Deep venous thrombosis of the legs after strokes: Part 2-Natural history.

Seven out of 76 patients who had sustained a cerebrovascular accident suffered a pulmonary embolism as diagnosed at necropsy or by unequivocal antemortem criteria. A further five patients had probable embolisation diagnosed only by clinical and chest x-ray criteria. Eleven of these 12 patients had DVT as diagnosed by the 125I-fibrinogen technique. Though 125I-fibrinogen technique has its limitations, thrombosis seemed to be able to develop at several independent sites in the venous system of the leg.     

G20210A prothrombin gene mutation identified in patients with venous leg ulcers

The G20210A mutation variant of prothrombin gene is the second most frequent mutation identified in patients withdeep venous thrombosis, after factor V Leiden. The risk for developing deep venous thrombosis is high in patients identified as heterozygous for G20210A mutation. In order to identify this polymorphism in the gene coding prothrombin, the 345bp fragment in the 3'- untranslated region of the prothrombin gene was amplified using amplification by polymerase chain reaction and enzymatic digestion by HindIII (restriction endonuclease enzyme). The products of amplification and enzymatic's digestion were analized using agarose gel electrophoresis. We investigated 20 patients with venous leg ulcers and we found 2 heterozygous (10%) for G20210A mutation. None of the patients in the control group had G20210A mutation. Our study confirms the presence of G20210A mutation in the Romanian population. Our study also shows the link between venous leg ulcers and this polymorphism in the prothrombin gene.     

After-exercise thermography and prediction of deep vein thrombosis.

A total of 112 patients participated in a prospective study of after-exercise thermography as a screening method for predicting risk of postoperative deep venous thrombosis. The fibrinogen-uptake test was used to detect thrombosis after elective surgery. The incidence of the complication showed no significant difference between patients who had had positive and those who had had negative thermograms. Thermography does not seem to be useful for predicting risk of postoperative thrombosis.     

Effectiveness of long term oral anticoagulation treatment in preventing venous thrombosis in hereditary protein S deficiency.

In eight of 14 patients who were deficient in protein S and who belonged to two unrelated families thrombosis presented as thrombophlebitis in seven and deep vein thrombosis in six, complicated by pulmonary embolism in four and leg ulcers in two. In four patients superficial thrombophlebitis preceded deep vein thrombosis by one to 11 years. Post-thrombotic varicose veins and venous insufficiency had developed in four patients. In three of those and in a fourth patient symptomatic superficial thrombophlebitis, deep vein thrombosis, and pulmonary embolism did not recur while they were taking oral anticoagulant treatment for six to 12 years. The anticoagulation intensity corresponded to international normalised ratio values of over 2.5. It is concluded that the benefits of anticoagulant treatment for patients with congenital thrombotic disease are great, and thus it is necessary to make an early diagnosis and treat patients at risk of developing thrombosis.     

Genetic analysis of factor V Leiden in a family with history of thrombosis and venous leg ulcers

Inherited resistance to activated protein C has been recognized as a major risk factor for thrombosis. The factor V Leiden mutation, which is detectable by molecular DNA techniques, is responsible for 95% of cases of activated protein C resistance. In our study one patient with venous leg ulcers from a family with a history of thrombosis showed factor V Leiden mutation. Genotypic analysis demonstrated that the patient was homozygous for factor V Leiden. All family members of the index subject showed the same abnormalities. Two were homozygous and 3 were heterozygous for factor V Leiden mutation. The polymerase chain reaction was used to amplify exon 10 of the factor V gene, followed by enzymatic digestion with MnlI for mutation detection. Patients with a family history of thrombosis and factor V Leiden have an increased risk of venous leg ulcers. Screening for factor V Leiden may be indicated in patients with venous leg ulcers and their family members.     

Deep venous thrombosis and occult malignancy: an epidemiological study.

