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Hyperviscosity Syndrome

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.


Presentation

Hyperviscosity syndrome patients present with three main symptoms [1]: 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 [2].

Patients may also present with symptoms of heart failure, hypertension, metabolic syndrome or anorexia [3], deafness [4], nystagmus or dementia [5].

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.

Congestive Heart Failure
  • Abstract Hyperviscosity syndrome (HVS) is characterised by high serum viscosity and the involvement of multiple organs, commonly causing retinal haemorrhage, bleeding diathesis, pulmonary hypertension, congestive heart failure (CHF), neurologic deficits[ncbi.nlm.nih.gov]
  • Physical examination disclosed hepatosplenomegaly, congestive heart failure, and multiple sites of bleeding.[ncbi.nlm.nih.gov]
  • 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.[symptoma.com]
  • Clinical sequelae of HVS can include congestive heart failure, ischemic acute tubular necrosis, and pulmonary edema with multiorgan system failure and death if treatment is not promptly initiated. [6] Thus, prompt recognition and expeditious treatment[emedicine.com]
Bleeding Gums
  • Abnormal bleeding: High levels of abnormal antibody can damage blood vessels, which can lead to problems like nosebleeds and bleeding gums.[cancer.org]
  • Patients usually present with non-specific symptoms such as epistaxis, bleeding gums, headaches, confusion, blurry vision, abdominal pain, fatigue, dyspnea, palmar erythema and stroke [2,5-15,17-19].[oatext.com]
Acrocyanosis
  • Type I cryoglobulinemia is frequently asymptomatic per se but patients may develop acrocyanosis, retinal hemorrhage, Raynaud's phenomenon, and arterial thrombosis.[orpha.net]
Severe Osteoporosis
  • At autopsy, almost all bones showed infiltration of multiple myeloma of IgA-kappa type and severe osteoporosis accompanied with proliferation of osteoclasts.[ncbi.nlm.nih.gov]
Blurred Vision
  • She also showed symptoms and signs of hyperviscosity syndrome; hemorrhagic diathesis, blurred vision and episodes of transient ischemic attacks of the brain, and fractures of the bones by small powers of trauma.[ncbi.nlm.nih.gov]
  • Blurred vision, headache, vertigo, dizziness, nystagmus, deafness, and ataxia also occur in HVS. 1 , 8 , 12 , 14 – 18 Patients with severe HVS may have confusion, dementia, stroke, or coma.[bloodjournal.org]
  • Hyperviscosity may be manifested by nasal bleeding, blurred vision, headaches, dizziness, nystagmus, deafness, diplopia, ataxia, paresthesias, or congestive heart failure.[mayomedicallaboratories.com]
  • Vision problems: Bleeding around the small blood vessels inside the eyes or poor circulation in these vessels caused by thickened blood might lead to blurred vision or blind spots.[cancer.org]
Sudden Hearing Loss
  • Intravascular lymphomatosis presenting with sudden hearing loss . Journal of the Neurological Sciences, Vol. 232, Issue. 1-2, p. 105. CrossRef Google Scholar[cambridge.org]
Epistaxis
  • Center) Edited by Alex Koyfman MD (@EMHighAK) and Stephen Alerhand MD (@SAlerhand) Scenario #1 A 72 year-old male recently diagnosed with multiple myeloma presents to your Emergency Department complaining of abrupt onset of ataxia, blurry vision, and epistaxis[emdocs.net]
  • Patients usually present with non-specific symptoms such as epistaxis, bleeding gums, headaches, confusion, blurry vision, abdominal pain, fatigue, dyspnea, palmar erythema and stroke [2,5-15,17-19].[oatext.com]
Headache
  • Abstract A 47-year-old man with hyperleukocytic chronic lymphocytic leukemia progressively developed retinal hemorrhages, headache, diplopia, dysequilibrium, slurred speech, nystagmus, ataxic gait, and hearing loss as his leukocyte count rose to a maximum[ncbi.nlm.nih.gov]
  • The remaining patients had transient complications such as headache, short of breath and hot flush probably due to the circulatory disturbance.[ncbi.nlm.nih.gov]
  • Reference work entry DOI: 10.1007/3-540-29662-X_1304 Definition Often found in paraproteinemias most common Waldenström's macroglobulinemia, polycythemia, leukocytosis; symptoms include visual changes, headache, vertigo, nystagmus, dizziness, sudden deafness[link.springer.com]
  • الصفحة 324 - Headache attacks lasting 4-72 hours (untreated or unsuccessfully treated). C. Headache has at least two of the following characteristics: 1 . Unilateral location. 2. Pulsating quality. 3.[books.google.com]
