Heparin-induced thrombocytopenia and thrombosis: presentation after cardiopulmonary bypass

Heparin-induced thrombocytopenia and thrombosis syndrome was diagnosed in a 63-year-old woman 11 days after coronary artery bypass grafting. Her only presenting complaints were incisional leg pain and vague chest discomfort. The syndrome was suspected when her platelet count was found to be 37,000/microL. A subsequent ventilation-perfusion lung scan showed findings highly probable for pulmonary embolism. An inferior venacavogram obtained before a pulmonary angiogram revealed a large retrohepatic thrombus at the right atrial junction. The patient was successfully treated with the defibrinogenating agent ancrod (Arvin). A diagnosis of heparin-induced thrombocytopenia and thrombosis syndrome should be considered and heparin therapy should be avoided in patients with low platelet counts who have been previously treated with heparin.     

Heparin-induced thrombocytopenia with thrombotic complications during prophylactic treatment with low-molecular-weight heparin

Heparin-induced thrombocytopenia is very uncommon with low-molecular-weight heparin, especially when given for prophylaxis of venous thromboembolism. In two of the four published cases, with thrombotic complications, thrombocytopenia may have been related to cross-reactivity between unfractionated heparin and low-molecular-weight heparin. We report one patient who received low-molecular-weight heparin for prophylaxis against venous thromboembolism without any previous injection of unfractionated heparin, and experienced thrombocytopenia with thrombotic complications. Heparin-induced thrombocytopenia was confirmed by several laboratory assays. This observation emphasizes the need for platelet count monitoring during low-molecular-weight heparin therapy.     

Cardiopulmonary bypass with danaparoid sodium and ancrod in heparin-induced thrombocytopenia

Heparin is the standard anticoagulant for patients undergoing cardiopulmonary bypass. There are some patients for whom heparin is unsuitable and ancrod (a defibrinogenating enzyme) has been used as an alternative. We present a patient with heparin-induced thrombocytopenia in whom treatment ancrod was ineffective. The addition of danaparoid sodium (a heparinoid) allowed safe cardiopulmonary bypass. We discuss the reasons for this and suggest that the combination of ancrod and danaparoid sodium is a logical one in such cases.     

Inhibition of repetitive thrombus formation in the stenosed canine coronary artery by enoxaparin, but not by unfractionated heparin

Experiments were designed to compare the antithrombotic efficacy of enoxaparin and unfractionated heparin (UH) in a model of platelet-dependent cyclic flow reductions (CFRs) in the stenosed canine circumflex coronary artery. Low-molecular-weight heparins (LMWHs) are safe and effective in the prevention and treatment of venous thromboembolism. The present experiments were designed to evaluate the potential use of LMWHs in arterial thrombotic indications by comparing the antithrombotic effect of an LMWH with that of UH in an animal model of unstable angina. After establishment of consistent CFRs by experimentally induced vascular stenosis and damage, vehicle (saline), enoxaparin, or UH was administered intravenously as a loading dose plus a continuous infusion for 1 hour. The inhibition of CFRs was taken as an indicator of antithrombotic efficacy. Enoxaparin inhibited repetitive platelet thrombus formation in a dose-dependent manner, with significant inhibition of CFRs achieved at 0.5 mg/kg + 5 microg/kg per minute. This dose of enoxaparin resulted in anti-Xa levels of 0.9 to 1.0 IU/mL, anti-IIa levels of 0.2 to 0.3 IU/mL, activated partial thromboplastin time (APTT) of 1.3-fold over baseline, and a 1.4-fold increase (NS) in template bleeding time. Near-complete abolishment of CFRs was achieved with enoxaparin at 1.0 mg/kg + 10 microg/kg per minute. This dose of enoxaparin produced anti-Xa levels of 2 to 2.2 IU/mL, anti-IIa levels of 0.5 to 0.6 IU/mL, an increase in APTT of 1.4- to 1.5-fold over baseline, and a 1.9-fold increase (P<0.05) in template bleeding time. In contrast, UH had no significant effect on CFRs at a dose (100 U/kg + 10 U/kg per minute) that resulted in anti-Xa levels of 1.2 to 1.6 IU/mL, anti-IIa levels of 1.8 to 2.4 IU/mL, an increase in APTT greater than 10-fold over baseline, and a 2.5-fold increase (P<0.05) in template bleeding time. Compared with the vehicle group, circulating platelet count and hematocrit were not changed significantly by any dose of enoxaparin or UH tested. Enoxaparin, unlike UH, prevented repetitive platelet-dependent thrombus formation in the dog, thereby supporting the potential use of enoxaparin as a replacement for heparin in the treatment of arterial thrombotic disorders such as unstable angina.     

