Rare Case of Idiopathic Thrombocytopenia Causing Retrobulbar Hemorrhage

Abstract

Immune thrombocytopenia purpura (ITP) is defined as a platelet count lower than 100 × 10ˆ9/L, in the absence of known abnormalities in white blood cells, normal hemoglobin with generalized purpuric rash: making it a diagnosis of exclusion.1–2 ITP is due to destruction of platelets in the spleen via autoantibodies, resulting in reduced platelet counts.3 Though rare, ITP is linked with spontaneous retrobulbar hemorrhage (SRH). If ITP is identified, prompt treatment is needed to prevent loss of vision. An 80-year-old non-smoking woman with a history of diabetes, hypertension, and alpha thalassemia minor presented with a one-day history of a right occipital lobe headache and right sided ocular dysfunction. Workup showed a very low platelet count of 35,000/mm³, and elevated D-Dimer at 12,485 ng/mL. MRI revealed a new hemorrhage in the retrobulbar area causing right-sided proptosis. MRA showed no arteriovenous shunting, and the right ophthalmic artery was patent. Therapy for seven days with cryoprecipitate, IVIG, and steroids was started, symptoms resolved, and patient was discharged. The relationship between ITP and non-traumatic sub-periosteal orbital hemorrhage (NTSOH) is unclear, but its occurrence in the setting of anemia is often seen. To best of our knowledge this is a rare case of NTSOH in a patient with mild anemia and acute ITP in the absence of other risk factors such as trauma or excessive Valsalva events.

1. Introduction

Immune thrombocytopenia purpura (ITP) is defined as a platelet count lower than 100 × 10ˆ9/L, in the absence of known abnormalities in white blood cells, normal hemoglobin with generalized purpuric rash: making it a diagnosis of exclusion.1,2 ITP is due to destruction of platelets in the spleen via autoantibodies, resulting in reduced platelet counts.3 In addition, this antibody also contributes to the complement-fixed destruction of platelets.¹¹. Though rare, ITP may be linked with spontaneous orbital hemorrhage (SOH). ITP is managed by increasing platelet count in three ways: (1) inhibiting platelet clearance (e.g., splenectomy), (2) modifying immune response (e.g., steroids), and (3) promoting platelet production (e.g., recombinant human thrombopoietin [rhTPO]).

Spontaneous retrobulbar hemorrhage (SRH) is a rare but rapidly progressing condition that may cause blindness. The exact cause is unclear and is associated with trauma, vascular anomalies, uncontrolled hypertension, childbirth, anticoagulation medications, and dyscrasia.4 In addition, conditions like coagulopathies (including ITP), liver disease, cancer, and sickle cell disease are implicated.5 The leading symptoms of orbital hemorrhage are pressure, severe pain, blindness and diplopia.6–8 Diagnosis of orbital hemorrhage is done via Computed Tomography (CT) or Magnetic Resonance Imaging (MRI). Therapy goals are to reduce intraorbital pressure and visual loss. Severe cases may require surgery, less severe cases are managed medically. Diagnosing is challenging, and often requires prompt surgical management. We present a rare case of ITP-associated SRH successfully diagnosed and medically treated.

2. Case

An 80-year-old non-smoking woman with a history of hypertension, CVA, and alpha thalassemia minor known previously via electrophoresis, came to the ED with a one-day history of a right occipital lobe headache with ocular symptoms; right sided eye pain, surrounding bruising leading to difficulty opening and blurred vision. Patient was taking daily 81 mg aspirin but was held 2–3 days before presentation. Patient reported upper extremity bruising for the last 5 days and denied any history of trauma, coughing, or Valsalva events.

Upon presentation, she was hemodynamically stable. However, a platelet count showed a decline from previous outpatient labs ranging from 160 to 220,000/mm³ over the last year to 35,000//mm³ at time of admission (Table 1). Physical exam showed right-sided eye proptosis with erythematous chemosis and difficulty opening the eye. Pupils were reactive. Tonometry showed a right orbital pressure of 33 mmHg. A slit-lamp exam revealed soft upper lid ecchymosis with mechanical ptosis, hemorrhagic chemosis, corneal endothelial pigment, 3+ nuclear sclerosis of the lens, and a formed anterior chamber. No pupillary abnormality or resistance to retropulsion on the globe was present. She denied nausea, hematuria, bleeding gums, diplopia, flashes of light, floaters, curtains, or veils. Upon admission, she got one unit of platelet transfusion (a second dose of 1 unit was given 2 days later) and 40 mg dexamethasone, and latanoprost 1 drop OU QHS OD. Patient reported that her second vaccination for COVID-19 was 12 months ago. Respiratory and COVID-19 viral PCR panel was negative.

Table 1.

Laboratory values during hospitalization and follow-up.

Laboratory Value	Reference Range	Baseline	On Admission	Day 8: Post Admission	At Discharge	5 Months After Discharge
Platelets	150,000–400,000/mm3	162,000/mm3	35,000/mm3	126,000/mm3	126,000/mm3	171,000/mm3
RBC	3.5–5.5 M/uL	3.8 M/uL	3.72 M/uL		3.77 M/uL
Hemoglobin	11.0–15.0 g/dL	11.0 g/dL	10.2 g/dL	10.8 g/dL	10.9 g/dL	11.0 g/dL
Hematocrit	36%–46%		32.7%

The complete blood count (CBC) showed hemoglobin of 10.2 g/dL and hematocrit of 32.7%, were close to her prior values. The patient’s thromboelastographic (TEG) platelet mapping (PLM) results demonstrated a low maximum amplitude (MA) with a Kaolin of <42 mm and TEGPLM MA ADP of <10 mm indicating a sharp decline in platelet clotting. D-Dimer was elevated (12,485 ng/mL) and PT was prolonged (14.4 s). Peripheral blood smear had few giant platelets and no schistocytes. Basic metabolic panel, vitals, liver function tests, LDH, fibrinogen, and APTT were within normal range.

