30 Therapeutic Apheresis: Indications, Efficacy and Complications

Question 1

Category I

Answer 1

Apheresis is an accepted first-line therapy for these disorders.

Question 2

Category II

Answer 2

Apheresis is an accepted second-line therapy for these disorders.

Question 3

Category III

Answer 3

Individualize decision making. The optimal role of apheresis has not been conclusively determined in these disorders.

Question 4

Category IV

Answer 4

Published evidence indicates that apheresis is ineffective or harmful in these disorders. Institutional review board approval is desirable if apheresis is planned.

Question 5

The term that refers to the removal of plasma from the circulation by manual or automated methods

Answer 5

Plasmapheresis

Question 6

The term that refers to a therapeutic procedure in which plasmapheresis is combined with replacement of the removed plasma by a substitute colloid fluid, most commonly a mixture of 5% human serum albumin and 0.9 percent saline solution

Answer 6

Plasma exchange

Question 7

The “sweet spot” for plasma exchange procedures is the processing of between ___________ plasma volumes.

Answer 7

1.0 and 1.5

Question 8

Class I Indications for TPE

Answer 8

• Catastrophic antiphospholipid syndrome
• Cutaneous T-cell lymphoma; mycosis fungoides; Sézary syndrome: Erythrodermic
• Erythrocytosis: Primary (Polycythemia vera)
• Hereditary hemochromatosis (Erythrocytapheresis)
• Hyperviscosity in monoclonal gammopathies: Symptomatic and as Prophylaxis for rituximab
• Sickle cell disease: Acute stroke and Stroke prophylaxis (RBC Exchange)
• Thrombotic microangiopathy-Drug-associated: Ticlopidine
• TTP
• Complement mediated TMA; Factor H autoantibody

Question 8

Hyperviscosity in monoclonal gammopathies: It is most common in ________________because of the highly red-cell–aggregating properties of immunoglobulin (Ig) M and, less often, in IgG or IgA myeloma.

Answer 8

Waldenström macroglobulinemia

Question 9

TRUE OR FALSE

The relationship between monoclonal protein level and serum viscosity is nonlinear; therefore, a relatively small (20%) decrease in plasma protein can affect a major change in viscosity.

Answer 9

TRUE

The relationship between monoclonal protein level and serum viscosity is nonlinear; therefore, a relatively small (20%) decrease in plasma protein can affect a major change in viscosity.

Question 9

Waldenström macroglobulinemia: - Symptoms typically emerge when serum viscosity rises above ________ relative viscosity units (normal being 1.4-1.8).

Answer 9

4.0 relative viscosity units

Question 9

Are immunoglobulins or complexes of immunoglobulins that reversibly precipitate when exposed to temperatures below 37°C.

Answer 9

Cryoglobulins

Question 10

Associations of Types of Cryoglobulinemia

Answer 10

Type I: lymphoproliferative disorders

Type II: hepatitis C

Type III: chronic infections or autoimmune disorders

Question 11

Types of Cryoglobulinemia

Answer 11

Type I: isolated monoclonal immunoglobulins

Type II: a mixture of immunoglobulins including a monoclonal component that exhibits antibody activity toward polyclonal IgG

Type III:mixed polyclonal immunoglobulins of one or more classes

Question 12

Results from combination of free light chains with Tamm-Horsfall mucoprotein in the distal nephron and the resultant precipitation of obstructing casts

Answer 12

Myeloma cast nephropathy (“myeloma kidney”)

Question 12

TRUE OR FALSE

Plasma exchange is currently considered to be part of first-line treatment for myeloma with cast nephropathy, and is an option when renal function does not rapidly improve with chemotherapy.

Answer 12

FALSE

Plasma exchange is not currently considered to be part of first-line treatment for myeloma with cast nephropathy, but may be a reasonable option when renal function does not rapidly improve with chemotherapy.

Question 12

A medical emergency that presents with microangiopathic hemolytic anemia and thrombocytopenia

Answer 12

Idiopathic thrombotic thrombocytopenic purpura (TTP)

Question 13

In acquired idiopathic TTP, this enzymatic defect is caused by an autoantibody inhibitor of __________that results in severe deficiency of the enzyme

Answer 13

ADAMTS-13

Question 13

TPE, using ________ as the colloid exchange fluid, was the only therapy for TTP that has been demonstrated highly effective in a randomized clinical trial.

Answer 13

Human plasma

Question 14

The chimeric anti-CD20 monoclonal antibody that has been shown to reduce the risk of relapse when administered to patients with TTP who achieve remission with TPE.

Answer 14

Rituximab

Question 15

A humanized immunoglobulin fragment that prevents interaction of platelets with the A1 domain of von Willebrand factor, appears to shorten the course of TPE required to achieve remission in patients with TTP.

Answer 15

Caplacizumab

Question 16

A thrombotic microangiopathy with acute oliguric or anuric renal failure, is rarely associated with severe deficiency of ADAMTS-13.