OBJECTIVE--To determine the risk of subsequent cancer in patients with deep venous thrombosis confirmed by venography. DESIGN--Follow up of all patients who had venography for suspected deep venous thrombosis during 1984-88. Patients were traced through a cancer registry up to 1 January 1991. SUBJECTS--4399 patients who had phlebography in one hospital. SETTING--General hospital in Malmö, Sweden, serving a population of 230,000. MAIN OUTCOME MEASURE--Number of cancers recorded. RESULTS--4399 patients had venography for suspected deep venous thrombosis; 604 were known to have a malignancy at the time of venography and were excluded from further analysis. 1383 had deep venous thrombosis, 150 of whom subsequently developed cancer. 182 of the 2412 patients without thrombosis developed cancer. During the first six months after venography 66 patients with thrombosis developed malignancy compared with 37 patients without thrombosis (P < 0.0001). 38 of the cancers in the deep venous thrombosis group were detected by history, physical examination, and laboratory tests. Three patients had postoperative or post-traumatic deep venous thromboses. Only two of the remaining patients would have benefited from early detection by extensive screening. After six months the incidence of cancer was identical in patients with and without thrombosis. CONCLUSION--Deep venous thrombosis is associated with a significantly higher frequency of malignancy during the first six months after diagnosis. Malignancies can be found with simple clinical and diagnostic methods and extensive screening is not required.     

Cerebral haemorrhagic infarction in young patients with hereditary protein C deficiency: evidence for "spontaneous" cerebral venous thrombosis.

Among 53 patients with hereditary protein C deficiency belonging to 20 families three women were encountered who, aged 27, 34, and 38 respectively, had had cerebral haemorrhagic infarction, probably due to intracranial venous thrombosis. All three had also had venous thrombosis of the leg and pulmonary embolism either before or after their cerebral infarction. One patient sustained cerebral infarction while receiving an oral contraceptive, but infarction in the two others occurred "spontaneously." One patient also had an intraventricular and subarachnoid haemorrhage during the induction phase of coumarin treatment, which was assumed to have resulted from haemorrhagic infarction of the chorioid plexus, analogous to coumarin provoked haemorrhagic skin necrosis in protein C deficiency. Hereditary protein C deficiency should be considered in young patients with acute or subacute cerebral symptoms, especially if they have a family or personal history of venous thromboembolism.     

Evaluation of 125I-fibrinogen test for venous thrombosis in patients with hip fractures: comparison between isotope scanning and necropsy findings.

The results of 125I-fibrinogen leg scanning during life were compared with the findings at a detailed post-mortem dissection of the leg veins in 31 patients with hip fractures who died during the period of isotope scanning or within seven days of the last scan. Thigh scanning on the side of the hip fracture proved valueless, and criteria for the confident isotopic diagnosis of venous thrombosis in the uninjured thigh could not be determined. In the lower leg a difference in uptake of 20% or more that persisted for 24 hours between adjacent positions on one leg or between corresponding positions on the two legs was consistently associated with the presence of venous thrombosis at necropsy.     

股神经阻滞和收肌管阻滞对全膝关节置换术后下肢静脉血栓形成的影响

目的:探究股神经阻滞(femoral nerve block,FNB)和收肌管阻滞(adductor canal block,ACB)对全膝关节置换术(total knee arthroplasty,TKA)后下肢静脉血栓形成的影响。方法:将2019年3月-2019年4月拟在全身麻醉下行全膝关节置换术的40例患者随机分为FNB组和ACB组,所有患者均给予超声引导下单次注射,术后均给予标准化抗凝治疗。术后评估两组患者不同时间节点的疼痛评分、股四头肌肌力及术后下肢静脉血栓形成情况。结果:两组患者术后2、6、12、24、48、72 h患肢术区局部疼痛的VAS评分差异无统计学意义(P0.05)。ACB组患者术后2、6、12、24、48 h股四头肌肌力均明显高于FNB组(P0.05),术后72 h两组患者股四头肌肌力无明显差异(P0.05)。ACB组在术后患者首次直腿抬高时间(4.5±4.6)h,显著低于FNB组在术后患者首次直腿抬高时间(25.6±12.6)h,两组对比差异有统计学意义(P0.05)。术后72 h给予两组患者复查双下肢血管超声,复查结果显示,FNB组19例患者中共有2例出现下肢静脉血栓,均为肌间隙静脉血栓形成;ACB组20例患者中无患者出现下肢静脉血栓形成,差异无有统计学意义(P0.05)。结论:FNB与ACB在全膝关节置换术后镇痛方面无明显差异,但ACB组较好的保留患者术后早期股四头肌肌力,对于术后功能锻炼和快速康复有较积极的作用,两种神经阻滞方式对患者VTE风险的影响相同。     

Complications of ascending phlebography of the leg.

