Purpura Fulminans Triggered by the Formation of Anti-Endothelial Autoantibodies in a Patient with Chronic Lymphocytic Leukemia

Case Report

Ann Hematol Oncol. 2022; 9(1): 1389.

Purpura Fulminans Triggered by the Formation of Anti-Endothelial Autoantibodies in a Patient with Chronic Lymphocytic Leukemia

Beckmann L¹, Lennartz M², Beitzen-Heineke A¹, Voigtlaender M¹, Rolling CC1,3, Holstein K¹, Bokemeyer C¹, Amirkhosravi A4 and Langer F¹*

1Medizinische Klinik und Poliklinik, Universitätsklinikum Eppendorf, Hamburg, Germany

2Institut für Pathologie, Universitätsklinikum Eppendorf, Hamburg, Germany

3Department of Medicine, New York University Grossman School of Medicine, New York, USA

4Department of Health Sciences, University of Central Florida, Orlando, FL, USA

*Corresponding author: Langer F, II. Medizinische Klinik und Poliklinik, Universitätsklinikum Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany

Received: February 16, 2022; Accepted: March 10, 2022; Published: March 17, 2022


Purpura fulminans (PF), a life-threatening disorder characterized by cutaneous microvascular thrombosis with secondary hemorrhagic infarction, is a rare complication of sepsis and may also be caused by severe protein C or protein S deficiency.

Here, we describe the case of a 58-year-old man who developed PF in close association with the onset of chronic lymphocytic leukemia (CLL). PF initially manifested with an ecchymosis of the right upper leg in the absence of sepsis or disseminated intravascular coagulation. PF was likely triggered by antiendothelial IgG autoantibodies functionally interfering with the anticoagulant protein C-protein S-thrombomodulin system on EA.hy926 endothelial cells in a modified thrombin generation assay. Although plasma exchange and immunosuppressive therapy with cyclophosphamide were temporarily effective, PF eventually progressed and the patient died from septic shock during treatment-associated neutropenia.

In rare occasions, CLL may be associated with autoimmune-mediated PF requiring prompt diagnosis and aggressive multimodal therapy.

Keywords: Chronic lymphocytic leukemia; Purpura fulminans; Antiendothelial antibodies; Plasma exchange therapy


AIC: Autoimmune Cytopenia; AIHA: Autoimmune Hemolytic Anemia; ANA: Antinuclear Antibodies; APS: Antiphospholipid Syndrome; ASA: Acetylsalicylic Acid; BID: Twice Daily; BTK: Bruton’s Tyrosine Kinase; CLL: Chronic Lymphocytic Leukemia; CRP: C-Reactive Protein; CT: Computed Tomography; DIC: Disseminated Intravascular Coagulation; EPCR: Endothelial Protein C Receptor; HIT: Heparin-Induced Thrombocytopenia; ISTH: International Society on Thrombosis and Haemostasis; ITP: Immune Thrombocytopenia; MBL: Monoclonal B-Cell Lymphocytosis; MRI: Magnetic Resonance Imaging; OD: Once Daily; PC: Protein C; PET: Plasma Exchange Therapy; PF: Purpura Fulminans; PNH: Paroxysmal Nocturnal Hemoglobinuria; PS: Protein S; SSC: Scientific and Standardization Committee; sTM: Soluble Thrombomodulin; TF: Tissue Factor; TM: Thrombomodulin

Case Presentation

A 58-year-old man (169cm, 80kg) was referred to our hospital with the rapid onset of a singular erythema-surrounded ecchymosis with central hemorrhagic bullae and necrotic lesions located at the right upper leg (Figure 1A, left image). The patient had several cardiovascular comorbidities, including atrial fibrillation complicated by a stroke, coronary artery disease, and arterial hypertension. In addition, he had a history of chronic bowel disease and not further specified mild thrombocytopenia and leukocytosis. At hospital admission, he was on oral anticoagulation with apixaban 5mg twice daily (BID) and antiplatelet therapy with acetylsalicylic acid (ASA) 100mg once daily (OD).

A skin punch biopsy revealed thrombotic vasculopathy with occlusions of cutaneous microvessels by hyaline thrombi (Figure 1B). Muscular and osseous involvement was ruled out by magnetic resonance imaging (MRI). Ultrasound analysis of the lower limbs was unremarkable with no evidence of arterial or venous thrombosis. In addition to Coombs-positive hemolytic anemia (hemoglobin, 10.8g/dL) and thrombocytopenia (platelet count, 41 × 109/L), laboratory workup revealed elevated inflammatory markers with a leukocyte count of 13.4 × 109/L and a C-reactive protein (CRP) of 70mg/L (Table 1). The absolute lymphocyte count was normal, and extensive analysis of coagulation parameters was unremarkable except for slightly elevated plasma D-dimers (0.96mg/L) (Table 1). The disseminated intravascular coagulation (DIC) score according to the Scientific and Standardization Committee (SSC) of the International Society on Thrombosis and Haemostasis (ISTH) [1] was 4. Spontaneous heparin-induced thrombocytopenia (HIT), systemic vasculitis, connective tissue diseases, antiphospholipid syndrome (APS), and paroxysmal nocturnal hemoglobinuria (PNH) were excluded (Table 1), and hence, thrombotic vasculopathy was attributed to a purpura fulminans (PF). Overt malignancy was ruled out by computed tomography (CT) scanning of chest, abdomen and pelvis, but cytological and immunophenotypic evaluation of bone marrow and peripheral blood (Supplementary Figure 1) revealed a high-count monoclonal B-cell lymphocytosis (MBL) without evidence of bone marrow failure. The karyotype was normal, and quantitative immunoglobulins were within the respective reference ranges (Table 1) with no evidence for a monoclonal paraprotein in serum electrophoresis. In light of co-existing autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP), diagnostic criteria for manifest chronic lymphocytic leukemia (CLL) were fulfilled, and an autoimmune pathogenesis of PF was suspected.

Citation: Beckmann L, Lennartz M, Beitzen-Heineke A, Voigtlaender M, Rolling CC, Holstein K, et al. Purpura Fulminans Triggered by the Formation of Anti-Endothelial Autoantibodies in a Patient with Chronic Lymphocytic Leukemia. Ann Hematol Oncol. 2022; 9(1): 1389.