A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis. Prévention du Risque d'Embolie Pulmonaire par Interruption Cave Study Group

BACKGROUND: The efficacy and safety of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis is still a matter of debate. METHODS: Using a two-by-two factorial design, we randomly assigned 400 patients with proximal deep-vein thrombosis who were at risk for pulmonary embolism to receive a vena caval filter (200 patients) or no filter (200 patients), and to receive low-molecular-weight heparin (enoxaparin, 195 patients) or unfractionated heparin (205 patients). The rates of recurrent venous thromboembolism, death, and major bleeding were analyzed at day 12 and at two years. RESULTS: At day 12, two patients assigned to receive filters (1.1 percent), as compared with nine patients assigned to receive no filters (4.8 percent), had had symptomatic or asymptomatic pulmonary embolism (odds ratio, 0.22; 95 percent confidence interval, 0.05 to 0.90). At two years, 37 patients assigned to the filter group (20.8 percent), as compared with 21 patients assigned to the no-filter group (11.6 percent), had had recurrent deep-vein thrombosis (odds ratio, 1.87; 95 percent confidence interval, 1.10 to 3.20). There were no significant differences in mortality or the other outcomes. At day 12, three patients assigned to low-molecular-weight heparin (1.6 percent), as compared with eight patients assigned to unfractionated heparin (4.2 percent), had had symptomatic or asymptomatic pulmonary embolism (odds ratio, 0.38; 95 percent confidence interval, 0.10 to 1.38). CONCLUSIONS: In high-risk patients with proximal deep-vein thrombosis, the initial beneficial effect of vena caval filters for the prevention of pulmonary embolism was counterbalanced by an excess of recurrent deep-vein thrombosis, without any difference in mortality. Our data also confirmed that low-molecular-weight heparin was as effective and safe as unfractionated heparin for the prevention of pulmonary embolism.     

Puerperal thromboprophylaxis: comparison of the anti-Xa activity of enoxaparin and unfractionated heparin

Low molecular weight heparins are used extensively for thromboprophylaxis. The aim of this study was to compare the activity of the low molecular weight heparin, enoxaparin, 20 mg and 40 mg, given once per day with unfractionated heparin, 7500iu given twice per day, in terms of their anti-Xa activity in puerperal women following caesarean section and with an additional risk factor for venous thromboembolism. Seventeen women were randomised to receive one of the three treatments. The anti-Xa activity associated with each treatment was measured prior to treatment and at 2, 4, 6, 12 and 24 hours. The mean anti-Xa values of the groups receiving enoxaparin, 20 mg and 40 mg, were significantly higher than those of the group receiving unfractionated heparin. There was no difference between the two enoxaparin groups in terms of the anti-Xa activity profiles. This study suggests that the use of enoxaparin is superior to unfractionated heparin in terms of anti-Xa activity.     

Hybrid myocardial revascularization after previous left pneumonectomy

Previous intrapericardial left pneumonectomy and irradiation necessitated an unorthodox, staged approach to myocardial revascularization in a patient with unstable angina pectoris, left main artery, and three-vessel coronary artery disease. A saphenous vein bypass graft was constructed from the descending thoracic aorta to the left anterior descending coronary artery via left thoracotomy, without cardiopulmonary bypass. Two days later the patient underwent stenting of the left main and circumflex coronary arteries. Recovery was uneventful.     

