A prospective double-blind trial of a low molecular weight heparin once daily compared with conventional low-dose heparin three times daily to prevent pulmonary embolism and venous thrombosis in patients with hip fracture

In a randomized, prospective, double-blind trial, the effect of conventional low-dose heparin (5,000 units every 8 hours) was compared with that of a low molecular weight fragment (2165 LMWH, Kabi Vitrum AB, starting 2,500 units 2 hr before surgery, and then 5,000 units subcutaneously every morning for 9 days). A total of 90 patients admitted because of hip fracture fulfilled the inclusion criteria and were analyzed for development of pulmonary embolism and deep vein thrombosis: 46 patients were included in the low molecular weight heparin (LMWH) group, and 44 in the conventional heparin group. Two and three, respectively, died before diagnostic tests were performed. In the remaining patients a ventilation-perfusion lung scan was performed 8 days after intervention. In the first 57 patients studied a bilateral ascending venography was performed on the ninth day only if clinical symptoms suggested a deep venous thrombosis. Because of the rate of venous thrombosis detected in those patients was unexpectedly low, venography was requested in the remaining 33 patients, even if the screening tests were negative. Pulmonary embolism occurred in six patients, all in the LMWH group. Deep vein thrombosis occurred in 14 patients in the LMWH group and in six patients in the conventional heparin group. Both differences are statistically significant. Mortality did not differ between the groups, nor did haemorrhagic complications. Our findings suggest that, in patients with hip fracture, LMWH is not useful at the dosage used.     

Use of plasma exchange and heparin during cardiopulmonary bypass for a patient with heparin induced thrombocytopenia: a case report

Patients with documented history of heparin-induced thrombocytopenia (HIT) pose a difficult problem during surgery using cardiopulmonary bypass (CPB). Several alternatives to heparin exist, but these products either are not approved for use in the United States or have more side effects than heparin. We report on a patient with documented heparin-induced antibody and left main coronary artery disease who underwent uneventful coronary artery bypass surgery and recovery by using preoperative plasmaphresis and limited use of porcine intestinal heparin during CPB.     

CABG without using heparin in a patient with heparin-induced thrombocytopenia

BACKGROUND: Despite the low incidence of heparin-induced thrombocytopenia and thrombosis, these two syndromes are much disputed in life-threatening conditions especially in cardiovascular surgery where heparin is routinely used. Nowadays a pharmacological agent that can exactly replace heparin does not exist. Many of the drugs called "alternative drugs to heparin" are associated with a high risk of hemorrhagic complications and an increased need of blood transfusions. Neither the use of heparin nor "alternative drugs to heparin" may be the best way to revascularize a patient with heparin-induced thrombocytopenia. METHODS: Coronary artery bypass grafting without using heparin was performed in a 62-year-old male patient with heparin-induced thrombocytopenia. He received clopidogrel and acethyl salicylic acid for 2 days before operation. He was operated off-pump using special maneuvers. RESULTS: He was discharged on postoperative day 5 after an uneventful course and is doing well in the sixth month postoperatively. CONCLUSIONS: According to our investigations in English literature, this surgical technique and coronary artery bypass grafting without using heparin is firstly described in this article. Increasing the number of cases will show the reliability and safety of this method.     

Low molecular weight heparin in hemodialysis patients with a bleeding tendency

Efficacy and safety of a low-molecular-weight heparin (LMWH) were studied in 33 stable maintenance hemodialysis patients who had a bleeding tendency on unfractionated heparin. The optimal dose of LMWH for each patient was titrated before the study; the mean total LMWH dosage was 1,152 +/- 574 IU. No major bleeding or clot formation was noted in a total of 2,470 hemodialysis sessions during 6 months of LMWH administration. The mean value of plasma anti-factor Xa (anti-Xa) activity increased from 0.05 +/- 0.03 IU/ml before dialysis to 0.34 +/- 0.28 IU/ml after 2 h of dialysis and returned to 0.15 +/- 0.09 IU/ml after 4 h of dialysis; the mean activated partial thromboplastin time was 26.1 +/- 4.4 s before dialysis, 30.7 +/- 9.5 s (an 18% increase) after 2 h of dialysis, and 26.2 +/- 4.4 s after 4 h of dialysis. No significant change in serum antithrombin levels was noted throughout the whole study period. We conclude that a low dosage of LMWH is safe and effective in hemodialysis patients who have a risk of bleeding with unfractionated heparin. Serum anti-Xa activity is better than activated partial thromboplastin time and antithrombin in assessing the optimal dose of LMWH. A plasma anti-Xa activity of 0.37 IU/ml after 2 h of hemodialysis may represent an optimal dosage of LMWH for most patients.     

