Spontaneous Venous Thrombosis Research Articles

Superior vena cava obstruction: bypass using spiral vein graft

Background. Previous midterm experience with the composite spiral saphenous vein graft to bypass the obstructed superior vena cava (SVC) has been favorable. This study looks at the long-term results in patients followed for up to 23 years.Methods. Sixteen patients aged 17 to 68 years had operation for obstruction of the SVC with SVC syndrome caused by benign disease. Eleven patients had fibrosing mediastinitis with or without caseous necrosis, 4 had thrombosis caused by a catheter or a pacemaker electrode, and 1 had spontaneous thrombosis. All operations were performed using a composite spiral vein graft constructed from the patient’s own saphenous vein. Graft diameter ranged from 9.5 to 15.0 mm. Ten grafts were from the left innominate vein, and six grafts were from the right or left internal jugular vein. The grafts were placed to the right atrial appendage in all patients except 1. Follow-up extends from 1 month to 23 years 8 months (mean follow-up, 10.9 years).Results. Fourteen of 16 grafts remain patent for up to 23 years, and all patients but 1 are free from SVC syndrome. One patient required revision of the graft for thrombosis 4 days after operation. Two grafts closed during the first year after operation: one because of recurrence of spontaneous venous thrombosis and the other because of aggressive fibrosing mediastinitis requiring operation for graft revision three times over a 12-year period prior to death.Conclusions. These data demonstrate that a spiral vein bypass graft for treatment of the obstructed SVC relieves SVC syndrome and has excellent long-term patency.

Antiphospholipid Antibodies

Although significant progress has been made during the last decade in our knowledge of the antiphospholipid antibodies (aPL), there are two major questions in clinical practice that require further guidelines: Indications for aPL determination and laboratory tests to choose. This article reviews the main clinical indications to search for aPL (systemic lupus erythematosus, selected autoimmune conditions, spontaneous venous and arterial thrombosis, recurrent fetal losses, and autoimmune thrombocytopenia, among others) as well as the routine tests to detect aPL (serological tests for syphilis, lupus anticoagulant tests, solid phase techniques to detect anticardiolipin and other aPL and antibodies to aPL cofactors). Finally, a complete work-up is suggested for those patients with clinical manifestations of the aPL syndrome but without detection of aPL in the routine tests ("seronegative" aPL syndrome).

Laboratory Evaluation and Clinical Characteristics of 2,132 Consecutive Unselected Patients with Venous Thromboembolism – Results of the Spanish Multicentric Study on Thrombophilia (EMET*-Study)

Previous studies on the prevalence of biological abnormalities causing venous thrombosis and the clinical characteristics of thrombotic patients are conflicting. We conducted a prospective study on 2.132 consecutive evaluable patients with venous thromboembolism to determine the prevalence of biological causes. Antithrombin, protein C, protein S, plasminogen and heparin cofactor-II deficiencies, dysfibrinogenemia, lupus anticoagulant and antiphospholipid antibodies were investigated. The risk of any of these alterations in patients with familial, recurrent, spontaneous or juvenile venous thrombosis was assessed. The overall prevalence of protein deficiencies was 12.85% (274/2,132) and antiphospholipid antibodies were found in 4.08% (87/2,132). Ten patients (0.47%) had antithrombin deficiency, 68 (3.19%) protein C deficiency, 155 (7.27%) protein S deficiency, 16 (0.75%) plasminogen deficiency, 8 (0.38%) heparin cofactor-II deficiency and 1 had dysfibrinogenemia. Combined deficiencies were found in 16 cases (0.75%). A protein deficiency was found in 69 of 303 (22.8%) patients with a family history of thrombosis and in 205/1,829 (11.2%) without a history (crude odds ratio 2.34, 95% CI 1.72-3.17); in 119/665 (17.9%) patients with thrombosis before the age of 45 and 153/1,425 (10.7%) after the age of 45 (crude odds ratio 1.81, 95% CI 1.40-2.35); in 103/616 (16.7%) with spontaneous thrombosis and in 171/1,516 (11.3%) with secondary thrombosis (crude odds ratio 1.58, 95% CI 1.21-2.06); in 68/358 (19.0%) with recurrent thrombosis and in 206/1,774 (11.6%) with a single episode (crude odds ratio 1.78, 95% CI 1.32-2.41). Patients with combined clinical factors had a higher risk of carrying some deficiency. Biological causes of venous thrombosis can be identified in 16.93% of unselected patients. Family history of thrombosis, juvenile, spontaneous and recurrent thrombosis are the main clinical factors which enhance the risk of a deficiency. Laboratory evaluation of thrombotic patients is advisable, especially if some of these clinical factors are present.

