Full Heparinization Research Articles

Usefulness of Antiplatelet Drugs in the Management of Heparin-Associated Thrombocytopenia and Thrombosis

Heparin-associated thrombocytopenia and thrombosis is a severe complication of systemic heparin therapy. Its treatment is mainly based upon discontinuation of heparin therapy. However in some patients requiring emergency cardiac or vascular surgery, reexposure to heparin may be unavoidable. We report the management of two such patients by use of antiplatelet drugs for a vascular procedure. In the two cases, a combination of iloprost, a stable prostacyclin analogue (1 to 2 ng/kg/mn) with aspirin and dipyridamole was shown to inhibit ex vivo the heparin-induced platelet aggregation. These antiplatelet agents were continued during the perioperative period. A successful vascular procedure was achieved with full heparinization without subsequent thrombocytopenia or thrombotic or hemorrhagic complications. This experience supports the hypothesis that heparin can be readministered early to patients with heparin-associated thrombocytopenia and thrombosis, provided antiplatelet therapy is given.

Thromboembolic phenomena in neurosurgical patients operated upon for primary and metastatic brain tumours

A retrospective study was designed to evaluate clinical thromboembolic phenomena (TEP) in patients operated upon for brain tumours. Among 492 patients treated surgically in the supratentorial area, the overall incidence of clinical TEP was 7%. There were 5% with deep vein thrombosis (DVT) and 4% with clinical pulmonary embolism (PE). Seven patients (1%) died from massive PE. Among 141 patients treated surgically in the infratentorial area there were no episodes of TEP. Significant risk factors for TEP development were operations in the supratentorial area, malignant gliomas (compared to meningiomas) and para- or hemiparesis. Age, sex and the specific location in the supratentorial area were not found to be statistically significant risk factors. Among 12 patients who presented initially with DVT two developed PE despite full heparinization. 7/19 patients with PE died within minutes to hours of the clinical episode despite full conservative measures. In 2/26 patients who were treated with full heparinization complications occurred. There was one case of diffuse subcutaneous bleeding and one case of tumour bed haematoma. The identification of risk factors for the development of TEP will allow the implementation of prophylactic measures in appropriate patients undergoing elective brain tumour surgery.

Coagulation Patterns in Perfusion with Low Systemic Heparinization

Cardiopulmonary bypass (CPB) with heparin coated perfusion equipment was realized in 13 patients undergoing myocardial revascularization with either low (ACT> 180) or full systemic heparinization (ACT>480). Blood samples for coagulation and other studies were drawn before, after heparin, and at regular intervals during and after CPB. Heparinization low full p< Preop ACT s 118±6 112±13 NS PTT s 38±4 35±2 NS TT s 14±1 14±1 NS D-dimers mg/L <05 <0.5 NS Heparin IU 103 8±2 51±9 .01 CPB 60 min ACT s 230±19 594±287 .05 PTT s 56±9 94±63 .10 TT s >200 >200 NS D-dimers mg/L <0.5 <0.5 NS Protamin IU 103 7±1 30±4 .01 60 min ACT s 110±11 109±9 NS PTT s 47±6 48±10 NS TT s 19±6 19±8 NS D-dimers mg/L 0.6±0.5 1.1±0.6 NS Blood loss day 1 L/m2 0.4±0.1 1.0±1.0 .05 We conclude, that low dose systemic heparinization (16% of full) resulted in adequate anticoagulation during perfusion with heparin coated equipment and in reduced blood loss.

Evolving experience with thoracoabdominal aortic aneurysm repair at a single institution