Answer 16

Hemolytic uremic syndrome (HUS)

Shiga toxin–associated HUS does not respond to TPE; atypical HUS (ie, with defects in regulation of the complement system) has shown only limited responses to TPE

Question 17

Shiga toxin–associated HUS does not respond to TPE; atypical HUS (ie, with defects in regulation of the complement system) has shown only limited responses to TPE and is more appropriately treated with_________________.

Answer 17

Eculizumab

Question 17

The two most common drugs reported to the FDA as associated with TTP are

Answer 17

Ticlopidine and clopidogrel

Question 18

# Drug-associated TTP Autoantibodies to ADAMTS-13 are seen in ____________-associated TTP

Answer 18

Ticlopidine-associated TTP

Question 18

TRUE OR FALSE Patients with clopidogrel-associated TTP do not appear to benefit from plasma exchange.

Answer 18

TRUE Patients with clopidogrel-associated TTP do not appear to benefit from plasma exchange.

Question 18

In TPE, most adverse effects were classified as _____________- and did not prevent the successful completion of the procedure.

Answer 18

Mild or moderate

Question 18

In patients receiving plasma as the colloid exchange fluid, most adverse events include

Answer 18

Fever, chills, or urticaria

Question 18

Muscle cramps, paresthesias, and mild nausea can be attributed to

Answer 18

Hypocalcemic toxicity ## Footnote Plasma-ionized calcium decreases as a result of the rapid infusion of calcium-free pharmaceutical albumin and, in part, to the use of calcium-chelating agents as anticoagulants in plasma exchange procedures.

Question 18

Refers to the removal of a patient’s red cells in exchange for donor red cells.

Answer 18

Red cell exchange ## Footnote Clinical disorder is caused by an abnormality (inherited or acquired) of the patient’s red blood cells

Question 18

The process when red cells are removed for therapeutic purposes, but not replaced with donor red cells

Answer 18

Erythrocytapheresis ## Footnote Used in situations characterized by an untoward elevation in circulating red cell volume or in iron-overload states.

Question 19

Advantage of automated red cell exchange than manual BT in Sickle cell disease

Answer 19

Mitigates the accumulation of iron while maintaining a low level of hemoglobin S in patients receiving chronic treatment

Question 20

The World Health Organization has suggested that exchange transfusion be considered for nonimmune (ie, not previously exposed) patients with Plasmodium falciparum malaria who have any of the following characteristics:

Answer 20

* Greater than 30% parasitemia in the absence of clinical complications * Greater than 10% parasitemia in the presence of severe disease * Greater than 10% parasitemia and failure to respond to optimal chemotherapy after 12 to 24 hours * Greater than 10% parasitemia and poor prognostic factors (elderly, late-stage parasites [schizonts] in the blood)

Question 20

Red cell exchange is indicated as first-line therapy in Sickle cell disease:

Answer 20

* Acute vaso-occlusive stroke * Acute chest syndrome refractory to standard management* * Prophylaxis (primary or secondary) for vaso-occlusive stroke* ## Footnote *red cell exchange may not be superior to simple transfusion

Question 21

Intraerythrocytic parasite that can be efficiently removed using automated red cell exchange.

Answer 21

Babesia microti ## Footnote Red cell exchange is recommended for patients with severe manifestations, high parasite burdens (>10%) or who are at high risk.

Question 21

Miscellaneous Uses of Red Cell Exchange

Answer 21

* To prevent Rh sensitization of an Rh-negative woman who received emergency transfusion with Rh-positive red blood cells * The macrolide immunosuppressant tacrolimus (and sirolimus) is highly erythrocyte-bound, and overdoses are not responsive to plasma exchange but can be mitigated using red cell exchange. * Refractory methemoglobinemia in patients with glucose-6-phosphate dehydrogenase deficiency or after ingestion of strong oxidants

Question 22

ASFA has designated **symptomatic hyperleukocytosis** (white blood cell count >100,000/μL in acute myeloid leukemias , white cell count >400,000/μL in acute lymphoblastic leukemia with leukostasis as a category ______ indication for therapeutic leukocytapheresis. **Asymptomatic hyperleukocytosis** is designated a category _____ indication

Answer 22

Category II Category III i

Question 23

ASFA lists **symptomatic thrombocytosis** in patients with myeloproliferative neoplasms as a category____indication for **thrombocytapheresis**

Answer 23

Category II

Question 23

Refers to the selective removal of platelets from a patient for therapeutic purposes using a blood-processing (apheresis) device

Answer 23

Thrombocytapheresis

Question 23

A treatment process in which a patient’s mononuclear white blood cells are manipulated outside of the body such that their reinfusion into the patient results in downregulation of cytotoxic T-cell activity.

Answer 23

Extracorporeal photochemotherapy (ECP)

Question 23

Uses of Extracorporeal photochemotherapy (ECP)

Answer 23

Palliative treatment of skin manifestations of cutaneous T-cell lymphoma unresponsive to other therapy Treatment of acute cardiac allograft rejection and chronic graft-versus-host disease unresponsive to standard treatments