Waldenström Macroglobulinemia and Hyperviscosity-Related Retinopathy

Waldenström Macroglobulinemia (WM) is a rare cancer of B-cells (a type of white blood cell). These cancer cells live mainly in the bone marrow and make a very large amount of one antibody called IgM. IgM is a big, heavy protein. When too much IgM is floating in the blood, the blood gets thick and slow. Doctors call this hyperviscosity. Thick blood does not flow well through tiny blood vessels, especially in the eyes, brain, and mucous membranes. That poor flow causes many symptoms like blurred vision, headaches, confusion, nosebleeds, and tiredness from anemia. WM is also called lymphoplasmacytic lymphoma when doctors look at it under the microscope. Many patients have specific gene changes in their cancer cells, most often MYD88 L265P and sometimes CXCR4 mutations; these changes help the cancer grow and can influence symptoms and treatment response. PMC

Hyperviscosity-related retinopathy means damage in the retina (the light-sensing layer at the back of the eye) caused by thick, slow-moving blood. Classic eye findings include dilated and tortuous (twisty) retinal veins, “sausage-link” segmentation of the veins, dot-blot or flame-shaped hemorrhages, cotton-wool spots, and sometimes optic disc swelling. Vision may blur because the macula (the center of the retina) gets swollen or because bleeding blocks the visual axis. If hyperviscosity is severe or lasts too long, it can even lead to a vein occlusion (a clot in a retinal vein). These retinal changes are important “red flags” because they can be the first sign of WM or other blood disorders that thicken the blood. ACEPAmerican Academy of OphthalmologyJAMA Network

• Too much IgM: IgM is large and sticky. When the WM tumor makes a lot of it, the blood’s thickness (measured as “serum viscosity”) rises. High viscosity slows flow through small vessels in the retina, creating back-pressure in veins, small leaks (hemorrhages), and less oxygen reaching the tissue. JAMA NetworkPMC

• Rouleaux formation: Red cells can stack like coins (called “rouleaux”), which further slows micro-circulation. This is often seen on a blood smear. PMC

• Gene mutations: Patients with CXCR4 mutations often have higher IgM levels and more symptoms like hyperviscosity; MYD88 helps drive the disease. These biology details explain why some people develop eye symptoms at lower or higher IgM levels. PMC

• Treatment effects: An “IgM flare” (a temporary rise in IgM) can happen after starting rituximab; this can worsen hyperviscosity early in therapy and sometimes triggers urgent plasmapheresis to thin the blood. PubMedAsh PublicationsWaldenstrom’s Foundation

---

Types

1. By disease activity (WM spectrum)

• IgM MGUS (monoclonal gammopathy of undetermined significance): small IgM spike, no symptoms, no organ damage.

• Smoldering (asymptomatic) WM: higher tumor burden/IgM but no clear organ damage yet.

• Symptomatic WM: active disease causing problems like anemia, hyperviscosity, neuropathy, or organ enlargement that requires treatment. (Genetics often shows MYD88, and 30–40% have CXCR4 mutations.) PMC

2. By dominant clinical picture

• Hyperviscosity-dominant: vision changes, nose/gum bleeding, neurologic symptoms.

• Anemia-dominant: fatigue, shortness of breath, pallor.

• Neuropathy-dominant: numbness or tingling, often due to anti-MAG antibodies.

• Cryoglobulinemia/cold-agglutinin-dominant: color changes in fingers/toes with cold. PMC

3. By retinal severity (eye-focused)

• Mild hyperviscosity retinopathy: venous dilation and mild hemorrhages, normal or slightly blurred vision.

• Moderate: tortuous “sausage-link” veins, scattered hemorrhages, cotton-wool spots, possible macular edema and disc swelling, more vision blur.

• Severe: disc edema, widespread hemorrhages, possible serous macular detachment or retinal vein occlusion; vision is significantly impaired and needs urgent blood-thinning by plasmapheresis plus WM treatment. ACEPThe Journal of Medical Optometry (JoMO)

---

Causes

Each item explains the “cause” in plain words; some are direct disease causes, others are triggers that worsen viscosity and tip a borderline patient into eye symptoms.