Fifty-seven patients underwent repair of atherosclerotic thoracoabdominal aortic aneurysms between 1978 and 1990. Five patients had urgent surgery for rupture. The 30-day operative mortality rate for the entire group was 18% (10 patients). Before July 1987, 19 patients (group 1) were operated on by use of a technique previously described. In these earlier patients the peritoneum was routinely entered, the diaphragm was divided radially, and no heparin was given. Among patients in group 1 there was a 30-day operative mortality rate of 42% (8 patients), and morbidity included myocardial infarction 4 (21%), respiratory failure 9 (47%), renal failure 12 (63%), bleeding requiring reoperation 4 (21%), and intestinal ischemia 3 (16%). Since July 1987 a standardized approach to all elective thoracoabdominal aortic aneurysms has been used in 38 patients (group 2). This method uses a left thoracoabdominal incision, circumferential division of the hemidiaphragm, retronephric totally extraperitoneal aortic exposure, single lung anesthesia, full heparinization, the graft inclusion technique, and liberal use of visceral endarterectomy. Patients in group 2 sustained a 30-day operative mortality rate of 5% (2 patients) and morbidity included myocardial infarction 2 (5%), respiratory failure 10 (26%), renal failure 11 (29%), bleeding requiring reoperation 1 (3%), paraplegia 6 (16%), and paraparesis 4 (11%). Modern surgery for repair of thoracoabdominal aortic aneurysm results in acceptably low operative mortality rates. Spinal cord ischemia remains an unresolved source of morbidity.

Prevention of stenosis after vascular reconstruction: Pharmacologic control of intimal hyperplasia — A review

Prevention of stenosis after vascular reconstruction: Pharmacologic control of intimal hyperplasia — A review

The Controversy of Heparin Therapy as an Adjunct to Thrombolysis in Acute Myocardial Infarction

Heparin is used routinely in the US as adjunct therapy for prevention of reocclusion after thrombolysis during acute myocardial infarction. A review of the literature shows controversy over the efficacy of heparin following thrombolysis. Both beneficial and a lack of beneficial effects have been reported with heparin. From a pathophysiologic viewpoint, there appears to be a need for full heparinization in the postlytic period because the residual stenosis is highly thrombogenic. However, optimal dose, time, and mode of heparin therapy has not been defined. Despite a lack of definitive data, it seems reasonable to administer intravenous heparin immediately after thrombolytic therapy to achieve a partial thromboplastin time 1.5-2.0 times control that is concurrent with an antiplatelet agent such as aspirin. These recommendations are consistent with the consensus opinion of the American College of Cardiology and the American Heart Association.

Effects of prolonged transesophageal echocardiographic imaging and probe manipulation on the esophagus—An echocardiographic-pathologic study

Transesophageal echocardiography is being increasingly utilized in the operating room and intensive care and ambulatory settings. However, to date no data are available concerning possible trauma of the transesophageal echocardiographic technique to the esophagus due to probe insertion, manipulation or direct ultrasound energy transmission. To test the hypothesis that transesophageal manipulations caused no traumatic or thermal injury to the esophageal mucosa, 12 animals were studied with continuous transesophageal echocardiography for a period of variable duration (mean 4.6 h +/- 51 min). The study group consisted of four monkeys (mean weight 5.7 +/- 0.6 kg and eight mongrel dogs (mean weight 29.8 +/- 1.4 kg). The eight dogs were studied during right heart bypass with full heparinization for 6.6 +/- 0.2 h, whereas the four monkeys were studied for 60 to 90 min in the absence of cardiopulmonary bypass and anticoagulation. Immediately after completion of transesophageal echocardiography in each case, the esophagus was entirely excised. Detailed macroscopic and microscopic examination of the esophagus revealed no significant mucosal or thermal injury. This preliminary animal study suggests that transesophageal echocardiography is safe for the esophageal mucosa in animals as small as 5 kg in weight, despite prolonged use and in the presence of systemic anticoagulation.

Pulmonary Thromboembolism Complicating Recurrent Placental Abruption at 29 Weeks' Gestation

A patient with major pulmonary thromboembolism associated with recurrent placental abruption is described. Delivery by Caesarean section was necessary, followed by full heparinization. The use of peripartum heparinization and Caesarean section is reviewed.

Heparin‐Coated Equipment Reduces Complement Activation during Cardiopulmonary Bypass in the Pig

Complement activation was studied during cardiopulmonary bypass (CPB) in the pig. One group of animals was perfused for 2 h using a standard extracorporeal circuit including a hollow fiber membrane oxygenator with full systemic heparinization. Another group was treated in the same way, except that bypass was performed through a heparin-coated CPB circuit (Carmeda Bio-Active Surface, CBAS) and systemic heparinization was reduced by 75%. It was found that complement activation during CPB, measured as changes in the ratio C3d/C3, was significantly less in the CBAS group, most probably reflecting a better biocompatibility.