Neonatal Thrombosis: Report of a Prospective Canadian and International Registry

We sought to obtain representative data on the risk factors, diagnosis, current management, and short-term outcome of neonatal thrombosis. A case registry was established at McMaster University. Standardized questionnaires were mailed to collaborators at participating centers every 4 to 6 months. Eighty-five level III and modified level II neonatal units in North America, Europe, and Australia were invited to join the registry. Eligible infants were born between January 1990 and June 1993. Large-vessel thrombosis was diagnosed during the first month of life or up to 44 weeks post-conception after premature birth. The clinical impression of thrombotic vessel obstruction was confirmed using at least one imaging technique. Physicians in 64 centers expressed their willingness to participate. A total of 97 cases (excluding stroke) were registered from 29 centers. Spontaneous renal venous thrombosis (n = 21) was diagnosed at a median age of 2 days. The other venous (n = 39), arterial (n = 33), and mixed (n = 4) thromboses presented later; 89% of them were associated with an intravascular catheter and 29% with systemic infection. Doppler ultrasonography was the definitive diagnostic test in 68% of cases; contrast angiography was performed infrequently (14%). A third of all patients (but 62% of infants with renal venous thrombosis) received supportive therapy only. Thrombolytic agents were prescribed for 28% of catheter-associated venous thromboses and 30% of all arterial thromboses. The remainder of the patients were given heparin. Most patients (82%) survived to hospital discharge. Mortality rates were highest among infants with aortic thrombosis or central venous line-associated thrombosis affecting the right atrium or the superior vena cava (33%). Neonatal thrombosis is diagnosed fairly rarely. With the exception of spontaneous renal venous thrombosis, almost all cases are associated with indwelling catheters. Doppler ultrasound techniques are the most popular means of confirming the diagnosis in virtually all centers. Treatment varies greatly among different centers, probably because of the lack of scientific evidence about the optimum management of affected infants.

Protein S deficiency: imaging findings.

Protein S deficiency is an autosomal-dominant inherited disorder of coagulation associated with spontaneous and recurrent venous thrombosis. Approximately 5% of patients with deep venous thrombosis of the lower extremities who are less than 45 years old have a deficiency of protein S. Patients frequently have spontaneous and recurrent deep venous thrombosis and pulmonary embolism during young adulthood. Thrombosis occurs less commonly in the splanchnic and cerebral veins. Arterial thrombosis is rare but is seen in the cerebral circulation. Radiologists should include protein S deficiency in the differential diagnosis of unexplained thrombosis in young patients. This pictorial essay illustrates the range of imaging findings encountered in patients with this disorder.

