Treatment of Post-Traumatic Hyphema with Intracameral T-PA in Sickle Cell Anemia

TREATMENT OF POST-TRAUMATIC TRABECULAR MASHWORK THROMBOSIS AND SECONDARY GLAUCOMA WITH INTRACAMERAL TISSUE PLASMINOGEN ACTIVATOR IN PREVIOUSLY UNRECOGNIZED SICKLE CELL ANEMIA

Assistant professor Ksenija Karaman MD PhD, Srdjana Culic1 MD, Ivana Erceg2 MD Vida Culic1 MD, Alen Sinicic MD, Ilza Salamunic3 spec. med. biochemistry

Department of Ophthalmology, Clinical Hospital Split and SplitSchool of Medicine, Split, Croatia

1ClinicalHospitalSplit, Pediatrics Clinic, Split, Croatia

2ClinicalHospitalSplit, Laboratory for Clinical and Forensic Genetics, Split, Croatia

3ClinicalHospitalSplit, Clinical Laboratory, Split, Croatia

Corresponding author:

Assoc. prof. Ksenija Karaman, MD, PhD

Palmotićeva 10, 21 000 Split, Croatia

Phone: +385 21 556408

Fax number:+385 21 556407

E-mail:

ABSTRACT

Background. Here we present a benefit of intracameral tissue plasminogen activator (t-PA) aplication in a child with previously unrecognized sickle cell anemia, post-traumatic hyphema, sickling of red cells, thrombosis in trabecular mashwork and consecutive acute glaucoma. Patient and Methods. Thirteen year-old African boy was admitted to hospital, with symptoms of acute glaucoma and partial hyphema after right eye trauma. Visual acuity of affected eye was 0.5 and intraocular pressure (IOP) 46 mm Hg. Despite a common therapy three days later clinical condition of patient's right eye was getting worst expressing total hyphema.Visual acuity was only hand motion (HM) and IOP 53 mmHg. Aqueous humor with hyphema was aspirated and 20 µg of t-PA was injected into anterior chamber contemporary. Cytological examination of aqueous humor revealed 10% sickled erythrocytes, hemoglobin electrophoresis discovered hemoglobin S and diagnosis of sickle cell disease (SCD) was confirmed. Unsolved trabecular mashwork thrombosis was indication for second intracameral aplication of 20 μg t-PA. Results. Intraocular aplication of t-PA has revealedexcellent results in post-traumatic hyphema with trabecular mashwork thrombosis in patient with sickle cell anemia. Complete resolution of blood cloth in the anterior chamber and trabecular mashwork was achieved. Two-years follow up revealed permanent normalisation of IOP and visual acuity. Conclusion.Successful outcome with anterior chamber paracentesis and intracameral injection of t-PA is our encouraging novel approach, which we highly recommend in treatment of post-traumatic hyphema in SCD.

Key words: post-traumatic hyphema; trabecular mashwork thrombosis; acute glaucoma; sickle cell anemia; tissue plasminogen activator

INTRODUCTION

Sickle cell disease is inherited hematological disordercharacterized with sickle cell hemoglobin (Hb S) which differs from the normal only by one amino acid substitution in the β-chain of hemoglobin (HbβS), resulting with less flexible sickle red blood cells (SS RBCs) (1).Sickle cell anemia is a recessive disease characterized with sickling of the red cells under reduced oxygen tension.The major cause of morbidity and mortality in SCD is vascular occlusion. Episodic occurence of vasoocclusive events precipitate acute painful episodes leading to organ failure and death. The severity of SCD increases with higher leukocyte count because of their adherence to vascular endothelium facilitating vaso-occlusion. The treatment modalities that reduce leukocyte adhesion molecules expression might confer clinical benefit (2).The ophthalmic manifestations of SDC are present in various segments of the eye which include the conjuctiva, iris, retina and optic nerve. After traumatic hyphema patients with SCD tend to have more severe ophthalmic complications, such as glaucoma and vaso-occlusive retinopathy leading to retinal detachments and vitreous hemorrhages(3). Sickling phenomenon and consecutive thrombosis may cause opturation of trabecular mashwork and increased IOP.

Most reports of traumatic hyphema indicate prevalence of 70% or greater in pediatric population, and the average duration of the uncomplicated hyphema is 5 to 6 days (4).Usually, traumatic hyphema is succesfuly treated topicaly with midriatics and antibiotics. There is no consensus regarding use of systemic antifibrinolytic agents, indications for hospitalization, or timing for surgical intervention in management of traumatic hyphema (5). Clinical benefit of so far used therapy is questionable. Up to date intracameral injection of t-PA seems to be safe and effective method for the treatment of unresolved total hyphema and several studies indicates the promising features of this drug. However, to our knowledge, intracameral application of t-PA in treatment of post-traumatic hyphema in patients with SCD was not recorded yet.

