Although thromboembolism is uncommon during pregnancy and the postpartum period, physicians should be alert to the possibility because the complications, such as pulmonary embolism, are often life threatening. Pregnant women who present with thromboembolic occlusion are particularly difficult to treat because thrombolysis is hazardous to the fetus and surgical intervention by any of several approaches is controversial.
A 22-year-old woman, in her 11th week of gestation, experienced an episode of pulmonary embolism and severe ischemic venous thrombosis of the left lower extremity. The cause was determined to be a severe protein S deficiency in combination with compression of the left iliac vein by the enlarged uterus.
The patient underwent emergency insertion of a retrievable vena cava filter and surgical iliofemoral venous thrombectomy with concomitant creation of a temporary femoral arteriovenous fistula. The inferior vena cava filter was inserted before the venous thrombectomy to prevent pulmonary embolism from clots dislodged during thrombectomy. When the filter was removed, medium-sized clots were found trapped in its coils, indicating the effectiveness of this approach. The operation resolved the severe ischemic venous thrombosis of the left leg, and the patency of the iliac vein was maintained throughout the pregnancy without embolic recurrence. At full term, the woman spontaneously delivered an 8-lb, 6-oz, healthy male infant. (Tex Heart Inst J 2002;29:130–2)
Femoral vein/surgery; heparin/therapeutic use; iliac vein/surgery; pregnancy complications, cardiovascular/surgery; pulmonary embolism/prevention & control; thrombectomy; thrombosis/therapy; vena cava filters; venous thrombosis/therapy
Venous thromboembolism, presenting as deep vein thrombosis or pulmonary embolism, is a major challenge for health care systems. It is the third most common vascular disease after coronary heart disease and stroke, and many hospitalized patients have at least one risk factor. In particular, patients undergoing hip or knee replacement are at risk, with an incidence of asymptomatic deep vein thrombosis of 40%–60% without thromboprophylaxis. Venous thromboembolism is associated with significant mortality and morbidity, with patients being at risk of recurrence, post-thrombotic syndrome, and chronic thromboembolic pulmonary hypertension. Arterial thromboembolism is even more frequent, and atrial fibrillation, the most common embolic source (cardiac arrhythmia), is associated with a five-fold increase in the risk of stroke. Strokes due to atrial fibrillation tend to be more severe and disabling and are more often fatal than strokes due to other causes. Currently, recommended management of both venous and arterial thromboembolism involves the use of anticoagulants such as coumarin and heparin derivatives. These agents are effective, although have characteristics that prevent them from providing optimal anticoagulation and convenience. Hence, new improved oral anticoagulants are being investigated. Dabigatran is a reversible, direct thrombin inhibitor, which is administered as dabigatran etexilate, the oral prodrug. Because it is the first new oral anticoagulant that has been licensed in many countries worldwide for thromboprophylaxis following orthopedic surgery and for stroke prevention in patients with atrial fibrillation, this compound will be the main focus of this review. Dabigatran has been investigated for the treatment of established venous thromboembolism and prevention of recurrence in patients undergoing hip or knee replacement, as well as for stroke prevention in atrial fibrillation patients with a moderate and high risk of stroke.
dabigatran etexilate; venous thromboembolism; stroke; prevention; treatment
Deficiencies of natural anticoagulants protein C, protein S, antithrombin and activated protein C resistance are components of inherited thrombophilia. Inherited thrombophilia was defined as a genetically determined tendency towards venous thromboembolism which characteristically occurs in young age (before 40 to 45 years) without apparent causes and tend to recur. In the recent years, there has been a lot of debate about the implication of these defects in arterial thromboses (peripheral artery disease, myocardial infarction, cerebral infarction). The screening for thrombophilia is recommended for young patients with spontaneous thromboses, arterial infarctions, family history of thromboses, personal history of recurrent abortions, with thrombosis of venous dural sinuses or strokes or myocardial infarctions, in patients with venous thrombosis at unusual sites, because the diagnosis of such a disease leads to a treatment that is lifesaving [1,2].
thrombophilia; myocardial infarction; stroke; venous thromboses
There is high incidence of venous thromboembolism, comprising of deep vein thrombosis and pulmonary embolism, in hospitalized patients. The need for systemic thromboprophylaxis is essential, especially in patients with inherited or acquired patient-specific risk factors or in patients undergoing surgeries associated with high incidence of postoperative deep vein thrombosis and pulmonary embolism. These patients, on prophylactic or therapeutic doses of anticoagulants, may present for surgery. General or regional anaesthesia may be considered depending on the type and urgency of surgery and degree of anticoagulation as judged by investigations. The dilemma regarding the type of anaesthesia can be solved if the anaesthesiologist is aware of the pharmacokinetics of drugs affecting haemostasis. The anaesthesiologist must keep abreast with the latest developments of methods and drugs used in the prevention and management of venous thromboembolism and their implications in the conduct of anaesthesia.
