Conservative Treatment of Chronic Subdural Hematoma in HIV-Associated Thrombocytopenia with Tranexamic Acid

Abstract

Chronic subdural hematomas (CSDHs) and its management comprise a majority work in a neurosurgical specialty. The effectiveness of surgery is beyond doubt and sometimes even lifesaving in severe cases. However, the straightforward surgery is sometimes complicated by the associated comorbidities of the patient. Comorbidities in the form of coagulopathies secondary to chronic liver diseases, drugs (warfarin, ecosprin, clopidogrel), thrombocytopenia secondary to systemic illness are always a challenge to deal with in patients with CSDH. The authors encountered a patient with thrombocytopenia secondary to systemic HIV infection who presented with CSDH. Her coagulation profile was severe enough to preclude surgery. She was managed conservatively with tranexamic acid and responded well. The authors present the challenges they faced in the course of successful management of this patient.

Case Report

A 42-year-old female patient was presented to us with the history of severe headache and vomiting of 2 days’ duration. Four months preceding her presentation, she had reported similar headache associated with double vision. On further enquiry, we learnt that there was a history of trauma to head as a result of domestic violence before 5 months. On examination, she was fully conscious oriented. Higher mental functions were normal; there were no cranial nerve deficit. Motor and sensory systems were normal. Cerebellar signs were negative and there was no papilledema. Computed tomography (CT) scan showed a chronic subdural hematoma (CSDH) in the left frontotemporal parietal region of maximum thickness 8.5 mm and a midline shift (MLS) of 12 mm to the right (Figure 1). She was posted for emergency burr hole evacuation surgery. Preoperative investigations showed that her platelet count was only 17 000 cells/mm³. HIV I and II enzyme-linked immunosorbent assays were reactive. CD4 count was done and was only 300. On further interrogation, we found that she was aware of it previously and she had concealed this fact from us. We also learnt that her husband died as a sequelae to infections related to AIDS. She was given multiple transfusions of platelet concentrates only to have a modest increase but not up to the mark to perform a safe surgery.

Figure 1.

Plain computed tomography scan of brain—chronic subdural hematoma in the left fronto temporo parietal region with mass effect and midline shift of 12 mm.

At this stage, surgery was withheld and rescheduled until her coagulation profile improved. The infectious disease team was involved, and they started her on highly active antiretroviral therapy (HAART). She was started on tranexamic acid (TXA) 250 mg 3 times daily as an alternative to surgery and mannitol 100 mg 3 times daily to relieve cerebral edema. There was some relief in headache in the first week following treatment after which she was weaned off from tapering doses of mannitol. She was continued on TXA on the same dosage. We checked her platelet count daily and at the end of first week it improved to 50 000 cells/mm.³ She was evaluated for the development of papilledema during this period as we were wary of the fact that she may go in for optic atrophy. Having assured of normal fundus, we continued her on the same line of management and a repeated imaging after 9 days, which showed that CSDH was resolving and the MLS had come down to 9.4 mm (Figure 2). After 2 weeks, her platelet count improved to 68 000, but she had mild increase in headache along with drowsiness. Repeat CT was taken that showed the hematoma size and mass effect were decreasing but with persistent MLS of 5.5 mm (Figure 3). She was managed with single dose of mannitol that relieved her headache. At this stage, we planned emergency twist drill craniostomy and evacuation under local anesthesia. A twist drill craniostomy was done and hardly any hematoma was drained when in the middle of the procedure, she developed seizures and the surgery was abandoned without drainage of the CSDH. Postoperatively she recovered well without any deficits. A CT scan repeat showed that CSDH was decreasing but was more hypodense measuring 13 mm and MLS of 4 mm (Figure 4). She again underwent ophthalmologic evaluation, showing no papilledema. She was continued on same treatment and her headache resolved. She was discharged after another week with advice to continue antiretroviral medications and TXA. After a 6-week treatment course, CT scan was repeated (Figure 5), showing good resolution of CSDH and no MLS.

Figure 2.

Repeat computed tomography scan of brain—chronic subdural hematoma in the left fronto temporo parietal region with mass effect and midline shift of 9.4 mm.

Figure 3.

Repeat computed tomography scan of brain showing persisting chronic subdural hematoma with mass effect and midline shift of 5.5 mm.

Figure 4.

Repeat computed tomography scan of brain showing chronic subdural hematoma more hypodense than previous. Mass effect and midline shift of 4 mm.

