day, during which period we recorded a lengthening of PT and aPTT, in relation to excessive peripheral utilization and to reduced synthesis of the coagulation factors; we also observed a drop in thrombocytosis, due to peripheral consumption and to a non regenerative bone marrow condition (4); hyperfibrinogenaemia, caused by increased synthesis and a reduction of losses (5) and also by pyrogens and other bacterial extracts, their efflect being mediated by the leukoeytes (é); and an increase in the FDP as a result of degradation of fibrin and fibrinogen at intravascular and interstitial level in the bum sites (5).
FDP concrentration remained above normal for most of the observation period, and we observed haemorrhagic manifestations in only one case; this parameter is thus only a rough guide to identifying the various haemocoagulative modifications following severe bums; FDP concentration is of greater significance in complicated cases of sepsis and shock, when accompanied by serious impairment of the other haemocoagulative parameters, particularly thrombocytopenia; however, even in this case, the finding is of poor predictive value as it comes too late.
This phase of fibrinolytic activation and of consumption lasted for variable periods, subsequently developing towards a return to conditions of normal coagulability, or to a new hypercoagulative phase for which a number of trigger mechanisms are responsible, such as endotoxins, circulating immunocomplexes, acidosis, hypoxia and a relatively inefficient RES clearance. Persistent thrombocytopenia is a negative prognostic sign, as the platelets, due to their rapid turnover, are an important warning signal of the degree of medullary inhibition and of the peripheral procoagulative stimulus (7).
Some other parameters, such as the concentrations of ATIll, FPA, Beta TBG, PF4, Protein C, D Dimers, t-PA and PK, have been introduced comparatively recently into laboratory practice. They help to cast light on the various phenomena that occur in haemostasis, regarding both coagulation and fibrinolysis; any modification of these parameters could be a warning signal of a condition which from an initial subclinical level might evolve towards a more serious condition like DIC.
The literature is beginning to describe the first limited data suggesting that some of these parameters ' in particular ATIII and PIC, might have some predictive value in the case of burn lesions (8).
The purpose of our ongoing study is to identify, if possible, among the data that will accumulate from a routine use of these tests a correlation with the survival of burn patients.
Also, whenever it is possible to perform tests on patients in a condition of general anaesthesia, the haemotopoietic condition will be examined by means of multiple needle aspirations and needle biopsies of bone marrow, the efficiency of RES clearance being checked at the same time.
We hope that these procedures will provide us with information on the basis of which it will be possible to draw up a protocol of clinical and laboratory control enabling us to formulate predictions regarding haemocoagulative conditions, i.e. to foresee the turning point towards conditions of hypercoagulation when there is still time to initiate correct therapy.

RÉSUMÉ. Les altérations hémo-coagulatrices au cours d'une grave brûlure sont constantes et représentent souvent un probl&me clinique considérable.
Nos observations préliminaires sur 15 patients que le Centre des Brûlés USL 58 nous a envoyés conduisent a reconnaitre dans la brûlure une dynamique des modifications hématologiques ou a une phase d'hypercoagulation, immédiatement aprés I'accident, suit une activation de la production de fibrine et enfin un "rebound" coagulateur. En certains cas, un choc, une septicémie ou la libération d'activateurs du tissu peuvent accélérer une condition aigiie de coagulation intra-vasculaire, dont le diagnostic n'est pas aisé a prévoir avec les tests dont on dispose actuellement pour 1'étude hémo-coagulatrice.
Parmi les tests traditionnels, 1'étude du nombre des plaquettes et de la foriction plaquettaire occupe une place importante. Par conséquent nos efforts se tournent actuellement vers la recherche de paramétres valables, à travers des enquétes d'exécution simple et rapide, de maniére à consentir une estimation plus précise des troubles hémostatiques pour prévoir d'éventuels déséquilibres graves en matiére d'hémo-coagulation. Nous retenons en outre qu'il faut introduire des tests pour évaluer la protéine C, les FPA, et les antiplasmines dans le contréle de laboratoire, parallélement à l'étude de la moelle osseuse et de la clearance du SRE, chaque fois que ce sera possible, pour nous fournir des indications plus complétes et utiles pour une surveillance clinique meilleure et une thérapic plus rationnelle.