|Year : 1999 | Volume
| Issue : 1 | Page : 43--6
Puerperal cerebral venous thrombosis : therapeutic benefit of low dose heparin.
D Nagaraja, T Haridas, AB Taly, M Veerendrakumar, DK SubbuKrishna
Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, 560029 India., India
Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, 560029 India.
Advances in imageology have improved the diagnostic yield of cerebral venous/sinus thrombosis (CVT). However, its management remains a challenge. The present study was carried out to study the role of heparin in CVT. Therapeutic outcome of 150 patients of puerperal CVT manifesting within one month of delivery or abortion, was analyzed. The diagnosis was supported by cranial computed tomography and/or angiography whenever required. Seventy three patients, 46 with non-haemorrhagic infarction and 27 with haemorrhagic infarction, received 2500 units of subcutaneous heparin, three times a day within 24 hours of hospitalization till 30th post partum day or symptomatic relief. Seventy seven patients during the same period, 50 with non-haemorrhagic infarction and 27 with haemorrhagic infarction, who did not receive heparin formed the control group. Repeat CT scans were done when indicated. Among the heparin group, 34 patients made full recovery. There were eight deaths, all among the patients with haemorrhagic lesion. In control group, only 14 patients recovered completely (P=<0.001) and 18 died (P=<0.001). There were no adverse effects of heparin. Low dose heparin is safe and efficacious in puerperal CVT, even in patients with haemorrhagic infarction.
|How to cite this article:|
Nagaraja D, Haridas T, Taly A B, Veerendrakumar M, SubbuKrishna D K. Puerperal cerebral venous thrombosis : therapeutic benefit of low dose heparin. Neurol India 1999;47:43-6
|How to cite this URL:|
Nagaraja D, Haridas T, Taly A B, Veerendrakumar M, SubbuKrishna D K. Puerperal cerebral venous thrombosis : therapeutic benefit of low dose heparin. Neurol India [serial online] 1999 [cited 2022 Oct 7 ];47:43-6
Available from: https://www.neurologyindia.com/text.asp?1999/47/1/43/1662
Cerebral venous thrombosis (CVT), an important cause of stroke in puerperium, is frequently observed in India., Treatment of CVT has been controversial and methods include steroids, decongestive measures, surgery, systemic or local thrombolytic agents and anticoagulants. Case control study by Einhaupl et al suggested beneficial effect of heparin in the treatment of CVT. They also reported absence of serious side effects even in patients with haemorrhagic infarction. Having observed favourable response to heparin, in an earlier control trial in patients with non-haemorrhagic puerperal CVT the authors planned to assess the use of low dose heparin in patients with haemorrhagic CVT as well. This communication describes our experience in treating 73 patients of CVT with low dose of heparin as compared to 77 patients treated without heparin during the same period.
Seventy three patients of CVT, presenting within one month of delivery or abortion and confirmed by cranial CT scan or angiography and admitted under care of the principle author (DN), were started on low dose heparin (2500 units subcutaneously three times a day) within 24 hours of admission to the hospital. The treatment was continued till 30th post-partum day or symptomatic relief, whichever was later. Heparin was then tapered and stopped over one week. Seventy seven other patients of CVT, admitted during the same period to another clinical unit but who did not receive heparin, formed the control group.
The clinical data was collected on a structured data sheet. Mannitol and/or oral glycerol were used in all patients. Anaemia was corrected with oral iron or blood transfusion wherever indicated. The diagnostic criteria for CVT were : 1) acute onset of headache, convulsion and/or focal neurological deficit within one month of delivery or abortion, 2) absence of past history of cerebrovascular disease or cardiac disease, 3) CT scan showing direct signs of CVT or evidence of bilateral infarction not conforming to any known arterial territory and/or bilateral cerebral oedema and 4) confirmation of diagnosis by trans-femoral angiogram in doubtful CT lesions.
Electrocardiogram was done routinely and echocardiogram was carried out whenever indicated. All patients were evaluated on Glasgow coma scale at admission to assess the severity. They were assessed for activities of daily living at the time of discharge and were categorized into five groups. The heparin and the control groups were compared with regard to the clinical features and the outcome.
There were 73 patients in the heparin group (46 with nonhaemorrhagic lesion and 27 with haemorrhagic infarction) and 77 in the control group (50 with non-haemorrhagic lesion and 27 with haemorrhagic infarction). Their clinical features are given in the [Table I]. The two groups were matched for most of the parameters, except for vomiting and status epilepticus which were more common in control group. The severity of illness as indicated by level of consciousness and score on Glasgow coma scale, was slightly more in the heparin group than in the control in the haemorrhagic group, while it was reverse in the non-haemorrhagic group. However, these differences did not reach significant level. In non-haemorrhagic CVT there were no deaths in the heparin group as compared to eight deaths in the control group. In patients with haemorrhagic lesion, there were 8 deaths in the heparin group as compared to 11 in the control group [Table II]. Heparin therapy was well tolerated and there were no complications. Serial CT scans were done in 30 patients who had clinical deterioration. There was no increase in haemorrhage and oedema was either same or increased slightly in 18 patients. At discharge, the heparin group fared better than the control group, both in patients with haemorrhagic as well as nonhaemorrhagic lesions.