Figure 5.

Repeat computed tomography scan of brain showing total resolution of chronic subdural hematoma with no mass effect and midline shift.

Discussion

As once remarked by Cushing that “there is nothing in the whole realm of surgery more gratifying than the successful removal of a meningioma with subsequent perfect functional recovery” holds good for certain cases of CSDH. Surgery in any form, be it a twist drill, burr hole, or conventional craniotomy, is undoubtedly the procedure of choice in CSDH. This is not without risk, which gets augmented disproportionately when it is associated with life-threatening comorbidities. It is in such situations that alternative therapy in the form of steroids or TXA play an important role.

Among many overlapping hypothesis, the recurrent hemorrhage model with resultant hyperfibrinolytic activity is postulated in the pathogenesis of CSDH. After traumatic brain injury, there is release of plasmin from the brain that activates both the kallikrein system and the hyperfibrinolytic system. The kallikrein system increases inflammation and thereby increases the permeability of subdural membranes. Tranexamic acid decreases plasmin activity by reversibly binding to it and thus in turn decreases the fibrinolysis and inflammation. ¹

Our patient had severe thrombocytopenia owing to her retroviral infection. This hematologic abnormality stands out among others in patients studied previously across the world. The prevalence of thrombocytopenia in HIV reported in literature is in the range of 2.4% (Korea), ² 15.6% (China), ³ 17.8% (Uganda), ⁴ and 21.7% (Cameroon). ⁵ The CSDH has been reported in patients with thrombocytopenia associated with idiopathic thrombocytopenic purpura. ⁶ However, literature regarding management and sequelae to HIV-associated thrombocytopenia is scanty and so are pertaining to spontaneous resolution of CSDH in such cases. There are mechanisms postulated as the cause for spontaneous resolution of CSDH but most lack class experimental evidence. Among them are the platelet plugging theory of Yamashima et al according to which the platelets plug the neovascular friable micro capillaries in the membranes of CSDH, thereby reducing rebleeding and recurrence. ⁷ The density of lesions that undergo spontaneous resolution does deserve special mention. Nearly all cases of CSDH that have been reported to have either a low-density or a mixed density lesion. ¹

There have been various described forms of conservative treatment of CSDH. Corticosteroids administrations are among the oldest drugs used in the conservative management of CSDH. This practice is common in 55% of neurosurgeons in the United Kingdom and Ireland, ⁸ 13% in Canada, ⁹ as published in various national surveys. There have been many prospective and retrospective studies in this regard, however, there is a clear dearth of randomized controlled trials (RCTs). The only RCT that is ongoing, Dexamethasone on reduction in the reoperation rate of Chronic Subdural Hematoma (DRESH) trial, ¹⁰ may show some solid evidence to support this practice. We did not give her steroids because she had low CD4 counts and she may be exposed to opportunistic infections due to immunodeficiency. Also having started her on HAART that is the first-line treatment of HIV-associated thrombocytopenia, ¹¹ her platelet counts improved.

Tranexamic acid ^1,12,13 (TXA), atorvastatin, ¹⁴ and etizolam ¹⁵ are the newer members in the arsenal against CSDH. However, there is also no concrete evidence to suggest the absolute advantage of these drugs. Tranexamic acid has produced good results in the management of CSDH in the 21 patients studied by Kageyama et al, with no recurrence rates. ¹² In patients with dialysis-associated coagulopathy who are at very high risk for surgery, TXA has been used successfully to treat CSDH. ¹⁶ However, further studies are required to use them as the first-line drugs. Along the same thought process, Lorio-Morin et al have initiated the Tranexamic acid in Chronic Subdural hematomas (TRACS) study, that is, TXA in CSDH. This is a double-blind prospective parallel design study in which they intend to treat 130 patients having CSDH with TXA 750 mg daily until total resolution or for a total of 20 weeks. ¹³ The results of this study should pave way for further larger randomized control trials and definitive class 1 evidence.

Whatever be the drugs used during the conservative management, there should be a very low threshold for performing surgery with added risk due to the life-threatening neurological signs. There should be a constant vigil for monitoring the fundus. Our patient was on regular follow-up with the ophthalmologist, and there was no papilledema in the course of the treatment. She recovered well, and there was full resolution of the CSDH as observed in the serial CT scans. Conservative management is a good alternate option in patients with CSDH who are at very high risk for surgery.