Hematologic emergency

Hyperviscosity Syndrome

Treat symptomatic hyperviscosity as an oncologic emergency: recognize retinal, mucosal bleeding, neurologic, and cardiopulmonary injury; obtain viscosity and cause-directed studies without delaying plasma exchange; then suppress the responsible paraprotein-producing or leukemic process.

Clinical question: How should physicians identify, stabilize, and definitively manage symptomatic hyperviscosity syndrome?

Updated August 24, 20265 minute readHematology and emergency medicine

What matters in practice

New mucosal bleeding, visual disturbance, or neurologic dysfunction in a patient with suspected or known paraproteinemia warrants urgent evaluation for symptomatic hyperviscosity and should not await a viscosity result before therapeutic plasma exchange. JAMA+2JAMASerum Hyperviscosity Syndrome ScienceDirectThe use of emergency apheresis in the management of plasma cell disorders PubMedMultiple Myeloma - StatPearls - NCBI Bookshelf
Serum viscosity above 4 relative to water is commonly associated with symptomatic hyperviscosity, but individual symptom thresholds vary and retinal disease may occur at lower serum viscosity or IgM levels. BMJ+2BMJHyperviscosity Syndrome JAMAHyperviscosity-Related Retinopathy in Waldenström ...NatureWaldenstrom macroglobulinemia: prognosis and ...
Waldenstrom macroglobulinemia is the predominant paraprotein-associated cause; symptomatic hyperviscosity is less common in IgG- or IgA-associated myeloma. ScienceDirect+2ScienceDirectHyperviscosity Syndrome - an overview | ScienceDirect Topics ScienceDirectThe use of emergency apheresis in the management of plasma cell disorders acepHyperviscosity Syndrome | Critical Care Medicine Section
Therapeutic plasma exchange rapidly removes circulating paraprotein but does not control the clone; start disease-directed cytoreduction concurrently to prevent recurrence. ScienceDirect+1ScienceDirectThe use of emergency apheresis in the management of plasma cell disorders acepHyperviscosity Syndrome | Critical Care Medicine Section
Separate paraprotein hyperviscosity from leukostasis: symptomatic hyperleukocytosis requires immediate cytoreduction, isotonic fluids, and avoidance of nonessential red-cell transfusion while the leukocyte count remains high. ScienceDirect+2ScienceDirectLeukostasis - an overview | ScienceDirect Topics ScienceDirectRapid Fire: Acute Blast Crisis/Hyperviscosity Syndrome acepHyperviscosity Syndrome | Critical Care Medicine Section

Immediate decision

When to treat as hyperviscosity syndrome

Act on a compatible clinical syndrome rather than a laboratory value alone.

Hospitalize patients with a compatible syndrome and immediately involve hematology plus an apheresis-capable center. The classic high-risk pattern is mucosal bleeding, retinal or visual symptoms, and neurologic dysfunction; reported manifestations also include blurred vision, retinal hemorrhage, headache, vertigo, hearing change, ataxia, confusion, seizures, somnolence, coma, dyspnea, and heart failure. JAMA+3JAMASerum Hyperviscosity Syndrome ScienceDirectHyperviscosity Syndrome - an overview | ScienceDirect Topics acepHyperviscosity Syndrome | Critical Care Medicine Section PubMedMultiple Myeloma - StatPearls - NCBI Bookshelf

Obtain serum viscosity before exchange when doing so does not delay treatment, but do not use one numeric threshold to exclude symptomatic disease. Relative serum viscosity is normally about 1.4 to 1.8 times water; symptoms often emerge around 4 to 7, and a value greater than 4 is commonly associated with hyperviscosity syndrome. Clinical thresholds vary substantially, particularly with coexisting retinal disease, and Waldenstrom-related retinopathy can occur at lower serum IgM and viscosity levels than historically expected. BMJ+2BMJHyperviscosity Syndrome JAMAHyperviscosity-Related Retinopathy in Waldenström ...NatureWaldenstrom macroglobulinemia: prognosis and ...