Subcutaneous low-molecular-weight heparin for treatment of Trousseau's syndrome

We report the case of a 76-year-old man with recurrent thromboses despite oral anticoagulation with phenprocoumon and low-grade chronic disseminated intravascular coagulation. Workup revealed a bronchial carcinoma (NSCCL) with hilar and mediastinal lymph node metastases. The clinical condition was consistent with Trousseau's syndrome. Based on reports in the literature, the therapy was changed to intravenous unfractionated heparin (UFH), which was effective in controlling the thrombotic coagulopathy. For practical reasons, despite a lack of evidence of its effectiveness in Trousseau's syndrome, therapy with UFH was changed to subcutaneous low-molecular-weight heparin (LMWH, nadroparine) in therapeutic doses of 100 IU/ kg body wt. 12 hourly. On an outpatient basis, five chemotherapy cycles were administered, and after metastases of the brain had been detected radiotherapy was initiated. Following 7.5 months of progressive neoplastic disease the patient died. He had remained free of thromboembolic complications under continued LMWH therapy during the last 6.5 months of his life. LMWH might be a convenient alternative to the established therapy with UFH in Trousseau's syndrome.     

Therapy and prevention of cerebral ischemia

Two large randomized studies - NINDS and ECASS - have shown that fibrinolytics, when given early enough, reduce morbidity and mortality in acute stroke. The treatment has to be initiated within three hours after onset of symptoms. In middle cerebral artery stroke, fibrinolysis can be performed within six hours from onset, guided by computed tomography criteria. Thereafter, s.c. low-molecular-weight heparin can still improve the fate of the patient. Currently, the potential benefit or harm of unfractionated heparin and aspirin is not yet known. However, large-scale studies using standard heparin, aspirin of low-molecular-weight heparin are in progress with results expected soon. After the acute stage of stroke, risk factors have to be eliminated or modified, and anticoagulants, platelet inhibitors and, in selected cases, carotid endarterectomy are useful in preventing recurrent stroke or other vascular events.     

Recognition, diagnosis, and management of heparin-induced thrombocytopenia and thrombosis

This case report describes a post-coronary artery bypass graft patient who developed arterial thrombosis and loss of a dominant hand as a result of the common and serious immune complication of heparin anticoagulation, heparin-induced thrombocytopenia and thrombosis. This report underscores the need for all surgeons who use heparin in the course of their practice to be aware of heparin-induced thrombocytopenia and the spectrum of its clinical presentations and management. Thrombocytopenia or thrombosis that occurs in a patient receiving heparin should prompt a surgeon to stop all heparin as soon as possible and seek appropriate hematologic consultation. Because heparin-induced thrombocytopenia and heparin-induced thrombocytopenia and thrombosis are mainly clinical diagnoses, one should not wait for objective test confirmation of heparin-induced thrombocytopenia before stopping all heparin treatment. Alternative anticoagulation, other than low molecular weight heparin, must be considered for the patient who develops either condition. For surgeons who perform hand surgery, it is necessary to be aware of the significance of upper extremity thrombosis in a patient who is receiving heparin when consulted for surgical management.     

Interventional coronary revascularization in a patient with chronic dissection of the ascending aorta

In a 74-year-old patient who had undergone coronary artery bypass grafting 8 years earlier, angiography was performed for recent onset of angina pectoris. Surprisingly, angiography revealed chronic dissection of the ascending aortic vessel with occlusion of a saphenous vein graft and partial thrombosis of the false lumen. Additionally, there was significant progression of coronary artery disease with new stenoses in both the ostium and body of the saphenous vein graft to the right coronary artery and a high grade left main coronary artery stenosis. Because any surgical intervention was refused by the patient, an interventional therapeutic strategy with percutaneous transluminal dilatation and stenting of both the bypass graft and the left main coronary artery was planned and successfully performed. This is the first report of a complex intervention and revascularization procedure carried out in a patient with type A aortic dissection. Thus, selected cases of chronic type A dissection my be amenable to interventional coronary revascularization in acute coronary syndromes.     