On admission, a CT scan of head showed a hyperdense lesion in the right retrobulbar area extending into the orbital apex, causing medial displacement of the orbital nerve with no intracranial hemorrhage, mass, or midline shift. A lower extremity venous duplex bilateral ultrasound had no evidence of DVT. Abdomen CT was unremarkable. Chest CT with contrast showed atelectasis. Head MRI showed hematoma measuring approximately 2.7 × 1.6 × 2.1 cm extending from the posterior globe margin towards the orbital apex. A dilated superior ophthalmic vein was seen anteriorly and inseparable from the hematoma (Fig. 1). Serology for ANA and anti-dsDNA was negative. These labs and the patient’s medical history made the diagnosis of systemic lupus erythematous (SLE) and giant cell arteritis (GCA) unlikely. Despite the administration of 2 units of platelets and steroids, patient’s thrombocytopenia (57 on day 7) worsened. On day 7, she experienced new-onset pain and bruising in her left eye, she denied any vision changes, flashes, floaters, curtains or veils, diplopia, or a new headache. Given concern for arterial venous malformation, an MRA was done and showed no evidence and no arterial or venous phase enhancement of the orbital lesion. The right ophthalmic artery was patent. But a new hematoma measuring 2.2 × 2 × 1.5 cm was seen resulting in severe proptosis. There was no stenosis, large vessel occlusion, or dural venous sinus thrombosis. By day 8, the patient’s right eye ecchymoses had improved, 1 g/kg of IVIG along with 1 unit of cryoprecipitate was given. Eventually a second dose of 1 g/kg IVIG was administered. Three days after starting treatment with IVIG and cryoprecipitate, her platelet count was 126,000/mm³ and vision improved. Visual acuity at discharge was 20/30 in the right and 20/40 in the left eye. She had no bleeding events. During hospitalization, patient received 2 units of platelets, 1 unit of cryoprecipitate, two days of 1 g/kg IVIG per day, and 40 mg of dexamethasone for 4 days. At discharge her platelet count returned to normal at 126 K/uL on day 11.

Fig. 1.

T1 and T2 Head MRI images demonstrating a 2.7 × 1.6 × 2.1 cm mass with predominantly low T2 signal and intermediate to low T1 signal extending from the posterior right globe margin towards the orbital apex.

Five months later, a follow-up MRI showed a reduction in the mass size at the posterior-lateral aspect of the right orbit between the superior and lateral rectus muscle and nerve sheath complex, measuring 1.4 × 6.5 × 7.7 mm. The right proptosis resolved with reduced mass effect on right optic nerve. The right superior ophthalmic vein was not dilated. The left globe, extraocular muscles, optic nerve sheath complexes, and lacrimal gland were unremarkable. No enhancing mass of proptosis of the left orbit was seen. Additionally, at follow-up the patient’s platelet count was 171,000/mm³.

3. Discussion

It is uncommon for ITP to cause ocular symptoms, and uncommon for vision changes as presenting complaint. There have only been three reported cases of ITP-associated orbital hemorrhage, all of which were seen in patients with a history of anemia, particularly hemoglobin levels less than 8 g/dL.9

Hematomas of the eye can occur either intraorbitally or suborbitally. NTSOH can present in various patterns such as diffuse intraorbital, subperiosteal, localized intraorbital (also known as hematic cyst), related to orbital floor implants, or to the extraocular muscle. NTSOH may present acutely, as in our patient. This is due to a spike in venous pressure, sickle cell crisis, an underlying bleeding disorder, sinus infection/mucocele, idiopathic, or a complication of general surgery or general anesthesia. Of all the bleeding disorders associated with NTSOH, location of the hematoma was in the superior orbit in all cases.

A workup for infectious causes, hematologic disorders, and malignancy was unrevealing.

While the patient in the past had electrophoresis proven alpha thalassemia, she never experienced prior bleeding events. Alpha Thalassemia is typically benign and can result in microcytic anemia but has no known association with thrombocytopenia. A follow-up MRI showed a reduction in hematoma size and resolution of proptosis with reduced mass effect on the right optic nerve. The features of this lesion compared to prior studies suggested a vascular lesion with resolved hemorrhage. From the patient’s unique presentation, history of anemia, resolution of thrombocytopenia and symptoms with two doses of IVIG and steroids, diagnosis of ITP associated with NTSOH and anemia was made.

4. Conclusion

The relationship between ITP and NTSOH is unclear, but it often occurs in the setting of anemia. This is a rare case of NTSOH in a patient with alpha thalassemia minor and acute ITP in the absence of risk factors. A thorough assessment and prompt treatment of patients with orbital hemorrhage is critical, especially with anemia, regardless of severity. If ITP is identified, prompt treatment including steroid and IVIG administration is needed to prevent permanent vision loss.