Perform urgent funduscopic examination when visual complaints, headache, or bleeding accompany a suspected paraproteinemia. Retinal venous congestion, hemorrhages around small retinal vessels, papilledema, and segmented “sausage-like” venous changes support impaired retinal microcirculation and provide a bedside marker of response to plasma exchange. ScienceDirect+1ScienceDirectHyperviscosity Syndrome - an overview | ScienceDirect Topics ScienceDirectThe use of emergency apheresis in the management of plasma cell disorders

Escalate immediately for declining consciousness, focal neurologic deficits, seizure, rapidly worsening vision, major bleeding, hypoxemia, or acute heart failure; these findings represent threatened end-organ perfusion or capillary injury. ScienceDirect+2ScienceDirectHyperviscosity Syndrome - an overview | ScienceDirect Topics Wolters KluwerPrimary CNS Lymphoma and Neurologic Complications of ...PubMedMultiple Myeloma - StatPearls - NCBI Bookshelf
Give crystalloid promptly if dehydration is present or suspected because dehydration worsens hyperviscosity. acepacepHyperviscosity Syndrome | Critical Care Medicine Section
Do not defer therapy for a high IgM or serum viscosity value in an otherwise asymptomatic patient; hyperviscosity syndrome is the clinical manifestation of increased viscosity, and symptom correlation is imperfect. BMJ+2BMJHyperviscosity Syndrome WileyManagement of macroglobulinaemia ScienceDirectHyperviscosity Syndrome - an overview | ScienceDirect Topics

Syndrome features that should trigger urgent serum viscosity testing and apheresis planning. JAMA+3JAMASerum Hyperviscosity Syndrome ScienceDirectHyperviscosity Syndrome - an overview | ScienceDirect Topics ScienceDirectThe use of emergency apheresis in the management of plasma cell disorders PubMedMultiple Myeloma - StatPearls - NCBI Bookshelf
Organ system	Actionable findings	Immediate implication
Eye	Blurred vision, visual loss, retinal hemorrhage, venous congestion, papilledema JAMA+2JAMASerum Hyperviscosity Syndrome ScienceDirectHyperviscosity Syndrome - an overview \| ScienceDirect Topics ScienceDirectThe use of emergency apheresis in the management of plasma cell disorders	Urgent fundus examination; organize plasma exchange when findings are compatible with symptomatic hyperviscosity. ScienceDirectScienceDirectThe use of emergency apheresis in the management of plasma cell disorders
Neurologic	Headache, vertigo, ataxia, diplopia, confusion, seizure, somnolence, coma ScienceDirect+1ScienceDirectHyperviscosity Syndrome - an overview \| ScienceDirect Topics PubMedMultiple Myeloma - StatPearls - NCBI Bookshelf	Treat as a microcirculatory emergency while assessing alternate neurologic diagnoses. ScienceDirect+2ScienceDirectHyperviscosity Syndrome - an overview \| ScienceDirect Topics Wolters KluwerPrimary CNS Lymphoma and Neurologic Complications of ...PubMedMultiple Myeloma - StatPearls - NCBI Bookshelf
Bleeding	Epistaxis or other mucous-membrane bleeding JAMA+1JAMASerum Hyperviscosity Syndrome PubMedMultiple Myeloma - StatPearls - NCBI Bookshelf	Assess for paraproteinemia and urgent plasma exchange indication. JAMA+1JAMASerum Hyperviscosity Syndrome ScienceDirectThe use of emergency apheresis in the management of plasma cell disorders
Cardiopulmonary	Dyspnea or heart failure ScienceDirect+1ScienceDirectHyperviscosity Syndrome - an overview \| ScienceDirect Topics PubMedMultiple Myeloma - StatPearls - NCBI Bookshelf	Assess volume status and end-organ compromise; avoid worsening dehydration while arranging definitive therapy. acep+1acepHyperviscosity Syndrome \| Critical Care Medicine Section PubMedMultiple Myeloma - StatPearls - NCBI Bookshelf

Etiologic branching

Identify whether viscosity is driven by paraprotein, cells, or cryoprotein

The cause determines the apheresis target and definitive treatment pathway.

