Thrombosis associated with the prothrombin G-->A20210 mutation in Behçet's disease

We describe 2 cases of Behcet's disease (BD) and thrombosis who were heterozygous for the prothrombin G-->A20210 mutation. In one case, progressive uncontrolled thromboses led to death. Case-control studies are needed to support the hypothesis of the role of the prothrombin A20210 allele as a risk factor for venous thrombosis in some patients with BD.     

Thrombosis in children with cardiac pathology: analysis of acquired and inherited risk factors

The present study was conducted to analyze the features and risk factors of childhood thrombotic events in patients with cardiac defect followed-up at our hospital. The clinical and laboratory findings of 59 patients diagnosed with cardiac defects and thromboses between 1997 and 2006 were retrospectively analyzed. Thirty-one children (52.5%) had venous system thromboses, 21 (35.6%) had arterial system thromboses, and seven (11.9%) had venous and arterial system thromboses. Presence of congenital heart disease and cardiomyopathy (CMP) were significant risk factors for developing intracardiac thrombosis. In addition, presence of congenital heart disease was the significant statistical risk factor for developing left atrium and right ventricle thromboses. Presence of congenital heart disease was a significant risk factor for developing a central nervous system thrombosis. Presence of pulmonary stenosis and aortic coarctation were significant risk factors for developing a peripheral arterial system thrombosis. Acquired risk factors including major surgery, angiography, central venous catheter, systemic infection, and hypoxia were identified in 49 of the 59 patients. Many patients had more than one of these acquired risk factors. Analysis of the relationship between thrombosis and type of major surgery demonstrated a statistically significant relationship between an intracardiac thrombosis and total correction of tetralogy of Fallot and a peripheral venous system thrombosis and a Blalock Taussig shunt. Twenty-three of the 52 patients (44.2%) had at least one thrombophilic mutation. Overall, a heterozygous factor V Leiden mutation was found in nine patients (17.3%), a methylenetetrahydrofolate reductase 677C-T mutation in 15 patients (28.8%), and a PT 20210G-A mutation in three patients (5.8%). Our data suggest that cardiac defects are common risk factors for developing a childhood thrombosis. The type of disorder determines the site of thrombosis. Acquired risk factors may contribute to the development of a thrombosis. The results of this study also indicate that to ensure early diagnosis, routine screening for thrombosis should be performed in patients with a cardiac defect and that screening for factor V Leiden and PT 20210G-A mutations and other genetic risk factors should be included when assessing all patients with cardiac defects who present with a thrombosis, whether or not a predisposing factor has been identified.     

Catastrophic thromboses and severe thrombocytopenia during heparin therapy in a patient with anti-phospholipid syndrome

Catastrophic anti-phospholipid syndrome (CAPS) is a medical emergency characterized by thromboses of multiple small vessels of internal organs and the brain. Herein we present a patient with primary anti-phospholipid syndrome who developed CAPS manifested by hepatic, renal and splenic artery thromboses, as well as cerebral venous thrombosis. The course was further complicated by severe thrombocytopenia and haemolytic anemia. Two episodes of catastrophic thrombosis developed within 24–36 h after the initiation of heparin therapy, suggesting a role of heparin in triggering thromboses. The patient had no anti-platelet-factor-4 antibodies in repeated measurements, making clinical diagnosis of heparin-induced thrombocytopenia unlikely. The possible role of heparin in induction of thromboses and its therapeutic implication are detailed.     

Catastrophic antiphospholipid syndrome in a patient with Behçet's disease

We report on a patient who had a life-threatening relapse of Beh?et's disease associated with a catastrophic antiphospholipid syndrome. The patient experienced over a short time a recurrent acute myocardial infarction, multiple venous thromboses, uveitis, and erythema nodosum. Search for thrombophilic factors was positive only for lupus anticoagulant (LAC) and criteria for the diagnosis of the antiphospholipid antibody syndrome were fulfilled. LAC was not found three months after the discharge. At that time the patient had no evidence of clinically active disease or thrombosis. We suggest that LAC was the main triggering factor for the repeated thromboses in this patient.     

