Bivalirudin for the treatment of patients with confirmed or suspected heparin-induced thrombocytopenia.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is an adverse immune-mediated response to unfractionated heparin and, less commonly, low molecular weight heparin. It is associated with a high thrombotic risk and the potential for limb and life-threatening complications. Argatroban is the only approved and currently available anticoagulant for HIT treatment in the USA. OBJECTIVES: To report safety and efficacy outcomes with bivalirudin for HIT treatment. METHODS: We retrospectively examined records from our registry of patients with a suspected, confirmed or previous history of HIT and who had received bivalirudin for anticoagulation in a single tertiary-care center over a 9-year period. RESULTS: We identified 461 patients who received bivalirudin: 220 (47.7%) were surgical patients, and 241 (52.3%) were medical patients. Of this population, 107 (23.2%) were critically ill, and 109 (23.6%) were dialysis-dependent. Suspected, confirmed and previous history of HIT were reported in 262, 124 and 75 patients, respectively. Of 386 patients with suspected or confirmed HIT, 223 patients (57.8%) had thrombosis at HIT diagnosis. New thrombosis was identified in 21 patients (4.6%) while they were on treatment with therapeutic doses of bivalirudin. No patient required HIT-related amputation. Major bleeding occurred in 35 patients (7.6%). We found a significant increase in major bleeding risk in the critically ill population (13.1%; odds ratio 2.4, 95% confidence interval 1.2-4.9, P = 0.014). The 30-day all-cause mortality rate was 14.5% (67 patients), and eight of 67 (1.7%) deaths were HIT-related. CONCLUSION: Bivalirudin may be an effective and safe alternative option for the treatment of both suspected and confirmed HIT, and appears to reduce the rate of HIT-related amputation.

Large artery occlusive disease.

Large artery occlusive disease is a common problem in the United States. It affects both the upper and lower extremities and is associated with significant morbidity and mortality. This article deals with the clinical recognition of this entity in hopes that the general internist and rheumatologist will more easily recognize it. In addition, the latest technology available to diagnose and treat large artery occlusive disease is discussed.

Angina and coronary ostial lesions in a young woman as a presentation of Takayasu's arteritis.

Diagnostic considerations in young patients presenting with coronary artery disease have conventionally included familial dyslipidemias, lipoprotein(a) elevation, hyperhomocysteinemia, cocaine toxicity, hypercoagulable states, connective tissue disorders, vasculitis and the presence of other established risk factors for coronary artery disease. The case of a young woman with unstable angina and a left main coronary artery ostial lesion on cardiac catheterization is discussed. She was subsequently diagnosed with Takayasu's arteritis 4 years later.

Eugenics in Japan: some ironies of modernity, 1883-1945.

Japanese eugenic discourse and institution building contrast sharply with comparable movements elsewhere. As a social-intellectual phenomenon, Anglo-American eugenics considered the Japanese racially inferior to Western peoples; yet eugenic ideals and policies achieved a remarkable popularity in Japan. Most of mainstream Japanese genetics was derived from orthodox Mendelian roots in Germany and (to a lesser degree) the United States. But French-style Lamarckian notions of the inheritability of acquired characters held surprising popularity among enthusiasts of eugenics. Japanese eugenicists could condemn the actions of foreign eugenicists like Charles Davenport in the United States for their efforts to forbid Japanese immigration in the 1920s, yet appeal to these same eugenicists as a source of legitimacy in Japan. These paradoxes can partly be explained against a background of relative isolation in a period of profound social change. Few Japanese eugenicists had close personal contact with foreign eugenicists, and most of their knowledge was acquired through reading rather than direct exposure. The eugenic ideal of ethnic purity was attractive to a society long accustomed to monoracial self-imagery. The need to defend national independence in an era of high imperialism seemed to require the most up-to-date policies and ideas. And Japan's own acquisition of an overseas empire seemed to demand a population management philosophy ostensibly based on scientific principles. These and other forces supported the implementation of eugenic policies and prescriptions among the Japanese people in the first half of the twentieth century.

Safety and efficacy of thrombolytic therapy for superior vena cava syndrome.

The experience at the Cleveland Clinic from 1982 to 1990 using thrombolytic therapy for superior vena cava (SVC) syndrome was retrospectively reviewed. Sixteen patients, 11 of whom had indwelling central venous catheters, were treated with either urokinase (n = 11) or streptokinase (n = 5). Either urokinase (4,400 U/kg bolus followed by 4,400 U/kg/h) or streptokinase (250,000 U bolus followed by 100,000 U/h) was used, and venograms were performed before and after. Overall, 56 percent of patients had complete clot lysis and relief of symptoms. Thrombolytic therapy was effective in eight (73 percent) of 11 patients receiving urokinase and one (20 percent) of five patients receiving streptokinase. Of those with a central venous catheter, eight (73 percent) of 11 patients were successfully lysed, whereas only one (20 percent) of five patients was successfully lysed if no catheter was present. If thrombolytic therapy was performed less than or equal to five days of symptom onset, seven (88 percent) of eight patients were successful, if thrombolytic therapy was performed greater than five days after symptom onset, two (25 percent) of eight patients were successful. Symptoms were relieved and the catheter was preserved in patients in whom thrombolytic therapy was effective. Factors predicting success were as follows: (1) the use of urokinase compared with streptokinase; (2) the presence of a central venous catheter; and (3) a duration of symptoms less than or equal to five days.