1. High monoclonal IgM from WM — main driver of thick, slow blood. PMC

2. Very high serum viscosity — once viscosity passes a critical level, retinal veins congest and leak. (In WM, eye findings may occur at “lower-than-expected” viscosity or IgM, so symptoms matter more than any single number.) JAMA Network

3. Rituximab-related IgM flare — early rise in IgM after first doses can acutely worsen hyperviscosity. PubMedAsh Publications

4. CXCR4 mutation — often linked to higher IgM and symptomatic disease, increasing risk of hyperviscosity. PMC

5. Concurrent anemia — paradoxically lowers blood oxygen delivery and may coexist with hyperviscosity; anemia-related retinopathy can add hemorrhages on top of viscous flow problems. Review of Optometry

6. Dehydration — less plasma volume makes proteins “more concentrated,” thickening blood further (a frequent real-world trigger).

7. Cold exposure with cryoglobulins — IgM can precipitate in the cold (cryoglobulins), making small-vessel flow worse in eyes and extremities.

8. Renal impairment — fluid shifts and uremic platelet dysfunction can worsen bleeding risk in the retina when viscosity is high.

9. Infections/inflammation — can transiently raise immunoglobulins and tip a borderline patient into symptoms.

10. Polycythemia/high hematocrit — more red cells = thicker blood; if it coexists, retinal congestion worsens.

11. Leukocytosis (very high white cells) — increases whole-blood viscosity and can mimic or add to hyperviscosity signs.

12. Hyperlipidemia (very high triglycerides) — increases serum thickness; may also create lipemia retinalis-like appearance that confuses the picture.

13. Large blood transfusion — briefly increases hematocrit/viscosity in a symptomatic WM patient.

14. High serum fibrinogen/acute-phase proteins — add to plasma thickness during inflammation.

15. Smoking — raises hematocrit and impairs microvascular flow, lowering the threshold for symptoms.

16. Poor room lighting or night driving — not a biological cause, but early retinal ischemia makes low-contrast vision harder and exposes symptoms sooner.

17. Hypertension — stresses retinal vessels; combined with sluggish flow, it increases hemorrhage risk.

18. Diabetes — fragile retinal microvessels bleed more easily when venous pressure rises from viscosity.

19. Stopping plasmapheresis too early — allows IgM to rebound and viscosity to rise again.

20. Progression from MGUS/smoldering WM to symptomatic WM — as the clone expands, IgM rises and eye problems appear. PMC

---

Symptoms

(These include whole-body and eye symptoms that commonly cluster in hyperviscosity; bold terms are the simple keywords.)

1. Blurred vision — often fluctuates, worse with reading or at night; caused by swollen veins, small retinal bleeds, or macular edema. ACEPAmerican Academy of Ophthalmology

2. “Dark spots” or floaters — from small retinal or vitreous hemorrhages. PMC

3. Double vision — from impaired retinal function or neurologic effects of thick blood. EyeWiki

4. Headache — brain blood flow is sluggish; pressure-type headache is common. EyeWiki

5. Dizziness/vertigo — reduced cerebral perfusion. EyeWiki

6. Confusion or slowed thinking — especially when viscosity is very high; improves rapidly after plasmapheresis. ACEP

7. Nosebleeds or gum bleeding — mucosal tissues bleed easily when venous pressure is high and platelets are “coated” by IgM. EyeWiki

8. Tinnitus/hearing difficulty — tiny vessels in the ear are sensitive to sluggish flow. EyeWiki

9. Numbness/tingling in feet or hands — WM can make antibodies (often anti-MAG) that injure nerves; sensory symptoms are common. PMC

10. Fatigue — usually from anemia or from the disease itself. PMC

11. Shortness of breath on exertion — anemia plus thick blood reduces oxygen delivery.

12. Weight loss/night sweats — “B-symptoms” sometimes seen with active WM.

13. Cold-induced color change in fingers/toes — cryoglobulins/cold agglutinins can cause acrocyanosis or Raynaud-like symptoms.

