Overview
Hyperviscosity Syndrome
Topic Overview
Summary
Hyperviscosity syndrome (HVS) is a clinical emergency caused by increased serum viscosity due to elevated paraproteins, most commonly IgM (Waldenström macroglobulinaemia). The classic triad is neurological symptoms (confusion, headache, stroke), visual disturbance (blurred vision, retinal haemorrhages), and bleeding (mucosal, spontaneous). Treatment is urgent plasmapheresis to reduce viscosity, followed by treatment of the underlying malignancy.
Key Facts
- Cause: High levels of paraprotein (usually IgM in Waldenström's; occasionally myeloma)
- Triad: Neurological symptoms + visual disturbance + bleeding
- Diagnosis: Serum viscosity over 4 cP (normal 1.4-1.8)
- Treatment: Urgent plasmapheresis + treatment of underlying disease
- IgM most viscous: HVS more common in Waldenström's than myeloma
Clinical Pearls
IgM is the largest immunoglobulin and most viscous — Waldenström's (IgM) causes HVS more often than IgA or IgG myeloma
Avoid transfusing RBCs before plasmapheresis if possible — increases viscosity further
Fundoscopy shows "sausage-link" or "box-car" retinal veins — pathognomonic
Why This Matters Clinically
HVS is a haematological emergency. Untreated, it causes stroke, retinal vein occlusion with blindness, and death. Prompt recognition and plasmapheresis are life-saving.
Visual Summary
Visual assets to be added:
- Fundoscopic image showing sausage-link veins
- Serum protein electrophoresis trace
- Plasmapheresis machine photograph
- HVS clinical algorithm
Epidemiology
Incidence
- Rare overall
- HVS occurs in:
- 10-30% of Waldenström macroglobulinaemia
- 2-5% of myeloma (usually IgA or IgG3)
- Rare in polycythaemia vera (cellular cause)
Demographics
- Reflects underlying disease (Waldenström's, myeloma)
- Peak age 60-70
- Slight male predominance
Causes
| Cause | Notes |
|---|---|
| Waldenström macroglobulinaemia | IgM paraprotein — most common cause |
| Multiple myeloma | IgA or IgG3 (less common) |
| Polycythaemia vera | Cellular hyperviscosity |
| Leukaemia (extreme hyperleukocytosis) | WCC over 100,000 |
| Cryoglobulinaemia | Cold-precipitable proteins |
Pathophysiology
Normal Viscosity
- Serum viscosity 1.4-1.8 cP (centipoise)
- Determined by plasma proteins, especially immunoglobulins
Why High Paraprotein Causes Hyperviscosity
- Paraproteins (especially IgM) increase viscosity exponentially
- Viscosity over 4 cP becomes symptomatic
- IgM is pentameric — much larger than IgG
Consequences of Hyperviscosity
- Reduced blood flow in microcirculation
- Tissue hypoxia: CNS, retina, mucosa
- Bleeding: Paraprotein coats platelets, impairs function
- Cardiac strain: Increased afterload
Sites Most Affected
- Brain: Confusion, stroke, coma
- Eyes: Blurred vision, retinal vein occlusion
- Mucosa: Epistaxis, gum bleeding
- Heart: Heart failure
Clinical Presentation
Classic Triad
| Feature | Frequency | Description |
|---|---|---|
| Neurological | 60-70% | Headache, confusion, dizziness, coma, stroke |
| Visual | 50-60% | Blurred vision, diplopia, vision loss |
| Bleeding | 40-50% | Epistaxis, gum bleeding, GI bleeding |
Other Features
Red Flags
| Finding | Significance |
|---|---|
| Acute confusion or stroke | CNS hyperviscosity — emergency |
| Sudden visual loss | Retinal vein occlusion |
| Spontaneous bleeding | Platelet dysfunction |
| Known Waldenström's/myeloma | High-risk population |
Dyspnoea (heart failure, anaemia)
Common presentation.
Fatigue
Common presentation.
Congestive heart failure
Common presentation.
Raynaud's phenomenon (if cryoglobulinaemia)
Common presentation.