The changing clinical spectrum of thromboangiitis obliterans (Buerger's disease).

Between 1970 and 1987, 112 patients were diagnosed as having thromboangiitis obliterans (TAO). The age was 42 +/- 11 years (mean +/- SD; range, 20-75 years); 23% were women, and 7% were more than 60 years old when they were first diagnosed. Ischemic ulcerations were present in 85 (76%) patients: 24 (28%) patients with upper-extremity, 39 (46%) patients with lower-extremity, and 22 (26%) patients with both upper- and lower-extremity lesions. Ninety-one (81%) patients had rest pain, 49 (44%) patients had Raynaud's phenomenon, and 43 (38%) patients had superficial thrombophlebitis. We were able to follow up 89 of the 112 (79%) patients for 1-460 months (mean follow-up time, 91.6 +/- 84 months). Sixty-five (73%) patients had no amputations, while 24 (27%) had one or more of the following amputations: finger, six (15%) patients; toe, 13 (33%) patients; transmetatarsal, four (10%) patients; below knee, 14 (36%) patients; and above knee, two (5%) patients. Forty-three (48%) patients stopped smoking for a mean of 80 +/- 105 months (median, 46.5 months; range, 1-420 months), and only two (5%) patients had amputations after they stopped smoking, while 22 (42%) patients had amputations while continuing to smoke (p less than 0.0001). The spectrum of patients with TAO is changing in that the male-to-female ratio is decreasing (3:1), more older patients are being diagnosed, and upper-extremity involvement is commonly present. In the 48% of patients who stopped smoking, amputations and continued disease activity were uncommon.

Control of bleeding in patients with immune and nonimmune thrombocytopenia with aminocaproic acid.

Patients with thrombocytopenia have an increased risk of bleeding. We have used 18 courses of aminocaproic acid in 17 patients with either immune or nonimmune thrombocytopenia to successfully control hemorrhage associated with reduced platelet counts. The types of hemorrhage controlled included the following: vaginal, gastrointestinal, intracerebral, cutaneous, mucous membrane, subconjunctival, and renal, as well as that associated with dental extractions, tracheostomy, and sites of Penrose drains. The number of platelet and red blood cell transfusions administered decreased substantially following institution of aminocaproic acid therapy. We conclude that therapy with aminocaproic acid is safe and useful in the management of bleeding in patients with both immune and nonimmune thrombocytopenia.

Abrupt reversal of gestational autoimmune thrombocytopenia after delivery. A case report.

Autoimmune thrombocytopenia purpura frequently is first noted during pregnancy. The severity of the disorder varies, but when the patient presents with active bleeding from any site, therapy is mandatory. Treatment generally consists of corticosteroids and/or splenectomy. A woman developed severe autoimmune thrombocytopenia purpura during pregnancy that proved refractory to corticosteroids and splenectomy. Six days after delivery her platelet count returned to normal. The etiology of autoimmune thrombocytopenia purpura remains unknown, but this experience suggests that in this patient the thrombocytopenia was related to her pregnancy.

A prospective study of the effect of dextran administration on compatibility testing.

The effects of dextran therapy on pretransfusion compatibility testing were evaluated in 24 patients with a variety of vascular disorders. Specimens were drawn before, during, and after the administration of low-molecular-weight dextran (average molecular weight, 40 kd). Forty-three specimens were studied extensively with several immunohematologic techniques. Dextran levels were measured to determine whether the concentration influenced the results of serologic tests. In no instance could we demonstrate any interference by dextran with pretransfusion tests, even at high serum levels of dextran.

Pulmonary thromboembolic disease.

PIP: This monograph includes a state-of-the-art discussion of pulmonary embolism, including its pathogenesis, predisposing factors, clinical presentation, diagnosis, and medical and surgical treatment. This remains one of the most common yet most difficult problems in medical practice. The disease affects 650,000 patients each year in the US, with over 200,000 fatalities. 40-60% of patients who die because of pulmonary emboli arrive at autopsy without the correct diagnosis and treatment. The major source of pulmonary embolism is the deep venous system of the legs and pelvis. Its frequency is greatest in patients ages 50-65 years, with no significant difference between men and women. An association has been identified with oral contraceptives. Figures in the monograph schematize an appropriate diagnostic plan of approach to the patient with suspected pulmonary embolism as well as a combined approach to both diagnosis and treatment. Elements of the latter include a history taking and physical examination for suspicion of pulmonary embolism, arterial blood gas, chest x-ray, electrocardiogram, ventilation-perfusion lung scan, pulmonary angiography, Doppler ultrasound, and thrombolytic therapy followed by heparin. A total of 572 references are cited.^ieng