Anaesthetic considerations; deep vein thrombosis; pulmonary embolism; thromboprophylaxis; venous thromboembolism
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.
Venous thromboembolism comprising pulmonary embolism and deep vein thrombosis is a common condition with an incidence of approximately 1 per 1,000 per annum causing both mortality and serious morbidity. The principal aim of treatment of a venous thromboembolism with heparin and warfarin is to prevent extension or recurrence of clot. However, the recurrence rate following a deep vein thrombosis remains approximately 10% per annum following treatment cessation irrespective of the duration of anticoagulation therapy. Patients with raised D-dimer levels after discontinuing oral anticoagulation treatment have also been shown to be at high risk of recurrence.
Post thrombotic syndrome is a complication of a deep vein thrombosis which can lead to chronic venous insufficiency and ulceration. It has a cumulative incidence after 2 years of around 25% and it has been suggested that extended oral anticoagulation should be investigated as a possible preventative measure.
Patients with a first idiopathic venous thromboembolism will be recruited through anticoagulation clinics and randomly allocated to either continuing or discontinuing warfarin treatment for a further 2 years and followed up on a six monthly basis. At each visit D-dimer levels will be measured using a Roche Cobas h 232 POC device. In addition a venous sample will be taken for laboratory D-dimer analysis at the end of the study. Patients will be examined for signs and symptoms of PTS using the Villalta scale and complete VEINES and EQ5D quality of life questionnaires.
The primary aim of the study is to investigate whether extending oral anticoagulation treatment (prior to discontinuing treatment) beyond 3–6 months for patients with a first unprovoked proximal deep vein thrombosis or pulmonary embolism prevents recurrence. The study will also determine the role of extending anticoagulation for patients with elevated D-dimer levels prior to discontinuing treatment and identify the potential of D-dimer point of care testing for identification of high risk patients within a primary care setting.
Venous thromboembolism; Deep vein thrombosis; Pulmonary embolism; Extended warfarin; Post thrombotic syndrome; D-dimer
Venous thromboembolism is associated with significant morbidity and mortality. Anticoagulation with heparin and warfarin has favorably altered the natural history of untreated venous thromboembolism. The role of thrombolysis and interventional therapy in the management of venous thromboembolism is less well appreciated. This review evaluates the role of thrombolytic therapy and mechanical interventions in the management of deep vein thrombosis and pulmonary embolism.
Objective To assess the safety of using single complete compression ultrasonography in pregnant and postpartum women to rule out deep vein thrombosis.
Design Prospective outcome study.
Setting Two tertiary care centres and 18 private practices specialising in vascular medicine in France and Switzerland.
Participants 226 pregnant and postpartum women referred for suspected deep vein thrombosis.
Methods A single proximal and distal compression ultrasonography was performed. All women with a negative complete compression ultrasonography result did not receive anticoagulant therapy and were followed up for a three month period.
Main outcome measures Symptoms of venous thromboembolism, second compression ultrasonography or chest imaging, a thromboembolic event, and anticoagulant treatment.
Results 16 women were excluded, mainly because of associated suspected pulmonary embolism. Deep vein thrombosis was diagnosed in 22 out of the 210 included women (10.5%). 10 patients received full dose anticoagulation despite a negative test result during follow-up. Of the 177 patients without deep vein thrombosis and who did not receive full dose anticoagulant therapy, two (1.1%, 95% confidence interval 0.3% to 4.0%) had an objectively confirmed deep vein thrombosis during follow-up.
Conclusions The rate of venous thromboembolic events after single complete compression ultrasonography in pregnant and postpartum women seems to be within the range of that observed in studies in the non-pregnant population. These data suggest that a negative single complete compression ultrasonography result may safely exclude the diagnosis of deep vein thrombosis in this setting.