CASE REPORT

A previously healthy 13-year-old boy, born in marriage of African father and Caucasian mother, was admitted to our department 4 hours after being accidentally hit in the right eye by handball. He complained of headache, right eye pain, photophobia and epiphora. His father died of heart attack when he was 36-year-old.

Slit-lamp examination revealed ciliary injected conjunctiva, corneal edema with 2 mm hyphema and marked cell and flare in the anterior chamber. Pupillary examination showed irregular and enlarged pupil with poor reaction to light. IOP was 46 mm Hg (normal <21 mm Hg) and visual acuity of the right eye was 0.5. Because of corneal edema the fundus of his right eye was not visualized in detail. A diagnostic work-up, including a complete blood count, electrolytes, urine analysis, x-ray and computed tomography of the orbit, was unremarkable.

Diagnosis of traumatic hyphema, iritis and secondary glaucoma of the right eye was made. Initial treatment included topical and subconjunctival steroids, topical timolol, oral acetozolamide, and systemic 10% mannitol.

Three days later there was total hyphema in the anterior chamber and IOP was 53 mm Hg, despite the treatment (Fig. 1). Visual acuity of the affected eye was only hand motion. According to clinical data, therapy failure, and boy’s background (African), suspicion of sickle cell anemia has appeared.

At this point, surgery was performed: anterior chamber lavage to evacuate hyphema, partial evacuation of blood cloth, and 20 µg of t-PA was injected into the anterior chamber.

After surgery transcorneal oxygen therapy was applied, as well as 1000 ml of 0.9% NaCl with 5% glucose solution per day.

Surgery temporarily decreased IOP and ameliorated symptoms, but day later IOP increased again and persisted. However, only partial hyphema remained (1mm) with cell and flare in the anterior chamber.

Second surgery was performed four days later. Lavage of anterior chamber was done and 20 μg of t-PA was injected again. During the second surgery aqueous humor with hyphema was aspirated by paracentesis and cytological examination was accomplished. Fresh preparation and staining of aqueous humor has revealed that 10% of erythrocytes from hyphema were sickle cells (Fig. 2). In the meantime hemoglobin electrophoresis revealed hemoglobin S (Fig.3).

After second surgery IOP normalized, cornea became completely clear, corneal edema resolved, cell and flare in the anterior chamber were negative, while the pupil remained irregular. Fundus examination revealed normal optic nerve disc and two blot hemorrhages at the periphery of the retina. Visual acuity was 1.0.

Folic acid, acetylsalicylic acid and vasodilators (verapamil) were included in therapy and patient was discharged home. He continued to do well and his IOP remained normal as well as his vision.

Fundus examination 24 days after injury showed peripheral retinal artery occlusions and ischemical lesions at 5, 6 and 11 hours. Closely associated with sickle cell retinopathy, in the same eye, partial iris atrophy was observed which is believed to be secondary to the vaso-occlusive process in the iris (Fig. 4).

Sickle cell retinopathy remained unchanged first three months, but follow-up after four months showed normal retina with no signs of retinal artery occlusions.

Pattern visual evoked potential (VEP) of his right eye showed normal P 100 wave amplitude and elongated P 100 wave latency (116.6 ms), but four months later, pattern VEP P100 wave latency normalized. Visual field was normal all the time.

DISCUSSION

In differential diagnosis of hyphema and increased IOP sickle cell anemia has to be considered. Although peripheral blood examination of our patient did not show sickle red cells, 10% of red cells from hyphema in the anterior chamber had sickle cell shape. All that points out how important is to perform aqueous humor examination when complications of traumatic hyphema occurs.

Successful outcome with anterior chamber paracentesis and intracameral injection of t-PA is our encouraging novel approach, which we highly recommend in treatment of post-traumatic hyphema in SCD. Tissue plasminogen activator is a fibrin specific fibrinolytic and potent thrombolytic agent that has been shown to be effective in accelerating the clearance of fibrin clots from anterior chamber. The results in five eyes with post-traumatic total hyphema (without sickle cell) suggest that t-PA is a useful addition in managing of total hyphema (6,7).

The management of traumatic hyphema has been controversial for many years. Various studies have left unanswered questions, such as whether antifibrinolytics are as effective in children as adults, in white patients as black, and in patients with normal hemoglobin as well as those with sickle cell hemoglobinopathies (8).In patients with hyphema and SCD application of antifibrinolytics are contraindicated for blocking the cloth lysis.

