Activated protein C resistance, Leiden mutation, anticoagulant proteins and fibrinogen levels in patients with deep venous thrombosis

Resistance to activated protein C (APC-R) is the leading cause of deep vein thrombosis (DVT). Deficiencies of protein C (PC) or its cofactor protein S (PS) are less frequent. Resistance usually results from nucleotide substitution (1691 GA) in the factor V gene (Leiden mutation). We searched for APC-R and the Leiden mutation (FVL) and measured the activities of PC, PS, antithrombin III (AT III) and Fb levels in patients with DVT. The results were analyzed against a history of thrombosis (idiopathic, risk factor related). We enrolled 29 patients aged 50 years or younger, with first symptoms of thrombosis detected before the age of 40 years. The control group consisted of 25 healthy volunteers of similar age. APC-R was established using Accelerimat (bioMerieux) assays. APC-R was diagnosed when the normalized sensitivity coefficient "r" was < 0.9. FVL was detected with the SSP-PCR (sequence specific primers-polymerase chain reaction) method. Abnormal APC-R "r" values were found in seven DVT patients (24%). Heterozygous (G/A genotype) form of the Leiden mutation was confirmed in six of them (all had a history of recurrent thrombosis). FVL carriers demonstrated lower PC levels in comparison with controls and DVT without FVL. Eight patients (27%) had PS activities below the cut-off point (60%). The deficiency in six of them was not associated with other abnormalities. Patients with recurrent thrombosis had markedly higher concentrations of Fb (usually without FVL) and reduced AT III activities. The study has shown that the APC-R test is useful for FVL screening. The Leiden mutation, elevated levels of Fb and reduced activities of PC are the main factors predisposing to DVT and its recurrence. Reduced activity of PS is usually an isolated abnormality tending to predispose to a single DVT episode.     

Detection of venous thrombosis of the legs by the iodine 125-labeled fibrinogen test in thoracic surgery. Apropos of 140 surgically-treated cases

The tracing of venous thromboses of the lower limbs by means of iodine 125 marked fibrinogen is possible in thoracic surgery thanks to the calibration of the apparatus on the femoral surface in cases of left thoracotomy or sternotomy. Twelve patients out of 128, i.c. 9.4%, had a positive test: 11 men and 1 woman of whom 11 had a minimum of 2 risk factors of venous thrombosis. These patients had 7 right and 5 left thoracotomies: 6 pneumonectomies (15.4% of pneumonectomies), 5 lobectomies (13% of lobectomies) and one enucleation; 11 positive tests occurred on patients operated on for cancer. There were 5 thrombo-embolic accidents: 2 fatal and 2 non fatal. Mortality was 4.28%: 6 patients of whom 3 died of infectious causes and 3 of pulmonary embolism: 2 after a pneumonectomy, respectively at 2 days and 2 months, and 1 after a lobectomy at 5 days. This examination was useful to known our percentage of isotopic thrombosis of the lower limb after thoracotomy: 9.4% which is small compared with those of the literature. However these results show the importance of instituting more prophylactic procedures to prevent venous thrombosis and thromboembolism by using heparin in all patients operated an for cancer with an exeresis and presenting 2 or more risk factors of venous thrombosis.     

Sleep apnea detection: accuracy of using automated ECG analysis compared to manually scored polysomnography (apnea hypopnea index)

Sleep and Breathing - Adequate sleep is fundamental to wellness and recovery from illnesses and lack thereof is associated with disease onset and progression resulting in adverse health outcomes....     

Prophylaxis of deep venous thrombosis with a low-molecular-weight heparin (Kabi 2165/Fragmin) in stroke patients

In a group of 60 patients in the acute phase of an ischemic stroke the assumption that low-molecular-weight heparin Kabi 2165 in the dose of 2 X 2,500 anti-Xa units s.c. could prevent thromboembolic complications was tested using a double-blind, placebo-controlled, randomized trial design. Thirty patients were allocated to each group. Both treatment groups were comparable with regard to neurological status and general condition. In the Kabi 2165 group there were 6 cases of deep venous thrombosis (DVT) compared to 15 in the placebo group (p = 0.05). In the placebo group there were 4 deaths during the trial versus 9 in the Kabi-2165-treated group (NS). Cerebral bleeding complicated 2 cases in the placebo group versus 4 in the Kabi 2165 group (NS). These results indicate that in ischemic stroke patients Kabi 2165 2 X 2,500 anti-Xa units s.c./24 h reduces the frequency of DVT. Because of the small number of patients it is impossible to evaluate the safety.     