Occlusive hyperemia: a new way to think about an old problem

A L-RODHAN and his coworkers at the Mayo Clinic' have introduced the new term to explain on a hemodynamic basis the edema, either with or without hemorrhage, that may complicate excision of arteriovenous malformations (AVM's), usually larger AVM's with high flows. An identical occlusive hyperemia may follow preoperative embolization and, in our institution for one, postembolization occlusive hyperemia has occurred more often than postexcision occlusive hyperemia. In fact, we have encountered a handful of cases in which occlusive hyperemia (cerebral edema with associated hemorrhage) caused abrupt neurological deterioration after spontaneous thrombosis of a major draining vein, a condition that we have termed overload. Venous overload is a common accompaniment of both symptomatic and asymptomatic AVM's, with the pathognomonic findings of venous outflow restriction and aberrant venous drainage patterns shown by angiography and findings of cerebral edema demonstrated on computerized tomography and magnetic resonance (MR) imaging. In our opinion, the evolution of a nidus aneurysm or angiographically obvious venous outflow restriction (or both) precedes rupture of many, if not most, AVM's that have spontaneous hemorrhage as their mode of presentation. Finally, precisely the same manifestations of occlusive hyperemia accompany dural arteriovenous fistulas (AVF's) when venous outflow becomes restricted and eventually occluded. Apart from ruptured aneurysms, interference with venous drainage represents the single factor responsible for almost all clinically significant complications of AVM's and AVF's preceding, during, and following treatment. Restriction of venous outflow becomes the most critical determinant of what happens within and surrounding an AVM nidus. What are the exceptions? First, rupture of an AVM nidus (which, incidentally, is believed to occur nearer the venous than the arterial end of the nidus) can undoubtedly occur in the absence of any venous occlusive process. Second, pure postoperative hemorrhage from a retained portion of an AVM represents rebleeding, whether it is a matter of blowing out a clotted plug or of arterial overload as blood is diverted to the retained nidus. However, in the instance of a retained nidus coupled with venous restriction, the venous overload (occlusive hyperemia) becomes malignant! To eliminate or reduce the possibility of a retained nidus, we rely on intraoperative postresection angiography and strongly recommend it. AI-Rodhan, et aL,~ do not speculate on the wide range of intervals, from less than 3 hours to 11 days, between the time the patient leaves the operating room and the onset of neurological deterioration. We suspect that early deterioration, possibly during the 1st day or so, reflects differing degrees of venous outflow restriction, and that later deterioration, certainly after several days, can be attributed to outright delayed thrombosis of one or more critical draining veins or even a dural venous sinus. Clearly, the matter of early versus late delay is not a black-and-white issue, but at least the possible mechanisms fit more or less into such a pattern. Stagnation of arterial flow may be difficult to characterize in a background of postoperative edema, intraoperative occlusion of feeding arteries, and coexisting venous obstruction. We have the impression that stagnation of arterial flow is common in the immediate postoperative period and more likely to occur after resection of larger AVM's. The person directing postoperative care may unwittingly promote venous thrombosis by keeping the patient dry as a well-accepted means of reducing postoperative reactive edema. Better postoperative management would be to assure an adequate blood volume, assiduously avoid hemoconcentration or even a hematocrit over 35%, and immediately after the operation commence a course of aspirin and low-dose heparin therapy. The known and unknown factors that cause spontaneous extracranial venous thrombosis after craniotomy must apply intracranially as well. A1-Rhodan, et al., ~ present two cases as examples, and both cases deserve comment. In Case 1 the respon-

Bilateral Deep Venous Thrombosis in Protein S Deficiency Detection by Radionuclide Venography

Patients with primary hypercoagulopathies often present with recurrent, spontaneous deep venous thrombosis and pulmonary embolism. An adolescent eventually diagnosed with protein S deficiency presented with unilateral deep venous thrombosis documented ultrasonographically. Scintigraphic studies showed no evidence of pulmonary embolism but revealed a complete absence of deep venous flow in both lower extremities, the pelvis, and the abdomen. Subsequent ultrasonography and CT scanning documented this marked thrombotic extension. Radionuclide scintigraphy may play an important role in the serial evaluation of primary hypercoagulable states, particularly when pulmonary scintigraphy is combined with bilateral, lower extremity venography.

