Unusual Manifestations of Paraprotein-Associated Hematological Diseases: Report of 2 Cases and Literature Review

Case Report

Ann Hematol Oncol. 2021; 8(3): 1333.

Unusual Manifestations of Paraprotein-Associated Hematological Diseases: Report of 2 Cases and Literature Review

Karakatsanis S¹*, Papadatos SS¹, Polyzos D¹, Gravani A¹, Syrigos N¹, Tsakania A², Kanellis G³, Marinos L³ and Papanikolaou A³

¹Department of Internal Medicine, National and Kapodistrian University of Athens, Greece

²Department of Blood Transfusion, “Sismanogleio” General Hospital, Greece

³Department of Hematopathology, Evangelismos General Hospital, Greece

*Corresponding author: Karakatsanis S, Department of Internal Medicine, National and Kapodistrian University of Athens,152 Mesogeion Avenue, 115 27, Athens, Greece

Received: February 04, 2021; Accepted: March 04, 2021; Published: March 11, 2021


With this review we firstly describe uncommon manifestations of paraprotein-associated hematological diseases in 2 patients presenting with hemoptysis. The differential diagnosis in both cases included qualitative and quantitative platelet abnormalities, infectious diseases, malignancies, vasculitis, collagen diseases and blood disorders. Among other interventions undertaken, bone marrow biopsy provided evidence of a primary hematological disease while serum protein electrophoresis and immunofixation indicated the presence of a paraprotein. As a “take-away” lesson from the literature review performed on the basis of these cases the bleeding diathesis that is occasionally associated with paraproteinemia should be pointed out, irrespectively of the primary hematological condition. Thus, while investigating a patient with bleeding diathesis, at least a serum protein electrophoresis should be among the requested laboratory tests. Moreover, clinical vigilance is required in order to recognize other unusual manifestations of not so unusual hematological abnormalities.

Keywords: Bleeding; Hemoptysis; Leukoerythroblastic reaction; Lymphadenopathy; Organomegaly; Paraprotein


A/G Ratio: Albumin to Globulin Ratio; AL: Systematic Immunoglobulin Light Chain Amyloidosis; AVWS: Acquired von Willebrand syndrome; BAL: Bronchoalveolar Lavage; BMB: Bone Marrow Biopsy; CLL: Chronic Lymphocytic Leukemia; CrCl: Creatinince Clearance; DAH: Diffuse Alveolar Hemorrhage; DAT: Direct Antiglobulin Test; ESR: Erythrocyte Sedimentation Rate; F: Factor; GGO: Ground-Glass Opacity; HBsAg: Surface Antigen of the Hepatitis B Virus; HBV: Hepatitis B Virus; Ig: Immunoglobulin; IGRA: Interferon-γ Release Assay; IMWG: International Myeloma Working Group; ITP: Immune Thrombocytopenia; LDH: Lactate Dehydrogenase; LPD: Lymphoproliferative Disease; MBL: Monoclonal B Lymphocytosis; MDRD: Modification of Diet in Renal Disease; MGUS: Monoclonal Gammopathy of Undetermined Significance; MM: Multiple Myeloma; MZL: Marginal Zone Lymphoma; PB: Peripheral Blood; PCD: Plasma Cell Disorder; PET/ CT: Positron Emitting Tomography Combined with Low-Dose Computed Tomography; POEMS: Polyneuropathy, Organomegaly, Endocrinopathy, Multiple Myeloma And Skin Changes; RBC: Red Blood Cell; R-ISS: Revised International Staging System; RLL: Right Lower Pulmonary Lobe; RUL: Right Upper Pulmonary Lobe; SMZL: Splenic Marginal Zone Lymphoma; TST: Tuberculin Skin Test; TTP: Thrombotic Thrombocytopenic Purpura; vWF: von Willebrand Factor


Multiple Myeloma (MM) is the second commonest hematological malignancy in the Western world since it accounts for 1% of all cancers and 10% of all hematological malignancies [1]. Most patients have characteristic clinical and laboratory findings, including bone pain with or without pathologic fractures, anemia and/or weakness, infections, hypercalcemia and renal failure [2]. On the other hand, Monoclonal Gammopathy Of Undetermined Significance (MGUS) is a much commoner premalignant, clonal Plasma Cell Disorder (PCD), present in 3% to 4% of the general population older than 50 years and characterized as well by the presence of a Monoclonal (M)- protein (or paraprotein), but lacks by definition MM clinical findings [3]. Paraproteins may be found among patients with rarer PCDs as well as lymphoplasmacytic malignancies and other low-grade B-cell non-Hodgkin lymphomas with plasmacytic differentiation [2,4,5]. The following 2 cases illustrate that paraproteins, irrespective of their association with benign or malignant blood disorders, can disrupt normal coagulation through various mechanisms, and therefore patients with bleeding diathesis should also be evaluated for the presence of a monoclonal protein. What is more, physicians should also be aware of other unusual manifestations of the aforementioned conditions.

Case Presentation

Case report 1

A 52-year-old female accountant, current smoker, presented at our Emergency Department because of 2 episodes of hemoptysis during the last 24 hours, yet her examination from the attending pulmonologist did not reveal a specific thoracic disease, and she was further referred to our Hematology Department because of the alleged hemoptysis in combination with thrombocytopenia that was found in her full blood count.

A comprehensive systems’ review came up with episodes of spontaneous bruising and epistaxis for the last 3 months, while the patient also mentioned increased blood loss during her last menstrual cycle. No other systemic or otherwise symptoms were reported. The patient’s personal history included only arterial hypertension under treatment and appendicectomy in young age, while her physical examination was remarkable for stage 1 obesity, bilateral tonsil hyperplasia, mild conjunctival pallor and a palpable spleen. Laboratory results included leukocytosis with absolute lymphocytosis, severe macrocytic anemia, mild thrombocytopenia (>50,000/μlt), high erythrocyte sedimentation rate (ESR), a low Albumin to Globulin (A/G) ratio, absent haptoglobins, and liver function tests abnormalities combined with positive surface antigen of the Hepatitis B Virus (HBsAg). The rest of her microbiology results were negative. HBV-DNA was subsequently sent and came up positive (2.12x107IU/ml or 1.03x108 copies/ml). Of note, routine coagulation tests (prothrombin time, activated thromboplastin time, fibrinogen) were all normal.

Peripheral Blood (PB) smear examination provided evidence of a leukoerythroblastic reaction, an absence of lymphocytosis surprisingly, macrocytosis, fine basophilic stippling, rouleaux formation and the presence of Red Blood Cell (RBC) agglutination, spherocytes, but no fragmented RBCs, and a limited number of plasma cells (Figure 1). Computed tomography scan revealed massive splenomegaly (measured dimensions were 13.7x14x10 cm³), hepatomegaly (cephalocaudal diameter measured at 18.7 cm), intraabdominal lymphadenopathy, multiple large uterine fibroids (with maximum diameter ~8cm) and a Ground-Glass Opacity (GGO) of the Right Upper Pulmonary Lobe (RUL).

Citation: Karakatsanis S, Papadatos SS, Polyzos D, Gravani A, Syrigos N, Tsakania A, et al. Unusual Manifestations of Paraprotein-Associated Hematological Diseases: Report of 2 Cases and Literature Review. Ann Hematol Oncol. 2021; 8(3): 1333.