Survival After Catastrophic Antiphospholipid Syndrome With Diffuse Alveolar Hemorrhage

Introduction

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by persistent antiphospholipid antibodies and the occurrence of arterial, venous, or microvascular thrombotic events.^1-3 Catastrophic antiphospholipid syndrome (CAPS) is a rare and fulminant variant of the antiphospholipid syndrome that has been reported since 1992. Its prevalence is less than 1% in patients with antiphospholipid syndrome and is characterized by generalized microvascular thrombosis, multiorgan failure, and high mortality rates exceeding 50% despite intensive treatment.^4,5

Diffuse alveolar hemorrhage is an uncommon but potentially fatal pulmonary manifestation of catastrophic antiphospholipid syndrome associated with immune-mediated pulmonary capillaritis. Clinically, it presents with hemoptysis, acute anemia, and respiratory failure, often requiring invasive mechanical ventilation. ⁶ The coexistence of thrombotic and hemorrhagic events, as in catastrophic antiphospholipid syndrome, represents a significant therapeutic challenge, particularly in patients with comorbidities such as chronic kidney disease. ⁷

The management of catastrophic antiphospholipid syndrome is based on a combined therapeutic approach, including anticoagulation, aggressive immunosuppression with glucocorticoids, intravenous immunoglobulin, plasmapheresis, and, in refractory cases, biologic agents such as rituximab or eculizumab. ⁸ Early identification and rapid initiation of multidisciplinary treatment are essential for improving prognosis.

The purpose of this publication is to present a present a case of a male patient with relevant cardiovascular and renal history who developed catastrophic antiphospholipid syndrome, presenting with severe respiratory, hematologic, renal, cutaneous, and hemodynamic involvement.

Case Presentation

A male patient in his early 50s residing in a Latin American country had a medical history of long-standing hypertension, deep vein thrombosis of the left lower limb, nephrolithiasis, and stage III chronic kidney disease. He denied any allergies or prior surgery. Current medications include losartan, amlodipine, doxazosin, quetiapine, and omeprazole. Both parents had diabetes mellitus.

Two months before admission, he was treated for a hypertensive emergency with neurological symptoms, including dysarthria and severe headache. Computed tomography (CT) revealed a left parietal hemorrhage without a midline shift, aneurysms, or vascular malformations. He was managed in the intensive care unit (ICU) with hemodynamic control and neurological monitoring, evolved favorably, and was discharged with antihypertensive therapy and outpatient follow-up.

Two months later, he returned to the emergency department with cough, hemoptysis, epistaxis, lipotomies, vasculitis, skin lesions on the lower extremities, and severe anemia. He was admitted to the ICU due because of acute respiratory failure requiring mechanical ventilation and vasopressor support for hypovolemic shock. Table 1 shows the vital signs on admission. CT revealed diffuse alveolar hemorrhage (Figure 1).

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Table 1.

Vital Signs on Admission to the Emergency Department

Vital sign	Value	Reference range
Blood pressure (mm Hg)	84/53	90–120/60–80
Heart rate (beats/min)	94	60–100
Respiratory rate (breaths/minute)	24	12–20
Oxygen saturation, SpO2 (%)	60	≥95% (room air)
Glasgow	15/15	15/15
Temperature (°C)	37	36.0–37.5

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Figure 1.

Axial chest computed tomography (CT) demonstrates bilateral patchy ground-glass opacities and areas of consolidation, predominantly involving the lower lobes, with associated interlobular septal thickening and scattered nodular opacities.

Given his clinical history, underlying autoimmune disease was suspected, prompting strict inpatient multidisciplinary management. Laboratory studies identified triple-positive antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, and anti-β2-glycoprotein I antibodies) along with decreased complement levels (C3 and C4), supporting the diagnosis of catastrophic antiphospholipid syndrome (Table 2). Owing to the severity of his condition, biopsies of the affected organs were not performed. Despite ICU stabilization, the patient had a guarded prognosis because of persistent hemorrhage, progression of renal disease, plateletopenia, and severe autoimmune pathology.

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Table 2.