14. Swollen lymph nodes or a feeling of fullness under the left ribs — lymphadenopathy or spleen enlargement from WM.

15. Eye strain and difficulty reading — subtle early sign when macular perfusion is borderline.

(When these appear together—visual changes + neurologic changes + mucosal bleeding—doctors strongly suspect hyperviscosity.) ACEP

---

Diagnostic tests

A) Physical Exam

1. General inspection for mucosal bleeding and skin spots
   What it is: Doctor looks for nosebleeds, gum bleeding, and small red or purple spots (petechiae).
   Why it matters: These are classic signs of hyperviscosity and platelet dysfunction from IgM coating platelets. EyeWiki

2. Lymph node, liver, and spleen check
   What it is: Palpation of neck, armpit, groin nodes; feeling for liver/spleen size.
   Why it matters: WM often causes lymphadenopathy and organ enlargement; it supports the diagnosis and the need for therapy. PMC

3. Neurologic screen
   What it is: Quick checks of balance (ataxia), eye movements (nystagmus), reflexes, and sensation.
   Why it matters: Thick blood and IgM-related nerve injury can cause neurologic symptoms that guide urgency. EyeWiki

4. Bedside dilated ophthalmoscopy
   What it is: Looking directly at the retina through a dilated pupil.
   What to see: Dilated, tortuous veins with “sausage-link” segmentation, hemorrhages, cotton-wool spots, and sometimes optic disc swelling.
   Why it matters: These are hallmark signs of hyperviscosity retinopathy and often trigger urgent action. ACEPAmerican Academy of Ophthalmology

B) Manual (bedside/office) Tests

5. Visual acuity (Snellen chart)
   Why it matters: Tracks how much the macula is affected by edema or hemorrhage.

6. Color vision (Ishihara plates)
   Why it matters: Subtle macular dysfunction can reduce color discrimination even when letters are still readable.

7. Confrontation visual fields
   Why it matters: Screens for field defects from macular involvement or optic nerve issues due to poor perfusion.

8. Pupillary light reflex and RAPD (swinging flashlight test)
   Why it matters: An afferent pupillary defect suggests asymmetric retinal or optic nerve dysfunction, which can occur with severe or uneven retinopathy.

C) Lab & Pathology

9. Complete blood count (CBC) with differential
   What it checks: Hemoglobin for anemia; white cell and platelet counts.
   Why it matters: Anemia is common; low platelets and high WBCs change bleeding risk and viscosity. Review of Optometry

10. Peripheral blood smear
    What it checks: Shape and stacking of red cells; rouleaux (coin-stacking) from high proteins.
    Why it matters: Supports the presence of a paraprotein and thick serum. PMC

11. Serum viscosity
    What it checks: The “thickness” of serum in centipoise (cP).
    Why it matters: Confirms hyperviscosity; note that eye symptoms can occur at lower numbers than expected, so treat the patient, not just the number. JAMA Network

12. Quantitative immunoglobulins (IgM, IgG, IgA)
    What it checks: Exact IgM level and the pattern of other antibodies.
    Why it matters: WM shows high IgM; level trends help assess risk and response. PMC

13. Serum protein electrophoresis (SPEP) and immunofixation (IFE)
    What it checks: The monoclonal “M-spike” and confirms it is IgM.
    Why it matters: These are core tests to document a monoclonal protein. PMC

14. Bone marrow aspirate/biopsy with flow cytometry and morphology
    What it checks: The WM tumor cells (lymphoplasmacytic lymphoma), their markers, and how much of the marrow they occupy.
    Why it matters: Establishes the tissue diagnosis of WM. PMC

15. Molecular testing for MYD88 L265P and CXCR4
    What it checks: Common driver mutations in WM.
    Why it matters: Helps confirm diagnosis; CXCR4 mutations are linked to higher IgM and more symptoms (including hyperviscosity) and may influence therapy choice. PMC

D) Electrodiagnostic

16. Visual Evoked Potentials (VEP)
    What it checks: Electrical signals from the visual pathway after a light pattern.
    Why it matters: If optic nerve function is reduced (e.g., from severe edema or ischemia), VEP latency/amplitude may be abnormal, supporting visual pathway involvement.

