Nine studies were included: five prospective observational studies (4 used historical controls), two retrospective chart reviews, one report pooling two studies already mentioned, and one report pooling data from three prospective observational studies. The number of patients is reported in the 'Results' section below.
Thrombosis in patients with HIT when heparin was discontinued.
The prospective study found high rates of thrombosis in hip-surgery patients with HIT: 89% (8 of 9) patients with HIT had thrombosis versus 18% (117 of 656) without HIT. Three further studies (retrospective chart reviews and prospective cohort with historical controls, n=314) found the risk for thrombosis after days or weeks in patients presenting with isolated HIT after stopping heparin ranged from 19 to 52%.
HIT.
Two prospective studies compared HIT patients treated with argatroban with the same pool of historical controls. One study found that HIT patients treated with argatroban (n=160) had a reduction in the combined outcome of death, amputation and new thromboembolic events compared with the 147 controls (25.6% versus 38.8%; RRR 0.34). The other study found similar results for the combined outcome among 189 patients treated with argatroban versus 139 controls (28.0% versus 38.9%; RRR 0.28).
HITTS.
The same two prospective studies (as above) found that HITTS patients treated with argatroban (n=144 and n=229) had a reduction in the combined outcome of death, amputation and new thromboembolic events compared with the 46 controls (43.8% and 41.5% versus 56.5%; RRR 0.23 and RRR 0.27, respectively).
One report of a subgroup analysis from two prospective observational studies described the effect of lepirudin treatment in patients with clinical HIT or HITTS, with HIT-IgG in their plasma, compared with historical controls. The study found that patients treated with lepiriudin (n=113) had a reduction in the combined outcome of death, amputation and new thromboembolic events compared with the 75 controls (22.1% versus 47.8%; RRR 0.53).
HIT or HITTS.
Argatroban (same two prospective studies as above): the prospective cohorts had a higher proportion of patients with HITTS than the historical control (47% and 55% versus 24/25%). Studies found that HIT or HITTS patients treated with argatroban (n=304 and n=418) had a reduction in the combined outcome of death, amputation and new thromboembolic events compared with the controls (n=193 and n=185) (34.2% and 35.4% versus 43.0%; RRR 0.20 and RRR 0.18, respectively).
Lepirudin (same two prospective studies as above with same controls used for both studies): the studies found that patients treated with lepirudin (n=71 and n=95) had a reduction in the combined outcome compared with 120 controls (25.4% and 30.5% versus 52.5%; RRR 0.52 and RRR 0.42, respectively).
Patients with a history of HIT requiring anticoagulation for coronary revascularisation.
One report combined three prospective studies with 91 patients undergoing 112 procedures. The combined outcome (death, MI, or revascularisation at 24 hours or hospital discharge) was found in 7.7% of cases (no deaths, 4 MI and 4 revascularisations). Major bleeding occurred in 1.1%.
Bleeding.
Two observational studies found major bleeding rates of 6.9% and 5.7% with argatroban versus 6.7% and 7.0%, respectively, with controls (RRR -2.56 and RRR 18.2, respectively).
Two observational studies found major bleeding rates of 13.4% and 17.0% with lepirudin.