Forty patients were studied prospectively for complications of ascending phlebography. The commonest immediate complication was pain at the site of injection and the commonest delayed complication pain in the foot or calf. Out of 30 patients with pain in the foot and calf, 15 had venous thrombosis. Review of 200 case notes disclosed only one recorded complication--namely, necrosis of the dorsal skin of the foot. Complications of the procedure reported by referring clinicians over 10 years comprised four cases of necrosis of the dorsum of the foot and two of gangrene of the foot, in one of which the gangrene spread to the leg. Major complications of ascending phlebography are rare, though when they occur may cause serious morbidity. If a scrupulous technique is used contrast phlebography remains the most accurate method of diagnosing venous disease of the leg.     

Fibrinolytic capacity of arm and leg veins after femoral shaft fracture and acute myocardial infarction.

The local fibrinolytic activity generated in the leg and arm veins during venous occlusion (fibrinolytic capacity) and the systemic fibrinolytic activity were measured at intervals in 11 patients after fracture of the femoral shaft and in 11 patients after acute myocardial infarction. In both groups the fibrinolytic capacity of the leg veins and the systemic fibrinolytic activity were significantly reduced two days after the onset of tissue injury. The fibrinolytic capacity of the arm veins was not altered. These results provide a possible explanation for the predilection of venous thrombosis for the leg veins after accidental trauma and acute myocardial infarction.     

Indications for Vena Caval Fenestration

A retrospective study of 20 patients who underwent vena caval fenestration showed that in 50% of the patients the procedure was done for prophylaxis and in 50% it was done for therapeutic reasons. After this procedure five patients had persistent leg swelling, two had deep venous thrombosis, two had pulmonary emboli and one died of a respiratory arrest. We recommend limiting the use of vena caval fenestration to those patients who have verified pulmonary embolism while adequately anticoagulated or patients who have pulmonary embolism and a major contraindication to anticoagulation.     

Arterial disease in chronic leg ulceration: an underestimated hazard? Lothian and Forth Valley leg ulcer study.

Six hundred patients with chronic leg ulcers were interviewed and examined for evidence of arterial impairment. There were 827 ulcerated legs. Pedal pulses could not be felt in 94 (11%). A Doppler resting pressure index of 0.9 or less was found in 176 legs (21%). Risk factors for arterial impairment included age, ulceration affecting the foot, and a history of claudication, ischaemic heart disease, or cerebrovascular disease. Roughly half the patients with arterial impairment also showed the clinical features of chronic venous insufficiency. Careful assessment for arterial disease is mandatory before patients with chronic leg ulcers are treated with elastic compression.     

Dextran 70 in Prophylaxis of Postoperative Venous Thrombosis. A Controlled Trial

A controlled prospective trial was carried out in a group of 80 women undergoing gynaecological surgery and thought to be at risk of developing postoperative venous thrombosis. The patients, who had been randomly allocated to prophylaxis with either dextran 70 or warfarin, were well matched in age, weight and other predisposing factors.In the warfarin group, 12 out of 40 patients developed deep vein thrombosis, six of these episodes being classified as major and six as minor. In the dextran 70 group, 4 out of 40 patients developed deep vein thrombosis, all of them minor. The protective effect of dextran 70 is significantly better than that of warfarin (P<0·01) as used in the present study.     

Co-activation of platelets by prolactin or leptin--pathophysiological findings and clinical implications.

Platelet activation is involved in the pathogenesis of atherosclerosis and venous thromboembolism, and might therefore be a possible link between the two entities. Prolactin and leptin have recently been recognized as potent co-activators of ADP-dependent platelet aggregation or P-selectin expression, and are therefore suspected as additional risk factors for both arterial and venous thrombosis. There are clinical situations that have a known association with higher prolactin or leptin levels (pregnancy, obesity or anti-psychotic therapy) and increased risk of thromboembolic events. We compared the impact of both hormones on platelet activation in vitro and in vivo, indicating that prolactin has a stronger effect on platelet activation as leptin in vitro and in vivo. We have also demonstrated that prolactin levels are increased in so called idiopathic thrombosis, and that conversely, patients with prolactinoma have an increased frequency of thrombosis during the hyperprolactinemic state, in a retrospective analysis. Moreover, we have demonstrated increased prolactin values in stroke and myocardial infarction. Prospective studies have yet to be performed to give this theory its final confirmation. The involvement of hormonal factors in platelet aggregation and venous or arterial thrombosis may have important clinical implications such as for risk stratification of patients with venous and arterial thrombosis or new therapeutic options such as decreasing pro-coagulant hormone levels in certain risk situations.     

