Buerger's disease or thromboangiitis obliterans

The Buerger's disease or thromboangiitis obliterants (TAO) is a non atheromatous inflammatory disease which alters medium and small-sized arteries and veins. It can be found world-wide, but it is more frequent in Eastern Europe, Middle East, Asia and Southeast Asia. Young men and smokers are the most affected. The incidence of this disease is increasing among women. The cause of this disease is unknown yet. The most striking fact is the relationship between TAO and tobacco. The diagnostic is most often late in front of a digital leg ischemia. Complementary exams help to its diagnostic and management but none of them are specific out of the pathology. The affection is evolving towards distal gangrene with amputation in 5 to 10% of cases. Prostacyclin demonstrated its efficiency. Revascularization surgery is difficult but sometimes possible. Sympathectomy, medular stimulation must be suggested. The patient survival is not at stake and the prognosis is above all functional. The most important element in the treatment is stop smoking definitively.     

Long-term outcomes of large artery thromboangiitis obliterans and comparison with small artery thromboangiitis obliterans

Although the distribution of arterial involvement is still the subject of controversy for defining the diagnostic criteria for thromboangiitis obliterans (TAO), several reports have described TAO involving the more proximal arterial segment. This study aimed to investigate the clinical characteristics and outcomes of large artery TAO in comparison with those of small artery TAO.Between January 2007 and July 2019, 83 consecutive symptomatic patients with a diagnosis of lower extremity TAO were stratified according to the most proximal arterial involvement, with the cutoff level of the adductor canal as a reference (large artery TAO versus small artery TAO), and analyzed retrospectively. The study outcomes included any amputations and major amputations.The large artery TAO group consisted of 30 patients (36.1%), and the small artery TAO group consisted of 53 patients (63.9%). In terms of clinical symptoms and signs, the proportion of major tissue loss (Rutherford class 6) was significantly higher among patients with large artery TAO than among those with small artery TAO (13.3% versus 0%, P = .02). Any amputation rate was similar between the large and small artery TAO groups during the median follow-up period of 148 months (range, 0–376 months) (43.3% versus 28.3%, P = .16). However, the major amputation rate was significantly higher among patients with large artery TAO (13.3% versus 0%, P = .02). On Kaplan–Meier survival analysis of the cumulative event-free rates, although there was a similar 10-year amputation-free survival rate (P = .24) between the 2 groups, the large artery TAO group had a significantly lower 10-year major amputation-free survival rate (P < .01) than the small artery TAO group.Large artery TAO is a limb-threatening condition and had a worse prognosis than small artery TAO.     

Dynamics of blood flow in thromboangiitis obliterans

The resting blood flow in the horizontal position in the foot-leg of seven subjects with moderately advanced thromboangiitis obliterans was found to be within normal limits, as measured by the plethysmographic method.The release of arterial occlusion in the thigh resulted in no significant increase in blood flow. No initial increase in limb volume and no significant cardiac acceleration followed the release of arterial occlusion in these subjects.Heat or lumbar sympathetic ganglionectomy, alone or in conjunction with arterial occlusion, was no more effective in increasing the volume of blood flow than was simple arterial occlusion.After the release of arterial occlusion, an initial decrease in blood flow was manifest. This was not prevented by local heat or by sympathetic ganglionectomy.     

Further experience with thromboangiitis obliterans in women

Twenty-five cases of thromboangiitis obliterans in women are presented. The greater tendency for the disease to manifest itself in the hands of women is pointed out. The differential diagnosis between Raynaud's disease and thromboangiitis obliterans is discussed. The etiological relationship of thromboangiitis obliterans to the use of tobacco is again demonstrated.     