A study on the safety, efficacy, and efficiency of sulodexide compared with acenocoumarol in secondary prophylaxis in patients with deep venous thrombosis

This study was carried out to study the safety and efficacy of a fixed dosage of sulodexide compared to adjusted dosages (INR) of acenocoumarol as secondary prophylaxis in patients with deep vein thrombosis (DVT) in lower limbs. An economic evaluation based on the criteria of use in normal clinical practice was also performed. One hundred and fifty patients of both sexes were included, all over 18 years of age and diagnosed with proximal DVT of the lower limbs by color echo-Doppler, and with clinical evolution of less than 1 month. The patients were initially treated with low-molecular-weight heparin (LMWH) and urokinase in accordance with the established protocol. They were then randomized to continue treatment with acenocoumarol and INR adjustments every 30 days, or with sulodexide. Treatment was extended for 3 months with monthly follow-up visits and a final visit at 3 months posttreatment. No differences between the groups were detected concerning demographic or basal characteristics in clinical evolution or adverse reactions. In the group treated with sulodexide, no major/minor hemorrhagic complications were detected. On the other hand, in the acenocoumarol group, 1 major hemorrhage and 9 minor hemorrhages were produced (13.3%), reaching statistical difference in relation to the sulodexide group (p = 0.014; CI from 95% of 4.7% to 19.4%). Regarding the economic impact, treatment costs with sulodexide are much less than those with acenocoumarol, the data confirmed by the sensitivity analyses performed. The results prove the efficacy, safety, and efficiency of sulodexide as a secondary prophylaxis in thromboembolic disease, avoiding hemorrhagic risks and the monitoring of patients, and providing significant savings to the health system.     

弹力袜护理对冠状动脉旁路移植术后患者下肢深静脉血栓形成的影响

目的:探讨专业弹力袜护理对冠状动脉旁路移植术(CABG)后患者,下肢深静脉血栓形成的影响。方法:根据研究纳入排除标准,收集96例拟行单纯CABG术的患者进行随机分组,其中对照组46例,干预组50例,对照组患者接受常规心外科护理,干预组患者在常规心外科护理基础上接受护士对于术后医用弹力袜穿戴的一对一床旁宣教。结果:研究发现,专业弹力袜护理宣教可以减少接受CABG手术患者术后静脉血栓的发生,缩短患者住院时长[(6. 12±1. 10) vs.(7. 34±3. 92) d,P=0. 04]。结论:由护士进行的一对一弹力袜宣教可以减少患者术后下肢深静脉血栓的发生,减少术后住院天数。     

Soluble platelet endothelial cell adhesion molecule 1 (sPECAM-1) improves diagnostic accuracy of D-Dimer in patients with suspected deep vein thrombosis (DVT)

Journal of Thrombosis and Thrombolysis - D-Dimer has a high sensitivity but a low specificity for the diagnosis of deep vein thrombosis (DVT) which limits its implementation as a general screening...     

Occurrence of thrombosis and haemorrhage, relationship with anti-Xa, anti-IIa activities, and D-dimer plasma levels in patients receiving a low molecular weight heparin, enoxaparin or tinzaparin, to prevent deep vein thrombosis after hip surgery

Studies in experimental animal models and in patients receiving low molecular weight heparin (LMWH) to prevent thromboembolic events after surgery have not demonstrated a clear relationship between anti-Xa and anti-IIa activities in plasma and either bleeding or prevention of thrombosis. The relationship between these clinical outcomes and ex vivo anti-Xa and anti-IIa activities, activated partial thromboplastin time (APTT) and D-dimers were evaluated in 440 patients undergoing total hip replacement and given prophylaxis once daily with a LMWH (tinzaparin or enoxaparin) in a multicentre double-blind randomized study. 221 patients received 4500 anti-Xa IU of tinzaparin; 219 patients received 40 mg (4000 anti-Xa IU) of enoxaparin. Both regimens were administered subcutaneously once daily. Blood samples for anti-IIa, anti-Xa, D-dimers levels and APTT were taken at baseline, on day 1, day 5 and on the day of discharge (days 8-14) and clinical assessments were performed dafly until day 14. All patients had bilateral venography between days 8 and 14. All coagulation tests were performed in central laboratories. A significant correlation was observed between anti-IIa activity and anti-Xa activity and the dose of each LMWH injected. The anti-Xa activity was significantly higher with enoxaparin and the anti-IIa activity was significantly higher with tinzaparin. No clear relationship between these two activities and the clinical outcomes was observed. This was also true with regards to APTT. Before and after surgery, D-dimers were significantly higher in patients with deep vein thrombosis (DVT) than in those without DVT but had no predictive value. Interestingly, a significant post-operative increase of D-dimers persisted in both groups of patients during the whole observation period, possibly suggesting that a longer duration of prophylactic treatment may be appropriate.     