Prolactin as a factor for increased platelet aggregation

Administration of antipsychotics appears to be related to increased risk of venous thromboembolism and cerebrovascular side effects. The biological mechanism responsible for this possible adverse drug reaction is unknown, but there is a growing number of elucidating hypotheses. Treatment with antipsychotics is associated with elevation of prolactin level. Prolactin has recently been recognized as potent platelet aggregation co-activator, and have therefore been postulated as an additional risk factor for both arterial and venous thrombosis. We briefly review the arguments for the role of hyperprolactinemia in pathogenesis of platelet aggregation.     

Diagnostic Accuracy in Venous Thrombosis

A group of 111 surgical patients at high risk of venous thrombosis were studied after operation by independent clinical assessment and with ¹²⁵I-fibrinogen to detect venous thrombosis. Almost half of the patients developed venous thrombosis. Of these, two-thirds were not suspected clinically despite careful scrutiny. In the patients in whom a clinical diagnosis of venous thrombosis was made this diagnosis was falsely positive in a quarter. More than half of all thrombotic episodes were detectable on the day after operation.The prevalence of venous thrombosis, together with the difficulty in diagnosing it, strongly supports the argument that a reduction in the incidence of pulmonary embolism must depend on widespread adoption of effective prophylaxis, especially in the large number of patients at high risk of venous thrombosis. Prophylactic trials must be objectively assessed, and it is in this field that the ¹²⁵I-fibrinogen technique probably has the most to offer.     

Investigation of Relation between Use of Oral Contraceptives and Thromboembolic Disease. A Further Report

The results of a previous study of the use of oral contraceptives by married women discharged from hospital with a diagnosis of thromboembolic disease in the years 1964–6 were reported by us last year. The present paper adds results relating to patients discharged during 1967 and a few data, that could not be sought previously, for patients discharged with cerebral or coronary thrombosis from three of the hospitals in the earlier period.Of 84 patients with deep-vein thrombosis or pulmonary embolism 42 (50%) had used oral contraceptives during the month preceding the onset of their illness, while only 23 of the 168 controls (14%) had done so. No differences in risk were found either for the types of preparation or for the duration of use. After allowance for age and height, the patients with venous thromboembolism were about 10 lb. (4,535 g.) heavier than the control patients, irrespective of whether they were using oral contraceptives or not. No appreciable difference was found between the smoking habits of patients with and without venous thromboembolism treated during 1967, nor between women who were using oral contraceptives and those who were not. The trend in hospital admissions for venous thromboembolism with time corresponded to the trend in the use of oral contraceptives, and there was no evidence to suggest that the number of admissions was affected by publicity about the risk of using the preparations. Of 19 patients with cerebral thrombosis 11 (58%) had been using oral contraceptives, compared with an expected figure of 3.5 from the experience of the control subjects. All the published data (clinical, angiographic, and post-mortem) show that the thrombosis affects the cerebral arteries rather than the cerebral veins. Of 17 patients with coronary thrombosis 2 (12%) had been using oral contraceptives, compared with an expected figure of 2.1. The patients with coronary thrombosis smoked more than the control patients and were, on average, 8.3 lb. (3,765 g.) heavier than control women of the same age and height.The new evidence strengthens the belief that oral contraceptives are a cause of venous thromboembolism and cerebral thrombosis but does not indicate that they are a cause of coronary thrombosis.     

Long-Term Survival in a Large Cohort of Patients with Venous Thrombosis: Incidence and Predictors

Background

Venous thrombosis is a common disease with a high mortality rate shortly after the event. However, details on long-term mortality in these patients are lacking. The aim of this study was to determine long-term mortality in a large cohort of patients with venous thrombosis.