Trial registration clinicaltrials.gov NCT00740454.
Although there are numerous risk factors for venous thromboembolic disease, the term 'thrombophilia' refers only to those familial or acquired disorders of the haemostatic system that result in an increased risk of thrombosis. The inherited thrombophilias include antithrombin III deficiency, resistance to activated protein C (factor V Leiden), protein C and protein S deficiencies as well as some rare forms of dysfibrinogenaemia. It is possible that other inherited conditions might also predispose to thrombosis. In contrast, when using the above definition, the antiphospholipid syndrome is the only genuine acquired thrombophilic state. Patients who have thromboembolic disease at a young age with no provoking event or who have a positive family history or whose thrombosis involves an unusual site should be investigated for thrombophilia. The management of a patient identified as having a laboratory abnormality associated with thrombophilia will depend on a variety of factors such as the patient's individual and family thrombotic history, the site of the thrombosis and the presence of other prothrombotic risk factors. The use of prophylactic anticoagulation during pregnancy and the puerperium requires particularly careful consideration in thrombophilic women. As more becomes known about the thrombophilias it will become possible to formulate more exact guidelines as to the management of these conditions.
Objective To determine how length of anticoagulation and clinical presentation of venous thromboembolism influence the risk of recurrence after anticoagulant treatment is stopped and to identify the shortest length of anticoagulation that reduces the risk of recurrence to its lowest level.
Design Pooled analysis of individual participants’ data from seven randomised trials.
Setting Outpatient anticoagulant clinics in academic centres.
Population 2925 men or women with a first venous thromboembolism who did not have cancer and received different durations of anticoagulant treatment.
Main outcome measure First recurrent venous thromboembolism after stopping anticoagulant treatment during up to 24 months of follow-up.
Results Recurrence was lower after isolated distal deep vein thrombosis than after proximal deep vein thrombosis (hazard ratio 0.49, 95% confidence interval 0.34 to 0.71), similar after pulmonary embolism and proximal deep vein thrombosis (1.19, 0.87 to 1.63), and lower after thrombosis provoked by a temporary risk factor than after unprovoked thrombosis (0.55, 0.41 to 0.74). Recurrence was higher if anticoagulation was stopped at 1.0 or 1.5 months compared with at 3 months or later (hazard ratio 1.52, 1.14 to 2.02) and similar if treatment was stopped at 3 months compared with at 6 months or later (1.19, 0.86 to 1.65). High rates of recurrence associated with shorter durations of anticoagulation were confined to the first 6 months after stopping treatment.
Conclusion Three months of treatment achieves a similar risk of recurrent venous thromboembolism after stopping anticoagulation to a longer course of treatment. Unprovoked proximal deep vein thrombosis and pulmonary embolism have a high risk of recurrence whenever treatment is stopped.
Venous aneurysms are uncommon in the lower limb and are more frequently found in the neck and thoracic and visceral veins. However, they have been reported to cause thrombosis, pulmonary thromboembolism, and other related complications. Popliteal venous aneurysms are often undetected because they are usually asymptomatic, but they may cause pulmonary thromboembolic events. We experienced a case of a 44-year-old man who was referred for recurrent pulmonary thromboembolism. He showed no other symptoms or signs except shortness of breath. A popliteal venous aneurysm was diagnosed incidentally because the examinations were performed to detect a deep vein thrombosis in relationship to the patient's history of pulmonary thromboembolism. We report a case of surgical treatment for a popliteal venous aneurysm that was complicated by pulmonary thromboembolism.
Pulmonary embolism; Aneurysm; Popliteal vein
Cerebral venous sinus thrombosis (CVST) is an uncommon condition with severe consequences. Although we do not know the exact incidence and prevalence of CVST, it is an important diagnosis. Over the past decade, it has been diagnosed more frequently due to greater awareness and availability of noninvasive diagnostic techniques. Furthermore, routine diagnostic neuroimaging has been used to monitor the clinical progress of these patients, especially in deteriorating cases. In order to decrease morbidity and mortality, an understanding of CVST treatment options is important. Treatment of extensive intracranial venous sinus thrombosis with intrasinus infusion of recombinant tissue plasminogen activator (rt-PA) is relatively controversial as there are no clear guidelines in regards to appropriate therapeutic management. We report a case of successful intrasinus thrombolysis of deep cerebral sinus thrombosis (DCST) resulting in rapid radiographic improvement associated with complete clinical recovery.