Although transcorneal oxygen therapy can reduce intraocular pressure in patients with glaucoma from sickle cell hyphema (9), our experience did not confirm that.

Hyphemas in patients with sickle cell hemoglobinopathies, whether traumatically or surgically induced, may have devastating effects on the eye. Early anterior chamber paracentesis may be the best treatment for this type of hyphema-induced secondary glaucoma(10). Complications of traumatic hyphema include increased IOP, peripheral anterior synechiae, optic atrophy, corneal bloodstaining, secondary hemorrhage, and accommodative impairment(11). In addition, occlusions of the retinal vasculature are the initiating event in sickle cell retinopathy. In our case acetylsalicilic acid and vasodilators improved reperfusion of the peripheral retinal vessels. Sickle cell retinopathy in its advanced form is complicated by preretinal neovascularization, vitreous hemorrhage, and retinal detachment(12).

The high risk of secondary thrombosis with potential ocular damage in patients with traumatic hyphema and sickle cell anemia supports the benefit of hospitalization.

The fact that acute chest syndrome is a leading cause of death among patients with sickle cell disease (13), it can be presumed that our patient’s father also had SCD, unfortunately unrecognized and untreated.

In conclusion, as blinding or sight-threatening damage may occur to the retina or optic nerve, appropriate screening and patient management of sickle cell are vital to the continued quality of life for these patients and it is very important public health issue.

REFERENCES

1. Turhan A, Weiss LA, Mohandas N, Coller BS, Frenette PS. Primary role for adherent leukocytes in sickle cell vascular occlusion: A new paradigm. Proc Natl Acad Sci 2002;99(5):3047-3051.

2. Okpala I, Daniel Y, Haynes R, Odoemene D, Goldman J. Relationship between the clinical manifestations of sickle cell disease and the expression of adhesion molecules on white blood cells. Eur J Haematol 2002;69(3):135-144.

3. To KW, Nadel AJ. Ophthalmologic complications in hemoglobinopathies. Hematol Oncol Clin North Am 1991;5(3):535-548.

4. Crouch ER Jr, Crouch ER. Management of traumatic hyphema: therapeutic options. J Pediatr Ophthalmol Strabismus 1999;36(5):238-250; quiz 279-280.

5. Kelly JL, Blomquist PH. Management of traumatic hyphema in Texas. Tex Med 2002;98(4):56-61.

6. Laatikainen L, Mattila J. The use of tissue plasminogen activator in post-traumatic total hyphaema. Graefes Arch Clin Exp Ophthalmol 1996;234(1):67-68.

7. Kim MH, Koo TH, Sah WJ, Chung SM. Treatment of total hyphema with relatively low-dose tissue plasminogen activator. Ophthalmic Surg Lasers 1998;29(9):762-766.

8. Gottsch JD. Hyphema: diagnosis and management. Retina 1990;10 Suppl 1:S65-71.

9. Benner JD. Transcorneal oxygen therapy for glaucoma associated with sickle cell hyphema. Am J Ophthalmol 2000;130(4):514-515.

10. Goldberg MF. Sickled erythrocytes, hyphema, and secondary glaucoma: I. The diagnosis and treatment of sickled erythrocytes in human hyphemas. Ophthalmic Surg 1979;10(4):17-31.

11. Walton W, Von Hagen S, Grigorian R, Zarbin M. Management of traumatic hyphema. Surv Ophthalmol 2002;47(4):297-334.

12. Cohen SB, Fletcher ME, Goldberg MF, Jednock NJ. Diagnosis and management of ocular complications of sickle hemoglobinopathies: Part V. Ophthalmic Surg 1986;17(6):369-374.

13. Vichinsky EP, Neumayr LD, Earles AN, Williams R, Lennette ET, Dean D, at all. Causes and outcomes of the acute chest syndrome in sickle cell disease. National Acute Chest Syndrome Study Group. N Engl J Med 2000;342(25):1855-1865.

FIGURE LEGENDS

Figure 1

Post-traumatic total hyphema of the right eye.

Figure 2

Photomicrograph of aqueous humor (May-Grunwald, Giemsa, x100). Arrow indicates erythrocyte from hyphema with alteration in sickle cell shape.

Figure 3

Hemoglobin electrophoresis on cellulose acetate at pH 8.6 following staining with Ponceau-S. Arrow indicates prominent band for HbS trait.

Figure 4

Right eye after treatment, arrow indicates partial iris atrophy.

1