Clinical Presentation of HIT
Thrombocytopenia. Thrombocytopenia usually commences between 6 and 12 days after instituting therapy. The platelet count typically drops to between 30,000 and 55,000/ml, a feature that distinguishes HIT from other forms of druginduced immune thrombocytopenia, which are typically associated with more precipitous falls in the platelet count. However, counts as low as 5,000/ml have been reported in patients with HIT
Thrombosis. Thromboembolic events are always accompanied by a fall in the platelet count, usually to thrombocytopenic levels, and the mean platelet count in patients with HIT who develop thromboses tend to be lower than that in those who do not develop thromboses . However, in any individual patient the risk of a thrombotic event cannot be predicted from the platelet count, and complications in the absence of absolute thrombocytopenia have been reported. The most common thrombotic complications attributed to HIT have been arterial events resulting in lower limb ischemia, cerebrovascular accident or myocardial infarction. Arterial thrombotic episodes at many other sites have also been reported, including arterial graft thrombosis, upper limb arterial thrombosis, renal artery thrombosis, mesenteric ischemia spinal artery thrombosis, aortic thrombosis splenic infarction, thrombosis of cardiac chambers and adrenal thrombosis resulting in acute adrenal insufficiency. These events, when they occur, often have serious sequelae; it has been estimated that patients with HIT and arterial thrombosis have a mortality rate of ;30% and have a risk of leg amputation of ;20% Extension of venous thrombosis with recurrent pulmonary embolism has frequently been described in patients after onset of HIT. Venothrombotic events may be severe—for instance, the progression of venous thrombosis to phlegmasia cerulea dolens, in some cases requiring amputation.
Other reported venous thrombotic events include renal vein thrombosis, cerebral venous thrombosis and thrombosis of the upper limb veins. Thromboses frequently occur at multiple sites, and arterial and venous events may occur together.
Predictors of risk and nature of thrombotic event. A number of studies have suggested that thrombotic events are more likely to occur at sites of preexisting pathology. In one reported series of 25 patients developing HIT and arterial or venous thrombosis, 19 had passage of an arterial or venous catheter or an intraaortic balloon ounterpulsation device in the affected extremity. Similarly, Singer et al. reported a series of four patients who developed thrombotic complications of HIT requiring limb amputation after cardiopulmonary bypass, all of whom had previous intravascular devices at those sites. A recent detailed review of 53 patients with HIT identified an association between cardiovascular disease (myocardial infarction or cardiovascular surgery) and arterial thrombotic events. These investigators also noted a recent operation to be strongly associated with venous thrombosis. In patients receiving heparin after a cerebrovascular accident, 7 of 21 patients with a significant fall in the platelet count experienced an arterial thrombotic event, either extension of their cerebrovascular accident or a myocardial infarction. There were no venous thrombotic events reported in this patient group.