Low-dose intravenous heparin infusion in patients with aneurysmal subarachnoid hemorrhage: a preliminary assessment

Abstract

Object: Aneurysmal subarachnoid hemorrhage (aSAH) predisposes to delayed neurological deficits, including stroke and cognitive and neuropsychological abnormalities. Heparin is a pleiotropic drug that antagonizes many of the pathophysiological mechanisms implicated in secondary brain injury after aSAH.

Methods: The authors performed a retrospective analysis in 86 consecutive patients with Fisher Grade 3 aSAH due to rupture of a supratentorial aneurysm who presented within 36 hours and were treated by surgical clipping within 48 hours of their ictus. Forty-three patients were managed postoperatively with a low-dose intravenous heparin infusion (Maryland low-dose intravenous heparin infusion protocol: 8 U/kg/hr progressing over 36 hours to 10 U/kg/hr) beginning 12 hours after surgery and continuing until Day 14 after the ictus. Forty-three control patients received conventional subcutaneous heparin twice daily as deep vein thrombosis prophylaxis.

Results: Patients in the 2 groups were balanced in terms of baseline characteristics. In the heparin group, activated partial thromboplastin times were normal to mildly elevated; no clinically significant hemorrhages or instances of heparin-induced thrombocytopenia or deep vein thrombosis were encountered. In the control group, the incidence of clinical vasospasm requiring rescue therapy (induced hypertension, selective intraarterial verapamil, and angioplasty) was 20 (47%) of 43 patients, and 9 (21%) of 43 patients experienced a delayed infarct on CT scanning. In the heparin group, the incidence of clinical vasospasm requiring rescue therapy was 9% (4 of 43, p = 0.0002), and no patient suffered a delayed infarct (p = 0.003).

Conclusions: In patients with Fisher Grade 3 aSAH whose aneurysm is secured, postprocedure use of a low-dose intravenous heparin infusion may be safe and beneficial.

Conflict of interest statement

Disclosure

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Author contributions to the study and manuscript preparation include the following. Conception and design: Simard, Schreibman. Acquisition of data: all authors. Analysis and interpretation of data: Simard, Aldrich, Polifka, Beaty. Drafting the article: Simard, Schreibman, James, Polifka, Beaty. Critically revising the article: all authors. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Simard. Statistical analysis: Simard.

Figures

Fig. 1

Values of aPTT associated with the Maryland low-dose intravenous heparin infusion protocol. Box plots as a function of time, of values of aPTT in patients administered the Maryland low-dose intravenous heparin infusion protocol (8 U/kg/hr by constant intravenous infusion for 12 hours, increasing by 1 U/kg/hr at 12-hour intervals to a final maintenance dose of 10 U/kg/hr intravenous). In the box plots, the large boxes indicate the 25th and 75th percentiles; whiskers, the 5th and 95th percentiles; x, the 1st and 99th percentiles; –, the maximum and minimum; horizontal line within the box, the median; and the small square, the mean. Normal aPTT at the University of Maryland, 25–38 seconds.

Fig. 2

Vasospasm-related outcomes. The incidence of angiographic vasospasm, clinical vasospasm, and CT infarctions in the control (CTR) and heparin (HEP) groups, as indicated. *p = 0.0002; **p = 0.003.

Fig. 3

Computed tomography scans obtained in representative patients from the control and heparin groups. A and B: Admission (A) and follow-up (B) CT scans obtained in a 50-year-old patient who presented with a ruptured anterior communicating artery aneurysm. The patient was neurologically intact upon presentation. The patient underwent successful surgical clipping. The patient’s hospital course was complicated by clinical vasospasm with associated aphasia. Despite multiple intravascular interventions, the patient developed frontal and parietal infarcts. At follow-up, the patient’s aphasia was improving. C and D: Admission (C) and follow-up (D) CT scans obtained in a 47-year-old patient who presented with a ruptured anterior communicating artery aneurysm. The patient was comatose upon presentation with a GCS score of 6T. The patient underwent successful surgical clipping and was subsequently treated with a low-dose intravenous heparin infusion. The patient developed angiographic vasospasm but did not require rescue intervention. At follow-up, the patient was neurologically normal, including normal cognition and short-term memory.