For suspected serum hyperviscosity, send serum viscosity, serum protein studies to identify a monoclonal immunoglobulin, complete blood count, and basic organ assessment while arranging treatment for symptomatic patients. Markedly elevated Westergren erythrocyte sedimentation rate and increased serum immunoglobulins are supportive clues, but neither substitutes for serum viscosity or clinical assessment. BMJ+1BMJHyperviscosity Syndrome NeurologyHyperviscosity‐induced dementia

Waldenstrom macroglobulinemia is the most frequent plasma-cell-dyscrasia context for symptomatic hyperviscosity because IgM overproduction promotes erythrocyte aggregation and impaired microvascular flow. Hyperviscosity occurs more often in Waldenstrom macroglobulinemia, reported at 10% to 30%, than in IgG- or IgA-associated myeloma, reported at 2% to 6%. ScienceDirect+2ScienceDirectHyperviscosity Syndrome - an overview | ScienceDirect Topics ScienceDirectThe use of emergency apheresis in the management of plasma cell disorders acepHyperviscosity Syndrome | Critical Care Medicine Section

Multiple myeloma remains an important alternative when a monoclonal protein accompanies anemia, marrow failure, kidney injury, or bone disease. Hyperviscosity is uncommon in myeloma but can cause epistaxis, blurred vision, retinal hemorrhage, neurologic symptoms, dyspnea, and heart failure; treat symptomatic cases as an emergency with immediate plasmapheresis. Nature+1NatureRheological properties of blood in multiple myeloma patients | Scientific Reports PubMedMultiple Myeloma - StatPearls - NCBI Bookshelf

When serum becomes visibly gel-like on cooling and reversibly liquefies with warming, consider cryoglobulinemia as the cause of hyperviscosity. In this branch, rapidly evolving life-threatening disease is an indication for plasmapheresis, while the underlying cryoglobulinemic process requires cause-directed management. The Lancet+1The LancetHyperviscosity syndrome caused by cryoglobulinemia ...ScienceDirectThe use of emergency apheresis in the management of plasma cell disorders

Do not conflate paraprotein hyperviscosity with leukostasis. Leukostasis is symptomatic hyperleukocytosis with neurologic and/or pulmonary manifestations; hyperleukocytosis is generally defined as a white blood cell count greater than 100,000 cells/μL. Whole-blood rather than serum viscosity is relevant when cellular burden is suspected, and acute leukemia requires immediate cytoreductive management. ScienceDirect+2ScienceDirectLeukostasis - an overview | ScienceDirect Topics ScienceDirectRapid Fire: Acute Blast Crisis/Hyperviscosity Syndrome NeurologyHyperviscosity‐induced dementia

In a patient with suspected Waldenstrom macroglobulinemia, obtain serum viscosity even if the IgM concentration appears only moderately elevated when visual or neurologic symptoms are present. JAMA+1JAMAHyperviscosity-Related Retinopathy in Waldenström ...NatureWaldenstrom macroglobulinemia: prognosis and ...
In suspected leukostasis, prioritize white blood cell count, blast evaluation, pulmonary and neurologic assessment, and immediate hematology-directed cytoreduction rather than plasma exchange as the primary intervention. ScienceDirect+1ScienceDirectLeukostasis - an overview | ScienceDirect Topics ScienceDirectRapid Fire: Acute Blast Crisis/Hyperviscosity Syndrome
A patient with hyperviscosity symptoms and an atypical neurologic presentation in an IgM-associated malignancy may have a CNS complication such as Bing-Neel syndrome; do not attribute persistent neurologic findings solely to viscosity after plasma exchange. ScienceDirectScienceDirectHyperviscosity Syndrome - an overview | ScienceDirect Topics

