The Clinical Usefulness of the Platelet Aggregation Test for the Diagnosis of Heparin-Induced Thrombocytopenia

 

PDF Download Buy Article Permissions and Reprints

Summary

The platelet aggregation test is widely used for the diagnosis of heparin-induced thrombocytopenia (HIT), a potentially serious complication of heparin therapy. We have evaluated its sensitivity and specificity in comparison with those of the ¹⁴C-serotonin release test. The sensitivity of the platelet aggregation test was found to vary with the heparin concentration and the donor of the platelets used in the test. The optimal heparin concentrations were between 0.1 and 1.0 U/ml. Using these heparin concentrations, the mean sensitivity varied from 39% (with the least reactive platelets) to 81% (with the most reactive platelets). In comparison, the sensitivity of the release test ranged from 65% to 94%. The specificities of the platelet aggregation test were 82%, 90% and 100% for the following control groups: (1) non-thrombocytopenic patients given heparin, (2) patients with thrombocytopenia due to other causes, and (3) normal controls not given heparin, respectively. The corresponding specificities for the release test was 94%, 90% and 100%. The specificities can be further increased to 100% for all controls with the adoption of a two-point system which defines a positive result as one in which platelet aggregation occurs with a low heparin concentration (0.5 U/ml) but not with 100 U heparin/ml. For optimal results, a two-point platelet aggregation test should be performed with heparin concentrations of 0.5 and 100 U/ml and using platelets of more reactive donors.

• References

• 1 Warkentin TE, Kelton JG. Heparin-induced thrombocytopenia. Annu Rev Med 1989; 40: 31-44
  CrossrefPubMedGoogle Scholar
• 2 Chong BH, Berndt MC. Heparin-induced thrombocytopenia. Blut 1989; 58: 53-57
  CrossrefPubMedGoogle Scholar
• 3 Chong BH, Pitney WR, Castaldi PA. Heparin-induced thrombocytopenia: association of thrombotic complications with heparin-dependent IgG antibody that induces thromboxane synthesis and platelet aggregation. Lancet 1982; 1246-1249
  PubMedGoogle Scholar
• 4 Cines DB, Kaywin P, Bina M, Tomaski A, Schreiber AD. Heparin-associated thrombocytopenia. N Engl J Med 1980; 303: 788-795
  CrossrefPubMedGoogle Scholar
• 5 Kapsch D, Silver D. Heparin-induced thrombocytopenia, thrombosis and haemorrhage. Arch Surg 1981; 116: 1423-1429
  CrossrefPubMedGoogle Scholar
• 6 Demers C, Ginsberg JS, Brill-Edwarks P, Paying A, Warkentin TE, Anderson DR, Turner C, Kelton JG. Rapid anticoagulation using Ancrod for heparin-induced thrombocytopenia. Blood 1991; 78: 2194-2197
  PubMedGoogle Scholar
• 7 Chong BH, Ismail F, Cade J, Gallus AS, Gordon S, Chesterman CN. Heparin-induced thrombocytopenia: Studies with a new low molecular weight heparinoid, Org 10172. Blood 1989; 73: 1592-1596
  PubMedGoogle Scholar
• 8 Leroy J, Lerclerc MH, Delahousse B, Guerois C, Goloppe P, Gruel Y, Touelemonde F. Treatment of heparin-associated thrombocytopenia and thrombosis with low molecular weight heparin (CY 216). Semin Thromb Hemostas 1985; 11: 326-329
  Article in Thieme ConnectPubMedGoogle Scholar
• 9 Kelton JG, Sheridan D, Brain H, Powers PJ, Turpie AG, Carter CJ. Clinical usefulness of testing for a heparin-dependent platelet-aggregating factor in patients with suspected heparin-associated thrombocytopenia. J Lab Clin Med 1984; 103: 606-612
  PubMedGoogle Scholar
• 10 Fratantoni JC, Pollet R, Gralnick HR. Heparin-induced thrombocytopenia: confirmation of diagnosis with in vitro methods. Blood 1975; 45: 395-401
  PubMedGoogle Scholar
• 11 Green D, Harris K, Reynolds N, Roberts M, Patterson R. Heparin immune thrombocytopenia: evidence for a heparin-platelet complex as the antigenic determinant. J Lab Clin Med 1978; 91: 167-175
  PubMedGoogle Scholar
• 12 Babcock RB, Dumper CW, Scharfman WB. Heparin-induced immune thrombocytopenia. N Engl J Med 1976; 295: 237-244
  CrossrefPubMedGoogle Scholar
• 13 Wahl TO, Lipschitz DA, Stechschute DJ. Thrombocytopenia associated with antiheparin antibody. JAMA 1978; 240: 2560-2562
  CrossrefPubMedGoogle Scholar
• 14 Lynch DM, Howe SE. Heparin-associated thrombocytopenia antibody binding specificity to platelet antigens. Blood 1988; 66: 1176-1181
  PubMedGoogle Scholar
• 15 Chong BH, Grace CS, Rozenberg MC. Heparin-induced thrombocytopenia: Effect of heparin platelet antibody on platelets. Br J Haematol 1981; 49: 531-540
  CrossrefPubMedGoogle Scholar
• 16 Gruel Y, Rupin A, Darnige L, Moalic-Roverdiau P, Poumier-Gaschard P, Binet C, Bardos P, Leroy J. Specific quantification of heparin-dependent antibodies for the diagnosis of heparin-associated thrombocytopenia using an enzyme-linked immunosorbent assay. Thromb Res 1991; 62: 377-387
  CrossrefPubMedGoogle Scholar
• 17 Sheridan D, Carter C, Kelton JG. A diagnostic test for heparin-induced thrombocytopenia. Blood 1986; 67: 27-30
  PubMedGoogle Scholar
• 18 Pfueller SL, David R. Different platelet specificities of heparin-dependent platelet aggregating factors in heparin-associated immune thrombocytopenia. Br J Haematol 1986; 64: 149-159
  CrossrefPubMedGoogle Scholar
• 19 Kelton Jg, Sheridan DP, Santos AV. et al. Heparin-induced thrombocytopenia: laboratory studies. Blood 1988; 72: 925-930
  PubMedGoogle Scholar
• 20 Chong BH, Ismail F, Chesterman CN, Berndt MC. Heparin-induced thrombocytopenia with platelets. Br J Haematol 1989; 73: 235-240
  CrossrefPubMedGoogle Scholar
• 21 Rosenfeld SL, Ryan DH, Looney RJ, Anderson CL, Abraham GN, Leddy JP. Human Fc gamma receptors; stable inter-donor variation in quantitative expression on platelets correlates with functional responses. J Immunol 1987; 138: 2869-2873
  PubMedGoogle Scholar
• 22 Nurden AJ, Laroche-Traineau J, Jallu V, Broult J, Durrieu C, Besse P, Brossel C, Hourdille P. Heparin-induced thrombocytopenias: Observations on the nature of the antibodies activities and on the use of gammaglobulin concentrates in a patient with thrombotic complications. Thromb Haemostas 1991; 65: 796 (Abstr)
  PubMedGoogle Scholar
• 23 Chong BH, Steel R, Chesterman CN. Heparin-induced thrombocytopenia: A study of platelet IgG Fc receptors. Blood 1990; 70: 451a (Abstr)
  PubMedGoogle Scholar
• 24 Greinacher A, Michels I, Klefel V, Mueller-Eckhardt C. A rapid and sensitive test for diagnosing heparin associated thrombocytopenia. Thromb Haemostas 1991; 66: 734-736
  PubMedGoogle Scholar