Arterial and venous thromboembolic diseases are a clinical and economic burden worldwide. In addition to traditional agents such as vitamin K antagonists and heparins, newer oral agents – such as the factor Xa inhibitors rivaroxaban, apixaban, and edoxaban, and the direct thrombin inhibitor dabigatran – have been shown to be effective across several indications. Rivaroxaban has been shown to have predictable pharmacokinetic and pharmacodynamic properties, including a rapid onset of action. In addition, there is no requirement for routine coagulation monitoring; and no dose adjustment is necessary for age alone, sex, or body weight. Rivaroxaban has successfully met primary efficacy and safety endpoints in large, randomized phase III trials across several indications, including: prevention of venous thromboembolism in orthopedic patients undergoing elective hip or knee replacement surgery; treatment of deep vein thrombosis and secondary prevention of deep vein thrombosis and pulmonary embolism; stroke prevention in patients with atrial fibrillation; and secondary prevention of acute coronary syndrome. Rivaroxaban and the other newer oral anticoagulants are likely to improve outcomes in the prevention and treatment of thromboembolic events, and will offer patients and physicians alternative treatment options.
acute coronary syndrome; atrial fibrillation; orthopedics; pulmonary embolism; rivaroxaban; stroke; venous thromboembolism; venous thrombosis
The eustachian valve is an embryological remnant of the inferior vena cava valve that is absent or inconspicuous in the adult. Even when prominent, it is considered to be a benign finding. The present report describes a patient with deep venous thrombosis who had recurrent pulmonary embolism despite thrombolysis and anticoagulation. He was found to have an adherent thrombus on the eustachian valve and his symptoms resolved completely following surgical thrombectomy. The present report highlights that the eustachian valve can, on rare occasions, harbour pathology and can adversely impact the outcomes of coexisting medical problems such as deep venous thrombosis. Infective endocarditis, pulmonary embolism and systemic embolism via a patent foramen ovale are the major complications of eustachian valve pathology. Transesophageal echocardiography appears to be superior to transthoracic echocardiography in identifying eustachian valve pathology and should be considered in all patients with thromboembolism without a known source.
Eustachian valve; Eustachian valve thrombosis; Valve of inferior vena cava; Venous thromboembolism
Deep vein thrombosis (DVT) is a common condition that is often under-diagnosed. Acquired or hereditary defects of coagulation or a combination of these defects may facilitate the development of DVT. Recurrent DVT, a positive family history or unusual presentation may warrant investigation for hereditary thrombophilia. Investigations are best when conducted at least one month after completion of a course of anticoagulant therapy. Most patients are managed with heparin in the acute stage overlapped by warfarin. The case presented here describes a 40-year old man undergoing three episodes of DVT. Investigations revealed protein C and protein S deficiency. Protein C, protein S and antithrombin deficiency either singly or in combination, are relatively common causes of hereditary thrombophilia. The case presented here serves as a reminder of the need to look into the underlying cause of venous thromboembolism.
Deep vein thrombosis; Thrombophilia
Introduction. Controversy remains over the optimal length of anticoagulation following idiopathic venous thromboembolism. We sought to determine if a longer, finite course of anticoagulation offered additional benefit over a short course in the initial treatment of the first episode of idiopathic venous thromboembolism. Data Extraction. Rates of deep venous thrombosis, pulmonary embolism, combined venous thromboembolism, major bleeding, and mortality were extracted from prospective trials enrolling patients with first time, idiopathic venous thromboembolism. Data was pooled using random effects meta-regression. Results. Ten trials, with a total of 3225 patients, met inclusion criteria. For each additional month of initial anticoagulation, once therapy was stopped, recurrent venous thromboembolism (0.03 (95% CI: −0.28 to 0.35); P = .24), mortality (−0.10 (95% CI: −0.24 to 0.04); P = .15), and major bleeding (−0.01 (95% CI: −0.05 to 0.02); P = .44) rates measured in percent per patient years, did not significantly change.
Conclusions: Patients with an initial idiopathic venous thromboembolism should be treated with 3 to 6 months of secondary prophylaxis with vitamin K antagonists. At that time, a decision between continuing with indefinite therapy can be made, but there is no benefit to a longer (but finite) course of therapy.
