Hyperviscosity syndrome causes, diagnosis, treatment

1. Hyperviscosity syndrome
DR Doha Rasheedy
Assisstant Professor
Geriatrics and Gerontology Department
ASU

2. Definition
• Viscosity refers to resistance to flow or
stickiness, from the Latin word “viscum alba”.
• Hyperviscosity syndrome (HVS) refers to the
clinical sequelae of increased blood viscosity.

3. Causes
• Elevated blood, plasma, or serum viscosity occurs in
a number of hematologic disorders;
1. Increased immunoglobulins;
1. Waldenström macroglobulinemia (WM)
2. Multiple myeloma (MM)
3. connective tissue diseases
2. Increased blood cells: hyperproliferative states such as:
1. the leukemias
2. Polycythemia
3. thrombocytosis
4. the myeloproliferative disorders.
3. reduced deformability of red blood cells
1. sickle cell disease
2. spherocytosis.

4. • Rheumatoid HVS is rare and may develop from
aggregates of rheumatoid factor or
intermediate IgG complexes.

5. Pathophysiology
1. As serum proteins or cellular components increase, the blood
becomes more viscous. Vascular stasis and resultant
hypoperfusion then lead to the clinical symptoms of
hyperviscosity syndrome (HVS).
2. Confusion and mental status changes result from the
increased viscosity of the blood and decreased cerebral blood
flow.
3. This sludging leads to segmental dilatation of retinal veins
and retinal hemorrhages.
4. Mucosal bleeding may occur from prolonged bleeding time
caused by myeloma proteins interfering with platelet
function.
5. Cardiopulmonary symptoms such as shortness of breath,
hypoxemia, acute respiratory failure, and hypotension also
result from this sludging of blood and decreased
microvascular circulation

6. The clinical presentation
1. the triad of mucosal bleeding, visual changes, and
neurologic symptoms.
2. Constitutional symptoms may be present
3. cardiorespiratory symptoms also contribute to the
clinical presentation.
4. Clinical sequelae of HVS can include congestive
heart failure, ischemic acute tubular necrosis, and
pulmonary edema with multiorgan system failure
and death if treatment is not promptly initiated

7. The tendency to bleed is the most
common manifestation of
hyperviscosity syndrome
• Spontaneous gum bleeding
• Epistaxis
• Rectal bleeding
• Menorrhagia
• Persistent bleeding after minor procedures.

8. •Visual changes range
from blurred vision to
vision loss.

9. Neurologic manifestations are
frequent and varied
• Vertigo
• tinnitus
• Hearing loss
• Paresthesias
• Ataxia
• Headaches
• Seizures
• Somnolence progressing to stupor and coma

10. Other manifestations may include
• heart failure
• shortness of breath
• Hypoxia
• Fatigue
• Anorexia
• Hypertension

11. • the clinician should have a high index of
suspicion for hyperviscosity syndrome in
patients with unexplained coma/altered
mental status or unexplained shortness of
breath, especially in those with an
underlying hematologic disorder.

12. • Blood hyperviscosity plays a role in the
pathogenesis of several cardiovascular
diseases, including hypertension,
atherosclerosis,and the
metabolic syndrome.

13. Physical findings
• bruises on the skin, blood blisters in the
mouth or the back of the eye.
• Ophthalmic examination may reveal
decreased visual acuity, dilated retinal veins,
"sausage-linked" or "boxcar segmentation" of
the retinal veins, or retinal hemorrhages.

16. Diagnosis
• The diagnosis of HVS is confirmed by
measurement of elevated serum viscosity in a
patient with characteristic clinical manifestations
of HVS. No exact diagnostic cut-off exists for
serum viscosity.
• Normal viscosity= 1.4-1.8 units centipoises
• Symptoms usually are not seen at viscosities of
less than 4 units
• HVS usually at viscosities above 5 units

17. Measuring the Viscosity
• Viscosity is classically measured in one of 2 ways:
– by determining the rate of fluid flow as a result of
applying a predefined force
– by measuring the amount of force required to
achieve a predefined rate of fluid flow.
• approximately 75% of clinical laboratories use a
“capillary tube” (ie, Ostwald tube) viscometer.
Viscosity is measured by the time required for a
serum or plasma sample to flow through a tube
under the influence of gravity.