17. Nerve conduction studies (± EMG)
    What it checks: Speed and strength of electrical signals in peripheral nerves.
    Why it matters: Helps document WM-related neuropathy (often anti-MAG), which can coexist with eye problems and influences overall management. PMC

E) Imaging Tests

18. Color fundus photography
    What it shows: Clear pictures of dilated, segmented (“sausage-link”) veins, hemorrhages, cotton-wool spots, and disc swelling.
    Why it matters: Baseline documentation and follow-up comparison after plasmapheresis or WM therapy. ACEPPubMed

19. Optical Coherence Tomography (OCT ± OCT-Angiography)
    What it shows: Cross-section of the retina for macular edema or serous macular detachment; OCT-A maps blood flow without dye.
    Why it matters: Explains blurred vision and tracks recovery as viscosity falls. The Journal of Medical Optometry (JoMO)PubMed

20. Fluorescein angiography (FA)
    What it shows: Dye highlights retinal circulation, showing delayed venous filling, leakage, and areas of capillary non-perfusion.
    Why it matters: Distinguishes hyperviscosity damage from other vascular retinopathies and guides urgency. PubMedScienceDirect

Non-pharmacological Treatments (therapies and others)

Goal: stabilize vision, reduce symptoms, prevent complications, and support whole-body health alongside medical treatment.

1. Urgent plasmapheresis (therapeutic plasma exchange).
   Purpose: Rapidly lowers circulating IgM and blood thickness.
   Mechanism: Removes plasma (which carries IgM) and replaces it with albumin/saline; usually 1–1.5 plasma volumes per session. Often repeated over 1–3 days until symptoms improve.

2. Head-elevated rest during acute eye symptoms.
   Purpose: Reduces venous pressure in the head/eyes.
   Mechanism: Gravity aids venous drainage to ease retinal congestion.

3. Aggressive oral hydration (unless your doctor limits fluids).
   Purpose: Lowers relative viscosity and supports kidney flow.
   Mechanism: Expands plasma volume so blood flows easier.

4. Avoid dehydration triggers (sauna, fever without fluids, vomiting/diarrhea).
   Purpose: Prevent sudden viscosity spikes.
   Mechanism: Conserves plasma water.

5. Strict cold protection if cryoglobulins are present.
   Purpose: Prevent cold-induced IgM precipitation and vessel plugging.
   Mechanism: Warm clothing, gloves, avoid cold drinks and cold exposure.

6. Manage blood pressure and diabetes carefully.
   Purpose: Protect fragile retinal vessels.
   Mechanism: Lowers risk of hemorrhage and leakage.

7. Fall-prevention and bleeding-risk safety at home.
   Purpose: Platelets may be low; minimize trauma.
   Mechanism: Non-slip mats, soft toothbrush, electric razor, protective gear when needed.

8. Eye-strain reduction (20-20-20 rule, adequate lighting).
   Purpose: Ease visual fatigue during recovery.
   Mechanism: Reduces accommodative stress and headaches.

9. Rapid infection control (report fever ≥38°C/100.4°F).
   Purpose: WM therapy can suppress immunity.
   Mechanism: Early testing and antibiotics/antivirals as prescribed.

10. Vaccinations (inactivated only; timed away from rituximab).
    Purpose: Prevent severe infections (influenza, pneumococcus, COVID-19).
    Mechanism: Prime immune system; schedule ≥2–4 weeks before anti-CD20 or ≥6 months after last dose for best response (doctor will time it).

11. Nutritional support with protein and micronutrients.
    Purpose: Support marrow, wound healing, and fatigue.
    Mechanism: Adequate calories, protein 1–1.2 g/kg/day unless restricted.

12. Gentle aerobic activity (as tolerated).
    Purpose: Improves circulation and reduces thrombosis risk.
    Mechanism: Muscle pump aids venous return; start with short walks.

