Biological changes following infusion of recombinant hirudin (HBW 023) in 10 patients with severe thromboembolism

ABSTRACTS OF 12TH INTNAT’L CONGRESS

Vol. 65, Suppl. 1

s221

P436 EVOLUTION BCUTANEOUS

OF MFIAMMATORY PARAMETERS ENOXAPARIN OR INTRAVENOUS

0. Sitbon, L. Cahcn,

D. Landauer,

S. Combe.

DURING TREATMENT OF DEEP VENOUS UNFRKTIONATED HEPARM

P. Sic, G. Simonneau,

for the TVPENOX

Group

THROMBOSIS

BY su-

Sludy. Paris, F

In experimental studies, unfractionated heparin (UFH) has anti-inflammatory properties. However, krc is no data concerning in viva inflammatory parameters during treatment for deep venous thrombosis (DVT), neither with UFH nor with low molecular weight heparin (L,MWH). The aim of the study was lo determine the plasma levels of 5 inflammatory parameters during treatment of DVT with UFH and LMW?f. One hundred and thirty four patients with a recent proximal DVT confirmed by vcnography wcrc included in a multicentric randomized controlled study comparing Enoxaparin (E) and UFH. According 10 the venographic evolution between DO and DIO, patients were classified in three subgroups: improvement (I), stabilization (S) and aggravation (A). Blood samples from 93 out of 134 patients wtrt collected (E group: n-49; UFH gmup: n-44). Plasma levels of C-reactive protein (CRP), haptoglobin (H), omsomucoid (0). fibrinogen (F) and alpha-l antitrypsin (AT) were measured at inclusion and after 2.6 and 10 days. Albumin (Al) levels were xqutntialIy determined in order lo estimate hemodilution. Data (mean f SEM) are shown on the tablt below:

Before treatment, E and UFH groups were comparable concerning clinical Dada. venographic scores and inflammatory paramelen. CRP, 0, H, and AT plasma levels significantly decreased between DO and DIO, within each group (p .c 0.0s). F level significanlly increased during the treatment period (p-z 0.05). There was no significant difference between Ihe IWO treatment groups. Ai DO, no correlation was found between inflammalory paramtwrs levels and Mardtr venographic score. Mean CRP and AT levels aI inclusion were significantly different in UIC A subgroup (114 r 38 and 4.5 + 0.7 respectively) compared IO S (59 + 8 and 3.7 iO.2) and I (37 f 7 and 3 f 0.1) subgroups (p < 0.05). In conclusion, in our study, there was a similar evolution of inflammatory paramelers during treatment of DVT by E and UFH. Mrh both treatment regimens CRP, 0 and H levels decreased. The most imponant variation was observed with CRP and this may be dut 10 its short half-life. Higher initial CRP and AT levels stem 10 be predictable of a worsened venographic tvolulion.

P437 BlOLOGlCAL TIENTS WITH

CHANGES SEVERE

FOLLOWING INFUSION THROMBOEMBOLISM

OF

RECOMBINANT

HIRUDIN

(HBW

023)

IN

10 PA-

E Bridey, M. Dreyfus, E Parent, H. Gr&schL, G. Simonneau, D. Meyer Departments of Hematology and of Pneumology, HBpital A. B&c&e, Clamart, F, and Hoechst AG, Frankfurt, D Ten patients with severe thromboembolism were treated for 5 days by a continuous intravenous infusion of 0.05 mg/kg/h

HBW023

following

a bolus

injection

of 0.07 mgkg.

There

were

no adverse

side effects

and the treatment

appeared to be efficient. Biological studies were performed prior to infusion (H-l) and at various times during the course of treatment. Thrombin time was consistently over 120 sec. (control I5 sec.) after H2 and thus was not a useful parameter to follow. Activated partial thromboplastin time (Automated APTT, Organon Teknika), expressed as a ratio of patient to control times, markedly increased from 1 * 0.2 at H-l (meanq t SD) to I .9 j; 0.4 at D2 (p-0.005). It remained stable within the therapeutic range (defined as a ratio from I .2 to 3) throughout the duration of treatment, with large individual variations (for example, 1.4 to 2.4 at D2). The plasma levels of HBW023, determined by an anti-lla chromogenic assay,increased till 757 + 335 q/ml 5 min. after bolus injection and reached a steady state at D2 (563 z 174 &ml, range: 261-796). They were significantly correlated with the APTT ratio (r-0.59, p-0.0001). There was a slight but significant decrease of prothrombin time (Neoplastine Diagnostica Stage) from

H-l

to D2 (p c 0.01)

followed

by a stabilization.

Values

remained

over 60% however,

and were correlated

with

the APTT ratio (r-0.41, p-0.003). We did not observe any modification of other hemostatic parameters including antithrombin 111cofactor activity (ATIII) or bleeding time. Interestingly, high levels of plasma hirudin did not interfere with the functional assays of fibrinogen (von Clauss) or ATIII. In conclusion, we found a correlation between APTT and plasma hirudin levels in 10 patients treated with continuous intravenous infusion o HBW023 suggesting that AP’IT is a reliable tool to monitor hirudin therapy.