20. • Laboratories using the Ostwald and pipette methods report
their data as ratios rather than in units of viscosity, such as
centipoise (cp). The results are reported as the ratio of time
for a patient sample to pass through the tube relative to the
time for a reference fluid (eg, water). Consequently,
commercial viscosity controls traceable to a National
Institute of Standards and Technology standard, reported in
centipoise, are not directly applicable.
• The Ostwald and pipette methods lack the kind of
standardized commercial calibrators and controls that are
commonplace for other hematology or chemistry assays.
• Because the viscosity of water at 20°C approximates 1.0 cp,
the viscosity ratio will be similar to the sample's viscosity in
centipoise at this temperature. The accuracy of this
generalization depends on the actual temperature at which
the samples are measured.

21. laboratory
1. Those with myeloma will typically display a
rouleaux formation on a peripheral smear
and a large globulin gap (total protein-
albumin> 4 gm/dl
2. A blood chemistry may demonstrate
hypercalcemia, hypophosphatemia, and
hyperkalemia

22. Types of hyperviscosity syndromes
• vary by pathology; including
1. serum hyperviscosity, which may cause
neurologic or ocular disorders;
2. polycythemic hyperviscosity, which results in
reduced blood flow or capillary perfusion and
increased organ congestion;
3. and syndromes of hyperviscosity, caused by
reduced deformability of red blood cells, often
evident in sickle cell anemia

23. N.B.
• in patients with Waldenström macroglobulinemia, neurologic
manifestations are common and are often due to;
1. hyperviscosity syndrome
2. or immune peripheral neuropathy.
3. Very rarely, neurologic signs and symptoms in these
patients may result from lymphoproliferative infiltration of
the central nervous system, a condition known as Bing-Neel
syndrome.
The diagnosis of Bing-Neel syndrome may be made by magnetic
resonance imaging and cerebrospinal fluid analysis, which may
show may show lymphocytic pleocytosis, elevated protein, and
IgM kappa or lambda light chain restriction. Treatment is with
cranial irradiation and/or intrathecal chemotherapy.

24. • Bing–Neel syndrome (BNS) is an extremely rare
neurologic complication of Waldenström
macroglobulinemia (WM).
• It involves central nervous system infiltration by
neoplastic lymphoplasmacytoid and plasma cells
with or without cerebrospinal fluid (CSF)
hyperglobulinemia.
• This increases blood viscosity, which impairs its
circulation through small brain and eye blood
vessels.
• Patients with BNS can be classified into Group A
and Group B based on the presence of these cells
within the brain parenchyma, leptomeninges, dura,
and/or the CSF

25. Treatment
• Plasmapheresis is the treatment of choice for
initial management and stabilization of
hyperviscosity syndrome (HVS) caused by the
paraproteinemias (the majority of cases).
Plasmapheresis is usually well tolerated and safe.
• Leukapheresis, plateletpheresis, and phlebotomy
are indicated for HVS from leukostasis,
thrombocytosis, and polycythemia, respectively.

26. Plasmapheresis
1. Plasmapheresis demonstrated to reverse retinopathy
and other clinical manifestations in most patients
with HVS.
2. Because bleeding is the most common sign of HVS,
urgent plasmapheresis using a cell separator should
be carried out for patients experiencing visual
symptoms to reduce the likelihood of blindness from
retinal hemorrhages/retinal detachment.
3. Plasmapheresis can reverse HVS-induced retinal
changes promptly, including reducing retinal venous
diameter and increased venous blood viscosity.
4. Plasma exchange reduces plasma viscosity
approximately 20% to 30% per session.