Pulmonary embolism (PE) and deep vein thrombosis are two elements of the same pathophysiological process referred to as venous thromboembolism. PE occurs when a thrombus migrates from a deep vein to the pulmonary arteries. Although the true incidence of PE is not known, it is estimated that 530,000 cases of PE occur annually in the United States. Clinical presentation varies from asymptomatic (incidentally diagnosed) to fatal. Development of symptoms depends on the embolic burden and the severity of any underlying cardiopulmonary disease. Several treatment options are available for patients diagnosed with PE. The mainstay of treatment is anticoagulation, but given the high mortality associated with some presentations of symptomatic PE, some advocate more aggressive therapy. In this article we discuss such therapies and their potential and appropriate use.
pulmonary embolism; thrombolysis; catheter-directed thrombolysis; pharmaco-mechanical thrombolysis
Pulmonary thromboembolism is a very rare event in children, but the mortality rate is reported to be approximately 10%. The majority of children with thromboemboli have multiple risk factors, such as a catheter-related thrombosis, an infection, and a congenital prothrombotic disorder. Hypereosinophilia is very rarely associated with pulmonary emboli in adults; however, this condition has not been reported in children. We present a 12-year-old boy who had a pulmonary thromboembolism and deep vein thrombosis associated with hypereosinophilia and thrombocytopenia. The thromboembolism was managed with anticoagulant therapy and the hypereosinophilia resolved spontaneously.
Pulmonary thromboembolism; Child; Eosinophilia
Thrombosis, the localized clotting of blood, occurs in both the arterial and venous circulation, and has a major impact on health outcomes. The primary etiology of myocardial infarctions, and approximately 80% of strokes, is acute arterial thrombosis. In combination this represents the most common cause of death in the Western world, while the third leading cause of cardiovascular-associated death is venous thromboembolism. An understanding of the pathogenic changes in the vessel wall and the blood that result in thrombosis is crucial for developing safer and more effective antithrombotic drugs. Dabigatran etexilate belongs to a new class of direct thrombin inhibitors. Following oral administration, dabigatran reaches peak plasma concentrations within 2 hours, shows linear pharmacokinetics, and a limited (but important) amount of direct drug interactions. Given once daily at 150 mg or 220 mg, it has proven to be competitive with enoxaparin in the prevention of venous thromboembolism after major orthopedic surgery, with a comparable safety profile. For stroke prevention in patients suffering from atrial fibrillation, dabigatran administered at a dose of 110 mg twice daily was associated with rates of stroke and systemic embolism that were similar to those associated with warfarin, as well as lower rates of hemorrhage. Dabigatran given at a dose of 150 mg twice daily, as compared with warfarin, was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage. Oral bioavailability of dabigatran, together with a rapid onset and offset of action and predictable anticoagulation response, makes this newly available antithrombotic drug an attractive alternative to traditional anticoagulant therapies for numerous thrombosis-related indications.
dabigatran etexilate; anticoagulation; direct thrombin inhibitors; thrombosis; prevention
The purpose of this study was to evaluate the early outcome of endovascular management in patients with iliofemoral deep venous thrombosis (DVT) due to iliac vein compression syndrome (IVCS) and protein C and/or S deficiency. Between September 2000 and January 2003, catheter-directed thrombolysis was performed in 11 patients with a diagnosis of acute iliofemoral DVT: 7 with protein C and/or S deficiency and 4 without protein C and/or S deficiency. After thrombolysis, the diagnosis of IVCS was confirmed in 6 patients: 4 with protein C and/or S deficiency and 2 without protein C and/or S deficiency. Further intervention consisted of angioplasty and stent placement was performed. Four patients with IVCS and protein C and/or S deficiency were included in this study. The immediate technical and clinical success rates were 100% in all 4 patients. There were no complications or clinically detectable pulmonary emboli. This initial experience suggests that endovascular management of iliofemoral DVT due to IVCS in patients with protein C and/or S deficiency is safe and effective.
Thrombolytic Therapy; Venous Thrombosis; Protein C Deficiency; Protein S Deficiency
The use of catheter-directed thrombolysis is a proven treatment for arterial ischemia, deep vein thrombosis, and severe pulmonary embolism. For arterial ischemia, thrombolysis has resulted in improved amputation-free survival and fewer subsequent surgeries to reestablish blood flow to the ischemic limb. The management of patients with thromboembolic diseases is complex, and the multiple thrombolytic drugs available to choose from compound this complexity. Although some believe the available thrombolytic agents are interchangeable, real biochemical differences exist that may prove otherwise. This article describes these pharmacologic differences and how they may affect the clinical practice of catheter-directed thrombolysis.
