A case of HITS managed with hirudin anticoagulation for bypass is presented. The rationale for choosing this option is discussed together with the alternatives described in the literature.
Management can be stratified by urgency of surgery. If delay is feasible, consider postponing surgery until heparin-induced anti-platelet antibodies are no longer detectable (median time 50-85 days) (2). Plasmapheresis to remove intravascular lgG (daily, x 5 days) has been reported to accelerate this process. Subsequent re-exposure to UFH confined to the surgical intervention then appears to have acceptably low risk of recurrence of HITS. Antibodies take at least 3 days to reappear and are only thrombogenic in the presence of heparin (3). Other perioperative anticoaguiation should be used pre- and especially post-op as the risk of complications is significant for several weeks.
If surgery is urgent there are a number of options, all of which have significant drawbacks. Common to all UFH alternatives is lack of reversibility with protamine, and consequently frequent and excessive postoperative bleeding.
Danaparoid (heparan/dermatan/chondroitin suffates mixture, Orgaran) has been used relatively widely since about 1990 but very little of the experience in CPB is published. It is predominantly an inhibitor of factor Xa. Initial dosing regime was associated with excessive bleeding (55%), rethoracotomy and death, but reduced dose regime (total dose limited to < 250U/kg) seems no better (4), Prolonged half-life (7-15 hrs, longer in RF), lack of bedside anticoagulation monitoring, and a X-reactivity of 10-30% to UFH antibodies are problems. The 80% cross-reactivity for LMWH (eg enoxaparin) generally precludes these as alternatives to UFH although a few case reports exist.
Hirudin (recombinant leech saliva extract, Revasc) acts by direct thrombin inhibition as well as having some anti-Xa activity and a yet undefined platelet effect. It has shorter half-life provided renal function remains normal (1.5 hrs, but over 70 hrs in RF and virtually non-dialysable). Monitoring test (TAS-ECT) not readily available. 56% of patients will develop anti-hirudin antibodies but preliminary reports suggest this is of no clinical import if re-exposure occurs. An in vitro reversal agent (r-meizothrombin) is not available clinically. One large series of 57 pts reports safe and effective use (5).
Ancrod (Malayan pit viper venom) has been used as a defibrinogenating agent, alone or with danaparoid, but has not found widespread application, Adequate defibrinogenation takes at least 12 hours, and one report exists of failure (6). Reversal requires blood products, precluding return to bypass.
Methods of negating platelet reactivity to antibodies in the presence of UFH have
intrinsic appeal. Earliest attempts used aspirin and dipyrimadole. More refined
approaches employ PGE1 or epoprostenol (prostacyclin, PG12). Both are effective,
have a short half-life with possible bedside monitoring, but cause hypotension
during infusion (7). More recently the use of the short-acting, hepatically-excreted
platelet llb / llla receptor blocker tirofiban (Aggrastat) by infusion with conventional
UFH dosing has been described (8). Both the ACT and Hemostatus II platelet
function assay are monitored. This approach needs further clinical experience but
appears the most promising option yet.
References:
1. Speiss. Editorial. JCTVA 14:3 (June) 2000 p239-42
2. Warkentin et al. NEJM 344:17. April 26, 2001. p1286-92
3. Potzsch et al. Letter. NEJM 343:7. Aug 17, 2000. p515
4. Olin et al. JCTVA 14:6 (Dec) 2000 p707-9
5. Koster et al. JCTVA 14:3 (June) 2000 p243-48
6. Kanagasaby et al. Case report. Ann Thorac Surg 1998;66:567-9
7. Mertzlufft et al. Case reports. JCTVA 14:3 (June) 2000 p304-8
8. Koster et al. Anesthesiology 2001;94:245-51