Bypass of superior vena cava: Fifteen years’ experience with spiral vein graft for obstruction of superior vena cava caused by benign disease

Nine patients had operations for obstruction of the superior vena cava with superior vena caval syndrome caused by benign disease. Three patients had fibrosing mediastinitis, four had fibrosing mediastinitis with caseous necrosis, one had thrombosis of the superior vena cava around a pacemaker electrode, and one had spontaneous thrombosis of the superior vena cava. Patients ranged in age from 25 to 68 years. All bypass operations were performed with a composite spiral vein graft constructed from the patient's own saphenous vein, split longitudinally and wrapped around a stent in spiral fashion. The edges of the vein were sutured together to form a large conduit ranging in diameter from 9.5 to 15.0 mm. Six grafts were from the left innominate vein and three grafts were from the internal jugular vein. The grafts were placed into the right atrial appendage in all except one case, in which the graft was to the distal superior vena cava. Follow-up extends from 1 to 15 years. One patient required reoperation at 4 days for thrombosis at the innominate vein-graft anastomosis. Resection of the anastomosis and reconstruction of the graft rendered the patient symptom free. Two grafts closed during the first year after operation. One patient had advancing fibrosing mediastinitis, and a second bypass graft from the external jugular veins remain patent. Another patient had recurrence of spontaneous venous thrombosis. Thus seven of nine grafts remain patent for up to nearly 15 years and all but one patient is free of superior vena caval syndrome. These data show that bypass of the obstructed superior vena cava with a spiral vein graft relieves superior vena caval syndrome and demonstrate long-term patency of the graft.

Johanson-Blizzard syndrome and hypopituitarism

1. Griffin JH, Evatt B, Zimmerman TS, Kleiss A J, Wideman C. Deficiency of protein C in congenital thrombotic disease. J Clin Invest 1981;68:1370-3. 2. Bertina RM, Broekmans AW, Van der Linden IK, Mertens K. Protein C deficiency in a Dutch family with thrombotic disease. Thromb Haemost 1982;48:1-5. 3. Broekmans AW, Veltkamp J J, Bertina RM. Congenital protein C deficiency and venous thromboembolism: a study of three Dutch families. N Engl J Med 1983;309:340-4. 4. Wintzen AR, Broekmans AW, Bertina RM, et al. Cerebral haemorrhagic infarction in young patients with hereditary protein C deficiency: evidence for spontaneous cerebral venous thrombosis. Br Med J 1985;290:350-2. . 5. Boyer C, Rothschild C, Wolf M, Amiral J, Meyer D, Larrieu MJ. A new method for the estimation of protein C by ELISA. Thromb Res 1984;36:579-89. 6. Francis RB, Patch MJ. A functional assay for protein C in human plasma. Thromb Res 1983;32:605-13. 7. Nardi M, Karpatkin M. Prothrombin and protein C in early childhood: normal adult levels are not achieved until the fourth year of life. J PED1ATR 1986;109:843-5. 8. Dusser A, Gouti6res F, Aicardi J. Ischemic strokes in children. J Child Neurol 1986;1:131-6. 9. Barbui T, Finazzi G, Mussoni L, et al. Hereditary dysfunctional protein C (protein C Bergamo) and thrombosis [Letter]. Lancet 1984;2:819. 10. Israels SJ, Seshia SS. Childhood stroke associated with protein C or S deficiency. J PED1ATR 1987;111:562-4. 11. Griffin JH, Mosher DF, Zimmerman TS, Kleiss AJ. Protein C, an antithrombotic protein, is reduced in hospitalized patients with intravascular coagulation. Blood 1982;60:261-4. 12. Vigano S, Mannucci PM, Solinas S, Botasso B, Mariani G. Decrease in protein C antigen and formation of an abnormal protein soon after starting oral anticoagulant therapy. Br J Haematol 1984;57:213-20.

