Hemorrhagic disease with circulating inhibitors of blood clotting: anti-AHF and anti-PTC in eight cases.

T HE association of henmmorrhagic disorders with circulating inmhibitors of blood clottiimg is relatively rare. A number of reports during the past 15 years,’’8 however, indicate that such problems can be clinically significant and that the physiologic uniderstandinmg of their types and modes of action is worthy of continmued investigation. No complete classification of these various inhibitors is possible at this time as their precise nature anmd the ways they act have not been worked out iim many instances. Theoretically, an inhibitor might be expected to act against omie or more of the numerous clotting factors, namely, AHF, PTC, PTA, Spaet’s “4th factor,”9 (pro)thrombinm, (pro)convertin, (pro)accelerin, fibrinogen, platelet factors, or tissue thrombopla.stin. In a recent panel discussioim’8 of the inhibitor problems, the following, although nmot all yet identified as “circulating” anticoagulanits, were mentionmed: heparin, heparin co-factor, anmtithrombimm, lipid antithromboplastinm, species-specific t hrombopla.stimm inhibitor, antiprocoimvertin (etc. ?), abnormal globulimms, protease (fibrinolysin) destructive to certaimm clotting factors, and perhaps some antiproteases, besides specific inhibitors of AHF amid PTC, which are especially relevant to the present studies. A survey of the literature pertinment to this study stresses that the etiology may involve some type of imnmmuimo-responmse, exhibiting demonstrable anmalogies to other antigenm-antibody reactions and often following some provoking iimcident, such as tranmsfusiomm, pregnancy, allergy to antibotic drugs, or occurrinmg concontitantly with sonic profound disturbance of proteimm metabolism such as collagen disease, genmeralized lyniphadenmopathy, or rarely nmeoplasia, etc. About half the reported cases are in patiemmts already afflicted with a severe coagulation deficiency, e.g., hemophilia, PTC-deficienmcy, and often in these cases tranisfusionm seems to be the provoking immcident. The remaining cases acquire an inhibitor de novo, and the term “idiopathic” covers real ignorance as to the cause, although aniy of the conmcomitanmts above nmmenmtioned may be recorded for the individual case. The present study resulted from the laboratory examination, with a battery of tests designed to shed light upon individual factors in the clottimig and hemostatic mechanmisms, of 240 patienmts with bleeding tendencies and another 160 without. Imi 8 cases, namely, 5 out of 52 hemophilics, 2 out of 26 PTC-deficients, and in one other, the presenmce of circulating inhibitors w’as demonstrated and special tests showed them to have anti-AHF or anti-PTC activities.