13. Compression stockings for dependent leg swelling (if no arterial disease).
    Purpose: Reduce venous stasis and clot risk.
    Mechanism: External pressure aids venous flow.

14. Neuropathy protection.
    Purpose: Some WM treatments and IgM paraprotein cause neuropathy.
    Mechanism: Foot care, wide shoes, check feet daily, physio referral.

15. Fatigue and sleep management.
    Purpose: Improve quality of life.
    Mechanism: Sleep hygiene, short daytime rests, pacing.

16. Psychological support / counseling.
    Purpose: Ease anxiety/depression, improve adherence.
    Mechanism: CBT, support groups, social work.

17. Medication review for bleeding interactions.
    Purpose: Reduce retinal/other bleeding.
    Mechanism: Discuss stopping non-essential NSAIDs, high-dose fish oil, ginkgo, turmeric if you’re on BTK inhibitors or have low platelets.

18. Thermal eyewear / eye protection in wind/cold.
    Purpose: Comfort and reduce exacerbations with cryoglobulinemia.
    Mechanism: Keeps periocular tissues warm.

19. Regular ophthalmology follow-up with OCT and fundus photos.
    Purpose: Track hemorrhage resolution and macular edema.
    Mechanism: Objective imaging guides timing of intravitreal therapy if needed.

20. Early travel/altitude planning.
    Purpose: Avoid hypoxia or dehydration that worsens viscosity.
    Mechanism: Hydrate, avoid extreme altitudes until IgM controlled.

---

Drug Treatments

Important: Some drugs can increase bleeding, interact with other medicines, or affect nerves/heart rhythm. Never start or adjust therapy without your oncologist.

1. Ibrutinib (BTK inhibitor).
   Dose/Time: 420 mg by mouth once daily; taken continuously.
   Purpose: First-line/relapsed WM; shrinks IgM-producing cells.
   Mechanism: Blocks Bruton’s tyrosine kinase → stops B-cell signaling and survival.
   Common side effects: Bruising/bleeding, atrial fibrillation, diarrhea, rash, hypertension, infections; drug–drug interactions via CYP3A4.

2. Zanubrutinib (BTK inhibitor).
   Dose/Time: 160 mg twice daily or 320 mg once daily; continuous.
   Purpose: Alternative BTK inhibitor; often better tolerated for some patients.
   Mechanism: Potent BTK blockade; reduces IgM levels.
   Side effects: Neutropenia, infections, bleeding, low rates of AF; CYP3A interactions.

3. Bendamustine + Rituximab (BR).
   Dose/Time: Bendamustine 90 mg/m² IV days 1–2 + rituximab 375 mg/m² day 1, every 28 days × 4–6 cycles.
   Purpose: Chemo-immunotherapy for symptomatic WM.
   Mechanism: Bendamustine damages DNA; rituximab targets CD20 on B-cells.
   Side effects: Low blood counts, infections, nausea, infusion reactions; vaccines work poorly around rituximab.

4. Dexamethasone + Rituximab + Cyclophosphamide (DRC).
   Dose/Time: Dexamethasone (e.g., 20 mg IV/PO day 1), rituximab 375 mg/m² day 1, cyclophosphamide 100 mg PO daily days 1–5; q21–28d × 6 cycles.
   Purpose: Non-neurotoxic regimen (helpful if neuropathy risk).
   Mechanism: Steroid + alkylator + anti-CD20 debulk IgM cells.
   Side effects: Immunosuppression, hyperglycemia, nausea, hair thinning.

5. Bortezomib ± Dexamethasone ± Rituximab (BDR).
   Dose/Time: Bortezomib 1.3 mg/m² subcut days 1, 8, 15 q28d (weekly SC to lower neuropathy risk) with rituximab/dexamethasone per protocol.
   Purpose: Effective for rapid IgM falls; avoid if significant neuropathy.
   Mechanism: Proteasome inhibition → B-cell apoptosis.
   Side effects: Neuropathy (less with SC/weekly), shingles (needs antiviral prophylaxis), low counts.

