Page 2015 - Hematology_ Basic Principles and Practice ( PDFDrive )

1786 Part XI Transfusion Medicine

been found, and no generally accepted assay of platelet dysfunction guided by clinical response and continued until the platelet count is
predicts which patients are at risk. A single cytapheresis procedure above 150,000/µL and lactate dehydrogenase is near normal for 2–3
can lower the platelet count by 30% to 50%. Plateletpheresis can consecutive days. The persistence of schistocytes on the peripheral
have dramatic effects for selected patients such as those with evolving blood smear does not preclude weaning or discontinuation of treat-
digital gangrene. Attempts to maintain thrombocythemic patients at ment. Typically, patients should respond within 2 or 3 days of
normal platelet counts by cytapheresis alone have not been successful; beginning treatment. In desperately ill and deteriorating patients,
more practical long-term chemotherapy should be instituted concur- escalating the intensity of plasma exchange to twice daily may be
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rently. Because most patients with thrombocytosis do not develop necessary. Despite initial reports of improved response rates in
symptoms, including patients with myeloproliferative disorders, certain patients, recent experience suggests that the use of
prophylactic plateletpheresis seems unwarranted regardless of the cryoprecipitate-poor plasma may not be more effective than the use
platelet count. One possible exception involves pregnant patients of standard FFP as a specific replacement fluid for plasma exchange
with essential thrombocythemia who may be at increased risk of first in patients with TTP. The effectiveness of plasma exchange in this
trimester abortion; Periodic plateletpheresis has been used in a limited setting may derive from removal of antibody to or replacement of the
series, with weekly procedures necessary to reduce the circulating von Willebrand factor–cleaving zinc metalloprotease, ADAMTS13.
platelet number until delivery. However, patients with clinical features of TTP and only moderate
ADAMTS13 deficiency or even normal activity may respond to
plasma exchange. Plasma exchange for hematopoietic progenitor cell
THERAPEUTIC PLASMAPHERESIS transplant recipients exhibiting clinical features of TTP, now gener-
ally referred to as transplantation-associated thrombotic microangi-
Common clinical indications for therapeutic plasmapheresis are opathy (TAM), has proved far less efficacious. This syndrome likely
outlined in Table 118.2. Most procedures are performed for treat- differs in pathogenesis from classic TTP in many aspects, including
ment of immunologic and hematologic disorders. A course of plas- the absence of severe ADAMTS13 deficiency, the spectrum of clinical
mapheresis generally consists of five to seven exchanges of 1–1.5 symptoms, and the lack of evidence of systemic microthrombus
plasma volumes each, either daily or with an interval of 1–2 days formation. Furthermore, plasma exchange has been unsuccessful in
between procedures; the course of therapy varies depending on the reversing most cases of TAM. Finally, atypical hemolytic uremic
specific disease indication and rate and duration of response. syndrome (aHUS), a rare form of thrombotic microangiopathy with
Several expert committees have published practice guidelines for high mortality, may be difficult to distinguish clinically from TTP in
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using plasmapheresis in a wide variety of disease states. Some of the adults. aHUS results from uncontrolled complement activation, does
least controversial indications for plasmapheresis are supported by not respond at all to plasma therapies, and is instead treated with
small series of uncontrolled cases that rely on some objective clinical eculizamab to block the terminal complement complex.
or laboratory measurement of patient improvement. Small, uncontrolled studies and extensive clinical experience
support the use of plasmapheresis as an adjunctive therapy for patients
with paraproteinemia and hyperviscosity syndrome and with some
Hematologic Indications paraproteinemias in the absence of hyperviscosity. Waldenström
macroglobulinemia manifests as a lymphoplasmacytic lymphoma
Two of the most common indications for plasmapheresis are treat- with a monoclonal IgM protein in the plasma. Because IgM is a large
ment of TTP and treatment of clinical syndromes associated with molecule and resides predominantly in the intravascular space, as
paraproteinemias. Plasma exchange with fresh-frozen plasma (FFP) little as one apheresis procedure will result in improvement in symp-
replacement has been estimated to improve survival rates of patients toms. Recurrence of symptoms and rising plasma viscosity will
with TTP from 10% to more than 75%. Comprehensive reviews of determine the need and frequency of repeated exchanges. Compre-
the clinical and laboratory evaluation and treatment of patients with hensive reviews describing the rationale and treatment schedules for
suspected TTP, including management with plasma exchange therapy, plasmapheresis in patients with a variety of paraproteinemias, includ-
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have been published. Treatment usually involves daily single-volume ing cryoglobulinemia and Waldenström macroglobulinemia have
plasma exchange with both frequency and duration of treatment been published.
Low-Density Lipoprotein Apheresis and Other
TABLE Common Indications for Therapeutic Plasmapheresis Metabolic Disease Indications
118.2
Hematologic Diseases (Including Blood Cell–Specific Autoimmune Diseases) Evidence that cutaneous lesions and vascular lesions regress in indi-
Thrombotic thrombocytopenic purpura viduals with familial hypercholesterolemia as LDL levels are controlled
by plasmapheresis has encouraged the use of apheresis column
Idiopathic thrombocytopenic purpura (immunoabsorption) absorption procedures in patients with homozygous disease and in
Hyperviscosity poorly controlled heterozygous patients. LDL apheresis removes
Posttransfusion purpura apolipoprotein B–containing lipoproteins from the blood by a variety
Cold agglutinin syndrome of techniques, including dextran sulfate cellulose adsorption, immu-
ABO-mismatched marrow transplant (recipient) noadsorption, and heparin-induced extracorporeal precipitation.
Autoimmune Diseases Short-term safety and efficacy have been demonstrated. Patients have
Cryoglobulinemia now been treated successfully for several years; however, additional
Rheumatoid arthritis (immunoadsorption, lymphoplasmapheresis) experience with this therapy will be required to prove long-term
Myasthenia gravis benefit for refractory hypercholesterolemia and coronary artery
Goodpasture syndrome disease for heterozygotes in particular. In 36 homozygous children
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Guillain-Barré syndrome in two studies, 20% to 22% developed new aortocoronary lesions or
Chronic inflammatory demyelinating polyneuropathy showed progression of existing lesions while on apheresis despite
Metabolic Diseases impressive reductions in mean LDL cholesterol. 20,21 Side effects such
Homozygous familial hypercholesterolemia (selective adsorption) as malaise, shivering, and pain at the phlebotomy site are common
Refsum disease but mild, and the treatments are generally well tolerated. Patients
Other with severe hypertriglyceridemia are at risk of developing acute
Drug overdose and poisoning pancreatitis. Plasma exchange appears to reduce recurrent episodes by
an average 67% but requires continuation of medical therapy.