Etiologic patterns that redirect emergency management. The Lancet+5The LancetHyperviscosity syndrome caused by cryoglobulinemia ...ScienceDirectHyperviscosity Syndrome - an overview | ScienceDirect Topics ScienceDirectLeukostasis - an overview | ScienceDirect Topics ScienceDirectThe use of emergency apheresis in the management of plasma cell disorders ScienceDirectRapid Fire: Acute Blast Crisis/Hyperviscosity Syndrome acepHyperviscosity Syndrome | Critical Care Medicine Section
Pattern	Discriminators	Immediate management priority	Definitive direction
Waldenstrom macroglobulinemia	IgM-associated paraproteinemia with retinal, bleeding, or neurologic syndrome; most common paraprotein-associated setting ScienceDirect+1ScienceDirectHyperviscosity Syndrome - an overview \| ScienceDirect Topics acepHyperviscosity Syndrome \| Critical Care Medicine Section	Therapeutic plasma exchange for symptomatic hyperviscosity ScienceDirect+1ScienceDirectThe use of emergency apheresis in the management of plasma cell disorders acepHyperviscosity Syndrome \| Critical Care Medicine Section	Concurrent hematology-directed cytoreductive therapy to prevent recurrence ScienceDirect+1ScienceDirectThe use of emergency apheresis in the management of plasma cell disorders acepHyperviscosity Syndrome \| Critical Care Medicine Section
IgG or IgA myeloma	Monoclonal protein with myeloma features; symptomatic hyperviscosity is less frequent than in Waldenstrom macroglobulinemia Nature+1NatureRheological properties of blood in multiple myeloma patients \| Scientific Reports ScienceDirectHyperviscosity Syndrome - an overview \| ScienceDirect Topics	Immediate plasmapheresis when symptomatic ScienceDirect+1ScienceDirectThe use of emergency apheresis in the management of plasma cell disorders PubMedMultiple Myeloma - StatPearls - NCBI Bookshelf	Myeloma-directed systemic therapy ScienceDirect+1ScienceDirectThe use of emergency apheresis in the management of plasma cell disorders PubMedMultiple Myeloma - StatPearls - NCBI Bookshelf
Cryoglobulinemia	Reversible serum gel formation with cooling and warming The LancetThe LancetHyperviscosity syndrome caused by cryoglobulinemia ...	Plasmapheresis for rapidly evolving life-threatening disease ScienceDirectScienceDirectThe use of emergency apheresis in the management of plasma cell disorders	Treat the causative cryoglobulinemic disorder ScienceDirectScienceDirectThe use of emergency apheresis in the management of plasma cell disorders
Leukostasis	Symptomatic hyperleukocytosis, often with neurologic and pulmonary manifestations; white blood cell count generally greater than 100,000 cells/μL ScienceDirect+1ScienceDirectLeukostasis - an overview \| ScienceDirect Topics ScienceDirectRapid Fire: Acute Blast Crisis/Hyperviscosity Syndrome	Isotonic fluids, emergency cytoreduction, tumor-lysis monitoring; limit red-cell transfusion unless symptomatic anemia requires it ScienceDirectScienceDirectLeukostasis - an overview \| ScienceDirect Topics	Acute leukemia-directed therapy ScienceDirect+1ScienceDirectLeukostasis - an overview \| ScienceDirect Topics ScienceDirectRapid Fire: Acute Blast Crisis/Hyperviscosity Syndrome

Acute treatment

Start plasma exchange promptly for symptomatic paraprotein hyperviscosity

Therapeutic plasma exchange is a bridge to clone-directed therapy, not definitive cancer control.

Initiate therapeutic plasma exchange as soon as possible for symptomatic paraprotein-mediated hyperviscosity. It rapidly lowers circulating paraprotein and can relieve clinical manifestations, including retinal microcirculatory compromise; early exchange may reduce blindness from retinal hemorrhage or retinal detachment. ScienceDirect+1ScienceDirectThe use of emergency apheresis in the management of plasma cell disorders acepHyperviscosity Syndrome | Critical Care Medicine Section

Use albumin replacement in routine exchanges: 4% to 5% human albumin in physiologic saline is commonly used. Consider fresh frozen plasma when a coagulation abnormality requires factor replacement. ScienceDirectScienceDirectThe use of emergency apheresis in the management of plasma cell disorders