27. COMPLICATIONS OF PLASMAPHERESIS
• Allergic reaction
• Excessive fluid in the circulatory system
• Mineral imbalance.
• Reduction in platelet count
• Medication removed from the blood stream

28. • Blood transfusions should be used with caution
as they can increase serum viscosity.
• Hydration is a temporizing measure to employ
while preparing pheresis, diuretic in treating
heart failure due to HVS may worsen the case .
• Even after pheresis, the condition will recur
unless the underlying disorder is treated

29. • Transient increases in IgM levels after single-
agent rituximab therapy (“flares”) occur in 30%
to 70% of WM patients
• It has been recommended that plasmapheresis
be carried out in advance of rituximab therapy
if serum viscosity is more than 3.5 cp or IgM
level is greater than 5 g/dL. The mechanism of
the rituximab flare may involve release of IL-6
after stimulation of monocytes

30. CASES

31. • a 65-year-old plumber who presents with fatigue,
headache, blurred vision, and intermittent
nosebleeds for the past 3 months.
• Examination demonstrates mild generalized
lymphadenopathy and a palpable spleen tip.
• The fundi show marked retinal vein engorgement
with “sausaging.”
• Laboratory tests disclose mild anemia and a large
monoclonal spike on serum protein
electrophoresis.
How should he be managed?

32. • A 72 year-old male recently diagnosed with
multiple myeloma presents to your Emergency
Department complaining of abrupt onset of
ataxia, blurry vision, and epistaxis 1 hour prior to
arrival. Vital signs on initial presentation: BP
134/76, HR 84, RR 18, Temp 98.6, O2 sat 97% on
RA. On physical exam he is alert and oriented x3.
Visual acuities are OS 20/40 OD 20/30 and OU
20/30. He is ataxic when you ask him to
ambulate. CNs II-XII are grossly intact and no
horizontal or vertical nystagmus is appreciated on
observation, no dysmetria on finger-to-nose,
normal heel-to-shin, and negative Romberg. No
other abnormalities are noted on his physical
exam.

33. • His initial laboratory work-up includes a
coagulopathy study (Coags), complete blood
count (CBC), complete metabolic profile (CMP),
blood alcohol level (BAC), urinalysis (UA), and
urinary drug screen (UDS). His CBC demonstrates
a significant white blood cell count at 123,157, his
CMP demonstrates a hypercalcemia at 11.0, a
hypophosphatemia at 2.0, and a hyperkalemia at
5.7—otherwise his lab values are unremarkable.
• What diagnosis do you suspect? What additional
diagnostic modalities do you want to order?
• How do you want to proceed with his treatment?

34. • A 65 year-old female recently diagnosed with
Waldenstrom’s macroglobulinemia presents to
your Emergency Department complaining of
spontaneous gum bleeding, sudden vision loss, and
vertigo x 1 day.
• Vital signs on initial presentation: BP 128/68, HR
76, RR 16, Temp 99, O2 sat 98% on RA.
• Her physical exam reveals blood oozing from both
her lower and upper gums.
• Visual acuities are: OS 20/30, OD able to perceive
motion, and OU: 20/30. Dix-Hallpike and HINTS
exams are negative, CNs II-XII are grossly intact,
and no horizontal or vertical nystagmus is
appreciated on observation, no dysmetria on
finger-to-nose, normal heel-to-shin, and negative
Romberg. Otherwise, her physical is unremarkable.

35. • Her initial laboratory work-up includes Coags,
CBC, CMP, BAC, UA, and UDS. Her CBC
demonstrates a significant white blood cell count
at 101,234, her CMP demonstrates mild
hypercalcemia at 12.1, hypophosphatemia at 2.3
and hyperkalemia at 5.9.
• What diagnosis do you suspect?
• What additional diagnostic modalities do you
want to order to confirm this suspicion?
• How do you want to proceed with her
treatment?