Laboratory Findings Associated With Catastrophic Antiphospholipid Syndrome

Laboratory test	Result	Reference range
Hemoglobin level (upon admission)	6.7	14-18 g/dl
Platelets (upon admission)	524	150-450 103/ul
Creatinine (upon admission)	1.5	0.5 – 1.2 mg/dl
SARS Cov19 – PCR (upon admission)	- Negative	Negative
ANCA C	- Negative	Negative
ANCA P	- Negative	Negative
ANA	1/160 AC 4/AC 19	1/80
ANTI DNA double chain	- Negative	- Negative
ANTI SMITH	- Negative	- Negative
ANTI C1Q	- Negative	- Negative
Lupus anticoagulant	2.26	Negative
Anticardiolipin antibody IgG	+ Positive, (120)	+ Positive > 17
Anticardiolipin antibody IgM	- Negative	Negative
Anti-β2-glycoprotein I antibody IgG	+ Positive (95.1)	Negative
Anti-β2-glycoprotein I antibody IgM	Negative (p <5)	Negative
Complement C3 levels (mg/dL)	↓ Decreased (67.5)	90–180 mg/dl
Complement C4 level (mg/dL)	↓ Decreased (6.4)	10–40 mg/dl
Serum creatinine level (mg/dL)	↑ Elevated	0.7–1.3

The patient received immunosuppressive and immunomodulatory therapy including pulse methylprednisolone (3 g over 3 days), intravenous immunoglobulin (0.4 g/kg/day for 5 days), a single intravenous dose of cyclophosphamide (1 g), and Pneumocystis jirovecii prophylaxis with trimethoprim-sulfamethoxazole until hospital discharge. Plasmapheresis was initially proposed as a rescue therapy due to a poor response to corticosteroids and immunoglobulin; however, it was deferred because of hemodynamic instability. After achieving stabilization, in coordination with nephrology, plasmapheresis was performed for five consecutive days, leading to clinical improvement.

The patient required vasopressor support, invasive mechanical ventilation, strict hemodynamic monitoring, fluid adjustment, and blood transfusion, as needed. Nephrology did not indicate urgent renal replacement therapy, as the criteria were not met; however, renal function was closely monitored. The nephrotoxic medications were adjusted, diuretics were initiated for fluid overload, and continuous bladder irrigation was required for hematuria. Based on these clinical manifestations, catastrophic antiphospholipid syndrome with severe pulmonary, hematologic, and cutaneous involvement was suspected. However, alternative diagnoses, including ANCA-associated small-vessel vasculitis and severe systemic lupus erythematosus flare, were initially considered. These were ruled out based on specific laboratory results.

During his 43-day hospitalization, the patient experienced multi-organ complications including thrombosis, hemorrhagic episodes, ventilator-associated pneumonia, and acute respiratory failure requiring ventilatory and vasopressor support. Despite a guarded prognosis, the patient was discharged after functional recovery, requiring initial nocturnal oxygen and rehabilitation therapies. He continued multidisciplinary follow-up every three months with anticoagulation treatment with warfarin 5 mg twice a week, 2.5 mg five times a week, hydroxychloroquine 300 mg daily, prednisone 5 mg daily, and regular antihypertensive medication.

Discussion

This case represents a severe and rare form of catastrophic antiphospholipid syndrome, characterized by multiorgan involvement and simultaneous thrombotic and hemorrhagic events. A history of deep vein thrombosis, intracranial hemorrhage, and chronic kidney disease suggests an underlying prothrombotic state that contributes to the development of CAPS.^3,4

Diffuse alveolar hemorrhage (DAH) is one of the most severe manifestations of CAPS and is associated with high mortality. Its pathophysiology involves immune complex-mediated pulmonary capillaritis and complement activation, which results in endothelial damage and persistent alveolar bleeding.^6,9 In this patient, acute respiratory failure required prolonged invasive mechanical ventilation and was complicated by ventilator-associated pneumonia, a common occurrence in this clinical context. ¹⁰ Severe hematologic involvement with hemolytic anemia and refractory thrombocytopenia contribute to persistent bleeding and limited full anticoagulation, which is central to CAPS management. ¹¹ Renal involvement likely reflects both lupus nephritis and catastrophic antiphospholipid syndrome-associated thrombotic microangiopathy. ¹²

The treatment approach is aligned with the current recommendations for catastrophic antiphospholipid syndrome, employing combined therapy with high-dose glucocorticoids, intravenous immunoglobulin, cyclophosphamide, and plasmapheresis. ⁸ “Triple therapy” has been associated with improved survival compared to incomplete regimens.^5,13 However, the inability to administer rituximab and delayed plasmapheresis owing to hemodynamic instability and resource limitations represent significant barriers.

Multidisciplinary management, involving intensive care, rheumatology, nephrology, pulmonology, hematology, and internal medicine, is fundamental. Despite the initial severe deterioration, the patient survived, defying the high mortality described in catastrophic antiphospholipid syndrome with severe multiorgan involvement.^4,14

Conclusions

Catastrophic antiphospholipid syndrome is a rare but severe condition that requires a high level of clinical suspicion and prompt initiation of combined therapy. Diffuse alveolar hemorrhage represents a life-threatening complication that significantly worsens the clinical course. In low-resource settings, limited access to advanced therapies may adversely influence patient outcomes. Early multidisciplinary management is therefore essential to optimize treatment strategies and reduce morbidity and mortality.