Q J Med 2002; 95: 763-764
© 2002 Association of Physicians
Correspondence |
Fibrin-nonspecific agents in the direct thrombolytic treatment of venous sinus thrombosis
1 Department of Neurology and 2 Department of Radiology, Kaohsiung Medical University Hospital, Kaohsiung, TaiwanROC email: ckliu@kmu.edu.tw (Dr Liu)
Sir,
We read the review of cerebral venous thrombosis by Dr Kimber1 with interest, but some other treatments beside his recommendations are worth examining, both in our experience and in recent reports.
Dural sinus thrombosis is not uncommon, and can at times carry a high rate of morbidity, and mortality. There are several treatments, but no definite results have been obtained. Systemic anticoagulant therapy has produced unpredictable clinical responses, and some side-effects, so a more effective recanalization for affected vessels may be required. With recent advances in angiographic technique, pharmacological preparation and catheter technology, we can now perform direct selective venography and thrombolytic therapy with fibrin-nonspecific agents. Recently, we successfully treated a case of acute superior sagittal sinus and right transverse sinus thrombosis in a 39-year-old male with streptokinase using high selective venography, and the recanalization of the dural venous sinus was visualized after treatment.
Mechanical thrombolysis via microballoon angioplasty or with a microsnare, direct thrombolysis with thrombolytic agents, and systemic anticoagulant agents are now used widely for the treatment of sinus thrombosis, but no definite guidelines have yet been established. Systemic heparin or warfarin treatment used to be considered effective,2 as Kimber mentions, but the systemic side-effects and need for frequent monitoring have limited its clinical use. We also agree that though subcutaneous low-molecular-weight heparin has been used in some clinical trials,3 its role remains unclear in the treatment of stroke.
Recently, direct thrombolytic agents have been increasingly advocated even in patients where sinus thrombosis coexists with intracranial haemorrhage.4 Several kinds of fibrin-specific and fibrin-nonspecific thrombolytic agents are available for clinical use, however, there is no clear choice, despite greater success with t-PA in recent reports.5
Various modes of pathogenesis have been suggested for sinus thrombosis, but no definite mechanisms have been proposed. As the pathogenesis appears complex, and the components of cerebral venous thrombus are unlike those in the normal physiological thrombosis cascade, fibrin-nonspecific agents may be more suitable than fibrin-specific agents.
Fibrin-nonspecific agents also seem to be more acceptable for use in venous thrombosis than fibrin-specific drugs, because the sub-acute progressive course of sinus venous thrombosis allows the use of fibrin-nonspecific agents with a much more longer plasma clearance time than that of fibrin-specific agents. The sub-acute evolution of venous sinus thrombosis also offers much more time to perform direct thrombolytic treatment than does arterial thrombosis.
Among the fibrin-nonspecific agents, urokinase seems to be used more commonly than streptokinase, perhaps because fewer anaphylactic reactions have been reported with in recent research (Table 1
).6 The anti-streptokinase titre rapidly rises to 50–100 times during pre-infusion level, remaining there for many months or even years within a few days of treatment. This makes repeated administration impractical unless the follow-up thrombolytic treatment is arranged very early after initial dosing. We have seen a similar phenomenon to the anaphylactic reactions reported: leukocytosis and fever, without any positive pathogenic culture, were noted in our patient after thrombolytic treatment with streptokinase.
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In our opinion, with improved angiographic technique and the pharmacological considerations arising from the complicated pathogenesis of venous sinus thrombosis, direct thrombolytic treatment with fibrin-nonspecific agents such as urokinase should be considered as initial therapy, with intravenous heparin reserved for when urokinase therapy is unavailable, or following secondary deterioration.
References
1. Kimber J. Cerebral venous sinus thrombosis. Q J Med2002; 95:137–42.
2. Einhäupl KM, Villringer A, Meister W, et al. Heparin treatment in sinus venous thrombosis. Lancet1991; 338:597–600.[Web of Science][Medline]
3. van den Berg JSP, Boerman RH, van der Stolpe A, Kremer HPH. Cerebral venous thrombosis: recurrence with fatal course. J Neurol1999; 246:144–6.[Medline]
4. Rael JR, Orrison, Jr WW, Baldwin N, Sell J. Direct thrombolysis of superior sagittal sinus thrombosis with coexisting intracranial hemorrhage. AJNR1997; 18:1238–42.[Abstract]
5. Niwa J, Ohyama H, Matumura S, Maeda Y, Shimizu T. Treatment of acute superior sagittal sinus thrombosis by t-PA infusion via venography: direct thrombolytic therapy in the acute phase. Surg Neurol1998; 49:425–9.[Medline]
6. D'Alise MD, Fichtel F, Horowitz M. Sagittal sinus thrombosis following minor head injury treated with continuous urokinase infusion. Surg Neurol1998; 49:430–5.[Web of Science][Medline]
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