Hyperviscosity syndrome is caused by elevated blood viscosity due to the liquid component- plasma or serum, like in Waldenstrom macroglobulinemia or multiple myeloma or to the cellular component, like in myeloproliferative diseases- polycythemia or leukemia. Other conditions associated with blood hyperviscosity include shock, rheumatic disease, and diabetes.
Hyperviscosity syndrome patients present with three main symptoms : neurologic symptoms, visual abnormalities, and bleeding tendencies. Neurological symptoms include vertigo, somnolence, ataxia, paresthesias and headaches. Bleeding may occur at various sites like gums, uterus, rectum or nasal mucosa or exaggerated cutaneous bleeding after minor injuries and bruising. Ophthalmic symptoms comprise decreased visual acuity, diplopia or vision loss .
Symptoms may vary from patient to patient and even in the same patient at different moments in time, according to viscosity levels. Patients may also present with dyspnea, chest pain or high output heart failure. In children, establishing the clinical diagnosis is even more difficult, as they exhibit nonspecific symptoms like tachypnea, cyanosis, hypotonia, seizures, irritability, apnea, apathy, weak suckling, plethora and abdominal distension.
Serum viscosity is the laboratory test that establishes the diagnosis of hyperviscosity syndrome. However, viscosity can be dependent on the sample temperature if cryoglobulins are present  . Furthermore, if macroglobulinemia is the cause of this pathology, then it can also lead to rouleaux formation, visible on blood smears  and platelet dysfunction.
Complete blood cell count may show high white blood cell numbers in leukemia and leukostasis. Patients are usually anemic, as a consequence of the underlying disease, but red blood cell number can also be high in polycythemia vera.
A bone marrow biopsy may diagnose the cause of the hyperviscosity syndrome: leukemia, myeloproliferative disorder, plasma cell dyscrasia.
Other informative tests include serum and urine protein electrophoresis (a monoclonal spike confirms the presence of a gammopathy), metabolic and electrolyte panels (hypercalcemia and hyponatremia are frequent), prothrombin time, activated partial thromboplastin time and international normalized ratio. Significant proteinuria also suggests a gammopathy like multiple myeloma or Waldenstrom's macroglobulinemia.
In presence of an infection cultures should be obtained and imaging studies, as appropriate, should be performed. Chest radiography, for instance, can help diagnose pulmonary infection and congestive heart failure, while craniocerebral computer tomography can exclude other causes of seizures and altered sensorium.
Ophthalmologic examination is important in establishing retinal vein engorgement , hemorrhages, exudates, and papilledema. These findings should be distinguished from those caused by hypertension, that may coexist in the same patient. Central vein occlusion may occur in late stages.
The clinician should keep in mind the fact that different methods of blood viscosity measurement may lead to different results. Hyperviscosity symptoms usually occur when the serum viscosity reaches 4-5 cp (normal range: 1.4-1.8 cp).
In children and newborns, hyperviscosity is more often due to polycythemia, therefore arterial or venous hematocrit should be measured. These patients often have associated hypoglycemia, hypocalcemia, thrombocytopenia, and hyperbilirubinemia due to increased red blood cell destruction. Further imaging studies demonstrate pulmonary hypertension, alveolar infiltrates, pleural effusions, increased systemic vascular resistance, increased myocardial strain and hypoperfusion of both peripheral (gut, kidney) and central (brain, myocardium) territories.