Clinical Examination
Neurological
- Altered mental status
- Focal neurological signs (stroke)
- Papilloedema
Ophthalmic — Fundoscopy is Key
- Sausage-link or box-car veins: Dilated, segmented retinal veins
- Retinal haemorrhages
- Papilloedema
- Retinal vein occlusion
Bleeding
- Epistaxis, gum bleeding
- Purpura (platelet dysfunction)
Cardiovascular
- Signs of heart failure (elevated JVP, oedema, crackles)
Investigations
Blood Tests
| Test | Finding |
|---|---|
| Serum viscosity | Over 4 cP symptomatic; over 6 cP = severe |
| Serum protein electrophoresis (SPEP) | Monoclonal band (M-spike) |
| Immunofixation | Confirms paraprotein type (IgM, IgA, IgG) |
| FBC | Anaemia, may show rouleaux |
| Blood film | Rouleaux formation |
| U&E, LFTs | Baseline |
| Calcium | Elevated in myeloma |
Normal Values for Reference
- Normal serum viscosity: 1.4-1.8 cP
- Symptoms usually when over 4 cP
- Severe symptoms over 6 cP
Imaging
- CT/MRI head if neurological signs
- Echocardiogram if heart failure
Classification & Staging
By Underlying Cause
| Cause | Paraprotein | Notes |
|---|---|---|
| Waldenström macroglobulinaemia | IgM | Most common |
| Multiple myeloma | IgA or IgG | IgG3 subclass most viscous |
| Polycythaemia vera | — | Cellular hyperviscosity |
By Severity
| Viscosity | Severity | Symptoms |
|---|---|---|
| Under 4 cP | Asymptomatic | None |
| 4-5 cP | Mild | Headache, fatigue |
| 5-6 cP | Moderate | Visual, neurological |
| Over 6 cP | Severe | Coma, stroke, major bleeding |
Management
Emergency Treatment — Plasmapheresis
| Aspect | Details |
|---|---|
| Mechanism | Removes paraprotein, rapidly reduces viscosity |
| Indication | Symptomatic HVS (neurological, visual, bleeding) |
| Effect | Single session reduces viscosity by 30-50% |
| Frequency | Daily until symptoms resolve |
Before Plasmapheresis
- Avoid RBC transfusion if possible (worsens viscosity)
- If transfusion essential, give slowly after starting plasmapheresis
- IV fluids for hydration
Supportive Care
- Analgesia for headache
- Treat heart failure if present
- Avoid dehydration
Definitive Treatment — Treat Underlying Disease
| Disease | Treatment |
|---|---|
| Waldenström's | Rituximab + chemotherapy ± ibrutinib |
| Myeloma | Chemotherapy, proteasome inhibitors, ASCT |
| Polycythaemia vera | Venesection, hydroxycarbamide |
Monitoring
- Serial viscosity measurements
- Repeat fundoscopy
- Monitor for neurological improvement
Complications
Of Hyperviscosity
- Stroke
- Retinal vein occlusion (permanent vision loss)
- Myocardial infarction
- Coma
- Death
Of Plasmapheresis
- Hypotension
- Hypocalcaemia (citrate anticoagulant)
- Bleeding (factor depletion)
- Infection (catheter-related)
Prognosis & Outcomes
Acute HVS
- Excellent response to plasmapheresis
- Rapid symptom improvement if treated early
- Delay leads to permanent sequelae (blindness, neurological impairment)
Long-Term
- Depends on underlying disease
- Waldenström's: Often indolent; median survival 5-8 years
- Myeloma: Variable; depends on stage and response to treatment
Evidence & Guidelines
Key Guidelines
- No specific HVS guideline
- Management based on case series and expert consensus
Key Evidence
- Plasmapheresis rapidly reduces viscosity and symptoms
- RBC transfusion before plasmapheresis worsens outcomes
- Rituximab-based regimens are standard for Waldenström's
Patient & Family Information
What is Hyperviscosity Syndrome?
Hyperviscosity syndrome happens when blood becomes too thick because of abnormal proteins. This can affect blood flow to the brain, eyes, and other organs.
Causes
- Usually caused by a blood cancer such as Waldenström macroglobulinaemia or myeloma
Symptoms
- Headache, confusion, dizziness
- Blurred or double vision
- Bleeding (nosebleeds, gum bleeding)
- Shortness of breath
Treatment
- Plasmapheresis — a procedure to "clean" the blood and remove the abnormal proteins
- Treatment for the underlying blood cancer
What Happens Next?
- Symptoms usually improve quickly after plasmapheresis
- You will need treatment for the underlying condition
Resources
References
Key Studies
- Gertz MA. Acute hyperviscosity: syndromes and management. Blood. 2018;132(13):1379-1385. PMID: 30104220
- Stone MJ, Bogen SA. Evidence-based focused review of management of hyperviscosity syndrome. Blood. 2012;119(10):2205-2208. PMID: 22223821
Reviews
- Dimopoulos MA, et al. Treatment recommendations for patients with Waldenström macroglobulinemia (WM) and related disorders: IWWM-7 consensus. Blood. 2014;124(9):1404-1411. PMID: 25000216