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Hyperviscosity Syndrome, Emergency Medicine

Basics

Description

- Hematologic: - Bleeding is the most common manifestation. Mechanism thought to be platelet dysfunction. - Epistaxis - Gingival, rectal, uterine bleeding - Prolonged postprocedural bleeding - Blood dyscrasias - Pruritus owing to red cell breakdown products - Splenic enlargement

- Ocular: - Change in visual acuity: - Blurring - Diplopia - Visual loss

- Characteristic "link-sausage effect"пїЅ on funduscopy - Alternating bulges and constrictions within the retinal veins - Retinal hemorrhage, detachment - Exudate, microaneurysm formation - Papilledema

- Renal: - Nephritic or nephrotic syndrome - Hematuria - Sterile pyuria

- Cardiovascular: - Angina or myocardial infarction - Dysrhythmias - CHF

- CBC with WBC differential: - Anemia or erythrocytosis can be seen in HVS. - Anemia usually normocytic and normochromic - Rouleaux of erythrocytes on the peripheral smear is an important diagnostic clue - WBC for leukemia

- Coagulation profile - Serum and urine protein electrophoresis - Measurement of serum viscosity (not routinely available in ED setting): - Ostwald viscosimeter - Normal range for the serum viscosity relative to water is 1.4-1.8. - Minimal viscosity at which symptoms develop is 4 centipoise (cp).

- Bleeding and clotting disorders: - Platelet disorders (qualitative and quantitative) - Hereditary factor deficiencies - Acquired disorders (vitamin K deficiency, liver disease) - Disseminated intravascular coagulation

- Plasmapheresis/leukapheresis: - In stable patients: 40 mL/kg of body weight - In critical patients: 60 mL/kg of body weight - Side effects include hypocalcemia with use of a citrate-containing anticoagulant and dysrhythmia (rare). - Many patients require more than 1 plasmapheresis. - Definitive treatment for HVS. Should be performed in consultation with plasmapheresis/hematology team. - Leukapheresis is reserved as the initial treatment in patients with hyperleukocytosis (usually WBC >100,000)

  • Hyperviscosity syndrome (HVS) is the clinical consequence of increased blood viscosity.
  • The classic clinical symptoms are the triad of mucosal bleeding, visual disturbances, and neurologic signs.
  • Viscosity is the resistance a material has to change in form.
  • The higher the blood viscosity, the more the internal resistance to blood flows.
  • Increased cardiac output is required to provide adequate perfusion of hyperviscous blood.
  • Oxygen delivery is impaired as transit through the microcirculatory system slows. This impaired microcirculatory oxygenation gives rise to the clinical symptoms of this syndrome.

Etiology

  • Hyperviscosity occurs when there is elevation of either the cellular or acellular components of circulating blood.
  • Acellular (protein) hyperviscosity:The most common cause (85-90%) of hyperviscosity is increased concentration of Оі globulins:Monoclonal gammopathies: From malignant diseases like Waldenstrom macroglobulinemia and multiple myelomaPolyclonal gammopathies: Usually rheumatic diseases (very rare)
  • Cellular (blood cell) hyperviscosity:Much less common (10-15%)Increased numbers of RBC, as in polycythemia veraIncreased concentration (>100,000) of WBC, as in acute and chronic leukemiaThrombocytosis

Diagnosis

Signs and Symptoms

  • Classic triad:Mucosal bleedingVisual disturbancesNeurologic
  • Hematologic:Bleeding is the most common manifestation. Mechanism thought to be platelet dysfunction.EpistaxisGingival, rectal, uterine bleedingProlonged postprocedural bleedingBlood dyscrasiasPruritus owing to red cell breakdown productsSplenic enlargement
  • Ocular:Change in visual acuity:BlurringDiplopiaVisual lossCharacteristic "link-sausage effect"пїЅ on funduscopyAlternating bulges and constrictions within the retinal veinsRetinal hemorrhage, detachmentExudate, microaneurysm formationPapilledema
  • Renal:Nephritic or nephrotic syndromeHematuriaSterile pyuria
  • Neurologic:HeadacheAtaxiaMental status changes/comaDizziness/vertigoNystagmusTinnitus, hearing lossParesthesia, peripheral neuropathySeizureIntracranial hemorrhage
  • Cardiovascular:Angina or myocardial infarctionDysrhythmiasCHF
  • Dermatologic:Raynaud phenomenonLivedo reticularisPalpable purpuraEruptive spider nevus-like lesionsDigital infarctsPeripheral gangrene

History

HVS should be considered in the following patient: пїЅ

  • Any patient presenting with the classic symptom triad of bleeding, visual disturbance, and neurologic dysfunction.
  • Any patient with an established immunoglobulin-producing hematologic disease that presents with signs or symptoms of microvascular end-organ damage or cardiac decompensation.
  • Any patient with an established hypercellular hematologic disease who presents with signs or symptoms of microvascular end-organ damage or cardiac decompensation.

