Igm 60G/L, Iga Low, Igg Low. What Is the Best Management?

SGH 2002 Haem

Question 15 78yo man, epistaxis and blurred vision. Echymoses noted on examination. Fundoscopy – retinal haemorrhages, dilated retinal vessels. Hb 80, MCV 102, plt 60, WCC normal. IgM 60g/L, IgA low, IgG low. What is the best management? (a) platelet transfusion (b) plasmaphoresis (c) IVIG (d) Antibiotic prophylaxis (e) Steroids

Aim: to recognise hyperviscosity associated with WM.

Hyperviscosity in Waldenstrom’s Macroglobulinaemia

IgM commonly between 40 and 80 g/L but the correlation with viscosity values is not linear. Total serum protein levels usually exceed 100 g/L.

Clinical Features of WM

 Most patients are anemic and the triad of anemia, hyperviscosity, and plasma volume expansion may precipitate or aggravate congestive heart failure.  The skin may show dependent purpura secondary to abnormalities in platelet function and hyperviscosity. Multiple flesh-colored pruritic papules on extensor surfaces may be present and are secondary to deposition of IgM reacting with epidermal basement membrane proteins.  In those patients having a cryoglobulin (type I) which precipitates at a high temperature (ie, >22°C), symptoms on cold exposure may include Raynaud's phenomenon, urticaria, purpura, and acral cyanosis.  Diarrhea and steatorrhea can result from infiltration of the gastrointestinal tract by monoclonal IgM; gastrointestinal bleeding is not common.  Pulmonary involvement is rarely the most prominent feature of WM. It is manifested by cough and dyspnea and the presence of pleural effusion, diffuse pulmonary infiltrates, or isolated masses. The pulmonary manifestations often respond to alkylating agents or irradiation and do not appear to affect prognosis adversely.

Hyperviscosity syndrome – In one series, hyperviscosity-related symptoms were present in 31 percent [14], producing neurologic complaints such as blurring or loss of vision, headache, vertigo, nystagmus, dizziness, sudden deafness, diplopia, or ataxia. Marked hyperviscosity can lead to confusion, dementia, disturbances of consciousness, stroke, or coma. Clinical manifestations are rarely attributable to hyperviscosity if serum viscosity is <4 centipoises (CP, normal value < or =1.8 CP). Although the correlation between serum viscosity and clinical manifestations is not precise, symptoms often begin when serum viscosity is >4 CP, and most patients are symptomatic when serum viscosity is >6 CP. As an example, in a compilation of two different series, zero, 67, and 75 percent of patients had symptoms of hyperviscosity when the serum viscosity was less than 3, greater than 4, and greater than 5 CP, respectively.

Fundi Funduscopic abnormalities were noted in 34 percent of patients in one series. A classic finding in WM associated with hyperviscosity is the presence of dilated, segmented, and tortuous retinal veins, giving a "sausage link" appearance. Other retinal lesions, including hemorrhages, exudates and papilledema may be impressive, and central retinal vein thrombosis can occur.

TREATMENT OF HYPERVISCOSITY – The clinician should make the decision to perform plasmapheresis on the basis of the patient's symptoms and physical findings, rather than on the magnitude of the viscosity measurement. Plasmapheresis will alleviate symptoms quickly, since the large size of the IgM molecule restricts it to the intravascular space, from which it can be rapidly removed using plasmapheresis.  Patients presenting with severe neurologic impairment, such as stupor or coma, should be treated with plasma exchange on an emergency basis.  Symptoms should subside with the lowering of serum viscosity. However, irreversible changes can occur, such as venous thrombosis of the inner ear, retinal vein, and other sites.  Plasmapheresis does not affect the disease process. Thus, cessation of plasma exchange treatments, in the absence of other therapy, will result in a return to high levels of serum IgM and recurrence of symptoms of hyperviscosity within a few weeks in most instances.  A reasonable initial prescription is a total plasma volume exchange (ie, 3 to 4 liters in an adult) replaced with albumin (rather than plasma), repeated daily until symptoms subside or until serum viscosity is normal.  Hyperviscosity syndromes are usually associated with an increased plasma volume. Thus, the volume of plasma needed for a "one volume exchange" may be greater than that calculated by commonly used formulae.  Transfusion with packed red blood cells may further increase whole blood viscosity and precipitate or aggravate congestive heart failure.

(a) Platelet transfusion does not make sense – pt is not bleeding and platelet count not at critical level. (c) IVIG – don’t want to INCREASE the immunoglobulin load (d) Antibiotic prophylaxis does not make sense. Need urgent plasmaphoresis to relieve the hyperviscosity, thus answer is (b)