  • 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.[symptoma.com]
Vertigo
  • Reference work entry DOI: 10.1007/3-540-29662-X_1304 Definition Often found in paraproteinemias most common Waldenström's macroglobulinemia, polycythemia, leukocytosis; symptoms include visual changes, headache, vertigo, nystagmus, dizziness, sudden deafness[link.springer.com]
  • 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.[symptoma.com]
  • Vertigo as the First Sign of Chronic Myeloid Leukemia: A Case Report and Literature Review . Case Reports in Otolaryngology, Vol. 2013, Issue. , p. 1.[cambridge.org]
  • Symptoms of high blood viscosity include spontaneous bleeding from mucous membranes, visual disturbances due to retinopathy, and neurologic symptoms ranging from headache and vertigo to seizures and coma.[en.wikipedia.org]
  • Streptococcal Disease 1156 Tuberculosis 1158 Tympanic Membrane Perforation 1164 Suicide Risk Evaluation 1166 Gastritis 1168 Syncope 1172 Ovarian CystTorsion 788 1195 Ventilator Management 1198 Ventricular Peritoneal Shunts 1202 Urinary Tract Fistula 1174 Vertigo[books.google.com]
Stroke
  • 1304 Definition Often found in paraproteinemias most common Waldenström's macroglobulinemia, polycythemia, leukocytosis; symptoms include visual changes, headache, vertigo, nystagmus, dizziness, sudden deafness, diplopia, ataxia, confusion, dementia, stroke[link.springer.com]
  • This can also enhance the risk of stroke instead of reducing the risk.[cardiophile.org]
  • These complications can include: stroke kidney failure decreased motor control loss of movement the death of intestinal tissue recurrent seizures Be sure to report any symptoms your baby is having to their doctor right away.[healthline.com]
  • Complications may include: Death of intestinal tissue (necrotizing enterocolitis) Decreased fine motor control Kidney failure Seizures Strokes Neonatal polycythemia; Hyperviscosity - newborn Diab Y, Luchtman-Jones L.[medlineplus.gov]
  • Differential diagnoses will depend on the patient's presenting symptoms, but include coagulopathy, hemorrhagic or ischemic stroke, congestive heart failure, pulmonary edema and diabetic ketoacidosis.[clinicaladvisor.com]
Dizziness
  • Reference work entry DOI: 10.1007/3-540-29662-X_1304 Definition Often found in paraproteinemias most common Waldenström's macroglobulinemia, polycythemia, leukocytosis; symptoms include visual changes, headache, vertigo, nystagmus, dizziness, sudden deafness[link.springer.com]
  • […] minutes: (1) Palpitations, pounding heart, or accelerated heart rate (2) Sweating (3) Trembling or shaking (4) Sensations of shortness of breath or smothering (5) Feeling of choking (6) Chest pain or discomfort (7) Nausea or abdominal distress (8) Feeling dizzy[books.google.com]
  • Hyperviscosity may be manifested by nasal bleeding, blurred vision, headaches, dizziness, nystagmus, deafness, diplopia, ataxia, paresthesias, or congestive heart failure.[mayomedicallaboratories.com]
  • She experienced progressive shortness of breath which culminated into persistent headaches, dizziness and bilateral chest pain.[oatext.com]
  • Blurred vision, headache, vertigo, dizziness, nystagmus, deafness, and ataxia also occur in HVS. 1 , 8 , 12 , 14 – 18 Patients with severe HVS may have confusion, dementia, stroke, or coma.[bloodjournal.org]
Paresthesia
  • 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.[symptoma.com]
  • Hyperviscosity syndrome is characterized by impaired tissue oxygen delivery with symptoms like headache, visual disturbances, loss of concentration, paresthesia, muscle weakness, and fatigue.[cardiophile.org]
  • […] discomfort (7) nausea or abdominal distress (8) feeling dizzy, unsteady, lightheaded, or faint (9) derealization (feelings of unreality) or depersonalization (being detached from oneself) (10) fear of losing control or going crazy (11) fear of dying (12) paresthesias[books.google.com]
  • Hyperviscosity may be manifested by nasal bleeding, blurred vision, headaches, dizziness, nystagmus, deafness, diplopia, ataxia, paresthesias, or congestive heart failure.[mayomedicallaboratories.com]
  • Review of systems was positive for fatigue and paresthesias of the hands but was negative for fevers, night sweats, weight loss, orthopnea, paroxysmal nocturnal dyspnea, history of deep veinous thrombosis or pulmonary embolus, joint pain/swelling, inflammatory[oatext.com]