Thrombolysis; catheter-directed thrombolysis; pharmacology; bleeding complications
Portal vein thrombosis (PVT) is a rare form of venous thrombosis that affects the hepatic portal vein flow, which can lead to portal hypertension. Treatment of PVT includes anticoagulants, thrombolysis, insertion of shunts, bypass surgery, and liver transplantation. Single anticoagulation therapy is not regarded as a curative treatment but can be associated with a reduction in new thrombotic episodes. We experienced a case of acute total occlusion of PVT provoked by protein C and S deficiency syndrome. PVT was completely recanalized with oral anticoagulant therapy following low molecular weight heparin therapy.
Protal vein; Thrombosis; Protein C deficiency; Protein S deficiency; Anticoagulation
Thrombophilia traditionally refers to rare inherited defects leading to enhanced coagulation, especially of the venous system. In recent years, a broader search for genetic polymorphisms of prothrombotic genes has been carried out to determine the relative impact on venous and arterial thrombosis. The bulk of evidence is drawn from numerous, often small, heterogeneous, case control association studies, with a variety of end points (deep venous thrombosis, myocardial infarction, or stroke). The data are often conflicting and inconclusive with only factor V Leiden and prothrombin polymorphisms having clear associations with venous thrombosis. Many of the polymorphisms interact with established cardiovascular risk factors, in particular smoking, to increase greatly the risk of a thrombotic episode. Future studies will need to consider the confounding factors of sample size, race, and clinical end points as well gene–environment interactions.
thrombophilia; polymorphism; thrombosis; vascular disease
Introduction. Primary venous tumours are a rare cause of deep vein thrombosis. The authors present a case where the definitive diagnosis was delayed by inconclusive complementary imaging.
Clinical Case. A thirty-seven-year-old female presented with an iliofemoral venous thrombosis of the right lower limb. The patient had presented with an episode of femoral-popliteal vein thrombosis five months before and was currently under anticoagulation. Phlegmasia alba dolens installed progressively, as thrombus rapidly extended to the inferior vena cava despite systemic thrombolysis and anticoagulation. Diagnostic imaging failed to identify the underlying aetiology of the deep vein thrombosis. The definitive diagnosis of primary venous leiomyosarcoma was reached by a subcutaneous abdominal wall nodule biopsy.
Conclusion. Primary venous leiomyosarcoma of the iliac vein is a rare cause of deep vein thrombosis, which must be considered in young patients with recurrent or refractory to treatment deep vein thrombosis.
Reports of thromboembolism following the use of oral contraceptives received by drug safety committees in the United Kingdom, Sweden, and Denmark have been analysed to investigate possible differences in the risks associated with the various preparations. For this purpose the numbers of reports of thromboembolism attributed to each product were compared with the distribution that would have been expected from market research estimates of sales, assuming that all products carried the same risk.
A positive correlation was found between the dose of oestrogen and the risk of pulmonary embolism, deep vein thrombosis, cerebral thrombosis, and coronary thrombosis in the United Kingdom. A similar association was found for venous thrombosis and pulmonary embolism in Sweden and Denmark. No significant differences could be detected between sequential and combined preparations containing the same doses of oestrogen, nor between the two oestrogens, ethinyloestradiol and mestranol.
Certain discrepancies in the data suggest that the dose of oestrogen may not be the only factor related to the risk of thromboembolism; thus there was a significant deficit of reports associated with the combination of mestranol 100 μg. with norethynodrel 2·5 mg. and a significant excess of reports associated with the combination of ethinyloestradiol 50 μg. with megestrol acetate 4 mg. An excess of reports also occurred with other combined preparations containing megestrol acetate.
The data obtained in earlier epidemiological studies were re-examined and, though no trend was obvious in any one of them, the combined results showed an excess of cases of thromboembolism at the highest dose of oestrogen.
The finding of a positive correlation between the dose of oestrogen and the risk of coronary thrombosis is of special interest since previous studies have failed to provide clear evidence of a relationship between oral contraceptives and this condition.