Repeat exchange based on persistent symptoms, retinal findings, and paraprotein burden rather than a single postprocedure number. In IgM-associated hyperviscosity, one to three daily procedures generally abate acute symptoms; IgG-associated hyperviscosity may require more procedures because removal is less efficient. ScienceDirectScienceDirectThe use of emergency apheresis in the management of plasma cell disorders

Document response clinically after each procedure, with repeat retinal examination when ocular findings were present. Serum paraprotein measurement provides an objective adjunct, but acute treatment should be continued until the clinical syndrome abates. ScienceDirectScienceDirectThe use of emergency apheresis in the management of plasma cell disorders

Do not use plasma exchange as sole treatment: it does not eradicate the underlying malignancy and recurrence is expected without cytoreduction. ScienceDirect+1ScienceDirectThe use of emergency apheresis in the management of plasma cell disorders acepHyperviscosity Syndrome | Critical Care Medicine Section
For active symptomatic hyperviscosity, begin disease-specific systemic treatment concurrently with plasma exchange under hematology direction. ScienceDirect+1ScienceDirectThe use of emergency apheresis in the management of plasma cell disorders acepHyperviscosity Syndrome | Critical Care Medicine Section
In myeloma, bortezomib and carfilzomib are cited as agents that can rapidly reduce viscosity; in the appropriate hematologic context, ibrutinib is also cited as a rapidly acting cytoreductive option. Regimen selection depends on the underlying disease and hematology assessment. acepacepHyperviscosity Syndrome | Critical Care Medicine Section

Procedure-focused monitoring for paraprotein-mediated symptomatic hyperviscosity. ScienceDirect+1ScienceDirectThe use of emergency apheresis in the management of plasma cell disorders acepHyperviscosity Syndrome | Critical Care Medicine Section
Time point	Assess	Action
Before first exchange	Bleeding, visual, neurologic, pulmonary, and heart-failure manifestations; serum viscosity and paraprotein burden when this does not delay treatment ScienceDirect+1ScienceDirectThe use of emergency apheresis in the management of plasma cell disorders acepHyperviscosity Syndrome \| Critical Care Medicine Section	Arrange urgent therapeutic plasma exchange and start concurrent hematology-directed therapy. ScienceDirect+1ScienceDirectThe use of emergency apheresis in the management of plasma cell disorders acepHyperviscosity Syndrome \| Critical Care Medicine Section
After each exchange	Symptoms, funduscopic findings when initially abnormal, and paraprotein level as an objective adjunct ScienceDirectScienceDirectThe use of emergency apheresis in the management of plasma cell disorders	Continue daily exchange if acute manifestations persist. ScienceDirectScienceDirectThe use of emergency apheresis in the management of plasma cell disorders
After symptom control	Evidence of recurrent visual, neurologic, or mucosal bleeding symptoms JAMA+1JAMASerum Hyperviscosity Syndrome ScienceDirectThe use of emergency apheresis in the management of plasma cell disorders	Maintain disease-directed therapy because plasma exchange alone does not prevent recurrence. ScienceDirect+1ScienceDirectThe use of emergency apheresis in the management of plasma cell disorders acepHyperviscosity Syndrome \| Critical Care Medicine Section

Avoid preventable worsening

Support microvascular perfusion while avoiding diagnosis-specific errors

Supportive interventions differ materially between paraprotein hyperviscosity and leukostasis.

Correct dehydration with crystalloid in suspected hyperviscosity because volume depletion increases viscosity and can worsen end-organ hypoperfusion. Monitor cardiopulmonary status closely in patients with dyspnea or heart failure manifestations, where fluid administration requires individualized balance. ScienceDirect+2ScienceDirectHyperviscosity Syndrome - an overview | ScienceDirect Topics acepHyperviscosity Syndrome | Critical Care Medicine Section PubMedMultiple Myeloma - StatPearls - NCBI Bookshelf

