HDCN Article Review/Hyperlink

Yamamoto S, Koide M, Matsuo M, Suzuki S, Ohtaka M, Saika S, Matsuo T

Heparin-induced thrombocytopenia in dialysis patients

Am J Kidney Dis (Jul) 28:82-85 1996

Heparin-induced thrombocytopenia (HIT) is an important complication of heparin therapy. Its incidence in hemodialysis patients, who receive heparin thrice weekly, is unknown. The objective of this study was to determine its incidence and to characterize its subtypes. Of 154 hemodialysis patients, six (3.9%) developed HIT. The diagnosis was suspected by clotting of the extracorporeal circuit in the presence of thrombocytopenia. Five had anti-platelet factor 4-heparin complex antibody detected by ELISA and were diagnosed with immunologic HIT (of note only three of these had heparin-induced platelet aggregation in an in vitro assay; see comment). The etiology in the other patient is not clear (this patient had a positive platelet aggregation test but negative antibodies). Heparin was discontinued and an alternate anticoagulant (either argatroban or nafamstat mesilate) used. In conclusion, the incidence of HIT in hemodialysis patients appears to be 4-5%, and can be diagnosed in most patients by the ELISA assay.

Comment: HIT is clinically suspected when thromobocytopenia occurs with or without thrombosis in patients receiving heparin. Diagnosis is usually made by a positive platelet aggregation test in which the ability of heparin to aggregate platelets incubated in platelet rich plasma is assessed. There appears to be two forms of HIT: a mild early onset thrombocytopenia, possibly due to non-immunologic mechanisms, and a more severe delayed-onset immunologically mediated disease which is often associated with clinical thrombosis. Diagnosis of inmmunologically-based HIT can be made by ELISA (as in this paper), by platelet aggregometry or by platelet serotonin release. ELISA is a more sensitive test than is platelet aggregometry but ELISA gives in more false positive results.

We initially reported HIT in two hemodialysis patients with thrombocytopenia (Leehey DJ et al. Int J Artif Organs 10: 37-39, 1987). Yamomoto et al report an incidence of HIT of 3.9% (6/154 patients) in their hemodialysis unit; however, testing was performed only when HIT was clinically suspected. When all patients in a chronic hemodialysis facility are screened, the prevalence of heparin-dependent antibodies is lower (1.5%) and not different from that in patients treated with short-term continuous heparin (Kappers-Klunne M, et al. Blood 1995; 86:900a).

Treatment of HIT generally involves discontinuation of heparin, although this may not always be necessary, especially after thrombocytopenia has resolved. In patients in whom heparin cannot be discontinued, heparin in combination with low dose aspirin may be helpful in prevention of thrombosis (Hall AV et al. Clin Nephrol 1992; 38: 86-9 and HL Messmore, Hines/Loyola Medical Center, personal communication). Use of low-molecular weight heparin (LMWH) will not in general be of use once HIT has developed, since such patients also generally react to LMWH (HL Messmore, personal communication). Another option (although not available in the U.S.) is the use of danaparoid (Org 10172; Organon), which is a low-molecular weight heparanoid consisting of a mixture of sulfated glycosaminoglycans including heparan sulfate, dermatan sulfate, and chondroitin sulfate which rarely cross reacts with heparin. This heparanoid has been used successfully in hemodialysis patients with HIT (Greinacher A et al, Nephrol Dial Transplant 1993; 8: 1176-7). (David J. Leehey, M.D., Loyola University at Chicago)