Hypertension control with daily dialysis

Hypertension is present in 60-90% of patients on maintenance hemodialysis (HD) and it is an important cause of cardiovascular (CV) mortality and morbidity. Frequent and prolonged HD has been uniformly shown to control hypertension in end-stage renal disease (ESRD) patients more effectively than conventional HD. The etiology of hypertension is predominantly volume dependent, but in a subset of patients increased renin, sympathetic overactivity, and endothelial dysfunction may play a role. Intradialytic hypotension precludes attainment of dry weight and hence optimal control of hypertension in conventional HD is challenging. Frequent and prolonged dialysis with gentle and persistent ultrafiltration allows time for refilling of the intravascular compartment and permits normalization of extracellular volume. It is also possible that intensive dialysis enables removal of pressor molecules and improves endothelial function. Improved blood pressure control translates into regression of left ventricular hypertrophy in patients on daily HD. Thus prolonged and frequent dialysis permits better control of hypertension via volume and volume-independent mechanisms and also improves cardiac geometry.     

Phosphorus balance with daily dialysis

Hyperphosphatemia is an almost universal finding in patients with end-stage renal disease and is associated with increased all-cause mortality, cardiovascular mortality, and vascular calcification. These associations have raised the question of whether reducing phosphorus levels could result in improved survival. In light of the recent findings that increased per-session dialysis dose, as assessed by urea kinetics, did not result in improved survival, the definition of adequacy of dialysis should be re-evaluated and consideration given to alternative markers. Two alternatives to conventional thrice weekly dialysis (CHD) are nocturnal hemodialysis (NHD) and short daily hemodialysis (SDHD). The elimination kinetics of phosphorus as they relate to these alternative daily dialysis schedules and the clinical implications of overall phosphorus balance are discussed here. The total weekly phosphorus removal with NHD is more than twice that removed by CHD (4985 mg/week +/- 1827 mg vs. 2347 mg/week +/- 697 mg) and this is associated with a significantly lower average serum phosphorous (4.0 mg/dl vs. 6.5 mg/dl). In spite of the observed increase in protein and phosphorus intake seen in patients on SDHD, phosphate binder requirements and serum phosphorus levels are generally stable to decrease although this effect is strongly dependent on the frequency and overall treatment time.     

Low molecular weight heparin compared with unfractionated heparin in prevention of postoperative thrombosis

Three consecutive randomized open studies have been carried out to determine the optimal dosage of low molecular weight heparin (LMWH) in the prevention of postoperative thrombosis in general surgery (892 patients). All patients undergoing abdominal, gynaecological, thoracic or urological surgery were over 40 years old and presented at least one of the following risk factors for thrombosis: previous thromboembolism, obesity, varicose veins, malignancy (30 per cent), pre-operative hospitalization over 5 days, oestrogen therapy, chronic cardiac disease or bronchitis. Isotopic venous thrombosis and bleeding complications were assessed after subcutaneous administration of a LMWH fragment (LMWH, Enoxaparine) or unfractionated heparin (UH). The three studies compared 3 X 5000 units UH daily with 1 X 60 mg, 1 X 40 mg, 1 X 20 mg LMWH daily. Thromboembolic events rates were not significantly different from group to group (UH: 3.8 per cent, 2.7 per cent, 7.6 per cent respectively compared with LMWH: 2.9 per cent, 2.8 per cent, 3.8 per cent). Bleeding episodes including wound haematoma formation, perioperative blood losses and systemic haemorrhage were not significantly different in patients receiving LMWH or UH. Significant decreases in haematocrit and haemoglobin were only observed in patients receiving 60 mg Enoxaparine (as compared to UH). An analysis using the 'intention to treat' approach gave results consistent with those of an analysis of good compliers. An overview of isotopic thromboses in the three studies gave no evidence of differences amongst the effects of the three doses of LMWH (P = 0.20), and pooling the results of the three studies using the Mantel-Haenszel procedure gave no evidence of a global difference between Enoxaparine and UH (P = 0.54). These results suggest that an optimal dosage of 20 mg/day of Enoxaparine is safe and effective in the prevention of postoperative thrombosis in this population.     