6. Acalabrutinib (BTK inhibitor; off-label in WM in some regions).
   Dose/Time: 100 mg twice daily.
   Purpose: Option when intolerance to other BTK inhibitors.
   Mechanism: BTK blockade.
   Side effects: Headache, cytopenias, bleeding, infections; CYP3A interactions.

7. Plerixafor (CXCR4 antagonist) for stem-cell mobilization or selected CXCR4-mut WM.
   Dose/Time: 0.24 mg/kg SC ~11 h before apheresis (mobilization); dosing schemes vary in trials for disease.
   Purpose: Helps collect stem cells; may aid in CXCR4-mut disease biology.
   Mechanism: Blocks CXCR4–SDF-1 axis, moving cells into blood.
   Side effects: GI upset, injection reactions, leukocytosis.

8. Prednisone or Dexamethasone (steroids) short courses.
   Dose/Time: Example: prednisone 0.5–1 mg/kg/day short term.
   Purpose: Temporize symptoms, shrink nodes, reduce IgM a little.
   Mechanism: Lympholysis and anti-inflammatory effects.
   Side effects: Mood changes, high sugar, infection risk, insomnia.

9. IVIG (intravenous immunoglobulin) for recurrent infections with low IgG.
   Dose/Time: 0.4 g/kg every 3–4 weeks.
   Purpose: Passive antibodies reduce serious infections.
   Mechanism: Replaces missing protective IgG.
   Side effects: Headache, thrombosis risk (hydrate), aseptic meningitis (rare).

10. Antiviral/antimicrobial prophylaxis when indicated (e.g., acyclovir with bortezomib; TMP-SMX if on prolonged steroids).
    Dose/Time: Acyclovir 400 mg PO BID; TMP-SMX DS 3x weekly or per protocol.
    Purpose: Prevent shingles/Pneumocystis during immunosuppression.
    Mechanism: Blocks viral replication; prevents opportunistic infection.
    Side effects: Nausea, kidney effects (acyclovir), allergy (sulfa).

Note on anticoagulants/antiplatelets: BTK inhibitors increase bleeding. Combining with aspirin, clopidogrel, warfarin, DOACs, NSAIDs, or high-dose omega-3 raises risk—must be coordinated by your doctor.

---

Dietary Molecular Supplements

These are supportive, not cancer cures. Avoid high-dose antioxidants around chemo days unless your doctor approves, and watch for bleeding or CYP3A interactions.

1. Vitamin D3: 1,000–2,000 IU daily (titrate to 25-OH D 30–50 ng/mL).
   Function/Mechanism: Bone and immune support; hormone-like effects on B/T cells.

2. Oral Magnesium: 200–400 mg elemental/day (glycinate or citrate).
   Function: Muscle/nerve function, may ease cramps from therapy; supports energy metabolism.

3. Omega-3 fatty acids (EPA/DHA): 500–1,000 mg/day total only if not on BTK inhibitors or other blood thinners.
   Function: Anti-inflammatory membrane effects; may modestly help triglycerides.
   Caution: Can increase bleeding—often avoided with ibrutinib/zanubrutinib.

4. Probiotics (Lactobacillus/Bifidobacterium blends): per label 1–10 billion CFU/day only if not severely immunosuppressed.
   Function: Gut barrier support; reduced antibiotic-associated diarrhea.

5. Whey protein or plant protein: 20–30 g/day.
   Function: Helps meet protein targets for recovery and immune protein production.

6. Vitamin B12 (if low): 1,000 mcg oral daily or monthly IM per labs.
   Function: DNA synthesis; supports red cell and nerve health.

7. Folate (if low): 400–800 mcg/day.
   Function: DNA synthesis; avoid mega-doses during certain chemo unless directed.

8. Zinc (short course if deficient): 15–25 mg/day for 2–3 months.
   Function: Innate/adaptive immunity; excess depletes copper—monitor.

9. Curcumin (turmeric extract): 500–1,000 mg/day avoid with blood thinners/BTK inhibitors.
   Function: NF-κB modulation; anti-inflammatory; many interactions—clear with clinician.

