History

One fourth of patients with primary myelofibrosis are asymptomatic, and the diagnosis is made as a result of detecting splenomegaly or checking blood cell counts for an unrelated cause. Symptoms may occur as a result of anemia, splenomegaly, hypermetabolic states, extramedullary hematopoiesis, bleeding, bone changes, portal hypertension, and immune abnormalities.

Anemia may occur as a result of ineffective erythropoiesis, erythroid hypoplasia, and hypersplenism. Anemia may cause easy fatigability, weakness, dyspnea, and palpitations.

Splenomegaly may result in early satiety and left upper quadrant discomfort. Splenic infarcts, perisplenitis, or subcapsular hematoma may occur, causing severe left upper quadrant or left shoulder pain. Occasionally, patients may have diarrhea related to pressure on the colon.

A hypermetabolic state occurs and can result in weight loss, night sweats, and low-grade fever. Gout and urate kidney stones may develop.

Bleeding is observed in one fourth of patients with primary myelofibrosis and varies in severity from insignificant cutaneous petechiae to severe, life-threatening gastrointestinal (GI) tract bleeding. Platelet dysfunction, acquired factor V deficiency, thrombocytopenia, disseminated intravascular coagulation (DIC), esophageal varices, and peptic ulcer disease may occur, contributing to bleeding.

Extramedullary hematopoiesis may cause symptoms, depending on the organ or site of involvement (see the image below). The condition may result in GI tract hemorrhage, spinal cord compression, focal seizures, symptoms related to brain tumors, ascites, hematuria, pericardial effusion, pleural effusion, hemoptysis, and respiratory failure.

Extramedullary hematopoiesis in the spleen of a patient with primary myelofibrosis. Courtesy of Wei Wang, MD, and John Lazarchick, MD, Department of Pathology, Medical University of South Carolina.

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Portal hypertension may occur as a result of markedly increased splenoportal blood flow and decreased hepatic vascular compliance. Ascites, esophageal and gastric varices, GI tract bleeding, and hepatic encephalopathy may occur. Hepatic or portal vein thrombosis may also arise as complications.

Patients with primary myelofibrosis develop osteosclerosis. This may cause severe joint and bone pain.

One half of patients with primary myelofibrosis have abnormalities of humoral immunity. A variety of autoantibodies and circulating immune complexes may be detected, and amyloidosis may develop. Infections, commonly pneumonia, may occur as a result of immune deficiency.

Physical Examination

Splenomegaly is the most common finding in patients with primary myelofibrosis, and it is present in approximately 90% of patients. Spleen size may vary from barely palpable to massive (observed in 35% of patients).

Hepatomegaly is found in 60-70% of patients with primary myelofibrosis, and pallor is observed in 60% of patients. Other physical findings include the following:

Petechiae and ecchymosis (20%)
Lymphadenopathy (10-20%)
Signs of portal hypertension (10-18%)
Gout (6%)

Differential Diagnoses

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Media Gallery

Primary myelofibrosis. Peripheral smear shows teardrop red blood cells (RBCs) and a leukoerythroblastic picture with nucleated RBC precursors and immature myeloid cells. Courtesy of Wei Wang, MD, and John Lazarchick, MD, Department of Pathology, Medical University of South Carolina.
Bone marrow biopsy from a patient with primary myelofibrosis shows extensive fibrosis. Courtesy of Wei Wang, MD, and John Lazarchick, MD, Department of Pathology, Medical University of South Carolina.
Reticulin stain on a bone marrow biopsy from a patient with primary myelofibrosis shows extensive fibrosis. Courtesy of Wei Wang, MD, and John Lazarchick, MD, Department of Pathology, Medical University of South Carolina.
Extramedullary hematopoiesis in the spleen of a patient with primary myelofibrosis. Courtesy of Wei Wang, MD, and John Lazarchick, MD, Department of Pathology, Medical University of South Carolina.

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Author

Asheesh Lal, MBBS, MD Physician, Department of Internal Medicine, Lexington Medical Center

Asheesh Lal, MBBS, MD is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

Karen Seiter, MD Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College

Karen Seiter, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Society of Hematology

Disclosure: Received honoraria from Novartis for speaking and teaching; Received consulting fee from Novartis for speaking and teaching; Received honoraria from Celgene for speaking and teaching.

Acknowledgements

Author: Asheesh Lal, MBBS, MD, Physician, Department of Internal Medicine, Lexington Medical Center.

Asheesh Lal is a member of the following medical societies: American Society of Clinical Oncology and American Society of Hematology.

Editors: Karen Seiter, MD, Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College; Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference; Emmanuel C Besa, MD, Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University.

Primary Myelofibrosis Clinical Presentation

History

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