Low-dose danaparoidb

Platelet transfusions

IVC filters

Use low-dose alternative anticoagulation or heparin in patients with low probability for HIT

Potential for increase in thrombin generation; high frequency of thrombosis despite stopping heparin

High frequency of thrombosis; potential for coumarin necrosis (venous limb gangrene and skin necrosis syndromes)

High frequency of exacerbating thrombocytopenia when given to patients with acute HIT

High frequency of thrombosis if low-dose danaparoid is given to patients with "isolated HIT"

May increase risk for platelet-mediated thrombosis

May increase risk for IVC thrombosis, pulmonary embolism, limb ischemia/ necrosis Risk of bleeding outweighs risk of thrombosis in patients with thrombocytopenia due to other reasons than HIT

Use heparin for cardiovascular surgery despite previous history of HIT

In patients with a history of HIT who subsequently test negative for HIT antibodies, heparin is safer for intravascular anticoagulation than alternative anticoagulants

Use an alternative, rapid-acting anticoagulant3 when heparin is stopped because of strongly suspected HIT Control thrombin generation with an alternative anticoagulant; postpone coumarin pending substantial platelet count recovery Although LMWH is less likely than UFH to cause HIT, LMWH is likely to maintain or worsen acute HIT caused by UFH High (therapeutic)-dose danaparoid recommended for patients strongly suspected (or confirmed) to have isolated HIT or HIT-thrombosis Spontaneous bleeding is uncommon in HIT even with severe thrombocytopenia; thus, prophylactic platelet transfusions are relatively contraindicated IVC filters should be avoided in acute HIT; if used, concomitant anticoagulation in therapeutic doses should be given The risk-benefit ratio of therapeutic-dose non-heparin anticoagulation is not favorable for non-HIT thrombocytopenia, given the high risk of bleeding and lower risk of thrombosis (overall, only 5-10% of patients evaluated serologically for HIT are shown to have heparin-dependent, platelet-activating antibodies) HIT antibodies usually disappear quickly (within a few weeks or months), and are not regenerated within 5 days following reexposure to heparin, thus allowing heparin use during surgery aRapidly acting alternative anticoagulants include danaparoid, lepirudin, and argatroban. bLow-dose danaparoid (750 U two or three times a day) is approved for prevention of thrombosis in acute HIT in some jurisdictions.

Abbreviations: HIT, heparin-induced thrombocytopenia; IVC, inferior vena cava; LMWH, low molecular weight heparin; UFH, unfractionated heparin.

treatment outcomes. Hence, we have no grade A and only one grade B recommendation. Grade C recommendations are based upon observational studies. Regarding HIT, this includes prospective cohort treatment studies with historical controls (Greinacher et al., 1999a,b, 2000; Lubenow et al., 2005; Lewis et al., 2001, 2003, 2006); case-control series (Warkentin et al., 1997; Lubenow et al., 2006); and large case series (e.g., Magnani, 1993, 1997; Magnani and Gallus, 2006; Warkentin and Kelton, 1996; Wallis et al., 1999). Thus, our recommendations are graded as follows, with the implications of the recommendation shown:

Grade 1B and Grade 1C: strong recommendations, which apply to most patients in most circumstances; and

Grade 2C: weak recommendations; other alternatives may be equally reasonable.

As no studies have directly compared the three major treatment options for HIT (danaparoid, lepirudin, and argatroban), any recommendation for use of one of these drugs does not imply any proven or consistent advantage over any of the others. However, there are important pharmacokinetic differences, which might well favor use of one in the particular circumstances of an individual patient situation (see Chapters 13-20).

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