Deficient t-PA release and elevated PA inhibitor levels in patients with spontaneous or recurrent deep venous thrombosis: Juhan-Vague I, Valadier J, Alessi MC, et al. Thromb Haemost 1987;57:67–72

Deficient t-PA release and elevated PA inhibitor levels in patients with spontaneous or recurrent deep venous thrombosis: Juhan-Vague I, Valadier J, Alessi MC, et al. Thromb Haemost 1987;57:67–72

Prosthetic graft thrombosis associated with lupus anticoagulant

The presence of an unique in vitro coagulation inhibitor in two patients with systemic erythematosis (SLE) was first described by Conley and Har tmann (1952). 1 A similar phenomenon in a patient without SLE was subsequently described by Frick (1955). 2 The term lupus (LA) was introduced in 19 72 by Feinstein and Rapaport. 3 For the clinician the term lupus ant icoagulant is misleading because this inhibitor of coagulation tests only rarely interferes with haemostasis in vivo. Furthermore it is not confined to patients with lupus. Its clinical implications, paradoxically,, are concerned with spontaneous venous and arterial thrombosis. 4 The identification of anticoagulant is hallmarked by the prolongation of phospholipid-dependent coagulation tests, which are not corrected by the addition of normal plasma but which will become normal with the addition of platelet phospholipid. This is due to the action of immunoglobulins of the IgG or IgM class, with affinity for phospholipid (platelet factor III), s hence the alternative term lupus antibody. We report two patients with peripheral vascular disease who underwent aorta-bifemoral and femoropopliteal bypass respectively, who were incidentally found to have LA. Both procedures were technically straightforward and a successful outcome was anticipated. Both patients suffered from unexpected-and in one case repeated--graf t thrombosis. We have been unable to find similar cases reported within the literature.

Deficient t-PA Release and Elevated PA Inhibitor Levels in Patients with Spontaneous or Recurrent Deep Venous Thrombosis

The fibrinolytic system was investigated in 120 patients with spontaneous or recurrent deep vein thrombosis (DVT) without any known organic disease able to explain by itself the occurrence of a thrombosis and without any known defect of antithrombin III, Heparin Cofactor II, Protein C, or Protein S. The assays included: Euglobulin fibrinolytic activity (EFA), tissue-type plasminogen activator related antigen (t-PA-Ag) and plasminogen activator inhibitor activity (PA inhibitor), which were measured before and after 10 min of venous occlusion (V.O.). On the basis of the results, the patients could be classified in 3 groups: good responders with an at least two-fold increase of EFA after venous occlusion (n = 76), poor responders with a lesser increase of EFA due to deficient release of t-PA (n = 12), and poor responders with a normal t-PA release but an increased level of PA-Inhibitor (n = 32). The poor responders due to deficient t-PA release (10% of total) had a higher incidence of recurrence of deep vein thrombosis, than the other groups (p less than 0.01). An overall correlation was found between the level of PA-Inhibitor activity and the triglyceride level (r = 0.40, p less than 0.01), suggesting that these elevations may be due to a common cause, at least in some of the patients. It is concluded that a poor fibrinolytic response to venous occlusion occurs in 35 percent of DVT patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormal plasminogen: A genetically determined cause of hypercoagulability

An inherited disorder of the fibrinolytic system has been discovered as a cause of unusual clotting. An abnormal immunoreactive plasminogen was identified in eight patients who presented with unexplained thrombosis. Six patients presented with spontaneous arterial or venous thrombosis, and two patients developed postoperative occlusion of an arterial reconstruction. Five of the six patients with spontaneous thrombosis had recurrent episodes involving both the arterial and venous system at time intervals between the thrombotic episodes varying from 1 month to several years. Detection of an abnormal plasminogen was made by immunoelectrophoresis of the patient's serum with an antiplasminogen sera. In normal patients, plasminogen migrates as a single band toward the anode. In these eight patients a separate immunoreactive band located nearer the anode and distinct from the normal band was detected. Examination of family members of two patients identified a similar abnormal plasminogen with an overall incidence suggestive of an autosomal dominant inheritance pattern. This study suggests the presence of a genetically determined plasminogen variant resulting in a functional deficiency of the plasminogen system causing a reduction of fibrinolytic activity and a latent thrombotic tendency. Recommended treatment is long-term warfarin anticoagulation.

Popliteal aneurysms.