Workup

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 [6] [7]. Furthermore, if macroglobulinemia is the cause of this pathology, then it can also lead to rouleaux formation, visible on blood smears [5] 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 [8], 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.

Liver Biopsy
  • This case suggests a new cause for labeling abnormalities on liver radionuclide scans in patients with a syndrome where liver biopsies would be unusually hazardous.[ncbi.nlm.nih.gov]

Treatment

  • The prominent microvasculopathy is reversible after appropriate treatment.[ncbi.nlm.nih.gov]
  • It is the treatment of choice in hyperviscosity syndrome, due to the presence of quantitatively or qualitatively abnormal plasma proteins such as paraproteins.[ncbi.nlm.nih.gov]
  • Treatment includes hydration with diuresis, plasmapheresis, and control of the underlying disease. The current treatment for WM is chemotherapy (i.e., alkylating agents and nucleoside analogs) and the monoclonal antibody rituximab.[ncbi.nlm.nih.gov]
  • In conclusion, we could not demonstrate a superior effect of cascade filtration as compared to conventional plasma exchange in the treatment of hyperviscosity syndrome.[ncbi.nlm.nih.gov]
  • Effects of combined myeloma treatment and prognostic value of serum IL-2 level and absolute number of CD3 determination are discussed.[ncbi.nlm.nih.gov]

Prognosis

  • Prognosis The overall prognosis for any patient will depend on the underlying condition and severity of any complications of hyperviscosity.[patient.info]
  • Prognosis Prognosis depends on the underlying cause of the hyperviscosity. For example, hyperviscosity secondary to an acute leukemia or multiple myeloma has a worse prognosis than that due to polycythemia vera or essential thrombocythemia.[clinicaladvisor.com]
  • Treatment and prognosis The International Prognostic Scoring System for Waldenström's macroglobulinemia is a predictive model for characterization of long-term outcome.[radiopaedia.org]
  • Tujuan penelitian ini untuk mengetahui luaran (outcome) dan prognosis LLA dengan leukosit 50000/μL. Metode . Penelitian rancang bangun kohort retrospektif dilakukan di Instalasi Kesehatan Anak RSUP DR.[saripediatri.org]
  • Clinical course, treatment, and prognosis of type I cryoglobulinemia largely depend on the underlying disorder. Patients with a benign monoclonal gammopathy of undetermined significance are generally asymptomatic or present with a mild disorder.[orpha.net]

Etiology

  • CONCLUSION: Hyperviscosity syndrome seems similar to central retinal vein occlusion and may be associated with systemic conditions such as diabetes and atherosclerosis; however, alternative etiologies should be considered in young otherwise healthy individuals[ncbi.nlm.nih.gov]
  • Cryoglobulinemia: study of etiologic factors and clinical and immunologic features in 443 patients from a single center. Medicine (Baltimore) 2001; 80:252. Kulger N, Sirvente J, Rigau V, Guillot B.[signavitae.com]
  • Etiology The pathogenetic processes in simple cryoglobulinemia generally appear to be related to those of the underlying lymphoproliferative diseases.[orpha.net]