Methods and Findings

4,947 patients from the Multiple Environmental and Genetic Assessment study of risk factors for venous thrombosis (MEGA study) with a first nonfatal venous thrombosis or pulmonary embolism and 6,154 control individuals without venous thrombosis, aged 18 to 70 years, were followed up for 8 years. Death and causes of death were retrieved from the Dutch death registration. Standardized mortality ratios (SMRs) were calculated for patients compared with control individuals. Several subgroups were studied as well.736 participants (601 patients and 135 controls) died over a follow-up of 54,948 person-years. The overall mortality rate was 22.7 per 1,000 person-years (95% CI 21.0–24.6) for patients and 4.7 per 1,000 person-years (95% CI 4.0–5.6) for controls. Patients with venous thrombosis had a 4.0-fold (95% CI 3.7–4.3) increased risk of death compared with controls. The risk remained increased up to 8 years after the thrombotic event, even when no additional comorbidities were present. The highest risk of death was found for patients with additional malignancies (SMR 5.5, 95% CI 5.0–6.1). Main causes of death were diseases of the circulatory system, venous thrombosis, and malignancies. Main limitation was a maximum age of 70 at time of inclusion for the first event. Therefore results can not be generalized to those in the highest age categories.

Conclusions

Patients who experienced a first venous thrombosis had an increased risk of death which lasted up to 8 years after the event, even when no comorbidities were present at time of thrombosis. Future long-term clinical follow-up could be beneficial in these patients. Please see later in the article for the Editors'' Summary     

Collaborative overview of randomised trials of antiplatelet therapy--III: Reduction in venous thrombosis and pulmonary embolism by antiplatelet prophylaxis among surgical and medical patients. Antiplatelet Trialists' Collaboration.

OBJECTIVE--To determine the efficacy of antiplatelet therapy as prophylaxis against deep venous thrombosis or pulmonary embolism in surgical and high risk medical patients. DESIGN--Overviews of all randomised trials of antiplatelet therapy that could have been available by March 1990 and in which deep venous thrombosis was assessed systematically. SETTING--53 trials (total 8400 patients) of an average of two weeks of antiplatelet therapy versus control in general or orthopaedic surgery; nine trials (600 patients) of antiplatelet therapy versus control in other types of immobility; 18 trials (1000 patients) of one antiplatelet regimen versus another. RESULTS--Overall, a few weeks of antiplatelet therapy produced a highly significant (2P < 0.00001) reduction in deep venous thrombosis. 25% of patients allocated antiplatelet therapy versus 34% of appropriately adjusted controls had deep venous thrombosis detected by systematic fibrinogen scanning or venography, representing prevention in about 90 patients per 1000 allocated antiplatelet therapy. There was an even greater proportional reduction in pulmonary embolism: such emboli were detected among 47 (1.0%) antiplatelet allocated patients versus an adjusted control total of 129 (2.7%), representing prevention among about 17 patients per 1000 treated (2P < 0.00001). In analyses confined to surgical trials, the proportional reductions were similar and separately significant for nonfatal pulmonary embolism (0.7% antiplatelet therapy v 1.8% control; 2P < 0.00001) and for deaths attributed to pulmonary embolism (0.2% v 0.9%; 2P = 0.0001). There was a slight but non-significant excess of deaths from other causes (1.0% v 0.7%), which made the difference in total mortality nonsignificant, though still favourable (1.2% v 1.5%). Information on adding antiplatelet therapy to heparin was limited but, at least for pulmonary embolism, suggested more protection from the combination than from heparin alone. The proportional reduction in the odds of suffering a deep venous thrombosis was roughly the same in patients having general surgery, traumatic orthopaedic surgery, and elective orthopaedic surgery (and in medical patients who were at increased risk of thromboembolism). For pulmonary embolism the numbers affected were smaller, but again the reductions were highly significant both in general surgery (16 (0.5%) v 58 (1.7%) pulmonary emboli; 2P < 0.0001) and in orthopaedic surgery (28 (2.7%) v 63 (6.1%) pulmonary emboli; 2P < 0.0002). CONCLUSION--It had previously been supposed that antiplatelet therapy did not influence venous thromboembolism, and many surgeons and physicians do not use it routinely for thromboprophylaxis, even for patients who are at substantial risk of deep venous thrombosis or pulmonary embolism. These results indicate that antiplatelet therapy--either alone or, for greater effect, in addition to other proved forms of thromboprophylaxis (such as subcutaneous heparin)--should be considered.