Reduced inhibition of activated prothrombin by heparin and venous thromboembolism: heparin resistance revisited.
OBJECTIVE
We evaluated a new test, based on prothrombin activation by Echis Carinatus snake venom in the absence/presence of unfractionated heparin, in patients with venous thromboembolism (VTE).


METHODS
The test (activated prothrombin heparin-inhibition test) was performed in 555 unselected, unrelated patients who had suffered from at least one objectively confirmed VTE and the results were compared with those obtained in 408 healthy controls.


RESULTS
In 71 (12.8%) of the 555 patients the results of the test, expressed as a normalized ratio, were below the cut-off. This compared with 19 (5% by definition) results below the cut-off in the control group. The crude OR for VTE in subjects with altered vs those with normal results was 3.00 (95% CI: 1.78-5.07). ORs did not significantly change after adjustment for age (2.86, 95% CI: 1.68-4.85) and age/sex (2.80, 95% CI: 1.64-4.77) by logistic regression. After adjustment for antithrombin III, fibrinogen and prothrombin levels the risk associated with altered results remained significantly high. The overall OR for VTE in females (3.22; 95% CI: 1.53-6.75) was higher than that in males (2.69; 95% CI: 1.27-5.69). However, for both sexes there was a sharp increase in the risk of VTE associated with altered results in patients aged less than 45 years (crude OR 9.61; 95% CI: 3.38-27.3).


CONCLUSIONS
Lower than expected thrombin inhibition by endogenous antithrombin action after full activation by heparin addition was found to be a common feature in patients who suffered from previous venous thrombotic events, and may reflect a hitherto unrecognized thrombophilic alteration.
Legnani
Cristina
C
Unità di Ricerca Clinica sulla Trombofilia Marino Golinelli, Divisione di Angiologia, Azienda Ospedaliera di Bologna, Policlinico S. Orsola-Malpighi, Italy. legnanic@tin.it
Preda
Luigi
L
Palareti
Gualtiero
G
Lunghi
Barbara
B
Rossi
Edoardo
E
Coccheri
Sergio
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000494:pharmacology*; D000990:Antithrombin III / Q000502:physiology; D001780:Blood Coagulation Tests; D002648:Child; D004351:Drug Resistance; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011516:Prothrombin / Q000037:antagonists & inhibitors*; D012008:Recurrence; D012307:Risk Factors; D019851:Thrombophilia / Q000097:blood* / Q000453:epidemiology; D020246:Venous Thrombosis / Q000188:drug therapy*
D000925:Anticoagulants; D000990:Antithrombin III; D011516:Prothrombin; D005340:Fibrinogen; D006493:Heparin