Deep thrombophlebitis and pulmonary embolism in thromboangiitis obliterans

Three cases of thromboangiitis obliterans have been presented in which at the reported stages of the disease the manifestations, in contradistinction to the common clinical course of this disease, were primarily those of a deep venous thromboembolic nature rather than occlusive arterial disease. This clinical variant, according to the literature on thromboangiitis, is rare; however, the knowledge of its possible occurrence is important to an early and correct diagnosis of the pulmonary manifestations. Other factors contributing to the confusion and delay in diagnosis of these cases were the relatively late age of the patients at the time of onset of the disease, the absence of clinical evidence of thrombophlebitis at the time of pulmonary embolization and the failure of the arterial occlusive disease to manifest activity simultaneously with the activity of thromboembolic disease.It is possible that the age of these individuals at the time of the greatest activity of the thromboangiitis was a factor contributing to the predominantly venous thromboembolic manifestations. Certainly in general, venous thromboembolic disease is more common in the older age groups. Two of these patients were over fifty years of age at the time of onset of the thromboangiitis and all three were considerably beyond the age group in which the disease is commonly most active clinically.The ages of Case I, fifty-two years, and Case III, fifty-seven years, together with the absence of any active thrombophlebitis or activity of the arterial disease, seemed to necessitate an investigation of the respiratory tract as the possible primary focus of their illness in spite of the knowledge that peripheral vascular disease existed.Pulmonary embolization and infarction occurred repeatedly in all three patients while they were apparently well and ambulatory and at a time when no clinical sign of active deep or even of superficial thrombophlebitis was evident. Iliofemoral thrombophlebitis had occurred in Case I a year prior to the episodes of pulmonary embolization and recurred somewhat over a month after their cessation while in Case II iliofemoral phlebitis was evident three and one-half years before and again two and one-half months before the embolic accidents. Case III never exhibited an iliofemoral thrombophlebitis but a deep thrombosis of the foot and calf veins developed five months after the last pulmonary embolic episode. These observations would tend to confirm the statement of Allen, Barker and Hines² that deep thrombophlebitis of the anterior and posterior tibial veins is common in thromboangiitis but that only rarely is it clinically evident. It appears most likely that the sources of the emboli in all three cases were the calf veins rather than the more usual iliofemoral veins as suggested by Edwards.⁴As stated by Allen, Barker and Hines² clinical evidences of arterial and venous involvement are not necessarily coincident in Buerger's disease. In Cases I and III the fact that they were dissociated increased the difficulty of the differential diagnosis considerably, whereas in Case II in whom arterial occlusion had been recently active, diagnosis of the pulmonary embolic episodes was greatly facilitated by this knowledge.The treatment of the thrombophlebitis and its attendant pulmonary embolization in thromboangiitis obliterans has not been clearly delineated in the literature. Irving Wright⁵ states that there is at present no generally satisfactory treatment for recurrent, migratory thrombophlebitis and that probably the best long term therapeutic procedure is disturbance of the clotting mechanism through the effect of dicumarol, apparently in the hope that protection against embolization will be provided and that the thrombophlebitic process will subside during this period. As regards the procedure of ligation of the larger venous trunks, aside from the general objections to this procedure which have become recently evident,⁶ there is reason to consider the venous congestion produced thereby specifically undesirable in Buerger's disease, in which the limb is already afflicted with an impairment of the circulatory function. Allen, Barker and Hines² have in their experience found that typhoid vaccine fever therapy has an almost specific effect on the superficial thrombophlebitis. If this is true it would be reasonable to expect that it might likewise exert some beneficial effect on deep thrombophlebitis.Case I was particularly instructive as regards the efficacy of the present therapy of the deep thrombophlebitis of Buerger's disease. While the patient was receiving treatment with typhoid vaccine and while the prothrombin time was satisfactorily and continuously elevated through dicumarol, the migratory superficial phlebitis continued to involve new veins and a deep thrombophlebitis occurred. This would lend some support to the view that the pathologic process in thromboangiitis is primarily endothelial and proliferative rather than primarily thrombotic, and that possibly for this reason the phlebitis continued active in spite of the dicumarol effect which, however, was apparently sufficient to prevent the formation of a type of thrombotic material necessary for the liberation of emboli. After the quiescence of the phlebitis the patient underwent a transabdominal bilateral lumbar sympathectomy and a simultaneous vena caval ligation. Subsequent to this procedure a severe thrombophlebitis developed which almost surely involved the anastomotic and collateral veins to such a degree as to produce severe impairment of the venous return and resulted in persistent massive peripheral edema. A similar treatment and outcome had occurred in Case I reported by Kahn.³ The possibility of immediate or long subsequent phlebitis obstructing the remaining venous channels and producing undesirable swelling would appear to be another contraindication to femoral or vena caval ligation. Surprisingly enough, the patient had an excellent result from the operative procedure as regards the arterial circulation of the extremities despite the venous obstruction.Case II has been under continuous dicumarol therapy for four months while ambulant and has had no further thrombophlebitis or pulmonary emboli.Case III was treated with anticoagulants and typhoid vaccine for a two-week period only while active thrombophlebitis was evident and has had no evidence of recurrent thromboembolic disease for five months. Whether one can attribute these results to therapy or to the natural course of the disease is problematic.At present the most logical and satisfactory course of therapy for such major thromboembolic manifestations as occur in Buerger's disease would appear to be a combination of anticoagulant and intravenous typhoid therapy during the active stage of the phlebitis, with continuation of the anticoagulants indefinitely thereafter with the patient ambulant in the hope that the phlebitic process will subside. Other measures, particularly cessation of smoking, which are commonly employed in the treatment of thromboangiitis are, of course, indicated.     