Reduced blood loss and transfusion requirements with low systemic heparinization: preliminary clinical results in coronary artery revascularization

In coronary artery revascularization, low systemic heparinization was compared to full systemic heparinization during perfusion with heparin surface-coated cardiopulmonary bypass equipment. Twelve patients were randomly assigned to two groups and perfused with low [activated clotting time (ACT) greater than 180 s] or full (ACT greater than 480 s) systemic heparinization. A standard battery of blood samples was taken before the procedure, after heparinization, and at regular intervals during and after cardiopulmonary bypass. No differences were seen between the two groups in regard to age, body surface area, preoperative hematocrit, duration of bypass, bypass hypothermia, cross-clamp time, and number of bypasses per patient. However, there were more internal thoracic artery (ITA) grafts in the group with low systemic heparinization (1.5 +/- 0.8 ITA grafts per patient versus 0.8 +/- 0.4 ITA grafts per patient with full heparinization; p less than 0.05). The oxygenator gradient at the end of perfusion (before weaning) was 107 +/- 40 mmHg for low versus 110 +/- 10 mmHg for full heparinization (difference not significant). The total amount of heparin used was 7200 +/- 1030 IU for low versus 51400 +/- 9700 IU for full (p less than 0.05). Postoperative hematocrit was 35.0 +/- 2.0% for low versus 24.7 +/- 2.7% for full (p less than 0.05). Total chest tube drainage was 428 +/- 153 ml/m2 for low versus 935 +/- 414 ml/m2 for full (p less than 0.05). Homologous transfusions of blood products were necessary in 3/6 patients for low versus 6/6 patients for full (p less than 0.10).(ABSTRACT TRUNCATED AT 250 WORDS)

Percutaneous Cardiopulmonary (Bypass) Support in the Cardiac Catheterization Laboratory: A New Application of Perfusion

Percutaneous cardiopulmonary bypass support (PCPS) has been introduced in the catheterization laboratory to support high risk coronary angioplasty, as well as emergencies. We report the safety and feasibility of PCPS in 45 patients. Thirty-seven patients (Group 1) were elective and eight were emergencies (Group 2). Group 1 (ages 41-82) were high risk coronary angioplasty, Group 2 (ages 40-82) were in cardiogenic shock due to myocardial infarction with two in cardiac arrest. Cannulation of femoral artery and vein was with 20 French cannulae. Priming of the system with 1400 ml of Normosol was achieved in 5-7 minutes. Cardiopulmonary bypass was then instituted using the Bard CPS system after full heparinization (300 units per kilogram). Flows ranged from 2.8-5.5 liters per minute (mean-3.8) and pulmonary diastolic pressures were 0-4 mm Hg. Two patients in cardiac arrest regained consciousness while still in ventricular fibrillation or asystole. The activated clotting time ranged from 317-880 seconds (mean=498). Mean bypass time was 37 minutes (range 10-73) in Group 1 and 66 minutes (range 44-120) in Group 2. Total infusion volume of Normosol during and prior to termination of bypass was 0-2500 cc (mean=338). There were no procedural complications associated with PCPS. We conclude that PCPS can be used safely in selected patients who are considered high risk for PICA or acute MI complicated by shock or cardiac arrest. This technology adds a new dimension in perfusion in the catheterization laboratory.

The in vitro Bleeding Time While Using a Stable Prostacyclin Analogue during Hemodialysis

A serious disadvantage of preventing clot formation by using prostacyclin (PGI2) to inhibit thrombocyte function during dialysis is that there exists no rapidly measurable monitoring parameter. The "in vitro bleeding time" (in vitro BT) is a new method for measuring primary hemostasis in vitro. Five chronic dialysis patients each underwent two dialyses: 1) with conventional full heparinization, and 2) with the stable PGI2 analogue CG 4203 and additional "low-dose" heparin. The predialytic in vitro BT is longer than normal values and values 1 h after the end of dialysis. While heparin has no significant effect on the in vitro BT, CG 4203 prolongs it concentration-dependently. Infusing CG 4203 at a rate of 25 ng/kg/min, the in vitro BT is extended beyond the measurable range of 800 microliter during the first approx. 150 min of dialysis. During the next approx. 90 min it steadily decreases.