A case of antiphospholipid syndrome associated with left subclavian artery thrombosis and left external iliac vein thrombosis]

Arterial thrombosis is one of the major symptoms of antiphospholipid syndrome (APS). However, thrombosis in a primary branch of the aorta has rarely been reported in APS. We report here a case of APS complicated by thromboses in both the left subclavian artery and the left external iliac vein. A 32-year-old woman was admitted in May, 1990 complaining of no pulse in the left superficial arteries (e.g., left radial artery) for the past 5 years and acute swelling of the left lower extremity. A left ascending phlebography showed an occlusion of the external iliac vein and arteriography revealed obstruction in the left subclavian artery. Collateral circulations were developed at the site of each thrombus. Clotting and immunological studies revealed a prolonged APTT, a high titer of anticardiolipin antibody and lupus anticoagulant positive. We ruled out various diseases and clinical risk factors predisposing to both arterial and venous thromboses. Accordingly, we concluded that both thromboses were based on APS. Following treatment with anticoagulants, aspirin and corticosteroid, the swelling of her left thigh was diminished and the antibody titer was decreased within 3 months.     

Factor V Leiden and antibodies against phospholipids and protein S in a young woman with recurrent thromboses and abortion

We describe the case of a 39-year-old woman who suffered two iliofemoral venous thromboses, a cerebral ischemic infarct and recurrent fetal loss. Initial studies showed high levels of antiphospholipid antibodies (APAs) and a moderate thrombocytopenia. After her second miscarriage, laboratory diagnosis revealed that the woman was heterozygous for the factor V Leiden mutation and had a functional protein S deficiency as well as anti-protein S and anti-beta 2-glycoprotein I antibodies. The impairment of the protein C pathway at various points could well explain the recurrent thromboses in the patient and supports the role of a disturbed protein C system in the pathophysiology of thrombosis in patients with APAs.     

Superficial venous thrombosis associated with congenital absence of the inferior vena cava and previous episode of deep venous thrombosis

Congenital malformations of the inferior vena cava (IVC) are uncommon and may be associated with an increased risk of venous thrombosis. We report the case of a man with congenital absence of the IVC and remote history of deep venous thrombosis who now presents with severe abdominal wall superficial thrombophlebitis. To our knowledge, this is the first report of a patient with IVC absence who has developed both deep and superficial venous thromboses.     

Prothrombin gene mutation G20210A, homocysteine, antiphospholipid antibodies and other hypercoagulable states in ocular thrombosis.

The purpose of the present study was to determine whether using an extended panel of laboratory tests increases the detection of a hypercoagulable state in patients with ocular thromboses. Twenty consecutive patients with ocular thromboses (vein, artery, or choriocapillaris occlusions) underwent testing for activated protein C resistance/factor V Leiden, prothrombin G20210A, lupus anticoagulant, anticardiolipin antibodies, hyperhomocysteinemia, and deficiencies of protein C, protein S, and antithrombin. For each patient, we selected two age-matched and gender-matched individuals without ocular thromboses as controls. Sixteen of the 20 patients (80%) had one or more laboratory tests that supported a hypercoagulable condition. Prothrombin G20210A (P < 0.02) and hyperhomocysteinemia (P < 0.0006) were significantly more frequent in ocular thrombosis patients compared with controls. The most common condition was antiphospholipid antibody syndrome, present in 40% of patients (confirmed by repeat testing at least 6 weeks later), but this did not reach statistical significance compared with the controls. No patients with ocular thromboses had hereditary abnormalities of protein S, protein C, or antithrombin. In conclusion, an extended panel of laboratory tests improved the detection of a hypercoagulable state in ocular thromboses. Testing for homocysteine, antiphospholipid antibodies, and the prothrombin G20210A mutation should be considered in patients with ocular thromboses.     

