Platelet Count Monitoring and Laboratory Testing for Heparin-Induced Thrombocytopenia

Archives of Pathology and Laboratory Medicine - Tập 126 Số 11 - Trang 1415-1423 - 2002
Theodore E. Warkentin1,2,3
1From the Department of Pathology and Molecular Medicine and the Department of Medicine, McMaster University; Transfusion Medicine, Hamilton Regional Laboratory Medicine Program; and Service of Clinical Hematology, Hamilton, Ontario
2Service of Clinical Hematology, Hamilton, Ontario
3Transfusion Medicine, Hamilton Regional Laboratory Medicine Program

Tóm tắt

Abstract Objective.—Heparin-induced thrombocytopenia (HIT) is an antibody-mediated adverse drug reaction that paradoxically is associated with a brief but dramatically increased risk for thrombosis (transient acquired thrombophilia). The objective of this article is to provide practical recommendations for platelet count monitoring in patients receiving heparin, as well as for selection of laboratory assays to detect pathogenic HIT antibodies. Study Selection.—Relevant literature that focused on frequency and timing of HIT in various clinical settings and that dealt with laboratory testing for HIT antibodies was critically appraised. Data Extraction and Synthesis.—The author prepared a preliminary manuscript including recommendations that was presented to participants at the College of American Pathologists Conference XXXVI: Diagnostic Issues in Thrombophilia (November 10, 2001). Support of at least 70% of conference participants was required for recommendations to be adopted. Conclusions.—The risk of immune HIT varies depending on the type of heparin (unfractionated heparin greater than low-molecular-weight heparin) and patient population (surgical greater than medical). Thus, the intensity of platelet count monitoring should be stratified depending on the clinical situation. Platelet count monitoring should focus on the period of highest risk (usually days 5 to 10 after starting heparin) and should use an appropriate platelet count baseline (generally, the highest platelet count beginning 4 days after start of heparin). However, earlier platelet count monitoring is appropriate if the patient received heparin within the past 100 days, as already circulating HIT antibodies can cause rapid-onset HIT with heparin reexposure. Although both antigen and (washed platelet) activation assays are very sensitive for detecting clinically significant HIT antibodies, activation assays have greater diagnostic specificity for clinical HIT.

Từ khóa


Tài liệu tham khảo

Warkentin, 1997, The pathogenesis of venous limb gangrene associated with heparin-induced thrombocytopenia., Ann Intern Med, 127, 804, 10.7326/0003-4819-127-9-199711010-00005

Greinacher, 2000, Heparin-induced thrombocytopenia with thromboembolic complications: meta-analysis of 2 prospective trials to assess the value of parenteral treatment with lepirudin and its therapeutic aPTT range., Blood, 96, 846, 10.1182/blood.V96.3.846

Warkentin, 1995, Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin., N Engl J Med, 332, 1330, 10.1056/NEJM199505183322003

Warkentin, 1998, Heparin-induced thrombocytopenia: towards consensus., Thromb Haemost, 79, 1, 10.1055/s-0037-1614206

Warkentin, Clinical picture of heparin-induced thrombocytopenia.

Warkentin, 1996, Heparin-induced skin lesions., Br J Haematol, 92, 494, 10.1046/j.1365-2141.1996.d01-1481.x

Warkentin, 1996, Heparin-induced thrombocytopenia, skin lesions, and arterial thrombosis: a new clinical syndrome [abstract]., Can J Cardiol, 12, 151

Warkentin, Laboratory testing for heparin-induced thrombocytopenia.

Warkentin, 2000, Impact of the patient population on the risk for heparin-induced thrombocytopenia., Blood, 96, 1703, 10.1182/blood.V96.5.1703

Lindhoff-Last, 2001, Determination of heparin–platelet 4–IgG antibodies improves diagnosis of heparin-induced thrombocytopenia., Br J Haematol, 113, 886, 10.1046/j.1365-2141.2001.02869.x

Alban, Role of sulfated polysaccharides in the pathogenesis of heparin-induced thrombocytopenia.

Amiral, Heparin-dependent antigens in heparin-induced thrombocytopenia., 10.1201/9780203027363.ch6

Horne, Nonimmune heparin–platelet interactions: implications for the pathogenesis of heparin-induced thrombocytopenia., 10.3109/9781420045093.004

Suh, 1997, Characterization of the humoral immune response in heparin-induced thrombocytopenia., Am J Hematol, 54, 196, 10.1002/(SICI)1096-8652(199703)54:3<196::AID-AJH4>3.0.CO;2-R

Amiral, 2000, Affinity purification of heparin-dependent antibodies to platelet factor 4 developed in heparin-induced thrombocytopenia: biological characteristics and effects on platelet activation., Br J Haematol, 109, 336, 10.1046/j.1365-2141.2000.02034.x

Newman, 2000, Heparin-induced thrombocytopenia: new evidence for the dynamic binding of purified anti-PF4–heparin antibodies to platelets and the resultant platelet activation., Blood, 96, 182, 10.1182/blood.V96.1.182