Heparin has been in use since 1942 but reports indicating the beneficial as well as harmful effects have been published. Krayenbulh, in a study of 17 patients of CVT, noted that heparin was safe and effective. Fairburn reported total recovery in CVT with heparin in two patients due to oral contraceptive use and good result in one patient during puerperium. In an uncontrolled trial of heparin in puerperal CVT, Srinivasan observed 5eaths in heparin group (n=42) as compared to 21 deaths (n=47) in the group who did not receive heparin. However, apprehensions have been expressed regarding bleeding into the infarcted brain and elsewhere due to heparin. Gettlefinger and Kokeman observed development of CVT in two of the three patients receiving anti-coagulants. In first ever reported control trial involving 20 patients of CVT, Einhaupl et a1 documented significant reduction in mortality and better rate of recovery in patients receiving heparin. Nagaraja et al in a control trial of 57 patients with non haemorrhagic puerperal CVT observed beneficial effect of low dose heparin without any haemorrhagic com haemorrhagic as well as non haemorrhagic, while one of the clinical units in the same hospital treated these patients without heparin. The two gups were more or less matched for clinical and CT parameters. There were no haemorrhagic complications in heparin group. Repeat cranial CT scan, done whenever there was a worsening (n=30), did not reveal any increase in bleeding and the oedema was either the same as before or increased (n=18). The results indicate favourable outcome with low dose heparin in non haemorrhagic CVT. Even in haemorrhagic CVT, despite lower GCS scores , there was a reduction in mortality in heparin group. However, it was not as striking as in the non-haemorrhagic group. At discharge 84.8% cases with non haemorrhagic infarct in the heparin group were independent as compared to 40% of controls. In patients with haemorragic lesions 48.2% were independent in heparin treated group as compared to 7.5% of control.While this study was not a randomised trial, it certainly establishes the safety and efficacy of low dose heparin in all forms of CVT. It is noteworthy that during low dose heparin therapy, monitoring of clotting parameters is not required. Low dose heparin does not alter the clotting parameters as most of it gets bound to endothelium and hence circulating free heparin is negligible., Thus the clotting parameters remain normal but progression of thrombosis is prevented. This makes the regimen suitable even for peripheral centers with limited facilities. However, it is still necessary to establish the safety of conventional dose of heparin in puerperal haemorrhagic CVT. It has been suggested that low molecular weight heparin (LMWH) may be more effective and safe in prevention of thrombo-embolism after spinal cord injury related deep venous thrombosis as compared to standard heparin. LMWH has also been used in acute ischaemic strokes, with favourable results. Convenient dosage schedule, more predictable anticoagulant response, efficacy and safety warrants trials of LMWH in `puerperal' cerebral venous thrombosis.
|1||Nagaraja D, Taly AB, Sarala Das : Puerperal cerebral venous thrombosis. In : Progress in Clinical Neurosciences, Sinha, K.K. and Chandra, P. (Eds) NSI Publication, Ranchi 1987; 325-338.|
|2||Nagaraja D, Taly AB and Sarala Das : Puerperal cerebral venous thrombosis in India. In : Progress in Clinical Neurosciences Sinha KK, Chandra P. (Eds), NSI Publication. Ranchi 1989; 165-177.|
|3||Einhaupl KM, Villringer A, Meister W et al : Heparin treatment in sinus venous thrombosis. Lancet 1991; 338 : 597-600.|
|4||Nagaraja D, Rao BSS, Taly AB et al : Randomized controlled trial of heparin in puerperal cerebral venous sinces thrombosis in India. National Institute of Mental Health and Neuro Sciences Journal 1995; 13 : 111-115. |
|5||Krayenbuhl HA : Cerebral venous and sinus thrombosis. Clin Neurosurg 1966; 14 : 1-24. |
|6||Fairburn B : Intracranial venous thrombosis complicating oral contraception : Treatment with anti-coagulant drugs, BMJ 1973; 2 : 647. |
|7||Srinivasan K : Cerebral venous and arterial thrombosis in pregnancy and puerperium. A study' of 135 patients. Angiology 1983; 34 : 731-746. |
|8||Gettelfinger DM, Kokmen E : Superior sagittal sinus thrombsis. Arch Neurol 1977; 34 : 2-6. |
|9||ISIS-3 (Third international study of Infarct survival) Collaborative group ISIS-3 : a randomized comparison of streptokinase vs tissue plasminogen activator vs anistreplase and of aspirin plus heparin vs aspirin alone among 41299 cases of suspected myocardial infarction. Lancet 1992; 339 : 753-760. |
|10||Shulman AG : Setting the record straight on low-dose heparin. Lancet 1991; 338 : 619-620. |
|11||Green D, Lee MY, Lim AC et al : Prevention of thrombo embolism after spinal cord injury using low-molecular-weight heparin. Ann Intern Med 1990; 113 : 571-574. |
|12||Kay R, Wong KS, Yu YL et al : Low molecular weight heparin for the treatment of acute ischaemic stroke. N Engl J Med 1995; 333 : 1588-1593. |