Sequelae of deep venous thrombosis, 5-year follow-up of 341 patients

In order to see whether thrombolytic therapy led to a reduction of CPT, a cause of long periods of inability to work, a study on the development of phlebothrombosis was carried out at the Department of Angiology at the Hospital Cantonal of Basle. Subjects presenting deep phlebothrombosis, either acute or sub-acute, were observed after 5 years... Or the 341 patients, 208 received streptokinase and 133 heparin. After the 5 years, 1 in 5 patients had developed CPT. The incidence of CPT was above all related to the extent of the thrombosis. If one considers not only the immediate therapeutic effect but also the extent of the thrombosis, then the incidence of CPT, especially in leg ulcers, is roughly twice as high in patients with extensive thromboses, and therapy is negative, as in the patients with thromboses limited to two stages only, in which group the therapy is positive. It has even been eliminated where the thrombosis had been limited to the leg. Prophylactic measures are therefore necessary in the groups at high risk. The diagnosis must be swift in order to commence correct therapy whilst the thrombosis is not as yet extensive. Heparin therapy seems to be enough for those thromboses limited to the leg. Whilst awaiting thrombolytic methods without serious side-effects, thrombolytic treatment should be reserved for extensive thromboses in young patients with no contraindications. It is a condition sine qua non that the patient and the parameters of coagulation should be monitored.     

Follow-up after deep venous thrombosis in azygos continuation

BACKGROUND: To determine the sequelae of patients after deep venous thrombosis inpatients with azygos continuation defined as agenesis of the inferior vena cava with collateral flow. PATIENTS AND METHODS: Five patients post deep venous thrombosis in the context of azygos continuation were followed up clinically and with colour duplex ultrasonography. RESULTS: All five patients had to our knowledge after the initial deep venous thrombosis no further thromboembolic events. Three patients after isolated iliac thromboses are symptom free or nearly symptom free, two after more extended thromboses still sufferfrom venous claudication. Four patients are without anticoagulation, one patient is permanently orally anticoagulated. CONCLUSIONS: Azygos continuation may not influence the risk of recurrent venous thrombo-embolism nor the outcome of a deep venous thrombosis. Careful deep venous thrombosis prophylaxis in patients with azygos continuation may be sufficient when a risk factor is present but conclusions lack due to the small numbers of patients of enough supportive data.     

Acute coronary and peripheral arterial thrombosis following percutaneous coronary intervention in a patient with previously undiagnosed inherited thrombophilia

Following pretreatment with ticlopidine 250 mg bid for three days, a 40-year-old man underwent successful angioplasty and stenting of the proximal left anterior descending coronary artery and balloon dilation of the midcircumflex coronary artery without stenting. He subsequently developed acute coronary thromboses at both arterial sites and cardiogenic shock. The patient survived after an additional percutaneous coronary intervention (PCI) and intra-aortic balloon pump assistance. This was followed by peripheral arterial thrombosis requiring repeated therapeutic interventions. Laboratory tests for thrombophilia revealed the presence of a G20210A prothrombin gene mutation. Two years later the patient remained free of angina and claudication, and underwent an unremarkable maximum exercise treadmill test. This is the first reported case of acute, multiple coronary and peripheral arterial thrombosis following PCI in a patient with previously unsuspected inherited thrombophilia. Inherited thrombophilia should be considered as a possible cause of arterial thrombosis following PCI.     

Bilateral iliac vein thrombosis after seat belt-related trauma revealing hypoplasia of the inferior vena cava--a case report

Hypoplasia of the inferior vena cava can be revealed by a deep venous thrombosis of the lower limbs. Associated precipitating factors or clotting defects leading to thrombosis are frequently observed. A case of bilateral iliac veins thrombosis occurring after a motor vehicle accident with seat belt injury is reported, revealing hypoplasia of the inferior vena cava. This young man was totally asymptomatic up to the crash, and did not have coagulation abnormalities. The patient had a very good outcome after anticoagulant treatment with complete regression of venous thromboses. Hypoplasia of the inferior vena cava was a predisposing anatomic abnormality that led to thrombosis, but seat belt trauma was probably the precipitating factor. This observation should be kept in mind in the evaluation of a deep venous lower limb thrombosis.     