Biodistribution in tumour-bearing mice of polycationic,amphoteric and polyanionic branched polypeptides with a poly(l-lysine) backbone labelled with125I and111In: Tumour accumulation less than that of labelled serum proteins

The biodistribution has been studied in mice with subcutaneously transplanted solid tumours (mammary carcinoma and melanoma) of synthetic branchedchain polypeptides based on poly(l-lysine). The polypeptides were a poly(l-lysine) backbone with sidechains of threedl-alanine residues (AK, which is polycationic), AK with additional glutamic acid residues at the end of the side-chains (EAK, which is amphoteric) and EAK in which the terminal glutamic acid amino groups had been acetylated (AcEAK, which is polyanionic) or succinylated (SucEAK, which is highly polyanionic). Polypeptides were labelled with¹²⁵I by reaction with Bolton and Hunter reagent, or with¹¹¹In by chelation to diethylenetriaminepentaacetic acid previously conjugated to them. As controls, natural plasma proteins (immunoglobulin G, albumin and transferrin) were similarly labelled. Over a study period of up to 7 days, even with the polypeptides showing most prolonged blood survival (EAK and AcEAK) there was no particular uptake or retention in tumour tissue, over and above what was seen with control plasma proteins and/or in normal tissues. Overall these findings suggest that any enhanced permeability and retention in tumour tissue, reported by other workers with other synthetic macromolecules, operates poorly with the present polypeptides and/or tumours. Specific tumour targeting, for example with monoclonal antibodies, would seem a better option than non-specific accumulation of macromolecules.Abbreviations AK branched-chain polypeptide poly[Lys-(dl-Ala _m )]. - DTPA diethylenetriamine pentaacetic acid - EAK polypeptide poly[Lys-(Glu₁-dl-Ala _m ] - AcEAK EAK in which the glutamic acid is acetylated - SucEAK EAK in which glutamic acid is succinylated - EPR enhanced permeability and retention - mAb monoclonal antibody - PBS phosphate-buffered saline, pH 7.2 - HPMA N-(2-hydroxypropyl)methacrylamide copolymer - SMANCS neocarzinostatin linked to poly(styreneco-maleic acid) - EPR enhanced permeability and retention     

Prevention of deep venous thrombosis of the leg by a very low molecular weight heparin fraction (CY 222) in patients with hemiplegia following cerebral infarction: a randomized pilot study (30 patients)

The effectiveness and safety of a very low molecular weight heparin fraction were evaluated in the prevention of deep-vein thrombosis in patients confined to bed due to hemiplegia consecutive to a recent cerebral infarction. CY 222 was administered within 48 hours of the stroke by one single daily subcutaneous injection of 0.6 ml (= 15,000 U AXa IC) during 14 days. This randomized pilot study involved 30 patients. The effects of CY 222 were assessed in a group of 15 patients compared with a control group of 15 untreated patients. No deep-vein thrombosis was detected by the labelled fibrinogen test in the treated group, as against 12 patients in the control group. Six patients (3 in each group) died during the study. One case of lethal pulmonary embolism was observed and confirmed at autopsy in the control group. In the remaining 5 patients, no systematic autopsy which would have asserted the absence of pulmonary embolism or drug-induced haemorrhage was performed. Numerous standard laboratory tests confirmed that CY 222 was well tolerated.     

Frequency of natural coagulation inhibitor (antithrombin III, protein C and protein S) deficiencies in Japanese patients with spontaneous deep vein thrombosis.

One hundred and thirteen consecutive Japanese patients with deep venous thrombosis (DVT) were studied for the incidences of antithrombin III (AT-III), protein C (PC) and protein S (PS) deficiencies, and the results were compared with those of normal subjects. Ten of the 392 normal Japanese subjects were found with PS deficiency (n = 8, 2.02%) or PC deficiency (n = 2, 0.5%). PS deficiencies comprised type I (1/8, 12.5%), type 11 (4/8, 50%), and type III (3/8, 37.5%). All PC deficiencies were type I. Among patients with DVT, 32 (28.3%) were deficient in AT-III, PC and PS. These patients consisted of two AT-III deficiency (1.77%), nine PC deficiency (7.96%), 20 PS deficiency (17.7%), and one combined deficiency of PC and PS (0.88%). Both of the patients with AT-III deficiency were classified as type II, all those with PC deficiency as type I, and those with PS deficiency as type I in 25% (5/20), type II in 55% (11/20) and type III in 20% (4/20). The frequency of PC and PS deficiencies in patients with DVT were 15.6 and 7.38 times the control population frequency, respectively, and this difference was statistically significant (P < 0.05). These data suggest that the Japanese population has a high frequency of PC and PS deficiencies. We recommend that PS activity should be measured for screening of thrombosis since type II deficiency accounted for approximately 50% of PS deficiency cases in both patients and the normal group in the Japanese.