10. Coenzyme Q10: 100–200 mg/day.
    Function: Mitochondrial support; may help fatigue in some.

---

Regenerative / Stem-cell–related” Medical Therapies

Interpreted as clinically used immune-support and stem-cell–associated options—not over-the-counter “boosters”.

1. IVIG (as above)
   Dose: 0.4 g/kg every 3–4 weeks for recurrent serious infections with low IgG.
   Function/Mechanism: Provides ready-made antibodies; reduces infections.

2. Filgrastim (G-CSF)
   Dose: 5 µg/kg/day SC during neutropenia or for stem-cell mobilization.
   Function: Stimulates neutrophil production; shortens neutropenia.

3. Sargramostim (GM-CSF)
   Dose: 250 µg/m²/day SC/IV per protocol.
   Function: Broader myeloid stimulation; may be used post-chemo or transplant.

4. Plerixafor (CXCR4 antagonist) with G-CSF for stem-cell mobilization
   Dose: 0.24 mg/kg SC pre-apheresis.
   Function: Frees stem cells from marrow so they can be collected for autologous transplant.

5. Palifermin (keratinocyte growth factor) in transplant settings
   Dose: 60 µg/kg/day IV for 3 days before and after conditioning.
   Function: Reduces severe oral mucositis; supports tissue recovery.

6. Autologous Hematopoietic Stem Cell Transplant (ASCT)
   Process: Collect own stem cells (with G-CSF ± plerixafor) → high-dose therapy → reinfuse cells.
   Function: Deepens/extends remission in selected, fit patients with relapsed WM.
   Note: Not first-line; careful selection due to age/comorbidities.

---

Procedures/“Surgeries” Relevant to WM and Hyperviscosity Retinopathy

1. Therapeutic Plasma Exchange (plasmapheresis).
   Procedure: Central line; plasma removed and replaced with albumin/saline; 1–1.5 volumes.
   Why: Immediate viscosity reduction to protect brain/eyes/heart.

2. Implantable Port or Tunneled Central Venous Catheter.
   Procedure: Minor surgical insertion under local anesthesia.
   Why: Reliable access for chemo, plasmapheresis, labs.

3. Intravitreal anti-VEGF injection (selected cases with macular edema/neovascularization).
   Procedure: Small needle into the eye under antisepsis.
   Why: Reduce retinal leakage/edema if persistent after systemic control (decision by retina specialist).

4. Retinal laser photocoagulation (if ischemia/neovascularization occurs).
   Procedure: Outpatient laser spots to ischemic retina.
   Why: Prevent/reduce bleeding from fragile new vessels.

5. Pars plana vitrectomy (for non-clearing vitreous hemorrhage).
   Procedure: Microsurgery to remove blood-filled vitreous gel.
   Why: Restore vision when hemorrhage does not clear after systemic control.

---

Prevention Strategies

1. Early diagnosis and routine monitoring of IgM and viscosity to act before vision symptoms.

2. Hydration habit: carry a water bottle; extra fluids during heat/illness (unless restricted).

3. Avoid unnecessary blood thinners/NSAIDs; review all meds/supplements with your doctor.

4. Sick-day plan: if vomiting/diarrhea/fever, increase fluids and call clinic early.

5. Vaccination schedule (flu, COVID-19, pneumococcal) timed around rituximab/BTK inhibitor use.

6. Cold avoidance if cryoglobulinemia: keep whole body and drinks warm.

7. Infection prevention: hand hygiene, dental care, prompt treatment of skin infections.

8. Blood pressure, sugar, and cholesterol control to protect retinal and brain vessels.

9. Travel planning: avoid high altitude/extreme heat until IgM is stable; carry medical summary.

10. Regular eye checks: baseline retina exam; urgent recheck with any new visual change.

---

When to See a Doctor Now (same day/ER)

• Sudden blurred or dim vision, new floaters, curtain-like shadow, or severe eye pain.

• Headache, confusion, slurred speech, one-sided weakness, fainting.

• Nosebleeds, gum bleeding, or any bleeding that won’t stop.