Physical Exam

There are no specific physical exam findings unique to HVS. However, patient will exhibit findings based on the affected end organs. Mucosal bleeding, petechial rash or bruising, focal neurologic findings, signs of decompensated heart failure, and funduscopic abnormalities have all been reported. пїЅ

Essential Workup

  • Evaluate end-organ ischemia and bleeding.
  • Measure serum or whole blood viscosity.
  • Suspect diagnosis if the lab evaluation is hampered by serum stasis and increased viscosity causing analyzer blockage

Diagnosis Tests & Interpretation

Lab

  • CBC with WBC differential:Anemia or erythrocytosis can be seen in HVS.Anemia usually normocytic and normochromicRouleaux of erythrocytes on the peripheral smear is an important diagnostic clueWBC for leukemia
  • Electrolyte, BUN, creatinine, and glucose levels:Renal dysfunction is commonly noted in HVS.Hypercalcemia and pseudohyponatremia in multiple myeloma
  • Urinalysis:ProteinuriaHematuriaSterile pyuria
  • Coagulation profile
  • Serum and urine protein electrophoresis
  • Measurement of serum viscosity (not routinely available in ED setting):Ostwald viscosimeterNormal range for the serum viscosity relative to water is 1.4-1.8.Minimal viscosity at which symptoms develop is 4 centipoise (cp).
  • Elevated leukocyte alkaline phosphatase, lactate dehydrogenase, and serum vitamin B12 levels

Imaging

One should consider CT of head in patients with signs or symptoms of central neurologic dysfunction to exclude intracranial hemorrhage. пїЅ

Differential Diagnosis

  • Bleeding and clotting disorders:Platelet disorders (qualitative and quantitative)Hereditary factor deficienciesAcquired disorders (vitamin K deficiency, liver disease)Disseminated intravascular coagulation

Treatment

Pre-Hospital

IV fluid resuscitation with hemorrhage пїЅ

Initial Stabilization/Therapy

  • Rehydrate with 0.9% NS IV fluid.
  • Bleeding or end-organ ischemia may not be controlled by any treatment except plasmapheresis.
  • In patients with anemia and a leukemic picture, avoid blood transfusion until plasmapheresis is performed to avoid exacerbation of HVS.

Ed Treatment/Procedures

  • Hydration, supportive care, and early hematologist consultation are initial ED management.
  • Phlebotomy or emergent plasma exchange: This temporizing measure can be performed in a patient with HVS and severe neurologic findings like coma or seizures:Easily performed in the ED and is useful in acute severe cases if plasmapheresis not readily availableSimply draw off (100-200 mL) of whole blood and replace volume with isotonic saline.Should be performed in consultation with hematologist when possible.Treatment of choice in patients with polycythemia vera.
  • Plasmapheresis/leukapheresis:In stable patients: 40 mL/kg of body weightIn critical patients: 60 mL/kg of body weightSide effects include hypocalcemia with use of a citrate-containing anticoagulant and dysrhythmia (rare).Many patients require more than 1 plasmapheresis.Definitive treatment for HVS. Should be performed in consultation with plasmapheresis/hematology team.Leukapheresis is reserved as the initial treatment in patients with hyperleukocytosis (usually WBC >100,000)
  • ED physician can help in urgent situations by establishing or facilitating the establishment of large-bore central dialysis catheter, caution should be taken to avoid bleeding complications of this procedure

Follow-Up

Disposition

Admission Criteria

  • Patients with hyperviscosity and significant symptoms or any evidence of end-organ ischemia or hemorrhage should be admitted for treatment of the underlying hematologic disorder.
  • ICU admission for the following:HemorrhageAltered mental statusAcute MI

Discharge Criteria

Discharge after definitive treatment of the underlying disorder. пїЅ

Issues for Referral

All patients with HVS should be referred to hematologist. пїЅ

Pearls and Pitfalls

  • Avoid diuretics in patients with HVS because they can increase blood viscosity.
  • The classic triad of symptoms of HVS includes visual disturbances, bleeding, and neurologic manifestations.

Additional Reading

  • Adams пїЅBD, Baker пїЅR, Lopez пїЅJA, et al. Myeloproliferative disorders and the hyperviscosity syndrome. Emerg Med Clin North Am. 2009;27:459-476.
  • Blum пїЅW, Porcu пїЅP. Therapeutic apheresis in hyperleukocytosis and hyperviscosity syndrome. Semin Thromb Hemost. 2007;33(4):350-354.
  • Kwaan пїЅHC. Role of plasma proteins in whole blood viscosity: A brief clinical review. Clin Hemorheol Microcirc. 2010;44(3):167-176.
  • Somer пїЅT, Meiselman пїЅHJ. Disorders of blood viscosity. Ann Med. 1993;25(1):31-39.

See Also (Topic, Algorithm, Electronic Media Element)

Disseminated Intravascular Coagulation пїЅ

Codes

ICD9

  • 273.3 Macroglobulinemia
  • 289.0 Polycythemia, secondary

ICD10

  • C88.0 Waldenstrom macroglobulinemia
  • D75.1 Secondary polycythemia

SNOMED

  • 11888009 hyperviscosity syndrome (disorder)
  • 95693006 Hyperviscosity retinopathy (disorder)