Abbreviated hospitalization for deep venous thrombosis with the use of ardeparin

BACKGROUND: Ardeparin sodium has recently received approval by the Food and Drug Administration for prophylaxis against venous thromboembolism in patients undergoing elective total knee replacement. However, this low-molecular-weight heparin has not been previously evaluated in a randomized controlled trial for treatment of established acute deep venous thrombosis. METHODS: The study included patients with ultrasound-documented acute symptomatic deep venous thrombosis of the legs. They had to be deemed appropriate for discharge home to receive subcutaneous low-molecular-weight heparin. Patients were randomized to receive ardeparin with a 2-day hospitalization or unfractionated heparin sodium with a 5-day hospitalization. Both groups received warfarin sodium. Follow-up ultrasound examinations were undertaken at 6 weeks. RESULTS: Of the 80 patients enrolled, 75 had follow-up ultrasonography. Evaluation of baseline vs 6-week venous scans demonstrated that, overall, 31 of the 39 ardeparin-treated patients improved, compared with 21 of the 36 patients assigned to receive unfractionated heparin (P=.05). The 95% confidence interval for the difference in improvement was 0.6% to 42% in favor of ardeparin. Median charges for ardeparin and unfractionated heparin were $2815 and $6500, respectively (P<.001). There were no differences in bleeding or patient satisfaction between the 2 groups. CONCLUSIONS: The results of this small preliminary trial suggest that ardeparin can be administered effectively and safely to selected patients with acute deep venous thrombosis and that, with proper nursing and home services, it can help decrease the duration of hospitalization.     

Tracking the MEN1 gene

Combined carotid endarterectomy and coronary artery bypass grafting was performed in 52 patients between January 1982 and September 1994. Forty-nine patients had stable or unstable angina and three had symptom-free coronary artery disease detected by stress testing. Thirty-one patients had triple-vessel disease and 17 had left main trunk or left main equivalent coronary artery disease. Five patients had symptom-free carotid artery disease, 12 had non-specific neurological symptoms, and 35 had transient ischaemic attacks. Carotid endarterectomy was performed first, followed by coronary artery bypass grafting. There were three postoperative deaths, two cardiac and one neurological, for a mortality rate of 5.8%. One patient suffered a permanent neurological deficit (1.9%). It is concluded that combined carotid endarterectomy/coronary artery bypass grafting can be performed in selected patients with acceptable neurological morbidity, although cardiac mortality was not eliminated by the combined approach.     

Gene organization and chromosome mapping of the testis-specific S-II

We report a patient with refractory angina in the postoperative period of a coronary artery bypass grafting. Ischemia was due to a large side branch of the left internal mammary artery causing steal phenomenon that was treated with transcatheter coil embolization.     

Cost effectiveness of low-molecular weight heparin versus warfarin following hip replacement surgery

Little information is available on the efficacy of low-molecular-weight heparin (enoxaparin) versus warfarin for treatment of deep vein thrombosis and pulmonary embolism following hip replacement surgery. Still less is known of the comparative cost effectiveness of these two therapies. A retrospective study was done on 56 patients who underwent elective hip surgery at an urban medical center between 1991 and 1996. All patients received enoxaparin or warfarin for purposes of thromboprophylaxis. An analysis of medication cost, therapy, laboratory monitoring, and bleeding events of the two antithrombolytic agents was undertaken. Total savings with enoxaparin averaged $1253 per patient, or $137,886 over the study period. The incidence of deep vein thrombosis or pulmonary embolism was 0% with enoxaparin and 3% with warfarin. These data indicate that enoxaparin is a more cost-effective and efficacious regimen for thromboprophylaxis following hip replacement surgery than warfarin.     

Successful aorto-circumflex coronary bypass grafting through left thoracotomy following aortic and mitral valve replacement

We report successful descending thoracic aorto-circumflex coronary artery bypass grafting using a saphenous vein graft through left thoracotomy in a 44-year-old female. The patient developed severe angina attack after aortic and mitral valve replacement. Coronary angiography showed 99% stenosis of the circumflex coronary artery. Under general anesthesia, left femoral vein to arterial partial cardiopulmonary bypass was performed via left 4 th intercostal space. Body temperature was lowered to 22 degrees centigrade, and spontaneous cardiac fibrillation occurred. After minimal exposure by pericardial dissection of the circumflex coronary artery, distal anastomosis and then proximal anastomosis at the descending thoracic aorta was carried out under cardiac fibrillation. This surgery was done with minimal intra-and postoperative bleeding. Postoperative course was very smooth, and the patient was discharged and leading a normal life for 6 months after surgery.     