Antiphospholipid antibodies in practice

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the occurrence of thrombotic or obstetrical events associated with the presence in the serum of patients of antibodies that are associated with thrombosis. For the diagnosis of APS, the presence of either lupus anticoagulant, anticardiolipin or anti-β2-glycoprotein1 antibodies of IgG or IgM isotype is required through laboratory testing. Other autoantibodies such as antiphosphatidylethanolamin or antiphosphatidylserin/prothrombin complex antibodies may be interesting in the diagnosis of APS when common antiphospholipid antibodies are missing. These autoantibodies are still under evaluation for their diagnostic contribution. Despite numerous attempts, the assays that are available for the identification of antiphospholipid antibodies have not been standardized yet, which leads to high variability between reagents and laboratories. Thus, to optimize the biological monitoring of APS syndromes, it is mandatory to have consecutive samples analyzed in the same laboratory.     

Antiphospholipid antibodies in children

Lupus anticoagulant (LA) is made up of heterogeneous IgG and IgM antibodies that prolong clotting times in vitro and is associated with an increased rate of both thrombosis and hemorrhage in vivo, although thrombosis is far more common. Many mechanisms of action have been explored, but none explains the coagulation abnormality of every sample tested. Binding of these antibodies to protein phospholipid complexes provides a unifying model. Antiphospholipid antibodies (APAs) are found in adult patients with a variety of disorders or as an isolated finding. The association of LA and anticardiolipin antibodies (ACAs) with thrombosis in adults has been established, although there is no test as yet to predict thrombotic risk for an asymptomatic affected individual. The presentation of thrombosis with postinfectious APA is uncommon in adults. Children who present with thrombosis and LA are found to have underlying disorders similar to those of adults. Although the presentation of thrombosis in children with postinfectious LA is rare, the association is established. LA-positive children with thrombosis have manifested a severe acquired deficiency of protein S; LA-positive children with hemorrhage have manifested an acquired deficiency of prothrombin. The association of thrombosis with ACA-positive children has been reported. Further work to determine the epidemiology, mechanism of action, and thrombotic potential of APA in children is warranted to better understand, prevent, and treat thrombotic and hemorrhagic complications.     

Antiphospholipid antibodies in pediatrics

Antiphospholipid antibody syndrome has been associated with vascular thrombosis, thrombocytopenia, hemolytic anemia, livedo reticularis, neurologic disorders, and recurrent fetal loss. The diagnosis of antiphospholipid syndrome is given in the presence of an elevated anticardiolipin antibody lupus anticoagulant in addition to a thrombotic event. Antiphospholipid antibodies are responsible for a majority of thrombotic events in children. These antibodies can present as a primary syndrome or secondary to other diseases, such as systemic lupus erythematosus. Anticoagulation therapy with heparin and low-dose aspirin is the recommended treatment in pediatric patients.