Treatment with danaparoid during pregnancy for a woman with a cutenous allergy to low-molecular-weight heparin]

The authors describe a case of heparin-induced skin reaction due to two preparations of low molecular weight heparin in a pregnant woman. The main characteristics of heparin-related cutaneous allergy are reported. The use of an heparinoid, usually indicated for patients with heparin-induced thrombocytopenia, appeared to be efficient and safe for the mother and her fetus. An epidural analgesia was performed for labor analgesia, 24 hours after the last injection of danaparid of sodium.     

Persistence of thrombopenia induced by heparin despite replacement with low molecular weight heparin

A 42 year old man, treated for phlebitis with subcutaneous heparin, developed vascular occlusion in both legs with thrombocytopaenia. After surgery, heparin was discontinued and replaced by low molecular weight heparin (CY 216 Choay) without any success. Both commercial heparin and CY 216 Choay produced platelet aggregation in vitro. Heparin was stopped and replaced by dextran 40,000 with anti-aggregating drugs (flurbiprofen) followed by antivitamin K drugs. Thrombocytopaenia resolved three days later and the patient was discharged without sequelae. It therefore appeared necessary to carry out aggregation tests both with heparin and low molecular weight heparin if thrombocytopaenia occurs whilst heparin is being used.     

Haemodynamic and haematologic alterations with protamine reversal of anticoagulation: comparison of standard heparin and a low molecular weight heparin fragment

Reversal of anticoagulation with protamine sulfate causes many adverse haemodynamic and haematologic effects which could be due to differences in the mechanism of action of standard and low molecular weight heparin. Three groups of dogs were investigated: one group received normal saline pretreatment followed by heparinisation with standard heparin 150 IU/kg followed by protamine sulfate reversal 1.5 mg/kg after aortic interposition grafting: the second group were given normal saline pretreatment followed by heparinisation with low molecular weight heparin 150 U antiXa/kg and after grafting protamine sulfate reversal 1.5 mg/kg. The third group were given protamine sulfate pretreatment 2.25 mg/kg followed by low molecular weight heparin 150 U antiXa/kg and later protamine sulfate reversal 1.5 mg/kg after grafting. The same haemodynamic changes were seen regardless of the type of heparin or pretreatment with protamine given along with low molecular weight heparin. There was a suggestion that regular heparin cause a more pronounced increase in pulmonary artery pressure and a decrease in heart rate. On the other hand the systemic hypotension and reduction of cardiac output seemed more pronounced in the low molecular weight heparin group. Platelet count decreased less in the low molecular weight heparin group, but white blood cell count was equally reduced. Pretreatment with protamine did not abolish the adverse effects of protamine when reversing anticoagulation achieved with low molecular weight heparin, a finding not shared with standard heparin-protamine interactions.     