Chong, 1994, Plasma P-selectin is increased in thrombotic consumptive platelet disorders., Blood, 83, 1535, 10.1182/blood.V83.6.1535.1535

Warkentin, 1994, Sera from patients with heparin-induced thrombocytopenia generate platelet-derived microparticles with procoagulant activity: an explanation for the thrombotic complications of heparin-induced thrombocytopenia., Blood, 84, 3691, 10.1182/blood.V84.11.3691.bloodjournal84113691

Warkentin, 1999, Generation of platelet-derived microparticles and procoagulant activity by heparin-induced thrombocytopenia IgG/serum and other IgG platelet agonists: a comparison with standard platelet agonists., Platelets, 10, 319, 10.1080/09537109975960

Visentin, 1994, Antibodies from patients with heparin-induced thrombocytopenia/thrombosis are specific for platelet factor 4 complexed with heparin or bound to endothelial cells., J Clin Invest, 93, 81, 10.1172/JCI116987

Greinacher, 1994, Heparin-associated thrombocytopenia: isolation of the antibody and characterization of a multimolecular PF4–heparin complex as the major antigen., Thromb Haemost, 71, 247

Pouplard, 2001, Induction of monocyte tissue factor expression by antibodies to heparin–platelet factor 4 complexes developed in heparin-induced thrombocytopenia., Blood, 97, 3300, 10.1182/blood.V97.10.3300

Arepally, 2001, Antibodies from patients with heparin-induced thrombocytopenia stimulate monocytic cells to express tissue factor and secrete interleukin-8., Blood, 98, 1252, 10.1182/blood.V98.4.1252

Greinacher, Treatment of heparin-induced thrombocytopenia: an overview., 10.1201/9780203027363.ch13

Warkentin, 2001, Temporal aspects of heparin-induced thrombocytopenia., N Engl J Med, 344, 1286, 10.1056/NEJM200104263441704

Warkentin, 2001, Delayed-onset heparin-induced thrombocytopenia and thrombosis., Ann Intern Med, 135, 502, 10.7326/0003-4819-135-7-200110020-00009

Warkentin, 1996, A 14-year study of heparin-induced thrombocytopenia., Am J Med, 101, 502, 10.1016/S0002-9343(96)00258-6

Nand, 1997, Heparin-induced thrombocytopenia with thrombosis: incidence, analysis of risk factors, and clinical outcomes in 108 consecutive patients treated at a single institution., Am J Hematol, 56, 12, 10.1002/(SICI)1096-8652(199709)56:1<12::AID-AJH3>3.0.CO;2-5

Wallis, 1999, Failure of early heparin cessation as treatment for heparin-induced thrombocytopenia., Am J Med, 106, 629, 10.1016/S0002-9343(99)00124-2

Pedersen-Bjergaard, 1997, Drug-induced thrombocytopenia: clinical data on 309 cases and the effect of corticosteroid therapy., Eur J Clin Pharmacol, 52, 183, 10.1007/s002280050272

Warkentin, 1995, Formation of heparin-induced thrombocytopenia IgG without thrombocytopenia: analysis of a clinical trial [abstract]., Blood, 86, 537

Warkentin, 1998, Frequency of upper limb deep venous thrombosis (UL-DVT) in relation to central venous catheter (CVC) use in patients with heparin-induced thrombocytopenia (HIT): evidence for interaction of systemic (HIT) and local (CVC) prothrombotic risk factors [abstract]., Blood, 92, 500

Warkentin, 1999, Multicentric warfarin-induced skin necrosis complicating heparin-induced thrombocytopenia., Am J Hematol, 62, 44, 10.1002/(SICI)1096-8652(199909)62:1<44::AID-AJH7>3.0.CO;2-F

Lee, Frequency of heparin-induced thrombocytopenia.

Pouplard, 1999, Antibodies to platelet factor 4–heparin after cardiopulmonary bypass in patients anticoagulated with unfractionated heparin or a low-molecular-weight heparin: clinical implications for heparin-induced thrombocytopenia., Circulation, 99, 2530, 10.1161/01.CIR.99.19.2530

Lee, 1996, A diagnostic test for heparin-induced thrombocytopenia: detection of platelet microparticles using flow cytometry., Br J Haematol, 85, 724, 10.1046/j.1365-2141.1996.d01-1944.x

Chong, 1993, The clinical usefulness of the platelet aggregation test for the diagnosis of heparin-induced thrombocytopenia., Thromb Haemost, 69, 344, 10.1055/s-0038-1651610

Warkentin, 2000, Laboratory testing for heparin-induced thrombocytopenia., J Thromb Thrombolysis, 10, 35, 10.1023/A:1027381103184

Sheridan, 1986, A diagnostic test for heparin-induced thrombocytopenia., Blood, 67, 27, 10.1182/blood.V67.1.27.27