Treatment of arterial occlusions of the lower extremities using 2-stage local application of urokinase

We report the results of a 2-phase urokinase protocol for treatment of 28 arterial occlusions of the lower extremities. 26 patients, aged 43-86, with up to 6 weeks old occlusions were treated. In Phase I (average duration 2.7 h) the urokinase solution was injected in intervals directly into the occlusion-material via a F-5 catheter (120,000 U/h). In the following phase II (average duration 26.1 h) 100,000 U/h were given as a continuous arterial infusion and a full heparin regimen was started. In 86% of the treatments there was an improvement as shown by angiography. 75% of the patients could be released from the hospital without a further surgical revascularisation. Alterations of the systemic coagulation-system and bleeding-complications at the puncture site must be expected.

Hereditary protein C deficiency during pregnancy

Hereditary protein C, a primary hypercoagulable state, has not been previously associated with preeclamptic toxemia. A woman with previous preeclamptic toxemia and fetal deaths presented with recurrent deep vein thrombosis during her third pregnancy. Hereditary protein C was diagnosed but full heparinization followed by low-dose heparin failed to prevent preeclamptic toxemia.

Management of Patients with Heparin-Associated Thrombocytopenia and Thrombosis Requiring Cardiac Surgery

Heparin-associated thrombocytopenia and thrombosis (HATT) is a serious complication of heparin therapy that results in intravascular platelet aggregation with arterial or venous thrombosis. Platelet aggregation to heparin in vitro is used to confirm the diagnosis. Cessation of heparin therapy with avoidance of reexposure to heparin is an important principle in the management of HATT. However, certain patients with HATT may require reexposure to heparin for emergency cardiac operations requiring cardiopulmonary bypass while still demonstrating positive in vitro platelet aggregation with heparin. The present report describes the management of 2 such patients. In each patient aspirin was shown to inhibit platelet aggregation to heparin in vitro; therefore, aspirin and dipyridamole were administered to each patient before heparin reexposure and continued throughout the perioperative period. Cardiopulmonary bypass with full heparinization was achieved without thrombotic or hemorrhagic complications in both patients. Despite the presence of a heparin-dependent platelet-aggregating factor in the plasma of these 2 patients, inhibition of platelet aggregation with aspirin and dipyridamole allowed uneventful reexposure to heparin.

New approaches for anticoagulation in extracorporeal therapy.

The need to fully heparinize patients undergoing extracorporeal therapy often leads to hemorrhagic complications. Two approaches have been used to solve this problem. The first involves full heparinization of blood entering the extracorporeal device followed by the elimination of heparin from the blood returned to the patient using an immobilized heparinase reactor system. Animal studies have demonstrated the successful elimination of heparin's anticoagulant activity using this reactor. The second approach uses very low molecular weight (VLMW) heparins with improved properties. Although low molecular weight heparins and heparinoids have been successfully used in hemodialysis, these preparations are polydisperse mixtures. New VLMW heparins are described which are pure, monodisperse, structurally defined drugs and show improved pharmacokinetics and greater specificity than heparin. The separation of ATIII and HCII mediated activity against factors IIa and Xa may permit extracorporeal therapy with only partial anticoagulation resulting in increased antithrombotic activity with decreased hemorrhagic side-effects. Finally, these VLMW heparins suggest certain desirable structural characteristics in the design blood compatible non-thrombotic synthetic polymers for use in extracorporeal devices.