Thrombolytic therapy for inferior vena cava thrombosis in paroxysmal nocturnal hemoglobinuria

Two patients with paroxysmal nocturnal hemoglobinuria had increasing abdominal girth and ascites. The Budd-Chiari syndrome or inferior vena cava thrombosis was shown by angiography. After thrombolytic therapy, both patients improved, and thrombolysis was shown by radiography. Neither patient had induction of hemolysis secondary to these agents. These studies suggest that both streptokinase and urokinase are safe and effective in the treatment of intra-abdominal venous thromboses associated with paroxysmal nocturnal hemoglobinuria.     

Paradoxical arterial emboli causing acute limb ischemia in a patient with essential thrombocytosis

Acute arterial occlusion can be the result of acute thrombosis or systemic embolism. Paradoxical embolism of a venous thrombosis through a right-to-left shunt is an important cause of acute limb ischemia. We describe a young patient with acute limb ischemia who was found to have multiple deep venous thromboses causing arterial embolization through a patent foramen ovale. Essential thrombocytosis was found to be the risk factor for venous thromboses in this patient. The patient was managed with embolectomy and anticoagulation along with chemotherapeutic cytoreduction of platelet count. This case illustrates the importance of considering the systemic embolism as a cause of acute arterial occlusion. The presence of a hypercoagulable status such as chronic myeloproliferative disorder does not eliminate the possibility of systemic embolism in the event of acute arterial occlusion. Patients presenting with acute limb ischemia should be evaluated for embolic sources. The presence of deep venous thrombosis in such a patient should prompt the evaluation for a patent foramen ovale.     

Ultrasound-guided fine needle aspiration biopsy of portal vein thrombosis in liver cirrhosis: Results in 15 patients

Between 1988 and 1992 ultrasound-guided fine needle aspiration biopsies of thromboses in the main branches of the portal vein were carried out in 15 patients with liver cirrhosis. The aims of the study were to evaluate the usefulness, feasibility and diagnostic accuracy of this procedure in cirrhotics with known or suspected hepatocellular carcinoma. The procedure was carried out only in patients with a platelet count ≥40 000/μL and prothrombin activity ≥40%. A single pass, with a 22 gauge spinal needle, was performed in the portal vein lumen. Diagnosis of the aetiology of the portal vein thrombosis was obtained in all 15 cases. In 12 cases, a cytological diagnosis of hepatocellular carcinoma was made. In one case, the neoplastic cells aspirated were compatible with adenocarcinoma, and a subsequent colonoscopy confirmed the presence of colonic cancer. The material aspirated was compatible with chemically-induced thrombosis in one patient who had undergone several percutaneous ethanol injection sessions for treatment of hepatocellular carcinoma, and in the last case only blood was aspirated, thus ruling out the coexistence of hepatic cancer. We conclude that fine needle aspiration biopsy of portal vein thrombosis is a feasible, low risk procedure that facilitates the diagnosis of hepatocellular carcinoma when fine needle biopsy of focal liver lesions fails. Fine needle aspiration biopsy of portal vein thrombosis is also useful in excluding neoplastic aetiology of portal vein thrombosis.     

Diabetic ketoacidosis complicated by generalized venous thrombosis: a case report and review

Venous thromboembolism is a rarely described complication of diabetic ketoacidosis (DKA). We describe a 21-year-old male patient with poorly controlled type 1 diabetes mellitus who was admitted with DKA, presumably secondary to noncompliance, whose clinical picture was complicated by generalized thrombosis involving multiple venous locations including renal vein, pulmonary vasculature, external iliac and common iliac veins. The patient had no family history of any coagulation disorders and a hypercoagulabilty work-up remained negative. The patient was subsequently anticoagulated with heparin and discharged home on warfarin. To the best of our knowledge, this is the first reported case of multiple venous thromboses occurring as a complication of DKA with no other risk factors. We also reiterate that although rare, venous thrombosis should always be considered as a potential complication of DKA.     

