Hyperviscosity syndrome

Question 1

Classical Triad

Answer 1

• Oncological emergency

=>Classical triad:
* Neurological deficits
* Visual changes
* Mucosal bleeding

Question 2

🔄 Causes

Answer 2

• Increased plasma proteins (e.g., paraproteins)
• Increased cellular components (RBCs, WBCs, platelets)
• Can occur due to RBC deformity or aggregation

Question 3

🧬 Etiology

Answer 3

• Polycythemia vera, leukemias,
• thrombocytosis
• Sickle cell disease
• Multiple myeloma, Waldenström
• macroglobulinemia (IgM)
• Cryoglobulinemia
• Autoimmune diseases (RA, SLE, Sjögren
  syndrome)

🔍 Key Type: Hypergammaglobulinemia
* Most common: IgM paraproteinemia (e.g., Waldenström macroglobulinemia)

Question 4

🧠 Clinical Presentation

Answer 4

• Headache, visual changes
• Auditory symptoms
• Lethargy, ↓ GCS
• Focal neurological signs
• Nose bleeds, mucosal bleeding
• Seizures or coma

Question 4

🧪 Mechanism

Answer 4

Viscosity influenced by:
* Size, shape, concentration of paraproteins
* Polymerization of abnormal proteins

Question 5

⚠️ Symptom Threshold

Answer 5

• Symptoms typically develop when serum viscosity:
  touches 4 centipoise (cP)
  normal se viscosity~1.4–1.8 cP

Question 6

🧬 Pathophysiology

Answer 6

• ↑ Viscosity → ↓ blood flow
  
  • Sludging through microcirculation
  • Tissue ischemia
  • Thrombosis
• Risk of:
  
  • Retinal, myocardial, cerebral ischemia

Question 7

⚠️ Clinical Features

Answer 7

=> Hypoperfusion signs due to passive venous congestion:
* Bleeding symptoms, especially mucosal (nasal & oral)
* GI tract: ulcers
* Ocular:
- Dilated, tortuous, engorged
“sausage like” retinal veins
- Retinal hemorrhages (seen on fundoscopy)
* Purpura & skin bruising common

Question 8

💊 Treatment (Tt)

Answer 8

• Hydration
  
  • Treat the underlying condition⚕️ Specific Therapy
  • Two-pronged approach:
    1. Immediate: Plasmapheresis to reduce serum viscosity
    2. Long-term: Chemotherapy for underlying hematologic malignancy

Question 9

📉 Effectiveness of Plasmapheresis

Answer 9

• IgM-related paraproteinemia:
  
  • ~50–60% reduction in viscosity with one session (IgM ~80–90% intravascular)
  • IgA/IgG-related paraproteinemia: -Requires multiple sessions for same effect (~50% is intravascular)

⸻

🚨 Alternatives
* Phlebotomy may be used if plasmapheresis is not available

⸻

❗ Caution
* Blood transfusions should be cautiously weighed due to risk of further increasing viscosity

Question 10

Complications

Answer 10

1. Predisposition to infection
2. VTE
3. pulmonary complications
4. Hypercalcemia

Question 10

Hypercalcemia
Definition
Mechanism

Answer 10

• Part of CRAB diagnostic criteria for MM
  
  • (C = calcium elevation)
  • Defined as: corrected calcium >11 mg/dL
  • Mechanism: osteolysis via activated osteoclasts

Question 11

Hypercalcemia
association

Answer 11

=> Associated with:
* Aggressive disease
* High tumor burden
* Poor prognosis

Question 12

Clinical signs of Hypercalcemia (may be subtle or severe):

Answer 12

• Malaise, fatigue
  
  • Arrhythmias, short QT
  • Confusion, ↓ GCS, seizures
  • Renal failure, polyuria
  • GI: anorexia, nausea, ileus, pancreatitis

Question 13

Treatment of hypercalcemia

Answer 13

💊 Treatment of Hypercalcemia

*	Fluid resuscitation (correct hypovolemia → enhance urinary Ca excretion)

*	Stop calcium-raising drugs (e.g., vit D, thiazides)

*	Loop diuretics after rehydration

*	Calcitonin:
  -	Inhibits bone resorption
  -	Works rapidly (4–6h), lasts 48–72h

*	Steroids:
  -	Decrease intestinal Ca absorption
-	Useful in myeloma-related 
     hypercalcemia

*	IV bisphosphonates (e.g., zoledronic acid):
  -	First-line for severe/symptomatic hypercalcemia
   -	Inhibit osteoclast activity
   -	Limitations in renal failure

*	Denosumab:
   -	Alternative to bisphosphonates
   -	Not renally excreted