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Proposed Classification of Resistances to Oral Anticoagulant Therapy

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Proposed Classification of Resistances to Oral Anticoagulant Therapy J Clin Pathol: first published as 10.1136/jcp.40.2.242-c on 1 February 1987. Downloaded from J Clin Pathol 1987;40:242-243 ond sentence of the second paragraph alised resistance according to the number of Letters to the Editor should have read: "The main purpose of drugs taken (only one or several); (iii) abso- these investigations ..." and not "the main lute or relative resistance judged by the of our It refers Scar adenocarcinoma of the lung purpose investigations ...". modification of the prothrombin time: to the ultrastructural studies by other absent effect (prothrombin time, 75%) or authors mentioned in the preceding sen- I am confused about the purpose of the slight effect (prothrombin time between 50 tence. and 75%). article by Edwards and Carlile.1 On the one not our intention to make a hand, they stated that the main purpose of It was The mechanisms of OAT resistance are detailed study of scar formation in these various: absence of drug intake, excessive their investigation was to define the cellular felt it necessary to discuss subtypes of adenocarcinoma in general and tumours, but we dietary vitamin K intake,' variations in the possible mechanisms in the light of previous pharmacokinetics of oral anticoagulants that little attention was paid to scar cancer The paper by Dr Kung et al' reached as such; on the other hand, they described work. (drug interaction),2 oral anticoagulant mal- us some time after our own paper had been absorption, enhanced metabolism,3 and the ultrastructure of five selected cases of It is clearly an peripheral adenocarcinomas associated with accepted for publication. hereditary resistance. Serial measurements important contribution, and the conclusions of the serum concentration permits esti- a focus of scarring. A lot of their discussion and reasonable. Nevertheless, it is was devoted to the and histo- are valid mation ofthe half life oforal anticoagulant' morphology difficult to rule out the possibility that a and provides information on the greatest genesis of scarring. reaction is responsible for this -The authors observed that the central desmoplastic part of the mechanisms of OAT resistance. appearance in some tumours, and the fur- Hereditary resistance is rare' and attributed nidus of scarring consisted ofelastic outlines ofmalignant transformation of partly collapsed alveoli containing fine ther possibility to a changed hepatic receptor site for the around pre-existing scars cannot be ignored. oral anticoagulant. Diagnosis is difficult collagen fibrils. Only in one case was dense The question still appears to be open. It may collagen seen. because a detailed genetic study is rarely be that all three mechanisms play a part. possible. This sort of resistance is always These features are described in detail in EDWARDS another paper.2 It is now quite clear that the CW primary. Department ofHistopathology, When resistance is not overcome by so called central scar is, in fact, the collapsed East Birmingham Hospital, elastic framework of alveoli. The fine col- progressive increase in doses of oral anti- Bordesley Green East. coagulant, change to another drug is neces- lagen fibrils within alveolar spaces are most Birmingham B9 5ST likely a result of organisation of exudate, sary. But this change cannot be arbitrary. If which appears after collapse. This localised a patient is resistant to ethylbiscoumacetate, Reference he or she will probably also be resistant to collapse also accounts for the pleural puck- copyright. phenindione. A change to acenocoumarol ering. One needs to be very careful about I Kung ITM, Lui IOL, Loke SL, Khin MA, fibrous tissue rather than warfarin is preferable (warfarin not mistaking between the Mok CK, Lam WK, So SY. Pulmonary scar associated with the least opposing surfaces ofthe puckered pleura for cancer. A pathologic reappraisal. Am J Surg is (statistically) pre-existing intrapulmonary fibrosis or Pathol 1985;9:391-400. resistance). Resistances to the drugs must be desmoplastic reaction. The cause of the col- taken into consideration following any lapse is most probably tumour obstruction change in OAT. of a peripheral airway. JEAN-JACQUES LEFRERE The term scar cancer should now be MARIE-HtLtNE HORELLOU restricted to those in which definite pre- JACQUELINE CONARD http://jcp.bmj.com/ existing collagenous fibrosis, either diffuse MEYER SAMAMA or localised, is found. Laboratoire Central d'Hematologie, ITM KUNG Hotel-Dieu, Institute ofPathology, 75181, Paris, Hong Kong Government Proposed classification of resistances to oral France Queen Elizabeth Hospital, anticoagulant therapy Wylie Road, Kowloon, Resistance to oral anticoagulant therapy References on September 23, 2021 by guest. Protected Hong Kong (OAT) is defined as the inability of OAT to bring the prothrombin time down to the 1 O'Reilly RA, Rytand DA. Resistance to war- adequate levels of anticoagulation when farin due to unrecognised vitamin K supple- References administered at a dose near or equivalent mentation. N Engi J Med 1980;303:160-1. to the normally recommended doses. We 2 MacLeod SM, Sellers FM. Pharmacodynamic studied a series of 220 and pharmacokinetic drug interactions with 1 Edwards C, Carlile A. Scar adenocarcinoma of retrospectively coumarin anticoagulants. Drugs 1976;11: the lung: a light and electron microscopic patients receiving OAT (acenocoumarol, 461-70. study. J Clin Pathol 1986;39:423-7. tioclomarol, ethylbiscoumacetate, warfarin, 3 Lewis RJ, Spivack M, Staet T. Warfarin 2 Kung ITM, Lui 101, Loke SL, et al. Pul- phenindione): 10 resistances to OAT were resistance. Am J Med 1967;42:620-4. monary scar cancer: a pathologic reap- found. Based on these and observations 4 Breckenridge A, Orme M. Kinetics of warfarin praisal. Am J Surg Pathol 1985;9:391-40. from other data, we propose a classification absorption in man. Clin Pharmacol Ther of different types of OAT resistance: (i) pri- 1973;14:955-61. mary or secondary resistance according to 5 O'Reilly RA. The second reported kindred Dr Edwards replies: the start with hereditary resistance to oral anti- The confusion arises from an error which the rapidity of occurrence (at of coagulants drugs. N Engl J Med 1970; was overlooked at the proof stage. The sec- treatment or later); (ii) selective or gener- 282:1448-51. 242.
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