Heterozygous prothrombin gene mutation G20210A and associated diseases

PURPOSE: Prothrombin gene mutation G20210A (factor II) is, in frequency, the second genetic polymorphism involved in venous thrombosis. We report a retrospective studies on 38 patients issued from our medical department, all heterozygous for the factor II mutation and a literature review. METHODS: We have studied 38 patients, all heterozygous for the factor II mutation, selected through a population of 516 tested patients issued from our medical department from 1997 to 2002. The research was performed face with history of thrombotic or obstetrical events, angiopathy or familial screening. RESULTS: Twenty out of thirty-eight patients have at least one episode of venous thrombosis: superficial thromboses, deep thromboses and/or pulmonary embolism. One case of cerebral thrombophlebitis is observed. Venous thrombotic risk factors are associated in 12 cases (60%). Four out of thirty-eight patients have one episode of arterial thrombosis: cardiovascular, peripheral or cerebral. Arterial thrombotic risk factors are associated in all cases. Median age of the first venous thrombosis is earlier than the one of arterial thrombosis (39.11 versus 49.25 years). CONCLUSION: Our studies confirms the interest to search the prothrombin gene mutation when faced with a venous thrombotic event (deep vein thrombosis and/or pulmonary embolism) with or without acquired risk factors. Its involvement in thrombotic arterial disease is still a matter of debate. Data concerning its involvement in systemic diseases and angiopathies (thromboangeitis obliterans, Raynaud's phenomenon and migraine) are still needed. Mechanisms of thromboses could be an increase of prothrombin plasma level with high thrombin synthesis.     

Simultaneous late stent thrombosis in two coronary arteries following drug-eluting stent implantation

Late stent thrombosis has emerged as an infrequent but serious complication of drug-eluting stent (DES) implantation. Premature cessation of dual antiplatelet therapy is the most common risk factor for its occurrence. In the era of multivessel stenting with DES, there is a potential for multivessel late stent thrombosis following cessation of dual antiplatelet therapy. We present a rare case of a patient who sustained simultaneous late stent thromboses in DESs implanted in two coronary arteries as a result of premature cessation of dual antiplatelet therapy.     

Recurrent coronary stent thromboses and myocardial infarctions

Although stent thrombosis is a recognized complication of coronary intervention, recurrent stent thrombosis is rarely reported. We present a patient who suffered 3 ST-segment elevation myocardial infarctions associated with repeated stent thromboses within a month and a half. Although a potentially mechanical cause of thrombosis was identified in the only baremetal stent implanted in this case, no predisposing factors were seen for the 2 drug-eluting stents (DES). While recent worrisome data have suggested a slight increase in the incidence of late angiographic stent thrombosis (defined as occurring beyond 30 days) with drug-eluting stents (DES), their risk of subacute thrombosis (from 1 to 30 days) is reported to be equivalent to that of BMS. Therefore, this rare occurrence serves as a sobering reminder of the risks of subacute thrombosis with both BMS and DES. Marked neointimal inhibition, allergic reactions, as well as thienopyridine resistance, may all contribute to the pathophysiology of DES thrombosis. The Food and Drug Administration advisory panel has concluded that when these devices are used for "on-label" indications, the counterbalance of dramatic target lesion revascularization reduction versus rare incidence of late angiographic stent thrombosis results in no overall increase in DES myocardial infarction or mortality risk. Furthermore, a minimum of 1 year of dual antiplatelet therapy is recommended for all recipients of DES at low risk of bleeding.     

"Downhill" esophageal varices and occlusion of superior and inferior vena cavas due to a systemic venulitis

A patient with a 10-year history of episodes of venous thrombosis, a high ESR, an elevated plasma polyclonal 1gG concentration, and bleeding from esophageal varices had obstruction of both superior and inferior vena cavas with "downhill" esophageal varices and a normal portal vein with normal portal pressure. Extensive investigations revealed no predisposing factor for the venous thromboses, but the patient made a good clinical response to steroids and dapsone, with no further episodes of bleeding nor evidence of major venous thrombosis. The causes and outcome of "downhill" varices are discussed.