Warkentin, 1992, Determinants of platelet variability when testing for heparin-induced thrombocytopenia., J Lab Clin Med, 120, 371

Greinacher, 1991, A rapid and sensitive test for diagnosing heparin-associated thrombocytopenia., Thromb Haemost, 66, 734, 10.1055/s-0038-1646493

Greinacher, 1994, Laboratory diagnosis of heparin-associated thrombocytopenia and comparison of platelet aggregation test, heparin-induced platelet activation test, and platelet factor 4/heparin enzyme-linked immunosorbent assay., Transfusion, 34, 381, 10.1046/j.1537-2995.1994.34594249047.x

Eichler, 1999, First workshop for detection of heparin-induced antibodies: validation of the heparin-induced platelet activation test (HIPA) in comparison with a PF4/heparin ELISA., Thromb Haemost, 81, 625, 10.1055/s-0037-1614536

Polgár, 1998, Adenosine diphosphate (ADP) and ADP receptor play a major role in platelet activation/aggregation induced by sera from heparin-induced thrombocytopenia patients., Blood, 91, 549, 10.1182/blood.V91.2.549

Warkentin, History of heparin-induced thrombocytopenia.

Favaloro, 1992, Heparin-induced thrombocytopenia: laboratory investigation and confirmation of diagnosis., Pathology, 24, 177, 10.3109/00313029209063169

Goodfellow, 1998, A comparison of laboratory tests for the diagnosis of heparin-induced thrombocytopenia [abstract]., Br J Haematol, 101, 89

Amiral, 1992, Platelet factor 4 complexed to heparin is the target for antibodies generated in heparin-induced thrombocytopenia [letter]., Thromb Haemost, 68, 95, 10.1055/s-0038-1656329

Collins, 1997, Diagnostic testing for heparin-induced thrombocytopenia (HIT): an enhanced platelet factor 4 complex enzyme linked immunosorbent assay (PF4 ELISA) [abstract]., Blood, 90, 461

Amiral, 1996, Pathogenicity of IgA and/or IgM antibodies to heparin–PF4 complexes in patients with heparin-induced thrombocytopenia., Br J Haematol, 92, 954, 10.1046/j.1365-2141.1996.407945.x

Newman, 1998, Heparin-induced thrombocytopenia: IgG binding to PF4-heparin complexes in the fluid phase and cross-reactivity with low molecular weight heparin and heparinoid., Thromb Haemost, 80, 292, 10.1055/s-0037-1615190

Vun, 2001, Anti-PF4–heparin immunoglobulin G is the major class of heparin-induced thrombocytopenia antibody: findings of an enzyme-linked immunofiltration assay using membrane-bound hPF4–heparin., Br J Haematol, 112, 69, 10.1046/j.1365-2141.2001.02495.x

Meyer, 1999, Rapid detection of heparin-induced platelet antibodies with particle gel immunoassay (ID-HPF4)., Lancet, 354, 1525, 10.1016/S0140-6736(99)03625-9

Eichler, 2001, The ID microtyping system for detection of heparin-induced antibodies in comparison with functional and antigenic assays [abstract]., Ann Hematol, 80, 15

Amiral, 1996, Generation of antibodies to heparin-PF4 complexes without thrombocytopenia in patients treated with unfractionated or low molecular weight heparin., Am J Hematol, 52, 90, 10.1002/(SICI)1096-8652(199606)52:2<90::AID-AJH4>3.0.CO;2-0

Bauer, 1997, Prevalence of heparin-associated antibodies without thrombosis in patients undergoing cardiopulmonary bypass surgery., Circulation, 95, 1242, 10.1161/01.CIR.95.5.1242

Amiral, 1996, Presence of auto-antibodies to interleukin-8 or neutrophil-activating peptide-2 in patients with heparin-associated thrombocytopenia., Blood, 88, 410, 10.1182/blood.V88.2.410.bloodjournal882410

Warkentin, Pseudo-heparin-induced thrombocytopenia.

Warkentin, 2001, Venous limb gangrene during warfarin treatment of cancer-associated deep venous thrombosis., Ann Intern Med, 135, 589, 10.7326/0003-4819-135-8_Part_1-200110160-00009

Harenberg, 2001, Improved laboratory confirmation of heparin-induced thrombocytopenia type II: time course of antibodies and combination of antigen and biologic assays., Am J Clin Pathol, 115, 432, 10.1309/ET2W-5J8E-MFVU-QYAH

Hirsh, 2001, Heparin and low-molecular-weight heparin: mechanisms of action, pharmacokinetics, dosing, monitoring, efficacy, and safety., Chest, 119, 64, 10.1378/chest.119.1_suppl.64S

Warkentin, 2001, Heparin-induced thrombocytopenia: yet another treatment paradox?, Thromb Haemost, 85, 947, 10.1055/s-0037-1615945

Greinacher, Recombinant hirudin for the treatment of heparin-induced thrombocytopenia.