Correction of Clotting Factor “Deficiencies” in Plasma from Patients with Lupus-Like Anticoagulants

Summary

Identification of spurious coagulation factor deficiencies that are known to occur in association with lupus-like anticoagulants (LLACs) requires the use of cumbersome laboratory procedures. To determine whether single-stage assays employing the APTT system may be used to identify such artifacts, we measured multiple clotting factor levels by several techniques in plasma of six patients with typical LLACs. While normal activities of factors VIII, IX, XI and XII were measured in only 4/24 APTT assays (17%) employing human plasma substrate, normal factor activities were present in all 24 APTT assays employing bovine, canine or rabbit plasma substrate. Normal factor II, V and X activities were recorded in all but one case in assays that utilized a modified Stypven time, while normal factor VIII levels were determined in 5/6 plasmas when the thromboplastin generation test was employed. These results indicate that the use of heterologous plasma substrates in the APTT system may provide a simple method to identify such coagulation factor “deficiencies”.

Keywords

Heterologous substrates - Lupus inhibitors - Coagulation factor assays

• References

• 1 Conley CL, Hartman RC. A hemorrhagic disorder caused by circulating anticoagulants in patients with disseminated lupus erythematosus. J Clin Invest 1952; 31: 621-622
• 2 Feinstein DI, Rapaport SI. Acquired inhibitors of blood coagulation. Prog Hemostas Thromb 1972; 1: 75-95
• 3 Yin ET, Gaston LW. Purification and kinetic studies on a circulating anticoagulant in a suspected case of lupus erythematosus. Thrombos Diathes Haemorrh 1965; 14: 88-115
• 4 Lechner K. Acquired inhibitors in nonhemophilic patients. Haemostasis 1974; 3: 65-93
• 5 Schleider MA, Nachman RL, Jaffe EA, Coleman M. A clinical study of the lupus anticoagulant. Blood 1976; 48: 499-509
• 6 Shapiro SS, Hutlin M. Acquired inhibitors to the blood coagulation factors. Semin Thromb Hemostas 1975; 1: 336-385
• 7 Clyne LP, Dainiak N, Hoffman R, Hardin JA. In vitro correction of anticoagulant activity and specific clotting factor assays in SLE. Thromb Res 1980; 18: 643-655
• 8 Veltkamp JJ, Kerkhoven P, Loeliger EA. Circulating anticoagulant in disseminated lupus erythematosus. Proposed mode of action Haemostasis 1973/74 2: 253-259
• 9 Bowie EJ W, Thompson JH, Paschuzzi CA, Owen CA. Thrombosis in systemic lupus erythematosus despite circulating anticoagulants. J Lab Clin Med 1963; 62: 416-430
• 10 Mueh JR, Herbst KD, Rapaport SI. Thrombosis in patients with the lupus anticoagulant. Ann Intern Med 1980; 92: 156-159
• 11 Cohen AS, Reynolds WE, Franklin EC, Kulka JO, Ropes MW, Shulman LE, Wallace SL. Preliminary criteria for the classification of systemic lupus erythematosus. Bull Rheum Dis 1971; 21: 643-645
• 12 Zarrabi MH, Zucker S, Miller F, Derman RM, Romano GS, Hartnett JA, Varma AO. Immunologic and coagulation disorders in chlorpromazine treated patients. Ann Intern Med 1979; 91: 194-199
• 13 Proctor PR, Rapaport SI. The partial thromboplastin time with kaolin. Am J Clin Pathol 1961; 36: 212-219
• 14 Bell WN, Alton HG. A brain extract as a substitute for platelet suspensions in the thromboplastin generation test. Nature 1954; 174: 880-881
• 15 Pool JG, Robinson J. Assay of plasma antihaemophilic globulin (AHG). Br J Haematol 1959; 5: 17-23
• 16 Müller-Berghaus G, Lasch HG. Consumption of Hageman factor activity in the generalized Shwartzman reaction induced by liquoid. Thrombos Diathes Haemorrh 1970; 23: 386-404
• 17 Exner T, Rickard KA, Kronenbert H. A sensitive test demonstrating lupus anticoagulant and its behavioral patterns. Br J Haematol 1978; 40: 143-151
• 18 Loeliger A. Prothrombin as co-factor of the circulating anticoagulant in systemic lupus erythematosus. Thrombos Diathes Haemorrh 1959; 3: 237-256
• 19 Rivard GE, Schiffman S, Rapaport SI. Cofactor of the “Lupus anticoagulant”. Thrombos Diathes Haemorrh 1974; 32: 554-563
• 20 Dodds WJ. Second Int’l Registry of Animal Models of Thrombosis and Hemorrhagic Diseases. Nat’l Acad Press; Washington D.C.: 1981. 24 4-25
• 21 Hougie C. Naturally occurring species specific inhibitor of human prothrombin in lupus erythematosus. Proc Soc Exp Biol Med 1964; 116: 359-361
• 22 Gonyea L, Herdman R, Bridges RA. The coagulation abnormalities in systemic lupus erythematosus. Thrombos Diathes Haemorrh 1968; 20: 457-464
• 23 Castro O, Farber LR, Clyne LP. Circulating anticoagulants against factors IX and XI in systemic lupus erythematosus. Ann Intern Med 1972; 77: 543-548
• 24 DiSabatino CA, Clyne LP, Malawista SE. A circulating anticoagulant directed against factor XI a in systemic lupus erythematosus. Arth Rheum 1979; 22: 1135-1138