Epidemiology

  • Little epidemiologic information is available on hyperviscosity symdrome.[emedicine.com]
  • […] circulating serum immunoglobulins (eg, macroglobulinaemia, multiple myeloma) and can also result from increased cellular blood components (eg, red or white blood cells) in hyperproliferative states - eg, leukaemias, polycythaemia and thrombocythaemia. [ 1 ] Epidemiology[patient.info]
  • Summary Epidemiology The prevalence is unknown.[orpha.net]
Sex distribution
Age distribution

Pathophysiology

  • This review provides an overview of the pathophysiology of leukostasis and its management with leukapheresis. The use of TPE in the management of hyperviscosity syndrome is also discussed.[ncbi.nlm.nih.gov]
  • A basic knowledge of the principles of rheology is important in the understanding of its pathophysiology, especially the relationship between viscosity and flow conditions.[ncbi.nlm.nih.gov]
  • Abstract The proper understanding of the causes, pathophysiology, diagnosis and management of the plasma hyperviscosity syndrome is based on good knowledge of malignant paraproteinaemias, properties of immunoglobulins, rheology of blood in the microcirculation[ncbi.nlm.nih.gov]
  • (Review of pathophysiology and effect of cytoreduction on prognosis in acute leukemia.) Porcu, P, Cripe, LD, Ng, EW. "Hyperleukocytic leukemias and leukostasis: a review of pathophysiology, clinical presentation and management".[clinicaladvisor.com]

Prevention

  • In most cases, plasmapheresis is used in combination with corticosteroids and immunosuppressive drugs to prevent production of abnormal proteins or to treat the underlying disease.[ncbi.nlm.nih.gov]
  • Long-term management is directed at control of the underlying disease to prevent production of the monoclonal protein.[scholars.northwestern.edu]
  • Partial plasma exchange transfusion(XT) has been recommended as the treatment of choice in neonatal hyperviscosity although there remains no statistical proof that it prevents long-term CNS or other sequelae.[nature.com]
  • HVS can include congestive heart failure, ischemic acute tubular necrosis, and pulmonary edema with multiorgan system failure and death if treatment is not promptly initiated. [6] Thus, prompt recognition and expeditious treatment are imperative in preventing[emedicine.com]

References

Article

  1. Adams BD, Baker R, Lopez JA, Spencer S. Myeloproliferative disorders and the hyperviscosity syndrome. Emerg Med Clin North Am. 2009;27(3):459-76.
  2. Rajagopal R, Apte RS. Seeing through thick and through thin: Retinal manifestations of thrombophilic and hyperviscosity syndromes. Surv Ophthalmol. 2016;61(2):236-47.
  3. Sloop G, Holsworth RE Jr, Weidman JJ, St Cyr JA. The role of chronic hyperviscosity in vascular disease. Ther Adv Cardiovasc Dis. 2015;9(1):19-25.
  4. Mehta J, Singhal S. Hyperviscosity syndrome in plasma cell dyscrasias. Semin Thromb Hemost 2003;29:467-471.
  5. Stone MJ. Waldenström's macroglobulinemia: hyperviscosity syndrome and cryoglobulinemia. Clin Lymphoma Myeloma 2009;9(1):97-99.
  6. Ramos-Casals M, Stone JH, Cid MC, Bosch X. The cryoglobulinaemias. Lancet 2012;379(9813):348-360
  7. Della Rossa A, Tavoni A, Bombardieri S. Hyperviscosity syndrome in cryoglobulinemia: clinical aspects and therapeutic considerations. Semin Thromb Haemost 2003;9(5):473-477.
  8. Stone MJ, Pascual V. Pathophysiology of Waldenström's macroglobulinemia. Haematologica 2010;95:359-364.

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Last updated: 2018-06-21 23:48