Increased platelet responsiveness following coronary stenting. Heparin as a possible aetiological factor in stent thrombosis

AIMS: Platelet activation may be a determinant of thrombotic and restenotic complications following intracoronary stenting. In order to measure the effect of stenting on platelet activation antigen expression we used whole blood flow cytometry in 18 patients undergoing Palmaz-Schatz stenting (treated with full anticoagulation) and compared these with a group of 18 patients undergoing elective angioplasty. The effects of low molecular weight heparin and unfractionated heparin on platelet behaviour were also studied, both in vitro and in vivo to determine the contribution of prolonged heparin therapy to platelet activation following stenting. METHODS AND RESULTS: Fibrinogen binding to activated GPIIb-IIIa, and surface expression of P-selectin, GPIb and GPIIb-IIIa antigens were measured in unstimulated peripheral blood samples (rest) and on stimulation with adenosine diphosphate (0.1-10 micromol x 1(-1)) and thrombin (0.02-0.16 U x ml(-1)). No changes were seen in resting samples following angioplasty or stenting. Agonist responsiveness was unaltered after angioplasty, but in stented patients antigen expression in response to thrombin was significantly reduced (P< or =0.04), whilst the adenosine diphosphate response was significantly increased (P=0.01). Similar effects were observed in patients with unstable angina treated with either low molecular weight heparin or unfractionated heparin in vivo. In vitro, both unfractionated and low molecular weight heparin inhibited thrombin-induced platelet activation, but stimulation of adenosine diphosphate responses was more marked with unfractionated than low molecular weight heparin. CONCLUSIONS: There was a significant increase in platelet responsiveness to adenosine diphosphate following intracoronary stenting in patients treated with conventional anticoagulants. This was probably a consequence of treatment with heparin. Activation of platelets by heparin may explain the increased rate of stent thrombosis in patients treated with anticoagulant therapy. Low molecular weight heparins stimulate platelets less than unfractionated heparin.     

Preventing the cardiotoxic effects of anthracyclines with Cardioxane]

An immune response to heparin, which is clinically manifested by the development of thrombocytopenia with or without thrombosis, is stimulated by a complex of heparin with platelet factor 4 (PF4). The primary thrombotic events in patients with heparin-induced thrombocytopenia (HIT) are more frequently venous than arterial. The development of antibodies, however, does not always result in thrombocytopenia or in catastrophic events. The antibodies, which are of the IgG, IgM, and IgA isotypes, can be easily measured by an ELISA that contains a complex of heparin-platelet factor 4 (PF4). Initial antibody formation can be greatly reduced by limiting the exposure to unfractionated heparin or by the use of low-molecular-weight heparin. For those patients who require anticoagulation and who have antibodies to heparin-PF4, danaparoid (Orgaran), a low-molecular weight heparinoid that does not react with the antibodies, is now commercially available; argatroban, a thrombin-specific inhibitor, can also be obtained for compassionate use. The use of these agents during anticoagulation with warfarin is preferable to the simple discontinuation of heparin and intitiation of warfarin, because the latter treatment can result in ongoing thrombosis.     

Coronary obstruction secondary to direct cannulation

Four patients are reported with obstruction of the proximal left main coronary artery that developed following prosthetic replacement of the aortic valve. Angina pectoris and ventricular arrhythmias were the presenting clinical manifestations. Anterior descending coronary artery bypass was used in 3 of the patients and vein patch angioplasty in the fourth. One patient died in the hospital. The 3 survivors achieved reflief from angina and ventricular arrhythmias. One patient died from nephropathy 2 1/2 years later. Two patients remained asymptomatic 1 1/2 and 3 years later, respectively. This review emphasizes the need for prompt coronary angiography in patients experiencing angina pectoris after aortic valve replacement, and it shows that coronary revascularization can be performed with satisfactory results.     

A case of coronary artery bypass grafting for single coronary artery complicated by angina pectoris

A case of coronary artery bypass grafting (CABG) for single coronary artery complicated by angina pectoris (AP) was reported. The patient was a 74-year-old male, complained of anginal discomforts. His single coronary artery originated in left coronary sinus, bifurcated to the left anterior descending artery (LAD) and the circumflex artery (CX), and then, an abnormal communicating branch, passing in front of the right ventricular outflow, was branched from the proximal region of LAD; it showed a route corresponding to the proximal region of the right coronary artery (RCA). The distal region of RCA and the posterior descending artery were angiographed in continuity from CX. Other findings included 75%-stenosis at LAD-#6 and 90%-stenosis at CX-#13. Using two saphenous vein grafts, CABG operation was carried out on those regions at LAD-#7 and distal CX corresponding to #3 normally. Postoperatively, anginal discomforts disappeared, and favorable results were obtained.