Clinical Presentation of HIT. Part 2
Less common manifestations. Premonitory symptoms. Skin necrosis occurring at sites of subcutaneous administration, thought to be mediated by microvascular thrombosis, may precede the development of thrombocytopenia. Administration of intravenous heparin to patients with these lesions may be catastrophic, with the development of severe systemic thromboembolic complications. Acute systemic reactions (resembling acute febrile transfusion reactions) to intravenous heparin bolus therapy have been described in patients with preexisting dermal lesions at sites of subcutaneous heparin administration. There have also been several reports of unexplained abdominal or limb pain, thought to be ischemic in origin, heralding thrombosis.
Heparin resistance. Impending events may also be heralded by the development of increasing heparin requirements to maintain adequate anticoagulation. Although the mechanism underlying this heparin resistance has not been elucidated, it may reflect platelet release of PF4, which has heparin-neutralizing properties, or it may be mediated by the production of platelet-derived microparticles with procoagulant activity.
Hemorrhage. Despite the presence of thrombocytopenia, hemorrhage is less common than thromboembolic complications in these patients, and there is no relation between the degree of thrombocytopenia and the likelihood of bleeding complications. However, when they occur, bleeding complications may be severe and have included intracranial, retroperitoneal, gastrointestinal or adrenal hemorrhage. Patients undergoing bypass surgery may be more prone to the bleeding manifestations of HIT.
Impact of HIT on patients with cardiovascular disease.
There have been several prospective studies investigating the frequency of HIT in patients receiving heparin in the coronary care unit or for coronary artery disease. The reported combined frequency of HIT types I and II ranged from 0% to 24%, and none of the patients reported in these studies experienced thrombotic events. Several early reports cited patients who developed deep venous thrombosis or pulmonary embolus associated with thrombocytopenia while receiving heparin for thromboprophylaxis after acute myocardial infarction. Heparin therapy has been used more aggressively in recent years, with the recognition of the integral role of intracoronary thrombus formation in the development of the acute coronary syndromes. In a recent analysis of 1,000 patients enrolled in four consecutive prospective thrombolytic trials, thrombocytopenia defined as either platelet counts ,100,000/ml or less than half baseline, occurred in 16.4% of patients, and these patients had a higher in-hospital mortality rate and a more complicated hospital course than patients without thrombocytopenia. In a significant number of these patients the fall in the platelet count occurred after 5 to 10 days (median 4) of heparin therapy, suggesting that HIT contributed to some of the detected thrombocytopenia. Patients undergoing bypass surgery for coronary artery disease have usually been exposed to heparin previously and require large doses for thromboprophylaxis during bypass surgery. Retrospective studies have reported a frequency of HIT in these patients of between 0.5% and 1.9%. In one of these reports, late recognition of the condition (i.e., postoperatively) was associated with a high frequency of bleeding (53%), arterial and venous thromboembolic complications (44%) and death (33%). Heparin is also routinely used during percutaneous coronary interventions, and these patients, too, have usually been exposed to the drug previously. Several patients have been described in whom an acute myocardial infarction occurred during coronary angioplasty in association with the abrupt onset of HIT. An association between femoral artery or venous punctures for cardiac catheterization, angiography or insertion of intraaortic balloon counterpulsation devices and arterial or venous thrombosis in the instrumented limbs of patients with HIT has been reported.