Preservation of Platelets during Cardiopulmonary Bypass with ZK36374: A New Prostacyclin Analogue

Extracorporeal circulation is associated with extensive alterations in platelet number and function. In certain individuals these adverse platelet changes are exacerbated by heparin. ZK36374 (ZK), a stable analogue of prostacyclin, reversibly inhibits all phases of platelet activation. A patient was presented with heparin induced platelet activation and paradoxical thrombosis who required cardiopulmonary bypass to correct severe tricuspid stenosis and ASD. We employed full heparinization and ZK to prevent surface and heparin induced thrombocytopenia. Prior to heparinization, a constant infusion of ZK was begun at 10 nanograms/kilogram/minute, tapered to 2 nanograms/kilogram/minute during bypass, and maintained until heparin was reversed with protamine. Prior to bypass, platelets demonstrated 50% reactivity and 2% reactivity when challenged by ADP and epinephrine, respectively, indicating inhibition of platelet function by ZK. Two hours after arrival in recovery 92% prebypass circulating platelet count, 90% preservation of platelet reactivity to ADP, and a template bleeding time near control were achieved. ZK was used safely to prevent both heparin and surface induced platelet changes during cardiopulmonary bypass in this patient.

Coronary artery thrombus as a risk factor for acute vessel occlusion during percutaneous transluminal coronary angioplasty: improving results.

Early experience with percutaneous transluminal coronary angioplasty (from October 1979 to March 1983 inclusive) showed that pre-existing coronary artery thrombus was associated with a significant increase in the incidence of acute coronary occlusion during angioplasty. Acute occlusion occurred in 11 (73%) of 15 patients with pre-existing thrombus compared with 18 (8%) of 223 patients without thrombus. The effect of improved technology (steerable guiding systems) and altered dilatation strategy (full intravenous heparinisation for 24 hours after the procedure and more intensive use of antiplatelet medications) was studied by review of angiograms from 297 consecutive patients without evidence of acute myocardial infarction who underwent angioplasty from April 1983 to March 1985 inclusive. Coronary artery thrombus was present in 34 (11%) patients, eight (24%) of whom had complete occlusion during or immediately after the procedure compared with 34 (13%) of 263 patients without thrombus. Patients with pre-existing coronary artery thrombus continue to be at greater risk of complete occlusion than patients without thrombus, but this risk has declined significantly since the modification of the angioplasty procedure.

14 - Anticoagulants in Pregnancy

Thromboembolic disorders are still a serious problem in pregnancy and anticoagulants have an important part to play in both treatment and prevention. Warfarin is the most convenient drug to give but can cause maternal and fetal bleeding problems, especially during late pregnancy and delivery. There are also small risks of embryopathy from warfarin in early pregnancy but these may have been overstated. Heparin, which has to be given parenterally, does not cross the placental barrier but can still cause bleeding problems in pregnancy. Full intravenous heparin is only suitable for short-term use, and subcutaneous heparin has been introduced for long-term therapy. This regimen is a useful advance but long-term use still has problems of bruising and maternal bone demineralization. The standard treatment of acute thromboembolic events in pregnancy is continuous intravenous heparin followed by either subcutaneous heparin or warfarin, the latter being changed at 36 weeks gestation. In the prophylaxis of thromboembolism, the trend istowards a more selective approach, anticoagulants being given during pregnancy to those at highest risk and during labour and the puerperium to all with a previous history of thromboembolism. Anticoagulants during pregnancy are necessary in patients with artificial heart valves and, because subcutaneous heparin is not sufficient, warfarin should be used until 36 weeks followed by continuous intravenous heparin until delivery. No method of anticoagulation during pregnancy is entirely free of risk and all management policies must be based on an estimate of risk-benefit ratio in individual patients.

Experimental and Clinical Experiences with Double-velour Woven Dacron Prostheses

Double-velour woven Dacron prostheses were investigated both experimentally and clinically. In 6 mongrel dogs, a tandem conduit between the right ventricle and the pulmonary artery was implanted, consisting of a plain woven and a double-velour woven graft. Following explanation after 2, 4, and 6 months, superior healing properties of the double-velour woven prostheses could be assessed by microscopy, as represented by an increase of tissue ingrowth, as well as by a thin and densely adherent inner healing capsule. Double-velour woven grafts were implanted in 50 patients undergoing open heart surgery. All grafts were presealed with fibrin glue and no bleeding could be detected at the time of implantation, even under the adverse influence of full heparinization and extracorporeal circulation.