Samuel Nobilluci DO
Jordan Miller DO
Ari Leib MD
Adena Regional Medical Center

Case presentation

A 88-year-old Caucasian female walks into the emergency department after her primary care physician told her she had an abnormal lab. She reports that she otherwise feels fine and denies visual changes, shortness of breath, chest pain, abnormal swelling or bowel and bladder changes. On physical exam you note a well-appearing elderly female who appears to be in no acute distress. Review of her labs reveal a platelet count of over 1 million. 

What is plasmapheresis?

In the process of plasmapheresis the liquid part of the blood, called plasma, is separated from the blood cells. During the process, normal saline or albumin replaces the plasma and then the cleaned plasma is replaced back into your body. In a process very similar to dialysis, plasma can be removed from the body to cleanse it to treat a variety of disorders such as:

  • Myasthenia gravis
  • Lambert Eaton syndrome
  • Guillian-Barre syndrome
  • Chronic inflammatory demyelinating polyneuropathy
  • Sickle cell disease complications
  • Wilson’s disease
  • Thrombotic thrombocytopenic purpura 
  • Hyper-viscosity syndrome secondary to certain types of cancers such as Waldenstrom’s macroglobulinemia

Risks of plasmapheresis include infection, hypotension, blood clots and allergic reaction to plasma replacement solutions. Contraindications to plasmapheresis include hypocalcemia, allergy to frozen albumin, heparin or plasma, and hemodynamic instability

Although plasmapheresis refers to the removal of plasma, it can also be used for therapeutic plasma exchange where a replacement product is transfused after removal of the plasma. This is referred to as cytapheresis, which is the selective removal of RBC’s, WBC’s and platelets. Indications for this are as follows:

  • Erythrocytapheresis – selective removal of RBCs in sickle cell disease, malarial infection
  • Leukapheresis – selective removal of WBCs in leukemia, allogeneic/autologous stem cell transplant
  • Platelet apheresis – selective removal of platelets in conditions with thrombocytosis in essential thrombocythemia and polycythemia vera.

More on conditions involving thrombocytosis…

  • Essential thrombocythemia
    • This is a myeloproliferative disorder where the body produces an increased number of platelets, defined as thrombocytosis. 
    • ET is a somatic mutation in the JAK2 gene and CALR gene. 
    • Symptoms include headaches, chest pain, recurrent TIAs, digital ischemia, ulcerations, and pregnancy complications. The average age of onset is 60.
    • Treatment is based on a risk classification and depends on the patient’s age and whether or not they have had a thrombus or gene mutation.
      • In the case of thrombosis, patient’s should be on anticoagulation
      • Hydroxyurea 
      • Aspirin can help control microvascular symptoms such as ischemia, gangrene, strokes and erythromalagia 
      • Anagrelide is FDA approved to reduce the elevated platelet count and risk of thrombosis
  • Polycythemia vera
    • This is a myeloproliferative disorder where the body procures an increased number of red blood cells in the bloodstream, which is defined as erythrocytosis. As there is an increase in blood volume, there is an increased risk for blood clots that can block blood flow in arteries and veins causing deep vein thrombosis. Patients are at an increased risk for heart attacks and strokes.
    • PV may be inherited as an autosomal dominant manner. However, most cases are acquired during a person’s lifetime. The average age of onset is 60 years old and is more common in men than women. Gene mutations include JAK2 and TET2. 
    • Symptoms include headaches, tinnitus, and visual changes. Patients classically complain about pruritis after a shower secondary to mast cell degradation. 
    • Treatment includes:
      •  Phlebotomy to keep the hematocrit less than 45%
      • Daily aspirin
      • Hydroxyurea to suppress cells in the bone marrow
      • Ruxolintinib

When is platelet apheresis acutely indicated?

The American Society for Apheresis 2016 indications for therapeutic apheresis and cytapheresis  procedures is outlined as adapted from Schwartz et al. on Uptodate in table format. A summary of this information lists the current Category I guidelines with level 1A evidence as: 

  1. Primary treatment for Guillain-Barré syndrome prior to the administration of IVIG or when combined with acute liver failure. 
  2. Rapidly progressive, dialysis-dependent granulomatosis with polyangiitis
  3. LDL apheresis in homozygotic familial hypercholesterolemia 
  4. RBC exchange for stroke prophylaxis or prevention of transfusional iron overload
  5. Thrombotic thrombocytopenic purpura 

Category I level 1B evidence includes:

  1. Rheopheresis in age-related dry macular degeneration 
  2. Dialysis independent Goodpasture’s syndrome 
  3. Chronic inflammatory demyelinating polyradiculoneuropathy
  4. Erythrodermic cutaneous T-cell lymphoma 
  5. Recurrent FSGS in transplanted kidneys 
  6. Erythrocytapheresis in Hereditary Hemochromatosis 
  7. Symptom management in hyperviscosity syndrome 
  8. Moderate to severe myasthenia gravis 
  9. IgA/IgG mediated paraproteinemic and chronic acquired polyneuropathies 
  10. Erythrocytapheresis is polycythemia vera 
  11. TPE and IA in living donor antibody mediated renal transplant rejection 

In the Emergency Department, urgent/emergent plasma exchange may be initiated in otherwise hemodynamically stable patients in a handful of these conditions with only three conditions meeting category I level 1A evidence based upon the ASFA 2010 guidelines. Russi and Marson list these conditions as:

  1. Thrombotic thrombocytopenic purpura 
  2. Myasthenia gravis 
  3. Acute inflammatory demyelinating polyneuropathy 

Category I level IB recommendations are provided for hyperviscosity syndromes, while Category III level 1B recommendations are indicated for acute pancreatitis due to hypertriglyceridemia. Category II/III with level 2B or lower recommendations are listed for Catastrophic antiphospholipid syndrome, intoxication by certain drugs or poisonings, and acute fulminant hepatitis. 

Disposition:

In the emergency department, the patient received fluids and repeat lab work. Hematology-oncology was consulted from the ED for further recommendations which included a renal artery ultrasound to rule out thrombosis. JAK2 gene was sent for analysis. At this time the patient didn’t require emergent plasmapheresis, as she did not have symptoms of hyper-viscosity. The patient was admitted for observation overnight and was discharged home the next day with recommendations to follow up with hematology-oncology.

References:

Fridey, J., & Kaplan, A. (2018, July 18). Therapeutic apheresis (plasma exchange or cytapheresis): Indications and technology. (A. J. Silvergleid, & J. S. Tirnauer, Editors) Retrieved November 15, 2019, from UpToDate: https://www.uptodate.com/contents/therapeutic-apheresis-plasma-exchange-or-cytapheresis-indications-and-technology?search=plasmapheresis&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1

Russi, Gianpaolo, and Piero Marson. “Urgent plasma exchange: how, where and when.” Blood transfusion = Trasfusione del sangue vol. 9,4 (2011): 356-61. doi:10.2450/2011.0093-10

Schwartz J, Padmanabhan A, Aqui N, et al. Guidelines on the use of therapeutic apheresis in clinical practice—evidence-based approach from the Writing Committee of the American Society for Apheresis: The seventh special issue. J Clin Apher 2016; 31:149.