Highly variable anticoagulant response after subcutaneous administration of high-dose (12,500 IU) heparin in patients with myocardial infarction and healthy volunteers.

Background. Inthisstudy, theanticoagulant responseof12,500 IUheparin s.c.was investigated in patients withmyocardial infarction andhealthy volunteers todetermine variabilities inresponseand modifying factors. Methods andResults. Onthefourth dayafter thrombolytic therapy, bloodsamples weretakenbefore and atfrequent intervals until 10hoursafter theinjection of12,500 IUheparin s.c.Plasmaanti-Xa activity, anti-Ha activity, andtheactivated partial thromboplastin time(APTT) weremeasured inaddition tobody weight andthickness oftheabdominal subcutaneous fatlayer. Contrary toexpectations, theincrease of anti-Xa activity, anti-lla activity, andAPTTcompared withbaseline (predrug) levels was verysmall, with an averagemaximal APYIT of42.6seconds (SD,12.4seconds; range,30.4-70.7 seconds). Subsequently, the influence ofthelength oftheinjection needle on theanticoagulant effect of12,500 IUheparin s.c.was studied in10healthy volunteers tofind a factor thatcouldberesponsible forthepoorresponseinthe patients. Thelength oftheinjection needle didnotinfluence theanticoagulant effect ofheparin. Large interindividual andintraindividual variabilities were seeninthevolunteers. Themajority ofvolunteers hadminimal prolongation oftheAPWT,butverystrong prolongation was also seen(maximal APIT,163 seconds). Therewas no correlation between theabdominal skinfold thickness andanti-Xa activity, anti-Ha activity, orAPTT(p>0.05), butinthepatient study, there was a correlation between weight and anti-Xa activity andanti-Ila activity (p<0.05), andinthevolunteer study, there was acorrelation between weight andanti-Xa activity andAPIT(p<0.05). Conclsions. Subcutaneous administration ofheparin ina fixed doseforprophylactic andtherapeutic purposesmay be inadequate because ofthelarge interindividual andintraindividual variations in anticoagulant effect. (Circulation 1992;86:1370-1375)