Mobile biatrial thrombus in a patient with mitral stenosis under heparin infusion

A 58-year-old female patient with complaints of sudden presenting pain and pallor on her left foot was referred to our clinic for urgent embolectomy. On her cardiovascular examination there was an apical grade 2/6 systolic murmur and a grade 2/4 diastolic murmur. The presenting electrocardiography revealed atrial fibrillation with rapid ventricular response. She underwent emergent femoro-popliteal embolectomy. Transthoracic echocardiography showed a mobile 1.4 x 1.7-cm sized left atrial thrombus, mild mitral regurgitation and 9 mmHg mean gradient on mitral valve after embolectomy. Unfractioned (UF) heparin infusion was initiated immediately after surgery. After three days, the control transthoracic echocardiography revealed left atrial thrombus and also a large 'snake-like' thrombus waving in right atrium. The patient underwent biatrial thrombectomy and mitral valve replacement. When she became haemodynamically stable, a bilateral lower limb venous Doppler ultrasonographic study was performed. This study indicated a thrombus formation in the deep veins of the left leg. The origin of the right atrial thrombus was probably a snapped piece of thrombus from the calf deep-veins after the initiation of intravenous UF heparin. In summary, we have reported an extremely rare case of biatrial thrombus in a patient under UF heparin infusion.     

Exploring daily affective changes in university students with a mindful positive reappraisal intervention: A daily diary randomized controlled trial

Brief and cost‐effective interventions focused on emotion regulation techniques can buffer against stress and foster positive functioning. Mindfulness and positive reappraisal are two techniques that can mutually enhance one another to promote well‐being. However, research testing the effectiveness of interventions combining mindfulness and reappraisal is lacking. The current pilot examined the effect of a combined mindful‐reappraisal intervention on daily affect in a 5‐day diary study with 106 university students. Participants were randomized to a mindful‐reappraisal intervention (n = 36), a reappraisal‐only intervention (n = 34), or an active control activity (n = 36). All participants described a negative event each day but only reappraised the event in the intervention conditions. Using multilevel growth modelling, results indicated that negative affect in both interventions declined over 5 days compared to the control; however, there were no differences in the growth of positive affect. Compared to reappraisal‐only, the mindful‐reappraisal group reported overall lower daily negative affect and marginally higher daily positive affect over the 5‐day intervention. These findings suggest that brief daily practice combining mindfulness and positive reappraisal can be trained as a self‐regulatory resource to promote positive affect and buffer negative affect above and beyond reappraisal practice alone.     

Ancrod: a practical alternative to heparin

To rapidly start systemic anticoagulation there are few alternatives to heparin; those that may be used are often less effective and are impractical substitutes for various reasons. We report the cases of seven patients in whom anticoagulant therapy was begun with ancrod instead of heparin for one or more of the following reasons: (1) failure to achieve systemic anticoagulation in response to heparin (e.g., antithrombin III deficiency), (2) heparin-associated complications (e.g., thrombocytopenia, thrombosis, or both), and (3) combined anticoagulation and improved blood rheology considered to be potentially more beneficial than anticoagulation alone (e.g., massive thrombosis). In the cases reported, ancrod permitted systemic anticoagulation equal to that of heparin; this was achieved without bleeding complications. In contrast to streptokinase or urokinase, ancrod does not degrade preformed, fully cross-linked thrombin fibrin; consequently hemorrhagic complications are uncommon. Ancrod appears to be an appropriate alternative to heparin and may be preferable to it in certain circumstances.     

Interference of heparin with peritoneal solute transport

To verify the action of heparin on peritoneal transport, we selected 20 patients on acute peritoneal dialysis and performed two 2-hour cycles with 2,000 cm3 of a 1.5% solution, adding 2,000 units of heparin to the second cycle. The patients were also randomized into 2 groups: group A, adding 1.5 mg gentamycin/kg to the dialysate of cycle I (without heparin), and group B, adding the same dose of gentamycin to cycle II (with heparin). At the end of each of the two cycles blood and dialysate were drawn for urea, creatinine, glucose, proteins and gentamycin levels, using peritoneal clearances of urea and creatinine, glucose absorption and net protein loss to compare cycle I with cycle II. We found that the peritoneal transport of creatinine and urea was improved (p less than 0.02; p less than 0.05) and glucose absorption increased (p less than 0.01) with heparin, without any significant change in protein loss. Contrary to common belief, heparin in a 1,000-U/l dose improved the absorption of gentamycin from the dialysate (p less than 0.01).