• Chest pain, shortness of breath, leg swelling/redness (possible clot).

• Fever ≥38°C (100.4°F), shaking chills, burning urine, or productive cough.

• Severe dehydration (very dry mouth, dizziness, little urination).

• Rapid weight gain, new swelling, or sudden severe fatigue.

---

What to Eat and What to Avoid

1. Drink water regularly; soups and oral rehydration during illness—hydration lowers viscosity.

2. Balanced meals: lean proteins, whole grains, colorful vegetables/fruits, healthy fats (olive oil, nuts).

3. Protein target: generally 1–1.2 g/kg/day unless restricted—helps repair and immune proteins.

4. Iron caution: do not self-supplement iron unless your labs show deficiency.

5. Limit alcohol: raises bleeding risk and interacts with many drugs.

6. Avoid grapefruit/Seville orange with BTK inhibitors (CYP3A4 interactions).

7. Avoid “blood-thinning” herbs/supplements (ginkgo, garlic pills, ginseng, turmeric/curcumin, high-dose vitamin E, high-dose omega-3) if you are on BTK inhibitors or anticoagulants.

8. Food safety when counts are low: thoroughly wash/cook foods; avoid raw sushi, unpasteurized dairy.

9. Small, frequent meals if early satiety or nausea; include gentle fiber and probiotics (if allowed).

10. Sodium and sugar moderation for blood pressure/diabetes control (protects retina and heart).

---

Frequently Asked Questions

1. Is hyperviscosity a true emergency?
   Yes. Vision and brain complications can develop quickly. Plasmapheresis can relieve symptoms within hours while long-term WM therapy starts.

2. Will my vision return to normal?
   Often yes, if treated promptly. Retinal hemorrhages usually resolve over weeks; some patients have small permanent blind spots if bleeding was severe.

3. Can I just get rituximab alone?
   Rituximab works, but it can initially raise IgM (“flare”) and worsen viscosity. Doctors often combine it with other drugs or do plasmapheresis first.

4. Which first-line is “best”: BTK inhibitor or chemo-immunotherapy?
   Depends on age, comorbidities, neuropathy risk, preference for continuous pills (BTK) vs finite cycles (BR/DRC), and gene mutations (e.g., MYD88/CXCR4). Your oncologist balances efficacy, side effects, and goals.

5. Do BTK inhibitors thin my blood?
   They don’t change viscosity directly; they increase bleeding risk by affecting platelet signaling. They lower IgM by shrinking the cancer cells.

6. Why avoid grapefruit?
   It blocks CYP3A4, raising levels of BTK inhibitors and some chemo drugs → more side effects.

7. Can I fly?
   After IgM is controlled and you’re well hydrated, most people can fly. Avoid long trips during acute hyperviscosity or severe anemia; move and hydrate during flights.

8. Will I need a stem cell transplant?
   Only some patients with relapsed disease and good fitness benefit from autologous transplant. It is not routine first-line therapy.

9. What if I already have neuropathy?
   Your team may avoid bortezomib and prefer DRC or BTK inhibitors with careful monitoring.

10. How fast will IgM fall?
    Plasmapheresis lowers IgM immediately (by removal). Drugs lower production over days to weeks; full responses take months.

11. Are live vaccines safe?
    No during and shortly after immunosuppressive therapy. Use inactivated vaccines and time them per your oncologist.

12. Can supplements cure WM?
    No. Supplements are supportive only. Rely on evidence-based therapies; discuss any supplement to avoid interactions.

13. Do I need to stop aspirin?
    Maybe. If you start a BTK inhibitor or have low platelets, your doctor may stop aspirin unless the heart/stroke benefit is essential.

14. What tests track progress?
    Serum IgM, serum viscosity, complete blood count, metabolic panel, and sometimes bone marrow. Eye: dilated fundus exam, OCT, retinal photos.

15. What is the long-term outlook?
    WM is chronic and treatable. Many patients live for years with good quality of life using modern therapies and careful monitoring.

Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical  history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.

The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members

Last Updated: August 30, 2025.