For leukostasis or marked hyperleukocytosis, use isotonic fluid resuscitation to reduce viscosity and maintain urine output while initiating emergency cytoreduction and tumor-lysis monitoring. Avoid diuretics unless clinically important volume overload is present. ScienceDirectScienceDirectLeukostasis - an overview | ScienceDirect Topics

Avoid routine red-cell transfusion before leukocyte reduction in hyperleukocytosis because increasing hematocrit can increase blood viscosity and worsen leukostasis; reserve transfusion for symptomatic anemia. This caution is specific to the cellular hyperviscosity branch and should not delay treatment of clinically significant anemia when necessary. ScienceDirectScienceDirectLeukostasis - an overview | ScienceDirect Topics

Reassess neurologic deficits after viscosity reduction; persistent or focal findings require evaluation for competing CNS pathology, including CNS complications of IgM-associated disease. ScienceDirect+1ScienceDirectHyperviscosity Syndrome - an overview | ScienceDirect Topics Wolters KluwerPrimary CNS Lymphoma and Neurologic Complications of ...
Use both serum and whole-blood viscosity determinations when hyperviscosity-associated cognitive decline is suspected and the contribution of cellular versus serum factors is uncertain. NeurologyNeurologyHyperviscosity‐induced dementia
Do not use absence of a universal serum viscosity threshold to reassure a symptomatic patient; comorbid disease, including diabetic retinopathy, can lower the threshold for clinical manifestations. BMJBMJHyperviscosity Syndrome

Management distinctions that prevent treating the wrong viscosity syndrome. ScienceDirect+2ScienceDirectLeukostasis - an overview | ScienceDirect Topics ScienceDirectThe use of emergency apheresis in the management of plasma cell disorders acepHyperviscosity Syndrome | Critical Care Medicine Section
Decision	Paraprotein hyperviscosity	Leukostasis/hyperleukocytosis
Primary emergency intervention	Therapeutic plasma exchange to remove circulating paraprotein ScienceDirect+1ScienceDirectThe use of emergency apheresis in the management of plasma cell disorders acepHyperviscosity Syndrome \| Critical Care Medicine Section	Prompt cytoreductive chemotherapy; leukapheresis has an uncertain role in preventing complications or induction death in pediatric evidence summarized in review literature. ScienceDirectScienceDirectLeukostasis - an overview \| ScienceDirect Topics
Fluid strategy	Prompt crystalloid when dehydration is suspected acepacepHyperviscosity Syndrome \| Critical Care Medicine Section	Isotonic fluids to reduce viscosity and maintain urine output ScienceDirectScienceDirectLeukostasis - an overview \| ScienceDirect Topics
Red-cell transfusion	Individualize to clinical need	Limit until white blood cell count is reduced unless symptomatic anemia requires transfusion. ScienceDirectScienceDirectLeukostasis - an overview \| ScienceDirect Topics
Recurrence prevention	Disease-specific systemic therapy concurrent with exchange ScienceDirect+1ScienceDirectThe use of emergency apheresis in the management of plasma cell disorders acepHyperviscosity Syndrome \| Critical Care Medicine Section	Definitive acute leukemia therapy and tumor-lysis prophylaxis/monitoring ScienceDirectScienceDirectLeukostasis - an overview \| ScienceDirect Topics

Common questions

Should plasma exchange wait for a serum viscosity result?

No. In a patient with a compatible symptomatic paraprotein-associated syndrome, initiate urgent plasma exchange planning and treatment without waiting for the result; serum viscosity supports diagnosis and monitoring, but symptom thresholds vary. BMJ+3BMJHyperviscosity Syndrome ScienceDirectThe use of emergency apheresis in the management of plasma cell disorders acepHyperviscosity Syndrome | Critical Care Medicine Section PubMedMultiple Myeloma - StatPearls - NCBI Bookshelf

How many plasma exchange procedures are usually required?

For IgM-associated hyperviscosity, one to three daily procedures generally relieve acute symptoms. IgG-associated disease may require more exchanges because immunoglobulin removal is less efficient; continue until acute manifestations abate. ScienceDirectScienceDirectThe use of emergency apheresis in the management of plasma cell disorders