Although popliteal aneurysm is reportedly common, there are few series reporting large numbers, and little uniformity in the method of treatment. Review of 52 popliteal aneurysms in this series showed that when thromboembolic complications occurred, the amputation rate was 28 per cent. When the aneurysm was patent at presentation, amputation was the outcome in one in 20 cases (5 per cent), indicating that repair is not without risk. An unsatisfactory outcome was usually caused by excessive delay before reconstructive arterial surgery was undertaken. In most cases delay was caused by failure to recognize the presence of the popliteal aneurysm. This review confirms the susceptibility of elderly males and emphasizes the need for considering the diagnosis of popliteal aneurysm in cases of acute lower limb ischaemia. Alternative presentations include spontaneous venous thrombosis, pain and swelling behind the knee, rupture and mycotic infection.

Spontaneous Venous Ilio-Femoral Thrombosis in an Infant

Spontaneous Venous Ilio-Femoral Thrombosis in an Infant

Paroxysmal nocturnal hemoglobinuria associated with hepatic and portal venous thrombosis

Paroxysmal nocturnal hemoglobinuria is a form of chronic hemolytic anemia characterized by an intracorpuscular red cell defect which makes it highly susceptible to acid hemolysis, especially at night, and one of whose major complications and causes of death is spontaneous venous thrombosis. The disease and two cases in which portal hypertension secondary to the thrombotic phenomenon occurred are discussed. The surgical therapy for decompression of the portal bed by portal-azygos disconnection in one of these cases is presented and discussed.

Spontaneous, lower-extremity venous thrombosis in children.

Spontaneous lower-extremity venous thrombosis, although common in adults, is not mentioned in current pediatric textbooks. Case records from 1952 to 1972 at the Children's Hospital of Denver were reviewed, and 28 cases of venous thrombosis unrelated to local venous catheterization or venous surgery were identified. Local infection, trauma, and immobilization were the most important predisposing factors. The most frequent diagnostic findings were local tenderness and increased size of the involved extremity. Complications developed in seven of 28 cases, including three suspected cases of pulmonary emboli and three cases of staphylococcal septicemia. There was one fatality. Specific conclusions about therapy from this study could not be made. However, with venous thrombosis in children, it is recommended to identify local predisposing infections, obtain blood cultures, and treat with antibiotics when indicated.

Hyperactive Connective Tissue in Seven Patients with Recurrent Thrombotic Occlusions

A saline extract from the fascia of musculus rectus abdominis with increased capacity to aggregate the platelets <i>in vitro</i> was found in two uraemic patients with recurrent obstructive thrombosis frequently complicating the shunts used for haemodialysis, and in five patients with recurrent spontaneous deep venous thrombosis. None of these patients had any other disorder known to predispose to thrombosis. The increased capacity of the fascia extract to induce platelet aggregation may be due to a hitherto unknown cause of thrombosis, namely a defect in the collagen structure or in the subendothelial substances.

Reflections on Spontaneous Venous Thrombosis and Thromboembolic Disease in the Light of 849 Consecutive Pulmonary Operations

Reflections on Spontaneous Venous Thrombosis and Thromboembolic Disease in the Light of 849 Consecutive Pulmonary Operations

Un Nouvel Anticoagulant : La 3 - (1′ - Phenylpropyl) 4 - Hydroxycoumarine.

SummaryThe 3 - (1’ - phenylpropyl) 4 - hydroxycoumarine (marcoumar) is an efficacious anticoagulant; because of its long and definite action, it is particularly maniable.Its action is characterized by a drop of Koller factor VII and prothrombine and can be controlled by Quick method or more easily by the Marbet and Winderstein method.During the treatment of acute thrombosis, simultaneous heparin administration is necessary until the full action of the drug is reached.36 patients have been submitted to the action of this drug. All the cases of spontaneous or postoperative venous thrombosis responded very well. No case of pulmonary emboli has been observed during the evolutionary course of venous thrombosis, and no recidive in patients having presented previously pulmonary emboli.Hemorragic accidents consisted in microscopic hematuria (8 times out of 36) and deep hematoma (one out of 36).Synthetic vit. K1 emulsion is an efficacious antidote bringing back quickly the prothrombine time to harmless levels.